We suggest that despite McLuhan’s claim not to have a theory of communication that in fact the body of his work does indeed constitute a theory of media and their effects which I have called his General Theory of Media (GToM) that also includes his Laws of Media (LoM). Both McLuhan’s GToM and his LoM are described. A comparison is made of three notions of law: i. McLuhan’s notion of law as used in his Laws of Media; ii. the notions of the Law in the legal sense and iii. the notion of law as formulated in scientific laws. McLuhan’s understanding of media is used to analyze some of the negative effects of social media suggesting that laws need to be formulated to prevent the misuse of social media that are antithetical to democracy and the invasion of the privacy of the individual users of these apps. McLuhan’s Laws of Media are then used to provide insights into the nature of scientific laws, the Law in the legal sense and his own Laws of Media.

Salmonella can cause acute and chronic infections in humans. Salmonella species are known to cause food poisoning and other diseases in developing countries. Their role in the pathogenesis of these diseases has received increased international attention. Despite numerous advances in sanitation, they still can infect humans and cause outbreaks in developed countries. For example, Salmonella causes about 1.2 million illnesses in the US each year with over 450 deaths. Additionally, Salmonella outbreaks cause significant losses to chicken producers globally. The Salmonella species is also prone to acquiring resistance to various classes of antibiotics. Hence, the need for a paradigm shift from antibiotics to bacteriophages to manage, control and treat bacterial infections. The ɛ34 phage belongs to Podoviruses and categorized into the P22-like phages. The P22-like phages include ɛ34, ES18, P22, ST104, and ST64T. In this work, we investigated the antibacterial property of ɛ34 phage tailspike protein against Salmonella newington (S. newington). We demonstrate here that, the phage’s tailspike protein enzymatic property as a LPS hydrolase synergizes with Vero Cell culture supernatant in killing S. newington. Using decellularized cartilage scaffold as an ex vivo tissue model, the ɛ34 TSP protected the scaffold from S. newington biofilm formation. Computational analysis of the ɛ34 TSP interaction with membrane proteins of S. newington demonstrated a higher probability (0.7318) of binding to ompA of S. newington, and when docked to ompA extracellular component, it produced a high free energy of -11.3kcal/mol. We also demonstrate the resistance/sensitivity of the tailspike to the digestive enzyme trypsin. The data obtained in this work indicates that the trypsin resistant tailspike protein of Ɛ34 phage can be formulated as a novel antibacterial agent against S. newington.

In antimicrobial-peptide/protein engineering, understanding the peptide/protein’s adaptability to harsh environmental conditions such as urea, proteases, fluctuating temperatures, high salts provide enormous insight into the pharmacokinetics and pharmacodynamics of the engineered peptide/protein and its ability to survive the harsh internal environment of the human body such as the gut or the harsh external environment to which they are applied. A previous work in our laboratory demonstrated that our cloned Eɛ34 TSP showed potent antimicrobial activity against Salmonella newington, and more so, could prevent biofilm formation on decellularized tissue. In this work, the effects of urea-acid on the Eɛ34 stability is studied, and the results demonstrates that at lower pHs of 3 and 4 with urea the protein was denatured into monomeric species. However, the protein withstood urea denaturation above pH of 5 and thus remained as trimeric protein. The mechanism of denaturation of Eɛ34 TSP seems to show that urea denatures proteins by depleting hydrophobic core of the protein by directly binding to the amide units via hydrogen bonds. The results of our in-silico investigation determined that urea binds with Eɛ34 TSP with relative free energies range of -3.4 to -2.9 kcal/mol at the putative globular head binding domain of the protein. The urea molecules interacts with with the protein’s predicted hydrophobic core, thus, disrupting and exposing the shielded hydrophobic moieties of Eɛ34 TSP to the solvent. We further showed that after the unfolding of Eɛ34 TSP via urea-acid, renaturation of the protein to its native conformation was possible within few hours. This unique characteristic of refolding of Eɛ34 TSP which is similar to that of the P22 phage tailspike protein is of special interest to protein scientists and can also be exploited in antimicrobial-protein engineering.

The prevalence of multidrug resistant bacterial diseases is a major global health risk. Multidrug resistant bacterial diseases are prevalent, and the need for novel methods of treatment is essential to the preservation of public health. Annually foodborne pathogens cause 1.35 million infections and 26,500 hospitalizations in the United States alone. Foodborne pathogens such as Salmonella spp. are a major threat to public health. Bacteriophages offer a unique method for the treatment of these multidrug resistant bacteria. We studied the infection dynamics of a potential mono-phage therapy of Salmonella typhimurium under various pathophysiological conditions. Furthermore, we determined the resistance dynamics of Salmonella typhimurium against P22 phage treatment. We also determined synergy with antibiotics such as ampicillin and kanamycin. This research helps to further define and show the versatility of bacteriophages as potential novel treatment methods.

Bacteriophages have been recognized as potential biocontrol agents in the food industry. Bacteriophages have been proposed for a variety of applications within this industry including bio preservation, pathogen detection, and as an alternative treatment method to antibiotics in animal health. The potential applications of bacteriophages are widespread throughout the entire food production process and serve to enhance food quality, prevent foodborne illnesses, and enhance the efficiency of production. The ability of bacteriophages to lyse bacterial targets with high specificity and pose no threat to mammalian cells or natural microbiota is unique and relevant in terms of suitability for food safety. This review will outline potential and current applications of bacteriophages and their respective impacts on the field.

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.

This research addresses the strategic issue of why key decision-makers fail to foresee potential extreme ‘black swan’ events. Following a review of the literature, a conceptual framework is developed that identifies two types of organisational blindness that are reflected in Tetlock’s hedgehog cognitive thinking style, being the oversimplification of uncertainty (e.g., inductive biases) and an unquestioned, top-down, reference narrative. This framework is tested using a case study approach and qualitative analysis of secondary data sources available from the Royal Commission of Inquiry and other published reports following the 2010 methane explosion at the Pike River Coal Ltd’s mine (Pike) in New Zealand, that killed 29 miners and caused the loss of all funds invested. The results indicate that the combined effect of both blindness’s meant that Pike’s collective intelligence was limited, and for the three key decision-makers at the Pike River mine, some type of extreme ‘black swan’ event was apparently inevitable. This research provides theoretical and practical contributions to the analysis of business and public policy decision-making under uncertainty.

The relationship between human health and gut microbiota is becoming more apparent. It is now widely believed that healthy gut flora plays a vital role in the overall well-being of the individual. There are spatial and temporal variations in the distribution of microbes from the esophagus to the rectum throughout an individual's lifetime. Through the development of genome sequencing technologies, scientists have been able to study the interactions between different microorganisms and their hosts to improve the health and disease of individuals. The normal gut microbiota provides various functions to the host, whereas the host, in turn, provides nutrients and promotes the development of healthy and resilient microbiota communities. Thus, the microbiota provides and maintains the gut's structural integrity and protects the gut against pathogens. The development of the normal gut microbiota is influenced by various factors. Some of these include the mode of delivery, diet, and antibiotics. In addition, the environment can also affect the development of the gut microbiota. For example, one of the main concerns of antibiotic use is the alteration of the gut microbiota, which could lead to the development of multidrug-resistant organisms. When microbes are disturbed, it can potentially lead to various diseases. Depending on the species' ability to adapt to the human body's environment, the fate of the microbes in the host and their relationship with the human body are decided. This review aims to provide a comprehensive analysis of microbe, microbes-host immune interactions, and factors that can disturb their interactions.

Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.

We conducted an in-situ crystal structure analysis of ferroselite at non-ambient conditions. The aim is to provide a solid ground to further the understanding of the properties of this material in a broad range of conditions. Ferroselite, marcasite-type FeSe2, was studied under high pressures up to 46 GPa and low temperatures, down to 50 K using single-crystal microdiffraction techniques. High pressure and low temperatures were generated using a diamond anvil cell and a cryostat. We found no evidences of structural instability in the explored P-T space. The deformation of the orthorhombic lattice is slightly anisotropic. As expected, the compressibility of the Se-Se dumbbell, the longer bond in the structure, is larger than that of the Fe-Se bonds. Less obvious is the behavior of the octahedral bonds, the shorter bond is the most compressible determining a small increase in the octahedron distortion with pressure. We also achieved a robust structural analysis of ferroselite at low temperature in the diamond anvil cell. Structural changes upon temperature decrease are small but qualitatively similar to those produced by pressure.

New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species it is important to examine potential interaction between CBD and common therapeutics such as broad-spectrum antibiotics. Here, we show that CBD-antibiotic co-therapy can effectively fight S. typhimurium via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics for potential antibiotic-CBD co-therapy. In this study, we reveal that Salmonella typhimurium (S. typhimurium) growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating Salmonella typhimurium.

Authentic learning opportunities that simulate full scale design and construction experiences using real materials offer ideal experiential learning environments for construction and civil engineering students by challenging students to apply building concepts in practical settings. However, the excessive cost of real building materials required for this mode of education limits access to the vast majority of students. As a result, educational researchers have explored potential alternatives to provide cost-effective experiential learning through activities using mock-up materials (e.g., plastic straws, popsicle sticks) and simulation of experiences using immersive technologies (e.g., virtual reality or augmented reality). While some of these alternatives approximate the environment and others provide physical interaction with mock-up materials, the lack of authenticity in the building materials used introduces some apparent differences between the “authentic” learning environments and their cost-effective approximations. Therefore, this research aims to identify the learning processes reported by students and faculty who participated in authentic learning experiences to understand the ways in which this mode of education offers unique value to construction education. Their interview responses illustrated characteristics of authentic learning experiences that were believed to be critical to the learning process, some of which included: working in groups; interdisciplinary participants; and use of real construction materials. Although some of these characteristics are intrinsically linked to the use of real materials, others do not explicitly refer to interaction with real materials. This may indicate to aspects of the authentic learning processes that educational researchers can strategically target through more cost-effective learning environments like virtual and augmented reality. The contribution of this paper is in identifying the characteristics of authentic learning experiences that may guide educational investment and research innovations that aim to replicate some of these learning experiences through more accessible learning environments.

In this paper, we present sums and partial sums of Horadam sequences via generating functions which extends a recent result of Prodinger.

Obesity during childhood has been associated with many important physiological and neurological health considerations. Specifically concerning are the associations between youth obesity and declines in mental health, as shown with increasing rates of adolescent depression and anxiety worldwide. The emergence of mental health disorders commonly arises during adolescent development, and approximately half the global population satisfy the criteria for at least one psychiatric disorder in their lifetime, suggesting a need for early intervention. Adolescence is critical time whereby brain structure and functions are not only negatively associated with obesity and declines in mental health, while also coinciding with significant declines in rates of physical activity among individuals in this age group. Physical activity is thus a prime candidate to address the intersection of obesity and mental health crises occurring globally. This review addresses the important considerations between physiological health (obesity, aerobic fitness, physical activity), brain health (structure and function), and mental wellbeing symptomology. Lastly, we pose a theoretical framework which asks important questions regarding the influence of physiological health on the association between brain health and the development of depression and anxiety symptoms in adolescence.

P-band radar remote sensing applied during the Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS) mission has shown great potential for estimation of root zone soil moisture. When retrieving the soil moisture profile (SMP) from P-band radar, a mathematical function describing the vertical moisture distribution is required. Because only a limited number of observations are available, the number of free parameters of the mathematical model must not exceed the number of observed data. For example, a second order polynomial that contains 3 free parameters was presumed based on in-situ SMP data. The polynomial is currently parameterized based on 3 backscatter observations provided by AirMOSS (i.e. one frequency at three polarizations of HH, VV and HV). In this paper, a more realistic, physically-based SMP model containing 3 free parameters is derived based on a solution to Richards’ equation for unsaturated flow in soils. Evaluation of the new SMP model based on both numerical simulations and measured data revealed that it exhibits greater flexibility for fitting measured and simulated SMPs than the currently applied polynomial. It is also demonstrated that the new SMP model can be reduced to a second order polynomial at the expense of fitting accuracy.

Development of K-Ras independence may explain failure of targeted therapy for pancreatic cancer (PC). In this paper active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown that depleting K-Ras reduced total Ras activity, while cell lines described as independent had no significant decline in total Ras activity. Knockdown of N-Ras showed it had an important role in controlling the relative level of oxidative metabolism but only K-Ras depletion caused a decrease in G2 cyclins, proteasome inhibition reversed this and other targets of APC/c were also decreased by K-Ras depletion. K-Ras depletion did not cause an increase in ubiquitinated G2 cyclins but instead caused exit from G2 phase to slow relative to completion of S-phase, suggesting mutant K-Ras may inhibit APC/c prior to anaphase but stabilizes G2 cyclins independently of this. We propose that during tumorigenesis, cancer cells expressing wild type N-Ras protein are selected because the protein protects cancer cells from the deleterious effects of cell cycle independent induction of cyclins by mutant K-Ras. Mutation independence results when N-Ras activity becomes adequate to drive cell division even in cells where K-Ras is inhibited. Keywords: Pancreatic Ductal Adenocarcinoma, K-Ras, N-Ras, G2 cyclins.

In this paper, closed forms of the sum formulas $\sum_{k=0}^{n}x^{k}W_{k}^{3}$ and $\sum_{k=1}^{n}x^{k}W_{-k}^{3}$ for the cubes of generalized Fibonacci numbers are presented. As special cases, we give sum formulas of Fibonacci, Lucas, Pell, Pell-Lucas, Jacobsthal, Jacobsthal-Lucas numbers.

The burden of chronic liver disease is globally increasing at an alarming rate. Chronic liver injury leads to liver inflammation and fibrosis (LF) as critical determinants of long-term outcomes such as cirrhosis, liver cancer and mortality. LF is a wound-healing process characterized by excessive deposition of extracellular matrix (ECM) proteins due to the activation of hepatic stellate cells (HSCs). In the healthy liver, quiescent HSCs metabolize and store retinoids. Upon fibrogenic activation, quiescent HSCs transdifferentiate into myofibroblasts, lose their vitamin A, upregulate -smooth muscle actin, and produce pro-inflammatory soluble mediators, collagens, and inhibitors of ECM degradation. Activated HSCs are the main effector cells during hepatic fibrogenesis. In addition, the accumulation and activation of profibrogenic macrophages in response to hepatocyte death play a critical role in the initiation of HSC activation and survival. The main source of myofibroblasts is resident HSCs. Activated HSCs migrate to the site of active fibrogenesis to initiate the formation of a fibrous scar. Single-cell technologies revealed that quiescent HSCs are highly homogenous, while activated HSCs/myofibroblasts are much more heterogeneous. The complex process of inflammation results from the response of various hepatic cells to hepatocellular death and inflammatory signals related to intrahepatic injury pathways or extrahepatic mediators. Inflammatory processes modulate fibrogenesis by activating HSCs and, in turn, drive immune mechanisms via cytokines and chemokines. Increasing evidence also suggests that cellular stress responses contribute to fibrogenesis. Recent data demonstrated that LF can revert even at advanced stages of cirrhosis if the underlying cause is eliminated, which inhibits the inflammatory and profibrogenic cells. However, despite numerous clinical studies on plausible drug candidates, an approved antifibrotic therapy still remains elusive. This state-of-the-art review presents cellular and molecular mechanisms involved in hepatic fibrogenesis and its resolution, as well as comprehensively discusses the drivers linking liver injury to chronic liver inflammation and LF.

Continuous-variable quantum key distribution (CV-QKD) shows potential for the rapid development of an information-theoretic secure global communications network; however, the complexities of CV-QKD implementation remain a restrictive factor. Machine learning (ML) has recently shown promise in alleviating these complexities. ML has been applied to almost every stage of CV-QKD protocols, including ML-assisted phase error estimation, excess noise estimation, state discrimination, parameter estimation and optimization, key sifting, information reconciliation, and key rate estimation. This survey provides a comprehensive analysis of the current literature on ML-assisted CV-QKD. In addition, the survey compares the ML algorithms assisting CV-QKD with the traditional algorithms they aim to augment, as well as providing recommendations for future directions for ML-assisted CV-QKD research.

Recycling information can be complex and often confusing which may subsequently reduce the participations in any waste recycling schemes. As a result, this research explored the roles as well as the importance of a holistic approach in designing recycling information using 15 expert-based in-depth interviews. The rationale was to offer a better understanding of what constitutes waste, recycling, and how recycling information should be designed and presented to make recycling more attractive/convenient. Based on the research participants’ perceptions with supports from the existing studies, this research sub-categorised recycling information into three different themes, termed the “WWW” of recycling information components. As a result, these components (or attributes) were extensively described (using findings of semi-structured interviews) to elicit pragmatic guidance for practitioners, policy-makers, and other stakeholders in designing structured communication or information strategies that may simplify and subsequently increase waste-recycling practices. The policy implications of holistic information in enhancing recycling are further discussed.

Precision agriculture (PA) is a holistic, sustainable, innovative systems approach that assists farmers in production management. Adopting PA could improve sustainable food security and community economic sustainability. Developing an understanding of PA adoption attributes is needed to assist extension practitioners to promote adoption and better understand the innovation adoption phenomena. A systematic review of literature was conducted to investigate PA adoption. Thirty-three publications were examined, and four themes were found among the reviewed publications. The results were interpreted using Rogers’ diffusion of innovations framework to address the research objectives. Of the reviewed literature, we found relative advantage and compatibility were two dominant attributes to strengthen the adoption of PA, and the complexity attribute was rarely used to promote the adoption of PA. This study shows that change agents do not fully use five attributes of innovation when they promote PA technology to stakeholders to adopt. Thus, we recommend studies from the agricultural extension specialists’ perspectives in the future may determine contributions to motivate farmers’ adoption of PA, in particular related to complexity.

Infection by human immunodeficiency virus type I (HIV-1) requires virus particle binding to host cell-surface receptor CD4 via the viral envelope glycoprotein gp120. HIV-1 therapy and prevention efforts involve development of mimetic or recombinant gp120 vaccines or deployment of antiviral agents that target specific epitopes of gp120. The unliganded conformational state of gp120 is closed, whereas the CD4-bound state is open. However, in between, there exist dynamic conformational states, indicating intrinsically flexible region(s) of structural dynamics, imposing a structural challenge for developing drug or antibody targets. Known conformational states of gp120 were determined by X-ray crystallographic and cryo-electron microscopy, and neither method captures the population of gp120 species arising from conformational plasticity, motions, and transitions. gp120 plasticity brings up several important questions. How will differences in conformation affect receptor binding, antibody recognition, and neutralization? Which regions are crucial for gp120 structural plasticity? How could structural dynamics influence HIV-1 evasiveness against host immunity and drugs or vaccines, and facilitate the viral entry into its host? This review explores the structural constraints presented by conformational states of the glycoprotein to antibodies or drugs and how these conformational states provide structural avenues for the virus to escape neutralizing agents and evade host immunity.

In the paper, the authors generalize the notion "k-Mittag-Leffler function'', establish some integral transforms of the generalized k-Mittag-Leffler function, and derive several special and known conclusions in terms of the generalized Wright function and the generalized k-Wright function.

Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P < 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (P<0.01) and CRP was increased (P<0.05) in the presence of chorioamnionitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age. In those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants born exclusively for maternal indications.

Much has been learned about the interaction between myosin and actin through biochemistry, in vitro motility assays and cryo-electron microscopy of F-actin decorated with myosin heads. Comparatively less is known about actin-myosin interactions within the filament lattice of muscle, where myosin heads function as independent force generators and thus most measurements report an average signal from multiple biochemical and mechanical states. All of the 3-D imaging by electron microscopy that has revealed the interplay of the regular array of actin subunits and myosin heads within the filament lattice has been accomplished using the flight muscle of the large waterbug Lethocerus sp. Lethocerus flight muscle possesses a particularly favorable filament arrangement that enables all the myosin cross-bridges contacting the actin filament to be visualized in a thin section. This review covers the history of this effort and the progress toward visualizing the complex set of conformational changes that myosin heads make when binding to actin in several static states as well as fast frozen actively contracting muscle. The efforts have revealed a consistent pattern of changes to the myosin head structures determined by X-ray crystallography needed to explain the structure of the different acto-myosin interactions observed in situ.

Environmental and occupational exposure to hexavalent chromium, Cr(VI), causes female reproductive failures and infertility. Cr(VI) is used in more than 50 industries and is a group-A carcinogen, mutagenic and teratogenic, and a male and female reproductive toxicant. Our previous findings indicate that Cr(VI) causes follicular atresia, trophoblast cell apoptosis, and mitochondrial dysfunction in metaphase II (MII) oocytes. However, the integrated molecular mechanism of Cr(VI)-induced oocyte defects are not understood. The current study investigates the mechanism of Cr(VI) in causing meiotic disruption of MII oocytes, leading to infertility in superovulated rats. Postnatal day (PND)-22 rats were treated with potassium dichromate (1 and 5 ppm) in drinking water from PND 22-29 and superovulated. MII oocytes were analyzed by immunofluorescence, and images were captured by confocal microscopy and quantified by Image Pro Plus software. Our data showed that Cr(VI) increased microtubule misalignment, missegregation of chromosomes, a bulged and folded actin cap, oxidative DNA and protein damage, increased DNA double-strand break, and DNA repair protein RAD51. Cr(VI) also induced incomplete cytokinesis and delayed polar body extrusion. Our study indicates that exposure to environmentally relevant doses of Cr(VI) caused severe DNA damage, distorted oocyte cytoskeletal proteins, and caused oxidative DNA and protein damage leading to infertility.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites between A-56 and A-75, and (ii) major C-terminal cleavage sites between T-383 and Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78, R-79, D-266 and A-267, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

Despite of over 20 years of community directed treatment with ivermectin (CDTI), a high prevalence of onchocerciasis and onchocerciasis-associated epilepsy were observed in rural villages in Mahenge, Tanzania. Therefore, we assessed the knowledge, attitude and practice about onchocerciasis in four rural villages in the Mahenge area. This was a qualitative study conducted between June and July 2019. Eleven focus group discussions were organized with persons with epilepsy and their caretakers, community resource persons, and community drug distributors (CDDs), and two in-depth interviews with district programme coordinators of neglected tropical diseases (NTD). Most participants were aware about symptoms of onchocerciasis using local terminologies such as “ukurutu/rough dry skin” and “kuwashwa/itching”. A small proportion of people did not take ivermectin during CDTI for fear of adverse reactions such as itching and swelling. Some men believed that ivermectin may decrease libido. Challenges for high CDTI coverage included, long walking distance by CDDs to deliver drugs to households, persons being away for farming, low awareness of the disease and limited supervision by the NTD coordinators. In conclusion, ivermectin uptake in Mahenge should be optimised by continuous advocacy about the importance of taking ivermectin to prevent onchocerciasis-associated morbidity and by improving supervision during CDTI.

This paper will explore analogs of groups formed by the transformations of two ropes as presented by Minh-Tam Quang Trinh.1 The two operations acting on these ropes are T and S, defined as twists and clockwise turns, respectively. These actions intertwine the ropes, creating tangles. T and S also have the ability to untangle the rope when used in certain combinations. In the two-rope case, these actions expressed as a group presentation were shown to be isomorphic to SL₂(Z). We explored the analog of these opera- tions, T and S, and conjectured the corresponding group to which they are isomorphic. Partial proofs for this conjecture are included and future work would include proving our conjecture as well as generalizing results to k ropes.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

Abstract. Background: This paper investigates the propagation of behaviorally transmitted traits with negative effect on host fitness. Methods: We analyze equilibrium between genetically transmitted and behaviorally transmitted competing propagators and consider whether a behavioral propagator is linked to reproduction (e.g. vertical culture transmission), or not. We employ combined genetic and behavior-induced fitness components for hosts, while behavioral propagators have replication factors to distinguish from what’s good for the host (fitness). Results: A trait which spreads faster than its marginal host fitness contribution reduces population will establish itself. The often transient nature of laterally transmitted traits may be a defense against accumulation of deleterious traits. Laterally transmitted traits with high spreading rate often do not equalize with genetic traits, spreading outside natural selection of the hosts. Vertical transmission reduces replication rate and allows group selection against deleterious behaviorally transmitted traits. Competing mutually exclusive propagators contribute to inequality and altruism, but compete through adverse fitness since exclusivity assumes low conversion. Conclusion: Behaviorally transmitted traits, in some cases a tremendous advantage, may also be a significant problem in the development of societies.

In the dynamic landscape of E-commerce, the proliferation of user-generated queries regarding products highlights the critical need for advanced automatic question answering (AQA) systems. These systems are instrumental in harnessing the vast array of information available online to deliver immediate and informative responses to potential buyers. Recognizing the complexity of such queries, which often require synthesis of reviews, product specifications, and responses to similar questions, we introduce a sophisticated model, the Comprehensive E-commerce Answer Generation System (CEAGS). This model adeptly navigates the challenges posed by irrelevant data and sentiment ambiguity in user-generated content. Our approach leverages a dual-phase process of relevance determination and sentiment clarity, setting the stage for a transformative response generation mechanism. Empirical analyses reveal the superiority of CEAGS, with our relevance assessment framework outstripping existing models by a notable margin in precision metrics, and our answer generation module achieving unprecedented gains in content preservation and coherence. Notably, CEAGS marks a pioneering contribution to the E-commerce domain by integrating disparate information sources to formulate responses that are not only accurate but also contextually rich and user-centric.

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K⁺ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K⁺ ions are at least 10,000 times more permeant than Na⁺ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na⁺ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.

The excessive intake of sodium (Na) and insufficient intake of potassium (K) are major concerns to prevent hypertension. Using low-Na/K seasonings (reducing 25% of the NaCl and adding K salt) may improve the dietary Na/K ratio and help prevent hypertension. To devise an intervention study using low-Na/K seasonings at a company cafeteria, we calculated the Na and K contents of the meals served at the cafeteria and estimated changes in the intakes when suitable low-Na/K seasonings were used. We also considered using milk as a good source of K. We used an ingredient list of a company cafeteria and calculated Na and K contents in each dish. The average amounts of NaCl and K per use were 5.04 g and 718 mg, respectively. Seasonings contributed 70.9% of the NaCl. With the use of low-Na/K seasonings, an estimated reduction in NaCl of 0.8 g/day and an estimated increase in K of 308 mg/day was achieved. An additional serving (200 mL) of milk, NaCl was reduced by 0.57 g/day and K was increased by 610 mg/day, with an overall decrease in the dietary Na/K ratio from 3.20 to 2.40. The use of low-Na/K seasonings and dairy may improve the dietary Na/K ratio among cafeteria users and help prevent hypertension.

Abstract The aim of the present review is to discuss the roles of vitamin K and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. Adequate vitamin K status is required for carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanism, such as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through dietary adequacy of vitamin K (phylloquinone or menaquinone). Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3 we find that an adequate supply of vitamin K on top of an optimal vitamin D status seems to add to the benefit for maintaining bone health. More research related to synergism and possible mechanisms of vitamins D3 and K interaction in bone health is needed.

Abstract: Background: With the growing trends in recreational marijuana use, our study aims at analyzing the association between Acute coronary syndromes (ACS) and Ventricular Fibrillation (Vfib) and cannabis use disorder in young adults (18 – 45) Methods: National In-patient Sample was used for population analysis. Probit logistic regression was used for analyzing the associations between diagnosis of ACS/ Vfib and documented cannabis use disorder. Propensity Score matched samples were made from the ACS/Vfib admissions with Cannabis use disorder to analyze the in-hospital outcomes. Results: Statistically significant association was found between admission diagnosis of ACS/ vfib, and documented cannabis use disorder in the study population. The association remained sig-nificant after accounting for potential confounders. Documented race as black, documented di-agnosis of uncontrolled hypertension and diabetes were found to have significant association with admissions for ACS among the population with documented Cannabis use disorder. No difference in mortality were found between ACS admissions with and without documented cannabis use disorder in the propensity matched cohorts. Conclusions: Documented diagnosis of Cannabis use disorder has statistically significant associ-ation with admission diagnosis of ACS/Vfib even after accounting for confounders. Documented race as black, and co existing diagnosis of uncontrolled hypertension and diabetes had significant association with admission diagnosis of ACS in population with documented cannabis use dis-order. Keywords: Cannabis use disorder; ACS; Ventricular fibrillation

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness world-wide. We recently reported that polyethylene glycol (PEG) can activate the alternative pathway of the complement system and induce choroidal neovascularization (CNV) in mice. Currently, no other investigator has demonstrated CNV after PEG injection in the mouse eye. The aim of this article is twofold: we review the histologic changes in mouse retina and retinal pigmented epithelium (RPE) after treatment with PEG, and we summarize a model of wet and dry AMD pathogenesis in mice through subretinal PEG treatment of RPE cells and retinal layers. We injected (subretinal) male C57BL/6 mice with 2 μL of solution containing 0.5 mg and 1.0 mg of PEG or PBS in control groups. Eyes were harvested at day 1, 3 and 5 after injection and processed for analysis. Sections were immunohistochemically stained for complement component C3, mem-brane attack complex (MAC), and cytokeratin 18. Light and laser confocal microscopy was used for image capturing. PEG increased deposition of C3 and MAC on RPE cells and on all retinal layers after 1.0 mg injection. PEG induced loss of cellular contacts between RPE cells and migration of RPE cells in the subretinal space at day 1 after PEG injection. After 0.5 mg PEG injection, increased size of RPE cells was detected at day 3 and 5. Apoptotic bodies were observed in outer nuclear layer at day 3 and 5 after 0.5 mg PEG treatment. RPE cells with dark cytoplasm and condensed chromatin were observed. Higher doses of PEG induce CNV, encouraged RPE cell proliferation and death, and damage photoreceptors in mice. This simple and fast model may be useful to explore the pathogenesis of both dry and wet AMD.

Nanoporous membranes promise energy-efficient water desalination. Hexagonal boron nitride (h-BN), like graphene, exhibits outstanding physical and chemical properties, making it a promising candidate for water treatment. We employed Car–Parrinello molecular dynamics simulations to establish accurate modeling of Na+ and Cl- permeation through hydrogen passivated nanopores in graphene and h-BN membranes. In these complex systems the classical potentials cannot properly account for the physics at play. We demonstrate that ion separation works well for the h-BN by imposing a barrier of 0.13 eV and 0.24 eV for Na+ and Cl- permeation respectively, compared to the graphene where the Cl- ion faces a negative barrier of 0.68 eV and is prone toward blockade and Na+ permeation is associated with a slightly negative barrier of 0.03 eV. From the change in the solvation shell, we get the following trend: Na/h-BN > Na/G > Cl/G > Cl/h-BN. We argue that the trend in the permeation barrier changes to Cl-h-BN > Na-h-BN > Na-G > Cl-G due to a combination of several interactions, including the distortion of the water network induced by the ions, the ion-water interaction, and the ion-nanopore interaction. Overall, the desalination performance of h-BN surpasses that of their graphene counterparts.

The objectives were to identify conditions under which mothers may be willing to use telelactation and explore associations between participant characteristics, willingness, and beliefs regarding telelactation use. Mothers 2-8 weeks postpartum were recruited from two Florida maternal care sites and surveyed to assess demographics, breastfeeding initiation, and potential telelactation use. Analyses included descriptive statistics and logistic regression models. Of the 88 participants, most were white, married, earned less than $50,000 per year, had access to technology, and were willing to use telelactation if it was free (80.7%) or over a secure server (63.6%). Fifty-six percent were willing to use telelactation if it involved feeding the baby without a cover, but only 45.5% were willing if their nipples may be seen. Those with higher odds of willingness to use telelaction under these modesty conditions were experienced using videochat, white, married, and of higher income. Mothers with security concerns had six times the odds of being uncomfortable with telelactation compared to mothers without concerns. While telelactation can improve access to critical services, willingness to use telelactation may depend on conditions of use and sociodemographics. During the COVID-19 pandemic and beyond, these findings offer important insights for lactation professionals implementing virtual consultations.

The $k$-means problem is to compute a set of $k$ centers (points) that minimizes the sum of squared distances to a given set of $n$ points in a metric space. Arguably, the most common algorithm to solve it is $k$-means++ which is easy to implement, and provides a provably small approximation factor in time that is linear in $n$. We generalize $k$-means++ to support: (i) non-metric spaces and any pseudo-distance function. In particular, it supports M-estimators functions that handle outliers, e.g. where the distance $\mathrm{dist}(p,x)$ between a pair of points is replaced by $\min {\mathrm{dist}(p,x),1}$. (ii) $k$-means clustering with $m\geq 1$ outliers, i.e., where the $m$ farthest points from the $k$ centers are excluded from the total sum of distances. This is the first algorithm whose running time is linear in $n$ and polynomial in $k$ and $m$.

Cortical actomyosin flows, among other mechanisms, scale up spontaneous symmetry breaking and thus play pivotal roles in cell differentiation, division, and motility. According to many model systems, myosin motor-induced local contractions of initially isotropic actomyosin cortices are nucleation points for generating cortical flows. However, the positive feedback mechanisms by which spontaneous contractions can be amplified towards large-scale directed flows remain mostly speculative. To investigate such a process on spherical surfaces, we reconstituted and confined initially isotropic minimal actomyosin cortices to the interfaces of emulsion droplets. The presence of ATP leads to myosin-induced local contractions that self-organize and amplify into directed, large-scale actomyosin flows. By combining our experiments with theory, we found that the feedback mechanism leading to a coordinated, directional motion of actomyosin clusters can be described as asymmetric cluster vibrations, caused by intrinsic non-isotropic ATP consumption, in conjunction with spatial confinement. By tracking individual actomyosin clusters, we identified fingerprints of vibrational states as the basis of directed motions. These vibrations may represent a generic key driver of directed actomyosin flows under spatial confinement in vitro and in living systems.

The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortae originating from either the right or left ventricular cavum. Mixing of blood in crocodilians cannot occur at ventricular level as in other reptiles, but instead takes place at aortic root level by a shunt, the Foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods. Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris, have been studied. Results and Conclusions. The outflow tract septation complex can be divided into 2 components. The aorto-pulmonary septum divides the pulmonary trunk from both aortae, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

Recent data suggest that K-Ras4B (hereafter K-Ras) can drive cancer cell stemness via calmodulin (CaM)-dependent, non-canonical Wnt-signalling. Here we examined whether another Ca2+-binding protein, the CaM-related centrin1, binds to K-Ras and could mediate some K-Ras functions that were previously ascribed to CaM. While CaM and centrin1 appear to distinguish between peptides that were derived from their classical targets, they both bind to K-Ras in cells. Cellular BRET-data suggest that CaM engages more with K-Ras than centrin1 and that the interaction with the C-terminal membrane anchor of K-Ras is sufficient for this. Surprisingly, binding of neither K-Ras nor its membrane anchor alone to CaM or centrin1 is sensitive to inhibition of prenylation. In support of an involvement of the G-domain of K-Ras in cellular complexes with these Ca2+-binding proteins, we find that oncogenic K-RasG12V displays increased engagement with both CaM and centrin1. This is abrogated by addition of the D38A effector-site mutation, suggesting that K-RasG12V is held together with CaM or centrin1 in complexes with effectors. When treated with CaM-inhibitors the BRET-interaction of K-RasG12V with centrin1 was also disrupted in the low micromolar range, comparable to that with CaM. While CaM predominates in regulating functional membrane anchorage of K-Ras, it has a very similar co-distribution with centrin1 on mitotic organelles. Given these results, a significant overlap of the CaM- and centrin1-dependent functions of K-Ras is suggested.

Lipases, a versatile class of biocatalysts, have been shown to function in non-aqueous media/organic solvents and to possess promiscuous catalytic activity for a wide range of organic transformations. In this study, we explore the biocatalytic properties of a library of commercially available lipases by screening them for catalysis of a one-pot synthesis of Wieland-Miescher Ketone, an important intermediate in the synthesis of biologically active compounds such as steroids and terpenoids, from methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. As a direct outgrowth of this screen, we have created an optimized procedure for Wieland-Miescher Ketone (WMK) synthesis using crude lipase preparations, characterizing both reaction yield and enantiomeric excess. We have also identified principal components of the crude lipase mixture through proteomics and present evidence for a non-lipolytic origin of the observed catalysis. Finally, using the optimized conditions developed in this study, we propose a general absorbance-based screening methodology for assessing biocatalytic potential of crude enzyme preparations for synthesis of WMK.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Nearest-neighbour clustering is a simple yet powerful machine learning algorithm that finds natural application in the decoding of signals in classical optical-fibre communication systems. Quantum k-means clustering promises a speed-up over the classical k-means algorithm; however, it has been shown to currently not provide this speed-up for decoding optical-fibre signals due to the embedding of classical data, which introduces inaccuracies and slowdowns. Although still not achieving an exponential speed-up for NISQ implementations, this work proposes the generalised inverse stereographic projection as an improved embedding into the Bloch sphere for quantum distance estimation in k-nearest-neighbour clustering, which allows us to get closer to the classical performance. We also use the generalised inverse stereographic projection to develop an analogous classical clustering algorithm and benchmark its accuracy, runtime and convergence for decoding real-world experimental optical-fibre communication data. This proposed `quantum-inspired' algorithm provides an improvement in both the accuracy and convergence rate with respect to the k-means algorithm. Hence, this work presents two main contributions. Firstly, we propose the general inverse stereographic projection into the Bloch sphere as a better embedding for quantum machine learning algorithms; here, we use the problem of clustering quadrature amplitude modulated optical-fibre signals as an example. Secondly, as a purely classical contribution inspired by the first contribution, we propose and benchmark the use of the general inverse stereographic projection and spherical centroid for clustering optical-fibre signals, showing that optimizing the radius yields a consistent improvement in accuracy and convergence rate.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

Clustering, or otherwise known as cluster analysis, is a learning problem that takes place without any human supervision. This technique has often been utilized, much efficiently, in data analysis, and serves for observing and identifying interesting, useful, or desired patterns in the said data. The clustering technique functions by performing a structured division of the data involved, in similar objects based on the characteristics that it identifies. This process results in the formation of groups, and each group that is formed, is called a cluster. A single said cluster consists of objects from the data, that have similarities among other objects found in the same cluster, and resemble differences when compared to objects identified from the data that now exist in other clusters. The process of clustering is very significant in various aspects of data analysis, as it determines and presents the intrinsic grouping of objects present in the data, based on their attributes, in a batch of unlabeled raw data. A textbook or otherwise said, good criteria, does not exist in this method of cluster analysis. That is because this process is so different and so customizable for every user, that needs it in his/her various and different needs. There is no outright best clustering algorithm, as it massively depends on the user’s scenario and needs. This paper is intended to compare and study two different clustering algorithms. The algorithms under investigation are k-mean and mean shift. These algorithms are compared according to the following factors: time complexity, training, prediction performance and accuracy of the clustering algorithms.

Tailings generated by mining account for the largest proportion of global waste from industrial activities. Copper is relatively uncommon world-wide, with low concentrations in sediments and waters, yet is very elevated around mining sites. On the Keweenaw Peninsula of Michigan, USA, jutting out into Lake Superior, 140 mines extracted native copper from the Portage Lake Volcanic Series, part of an intercontinental rift system. Between 1901-1932, two mills at Gay (Mohawk, Wolverine) sluiced 22.7 million metric tonnes (MMT) of copper-rich tailings (stamp sands) into Grand (Big) Traverse Bay. Here we examine: 1) 3D coastal elevation and reef bathymetry, 2) particle dispersal, 3) copper concentrations and leaching, plus 4) shoreline toxicity. About 10 MMT of tailings created a migrating coastal beach that stretches 7 km from the Gay pile to the Traverse River Seawall. Another 10 MMT are moving underwater on the coastal shelf, threatening Buffalo Reef, an important lake trout and whitefish breeding ground. Aerial photos, ALS (plane) LiDAR, and relatively inexpensive UAS (drone) surveys characterize shoreline structure and aid initial remediation. Because sands (natural beach quartz, stamp sand basalt) are silicates of similar density, particle dispersal is similar and challenging. However, stamp sand beaches contrast greatly with natural sand beaches in both physical profile and chemistry. Dispersing particles retain copper, and release toxic concentrations. Leaching is elevated by exposure to high DOC and low pH waters. Field experiments, shoreline seining, and benthic sampling confirm serious impacts on aquatic biota, supporting tailings removal.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

Farmers are continually looking for new reliable, objective and non-invasive methods for evaluation of ewe condition. Live weight (LW) and body condition score (BCS) are used by farmers as a basis to determine the condition of the animal. Body composition is an important aspect of monitoring animal condition. The body composition is the amount of fat, lean and bone; knowing the amount of each is important because the information can be used for better strategic management interventions. Experiments were conducted to establish the relationship between body composition and body parameters, at key life’s stages (weaning and pre-mating), using measurements automatically determined by an image processing ap-plication at Lincoln University sheep farm for 88 Coopworth ewes. Computerized Tomography technology was used to develop relationship with body parameters and a subset was used to validate the predicted model. Multivariate linear regression (MLR), artificial neural network (ANNs) and regression tree (RT) statistical analysis methods were evaluated to determine their efficacy to predict body fat, lean and bone. The results showed a correlation between fat, lean and bone determined by CT and the fat, lean, bone weight estimated by live weight and body parameters calculated using the image processing application with R2 values of 0.90 for fat, 0.72 for lean and 0.50 for bone using ANNs statistical model. From these results, farmers can utilize accurate measures of fat which will enhance nutritional and management practices.

In the particular configuration of the scalar field K-essence in the Wheeler-DeWitt quantum equation, for some age in the Bianchi type I anisotropic cosmological model, a fractional differential equation for the scalar field arises naturally. The order of the fractional differential equation is $\beta=\frac{2\alpha}{2\alpha - 1}$. This fractional equation belongs to different intervals, depending on the value of the barotropic parameter; when $\omega_{X} \in [0,1]$, the order belongs to the interval $1\leq \beta \leq 2$, and when $\omega_{X}\in[-1,0)$, the order belongs to the interval $0<\beta \leq 1$. In the quantum scheme, we introduce the factor ordering problem in the variables $(\Omega,\phi)$ and its corresponding momenta $(\Pi_\Omega, \Pi_\phi)$, obtaining a linear fractional differential equation with variable coefficients in the scalar field equation, then the solution is found using a fractional power series expansion. The corresponding quantum solutions are also given. We found the classical solution in the usual gauge N obtained in the Hamiltonian formalism and without a gauge. In the last case, the general solution is presented in a transformed time $T(\tau)$, however in the dust era we found a closed solution in the gauge time $\tau$.

The main objective of this paper is to introduce k-fractional derivative operator by using the definition of k-beta function. We establish some results related to the newly defined fractional operator such as Mellin transform and relations to k-hypergeometric and k-Appell's functions. Also, we investigate the k-fractional derivative of k-Mittag-Leffler and Wright hypergeometric functions.

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

The tryptophan catabolite (TRYCAT) pathway is implicated in the pathophysiology of schizophrenia (SCZ) since the rate-limiting enzyme indoleamine-dioxygenase (IDO) may be induced by inflammatory and oxidative stress mediators. This systematic review searched PubMed, Web of Science, and Google Scholar for papers published from inception until August 2021 and meta-analyzed the association between SCZ and TRYCATs in the central nervous system (CNS) and peripheral blood. We included 61 studies comprising 2813 patients and 2948 healthy controls. In the CNS we found a significant (p<0.001) increase in the kynurenine/tryptophan (KYN/TRP) (standardized mean difference, SMD=0.769, 95% confidence interval, CI: 0.456; 1.082) and kynurenic acid (KA)/KYN+TRP (SMD=0.697, CI:0.478-0.917) ratios, KA (SMD=0.646, CI: 0.422; 0.909) and KYN (SMD=1.238; CI: 0.590; 1.886), while the 3OH-kynurenine (3HK) + KYN-3-monooxygenase (KMO)/KYN ratio was significantly reduced (SMD=-1.089, CI: -1.682; -0.496). There were significant differences between KYN/TRP, (KYN+KA)/TRP, (3HK+KMO)/KYN, KA, and KYN levels among the CNS and peripheral blood, and among serum and plasma KYN. The only useful peripheral marker of CNS TRYCATs findings was the increased KYN/TRP ratio in serum (SMD=0.211, CI: 0.056; 0.366, p=0.007), but not in plasma. There was no significant increase in a neurotoxic composite score based on KYN, 3HK, and picolinic, xanthurenic, and quinolinic acid. SCZ is accompanied by increased IDO activity in the CNS and serum, and reduced KMO activity and a shift towards KA production in the CNS. This CNS TRYCATs profile indicates neuroprotective, negative immunoregulatory and anti-inflammatory effects. Peripheral blood levels of TRYCATs are dissociated from CNS findings except for a modest increase in serum IDO activity.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

High surface area carbon was obtained from -carrageenan – urea cryogels doped with 1.25 – 5 wt% graphene oxide (GO). Incorporation of GO resulted in multifaceted modification in the textural and chemical properties of the carbon cryogel. The thermal decomposition of GO facilitated the formation of micropores resulted in a substantial increase in the apparent surface area (up to 1780 m2/g). The annealing at 1000 °C removed part of the heteroatoms but left behind a high number of defects. While the volatile thermal degradation products of GO affected the porous texture and the surface chemistry in a complex way, its reduced residue resulted in a gradually increasing electrical conductivity. The influence of GO was studied in oxygen reduction reaction (ORR) and in Li-ion storage application. GO affected the electron transfer mechanism in the ORR tests and challenged the stability of the electrodes. Even if the electrode has been stabilized under oxygen-free conditions, later may undergo destabilization processes during the ORR. The 5 wt% GO doped sample was the most sensitive under oxidative conditions, but finally it exhibited the highest capacitance. In the Li-ion battery tests the coulombic efficiency of all the samples was consistently above 98 %, indicating the great potential of such carbons for efficient Li-ion insertion and reinsertion during the charge – discharge process, thereby providing a promising alternative for graphite-based anodes. The cell from the 1.25% sample showed an initial discharge capacity of 313 mAh/g, 95.1 % capacity retention and 99.3 % coulombic efficiency after 50 charge – discharge cycles.

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

Background: Recently some photon models of a Wigner's friend experiment have led investigators to suggest objective reality does not exist, and to publish non-academic articles with such claims. The public is not equipped to evaluate the severe limitations of these experiments. The separation of Wigner from the experiment and use of only reversible coherent processes for the friend allow operations that are not possible in ordinary reality according to the latest quantum research. Methods: We suggest directly testing the implied claim that objective reality, including incoherent objects with irreversible non-destructive memory, can be held in superposition. We suspect it will fail, but provide for a graduated approach that may discover something about the conditions for superposition collapse. To this end we design a thought experiment to model the objective world, investigating under what conditions experimenters in the same world (ensemble member) will be able to record a result and find it does not appear to change. An observer has a viewing apparatus and a memory apparatus. A second uncorrelated viewer of the same recorded result is employed to obtain objectivity. By hypothesis the uncorrelated second viewer obtains the same view of the measurement record as the first observer. There are not two measurements. This is not an investigation of hidden variables. Results: To model the objective world, incoherent and irreversible processes must be included. To test for superposition, coherence has to be established. These seem to present a contradiction. Conclusions: The thought experiment has suggested new places to look other than size for the origin of objective reality from the quantum world, casts doubt on the Many-Worlds interpretation, and provides a method of testing it.

The visualization of hyperspectral images in display devices, having RGB colour composition channels is quite difficult due to the high dimensionality of these images. Thus, principal component analysis has been used as a dimensionality reduction algorithm to reduce information loss, by creating uncorrelated features. To classify regions in the hyperspectral images, K-means clustering has been used to form clusters/regions. These two algorithms have been implemented on the three datasets imaged by AVIRIS and ROSIS sensors.

Concept Knowledge (C-K) theory has been used in engineering and science-based research for more than a decade. Design of an Information Technology (IT) artefact is mostly pragmatic in nature. Design Science Research (DSR) methodology applied and studied in many Information Systems (IS) research. Many sub design decisions involved through the design of an IT artefact from a concept (idea) to a working prototype. A DSR artefact is based on a combination of decisions made during several sub-design stages. Artefacts are built based on the selection of elements in each sub-design space. Recording the design decisions on each sub-design space would be beneficial for future researchers. By knowing the design decisions on each sub-design space, researchers would be able to try different combinations of the design. C-K theory provides the ability to capture the design processes’ several sub-design spaces. In this paper, we discuss the DSR research methodology by looking at the stages proposed in the literature, and the application of C-K theory in an IT-based DSR. This paper also proposed a C-K theory-based protocol called Concept Tree for tracking and reporting artefact design steps. The application of C-K theory in DSR is exhibited using the implementation of the Concept Tree for a prototype design IT artefact.

In this paper, some convexity properties and some inequalities for the (p,k)-analogue of the Gamma function, Г_p,k(x) are given. In particular, a (p,k)-analogue of the celebrated Bohr-Mollerup theorem is given. Furthermore, a (p,k)-analogue of the Riemann zeta function, ζ_p,k(x) is introduced and some associated inequalities are derived. The established results provide the (p,k)-generalizations of some known results concerning the classical Gamma function.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

The goal of this paper is to contribute the perspective of a systems engineer to the effort to fight pandemics. The availability of low latency case data and effectiveness of social distancing suggest there is sufficient control for successful smoothing and targeting almost any desired level of low or high cases and immunity. This control proceeds from spontaneous public reaction to caseloads and news as well as government mediated recommendations and orders. We simulate multi-step and intermittent-with-feedback partial unlock of social distancing for rapidly-spreading moderate-mortality epidemics and pandemics similar to COVID-19. Optimized scenarios reduce total cases and therefore deaths typically 8% and up to 30% by controlling overshoot as groups cross the herd immunity threshold, or lower thresholds to manage medical resources and provide economic relief. We analyze overshoot and provide guidance on how to damp it. However, we find overshoot damping, whether from expert planning or natural public self-isolation, increases the likelihood of transition to an endemic disease. An SIR model is used to evaluate scenarios that are intended to function over a wide variety of parameters. The end result is not a case trajectory prediction, but a prediction of which strategies produce near-optimal results over a wide range of epidemiological and social parameters. Overshoot damping perversely increases the chance a pathogen will transition to an endemic disease, so we briefly describe the undershoot conditions that promote transition to endemic status.

The current study aims to produce a material that has a dual effect of healing and anti-inflammatory. For this target k-carrageenan/polyacrylamide hydrogel film loaded with cetrimide (k-CAR/PAAm/CI) was performed by manual casting technique. Definite concentrations of k-CAR and AAm was heated at 80°C for 2 hours, CI and glycerol were added. The solution was cast without using initiator and cross-linker. The reaction of the sulfonic acid group -SO3H of k-CAR with -CONH2 group of PAAm lead to the formation of a sulfonamide (-SO2NH-) linkage. The characteristics of the produced films were investigated by FTIR, TGA, contact angle, and mechanical properties. Improvement in the thermal stability was performed in k-CAR/PAAm/CI2 film containing 1.5% CI compared to the film has 0.5% CI (k-CAR/PAAm/CI1). The contact angle measurement proved the films are hydrophobic that enhanced by increasing CI content. The tensile strength and elongation percent values are considered adequate for materials used in wound care. k-CAR/PAAm/CI2 (1.5% CI) film showed superior antimicrobial activity against P. aeruginosa, moderate activity against S. aureus, and low activity against E. coli. The film k-CAR/PAAm/CI2 was effectively inhibiting the heat-induced hemolysis and may offer a promising approach for the development of effective wound dressings.

First, we examine how spin is treated in special relativity and the necessity of introducing spin supplementary conditions (SSC) and how they are related to the choice of a center-of-mass of a spinning particle. Next, we discuss quantum electrodynamics and the Foldy-Wouthuysen transformation which we note is a position operator identical to the Pryce-Newton-Wigner position operator. The classical version of the operators are shown to be essential for the treatment of classical relativistic particles in general relativity, of special interest being the case of binary systems (black holes/neutron stars) which emit gravitational radiation.

A temperature-modulated pyroelectricity measurement system for a small single crystal is developed and applied to standard sample measurements performed on a thin single crystal of lithium niobate. The modulation measurement is based on the AC technique, in which the temperature of the sample is periodically oscillated, and the synchronized pyroelectric signal is extracted using a lock-in amplifier. Temperature modulation is applied by irradiating periodic light on the sample placed in the heat exchange gas. To apply this technique to the transparent reference sample, a commercially available black resin is coated on the sample’s surface to absorb the light energy and transmits it to the specimen. The experimental results are analyzed using a two-layer heat transfer model to verify the effect of the light-absorbing layer as well as the non-contact temperature modulation system.

While lidar-based forest inventory methods have been widely demonstrated, prediction of tree diameters with lidar is not well understood. The performance metrics typically used in studies for prediction of diameters can be difficult to interpret and may not support comparative inferences between sampling designs or study areas. We evaluate a variety of lidar and k nearest neighbor (k-NN) strategies for prediction of tree diameter distributions using two indices which are easier to interpret and compare. The indices are based on the coefficient of determination (R²), and root mean square deviation (RMSD). These indices facilitate comparisons with alternative (non-lidar) inventory strategies, and with other project areas. We evaluate k nearest neighbors (k-NN) dbh density (relative frequency by dbh class) prediction strategies with lidar for 190 training plots distribute across the 800 km² Savannah River Site in South Carolina, USA. We evaluate the performance of k-NN with respect to distance metrics, number of neighbors, predictor sets, and response sets. Amongst the examined strategies we found Mahalanobis distance with k = 3 neighbors performed best according to a number of criteria.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

(1) Background: Vitamin K deficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and increased risk of vascular calcifications. A method to indirectly measure Vitamin K status is measuring the blood level of Vitamin K dependent proteins (VKDP)- osteocalcin (OC) and matrix GLA protein (MGP). The aim of this study is to correlate the level of OC and MGP with markers of CKD mineral bone disorder (CKD-MBD). (2) Methods: We conducted a single-center cross-sectional study that included 45 CKD G5D patients and measured blood biochemistry, complete blood count and intact osteocalcin and matrix GLA protein. (3) Results: We found a strong statistically significant correlation of OC with the markers of CKD-MBD such as: iPTH , serum calcium and serum phosphorus and a strong indirect statistically significant correlation with abdominal circumference. There was also a statistically significant correlation of MGP with markers of inflammation (CRP). Higher levels of MGP were found in patients treated with vitamin K antagonists, non-calcium based phosphate binders and vitamin D receptor activator- paricalcitol. (4) Conclusions: In our study, we found that vitamin K deficiency, measured indirectly using the level of VKDP is associated to CKD-MBD. The use of medication such as phosphate binders, that reduce vitamin K absorbtion, Vitamin D that increases Vitamin K requirements and also vitamin K antagonists, seem to have an influence on the blood level of VKDPs.

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

Abstract: Doppler renal resistive index (RRI) has been used for several decades as a potential indi-cator for renal disease and progression. In recent years, RRI has emerged as a useful prognostic indicator for a range of co-morbidities in patients who are acutely unwell and as a potential marker for sub-clinical acute kidney injury (AKI) and post procedural AKI risk. Despite this, the clinical and theoretical determinants of RRI are poorly understood and remain contentious. Method: A narrative review of studies exploring the theoretical, experimental, and clinical evidence for factors affecting RRI. No date restrictions were set. Findings: Both experimental and clinical data confirm that RRI is markedly affected by a range of systemic and renal determinants and is influenced closely by the underlying risk factors and sys-temic vascular changes that lead to progressive renal damage. Discussion: This paper provides an overview of the key haemodynamic determinants of renal re-sistive index and aims to clarify their relative importance. With reference to a simplified theoretical model, evidence from experimental and clinical studies is reviewed. Pathophysiological factors and patient characteristics that influence RRI are explored to provide a better understanding of why RRI values change in the presence of common or complex pathologies. Conclusion: By gaining a better understanding of the complex systemic and renal factors that influ-ence RRI, ultrasound users will be better prepared to understand and interpret changes in RRI across a range of patient presentations.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

New information suggests female autistic spectrum disorder (ASD) is much more common than previously thought, with a likely prevalence of 6% and with 80% undiagnosed at the age of 18. ASD then becomes a common comorbidity of female mental illness with nearly one in five women who develop a mental illness being autistic. ASD has heretofore been regarded as a pediatric condition and though now thought to be life long it is still not well recognized by adult health services. Most mental illness first presents in the teens and early twenties. Comorbid ASD is more difficult to diagnose due to diagnostic overshadowing, and ASD comorbidity maks the mental illness more severe and mor difficult to treat. Recognized ASD is readily treatable with an approach sympathetic to neurodiversity. Improving the pathway from adolescence to adulthood by increasing knowledge of autism in adult health services would dramatically improve female mental health at surprisingly little extra cost. It is low hanging fruit in a very fraught area of healthcare. This paper will examine the extent of the problem. It will explore solutions and quantify the gains of appropriate therapy.

This new study revised interlinked issues of global soil organic carbon (SOC), annual net primary productivity (NPP) and atmospheric CO₂ turnover time (τ). Soil is confirmed as both the greatest sink and source for excess atmospheric CO₂. Most terrestrial NPP (~218 Gt C/yr) is ultimately processed in topsoil and SOC stocks now total >10,000–12,000 Gt. More excess carbon is released into the air and water from SOC loss (>20 Gt C/yr) due to land clearance for pasture/crops, fires, agrichemical poisoning and erosion, than from fossil fuels (~10 Gt C/yr). NOAA’s Barrow bounce and isotopic analyses support high terrestrial flux up to ~800 Gt C/yr and CO₂ turnover time of ~1–4 years. Earth’s re-humification via compost offers the best and only practical/time-critical fix for climate, strategy for species extinction plus remedy for human health.

Shutdown for just six days enables land plants to entirely fix CO₂ excess of +4 Gt C per yr. Rebuilding soil organic carbon (SOC) in worm-worked humus is the only practical carbon capture and storage (CCS) capable of freely offsetting annual anthropogenic emissions. A case is made to redirect all available resources towards proven, earthworm-based, organic husbandry. Priority is to safely combat mounting global threats due to irreversible species extinction, perilous climate change and deteriorating human wellbeing (mental/physical health). All three interlinked risks are underpinned by a relentless, yet largely ignored, critical loss of precious topsoil. A first step to topsoil recovery is vermi-composting all vegetable and animal ‘wastes’ for return to the field.

The ratio of males to females with ASD is generally quoted as 4:1 though it is believed that there are biases preventing females being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male to female ratio appears to be 3:4. Eighty per cent of females remain undiagnosed at age 18 which has serious consequences for the mental health of young women.

Two conundrums have puzzled COVID-19 investigators: 1) morbidity and mortality is rare among Infants and young children and 2) rates of morbidity and mortality exhibit very large variances across nations, locals and even within cities. These differences correlate with rates of Haemophilus influenzae type B (Hib) and pneumococcal vaccination, which are almost universal among infants and vary widely by geography among adults and the elderly. The higher the rate of vaccination, the lower the COVID-19 morbidity and mortality. Vaccination rates with other vaccines, including BCG and poliovirus, do not correlate with COVID-19 risks. Notably, both Hib and pneumoccoci are common co-infections with influenza and coronaviruses and are associated with more severe disease and risk of death. Whether the vaccines simply protect against COVID-19 complications, directly protect against COVID-19 infection by inducing cross-reactive immunity, or are markers for some other types of protection such as availability of better healthcare, is not yet known. What is known is that improving coverage rates of Hib and pneumococcal vaccination has significantly lowered severe morbidity and mortality in influenza epidemics and might have similar efficacy for mitigating coronavirus outbreaks. If infants and children are valid indicators, the beneficial effects might be very significant. The possibility that anti-viral proteins in milk (e.g., lactoferrin) protect against COVID-19 is also explored.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Stellar NGC 6853, also known as the Dumbbell Nebula, is a remarkable example of an elliptical morphological type 1 multiple shell planetary nebula, which is now in one of its last evolutionary stages. This project focuses on examining the distinct varieties of the nebula temperatures and densities using observation data from the Issac Newton Group of Telescopes and comparing them with the observation data from Observatoire de Haute Provence from 14th to 18th of October 2019, with a primary focus on the data from the Issac Newton Telescope (INT). The densities ranged from diffused regions of 376.63 ± 228.97 atoms per cm³ to dense regions of 6441.11 ± 228.90 atoms per cm³; these values are slightly lower approximately by 2000 than the values from the Observatoire de Haute Provence. The radial velocity and the expansion velocity were also calculated using the spectroscopic data and were found to be 29.50 ± 0.38 km⁻¹ and 37.40 ± 0.38 km⁻¹ respectively. This result is expected from a multi-shell nebula that consists of the main body and surrounding halo

Background: A large percentage of deaths in an epidemic or pandemic can be due to overshoot of population (herd) immunity, either from the initial peak or from planned or unplanned exit from lockdown or social distancing conditions. Objectives: We study partial unlock or reopening interaction with seasonal effects in a managed epidemic to quantify overshoot effects on small and large unlock steps and discover robust strategies for reducing overshoot. Methods: We simulate partial unlock of social distancing for epidemics over a range of replication factor, immunity duration and seasonality factor for strategies targeting immunity thresholds using overshoot optimization. Results: Seasonality change must be taken into account as one of the steps in an easing sequence, and a two step unlock, including seasonal effects, minimizes overshoot and deaths. It may cause undershoot, which causes rebounds and assists survival of the pathogen. Conclusions: Partial easing levels, even low levels for economic relief while waiting on a vaccine, have population immunity thresholds based on the reduced replication rates and may experience overshoot as well. We further find a two step strategy remains highly sensitive to variations in case ratio, replication factor, seasonality and timing. We demonstrate a three or more step strategy is more robust, and conclude that the best possible approach minimizes deaths under a range of likely actual conditions which include public response.

The present study comprises the second part of our previous work that dealt mainly with the phytochemical and physicochemical characterization of green coffee, clove, cinnamon/clove and nutmeg ethanolic extracts of grape origin. In the present study, we focused on producing a discriminating model concerning green coffee, clove, cinnamon, cinnamon and clove, and nutmeg fine powders based on multivariate analysis of variance and supervised learning on data of volatile compounds analysis, carried out with solid phase dynamic extraction in combination with gas chromatography/mass spectrometry. Results showed that 7 volatile compounds namely ethylene, methanol, 3-methylpentane, ethyl acetate, 9-hexadecen-1-ol, toluene, and methyl acetate could differentiate the investigated samples resulting in a 100% classification rate using the cross-validation method of linear discriminant analysis. Results were further confirmed using partial least squares regression analysis. The study contributes to the typification of green coffee, cinnamon, clove, cinnamon and clove and nutmeg, based on selected volatile compounds, and provides further support to the literature by means of possible adulteration given the statistical models developed.

Past public health crises (e.g. tobacco, alcohol, opioids, cholera, HIV, lead, pollution, venereal disease, even COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCD’s) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation — addiction, toxicity, ubiquity, and externalities (how does your consumption affect me?). To its credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCD’s within their borders. This article also supplies scientific counters to food industry talking points, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

In this paper, closed forms of the sum formulas $\sum_{k=0}^{n}W_{k}^{2}$ \ for the squares of generalized Tetranacci numbers are presented. We also present the sum formulas $\sum_{k=0}^{n}W_{k+1}W_{k},$ $\sum_{k=0}^{n}W_{k+2}W_{k},$ and $\sum_{k=0}^{n}W_{k+3}W_{k}.$ As special cases, we give summation formulas of the of Tetranacci, Tetranacci-Lucas and some other fourth order linear recurrance sequences.

Introduction. Strontium-82/Rubidium-82 (⁸²Sr/⁸²Rb) generators are used widely for positron emission tomography (PET) imaging of myocardial perfusion. In this study, the ⁸²Rb isotope yield and production efficiency of two FDA-approved ⁸²Sr/⁸²Rb generators were compared.Methods. N=515 sequential daily quality assurance (QA) reports from 9 CardioGen-82® and 9 RUBY-FILL® generators were reviewed over a period of 2 years. A series of test elutions was performed at different flow-rates on the RUBY-FILL® system to determine an empirical correction-factor used to convert CardioGen-82® daily QA values of ⁸²Rb activity (dose-calibrator ‘maximum’ of 50 mL elution at 50 mL/min) to RUBY-FILL® equivalent values (integrated ‘total’ of 35 mL elution at 20 mL/min). The generator yield (⁸²Rb) and production efficiency (⁸²Rb yield / ⁸²Sr parent activity) were measured and compared after this conversion to a common scale. Results. At the start of clinical use, the system reported ⁸²Rb activity from daily QA was lower for CardioGen-82® vs RUBY-FILL® (2.3 ± 0.2 vs 3.0 ± 0.2 GBq, p<0.001) despite having similar ⁸²Sr activity. Dose-calibrator ‘maximum’ (CardioGen-82®) values were found to under-estimate the integrated ‘total’ (RUBY-FILL®) activity by ~24% at 50 mL/min. When these data were used to convert the CardioGen-82 values to a common measurement scale (integrated total activity) the CardioGen-82® efficiency remained slightly lower than the RUBY-FILL® system on average (88 ± 4% vs 95 ± 4%, p<0.001). The efficiency of ⁸²Rb production improved for both systems over the respective periods of clinical use.Conclusions. ⁸²Rb generator yield was significantly under-estimated using the CardioGen-82® vs RUBY-FILL® daily QA procedure. When generator yield was expressed as the integrated total activity for both systems, the estimated ⁸²Rb production efficiency of the CardioGen-82® system was ~7% lower than RUBY-FILL® over the full period of clinical use.

Earth’s land surface area is raised from conventionally flat 15 to 64 Gha to account for hilly undulation and soil relief detail. Three main aspects are: topography, rugosity/tortuosity and micro-relief/porosity of vegetation-free ground. Recalibration is arrived at from four approaches: first, direct empirical estimates from the few compiled satellite or LiDAR data with means of +2.5–26% progressively overlain by +94% at cm² scale for soil ruggedness then +108% for mm² micro-relief; second, from digital elevation models with 1.6–2.0 times flat areas; third, by ‘reverse engineering’ global soil bulk densities and carbon reserves requiring x 2–6 land. Finally, a Fermi estimation conveniently sets the World’s new surface area – that exposed to Sun, air and rain – at 100 Gha (with 36 Gha flat ocean). Soil organic carbon (SOC) is thence raised to 8,580 Gt mainly in SOM/humus with its biotic complexity plus roots, VAM-fungi and leaf-litter, that itself = 17,800 Gt. Although four to six times IPCC’s or NASA/NOAA’s calculations of just 1,500–2,300 Gt SOC, this is likely an underestimation. Global biomass and biodiversity are at least doubled (x 2–3.5) and net primary productivity (NPP) similarly increased on land to >270 Gt C yr^-1 due to terrain.

Rainfall, or more generally the precipitation process (flux), is a clear example of chaotic variables resulting from a highly nonlinear dynamical system, the atmosphere, represented by a set of physical equations such as the Navier-Stokes equations, energy balances and hydrological cycle among others. As a generalization of the Euclidean (ordinary) measurements, chaotic solutions of these equations are characterized by fractal dimensions, which are non-integer values that represent the complexity of variables like the precipitation. However, observed precipitation is measured as an aggregate variable over time, thus physical analysis of the observed fluxes is very limited. Therefore, this review aims to go through the different approaches used in the identification and analysis of the complexity of the observed precipitation, taking advantage of its geometry footprint. To address the review, it ranges from classical perspectives of fractal-based techniques to new perspectives at temporal and spatial scales as well as for classification of climatic features, including monofractal dimension, multifractal approaches, Hurst exponent, Shannon entropy and time scaling in intensity-duration-frequency curves.

Some of the key features of inclusive and equitable teaching approaches encourage prompt feedback, student cooperation in communities of learning, active learning, and promotes diverse ways of knowing in the classroom. In my article, I present step-bystep tips to help instructors create guided microlearning inquiry questions within an inclusive and equitable general biology classroom setting. Microlearning is a special approach that helps students complete a specific task linked to a specific learning objective that would be completed in a short time window around five minutes. The step-by-step tips presented in my article helps instructors to develop questions aligned to specific learning objective to help clarify unclear or confusing topics in general biology using the Kahoot e-Learning platform. This guided microlearning inquiry toolkit provides a blueprint for helping instructors to infuse student-centered approaches to help clarify difficult concepts in general biology and further develop avenues refine students’ critical thinking and experimental design in biology research.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

Heart Rate Monitors (HRMs) are an indispensable tool for controlling training parameters of healthy athletes. They became a source of information about stress heart rhythm disturbances, recognized as unexpected increases in heart rate (HR), which can be life-threatening for athletes. Most HRMs do not recognize the type of arrhythmia, confusing them with artifacts. The aim of the study was to assess the usefulness of ECG recording functions by sports HRMs among endurance athletes, coaches, and physicians in comparison with other basic and hypothetical functions. We conducted 3 surveys among endurance athletes (76 runners, 14 cyclists, and 10 triathletes), as well as 10 coaches and 10 sports doctors to obtain information on how important ECG recording is, and what functions of HRMs should be improved to meet their expectations in the future. The respondents were asked questions regarding use and hypothetical functions, as well as preference for HRM type (optical/strap). For athletes, the 4 most important functions were distance traveled, pace, instant heart rate, and information about reaching the oxygen threshold. ECG recording was the 8th and 9th most important for momentary and continuous, respectively. Coaches opined more importance to ECG recording. Doctors placed ECG recording as most important. All participants preferred optical HRMs to strap HRMs. Research on the improvement and implementation of HRM functions shows slightly different preferences of athletes compared to coaches and doctors. Suspected arrhythmia increases the value of the HRM’s ability to record ECGs during training by athletes and coaches. For doctors, this is the most desirable feature in any situation. Considering the expectations of all groups continuous ECG recording during training will significantly improve the safety of athletes.

In document forensic, Ink mismatch relays very important information about forgeries in this way we can find out the authenticity of documents. Finding out and distinguishing these unique inks from the multispectral document is very challenging task. In this paper we proposed the method to identify the inks using clustering. We used K-Mean clustering instead of widely known Fuzzy C-Means Clustering (FCM) and successfully identity the number of inks. For the purpose of optimizing and improving our results we used two optimization techniques such as Elbow and silhouette optimization techniques.

The k-means is one of the most popular and widely used clustering algorithm, however, it is limited to only numeric data. The k-prototypes algorithm is one of the famous algorithms for dealing with both numeric and categorical data. However, there have been no studies to accelerate k-prototypes algorithm. In this paper, we propose a new fast k-prototypes algorithm that gives the same answer as original k-prototypes. The proposed algorithm avoids distance computations using partial distance computation. Our k-prototypes algorithm finds minimum distance without distance computations of all attributes between an object and a cluster center, which allows it to reduce time complexity. A partial distance computation uses a fact that a value of the maximum difference between two categorical attributes is 1 during distance computations. If data objects have m categorical attributes, maximum difference of categorical attributes between an object and a cluster center is m. Our algorithm first computes distance with only numeric attributes. If a difference of the minimum distance and the second smallest with numeric attributes is higher than m, we can find minimum distance between an object and a cluster center without distance computations of categorical attributes. The experimental shows proposed k-prototypes algorithm improves computational performance than original k-prototypes algorithm in our dataset.

Developmental, clinical, and epidemiological research have demonstrated the salience of perceived racial discrimination (PRD) as a contributor to negative mental health outcomes in adolescence. This article summarizes secondary analyses of cross-sectional data from a large-scale youth survey within a predominantly rural state to estimate the prevalence and strength of association between PRD and serious psychological distress, suicidal ideation, and prior suicidal attempts. Data from 93,812 students enrolled in Grades 6, 8, 10, and 12 within 129 school districts across Kentucky were examined to determine prevalence rates for subgroups within the cohort. Logistic regression analyses assessed differences and established comparative strength of association among these variables for racial/ethnic subgroups. PRD was self-reported at high rates across several demographic subgroups and was most evident among Black (24.5%) and Asian (22.1%) students. Multiracial students experienced the highest rates of both SPD and suicidality. Both for the entire cohort and for each racial/ethnic subgroup, PRD was significantly associated with increased likelihood of negative mental health outcomes, although the strength of these associations varied across subgroups and developmental levels. Implications for early intervention and prevention are discussed.

Displacement mapping is a computer graphics technique that enables the design of components with regularly or randomly textured surfaces that can be quickly materialized on a three-dimensional (3D) printer when needed. This approach is in principle more flexible, faster and more economical compared to conventional texturing methods, but the accuracy of the texture depends heavily on the parameters used. The purpose of this study is to demonstrate how to produce a surface-textured part using polygonal (mesh) modeling software and a photopolymerizable resin, and to develop a universal methodology to predict the dimensional accuracy of the model file log combined with a resin 3D printer. The printed components were characterized on a scanning confocal microscope. In the setup used in this study, the mesh size had to be reduced to 10% of the smallest feature size and the textured layer had to be heavily (x4) overexposed to achieve the desired accuracy. As a practical application, two functional stamps with a regular (honeycomb) and a random texture, respectively, were successfully manufactured. The insights gained will be of great benefit in quickly and cost-effectively producing components with innovative patterns and textures for a variety of hobby, industrial and biomedical applications.