Computer vision is a rapidly developing field that focuses on highly sophisticated picture analysis, manipulation, and comprehension. Its objective is to analyze what is happening in front of a camera and utilize that understanding to control a computer or robotic system or to present users with fresh visuals that are more enlightening or appealing than the original camera images. Computer vision technologies make it feasible for new user interfaces, augmented reality gaming, biometrics, automobile, photography, movie creation, Web search, and many more applications. This essay seeks to explain how computer vision can be utilized to play blackjack successfully.

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipozyme, or lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the non-polar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by collections of small, nonpolar or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two phase octanol-water system with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol was then replaced with DOPC added to the water in the form of vesicles, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence which revealed catalytic turnover numbers on a scale of 10−4s−1 for each system, which is comparable to some slow enzymes. The reaction product was characterized by 1H-NMR measurements which were consistent with ester hydrolysis. The implications of thinking about lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology and synthetic biology.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Current sampling methods for detecting the presence of the invasive freshwater hydrozoan Craspedacusta sowerbii rely mainly on visual confirmation of the medusa stage. Confirming the presence of the polyp stage is equally important to observing medusae since typical late summer/early fall occurrences or observations of medusae are sporadic though becoming more frequent. The polyp stage is important as it is the organism’s primary stage and is present throughout the year depending on water temperatures. Therefore, sampling methods for the polyp stage are commonly the collection of substrates such as rocks, plants or pieces of wood in a given body of water and can be cumbersome to examine. Based on preliminary culturing of the polyp stage on glass and plastic microscope slides in the lab, we designed a novel sampling methodology based on submerging 4 substrate types (small glass petri dishes, Hester-Dendy plates, plastic and glass microscope slides) to confirm the presence of C. sowerbii polyps in the field. We tested this method in various lakes in the Illinois-Indiana region (USA). The sampling method we designed was effective in that C. sowerbii polyps (and sometimes colonies) were found on both plastic and glass slides. While this method can be sufficient for detection of the polyp stage, it also shows significant potential for improvement; we highlight water flow and competition and predation from other organisms as significant factors influencing the collection of C. sowerbii polyps for future methodologies.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

This retrospective study assesses the efficacy and tolerability of anti-CGRP therapy in adolescents and young adults (ages 12-21) with migraines and chronic daily headaches unresponsive to standard treatments. Migraines severely affect school performance, self-esteem, psychological well-being, and cognitive health in this demographic, who are also sensitive to the side effects of conventional medications often prescribed off-label and face high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels during migraines suggest that anti-CGRP therapies, which have shown success in adults, might benefit this age group. Over three years, patients at a specialized headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small molecule CGRP receptor antagonists (ubrogepant, rimegepant, atogepant), either alone or in combination with OnabotulinumtoxinA. The study found significant improvements in migraine management, especially among older adolescents, with reduced rescue medication use and emergency visits. Longer treatment courses and combination therapy with traditional medications were more effective than monotherapy, reducing migraine intensity and frequency. Adverse effects were minimal, and no significant medication interactions were noted. Anti-CGRP therapy demonstrates substantial potential in improving outcomes for this age group with chronic and episodic migraines.

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

This paper represents a groundbreaking paradigm shift in network optimization. Departing from traditional static methodologies, this innovative approach harnesses the power of Generative Artificial Intelligence (AI) and Large Language Models (LLMs) to optimize cloud networks dynamically. By integrating advanced AI algorithms, this framework continuously adapts and evolves, ensuring optimal real-time performance. This dynamic optimization enhances efficiency and resilience, allowing cloud networks to adjust seamlessly to changing demands and conditions. Through the fusion of cutting-edge technology and adaptive intelligence, this approach heralds a new era in network optimization, empowering organizations to achieve unprecedent-ed levels of agility and scalability in their cloud infrastructures.

Objective: To develop an algorithm that accurately identifies children with Down syndrome (DS) using administrative data. Methods: We identified a cohort of children born 2000-2017, enrolled in a state Medicaid program, who either had DS coded on the birth certificate or had a diagnosis listed using an International Classification of Diseases (ICD) code (suspected DS), and who received care at a comprehensive academic medical center in the United States. Children with suspected DS were defined as having DS if they had a) karyotype confirmed DS indicated on their birth certificate; b) karyotype pending DS indicated on their birth certificate (or just DS if test type was not specified) and at least two healthcare encounters for DS during the first 6 years of life; or c) at least three healthcare encounters for DS, with the first and last encounter separated by at least 30 days, during the first six years of life. Positive predictive value (PPV) of the algorithm and 95% confidence interval (CI) were reported. Results: Of the 411 children with suspected DS, 354 (86.1%) were defined as having DS by the algorithm. According to medical chart review, the algorithm correctly identified 347 children with DS (PPV=98%, 95%CI: 96.0%-99.0%). Of the 57 children the algorithm defined as not having DS, 50 (97.7%, 95%CI: 76.8%-93.9%) were confirmed not having DS by medical chart review. Conclusions: An algorithm that accurately identifies individuals with DS using birth certificate data and/or ICD codes provides a valuable tool to study DS using administrative data.

Prostate cancer (PCa) ranks as the second most fatal and sixth most prevalent cancer among males globally. This study focuses on leveraging deep learning networks to detect the Gleason grading of prostate cancer from histopathology images stained with Hematoxylin and Eosin (H&amp;E). Six pathologists annotated the images, resulting in six distinct labels for each input image. A common ground truth label was established through majority voting approach. Subsequently, the dataset was trained using architectures: UNeT, UNeT++, DeepLabV3, DeepLabV3+, and GAN based segmentation network. Notably, GAN based network demonstrated superior performance, achieving an F1-score of 0.872 and a Jaccard Index of 0.777, outperforming the other architectures considered in this study.

With the increasing use of data-driven modeling methods new approaches to complex problems in the field of wind energy can be addressed. Topics reviewed through literature include wake modeling, performance monitoring and controls applications, condition monitoring and fault detection, and other data-driven research. Literature shows the advantages of data-driven methods reduce computational expense or complexity, particularly in the cases of wake modeling and controls, as well as various data-driven methodologies’ aptitude for predictive modeling and classification, as in the cases of fault detection and diagnosis. Significant work exists for fault detection while less work is found for controls applications. A methodology for creating data-driven wind turbine models for arbitrary performance parameters is proposed. Results are presented utilizing the methodology to create wind turbine models relating active adaptive twist to steady-state rotor thrust as a performance parameter of interest. Resulting models are evaluated by comparing root-mean-square-error (RMSE) on both the training and validation data sets, with Gaussian Process Regression (GPR), deemed an accurate model for this application. The resulting model undergoes particle swarm optimization to determine the optimal aerostructure twist shape at a given wind speed with respect to the modeled performance parameter, aerodynamic thrust load. The optimization process shows an improvement of 3.15% in thrust loading for the 10 MW reference turbine, and 2.66% for the 15 MW reference turbine.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

New setting is introduced to study chromatic number. Neutrosophic chromatic number and chromatic number are proposed in this way, some results are obtained. Classes of neutrosophic graphs are used to obtains these numbers and the representatives of the colors. Using colors to assigns to the vertices of neutrosophic graphs is applied. Some questions and problems are posed concerning ways to do further studies on this topic. Using strong edge to define the relation amid vertices which implies having different colors amid them and as consequences, choosing one vertex as a representative of each color to use them in a set of representatives and finally, using neutrosophic cardinality of this set to compute neutrosophic chromatic number. This specific relation amid edges is necessary to compute both chromatic number concerning the number of representative in the set of representatives and neutrosophic chromatic number concerning neutrosophic cardinality of set of representatives. If two vertices have no strong edge, then they can be assigned to same color even they’ve common edge. Basic familiarities with neutrosophic graph theory and graph theory are proposed for this article.

Nucleosomes are non-uniformly distributed across eukarytic genomes, with stretches of ‘open’ chromatin strongly associated with transcriptionally active promoters and enhancers. Understanding chromatin accessibility patterns in normal tissue and how they are altered in pathologies can provide critical insights to development and disease. With the advent of high-throughput sequencing, a variety of strategies have been devised to identify open regions across the genome, including DNase-seq, MNase-seq, FAIRE-seq, ATAC-seq, and NicE-seq. However, the broad application of such methods to FFPE (formalin-fixed paraffin embedded) tissues has been curtailed by the major technical challenges imposed by highly fixed and damaged genomic material. Here we review the most common approaches for mapping open chromatin regions, recent optimizations to overcome the challenges of working with FFPE tissue, and a brief overview of a typical data pipeline with analysis considerations.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)- associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs) including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines.

With advancements in remote sensing technology and affordable design, uncrewed aerial systems (UAS), commonly known as drones, have become prevalent in both civil and military applications, such as agriculture, public safety, and aerial imaging. However, the rise in unlawful UAS activities, such as non-compliance with legal standards and potential terrorist attacks, has raised significant public concern, necessitating effective detection and mitigation solutions. Despite the growing importance of this issue, comprehensive and detailed examinations of existing counter-UAS solutions are lacking. To address this gap, this study conducts a bibliometric analysis and scoping review of the current literature to identify key topics and emerging trends in counter-UAS approaches. Utilizing co-word and social network analyses, the study identifies strong and weak connections between selected keywords from academic articles. This study summarizes the limitations and potential opportunities within counter-UAS research, suggesting an increasing focus on multisensory fusion and machine-learning approaches for drone detection and mitigation. Additionally, areas such as swarm drone operations, UAS traffic management (UTM), and UAS networks are identified as important but promising fields for further investigation. The findings of this study provide a foundation for enhancing air and ground safety through improved counter-UAS applications.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

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.

Entanglement is one of the most striking features in quantum systems. Today, quantum entanglement plays a vital role in quantum technology, the non-classical correlation of quantum entanglement is an important resource for quantum communication and quantum computing. Entanglement can be divided into two categories: between multi-particle systems and between various degrees of freedom in a single-particle system (intraparticle entangled states). This work first analogized the distinctions and connections between two kinds of entangled states. Then it designed three types of entanglement-swapping methods based on Bell state joint measurement, cross-Kerr medium, and linear optical elements for intraparticle entangled states by analogizing the entanglement swapping between multiple particles. Intraparticle entanglement swapping can be applied in super quantum dense encoding, quantum information transmission, and quantum teleportation. This work is beneficial for promoting the development of quantum information technologies.

Prostate Cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. Accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep-learning techniques with comprehensive datasets, our approach presents a step forward in the pursuit of personalized and targeted cancer care.

The chiral optical Tamm state (COTS) is a special localized state at the interface of a handedness-preserving mirror and a structurally chiral medium such as a cholesteric liquid crystal or a chiral sculptured thin film. The spectral behavior of COTS, observed as reflection resonances, is described by the temporal coupled-mode theory. Mode coupling is different for two circular light polarizations because COTS has a helix structure replicating that of the cholesteric. The mode coupling for co-handed circularly polarized light exponentially attenuates with the cholesteric layer thickness since the COTS frequency falls into the stop band. Cross-handed circularly polarized light freely goes through the cholesteric layer and can excite COTS when reflected from the handedness-preserving mirror. The coupling in this case is proportional to anisotropy of the cholesteric and theoretically it is only anisotropy of magnetic permittivity that can ultimately cancel this coupling. These two couplings being equal results in a polarization crossover (the Kopp--Genack effect) for which a linear polarization is optimal to excite COTS. The corresponding cholesteric thickness and scattering matrix for COTS are generally described by simple expressions.

Cancer diagnosis and classification are pivotal for effective patient management and treatment planning. In this study, we present a comprehensive approach utilizing ensemble deep learning techniques to analyze breast cancer histopathology images. Our datasets are based on two widely employed datasets from different centers for two different tasks: BACH and BreakHis. Within the BACH Dataset, we deployed an ensemble strategy incorporating VGG16 and ResNet50 architec-tures to achieve precise classification of breast cancer histopathology images. Introducing a novel image patching technique, to preprocess a high-resolution image, which facilitates focused analysis of localized regions of interest. The annotated BACH dataset encompasses 400 WSIs across four distinct classes: Normal, Benign, In Situ Carcinoma, and Invasive Carcinoma. In addition, we employed the BreakHis dataset, utilizing VGG16, ResNet34, and ResNet50 models to classify mi-croscopic images into eight distinct categories (four benign and four malignant). For both models we leveraged a five-fold cross-validation approach for rigorous training and testing. Preliminary ex-perimental results indicate a Patch classification accuracy of 95.31% (on BACH dataset) and WSI image classification accuracy of 98.43% (BreakHis). This research significantly contributes to on-going endeavors in harnessing artificial intelligence to advance breast cancer diagnosis, potentially fostering improved patient outcomes and alleviating healthcare burdens.

We introduce a full binary directed tree structure to represent the set of natural numbers, further categorizing them into three distinct subsets: pure odd numbers, pure even numbers, and mixed numbers. We adopt a binary string representation for natural numbers and elaborate on the composite methodology encompassing odd- and even-number functions. Our analysis focuses on examining the iteration sequence (or composition) of the Collatz function and its reduced variant, which serves as an analog to the inverse function, to scrutinize the validity of the Collatz conjecture. To substantiate this conjecture, we incorporate binary strings into an algebraic formula that captures the essence of the Collatz sequence. By this means, we transform discrete powers of 2 into continuous counterparts, ultimately culminating in the smallest natural number, 1. Consequently, the sequence generated through infinite iterations of the Collatz function emerges as an eventually periodic sequence, thereby validating an enduring 87-year-old conjecture.

Contrasting results have suggested that the prevalence and intensity of post abortion emotional distress (PAD) either diminishes rapidly or persists over time. Few studies have followed women for longer than five years. This study examines retrospective population data on 226 ever aborting U.S. women aged 41-45, at an average of 20 years following the abortion, with extensive measures of PAD. Most post abortive women (55.2%) experienced little or no distress from their abortion(s) and 74.6% were confident it had been the right decision, but 44.8% reported moderate (20.7%) to high (24.1%) distress related to their abortion(s), including 37.7% who reported negative emotions; 31.2% “frequent feelings of loss, grief or sadness;” 24.6% “frequent thoughts, dreams, or flashbacks;” 23.2% for whom thoughts and feelings about their abortion “negatively interfered with life, work, or relationships.” Time since the abortion (mean 20 years, range 0-31 years) was not correlated with PAD (r = -.02, p .71). For the minority of women who experienced it, PAD did not diminish but persisted for decades. An estimated 7.5 million U.S. women currently experience persistent high PAD. Further research to specify risk factors and possible interventions for postabortion distress would be of value for this group of women.

Tomato brown rugose fruit virus (ToBRFV) is an emerging tobamovirus infecting tomatoes and peppers. Due to its ability to trigger seed contamination, efficient mechanical transmission, and to break the popular resistance genes (Tm-1, Tm-2 and Tm-22), the virus has resulted in a global pandemic on greenhouse tomato production in recent years despite the implementation of strict hygiene and disinfection measures. The objective of this study was to evaluate whether ToBRFV can be transmissible through recirculating hydroponic systems and search for effective approach to contain its spread under such circumstances. We not only detected the presence of ToBRFV in the runoff water solutions collected from ToBRFV-infected tomato greenhouses, but also demonstrated the infectivity of detected virus through initiating ToBRFV infection on tomato plants using bioassay. We then conducted treatment using cold plasma-generated ozone on ToBRFV-contaminated water reservoir and further assessed the efficacy of the treatment to inac-tivate the virus. Results showed the effectiveness of the cold-plasma ozone treatment was de-pendent on the ozone concentrations (0.1 mg/L to 1.0 mg/L), the periods of exposure (24 min to 72 min), and the relative virus titers (1:100 to 1:10,000 - dilution of virus-infected tissue extract), demonstrating the cold-plasma ozone treatment could offer a promising solution to cope with the potential ToBRFV spread through a recirculating hydroponic system in a greenhouse.

A structure based analysis of the pion’s decay path reveals that neutrinos can show up in three eigenstates. It requires a proper understanding of the nature of charged leptons, such as why the loss of binding energy stops the lepton generation at the tauon level. The analysis quantifies this binding energy in terms of the weak interaction strength as embodied by the weak interaction boson and the strength of the energetic background field as embodied by the Higgs boson. Next to this it is shown that a reconstruction of Fermi’s neutrino theory allows a quantitative assessment of the Fermi constant straightforwardly from the weak interaction strength. The article ends with the conclusion that neutrino oscillation is not a physical phenomenon, but, instead, a measurement interpretation induced from projecting the statistical behaviour of a multi-particle ensemble onto a single particle.

In this essay, the new notion concerning longest path is introduced. Longest path has a close relation with the notion of diameter in graph. The classes of graph are studied in the terms of having the vertex with longest path. Valued number is the number of edges belong to the longest path in the matter of vertex. For every vertex, there’s a valued number and new notion of valued set is the generalization of valued number for the vertex when all vertices of the graphs are corresponded to a vertex which has the greater valued number. For any positive integer, there’s one graph in that, there’s vertex which its valued number is that. By deleting the vertices which don’t belong to valued set, new notion of new graph is up. It’s called valued graph. The comparison amid valued graph and initial graph is up, too.

In this article, some notions about set, weight of set, number, number's position, special vertex are introduced. Some classes of graph under these new notions have been opted as if the study on the special attributes of these new notion when they've acted amid each other is considered. Internal and external relations amid these new notions have been obtained as if some classes of graphs in the matter of these notions are been pointed out.

We report the case of a 44-year-old woman who suffered gastric perforation after receiving bag-valve-mask (BVM) ventilation in the setting of alcohol intoxication. She had a markedly distended abdomen and cold, dusky lower extremities upon arrival to the emergency department. Imaging revealed a large volume intraabdominal accumulation of air with compression of the aorta. Needle decompression relieved symptoms of lower extremity arterial insufficiency. However, the patient quickly decompensated and subsequent exploratory laparotomy confirmed gastric rupture. A subtotal gastrectomy was performed but the patient ultimately passed on post-operative day two due to multi-organ dysfunction. Although BVM ventilation is commonplace in both the hospital and field, there is a lack of awareness of the serious complications of abdominal air accumulation due to their rareness in the adult population. Checking for abdominal distention during resuscitation ought to be routine in all patients. Signs of arterial insufficiency accompanying abdominal distention, once confirmed by diagnostic imaging that shows extensive pneumoperitoneum, are indicators of having reached a life-threatening level of air accumulation, calling for immediate needle decompression and exploratory laparotomy.

The motor protein Prestin found in the outer hair cells (OHCs) of the inner ear is responsible for producing high sensitivity and sharp frequency selectivity for mammalian hearing. Some studies have suggested that Prestin could serve as a serological biomarker for cochlear damage since OHCs are highly vulnerable to damage from various sources of insults. However, the reported data are inconsistent and lack appropriate negative controls. To investigate this further, we measured Prestin quantities in the bloodstream using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that kill OHCs rapidly. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect Prestin specifically. The ELISA kit that could detect Prestin protein from cochlear homogenates failed to detect Prestin in the bloodstream despite significant damage to OHCs in cochleae. Furthermore, the optical densities of samples, which correlate to Prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice.

Drag reduction by laminarization, an innovative technology in aerodynamics design, provides the possibility to improve significantly the aerodynamic performance of aircraft and remains to be one of the most promising and effective technologies. In this paper, the design method for transonic natural laminar flow (NLF) wing at high Reynolds number is investigated in details and a new optimization model is established to solve conflicts between the increase of a laminar flow region and the shock wave strength at the trailing edge. In order to numerically handle this competitive situation efficiently, a two-objective hierarchical variable fidelity Pareto evolutionary optimization model based on search space contraction is proposed and implemented. Numerical experiments show that it can capture simultaneously a Pareto front of the two-objectives: a wave drag minimization and a laminar flow region maximization. The results also show that both wave drag and skin friction drag performances of non-dominated Pareto members can be significantly improved via the optimal laminar wing shape and shock wave control device. Nearly 40% of the laminar flow area on the wing surface is achieved at the Reynolds number of 107. It is concluded that the present hierarchical variable-fidelity multi-objective evolutionary optimization method is computationally efficient, and illustrate its potential for solving complex engineering design problems.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

This study aimed to evaluate the effect of three yeast strains, Pichia guilliermondii (Levica 27), Candida norvegensis (Levazoot 15), and a commercial product (Levucell® SC 10) containing Saccharomyces cerevisiae, on in vitro rumen fermentation of two substrates: corn stover and a total mixed ration (TMR). Samples were taken 24 hours post-fermentation to measure pH, ammonia nitrogen (NH3-N), gas production, and volatile fatty acid (VFA) concentrations. The addition of yeasts did not affect gas production at 24 hours for either diet. For pH, differences between yeast strains were noted when TMR was used. The lowest NH3-N concentration (6.1 mM) was recorded with corn stover, showing similar results across strains. Conversely, NH3-N levels with TMR ranged from 47 mM to 66 mM. The inclusion of all three yeast strains increased the molar concentrations of total VFA, as well as acetic (C2), propionic (C3), and butyric (C4) acids in the rumen fluid. The C2:C3 ratio remained unchanged with corn stover but decreased with the inclusion of Levica 27 and Levazoot 15 in the TMR. With the commercial product Levucell® SC 10, this ratio was comparable to the control treatment. In conclusion, Levica 27 and Levazoot 15 demonstrated a stimulatory effect on in vitro rumen fermentation for the evaluated diets, evidenced by increased VFA concentrations.

The emergence of antimicrobial resistance (AMR) Candida auris presents a formidable global health challenge, causing severe healthcare-associated infections with high mortality rates. Its ability to colonize surfaces and resist standard disinfectants undermines traditional hygiene practices, prompting an urgent need for novel strategies. Ultraviolet C (UVC) light offers a promising approach due to its rapid and broad-spectrum germicidal efficacy. This review comprehensively examines the current knowledge of UVC LED technology in combating C. auris, highlighting its effectiveness, limitations, and potential applications in healthcare hygiene. UVC light has potent activity against C. auris, including multidrug-resistant (MDR) strains. UVC can reduce C. auris on contaminated surfaces, aiding in transmission prevention. This review explores implementation strategies, including mobile UVC systems for targeted disinfection of high-risk areas and equipment, integration into air handling units (AHUs) to continuously disinfect recirculating air, and incorporation into water treatment systems. Current limitations in our understanding of UVC safety and effectiveness necessitate further research to optimize application protocols and ensure treatment safety while maintaining efficacy against C. auris. Integrating UVC disinfection technology into infection control programs holds promise for strengthening hygiene practices that will curb the global spread of C. auris and improve patient outcomes.

This study aims to examine the non-volatile Particle Number (PN) emissions of a retrofitted Heavy-Duty Spark-Ignition (HD-SI) engine powered by liquefied petroleum gas (LPG) under both steady-state and transient conditions. The engine was tested under seven steady-state operating points to investigate the PN behavior and Particle Size Distribution (PSD) upstream and down-stream of the Three-Way Catalyst (TWC). This analysis intends to assess the impact of including particles with diameters ranging from 10 nm to 23 nm in the total particle count, a consideration for future regulations. The study employed the World Harmonized Transient Cycle (WHTC) for transient conditions to encompass the same engine working region used in the steady-state analysis. A Dekati FPS-4000 diluted the exhaust sample to measure the PSD and PN for particle diameters between 5.6 nm and 560 nm using the TSI-Engine Exhaust Particle Sizer (EEPS) 3090. Findings indicate that PN levels tend to increase downstream of the TWC under steady-state conditions in operating points with low exhaust gas temperatures and flows (equal to or less than 500 °C and 120 kg/h). Furthermore, the inclusion of particles with diameters between 10 nm and 23 nm leads to an increase in PN emissions by 17.70% to 40.84% under steady conditions and by an average of 40.06% under transient conditions, compared to measurements that only consider particles larger than 23 nm. Notably, in transient conditions, most PN emissions occur during the final 600 seconds of the cycle, linked to the most intense phase of the WHTC.

Pharmaceutical packaging is very crucial in as much as it plays the role of enhancing the stability, efficacy as well as safety of the produced medicine through the material used in packaging. It is important to note that cGMP Chapters 661 and 671 are focused on explaining how one should assess the quality of container materials in the sphere of pharmaceuticals. These chapters encompass a number ofmatters among them being Plastic and glass containers and performance testing; they serve as a resource that aids in assuring all standards are met with profound proficiency. Following this, the performance of two core chapters of USP known as Chapter 661 on “Containers—Glass” and Chapter 671 on “Containers—Performance Testing” will be dealt with in a step-by-step manner in the following paper while providing a comprehensive review of both at the same time. Understanding and legal obedience to these rules, as stipulated in the above-mentioned chapter, are indispensable for almost all the parties involved in the production of the drugs, together with the policies and legislation on the same. Thus, the purpose of this paper is to describe and discuss the major aspects of the understanding, application, requirements and evaluation procedures depending on the USP Chapters 661 and 671 in the sphere of the pharmaceutical market.

The many-body problem in quantum physics originates from the difficulty of describing the non-trivial correlations encoded in the exponential complexity of the many-body wave function. Motivated by the Giuseppe Carleo's work titled solving the quantum many-body problem with artificial neural networks [Science, 2017, 355: 602], we focus on finding the NNQS approximation of the unknown ground state of a given Hamiltonian $H$ in terms of the best relative error and explore the influences of sum, tensor product, local unitary of Hamiltonians on the best relative error. Besides, we illustrate our method with some examples.

Rabbit hemorrhagic disease virus disease 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly between infected individuals. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

this paper we present approaches for generating random numbers along with potential applications. Rather than trying to provide extensive coverage of several techniques or algorithms that have appeared in the scientific literature, we focus on some representative approaches presenting their workings and properties in detail. Our goal is to delineate their strengths and weaknesses as well as their potential application domains so as the reader can judge what would be the best approach for the application in hand, possibly a combination of the available approaches. For instance, a physical source of randomness can be used for the initial seed, then suitable preprocessing can enhance its randomness and then the output of the preprocessing can feed different types of generators, e.g. a linear congruential generator, a cryptographically secure one and one based on the combination of one way hash functions and shared key cryptoalgorithms in various modes of operation. Then, if desired, the outputs of the different generators can be combined giving the final random sequence. Moreover, we present a set of practical randomness tests which can be applied on the outputs of random number generators in order to assess their randomness characteristics. In order to demonstrate the importance of unpredictable random sequences, we present an application of cryptographically secure generators in domains where unpredictability is one of the major requirements, i.e. eLotteries and cryptographic key generation.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

The P versus NP problem is a fundamental question in computer science. It asks whether problems whose solutions can be quickly verified can also be quickly solved. Here, "quickly" refers to computational time that grows proportionally to the size of the input (polynomial time). While the problem's roots trace back to a 1955 letter from John Nash, its formalization is attributed to Stephen Cook and Leonid Levin. Despite extensive research, a definitive answer remains elusive. Closely tied to this is the concept of NP-completeness. If a single NP-complete problem could be solved efficiently, it would imply that all problems in NP can be solved efficiently, proving that P equals NP. This work posits that MONOTONE ONE-IN-THREE 3SAT, a notoriously difficult NP-complete problem, can be solved efficiently, thereby establishing the equivalence of P and NP.

A prime gap is the difference between consecutive prime numbers. The $n^{\text{th}}$ prime gap, denoted $g_{n}$, is calculated by subtracting the $n^{\text{th}}$ prime from the $(n+1)^{\text{th}}$ prime: $g_{n}=p_{n+1}-p_{n}$. Oppermann's conjecture is a prominent unsolved problem in pure mathematics concerning prime gaps. Despite verification for numerous primes, a general proof remains elusive. If true, the conjecture implies that prime gaps grow at a rate bounded by $g_{n}<{\sqrt {p_{n}}}$. This note presents a proof of Oppermann's conjecture using the square root function on inequalities involving prime numbers. This proof simultaneously establishes Andrica's, Legendre's, and Brocard's conjectures.

The Goldbach's conjecture has been described as the most difficult problem in the history of Mathematics. This conjecture states that every even integer greater than 2 can be written as the sum of two primes. This is known as the strong Goldbach's conjecture. The conjecture that all odd numbers greater than 7 are the sum of three odd primes is known today as the weak Goldbach conjecture. A principal complexity class is NSPACE(S(n)) for some S(n). We show if the weak Goldbach's conjecture is true, then the problem PRIMES is not in NSPACE(S(n)) for all S(n) = o(log n). This proof is based on the assumption that if some language belongs to NSPACE(S(n)), then the unary version of that language belongs to NSPACE(S(log n)) and vice versa. However, if PRIMES is not in NSPACE(S(n)) for all S(n) = o(log n), then the strong Goldbach's conjecture is true or this has an infinite number of counterexamples. Since Harald Helfgott proved that the weak Goldbach's conjecture is true, then the strong Goldbach's conjecture is true or this has an infinite number of counterexamples, where the case of infinite number of counterexamples statistically seems to be unlikely. In addition, if PRIMES is not in NSPACE(S(n)) for all S(n) = o(log n), then the Twin prime conjecture is true. Moreover, if PRIMES is not in NSPACE(S(n)) for all S(n) = o(log n), then the Beal's conjecture is true. Since the Beal's conjecture is a generalization of Fermat's Last Theorem, then this is also a simple and short proof for that Theorem. In mathematics, the Riemann hypothesis is consider to be the most important unsolved problem in pure mathematics. If PRIMES is not in NSPACE(S(n)) for all S(n) = o(log n), then the Riemann hypothesis is true.

Around $1637$, Pierre de Fermat famously scribbled, and claimed to have a proof for, his statement that equation $a^{n} + b^{n} = c^{n}$ has no positive integer solutions for exponents $n>2$. The theorem stood unproven for centuries until Andrew Wiles' groundbreaking work in $1994$, with a notable caveat: Wiles' proof, while successful, relied on modern tools far beyond Fermat's claimed approach in terms of complexity. The present work potentially offers a solution which is closer in spirit to Fermat's original idea.

The Riemann hypothesis is the assertion that all non-trivial zeros are complex numbers with real part $\frac{1}{2}$. It is considered by many to be the most important unsolved problem in pure mathematics. There are several statements equivalent to the famous Riemann hypothesis. Robin's criterion states that the Riemann hypothesis is true if and only if the inequality $\sigma(n) < e^{\gamma} \cdot n \cdot \log \log n$ holds for all natural numbers $n > 5040$, where $\sigma(n)$ is the sum-of-divisors function of $n$, $\gamma \approx 0.57721$ is the Euler-Mascheroni constant and $\log$ is the natural logarithm. We require the properties of superabundant numbers, that is to say left to right maxima of $n \mapsto \frac{\sigma(n)}{n}$. In this note, using Robin's criterion on superabundant numbers, we prove that the Riemann hypothesis is true.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on breast reconstruction trends in the United States, focusing on implant-based and autologous techniques, as well as the timing of reconstruction (immediate vs. delayed). Methods: A retrospective analysis of data from the American Society of Plastic Surgeons' National Plastic Surgery Statistics from 2015 to 2022 was conducted. Annual trends in breast reconstruction procedures were analyzed, comparing the pre-pandemic (2015-2019) and pandemic (2020-2022) periods. Results: The total number of breast reconstructions increased from 106,338 in 2015 to 151,641 in 2022. The proportion of implant-based reconstructions decreased from 81.41% pre-pandemic to 76.51% during the pandemic (p < 0.001), with a notable rise in direct-to-implant procedures from 10.37% to 19.12% (p < 0.001). Autologous reconstructions increased from 18.59% to 23.49% (p < 0.001). Among autologous techniques, DIEP flaps remained the most popular. Immediate reconstruction rates increased from 72.61% pre-pandemic to 75.57% during the pandemic, while delayed recon-struction rates decreased from 27.39% to 24.43% (p < 0.001). Conclusions: The COVID-19 pandemic has significantly influenced breast reconstruction trends in the United States, with a shift towards autologous techniques, particularly DIEP flaps, and an in-crease in immediate reconstructions. These changes may reflect adaptations in surgical practice and decision-making processes in response to the unique challenges posed by the pandemic. Further research is needed to assess the long-term outcomes and patient satisfaction associated with these trends.

This review explores the crucial role of glycosphingolipids (GSLs) in the context of cardiovascular diseases (CVD), focusing on their biosynthesis, metabolic pathways, and implications for clinical outcomes. GSLs are pivotal in regulating a myriad of cellular functions that are essential for heart health and disease progression. Highlighting findings from both human cohorts and animal models, this review emphasizes the potential of GSLs as biomarkers and therapeutic targets. We advocate for more detailed mechanistic studies to deepen our understanding of GSL functions in cardiovascular health, which could lead to innovative strategies for diagnosis, treatment, and personalized medicine in cardiovascular care.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

Vascular rings are a rare congenital anomaly of the aortic arch in which a ring-shaped structure forms surrounding the trachea and/or esophagus, potentially causing compression. We describe the case of a 14-month-old female patient with failure to thrive secondary to dysphagia, and a vascular ring formed by a right aortic arch, an aberrant left subclavian artery, and a left liga-mentum arteriosum. Surgical repair involved ligamentum arteriosum division, Kommerell’s di-verticulum obliteration, and left subclavian artery re-implantation into the left carotid artery. Endoscopy and EndoFLIPTM evaluated intraoperative improvement in esophageal narrowing and impedance, respectively. Postoperative period was uneventful and follow-up visits demonstrated dysphagia resolution and a patent re-implanted left subclavian artery.

Sustainable water resource management in Bangladesh's Gumti River Basin faces challenges from climate change, urbanization, and population growth. This study aimed to calibrate and validate the HEC-HMS model for the Gumti River to enhance flood prediction and water resource planning. The model was set up using precipitation, temperature, and discharge data from 2019-2021, with SRTM elevation data for catchment delineation. Manual calibration was performed for 2019-2020, followed by validation for 2021, using parameters such as Muskingum routing and SCS Curve Number. Model performance was evaluated using R², Nash-Sutcliffe efficiency (NSE), RSR, and PBIAS metrics. Results showed satisfactory to good performance, with R² values of 0.64 and 0.68 for calibration and validation, respectively. NSE values were within the satisfactory range, while PBIAS indicated very good performance with slight underestimation. The study concludes that the calibrated HEC-HMS model provides a reliable tool for simulating the Gumti River's hydrology, though there's room for improvement. Integration with flood frequency analysis, water quality monitoring, and climate change projections is recommended for comprehensive water resource management, alongside the implementation of Sustainable Water Resource Management principles and community engagement strategies.

The purpose of this paper is to build a new bridge between category theory and a generalized probability theory known as noncommutative probability or quantum probability, which was originated as a mathematical framework for quantum theory, in terms of states as linear functional defined on category algebras. We clarify that category algebras can be considered as generalized matrix algebras and that the notions of state on category as linear functional defined on category algebra turns out to be a conceptual generalization of probability measures on sets as discrete categories. Moreover, by establishing a generalization of famous GNS (Gelfand-Naimark-Segal) construction, we obtain a representation of category algebras of †-categories on certain generalized Hilbert spaces which we call semi-Hilbert modules over rigs.

The recent growth of wearable medical device technology in the form of fitness trackers, smart watches, smartphone apps, and patient monitoring systems has created people-generated health data (PGHD) that may benefit medical science with large amounts of continuous real-world data. The prevalence of these devices speaks to their broad popularity and user-friendliness and may lead us one day to a more fully “connected healthcare system.” Meanwhile, data security, confidentiality, and privacy issues have emerged in these hackable systems. Despite the promise of anonymized data, data can sometimes be re-identified, but even without that step, data breaches may reveal information (name, address, date of birth, social security number, and so on) sufficient for identity theft. Clinicians are often asked about the utility and value of wearable devices or monitors, but most are unaware that data from these systems may be transmitted, stored, and even sold without the user’s specific knowledge. Despite the confidentiality of medical information, cybersecurity surrounding wearables and monitors remains relatively lax, making them comparatively easy targets for cyber-villains. It is also important that efforts be taken to make PGHD more secure, since medical data may have great value to telehealth applications and AI-physician assistants. Clinicians should take an active role in informing patients about both risks and benefits of wearables and similar devices.

Automatic and blind parameter estimation based on the inherent features of wireless signals is a major research area due to the fact that these techniques lead to the simplification of receivers, especially in terms of coarse synchronization, more importantly reduce down the signaling load at the control channels. Thus, in the literature many techniques are proposed to estimate a vast set of parameters including modulation types and orders, data and chip rates, phase and frequency offsets and so on. In this paper, a cyclostationary feature detection based method is proposed to estimate the carrier numbers and carrier spacing of carrier-aggregated direct sequence spread spectrum cellular signals blindly. The particular chip rate of the signal is also estimated through the process jointly. In the paper, after the proposed method is formulated, the measurement setup which is developed to collect the data for the validation of the proposed method is introduced. The measurement results are post-processed for performance analysis purposes. To that end, the method is investigated in terms of SNR values, different channel conditions, and measurement durations. Furthermore, the performance of the proposed method is compared with that of energy detection. Measurement results indicate superior performance of the proposed method under significant wireless channel impairments and in low-SNR regions.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

In this paper, we suggest an expansion of the Planck distribution function derived from the Boltzmann principle. Thereby, we consider expanding Planck's law with a new distribution function, and discuss fine structure constant. Furthermore, using ideas applied to the expansion of the Planck distribution function, we show that Von Koch's inequality can be derived without using the Riemann Hypothesis, that is, the Riemann Hypothesis is true, and that the abc conjecture is not true. Furthermore, we define a generalization of Entropy and discuss that Entropy is relevant to dynamical systems described by logistic function models, such as the growth of bacteria and populations.

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Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Previous reviews by the authors [1, 2] indicate the continuing development and improvement of thermal protective systems through the introduction of polymer nanocomposites into polymer matrix composites. These materials perform as thermal protective systems for a variety of aerospace applications, such as thermal protection systems (TPS), solid rocket motors (SRM) nozzles, internal insulation of SRM, leading edges of hypersonic vehicles, and missile launch structures. A summary of the most recent, global technical research is presented. Polymeric resin systems continue to emphasize phenolic resins and other materials. New high-temperature organic resins based on phthalonitrile (PN), and polysiloxane are described and extend the increased temperature range of resin matrix systems.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but is critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterioembolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G''), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from &lt;50 µm to &gt;1 mm. Gel particle size and morphology correlate most significantly with tan(δ). Conversely, arterial flow rates do not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction is affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings highlight the importance of gel viscoelasticity and flow parameters in determining particle size, dispersibility, and occlusive potential.

Background: Mental health has a special relevance in adolescence. Therefore, this study aimed to analyze the possible association between emotional distress and suicidal ideation among adolescents. Methods: The article presents the results of a survey of secondary school students (N=1419) in the city of Tarragona, Spain. The aim of the analysis was to verify the existence of an association between suicidal ideation and risk factors such as emotional distress and low self-esteem. All the data were also analysed to determine the existence of statistically significant differences between girls and boys. Bivariate analyses were performed with chi-square, point-biserial coefficient and non-parametric tests for independent groups. Logistic regression analysis was also performed to calculate the probability of suicidal ideation. Results: These analyses showed that both emotional distress and low self-esteem increase the likelihood of suicidal ideation among adolescents. This was more evident among boys with high levels of emotional distress. Conclusion: Schools should develop suicide ideation prevention programs for adolescents based on situations that cause emotional distress.

For better solving both fuzziness and reliability occurring in practical issues simultaneously, Z-number deserves further exploration under uncertainty environment. Based on the credibility distribution and conversion rules, we define its expected value, variance, and semi-variance, and realize the feasibility of calculation by deriving calculation formulas. Moreover, we delve into three characteristics inherent in symmetrical Z-numbers. The link that followed between the variance and the semi-variance of Z-numbers is discovered and proved. Furthermore, we apply the formulas of expected value and variance on Z-numbers to examples, whose consequences validate our proposed formulas. The findings indicate the significance of our study in applying the expected value and variance of fuzzy sets across diverse fields.

We develop a primality test for Mersenne numbers and investigate the primality of the sequence of Catalan-Mersenne numbers. We use induction as a proof to show that the 5th Catalan-Mersenne number is a prime number, thus demonstrating the infinitude of Mersenne primes.

Introduction This study was conducted to validate the findings of a prior study published in JDD in September 2023, which reported that a topical firming and toning body lotion (FTB – SkinMedica®, Allergan Aesthetics, an AbbVie Company, Irvine, CA) upregulated several genes in a UV irradiated 3D full-thickness human skin model, outperforming other products, including TransFORM Body Treatment with TriHex Technology® (ATF – Alastin Skincare®, a Galderma company Fort Worth, Texas, USA ). Given the unique response reported for FTB, we conducted this study to assess the reproducibility of these results and explore gene expression at multiple time points, along with validating protein expression in an ex vivo model. Materials and Methods Experiments were conducted using an ex vivo model with photodamaged skin from facelift patients, under an Institutional Review Board approved study. Skin samples were processed, cultured in transwells with Skin Media, and treated daily with either TransFORM or FTB for 7 days. A control group was left untreated. Gene expression was assessed using RT-PCR on days 1 and 3, immunofluorescence after 3 and 7 days of treatment. Skin samples were fixed, paraffin-embedded, sectioned, and stained with an anti-tropoelastin antibody. Fluorescence detection and imaging were conducted to assess protein expression changes. Results Gene expression data from our study and the initial study showed a few similarities but multiple discrepancies. In particular, as opposed to results previously reported at only the 24-hour time point, additional time points showed complete reversal of many of these results. For example, COL1A1 expression at 24 hours was similar for FTB in both studies but differed for TransFORM which showed higher levels at 24 hours. However, at day 3, COL1A1 expression decreased markedly for FTB and was sustained for TransFORM. Other genes, such as COL3A1, COL5, ELN, VEGFC, ATG7, ATG12, BECN1, POMP, PSMB5, and PSMB6, exhibited varying expression patterns between the studies and across different time points. From a translational perspective, histological analysis showed that TransFORM enhanced elastin fiber presence in the dermal-epidermal junction (DEJ) more effectively than FTB at both day 3 and day 7. FTB-treated samples maintained a gap in the DEJ, while TransFORM-treated samples exhibited increased cellular proliferation and DEJ undulation, indicative of a healthier regenerative response. Conclusion This study highlights the problems of examining data and drawing conclusions using a single point of examination. In addition, when a study reports positive results for only 1 product among a range of 8 competitive products, further questioning is essential to exclude the possibility of the experimental model favoring that particular product. The additional 3-day timepoint and further translational examination of histological changes, paints a completely different picture to that reported in the prior publication TransFORM outperformed FTB in most gene expression and histological parameters when assessed over multiple time points in a physiologically relevant ex vivo model.

Background: Regular moderate-vigorous intensity exercise is recommended for adults as it can improve longevity and reduce health risks associated with a sedentary lifestyle. However, there are barriers to achieving intense exercise that may be addressed using virtual reality (VR) as a tool to promote exercise intensity and adherence, particularly through visual feedback and competition. The purpose of this work is to compare visual feedback and competition within fully-immersive VR to enhance exercise intensity and user experience of exercise for young adults; and to describe and compare visual attention during each of the conditions. Methods: Young adults (21- 34 years old) bicycled in three 5-minute VR conditions (visual feedback, self-competition and competition against others). Exercise intensity (cycling cadence and % of maximum heart rate) and visual attention (derived from a wearable eye tracking sensor) were measured continuously. User experience was measured by an intrinsic motivation questionnaire, perceived effort and participant preference. A repeated measures ANOVA with paired t-test post-hoc tests was conducted to detect differences between conditions. Results: Participants exercised at a higher intensity and had higher intrinsic motivation in the two competitive conditions compared to visual feedback. Further, participants preferred the competitive conditions and only reached a vigorous exercise intensity during self-competition. Visual exploration was higher in visual feedback compared to self-competition. Conclusion: For young adults bicycling in VR, competition promoted higher exercise intensity and motivation compared to visual feedback.

This review paper presents a comprehensive synthesis of current knowledge on the contamination of water systems by polycyclic aromatic hydrocarbons (PAHs). PAHs, organic contaminants characterized by two or more fused aromatic rings, are notably problematic due to their persistence, bioaccumulation, and significant health risks. The review commences with an examination of various sources of PAHs in aquatic environments, encompassing both anthropogenic activities, such as industrial discharges, urban runoff, and oil spills, and natural phenomena including volcanic eruptions and wildfires. Subsequently, the discussion shifts to the distribution patterns of PAHs within different aquatic ecosystems, with an analysis of factors that influence their transport. Considerable focus is placed on the entry mechanisms of PAHs into water systems and their interactions with diverse environmental matrices. Additionally, the ecotoxicological effects of PAHs on aquatic life are scrutinized, with particular emphasis on molecular, individual, and ecosystemic impacts. This includes an exploration of PAH bioaccumulation in aquatic organisms and their potential mutagenic and carcinogenic consequences. The review further addresses the challenges associated with detecting and quantifying PAHs in aquatic settings, reflecting on the advancements in analytical methodologies and the complexities introduced by their varied physicochemical properties. The paper concludes with a summary of existing regulatory frameworks and guidelines governing PAH contamination in water systems, underscoring the imperative for global collaboration in the monitoring and management of PAH pollution.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

With the rapid development of new energy vehicles and the digital electronics industry, the demand for lithium has surged, necessitating advanced lithium extraction technologies. Electrochemical methods, noted for their high selectivity and efficiency in extracting target ions from liquid sources in an environmentally friendly manner, have become increasingly vital. These methods are versatile, applicable in scenarios such as lithium extraction from saline lakes, mother liquor separation, and lithium enrichment. They include electrochemical deintercalation, electrochemical ion pumps, and electrodialysis, each offering unique benefits and challenges depending on the application context. This review provides a detailed exploration of the research progress in lithium extraction using electrochemical methods and discusses future prospects for these technologies, emphasizing their potential to meet the growing demand for lithium.

We assessed the impact of social determinants of health (SDOH) and psychosocial factors on screening behavior in a nationally representative sample of women in the US. A retrospective population-level cross-sectional sample was extracted from the 2022 Health Information National Trends Survey. Descriptive statistics were conducted for demographic characteristics and covariates. Population-based estimates with 95% confidence intervals (95% CI) were produced for Pap testing behaviors across study years. We used logistic regression models to assess Pap testing differences based on SDOH and psychosocial factors, adjusting for covariates, with a significance level of 0.05 for hypothesis testing. Women (n=2,224) with a mean age of 46.96 participated in the study. Our study found that 90% of women were interested in cervical cancer screening, with an 80% actual screening rate. Screening rates differed by age group and rurality. SDOH and psychosocial factors were associated with participants’ interest in screening and in actual screening behavior. The impacts of SDOH and psychosocial factors on screening behavior were 3% and 1%, respectively. The SDOH and psychosocial factors are associated with the uptake of cervical cancer screening among women in the United States. Policies must be directed at bridging the gap created by these SDOHs.

In this paper, we propose a quantitative definition of emergence from the density matrix framework as a state of knowledge of the system and its generalized probability formulation, in order to detect emergent properties. We propose the use of a descriptor based on the difference of von Neumann entropy, to calculate if subsystems of systems have inner correlations by defining emergent systems in terms of emergent information.

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in and presents the lowest 5-year survival rate for any form of cancer in the US. Only 20% of PDAC patients are suitable for surgical resection and adjuvant chemotherapy which remains the only curative treatment. Chemotherapeutic and genetherapy treatments are associated with adverse effects and lack specificity/efficacy. In this study we assess the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP-1 or mCCL2), and mouse interleukin (mIL)-2, in human pancreatic BxPc-3 cells, using immunocompromised and CD-3+ T-cell reconstituted mice. Intratumoral treatment with TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 resulted in regression of BxPc-3 xenograft volume as compared to control in immunocompromised mice; mCCL-2 expressing TPV OV resulted in significant difference from control at p

In vertical coordinates, (x,y,z), the gradient Richardson number Ri=N^2⁄S^2 is the square of the ratio between buoyancy frequency N and vertical-shear amplitude S, where N^2=-(g⁄ρ) ∂ρ⁄∂z and S^2=(∂u⁄∂z)^2+ (∂v⁄∂z)^2, with ρ potential density, (u,v) the horizontal velocity components and g gravity acceleration, so that a decrease in stratification brings a decrease in dynamic stability and vice versa. In the isopycnic coordinate system, (x,y,ρ), however, Ri=M^2⁄〖S_ρ〗^2 , is the ratio between 〖M^2≡N〗^(-2) and the squared diapycnal shear 〖S_ρ〗^2=(ρ⁄g)^2 [(∂u⁄∂ρ)^2+ (∂v⁄∂ρ)^2 ], so a decrease in stratification leads to an increase in dynamic stability and vice versa. The apparently different role of stratification arises because S and S_ρ are related through the stratification itself, S_ρ=S⁄N^2 or, equivalently, τ=〖t_o〗^2⁄t_d , which is interpreted as a natural oscillation time τ≡S_ρ that equals the buoyancy or oscillation time t_o=N^(-1) normalized by the ratio t_o⁄t_d , where the deformation time is t_d=S^(-1). Here we follow simple arguments and use field data from three different situations (island shelf-break, Gulf Stream and Mediterranean outflow) to endorse the usefulness of the isopycnal approach. In particular, we define the reduced squared vertical σ^2= S^2-N^2 and reduced squared diapycnal shear 〖σ_ρ〗^2= 〖S_ρ〗^2-M^2, which are positive for unstable conditions and negative for stable conditions. It turns out that Ri and σ^2 remain highly variable for all stratification conditions; in contrast, the mean 〖σ_ρ〗^2 values display a univocal tendency, its magnitude decreasing with stratification. We propose 〖σ_ρ〗^2 and 〖S_ρ〗^2 to be good indexes for the occurrence of effective mixing under high stratification conditions.

The UNUSUAL FLORAL ORGANS (UFO) gene is an essential regulatory factor of class B genes and plays a vital role in the process of inflorescence primordial and flower primordial development. We investigated the role of UFO genes in soybean to better understand the development of floral organs through gene cloning, expression analysis, and gene knockout. In situ hybridization demonstrated predominant expression of the GmUFO1 gene in the flower primordium. Phenotypic observation of GmUFO1 knockout mutant lines (Gmufo1) showed obvious alteration in floral organ number and shape, and mosaic organ formation. In contrast, GmUFO2 knockout mutant lines (Gmufo2) showed no obvious difference in floral organs. However, the GmUFO1 and GmUFO2 double knockout lines (Gmufo1ufo2) showed a more severe mutant phenotype than the Gmufo1 lines. Gene expression analysis also showed differences in the expression of major ABC function genes in the knockout lines. Based on the phenotypic and expression analysis, our results suggest the major role of GmUFO1 in the regulation of flower organ formation in soybean and that GmUFO2 does not have any direct effect, but it might have an interaction role with GmUFO1 in the regulation of flower development. In conclusion, the present study identified UFO genes in soybean and improved our understanding of floral development that could be useful for flower design in hybrid soybean breeding.

In this paper, we introduce hybrid numbers with Fibonacci and Lucas hybrid number coefficients. We give the Binet formulas, generating functions, exponential generating functions for these numbers. Then we define an associate matrix for these numbers. In addition, using this matrix, we present two different versions of Cassini identitiy of these numbers.

Introduction: Lower respiratory tract infections, including pneumonia, are one of the leading causes of child mortality, especially in low-resource settings. Current guidelines rely on clinical signs for diagnosis, leading to over-prescription of antibiotics, which in turn contribute to antimicrobial resistance. Lung point of care ultrasound (L-POCUS) offers potential to improve diagnostic accuracy and reduce unnecessary antibiotic use, but lacks standardized guidelines for diagnosis and management of paediatric pneumonia. Methods and Analysis: This study utilizes a modified Delphi process to develop expert consensus guidelines for L-POCUS interpretation in paediatric pneumonia that would constitute a framework for effective guidelines for judicious antibiotic prescribing. The 5-stage iterative process includes: i) creation of a literature summary and conceptual framework, ii) first round of online surveys for expert feedback, iii) virtual meetings to discuss survey results and refine guidelines, iv) second round of online surveys, v) final analysis and development of consensus guidelines. A panel of 12-15 experts, chosen for their paediatric POCUS experience, geographic diversity, and gender balance, will participate. Consensus will be defined as ≥75% agreement. Ethics and Dissemination: Participation is voluntary, with consent obtained at the start and the option to withdraw at any time. The protocol was approved by the Ethics Commission of Bern, Switzerland. Findings will be disseminated through open access publication.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

In our investigation of the time evolution of energy states Einstein’s interpretation from more than a century ago is found to have greater internal consistency than that of non-relativistic quantum mechanics. We choose to align more closely with his methods by abandoning the non-relativistic Hamiltonian method, which has been the standard for nearly a century, in favor of a relativistically correct Lagrangian method. Integral equations of motion for the absorption and emission of radiation are derived that underlie and anticipate the differentially motivated Schrödinger equation. This new interpretation applies to a large volume of experimental evidence of both classical and quantum mechanical origin. Among the examples discussed in support are Planck’s law describing black body radiation, matrix mechanics, the function of the simplest quantum mechanical system an electron cyclotron, chaos theory, and evolutionary biology.

The young adolescents’ sexual behaviors are under-investigated. In this quantitative descriptive study, we examined the 2019 Middle School Youth Risk Behavior Survey data of 66,366 young adolescents ages 10-14 from 10 states to determine the prevalence of early sexual debut among young adolescents. Complex sampling design was used to produce descriptive statistics and cross-tabulations to describe young adolescents' sexual behaviors. Early sexual debut was reported at nearly 8%, and 4% of those reporting the age of first sex had their first sexual intercourse before 13 years. Compared to the Whites, Black/African Americans (13.2% vs 5.1%, OR=4.51, 95% CI: 2.78-7.31) and Hispanic young adolescents (8.3 % vs 5.1 %, OR=1.44, 95% CI=1.13-1,84) were more likely to report having early sexual intercourse. Males were more likely to report having multiple sexual partners than females (48.1% vs 36.5%, OR = 1.68, 95% CI = 1.22-2.29) and were more likely to report using condoms during the last sex compared to their female counterparts (59.7% vs 50.8%, OR = 1.43, 95% CI = 1.06-1.94). This study suggests the need for more research on young adolescents’ sexual behaviors and develop sexual health interventions that target preadolescence.

New setting is introduced to study neutrosophic failed-independent number and failed independent neutrosophic-number arising neighborhood of different vertices. Neighbor is a key term to have these notions. Having all possible edges amid vertices in a set is a key type of approach to have these notions namely neutrosophic failed-independent number and failed independent neutrosophic-number. Two numbers are obtained but now both settings leads to approach is on demand which is finding biggest set which have all vertices which are neighbors. Let NTG : (V,E,σ,μ) be a neutrosophic graph. Then failed independent number I(NTG) for a neutrosophic graph NTG : (V,E,σ,μ) is maximum cardinality of a set S of vertices such that every two vertices of S are endpoints for an edge, simultaneously; failed independent neutrosophic-number In(NTG) for a neutrosophic graph NTG : (V,E,σ,μ) is maximum neutrosophic cardinality of a set S of vertices such that every two vertices of S are endpoints for an edge, simultaneously. As concluding results, there are some statements, remarks, examples and clarifications about some classes of neutrosophic graphs namely path-neutrosophic graphs, cycle-neutrosophic graphs, complete-neutrosophic graphs, star-neutrosophic graphs, complete-bipartite-neutrosophic graphs and complete-t-partite-neutrosophic graphs. The clarifications are also presented in both sections “Setting of Neutrosophic Failed-Independent Number,” and “Setting of Failed Independent Neutrosophic-Number,” for introduced results and used classes. Neutrosophic number is reused in this way. It’s applied to use the type of neutrosophic number in the way that, three values of a vertex are used and they’ve same share to construct this number to compare with other vertices. Summation of three values of vertex makes one number and applying it to a comparison. This approach facilitates identifying vertices which form neutrosophic failed-independent number and failed independent neutrosophic-number arising neighborhoods of vertices. In path-neutrosophic graphs, two neighbors, form maximal set but with slightly differences, in cycle-neutrosophic graphs, two neighbors forms maximal set. Other classes have same approaches. In complete-neutrosophic graphs, a set of all vertices leads us to neutrosophic failed-independent number and failed independent neutrosophic-number. In star-neutrosophic graphs, a set of vertices containing only center and one other vertex, makes maximal set. In complete-bipartite-neutrosophic graphs, a set of vertices including two vertices from different parts makes intended set but with slightly differences, in complete-t-partite-neutrosophic graphs, a set of t vertices from different parts makes intended set. In both settings, some classes of well-known neutrosophic graphs are studied. Some clarifications for each result and each definition are provided. Using basic set to extend this set to set of all vertices has key role to have these notions in the form of neutrosophic failed-independent number and failed independent neutrosophic-number arising neighborhood of vertices. The cardinality of a set has eligibility to neutrosophic failed-independent number but the neutrosophic cardinality of a set has eligibility to call failed independent neutrosophic-number. Some results get more frameworks and perspective about these definitions. The way in that, two vertices have connections amid each other, opens the way to do some approaches. A vertex could affect on other vertex but there’s no usage of edges. These notions are applied into neutrosophic graphs as individuals but not family of them as drawbacks for these notions. Finding special neutrosophic graphs which are well-known, is an open way to pursue this study. Some problems are proposed to pursue this study. Basic familiarities with graph theory and neutrosophic graph theory are proposed for this article.

New setting is introduced to study chromatic number. Different types of chromatic numbers and neutrosophic chromatic number are proposed in this way, some results are obtained. Classes of neutrosophic graphs are used to obtains these numbers and the representatives of the colors. Using colors to assign to the vertices of neutrosophic graphs is applied. Some questions and problems are posed concerning ways to do further studies on this topic. Using different types of edges from connectedness in same neutrosophic graphs and in modified neutrosophic graphs to define the relation amid vertices which implies having different colors amid them and as consequences, choosing one vertex as a representative of each color to use them in a set of representatives and finally, using neutrosophic cardinality of this set to compute types of chromatic numbers. This specific relation amid edges is necessary to compute both types of chromatic number concerning the number of representative in the set of representatives and types of neutrosophic chromatic number concerning neutrosophic cardinality of set of representatives. If two vertices have no intended edge, then they can be assigned to same color even they’ve common edge. Basic familiarities with neutrosophic graph theory and graph theory are proposed for this article.

New setting is introduced to study chromatic number. vital chromatic number and n-vital chromatic number are proposed in this way, some results are obtained. Classes of neutrosophic graphs are used to obtains these numbers and the representatives of the colors. Using colors to assign to the vertices of neutrosophic graphs is applied. Some questions and problems are posed concerning ways to do further studies on this topic. Using vital edge from connectedness to define the relation amid vertices which implies having different colors amid them and as consequences, choosing one vertex as a representative of each color to use them in a set of representatives and finally, using neutrosophic cardinality of this set to compute vital chromatic number. This specific relation amid edges is necessary to compute both vital chromatic number concerning the number of representative in the set of representatives and n-vital chromatic number concerning neutrosophic cardinality of set of representatives. If two vertices have no vital edge, then they can be assigned to same color even they’ve common edge. Basic familiarities with neutrosophic graph theory and graph theory are proposed for this article.

Shiga toxin-producing Escherichia coli (STEC) is a significant public health threat due to its ability to cause severe gastrointestinal diseases in humans, ranging from diarrhea to life-threatening conditions such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). As the primary reservoir of STEC, cattle play a crucial role in its transmission through contaminated food and water, posing a considerable risk to human health. This comprehensive review explores host-pathogen interactions during STEC colonization of the bovine gut, focusing on the role of gut microbiota in modulating these interactions and influencing disease outcomes. We integrated findings from published transcriptomics, proteomics, and genomics studies to provide a thorough understanding of how STEC adheres to and colonizes the bovine gastrointestinal tract. The insights from this review offer potential avenues for the development of novel preventative and therapeutic strategies aimed at controlling STEC colonization in cattle threby reducing the risk of zoonotic transmission.

A number of chemical modifications were carried out in order to synthesize new compounds based on the triterpenoid betulonic acid. Triazolation reactions were carried out for the synthesis of new 1,2,3-triazole derivatives based on betulonic acid. Chemical changes were made on the carbonyl group at the C-3 position of the initial molecule and on the carboxyl and hydroxyl groups at the C-28 position. Chromatographic methods were used to separate and purify the formed products. Spectroscopic (NMR-, mass-) methods were used to establish the structure of synthesized compounds. As a result of the chemical transformations carried out, a number of new derivatives of betulonic acid were obtained. All synthesized compounds were tested for antimicrobial and cytotoxic activity. As a result, compounds with pronounced antimicrobial activity were identified.

In this four-month-long study (from April 1, 2020 to August 1, 2020), we have collected, modeled, and analyzed COVID-19 data from the top five most infected counties per top six most infected states in the United States (30 counties total). More specifically, we collected data on each state’s total COVID-19 cases, deaths, tests conducted, and their counties’ population, density, percentage of seniors, number of hospitals, total COVID-19 cases, and total COVID-19 related deaths. In this study, we have models illustrating the growth of COVID-19 cases and deaths per county, growth of COVID-19 cases and deaths per state (which is really the sum of our chosen five counties), and growth of COVID-19 tests conducted per state. In addition, our study also contains models illustrating the statistics of several variables that might have affected a county’s COVID-19 data, which has been mentioned above: population, density, percentage of seniors, and number of hospitals. An interesting finding we have noticed upon modeling the 30 counties’ density and total COVID-19 cases as an xy scatter plot is that there is a considerably strong relationship between the two variables. Los Angeles County (which was an extreme outlier), in particular, supports the idea that a county’s most populous city can greatly affect its entire county’s COVID-19 cases; if the largest city is extremely dense, it appears that the entire county has a greater total COVID-19 case count.

Abstract: Emerging risk factors for childhood (

Ambitious biodiversity goals to protect 30% or more of the Earth’s surface by 2030 (30x30) require strategic near-term targets. To define areas that must be protected to prevent the most likely and imminent extinctions, we propose Conservation Imperatives—16,825 unprotected sites harboring rare and threatened species and spanning ~164 Mha of the terrestrial realm. We estimate that protecting the Conservation Imperatives would cost approximately US$169 billion [90% probability: $146 — $228 billion]. Globally, 38% of the 16,825 sites are either adjacent to or within 2.5 km of an existing protected area, potentially reducing land acquisition and management costs. These sites should be prioritized for conservation action over the next five years as part of a broader strategy to expand the global protected area network. The expansion of global protected areas between 2018–2023 incorporated only 7% of sites harboring range-limited and threatened species, highlighting a renewed urgency to conserve these habitats. Permanently protecting only 0.74% of land found in the tropics, where Conservation Imperatives are concentrated, could prevent the majority of predicted near-term extinctions once adequately resourced. We estimate this cost to be US$29 billion to US$46 billion per year over the next five years. Multiple approaches will be required to meet long-term protection goals: providing rights and title to Indigenous Peoples and Local Communities (IPLCs) conserving traditional lands, government designation of new protected areas on federal and state lands, and land purchase or long-term leasing of privately held lands.

Chymotrypsin from the digestive organs of bigfin reef squid, a major commercial squid species in Thailand, was purified to 41.27-fold with 5.74% yield by a sequential purification process including ammonium sulfate precipitation, size exclusion and ion exchange chromatography. According to SDS-PAGE, the molecular weight of purified chymotrypsin was 43 kDa. Native-PAGE analysis revealed a single band for this purified enzyme. Optimum pH and temperature for chymotrypsin activity of the purified enzyme were pH of 7.0 with a temperatures of 55°C. The purified chymotrypsin remained stable throughout a wide range of pH levels (6–11) and at relatively high temperature (50°C). It was significantly inhibited by PMSF and TPCK. The values of the kinetic constants Km and Kcat were found to be 1.33 mM and 31.46 s‒1, respectively. The purified chymotrypsin has the N-terminal amino acid IVGGQEATPGEWPWQAALQV. This study provided new information about the biochemical properties of pure chymotrypsin from bigfin reef squid, which is useful in the future investigation, aquaculture and application of bigfin reef squid.

Heavy rains result in significant threats to human health and life. Floods and other natural disasters, which have a global impact annually, can be attributed to extended periods of intense precipitation. Accurate rainfall prediction is crucial in nations such as Bangladesh, where agriculture is the predominant field of occupation. The efficiency of machine learning methods is enhanced by the nonlinearity of rainfall, surpassing the effectiveness of other approaches. This study proposes the novel combination of rainfall occurrence prediction, rainfall amount prediction, and daily average temperature prediction. This research implements machine learning techniques and an ensemble-based classifier to predict rainfall occurrence, as well as machine learning regressor models and an ensemble-based regressor to predict the rainfall amount and daily average temperature, using the Bangladesh Weather Dataset. The ensemble classifier demonstrated an accuracy of 83.41% and a recall of 78.17%, exhibiting the best performance in predicting when it will rain, but its precision was the lowest, at 51.16%. The ensemble regression model outperformed the base models, including linear regression, random forest, and support vector regression in rainfall amount prediction, with the lowest mean absolute error of 0.36 and root mean squared error of 0.90. Additionally, this model provided the most precise daily average temperature prediction results with the lowest mean absolute error of 0.42 and root mean squared error of 0.54, highlighting its superiority over the other regression models in forecasting temperature. Ensemble approaches consistently exhibit superior task performance metrics.

the process of rapidly digitalizing and transforming businesses, known as Industry 4.0, was already underway before COVID-19. However, the imposed restrictions during the pandemic significantly amplified the need and motivation for both businesses and consumers to utilize digital tools across all sectors including the sectors of bioeconomy. The agricultural and food production sectors have a predominant role in the bioeconomy of the European Union (EU), followed by wood production. These sectors make significant contributions not only to national economies but also to rural areas. Consequently, the digitalization of businesses within the bioeconomy sector not only transforms the enterprises and value chains themselves but also benefits the rural communities in which these enterprises are situated. This study aims to assess the barriers of the bioeconomy sector and ways to support digital transformation within this sector. The paper analyses bioeconomy in EU and the state of digitalisation in the EU. The empiric analysis is based on the cluster analysis of the digitalisation and R&D indicators of the EU and the AHP analysis that allows determining the digitalisation scenarios in Latvia, Lithuania and Poland carried out by four stake-holder groups - national government; advisory and extension; research and entrepreneurship. The results of the AHP indicate that experts from Lithuania and Poland preferred the scenario that suggested the self-initiative from the entrepreneurs of the sector, but experts from Latvia – prioritization of support for digital transformation using national and EU funding. The AHP results also indicate that the opinions of the national government, consulting, and research experts are more aligned throughout all three countries, but the opinion of entrepreneurs differs from these groups.

Snowpack seasonality in the conterminous United States (U.S.) is explored using a daily,14 km horizontal resolution gridded snow water equivalent and snow depth reanalysis product. I2calculated seasonal snowpacks using two established methods: (1) the classic Sturm approach that3requires 60 days of snow cover with a peak depth >50 cm and (2) the snow seasonality metric (SSM)4that only requires 60 days of continuous snow cover. The latter approach yields continuous values5from -1 to +1, where -1 (+1) indicates an ephemeral (seasonal) snowpack. Both approaches identify6seasonal snowpacks in western mountains and the northernmost central and eastern U.S. By relaxing7the depth constraint and providing continuous values, the SSM identifies greater areas of seasonal8snowpacks compared to the Sturm method, particularly in the upper Midwest, New England, and the9Intermountain West. Ephemeral snowpacks are identified throughout lower elevation regions of the10western U.S. and across a broad swath centered near 35°N spanning the lee of the Rocky Mountains11to the Atlantic coast. Because it lacks a depth constraint, the SSM approach is sensitive to interannual12variability, indicating it may inform the location of shallow but long-duration snowpacks at risk13of transitioning to becoming ephemeral with climatic change. A case study in Oregon during an14extreme snow drought year highlights seasonal to ephemeral snowpack transitions.

Contact tracing has become a vital tool for public health officials to effectively combat the spread of new diseases, such asthe novel coronavirus disease COVID-19. Contact tracing is not new to epidemiologist rather, it used manual or semi-manualapproaches that are incredibly time-consuming, costly and inefficient. It mostly relies on human memory while scalabilityis a significant challenge in tackling pandemics. The unprecedented health and socio-economic impacts led researchersand practitioners around the world to search for technology-based approaches for providing scalable and timely answers.Smartphones and associated digital technologies have the potential to provide a better approach due to their high level ofpenetration, coupled with mobility. While data-driven solutions are extremely powerful, the fear among citizens is thatinformation like location or proximity associated with other personal data and can be weaponised by the states to enforcesurveillance. Low adoption rate of such apps due to the lack of trust questioned the efficacy and demanded researchers tofind innovative solution for building digital-trust, and appropriately balancing privacy and accuracy of data. In this paper,we have critically reviewed such protocols and apps to identify the strength and weakness of each approach. Finally, wehave penned down our recommendations to make the future contact tracing mechanisms more universally inter-operable andprivacy-preserving.

It is well established the complex exponential and logarithm are multivalued functions, both failing to maintain most identities originally valid over the positive integers domain. Moreover the general case of complex logarithm, with a complex base, is hardly mentionned in mathematic litterature. We study the exponentiation and logarithm as binary operations where all operands are complex. In a redefined complex number system using an extension of the C field, hereafter named E, we prove both operations always produce single value results and maintain the validity of identities such as log_u (w v) = log_u (w) + log_u (v) where u, v, w in E. There is a cost as some algebraic properties of the addition and subtraction will be diminished, though remaining valid to a certain extent. In order to handle formulas in a C and E dual number system, we introduce the notion of set precision and set truncation. We show complex numbers as defined in C are insufficiently precise to grasp all subtleties of some complex operations, as a result multivaluation, identity failures and, in specific cases, wrong results are obtained when computing exclusively in C. A geometric representation of the new complex number system is proposed, in which the complex plane appears as an orthogonal projection, and where the complex logarithm and exponentiation can be simply represented. Finally we attempt an algebraic formalization of E.

Time can be a difficult concept to understand. Albert Einstein, who viewed time as an illusion, explained the passage of time is relative to the observer’s frame of reference in the space-time continuum. However, the state of consciousness of the observer also influences the passage of time. This paper examines the relationship between the experience of time and different states of consciousness including near-death experiences, mystical states of consciousness, and psychedelic medicine-induced states of consciousness. Two different experiences of time are described. These are Chronos and Kairos. Chronos is described as 4th dimensional time whereas Kairos is 5th dimension time. Methods for facilitating the experience of Kairos are discussed and the potential benefits of experiencing Kairos are reviewed.

Acute myeloid leukemias are characterized by genetic alterations that lead to a complete or partial block at various stages of myeloid differentiation, leading to continual proliferation of myeloid progenitor cells. These alterations can include a well-documented chromosomal translocation that leads to the synthesis of the PML-retinoic acid receptor fusion protein that leads to a block in differentiation and the ability to induce differentiation with all-trans retinoic acid and other small molecules. In essence, in large part, the disease is due to stem cell-like cells that are blocked in their ability to undergo terminal differentiation to more mature, non-proliferative cell types. We discovered a long non-coding RNA (lncRNA), lncRNAp53int1, encoded from the first intron of the p53 tumor suppressor gene. Interestingly, lncRNAp53int1 appears to play an important regulatory role in maintaining the undifferentiated and proliferative state in a manner independent from p53 gene expression. lncRNAp53int1 is expressed at high levels in proliferating, undifferentiated promyelocytes and its levels fall significantly during their terminal differentiation to non-proliferating granulocytes or macrophages. Furthermore, forced overexpression of lncRNAp53int1 blocks terminal differentiation. The observation that the expression of this lncRNA is repressed during terminal differentiation of human leukemic cells and its expression blocks differentiation of leukemic myeloid progenitor cells, is likely to have clinical implications with regards to differentiation therapy for myeloid leukemia. Ongoing research aims to identify the molecular partners that it associates with and the signaling pathways that this lncRNA participates in with the long-term goal of identifying molecules that inhibit lncRNAp53int1 activity and serve as potential therapeutic drugs. The goal of this mini-review is to disseminate these novel and interesting findings to readers and to describe where we think this research is headed and the impact it can have on myeloid leukemias.