The most widespread intracellular bacteria in the animal kingdom are maternally-inherited endosymbionts of the genus Wolbachia. Their prevalence in arthropods and nematodes worldwide and a stunning arsenal of parasitic and mutualistic adaptations make these bacteria a biological archetype for basic studies of symbiosis and applied outcomes for curbing human and agricultural diseases. Here, we conduct a summative, centennial analysis of living in the Wolbachia world. We synthesize literature on Wolbachia’s host range, phylogenetic diversity, genomics, cell biology, and applications to filarial, arboviral, and agricultural diseases. We also review the mobilome of Wolbachia including phage WO and its essentiality to hallmark phenotypes in arthropods. Finally, the Wolbachia system is an exemplar for discovery-based science education using biodiversity, biotechnology, and bioinformatics lessons. As we approach a century of Wolbachia research, applications, and education, the interdisciplinary science and knowledge from this symbiosis stand as a model for consolidating and teaching the integrative rules of endosymbiotic life.

Purpose: To report a novel application of excimer ablation for normalization of central corneal refractive irregularity, combined with higher fluence CXL in the effective management and visual rehabilitation of progressive keratoconus. Methods: 17 cases with progressive keratoconus were treated with a corneal surface excimer laser ablation normalization using the topographyguided (Contura) myopic ablation for customized corneal re-shaping using a 6mm optical zone. The epithelial removal was accounted for by adding a -2.75 diopters correction in the topographyguided normalizing surface ablation followed by, a second, wavefront-optimized hyperopic excimer treatment of + 2.75 diopters at 6mm optical zone. The 2 sequential excimer ablations were followed by the corneal crosslinking (CXL). Visual acuity, refraction, and keratoconus documentation via keratometry, topography, and pachymetry, as well as endothelial cell density were evaluated over 36 months. Results: Keratoconus stabilized in all cases. The severity of keratoconus stage by Amsler-Krumeich criteria improved for the OD from an average 2.2 to 1. Mean UDVA showed marked improvement at one-year follow-up all values in decimal: from 0.21±0.18 pre-operative to 0.51±0.25 at 12 months, with small additional improvement through the 3 years to 0.51±0.16. CDVA respectively increased from 0.55±0.11 to 0.77±0.14 at 1 year, and to 0.79±0.16 at 3 years. Mean minimal corneal thickness decreased significantly from 466.74±34.25 µm to 396.17±45.17 µm (P<.01) as recorded the first year postoperatively and then slightly increased to 405.17±32.21 µm at the 3-year follow-up. Conclusions: We introduce herein initial clinical data with the use of novel, off-label therapeutic excimer laser surface ablation application: Designed to perform both epithelial removal and anterior corneal stroma reshaping, to be combined with CXL, in order to apply the Athens Protocol CXL with US excimer laser approved specifications.

Burkholderia are a group of Gram-negative bacteria that can cause a variety of diseases in at-risk populations. B. pseudomallei and B. mallei, the etiological agents of melioidosis and glanders, respectively, are the two clinically relevant members of the B. pseudomallei complex (Bpc). The development of vaccines against Bpc species has been accelerated in recent years, resulting in numerous promising subunits and glycoconjugate vaccines incorporating a variety of antigens. However, a second group of pathogenic Burkholderia species exists known as the Burkholderia cepacia complex (Bcc), a group of opportunistic bacteria which tend to affect individuals with weakened immunity or cystic fibrosis. To date there have been few attempts to develop vaccines to Bcc species. Therefore, the primary goal of this review is to provide a broad overview of the various subunit antigens that have been tested in Bpc species, their protective efficacy, study limitations, and known or suspected mechanisms of protection. Then, we assess the reviewed Bpc antigens for their amino acid sequence conservation to homologous proteins found in Bcc species. We propose that protective Bpc antigens with a high degree of Bpc-to-Bcc sequence conservation could serve as components of a pan-Burkholderia vaccine capable of protecting against both disease-causing groups.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an electron acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H...O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine C-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine C-H. We show that electronic factors associated with the C-H bond strengthen the C=O oscillator by increasing the s-character of the -bond, lowering the hyperconjugative disruption of the -bond. In addition, a reduction of the acceptor C=O bond’s polarity is observed upon the formation of the C-H...O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

In response to the COVID-19 pandemic, and resultant cancellation of geoscience fieldwork, as well as outstanding accessibility issues inherent in conducting fieldwork, we developed a virtual geological fieldtrip (VFT) to the Huronian age deposits in the Whitefish Falls area, Ontario, Canada. This region is a geologically significant site in which many Ontario universities conduct undergraduate teaching due to the high-quality exposures. In this contribution we describe and comment on the development of this openly available resource, the motivations in doing so, the challenges faced, its pedagogical impact and relevance, as well as provide suggestions to others in the development of such resources. Our multimedia VFT combines 360° imagery, georeferenced data on integrated maps, and multi-scale imagery (aerial/drone, outcrop, and thin section images). The VFT was built using the Esri Storymaps platform, and thus offers us the opportunity to review the effectiveness of building such resources using this medium, as well as our approach to doing so. We conclude that the Esri Storymaps platform provides a sound medium for the dissemination of multimedia VFTs, but that some aspects of in-person fieldwork remain hard to replicate. Most notably, ‘hands on experience’ and specific activities such as geological mapping. In addition, while VFTs alleviate some accessibility barriers to geoscience fieldwork, substantial barriers remain that should remain the focus of both pedagogical and geoscience work.

Deterioration of concrete subjected to freezing and thawing climatic conditions is one of most important factors affecting the durability of concrete infrastructure in cold climates. The freeze-thaw resistance of cementitious materials like concrete and mortar can be determined by the CDF test (Capillary Suction of De-icing chemicals and Freeze-Thaw Test). Here, concrete specimens are subjected to repeated freeze-thaw cycles with simultaneous addition of de-icing salt and the amount of material weathered near the surface is determined. For concretes with adequate freeze-thaw resistance, this test method works very well. However, specimens with inadequate or unknown performance often experience increased edge weathering, which is caused by the detachment of the lateral isolation tape. The increasing edge influence thus leads to a falsification of the results and consequently to an underestimation of the actual freeze-thaw resistance of the material. In materials research in particular, however, concretes with high levels of weathering are studied in order to be able to investigate various factors of influence on the freeze-thaw resistance of concretes in a targeted manner. This paper presents a novel methodology that delivers new information regarding the weathering of CDF test samples and the associated distribution function of the height decrease using high resolution 3D scan data. The results indicate a correlation between the progression of the distribution function and the sample's maximum aggregate size. The change of the sample volume can be used to support the weathering results of the standard CDF methodology. The increase of the surface area is used to estimate the tortuosity of the sample surface. It indicates an asymptotic curve approaching a specific maximum value, which is dependent on the the weathering depth of the sample.

Cutaneous melanoma (CM) is a candidate for screening programs, since its prognosis is excellent when diagnosed in an early disease stage. Targeted screening of those at high risk for developing CM, a cost-effective alternative to population-wide screening, requires valid procedures to identify the high-risk group. Self-assessment of the number of nevi has been suggested as a component of such procedures, but its validity has not yet been established. We analyzed the level of agreement between self-assessments and expert assessments of the number of melanocytic nevi in the area between the wrist and the shoulder of both arms based on 4548 study subjects in whom mutually blinded double counting of nevi was performed. Nevus counting followed the IARC protocol. Study subjects received written instructions, photographs, a mirror, and a “nevometer” to support self-assessment of nevi larger than 2 mm. Nevus counts were categorized based on the quintiles of the distribution into five levels defining a nevus score. Cohen’s weighted kappa-coefficient was estimated to measure the level of agreement. In the total sample, agreement between self-assessments and expert-assessments was moderate (raw agreement: 50.29%, weighted κ=0.596). Self-assessed nevus counts were higher than those determined by experts (mean differ-ence: 3.33 nevi). The level of agreement was independent of sociodemographic and cutaneous factors; however, participants’ eye color had a significant impact on the level of agreement. Our findings show that even with comprehensive guidance, only a moderate level of agreement between self-assessed and expert-assessed nevus counts can be achieved. Self-assessed nevus information does not appear to be reliable enough to be used in individual risk assessment to target screening activities.

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

HepG2 cells reconstituted with Hepatitis B virus (HBV) entry receptor sodium taurocholate co-transporting polypeptide (NTCP) are widely used as a convenient in vitro cell culture infection model for HBV replication studies. As such, it is pertinent that HBV infectivity is maintained at steady-state levels for accurate interpretation of in vitro data. However, variations in HBV infection efficiency due to imbalanced NTCP expression levels in the HepG2 cell line may affect experimental results. In this study, we performed single cell cloning of HepG2-NTCP-A3 parental cells via limiting dilution and obtained multiple subclones with increased permissiveness to HBV. Specifically, one subclone (HepG2-NTCP-A3/C2) yielded more than 4-fold higher HBV infection compared to the HepG2-NTCP-A3 parental clone. In addition, though HBV infectivity was universally reduced in the absence of polyethylene glycol (PEG), subclone C2 maintained relatively greater permissiveness under PEG-free conditions, suggesting the functional heterogeneity within parental HepG2-NTCP-A3 may be exploitable in developing a PEG-free HBV infection model. The increased viral production correlated with increased intracellular viral antigen expression as evidenced through HBcAg immunofluorescence staining. Further, these subclones were found to express different levels of NTCP, albeit with no remarkable morphology or cell growth differences. In conclusion, we isolated subclones of HepG2-NTCP-A3 which support efficient HBV production and thus provide an improved in vitro HBV infection model.

Agrilus planipennis is a devastating invasive pest of ash trees. This wood-boring insect native to Asia and established in European Russia about 20 years ago poses a serious threat to ash trees all over Europe. In 2019 we first detected Agrilus planipennis in Ukraine. More than 20 larvae have been collected from under the bark of Fraxinus pennsylvanica trees on 5 September 2019 in Markivka District of Luhansk Region. Coordinates of the localities of collection: 49.614991 N, 39.559743 E; 49.614160 N, 39.572402 E and 49.597043 N, 39.561811 E. The photos of damaged trees with larval galleries, exit holes and larvae are presented. There is no doubt that the pest is established in Ukraine. This fact is important for development of quarantine protocols to prevent or at least slow the further spread of this invasive pest in Europe.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Originating in the 1970s, Magnetic Compression Anastomosis (MCA) has lately been revisited with a focus on minimal invasive surgery (MIS). The aim of this report is to reappraise our earlier experience with MCA with the intention of facilitating future MCA advancement. A retrospective review was conducted regarding preclinical experiments and clinical trials at a single institution from 1980 through 1995. The reviewed information was compiled and appraised to generate proposals for future MCA use. The experimental studies, including 250 MCA cases in gastrointestinal and urinary tract animal models, demonstrated the technical versatility of MCA as well as the superior biomechanical characteristics in comparison to hand-sewn anastomoses. Clinical trials encompassed 87 MCA procedures in 86 children, 2 to 10 years of age, involving the following techniques: non-operative esophageal recanalization (n=15), non-operative ileostomy undiversion (n=46), Swenson pull-through (n=10), non-operative urethral recanalization (n=5), and extravesical ureterocystoneostomy (n=11). Clinical MCA was found to be successful in over 87% of cases. MCA limitations concerning anastomotic failure and scarring were thought to be mostly due to inadequate magnetic compression. Based on our historic experience, we propose further research on the technical aspects of MCA, along with the biologic aspects of anastomotic tissue remodeling. Magnets should be designed and manufactured for a wide spectrum of pediatric surgical indications, particularly in combination with novel MIS techniques.

Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.

Vaccination, particularly against pneumoccus and influenza, is a low-cost primary prevention, useful to avoid hard complications, particularly among frail older people. In this study, we aimed to assess the effect of a strategy for influenza and pneumococcal vaccination for outpatients, never practiced before, evaluating what could stimulate or demotivate vaccination among older people. This study was conducted during the 2023-2024 influenza season at the outpatient clinics of the Geriatrics section, University Hospital of Palermo (Italy). A total of 101 vaccinations were carried out. Half of the patients could be considered as pre-frail and about 20% frail, according to a comprehensive geriatric evaluation. Among participants, 46.3% received only vaccination against Pneumococcus and 26.8% only anti-influenza or the combination of anti-pneumococcus and anti-influenza. Compared with the previous seasons, a 19.5% increase of influenza and 90.2 % of pneumococcal vaccine uptake was observed. Side effects of vaccination were the main reason of the previous rejections, namely 74.8% for influenza and 29.5% for anti-pneumococcal vaccination. In conclusion, our study indicates how a new vaccination strategy in different settings is possible. Proposing influenza and pneumococcal vaccination for outpatients could be an effective instrument to improve immunization coverage that is still low among older people.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

This review focuses on developments that quantify grain quality with a range of spectral sensors in an on-farm setting. If the application of sensor technologies were expanded and adopted on-farm, growers could identify the impact and manage the harvesting operation to meet a range of quality targets and provide an economic advantage to the farming enterprise.

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Considered one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13th October, 2020, had been categorised as a Eurocentric writer. This work assesses the authenticity or otherwise of this critics’ perception of Clark by critiquing his America, their America. By analysing this autobiography vis-à-vis the notion of self and other which is a theoretical concern in contemporary travel writing, it was established, among other things, that every culture has its dark sides which it must not feel too proud to change as time and situation demand; that Clark vehemently rejects the Americans’ claim of sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural, political and diplomatic compromises between the Self and the Other since the gulf may be difficult to close altogether.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

This study reports the synthesis and characterization of novel per-fluorinated organic polymers with azo- and azomethine-based linkers using nucleophilic aromatic substitution. The polymers reveal variations in the fluorine content via the incorporation of decafluorobiphenyl and hexafluorobenzene linkers, which enhanced their hydrophobic nature. The rich fluorine polymers were slightly soluble in THF and have shown molecular weights between 4886 to 11948 g/mol. All polymers exhibit thermal stability in the range of 350-500°C, with varying thermal stability depending on the fluorine and nitrogen content. Conjugation of the polymers was confirmed through changes in the UV-Vis spectra, with a hypsochromic shift observed in all cases, more pronounced in azo-based fluorinated chains due to H-bonding on the nitrogen sites, chain conformations, and planarity. The optical band gap (Eg) of the polymers was determined from the UV-Vis data, with the Eg values of the azo-based fluorinated polymers being 1 eV higher than those of their corresponding linkers. The cross-linking formation was characterized by porosity measurements, with the azo-based polymer exhibiting the highest surface area of 770 m²/g with a pore volume of 0.35 cm³/g, while the open-chain azomethine-based polymer exhibited the lowest surface area of 285 m²/g with a pore volume of 0.0872 cm³/g. Porous structures with varied hydrophobicities were investigated as adsorbents for separating water-benzene and water-phenol mixtures and selectively binding methane/carbon dioxide gases from the air. The most hydrophobic polymers containing the decafluorbiphenyl linker were suitable for benzene separation, while the best methane uptake values were 6.14 and 3.46 mg/g for DAB-Z-1O and DAB-A-1O, respectively. DAB-Z-1h, with the highest surface area and rich in nitrogen sites, exhibited the highest CO₂ uptake at 298 K (17.25).

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

COVID-19 is a contagious respiratory disease that is causing significant global morbidity and mortality. Understanding the impact of a SARS-CoV-2 infection on the host metabolism is still in its infancy but of great importance. Herein, we investigated the metabolic response during viral shedding and post-shedding in an asymptomatic SARS-CoV-2 ferret model (n=6) challenged with two SARS-CoV-2 isolates. Virological and metabolic analyses were performed on (minimally invasive) collected oral swabs, rectal swabs, and nasal washes. Fragments of SARS-CoV-2 RNA were only found in the nasal wash samples in four of the six ferrets, and in the samples collected 3 to 9 days post-infection (referred to as viral shedding). Central carbon metabolism metabolites were analyzed during viral shedding and post-shedding periods using a dynamic MRM (dMRM) database and method. Subsequent untargeted metabolomics and lipidomics of the same samples were performed using an LC-QToF-MS methodology, building upon the identified differentiated central carbon metabolism metabolites. Multivariate analysis of the acquired data identified 29 significant metabolites and three lipids that were subjected to pathway enrichment and impact analysis. The presence of viral shedding coincided with the challenge dose administered and significant changes in the citric acid cycle, purine metabolism, and pentose phosphate pathways, amongst others, in the host nasal wash samples. An elevated immune response in the host was also observed between the two isolates studied. These results support other reported metabolomic-based findings found in clinical observational studies and indicate the utility of metabolomics applied to ferrets for further COVID-19 research that advances early diagnosis of asymptomatic and mild clinical COVID-19 infections, in addition to assessing the effectiveness of new or re-purposed drug therapies.

A class of controlled plants, whose dynamics is governed by a vector system of ordinary differential equations with a partially known right-hand side, is considered. The state variables and their velocities are assumed to be measurable. The aim is to design a controller which minimizes a loss function under certain constraints which arguments is the current state of the controlled plant. The designed control action is admitted to be a function of the current sub-gradient only, which supposed to be measurable on-line. The control design is based on ASG (Average Sub-Gradient method) — version of Integral Sliding Mode (ISM) concept, aimed to minimize on average a given convex (not obligatory strongly convex) cost function of the current state under a set of given constraints. An optimization type algorithm is developed and analyzed using ideas of SDM technique. The main results consist in proving the reachability of the "desired regime" (nonstationary analogue of sliding surface) from the beginning of the process and obtaining an explicit upper bound for the averaged loss function decrement, that is, the averaged in time functional convergence is proven and the rate of such convergence is estimated.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

Companies are increasingly focusing on sustainable business practices. Internal and external stakeholders’ expectations manifest in legal requirements, national and international standards, and market and customer expectations, among other things, must be considered. In addition to profit maximization as the usual target for corporate management, management must consider environmental sustainability aspects such as resource efficiency, greenhouse gas intensity, and a company's emissions behavior. In addition, social aspects relating to the company's employees, the immediate urban environment, the situation in the supply chain, and effects on the market environment must increasingly be considered. Specifically, companies are faced with the chal-lenge of dealing with conflicting objectives regarding the various aspects of sustainability and, if necessary, weighing them up against each other. These trade-offs must be made against the company's socio-economic and ecological environment, corporate strategy, and sustainability goals. This paper provides an overview of current approaches and research gaps on this topic through a literature review. It shows a lack of methods and frameworks to specifically deal with trade-offs and conflicts of goals.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs known as SINE-VNTR-Alu (SVA) demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), however the exact mechanism has yet to be identified. In this study we used whole genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Center ALS Consortium, to elucidate the influence of reference SVA elements on gene expression genome-wide within central nervous system (CNS) tissues. To investigate this, we applied matrix expression quantitative trait loci analysis and demonstrated that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position, and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative disease. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

Wireless Sensor Networks (WSN) are the core of Internet of Things and require cryptographic protection due to the increase number of attacks. Cryptographic methods for WSN should be fast and consume low power as these networks consist of battery-powered devices and constrained microcontrollers. NTRU, the fastest and secure public key cryptosystem, uses high degree polynomials, and is susceptible to the lattice basis reduction attack (LBRA). CPKC, proposed by NTRU authors, works on integers modulo $q$ and is easily attackable by LBRA since it uses small numbers for the sake of the correct decryption. Herein, RCPKC, a random congruential public key cryptosystem working on integers modulo $q$ is proposed, such that the norm of a two-dimensional vector formed by its private key is greater than $\sqrt{q}$. RCPKC works similar to NTRU, and it is a secure version of insecure CPKC. RCPKC specifies a range from which the random numbers shall be selected, and it provides correct decryption for valid users and incorrect decryption for an attacker using LBRA by Gaussian lattice reduction. Because of its resistance to LBRA, RCPKC is more secure. Simultaneously, due to the use of big numbers instead of high degree polynomials, RCPKC is about 24 (7) times faster in encryption (decryption) than NTRU. Also, RCPKC is more three times faster than the most effective known NTRU variant, BQTRU. Compared to NTRU, RCPKC reduces energy consumption at least seven times that allows increasing life-time of unattended WSN more than seven times.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

The global threat of COVID-19 has led to the increasing use of metabolomics to study SARS-CoV-2 infection in humans and animals. Despite this, understanding SARS-CoV-2's metabolome during infection remains difficult and incomplete. Here, metabolic responses were characterized from sampled nasal washes collected from an asymptomatic ferret model (n = 20) at different time points before and after the SARS-CoV-2 challenge using an LC-MS-based metabolomics approach. Multivariate analysis of the nasal wash metabolome data resulted in several statistically significant features being observed. Despite no effects of gender or interaction between gender and time on the time course of SARS-CoV-2 infection, 16 metabolites were significantly different at every time point post-infection. Among these altered metabolites, the relative abundance of taurine was elevated post infection which could be an indication of hepatotoxicity, while the accumulation of sialic acids could indicate SARS-CoV-2 invasion. The pathway analysis identified several pathways influenced by SARS-CoV-2 infection. Of these, sugar, glycan, and amino acid metabolisms were the key altered pathways in the upper respiratory channel during infection. These findings provide some new insights into the progression of SARS-CoV-2 infection in ferrets at the metabolic level which could be useful for the development of early clinical diagnosis tools and new or repurposed drug therapies.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Development of load-bearing polymer composite constructions in civil engineering, such as industrial chimneys and gas ducts, requires filling some research gaps. These gaps are related to long-term behavior under mechanical and temperature loads, cyclic ones as well. Such conditions mean that viscoelasticity should be considered. First of all, viscoelastic parameters should be calculated, based on the used inner structure model. Then, due to the high working temperatures, thermal aging should be considered as well. This research is devoted to effects of thermal aging on viscoelastic behavior of polymers. Two sets of experiments were conducted: creep tensile tests and cyclic heating in constrained state. The Kelvin-Voigt viscoelasticity model was used to determine the rheological parameters of binder from experimental creep curves. Thermally-aged binder turned out to lose its viscous properties and became elastic. Cyclic heating was used to compare the behavior of normal and thermally-aged binder and to evaluate the possibility of temperature stress accumulation. Similar to creep tests, cyclic heating showed that aged binder lost viscosity and worked almost perfectly elastic. Non-aged binder was prone to stress accumulation much more. As a result, the rheological behavior of aged and non-aged binder was compared and showed a significant difference. In addition, the influence of temperature stress accumulation on stress—strain state was evaluated and turned out to be significant as well. The obtained results can be further used to predict the mechanical behavior of structures made of polymer composites operating for a long time at elevated temperatures, including those exceeding the glass transition temperature.

Driven by the growing interest of the scientific community and the proliferation of research in this field, cranial implants have seen significant advancements in recent years regarding design techniques, structural optimisation, appropriate material selection and fixation system method. Custom implants not only enhance aesthetics and functionality but are also crucial for achieving proper biological integration and optimal blood irrigation, critical aspects in bone regeneration and tissue health. This research aims to optimize the properties of implants designed from triply periodic minimal surface structures. The gyroid architecture is employed for its balance between mechanical and biological properties. Experimental samples were designed varying three parameters of the surface model: cell size, isovalue and shape factor. Computational simulation tools were used for determining the relationship between those parameters and the response variables: the surface area, permeability, porosity and Young modulus. These tools include computer aided design, finite element method and computational fluid dynamics. With the simulated values, the corresponding regression models were fitted. Using the NSGA-II, a multi-objective optimisation was carried out, finding the Pareto set which includes surface area and permeability as targets, and fulfil the constraints related with the porosity and Young modulus. From these non-dominated solutions, the most convenient for a given application was chosen, and an optimal implant was designed, from a patient computed tomography scan. An implant prototype was additively manufactured for validating the proposed approach.

The article presents a new approach to the analysis of the stability of automatic systems with discrete links.In almost all modern automatic control systems, there are links that break signals in time. These are power controlled switches - transistors or thyristors operating in a pulsed mode and digital links in regulators.Time discretization significantly affects the stability of processes in the automatic control system. The theoretical analysis of such systems is rather complicated and requires a significant change in engineering approaches to analysis. In connection with the improvement of digital controllers and a significant increase in their performance, in recent years this problem has practically not been remembered. However, its mathematical "content" has not changed since the 80s of the 20th century, when discreteness began to play a major role among the problems hindering progress in automatic control systems, in terms of the transition to digital systems.In this paper, a new approach is proposed, which consists in interpreting the sampling operation by a link with the proposed frequency characteristic, which determines the suppression of input high-frequency signals. This link greatly simplifies engineering calculations and demonstrates the new capabilities of sampling systems. These possibilities include the rational distribution of digitalization resources - the number of bits and the sampling interval between the regulator channels, depending on the frequency range of the efficiency of these channels. Theoretical statements have been verified and confirmed by simulation. It is shown how this approach makes it possible to formulate new principles of construction of seemingly well-known controllers - PID controllers and variable structure systems (VSS).

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

This research is completed in development of researches devoted to relations between elastic modulus (MoE) and thermal expansivity (CTe) of different materials. This study experimentally confirmed the relation of MoE and CTe for thermosetting polymers and FRPs both under normal and heating temperatures. As the thermosetting polymers, the epoxy compositions were used and glass fiber and mineral additives for FRP. The experiment was based on dilatometric and elastic deformations’ testing. Also, the relaxation model of MoE/CTe was proposed, that is based on physical properties of polymers’ supramolecular structures. The comparative analyzing of MoE/CTes’ different models is done. The most accurate models are determined, and the relaxation model has demonstrated the high accuracy.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

A proposed low-temperature forging method aims to enhance stainless steel bearings by creating a martensitic subsurface layer, significantly boosting bearing fatigue life due to increased surface hardness. This technique induces beneficial residual stresses, particularly in axial bearings, streamlining their construction and improving machine elements. Challenges persist, especially with radial bearings, but simplicity in axial bearing forging promotes compact, resource-efficient facility construction. Future research will focus on applying this technique to axial bearing washers, potentially replicating success in other bearing components. Despite the energy ex-penditure for cooling during forging, the substantial increase in bearing fatigue life offsets this, enhancing overall longevity and reliability of critical machine components. Integration of this forging technique into bearing fabrication appears seamless, offering a promising trade-off be-tween energy use and enhanced performance.

Machine learning (ML) is growing in popularity for various particle accelerator applications including anomaly detection such as faulty beam position monitor or RF fault identification, for non-invasive diagnostics, and for creating surrogate models. ML methods such as neural networks (NN) are useful because they can learn input-output relationships in large complex systems based on large data sets. Once they are trained, methods such as NNs give instant predictions of complex phenomenon, which makes their use as surrogate models especially appealing for speeding up large parameter space searches which otherwise require computationally expensive simulations. However, quickly time varying systems are challenging for ML-based approaches because the actual system dynamics quickly drifts away from the description provided by any fixed data set, degrading the predictive power of any ML method, and limits their applicability for real time feedback control of quickly time-varying accelerator components and beams. In contrast to ML methods, adaptive model-independent feedback algorithms are by design robust to un-modeled changes and disturbances in dynamic systems, but are usually local in nature and susceptible to local extrema. In this work, we propose that the combination of adaptive feedback and machine learning, adaptive machine learning (AML), is a way to combine the global feature learning power of ML methods such as deep neural networks with the robustness of model-independent control. We present an overview of several ML and adaptive control methods, their strengths and limitations, and an overview of AML approaches. A simple code for the adaptive control algorithm used here can be downloaded from: https://github.com/alexscheinker/ES_adaptive_optimization

We study the Kelvinons: monopole ring solutions to the Euler equations, regularized as the Burgers vortex in the viscous core. There is finite anomalous dissipation in the inviscid limit. However, in the anomalous Hamiltonian, some terms are growing as logarithms of Reynolds number; these terms come from the core of the Burgers vortex. In our theory, the turbulent multifractal phenomenon is similar to asymptotic freedom in QCD, with these logarithmic terms summed up by an RG equation. The small effective coupling does not imply small velocity; on the contrary, velocity is large compared to its fluctuations, which opens the way for a quantitative theory. In the leading order in the perturbation theory in this effective coupling constant, we compute running multifractal dimensions for high moments of velocity circulation, in good agreement with the data for quantum Turbulence and available data for classical Turbulence. The logarithmic dependence of fractal dimensions on the loop size comes from the running coupling in anomalous dimensions. This slow logarithmic drift of fractal dimensions would be barely observable at Reynolds numbers achievable at modern DNS.

The creative potential of homo sapiens is the biological basis of his spirituality. To take into account factor of spirituality in analysis of global problems of demography and ecology used analogies of chemical kinetics. Stable in the historical time, population of people was modeled by open thermodynamic system, equilibrium state of which depends on climate and geophysics. The demography of creative potential was divided into two geographical zones - north and south. Process of society sapientation was formalized by introducing into logistic equation of Verhulst, in addition to a couple of parents, at least one more teacher from among educated people. Stationary solution of the modified kinetic equations determines optimal demography for sustainable development of population in accordance with its education index. The solution of the demographic, energy and environmental problems of mankind is determined by the level of world creative potential, the growth of which is currently limited by the consumption paradigm.

Social biases may concentrate attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in significant part of responses to toxicity. It is unclear, however, if there are other molecular mechanisms which play important role in toxicity events but are overlooked by toxicology. To identify overlooked genes sensitive to chemical exposures we used publicly available databases. First, we used data on published chemical-gene interactions for 17,338 genes to estimate their sensitivity to chemical exposures. Next, we extracted data on publication numbers per gene for 19,243 human genes from Find My Understudied Genes database. Threshold were applied to both datasets using our algorithm to identify chemically sensitive and chemically insensitive genes and well-studied and underexplored genes. 1,110 underexplored genes highly sensitive to chemical exposures were used in GSEA and Shiny GO analyses to identify enriched biological categories. Metabolism of fatty acids, amino acids, and glucose were identified as underexplored molecular mechanisms sensitive to chemical exposures. These findings suggest that future effort is needed to uncover the role of xenobiotics in the current epidemics of metabolic diseases.

The existence of multiple copies of genes is a well-known phenomenon. A gene family is a set of sufficiently similar genes, formed by gene duplication. In earlier works conducted on limited number of completely sequenced and annotated genomes it was found that size of gene family and size of genome are positively correlated. Additionally, it was found that several atypical microbes deviated from the observed general trend. In this study, we reexamined these associations on a larger dataset consisting of 1484 prokaryotic genomes and using several ranking approaches. We applied ranking methods in such a way that genomes with lower number of paralogs would have lower rank. Until now only simple ranking methods were used; we applied the Kemeny optimal aggregation approach as well. Regression and correlation analysis were utilized in order to accurately quantify and characterize the relationships between measures of paralog indices and genome size. In addition, boxplot analysis was employed as a method for outlier detection. We found that, in general, all paralog indexes positively correlate with an increase of genome size. As expected, different groups of atypical prokaryotic genomes were found for different types of paralog quantities.

This paper considers two types of Protestant ethnic groups of some areas of Urals and Western Siberia. The first type consist of representatives of members of different ethnic groups consisting of well-educated professionals, incorporated into industrial society and associated with the intellectualism of Protestantism. The second type is represented by the indigenous peoples of the Polar Urals and Western Siberia, who use the Protestant religious organizations as tool for restoring life-sustaining elements of the native peoples’ traditional economy. I employed the inductive approach and the comparison method; during the fieldwork I used ethnographic participant observations, sociological structured interviews and closed-ended questionnaires. The empirical data have been collected in the Southern, Middle and Polar Urals and Western Siberia.

Medical image segmentation is a critical step in various healthcare applications, aiding in diagnosis, treatment planning, and disease monitoring. In this study, we investigate the efficacy of a segmentation approach based on the 2D wavelet transform. Leveraging a dataset comprising 10 diverse medical images, we evaluate the performance of our segmentation method using three key metrics: accuracy, precision, and recall. Our findings demonstrate that the proposed approach enhances segmentation accuracy, offering promising results compared to existing methods. By harnessing the multi-resolution feature extraction capabilities of the 2D wavelet transform, our method achieves improved delineation of medical image structures, paving the way for more accurate and efficient healthcare interventions.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Long-range interactions are relevant for a large variety of quantum systems in quantum optics and condensed matter physics. In particular, the control of quantum-optical platforms promises to gain deep insights in quantum-critical properties induced by the long-range nature of interactions. From a theoretical perspective, long-range interactions are notoriously complicated to treat. Here, we give an overview of recent advancements to investigate quantum magnets with long-range interactions focusing on two techniques based on Monte Carlo integration. First, the method of perturbative continuous unitary transformations where classical Monte Carlo integration is applied within the embedding scheme of white graphs. This linked-cluster expansion allows to extract high-order series expansions of energies and observables in the thermodynamic limit. Second, stochastic series expansion quantum Monte Carlo which enables calculations on large finite systems. Finite-size scaling can then be used to determine physical properties of the infinite system. In recent years, both techniques have been applied successfully to one- and two-dimensional quantum magnets involving long-range Ising, XY, and Heisenberg interactions on various bipartite and non-bipartite lattices. Here, we summarise the obtained quantum-critical properties including critical exponents for all these systems in a coherent way. Further, we review how long-range interactions are used to study quantum phase transitions above the upper critical dimension and the scaling techniques to extract these quantum critical properties from the numerical calculations.

In the work, the nuclei structure was modeled by a system of shells consisting of combinations of spherical and annular vortices. Having connected the spin and the magnetic moments of the nuclei with the dynamics of the outer shell of the nucleus, we determined its type and carried out a semiempirical calculation of the parameters of its structure for stable and unstable nuclear isotopes in the sequence of the order number Z from 1 to 37. Comparison of the obtained nuclear sizes with the radii of the electron shells of atoms made it possible to reveal a definite correlation. On the basis of it, it was concluded that the periodic law of Mendeleyev can determine the patterns in the change in the structure of the atomic nucleus.

Background: The febrile patient from tropical areas, in which emerging arboviruses are endemic, represent a diagnostic challenge and potential co-infections with other pathogens (i.e bacteria or parasites) are usually overlooked. Objectives: We present a case of an elderly woman diagnosed with dengue, chikungunya and Leptospira interrogans co-infection. Study Design: Case report. Results: An 87-year old woman from Colombia complained of upper abdominal pain, arthralgia, myalgia, hyporexia, malaise and intermittent fever accompanied with progressive jaundice. She had a medical history of chronic heart failure (Stage C, NYHA III), without documented cardiac murmurs, right bundle branch block, non-valvular atrial fibrillation, hypertension, and chronic venous disease. Her cardiac and pulmonary status quickly deteriorated after 24 hours of her admission without electrocardiographic changes and she required ventilatory and vasopressor support. In the next hours the patient evolved to pulseless electrical activity and then she died. Dengue IgM, NS1 ELISA, MAT for Leptospira interrogans and RT-PCR for chikungunya, were positive. Discussion: This case illustrates a multiple co-infection in a febrile patient from a tropical area of Latin America that evolved to death.

We propose a promising model of discrete spacetime based on nonassociative geometry and complex networks. Our approach treats space as a simplicial 3-complex (or complex network), built from "atoms" of spacetime and entangled states forming n-dimensional simplices (n=1,2,3). At large scales, a highly connected network is a coarse, discrete representation of a smooth spacetime. We show that for high temperatures, the network describes disconnected discrete space. At the Planck temperature, the system experiences the phase transition, and for low temperatures, the space becomes a triangulated discrete space. We show that the cosmological constant depends on the universe’s topology. The "foamy" structure, analogous to Wheeler’s "spacetime foam," significantly contributes to the effective cosmological constant, which is determined by the Euler characteristic of the universe.

Quantification of physical activity (PA) depends on the type of measurement and analysis method making it difficult to compare adherence to PA guidelines. Therefore, test-retest reliability, criterion validity, and stability for self-reported (i.e. questionnaire and diary) and device-based measured (i.e. accelerometry with 10/60 second epochs) PA was compared in 32 adults and 32 children from the SMARTFAMILY study to examine if differences in these measurement tools are systematic. PA was collected during two separate measurement weeks and the relationship for each quality criteria was analyzed using Spearman correlation. Results showed the highest PA values for questionnaires followed by 10-second and 60-second epochs measured by accelerometers. Levels of PA were lowest when measured by diary. Only accelerometry demonstrated reliable, valid, and stable results for the two measurement weeks, the questionnaire yielded mixed results and the diary showed only few significant correlations. Overall, higher correlations for the quality criteria were found for moderate than for vigorous PA and the results differed between children and adults. Since the differences were not found to be systematic, the choice of measurement tools should be carefully considered by anyone working with PA outcomes, especially if vigorous PA is the parameter of interest.

This is the second paper in a cycle investigating the exact solution of loop equations in decaying turbulence. We perform numerical simulations of the Euler ensemble, suggested in the previous work, as a solution to the loop equations. We designed novel algorithms for simulation, which take a small amount of computer RAM so that only the CPU time grows linearly with the size of the system and its statistics. This algorithm allows us to simulate systems with billions of discontinuity points on our fractal curve, dual to the decaying turbulence. For the vorticity correlation function, we obtain \textbf{quantum fractal laws} with regime changes between universal discrete values of indexes. The traditional description of turbulence with fractal or multifractal scaling laws does not apply here. The measured conditional probabilities of fluctuating variables are smooth functions of the logarithm of scale, with statistical errors being negligible at our large number of random samples $T = 167,772,160$ with $N = 200,000,000$ points on a fractal curve. The quantum jumps arise from the analytical distribution of scaling variable $X = \frac{\cot^2(\pi p/q)}{q^2}$ where $\frac{p}{q}$ is a random fraction. This distribution is related to the totient summatory function and is a discontinuous function of $X$. In particular, the energy spectrum is a devil's staircase with tilted uneven steps with slopes between $-1$ and $-2.03$. The logarithmic derivative of energy decay $n(t)$ as a function of time is jumping down the stairs of universal levels between $1.50$ and $1.53$. The quantitative verification of this quantization would require more precise experimental data.

The participation of civil society is essential for environmental health policies to be effective. The objective of this study was to know the perceptions of government officials, members of civil society, and academics about environmental health problems and its governance in Bucaramanga Metropolitan Area, Colombia. In the region there is a strong citizen movement that defends the moorland ecosystem (paramo) as source of drinking water, of large-scale mining projects. A multi-method study was carried out including the review of newspaper and scientific articles, a citizen survey, and interviews and focus groups with identified key stakeholders. The findings indicate that government officials prioritize their actions on issues related to air and water pollution and environmental education. In contrast, citizens prioritize water availability from the moorland ecosystem. There are some advances in the management of environmental health, mainly related to greater citizen awareness. The participation of civil society in the environmental health governance must be enforced to broaden the issues of interest and prioritize the activities in the short- and long-term policy planning. An experience between high school students and the academy that measures air pollutants can be the first meeting point with government officials in the pathway to improve the environmental governance in the territory.

The results of measuring the capacity of a thin-film solid-state lithium-ion battery (SSLIB) Ti|Si@O@Al|LiPON|LiCoO₂|Ti at different charge currents are reported. It is shown that the dependence of the capacity on the current density follows the Peukert's law, which is characterized by a low value of the Peukert’s exponent in the region of low currents and a high value of the exponent in the region of high currents. A capacity model for a SSLIB based on the balance of diffusion and migration currents is proposed and the dependence of the capacity on the charge current is derived. The obtained dependence is well approximated by Peukert's law with an exponent of 1.39, which is intermediate between the exponents for lithium-ion batteries with liquid electrolyte and SSLIBs.

The evolution of manual grooming and its implications have received little attention in the quest to understand the origins of simian primates and their social and technical intelligence. All simians groom manually, whereas prosimians groom orally despite comparable manual dexterity between some members of the two groups. Simians also exhibit a variable propensity for the manipulation of inanimate, non-food objects, which has culminated in tool making and tool use in some species. However, lemuriform primates also seem capable of tool use with training. Furthermore, lemuriforms appear to understand the concept of a tool and use their own body parts as “tools”, despite not using inanimate objects. This suggests that prosimian primates are pre-adapted for proprioceptive object manipulation and tool use, but do not express these cognitive abilities by default. This essay explores the paleontological, anatomical, cognitive, ethological, and neurological roots of these abilities and attempts to explain this behavioural divide between simians and prosimians. Common misconceptions about early primate evolution and captive behaviours are addressed, and chronological inconsistencies with Machiavellian Intelligence are examined. A “licking to picking” hypothesis is also proposed to explain a potential link between manual grooming and object manipulation, and to reconcile the inconsistencies of Machiavellian Intelligence. Bayesian decision theory, the evolution of the parietal cortex and enhanced proprioception, and analogies with behavioural changes resulting from artificial selection may help provide new insights into the minds of both our primate kin and ourselves.

The paper presents the results of experimental studies and mathematical modeling of the effect of stress accumulation in thermosetting epoxy polymer "hot" curing on anhydride hardener. Stress accumulation occurs under cyclic thermomechanical action in a locked rod, similar effects are observed, for example, in thermoplastic elements subjected to the combined effect of mechanical loads and variable temperatures. Experimental results have shown that under cyclic thermomechanical loading during exploitation it is possible to accumulate residual stresses in the thermosetting polymer. A multi-element structural mathematical model with memory for thermomechanical load, which allows to consider the accumulation of residual thermal stresses, has been proposed. The results of modeling and experiment are compared. Based on the results, corrections are made in the approach to the application of this model to thermosetting polymers such as the epoxy resin under study. Considering the corrections, a good agreement (the difference is from 1 to 6%) with the results of experimental determination of stresses under complex cyclic thermomechanical load was obtained.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Guessing effects frequently occur in testing data in educational or psychological applications. Different item response models have been proposed to handle guessing effects in dichotomous test items. However, it has been pointed out in the literature that the oftenemployed three-parameter logistic model poses implausible assumptions regarding the guessing process. The four-parameter guessing model has been proposed as an alternative to circumvent these conceptual issues. In this article, the four-parameter guessing model is compared with alternative item response models for handling guessing effects through a simulation study and an empirical example. It turned out that model selection for item response models should be rather based on the AIC than the BIC. However, the RMSD item fit statistic used with typical cutoff values was found to be ineffective in detecting misspecified item response models. Furthermore, sufficiently large sample sizes are required for sufficiently precise item parameter estimation. Moreover, it is argued that the criterion of statistical model fit should not be the sole criterion of model choice. The item response model used in operational practice should be valid with respect to the meaning of the ability variable and the underlying model assumptions. In this sense, the four-parameter guessing model could be the model of choice in educational large-scale assessment studies.

The comparison of group means in latent variable models plays a vital role in empirical research in the social sciences. The present article discusses extensions of invariance alignment and Haberman linking concerning the choice of linking functions for comparisons of many groups. Robust linking functions are proposed for invariance alignment and robust Haberman linking that are particularly suited to item response data under partial invariance. In a simulation study, it is shown that both linking approaches have comparable performance, and in some conditions, the newly proposed robust Haberman linking outperforms invariance alignment.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

The paper proposes a game theory model of price oligopoly with a heterogeneous product, where total demand depends linearly on the minimum market price. This model develops the Bertrand oligopoly for the case of imperfect price elasticity of demand. The most interesting result is an asymmetric Nash equilibrium with different prices and sales in the situation of symmetric oligopolists. The asymmetry is explained by the fact that a decrease in the minimum market price leads not only to a reallocation of consumers among firms, but also to an increase in total demand. Modifications of a two-stage game with a leader and followers and the price discrimination model are also considered. Microeconomic substantiation of the model is given on the basis of the spatial differentiation approach.

In the first part of this article, we discuss and generalize the complete convergence introduced by Hsu and Robbins (1947) to the r-complete convergence introduced by Tartakovsky (1998). We also establish its relation to the r-quick convergence first introduced by Strassen (1967) and extensively studied by Lai (1976). Our work is motivated by various statistical problems, mostly in sequential analysis. As we show in the second part, generalizing and studying these convergence modes is important not only in probability theory but also to solve challenging statistical problems in hypothesis testing and changepoint detection for general stochastic non-i.i.d. models.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

This paper presents one of the approaches to solution of the problem of the repulsion origin in gravity. The approach is based on the property of compactness characteristic for a self-gravitating object in General Relativity. Here we understand compactness as estimation of the upper boundary for mass such an object in a static two--dimensional sphere. Repulsion originates when this boundary is violated. The main hypothesis is formulated in the form of the principle of maximal mass within a two-dimensional static sphere. It is demonstrated that the principle is true for Schwarzschild black holes on absorption of the matter in the process of accretion, both in the classical case and with due regard for quantum-gravitational corrections. The results have been extended to black holes with the Schwarzschild-de Sitter metric in the early Universe. The applicability of the principle suggested is analyzed for the early and for the present Universe.

The invariant mass of free particles is used to derive a bound-state equation for several particle atomic systems at rest. This relativistic-kinematic bound-state equation is applied to the hydrogen and helium atoms. The derived equation has the well-known solutions for the single-electron bound states of the hydrogen atom, and the two-electron states of the helium atom. For the hydrogen atom, existence of the two-particle bound states, for which the electron and the proton kinetic energies are of the same order of magnitude, is predicted. The three-particle bound states with the same feature of the kinetic energies can exist in the helium atom. Radiative operators for processes involving the hydrogen two-particle bound states, are obtained. It is discussed that these new two- and three-particle bound states should be optically inactive.

We consider the Dirac electron as a nonperturbative particle-like solution consistent with its own Kerr-Newman (KN) gravitational and electromagnetic field. We develop the earlier models of the KN electron regularized by Israel and López, and consider the non-perturbative electron model as a bag model formed by Higgs mechanism of symmetry breaking. The López regularization determines the unique shape of the electron in the form of a thin disk with a Compton radius reduced by 4π. In our model this disk is coupled with a closed circular string which is placed on the border of the disk and creates the caused by gravitation frame-dragging string tension produced by the vector potential of the Wilson loop. Using remarkable features of the Kerr-Schild coordinate system, which linearizes the Dirac equation, we obtain solutions of the Dirac equation consistent with the KN gravitational and electromagnetic field, and show that this solution takes the form of a massless relativistic string. Parallelism of this model with quantum representations in Heisenberg and Schrodinger pictures explains remarkable properties of the stringy electron model in the relativistic scattering processes.

Six bacterial strains with differing abilities to produce varying concentrations of Indole Acetic Acid were tested individually and in consortia for plant growth promoting and fitness related traits of Cicer arietinum. In all experiments the presence of the nitrogen fixer Mesorhizobium ciceri resulted in increased biomass production. In the absence of this strain, IAA Psedomonas putida and Bacillus megaterium hinder plant growth and fitness related traits. The application of mixes of the three strains always resulted in better plant performance when M. ciceri was present. Whereas P. putida has a noticeable plant growth-promoting effect B. megaterium resulted less effective. The low levels of IAA produced by the selected strains had a significantly greater positive effect on plant biomass accumulation, flower, pods and seed production as well as on total plant nitrogen and nitrogen concentration in seed than high IAA producer strains.

Power sources that can consistently deliver high levels of energy over extended periods are crucial for various space applications. Among the many methods of energy generation, direct heat-to-electricity conversion without intermediate steps or moving components shows particular promise but also presents significant challenges. The aim of this research is to address these challenges by enhancing the energy efficiency of thermionic conversion, which transforms thermal energy into electrical energy, through the development and utilization of a novel class of emission nanomaterials known as multilayer carbyne-enriched 3D-shaped nano-interfaces. By manipulating the topological, physicochemical, and functional characteristics of these interfaces, we seek to optimize their thermionic conversion capabilities. Building on the recent discovery of collective atomic vibrations called phonon waves within transition domains of multilayer nanostructures, we have devised a new approach to enhance the efficiency of thermionic energy converters. This involves unlocking the predictive functionality of 2D-ordered linear-chain carbon-based multilayer emitters through the excitation and fine-tuning of collective atomic vibrations and nanoarchitecture. To achieve this, we propose employing a combination of techniques that leverage interface effects, enable phonon wave propagation, facilitate energy exchange, and capitalize on synergistic effects offered by the multilayer nano-enhanced interfaces. The resulting devices for thermionic energy conversion have the potential to significantly surpass the efficiency of existing plasma thermionic converters by several orders of magnitude. Moreover, these electricity-generating sources based on thermionic conversion represent fundamental options for the advancement of Lunar and Martian research missions, opening up possibilities for sustainable energy production in extraterrestrial environments.

Acute vertigo and dizziness are frequent presenting symptoms in patients on the emergency department. With a broad differential diagnosis and symptoms/signs often subtle and transient, the diagnostic approach to the dizzy patient remains challenging. Previous work emphasized the value of combining structured history-taking and a targeted examination focusing on subtle oculomotor signs. Here I review different bedside algorithms proposed for the acutely dizzy patient. Comparing area-under-the-curve ROC-characteristics and sensitivity/specificity, highest diagnostic accuracy was observed for algorithms focusing on subtle oculomotor signs. Both the HINTS+ bedside-exam and the STANDING algorithm have demonstrated higher diagnostic accuracy for identifying strokes than early (<24-48h after symptom-onset) MRI-DWI. Importantly, HINTS and STANDING require moderate training to allow reliable application. Thus, for physicians lacking dedicated training, other approaches are needed. Various scores that rely on vascular risk-factors, clinical symptoms and focal neurologic findings have been proposed (e.g., ABCD2-score, PCI-score, TriAGe+-score). While these scores are more readily applicable for frontline providers, they provide intermediate diagnostic accuracy at best and often lack external validation, thus are an insufficient substitute for algorithms assessing subtle oculomotor findings. Providing dedicated training in HINTS+ or STANDING techniques will be key to improve the diagnostic accuracy and to avoid unnecessary brain imaging.

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

The exponential growth of user-contributed data provides a comprehensive basis for assessing collective perceptions of landscape change. A variety of possible public data sources exist, such as geospatial data from social media or Volunteered Geographic Information (VGI). Key challenges with such ‘opportunistic’ data sampling are variability in platform popularity and bias due to changing user groups and contribution rules. In this study, we use five case studies to demonstrate how intra- and inter-dataset comparisons can help to assess the temporality of landscape scenic resources, such as identifying seasonal characteristics for a given area, or testing hypotheses about shifting popularity trends observed in the field. By focusing on the consistency and reproducibility of temporal patterns for selected scenic resources and comparisons across different dimensions of data, we aim to contribute to the development of systematic methods for disentangling the perceived impact of events and trends from other technological and social phenomena included in the data. The proposed techniques may help to draw attention to overlooked or underestimated patterns of landscape change, fill in missing data between periodic surveys, or corroborate and support field observations. Despite limitations, the results already provide a comprehensive basis for developing indicators with a high degree of timeliness for monitoring perceived landscape change over time.

The recent past has witnessed a growing interest in technologies for creating chatbots. Advances in Large Language Models for natural language processing are underpinning rapid progress in chatbot development, and experts predict revolutionary changes in the labour market as many manual tasks are replaced by virtual assistants in a range of business functions. As the new technology becomes more accessible and advanced, more companies are exploring the possibilities of implementing virtual assistants to automate routine tasks and improve service. This article reports on qualitative inductive research undertaken within a chatbot development team operating in a major international enterprise. The findings identify critical success factors for chatbot projects, and, based on the in-depth case study, a model is put forward to aid the manageability of chatbot implementation. The presented model can serve as an exemplar guide for researchers and practitioners working on the design, development and implementation of virtual assistants. It is flexible and applicable in a wide range of business contexts, linking strategic business goals with execution steps. It is particularly applicable for teams with no experience of chatbot implementation, reducing uncertainty and managing decisions and risks throughout the project lifecycle, thereby increasing the likelihood of project success.

A new generation of nano-technologies is expanding solid propulsion capabilities and increasing their relevance for versatile and manoeuvrable micro-satellites with safe high-performance propulsion. We propose the innovative concept, connected with application of new synergistic effect of the energetic materials performance enhancement and reaction zones programming for the next generation small satellite multimode solid propulsion system. The main idea of suggested concept is manipulating by the self-organized wave patterns excitation phenomenon, by the properties of the energetic materials reaction zones and by localization of the energy release areas. This synergistic effect can be provided through application of the functionalized carbon-based nanostructured metamaterials as a nano-additives along with simultaneous manipulating by their properties through the electrostatic field. Mentioned effect will be controlled through predictive programming both by the spatial structure and physics-chemical properties of the functionalized carbon-based nano-additives and through the electromagnetic control of the self-organized wave pattern excitation and micro- and nano- scale oscillatory networks in the energetic material reaction zones. Suggested new concept makes it possible to increase the energetic material regression rate and increase the thrust of the solid propulsion system with minimal additional energy consumption.

Uranium isotopes actively investigated as mechanistic or time scale tracers of natural processes. This paper describes the occurrence and redistribution of U in the Vendian aquifer of the paleo valley at NW Russia. Forty-four rock samples were collected from boreholes, and twenty-five groundwater samples. The U, Fe concentration, and 234U/238U activity ratio were determined in the samples. We estimated the 14C and 234U-238U residence time of groundwater in an aquifer. It has been established that the processes of chemical weathering of Vendian deposits led to the formation of a strong oxidation zone, developed above -250 m.a.s.l. The inverse correlation between the concentrations of uranium and iron is a result of removal of U from paleo valley slopes in oxidizing conditions and accumulation of U at the bottom of the paleo valley in reducing conditions, and accumulation of Fe on the slopes and removal from bottom. Almost all U on the slopes replaced by a newly formed hydrogenic U with a higher 234U/238U activity ratio. After that dissolution and desorption of hydrogenic U was occurred from the slopes during periods without any glaciations and marine transgressions. Elevated concentrations of U preserved in not oxidized lenses at the paleo valley bottom.

This article shows that the recently proposed latent D-scoring model of Dimitrov is statistically equivalent to the two-parameter logistic item response model. An analytical derivation and a numerical illustration are employed for demonstrating this finding. Hence, estimation techniques for the two-parameter logistic model can be used for estimating the latent D-scoring model. In an empirical example using PISA data, differences of country ranks are investigated when using different metrics for the latent trait. In the example, the choice of the latent trait metric matters for the ranking of countries. Finally, it is argued that an item response model with bounded latent trait values like the latent D-scoring model might have advantages for reporting results in terms of interpretation.

Response of tomato and eggplant to continuous lighting (CL) and abnormal light/dark (L/D) cycles was studied to elucidate the role of the absence of the dark period in the diurnal cycle in the development of leaf injuries under CL. Four light treatments were set: 16/8 h (control), 24/0 h (CL), 6/6 h, and 24/24 h (abnormal L/D cycles). These light treatments provided average daily light integrals of 17.3, 25.9, 13.0 and 13.0 mol m-2 day-1, respectively. Results of this work have shown that in both tomato and eggplant abnormal L/D cycles caused photoinhibition and leaf injuries similar to those in CL-grown plants. Induced defense mechanisms were not strong enough to contend against oxidative stress caused by light treatments that provided plants with even smaller DLI than 16/8 h photoperiod did. Half time during abnormal L/D cycles were dark periods. Despite these facts, abnormal L/D cycles were injurious. It is concluded that photooxidative stress induced by CL can not be attributed to excessive DLI or the continuity of light itself (the absence of dark periods). Therefore, we believe that the hypothesis suggesting circadian asynchrony to be the main triggering factor of CL-induced leaf injuries is the most plausible among many others proposed.

Anastomotic insufficiencies are severe complications of abdominal surgery, often leading to pro-longed hospitalization, serious tissue inflammation, even sepsis and the need for recurrent sur-gery. Current non-surgical treatments such as self-expanding metal stents (SEMS) and endoscopic vacuum therapy (EVT) have limitations, including stent migration or perforation. This review evaluates the effectiveness of the VacStent GITM, a novel medical device combining SEMS and negative-pressure wound therapy in treating gastrointestinal leaks. Data were gathered from four prospective studies and compared with existing treatments. Studies on the VacStent GITM applica-tion demonstrate technical success and competitive closure rates in upper gastrointestinal leaks, with minimal complications reported. Comparative analyses with SEMS and EVT reveal prom-ising and most importantly equally good outcomes while maintaining the possibility for sus-tained enteral nutrition and reducing stent migration risk. The VacStent GITM presents a promis-ing alternative to current non-surgical treatments. Ongoing research aims to validate its efficacy in lower gastrointestinal leaks and establish its role in leak management comprehensively. Fur-ther investigation is necessary to confirm these findings and optimize treatment protocols. Future usages of the VacStent GITM in colonic anastomotic insufficiencies promise an effective approach and might be able to lower the rates of necessary implementations of a stoma.

Over the last decade, a lot of research has been conducted on memristors. Most of this research focusses on using memristors for Artificial Intelligence (AI) applications and to fabricate non-volatile memory, but also the security aspects of memristors have been examined. The current study summarises and compares five reviews on the security aspects of memristors. These reviews cover two different perspectives: (1) security applications of memristors such as Physical Unclonable Functions (PUFs) or True Random Number Generators (TRNGs), and (2) potential threats when using memristors to train and store neural networks. The comparison of the reviews reveals that different sets of studies are included in the reviews and different characterisations of the studies are provided. This shows that different perspectives are necessary to get a comprehensive overview of the security aspects of memristors. By synthesising the perspectives of different reviews, this study helps to get such an overview.

Graph visualization has evolved significantly over time, offering various methods to effectively represent complex data structures. This study introduces a novel force-directed algorithm for 3D data visualization, specifically tailored for commonly used datasets in linked data visualization. Leveraging the power of graph theory and methods, the algorithm aims to address the challenge of creating visually appealing and easily interpretable visualizations, which often necessitate advanced user interaction. By utilizing 3D space and the Unity Engine, the research successfully visualizes data and develops interactive visualizations, overcoming limitations of basic force-directed implementations. The main contribution of presented research is in the force-directed algorithm with springs and controlled placement as a visualization technique that combines the use of springs and attractive forces to stabilize a graph in a 3D environment. The combination of these two techniques also helps prevent the formation of a single large cluster within the graph, enhancing the overall visualization quality.

A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ soluble protofibrils was approved by US FDA for AD therapy thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms are widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7- Aβ) and the α4β2 nicotinic acetylcholine receptor.

Stairs are among the key elements in architectural composition, both aesthetically and spatially. They are also one of the main innovations in architecture and building, allowing pedestrians to bridge considerable height differences with relative efficiency. It is therefore surprising that, in spite of all stair regulations in building codes, stairs are responsible for a huge number of accidents – second only to motorcars. The extent of safety failures suggests that user interaction with stairs is poorly understood by designers and policy makers. This is not unrelated to the lack of research into the design and use of stairs. Templer’s seminal work is the exception but it dates from 1992 and since then little has been done to understand the relation between architectural design and stair performance, including safety. To redress this, we can build on affordance-based analyses of stair climbability, which establish a clear connection between the form of a stair and the perception of action possibilities and dangers by all kinds of users. By doing so affordances establish a comprehensive and consistent framework for the analysis of architectural designs, which utilizes both domain and psychological knowledge, including as a foundation for computational applications.

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus), identified 268 proteins with age-related structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I, II and V α-chains (COL1A2, COL2A1, COL5A1), were located within their triple helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance in ageing. Several proteins (COL5A1, COL2A1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young, suggesting that some ageing mechanisms may act locally within tissues. This study not only provides evidence of age-related changes in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF to identify potential protein biomarkers of localised tissue remodelling.

The exceptional increase in molecular DNA sequence data in open repositories is mirrored by an ever-growing interest among evolutionary biologists to harvest and use those data for phylogenetic inference. Many quality issues, however, are known and the sheer amount and complexity of data available can pose considerable barriers to their usefulness. A key issue in this domain is the high frequency of sequence mislabelling encountered when searching for suitable sequences for phylogenetic analysis. These issues include the incorrect identification of sequenced species, non-standardised and ambiguous sequence annotation, and the inadvertent addition of paralogous sequences by users, among others. Taken together, these issues likely add considerable noise, error or bias to phylogenetic inference, a risk that is likely to increase with the size of phylogenies or the molecular datasets used to generate them. Here we present a software package, phylotaR, that bypasses the above issues by using instead an alignment search tool to identify orthologous sequences. Our package builds on the framework of its predecessor, PhyLoTa, by providing a modular pipeline for identifying overlapping sequence clusters using up-to-date GenBank data and providing new features, improvements and tools. We demonstrate our pipeline’s effectiveness by presenting trees generated from phylotaR clusters for two large taxonomic clades: palms and primates. Given the versatility of this package, we hope that it will become a standard tool for any research aiming to use GenBank data for phylogenetic analysis.

Smell loss affects around 15-20% of the population, with a major effect on the quality of life. The most common complaint is the impairment of the eating experience, with around 90% of patients reporting this issue. A study conducted at a specialized taste and smell clinic investigated if food and cooking can have a positive effect on the enjoyment of food, subjective cooking skills, and quality of life in patients with smell loss. The 49 participants in the study received a 5-week cooking school course that focused on emphasizing the other senses to regain the enjoyment of food. Participants gained more confidence in cooking, and their quality of life improved significantly. Positively evaluated recipes were adjusted based on feedback and published as free e-books in Danish, German, and English. Eating and cooking are multisensory experiences, and the perception of food depends on the complex interaction of senses and surroundings. If the olfactory input is reduced or absent, both the enjoyment and cooking experience can be negatively affected. Therefore, focusing on food and cooking can have a positive impact on patients with smell loss.

A university campus is a place full of memorable experiences and a sense of place. It is an environment that potentially creates a social and intellectual exchange of ideas and brings together diverse people. Campus planning is one essential need for any higher institution and is an instrument used for directing, promoting, and securing orderly physical development of an institution Campus planning present unique opportunities for demonstrating and popularizing contemporary tendencies in urban planning. The purpose of this study is to explore the overall concepts of the campus planning and architecture of the Kwame Nkrumah University of Science and Technology (Knust) And University of Ghana (Legon). The Study was based mainly on two methods; Documentary research and qualitative Observation to have in depth knowledge about the campuses. Through field observation, the study was limited to the spatial organization and planning, site layout and master planning, land use, use of space, and architectural details. The study adopts A Comparative Analysis Approach and found out that Campus Planning Concept varies and unique to campuses and in developing a campus plan, it involves a time-consuming dynamic process and besides, there are neither shortcuts nor one approach or generic solution to that. The study also revealed that Iconic and unique buildings are usually found on university campuses.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Biohydrogen is a versatile energy carrier for the generation of electric energy from renewable sources. Hydrogenases can be used in enzymatic fuel cells to oxidize dihydrogen. The rate of electron transfer (ET) at the anodic side between the [NiFe]-hydrogenase enzyme distal iron-sulfur cluster and the electrode surface can be described by the Marcus equation. All parameters for the Marcus equation are accessible from DFT calculations. The distal cubane FeS-cluster has a three cysteine and one histidine coordination [Fe₄S₄](His)(Cys)₃ first ligation sphere. The reorganization energy (inner- and outer-sphere) is almost unchanged upon a histidine-to-cysteine substitution. Differences in rates of electron transfer between the wild-type enzyme and the all-cysteine mutant can be rationalized by a diminished electronic coupling between the donor and acceptor molecules in the [Fe₄S₄](Cys)₄ case. The fast and efficient electron transfer from the distal iron-sulfur cluster is realized by a fine-tuned protein environment which facilitates the flow of electrons. This study enables the design and control of electron transfer rates and pathways by protein engineering.

Within the framework of the previously proposed formulation of the quantum theory of gravity in terms of world histories, it was suggested that the universe has its own mass. This quantity is analogous to the mass of a particle in relativistic mechanics. The mass of the universe is a distribution of non-zero values of gravitational constraints, which arises and changes in time as a consequence of the initial conditions for fundamental dynamic variables. A formulation of the Euclidean quantum theory of gravity is also proposed to determine the initial state, which can be the source of the universe’s own mass. Being unrelated to ordinary matter, the distribution of its own mass affects the geometry of space and forms a dedicated frame of reference. The existence of selected reference systems is taken into account by the corresponding modification of the system of quantum gravitational constraints. A variant of such a modification of the Wheeler-De Witt equation is the operator representation of gravitational constraints, which, together with the state of the universe, determines the parameters of the reference system in the form of a distribution of the spinor field on a spatial section.

One of the important features of polymethine (cyanine) dyes is isomerization around one of C–C bonds of the polymethine chain. In this review, spectral properties of the isomers, photoisomerization and thermal back isomerization of carbocyanine dyes, mostly meso-substituted carbocyanine dyes, are considered. meso-Alkyl-substituted thiacarbocyanine dyes are present in polar solvents mainly as cis isomers and, hence, exhibit no photoisomerization, whereas in nonpolar solvents, in which the dyes are in the trans form, photoisomerization takes place. In contrast, the meso-substituted dyes 3,3′-dimethyl-9-phenylthiacarbocyanine and 3,3′-diethyl-9-(2-hydroxy-4-methoxyphenyl)thiacarbocyanine occur as trans isomers and exhibit photoisomerization in both polar and nonpolar solvents. The behavior of these dyes may be explained by the fact that the phenyl ring of the substituent in their molecules can be twisted at some angle, removing the substituent from the plane of the molecule and reducing its steric effect on the conformation of the trans isomer. In some cases, photoisomerization of cis isomers of meso-substituted carbocyanine dyes is also observed (for some meso-alkyl-substituted dyes complexed with DNA and chondroitin-4-sulfate; for 3,3′-diethyl-9-methoxythiacarbocyanine in moderate polarity solvents). The cycle photoisomerization–thermal back isomerization of cyanine dyes can be used in various systems of information storage and deserves further investigation using modern research methods.

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

Olfactory dysfunction affects often has severe consequences on patients’ quality of life. The most common complaint in these patients is their reduced enjoyment of food in both patients with olfactory loss and parosmia. How the different types of olfactory dysfunction differ in relation to food and cooking habits, sensory awareness, and food-related quality of life has not yet received much attention. By applying questionnaires on cooking, food, olfactory function, weight changes, sensory awareness, and food-related quality of life, we investigate how various aspects of eating differ between participants with olfactory loss (n=271), parosmia(n=251), and normosmic controls(n=166). Cooking habits in olfactory dysfunction revealed pronounced differences as compared with normosmic controls. Cooking with olfactory dysfunction was associated with e.g., a lack of comfort and inspiration for cooking and an inability to make new foods successfully. Significant differences in cooking were also found between olfactory loss and parosmia. Food items were less familiar in participants with olfactory loss and parosmia, while the ratings of liking food items differed between olfactory loss and parosmia, indicating the importance of adapting ingredients in meals separately for olfactory loss and parosmia. Parosmia was associated with a higher incidence of weight loss, but we found no difference in the food-related quality of life between participants with olfactory loss and parosmia. While olfactory loss and parosmia have wide-ranging consequences on patients’ cooking and food habits, adapting meals to include ‘safer food items’ and integrating multisensory stimulation may be a possible avenue for improving the enjoyment of food.

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed &gt; 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

Loneliness is becoming prevalent across Japan in spite of its a dense population and communal culture. Surveys show 40% of adults report isolation across demographics. The contradiction emerges due to deteriorating social structure with modernization, economic parity, urbanization, and fading conventional setup. The continually social withdrawals, called “hikikomori." Relief seekers have embraced AI based emotive robots, digital avatars, and immersive VR as low-stakes social surrogates despite limited capacity to cultivate human intimacy. To stabilise government attempts awareness through reforms, scheme and support services. But a concrete transformation can be brough in with work-life balance, gender equality and rewire the metrics for self-esteem. Even a perfectly personalized AI cannot replace the human affection lacking in the society. Lasting solutions demand technological aids be balanced by confronting and reinventing community purpose and bring in structural change. Overall Japan’s endemic isolation reveals the societal fraying when modernization privileges independence over interdependence. The path forward rests on restoring cultural foundations to reverse loneliness and social isolation.