cssi/SciSciGPT-SciSciNet huggingface dataset:
Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma

Objective To investigate the potential tumour suppressor functions of glutathione peroxidase 7 (GPX7) and examine the interplay between epigenetic and genetic events in regulating its expression in oesophageal adenocarcinomas (OAC). Design In vitro and in vivo cell models were developed to investigate the biological and molecular functions of GPX7 in OAC. Results Reconstitution of GPX7 in OAC cell lines, OE33 and FLO-1, significantly suppressed growth as shown by the growth curve, colony formation and EdU proliferation assays. Meanwhile, GPX7-expressing cells displayed significant impairment in G1/S progression and an increase in cell senescence. Concordant with the above functions, Western blot analysis displayed higher levels of p73, p27, p21 and p16 with a decrease in phosphorylated retinoblastoma protein (RB), indicating its increased tumour suppressor activities. On the contrary, knockdown of GPX7 in HET1A cells (an immortalised normal oesophageal cell line) rendered the cells growth advantage as indicated with a higher EdU rate, lower levels of p73, p27, p21 and p16 and an increase in phosphorylated RB. We confirmed the tumour suppressor function in vivo using GPX7-expressing OE33 cells in a mouse xenograft model. Pyrosequencing of the GPX7 promoter region (−162 to +138) demonstrated location-specific hypermethylation between +13 and +64 in OAC (69%, 54/78). This was significantly associated with the downregulation of GPX7 (p Conclusions Our data suggest that GPX7 possesses tumour suppressor functions in OAC and is silenced by location-specific promoter DNA methylation.
Does test have a greater role to play in the DFM process

Test and diagnostics of SRAM vehicles, test chips and products has the potential to provide the feedback to identify and quantify DFM-related issues including both functional yield and parametric issues (power and performance). Does testing have a greater role to play in the DFM process? The scope of tests includes product test, test of test-structures and on-product structures like ring-oscillators. It also includes not just wafer and final tests but also characterization and even field tests. Broadly, it is learning from silicon using tests.
Design of Service Component Layer in SOA Reference Architecture

This paper introduces the design of a template of architectural building blocks (ABBs) for the Service Component layer in the SOA Solution Stack (S3) reference architecture. SOA solution architects can use the industry practice-based template as a starting point to quickly configure, customize, and prototype their application-specific service component layer that provides code containers that implement services. We then formalize the issue of service component implementation selection into a one-sided sealed English auction problem. Along with architectural decisions, a cost decision model is deduced to help solution practitioners in selecting proper service component providers for the most cost-effective design of service-oriented solution design.
Insights into the pathogenesis of inflammatory bowel diseases provided by new rodent models of spontaneous colitis

New molecular techniques that permit over-expression or deletion of targeted genes have created a new class of rodent models of intestinal inflammation. Spontaneous colitis, with variable small bowel, duodenal, and systemic inflammation, develops in transgenic HLA-B27/β2-microglobulin rats; interleukin-2, interleukin-10, transforming growth factor-β1, T cell receptor, and G protein deficient (knockout) mice; the new C3H/HeJ Bir mouse substrain; following transfer of CD45RBhigh lymphocytes into immunodeficient mice; and following bone marrow transplantation into cyclosporin A-treated mice. These models provide the following important insights into the mechanisms of chronic intestinal inflammation: (a) Ubiquitous luminal bacteria have a critical role in induction and perpetuation of chronic intestinal and systemic inflammation in genetically susceptible hosts. (b) Defective immunoregulation, especially immunosuppression, can lead to chronic colitis, (c) Alteration of any of a number of immunoregulatory molecules can induce almost identical phenotypes of intestinal inflammation. (d) Host genetic susceptibility determines the incidence and aggressiveness of disease. (e) The immune system, especially immunoregulatory T lymphocytes, mediates chronic colitis. Results in these models are consistent with the hypothesis that chronic intestinal and related systemic manifestations are the result of an inappropriately aggressive immune response to ubiquitous luminal bacterial constituents, mediated by genetically determined defective immunosuppression. Furthermore, the diverse nature of immunoregulatory defects in these models that share similar clinical manifestations suggests that ulcerative colitis and Crohn's disease are heterogeneous groups of disorders with multiple etiologies.
All-optical particle trap using two orthogonally intersecting beams

We introduce a novel optical particle trap using two orthogonally intersecting beams. The trapping principle is described and an optofluidic implementation using liquid-core waveguides is discussed.
Peirce and the Founding of American Sociology

This paper argues that Charles Sanders Peirce contributed significantly to the founding of American sociology, doing so at the level of philosophical presuppositions or meta-sociology. I emphasize two of his ideas. One is semiotics, which is virtually the same as the anthropologists’ concept of culture. This latter concept in turn was essential to clarifying the sociologists’ idea of the social or society. Peirce also created the modern theory of the dialogical self, which explained the symbolic character of human beings and proved foundational for social psychology. Politically Peirce was a right-wing conservative, but his ideas eventually contributed to the egalitarian views of cultures and sub-cultures. In addition his ideas contributed, by way of unanticipated consequences, to the 20th-century human rights revolutions in the American legal system. Thus he was both a founder of sociology and a founder of American political liberalism.
Herpes zoster ophthalmicus-induced oculomotor nerve palsy

Herpes zoster ophthalmicus (HZO) may cause a variety of ocular conditions including: dermatitis, corneal pseudo-dendrites, uveitis, retinitis, and cranial nerve palsies. Cranial nerve palsies caused by herpes zoster (HZ) are relatively uncommon clinical findings. Previous case reports have looked at this relationship, but the overall case studies are few. Other causes of nerve palsies typically need to be ruled out first with neuro-imaging and blood evaluations. However, when HZ is confirmed, treatment with oral antiviral therapy and/or oral corticosteroids along with monitoring the individual usually results in a self-limiting ophthalmoplegia that improves on its own over several months. We report a case of cranial nerve III palsy resulting from HZO.
Reinstatement of Polygonatum yunnanense (Asparagaceae)

Polygonatum yunnanense is reinstated to specific status based on morphology which differs strongly in key diagnostic characters from P . nodosum . The limited original diagnosis is expanded based on examination of the holotype, exsiccata, and three cultivated accessions. Its hypothesized relationship to P . adnatum and P . omeiense is discussed and a key to these three taxa is provided.
A Model of Bubbles and Crashes

This paper presents a model in which an asset bubble may persist despite the presence of a large mass of rational arbitrageurs whose joint responses would suffice to burst the bubble. The resilience of the bubble stems from the inability of arbitrageurs to temporarily coordinate their selling strategies. This synchronization problem together with the individual incentive to time the market results in the persistence of bubbles over a substantial period. The analysis suggests that behavioral influences on prices are immune to arbitrage in the short and medium run. The model provides a natural setting in which news events, by enabling synchronization, may have a disproportionate impact relative to their intrinsic informational content.
Energetics of Halogen Amine Reactions with Triplet Metastables: NFCl2 with Ar(3P0,2), He(23S), and N2(3Σ+u) and NF2Cl and NCl3 with Ar(3P0,2)

The collisions of NFCl2 with the metastable species Ar(3P0,2), He(23S, 21S), and N2(3Σ+u) and of NF2Cl and NCl3 with Ar(3P0,2) were carried out using a discharge flow system, and diatomic product channels were identified on the basis of emission from the fragments. The mechanisms for these reactions were determined from the emission spectra of the products, the energy available in the reacting species and released in the fragments, and the conservation of spin angular momentum. To carry out the energy analysis, the ΔHform's of NF2Cl, NFCl2, and NCl3 were calculated using G1 and G2 methods with Gaussian 94, yielding average theoretical values of −5.3, 23.0, and 48.3 kcal/mol, respectively. These values are compared to estimated experimental ΔHform's which have been reported for NF2Cl and NCl3.
Study and Computational Simulation of Nanomaterial Coating to Reduce Crevice Corrosion

The crevice correction is a common type of localized corrosion which costs multibillion dollar losses in many different fields including aerospace, automobile, and building structures. The crevice geometry can easily catch moisture and impurity which accelerates the chemical corrosion. It is one of the dangerous corrosions that can cause sudden failure of the products and involve the human injury in some cases. Nanomaterial coating can disperse extremely tiny platelets into the crevice geometrical surfaces and make much strong and durable material coating to significantly reduce the crevice corrosion. This paper focuses on reducing the crevice corrosion damage by introducing the computer-aided modeling and simulation of nanomaterial coating on crevice structure to verify the nano-coating performance. The sample experiment to prove the strong anti-corrosion of nano-coating on crevice structure has also been performed to compare with the computational simulation results. Both results show that the nano-coating has much strong anti-corrosion performance over currently existing anti-corrosion coating techniques.
Influence of physical activity on prevalence of obesity and hypertension among residents in Nanjing City

[Objective]To explore the current status of physical activity,as well as the prevalence of obesity and hypertension among residents in Nanjing City,analyze the influence of physical activity on prevalence of obesity and hypertension. [Methods] 1 983 residents above 18 years old were randomly selected in an urban district,an suburban district and an rural district in Nanjing City. The questionnaire survey and physical examination were performed.[Results]The prevalence rate of obesity and hypertension was 14. 3% and 33. 6% respectively. The results of univariate logistic regression analysis showed that the prevalence rate of hypertension was associated with age,occupation and housework time( P 0. 05),while the prevalence rate of obesity was associated with gender and occupation( P 0. 05). The multifactor logistic regression analysis showed that increased age displayed an inverse correlation with the prevalence of hypertension,and female was the risk factor for obesity. [Conclusion]The residents in Nanjing City are lack of physical activity,especially young worker and farmers. The gap of the prevalence of obesity and hypertension between urban and rural areas has significantly narrowed. Age is a factor which can influence the prevalence of hypertension,and gender is an influencing factor of obesity.
Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease

Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer's disease (AD). In addition to astrocyte and microglial reactivity, emerging evidence suggests a role of gut microbiota in regulating innate immunity and influencing brain function. Here, we examine the role of the host microbiome in regulating amyloidosis in the APPSWE/PS1ΔE9 mouse model of AD. We show that prolonged shifts in gut microbial composition and diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. We also show that levels of soluble Aβ are elevated and that levels of circulating cytokine and chemokine signatures are altered in this setting. Finally, we observe attenuated plaque-localised glial reactivity in these mice and significantly altered microglial morphology. These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis.
Paradigms for Studying Economies across Cultures

The analysis of economies across cultures has been grounded in economic anthropology, a subfield of anthropology that deals with the entire range of economies and cultures found in the prehistoric, historic and ethnographic records.1 If we think of economic anthropology in this broad sense, then it is the subfield with the greatest potential for creating a cross-cultural science of the economy. Such a science would be able to describe, explain, and, perhaps, eventually to predict pattern, variability and change in economic processes and systems through time and across cultures.
Confronting Injustice: Moral History and Political Theory

Acknowledgments Introduction 1. The Balance of Injustice and the War for Independence 2. Slavery and the Rule of Law in Early Virginia 3. The Legal Entrenchment of Illegality 4. Unfinished Business: Racial Junctures in US History and Their Legacy 5. Corrective Justice, Equal Opportunity, and the Legacy of Slavery and Jim Crow 6. Normal Law, Nearly Just Societies, and Other Myths of Legal Theory 7. Moral Judgment, Historical Reality, and Civil Disobedience 8. Political Responsibility and Resistance to Civil Government 9. Courage and Political Resistance 10. Epilog: From Politics to Philosophy References Index
Dendritic cell-based immunotherapy

Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells in metastatic hormone-refractory cancer. Overall, although many DC vaccines have been tested in the clinic and proven to be immunogenic, and in some cases associated with clinical outcome, there remains no consensus on how to manufacture DC vaccines. In this review we will discuss what has been learned thus far about human DC biology from clinical studies, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity.
Manipulating Human Memory Through Reconsolidation: Stones Left Unturned.

Memory reconsolidation is the process by which a previously stored memory, when recalled, becomes unstable and susceptible to modification before being re-stored. Reconsolidation disruption protoco...
A Switch and Wave of Neuronal Activity in the Cerebral Cortex During the First Second of Conscious Perception

Conscious perception occurs within less than 1 s. To study events on this time scale we used direct electrical recordings from the human cerebral cortex during a conscious visual perception task. Faces were presented at individually titrated visual threshold for 9 subjects while measuring broadband 40-115 Hz gamma power in a total of 1621 intracranial electrodes widely distributed in both hemispheres. Surface maps and k-means clustering analysis showed initial activation of visual cortex for both perceived and non-perceived stimuli. However, only stimuli reported as perceived then elicited a forward-sweeping wave of activity throughout the cerebral cortex accompanied by large-scale network switching. Specifically, a monophasic wave of broadband gamma activation moves through bilateral association cortex at a rate of approximately 150 mm/s and eventually reenters visual cortex for perceived but not for non-perceived stimuli. Meanwhile, the default mode network and the initial visual cortex and higher association cortex networks are switched off for the duration of conscious stimulus processing. Based on these findings, we propose a new "switch-and-wave" model for the processing of consciously perceived stimuli. These findings are important for understanding normal conscious perception and may also shed light on its vulnerability to disruption by brain disorders.
Implementing a remote laboratory on a chip

In light of the recent advances in the Internet of Things and embedded networking technologies, online Internet access for computing devices has been extended from classic computers and servers to virtually all embedded devices with minimal networking capabilities. In this context, our efforts targeted applying this approach to the field of remote learning, by transcending the infrastructure needed for a remote laboratory from mainframe servers and computers to embedded devices: FPGA/System-on-Chip (SoC). This paper describes the internal architecture of a FPGA-based SoC with its components: networking interface (including a Web Server), data acquisition interface (through the on-board Analog-to-Digital converter) and configuration and control software. Also, the article presents the implementation of the Web interface available online that provides an easily accessible, real-time interactive interface for the data visualization and control of the remote FPGA-based SoC, which enables remote access for students and faculty to perform remote experiments and data analysis.
Characterization of Human Body Forward Path Loss and Variability Effects in Voltage-Mode HBC

Human body communication (HBC) has recently emerged as a promising modality for connecting ultralow power wearable/implantable devices. The wide variations in HBC channel characteristics in previously reported literature call for an in-depth analysis of the sources of such variations. It is also important to identify whether most of the loss is due to propagation through human body (forward path), or the lack of common ground among the communicating devices. Our experiments show that along with frequency dependence, multiple other factors, such as excitation/termination modality, electrode area, and pressure, significantly affect HBC loss. In this letter, we focus on measuring human body loss with common ground up to 1 MHz (i.e., megabits of data rate using broadband signaling), and investigate the effects of abovementioned variation sources. Our experiments show: 1) high-impedance termination along with voltage-mode communication maximizes received signal; 2) in capacitive HBC, the forward path loss is significantly lower (average: 0.5 dB and variation: 0.5 dB) compared to the return path loss due to noncommon ground; 3) variation in excitation/termination dependent losses explained by a simplified lumped HBC model; and 4) the effect of coupler area/pressure on forward-path channel loss in common ground scenario.
Abstract 12141: ApoE-HDL Cholesterol Predicts Incident Cardiovascular Events: Aric Study

Background: ApoE-HDL-C, a subfraction of HDL-C that contains ApoE, is thought to be cardioprotective via its inhibition of arterial stiffening and its role in reverse cholesterol transport. Objective: We examined the relationship between ApoE- HDL-C and incident cardiovascular events in the biracial Atherosclerosis Risk in Communities (ARIC) study. Methods: ApoE-HDL-C was measured in 9,258 ARIC participants using a novel automated homogeneous assay (Denka Seiken). The association between ApoE-HDL-C and HDL-C with incident cardiovascular events was assessed using Cox proportional hazard regression models. Covariates included age, race, gender, race, BMI, systolic blood pressure, use of anti-hypertensive medications, diabetes, smoking status, total cholesterol and triglycerides. Results: Mean ApoE-HDL-C and HDL-C levels were 5.06 ± 1.79 mg/dL and 51.10 ± 16.74 mg/dL, respectively. ApoE-HDL-C comprised roughly 10% of total HDL-C levels. ApoE-HDL-C levels were higher in non-diabetics, women and African Americans and showed strong positive correlations with HDL-C and total cholesterol levels. Both apoE-HDL-C and HDL-C were associated with incident CVD, driven mainly by CHD (Table 1). Each 10 mg/dL increase in HDL-C levels was associated with a decreased risk of incident CVD after multivariate adjustment (HR 0.89, 95% CI 0.85, 0.93, p Conclusion: ApoE-HDL-C predicts incident CVD similarly to HDL-C in the biracial ARIC cohort.
Modelling category goodness judgments in children with residual sound errors.

ABSTRACTThis study investigates category goodness judgments of /r/ in adults and children with and without residual speech errors (RSEs) using natural speech stimuli. Thirty adults, 38 children wit...
The transport of Asian dust and combustion aerosols and associated ozone to North America as observed from a mountaintop monitoring site in the California coast range

Author(s): Asher, EC; Christensen, JN; Post, A; Perry, K; Cliff, SS; Zhao, Y; Trousdell, J; Faloona, I | Abstract: Aerosol and tropospheric ozone transport to North America has important implications for regional air quality and climate. We present data from Chews Ridge, a remote mountaintop site in California, in February–September 2012, which identifies separate Asian dust and Asian combustion aerosol signals and quantifies exogenous ozone. We use positive matrix factorization of size-fractionated aerosol X-ray fluorescence data and 206Pb/207Pb and 208Pb/207Pb isotope measurements to isolate aerosol signals of Asian origins and find good agreement between both types source attribution techniques. Power spectra of Asian dust and Asian combustion signals reveal two distinct peaks, one seasonal (~90ndays) and one monthly (~25–30ndays). Overall, 89% of the Asian dust signal occurs in March–May, compared with June–September, whereas only 51% of the Asian combustion signal occurs in March–May. Nearly half the Pb observed at Chews Ridge was derived from Asia (46%; 8.3% from Asian dust, 23% from Asian combustion, and 15% of the Asian Pb signal was not explained by the positive matrix factorization). A positive correlation between deseasonalized ozone concentrations and the Asian factors suggests that ozone is elevated by 6.3n±n0.8nppb due to transpacific transport. Scanning mobility particle size spectra were also measured from May to September and indicate that new particles are often produced and grow throughout the afternoon during onshore flow. We hypothesize that particle nucleation on the windward edge of the continent is an important source of new particles.
Experiencing the Environment as Hazard

The environment as hazard has been under intensive study for some 20 years, and has mostly focused on natural hazards. Industrialized countries exhibit a pattern of declining death rates and increasing damage, despite substantial investment in technical means for coping. In developing countries, both damage and deaths are high. A conceptual model in which hazard events and consequences arise from the interaction of environment and society and are mediated by coping actions helps to explain these divergences. The observed and perceived experience are described for each of the model elements.
Deriving the Two Argument Restriction without Recursion

It is a universal property of argument structure that verbs cannot take more than three arguments –one external and two internal (Hale K, Keyser SJ, On argument structure and the lexical expression of syntactic relations. In: Hale K, Keyser J (eds) The view from Building 20: essays in linguistics in honor of Sylvain Bromberger. MIT, Cambridge, 2002, henceforth HK any additional (pseudo)arguments are introduced via (possibly recursive) syntactic or discursive procedures, not lexical. This is the Two (internal) Argument Restriction (TAR), which is part of the basic architecture of natural language. It is argued that a modified version of the theory presented in H&K can account for this restriction. In this proposal, the TAR crucially depends on the lack of recursion in the lexicon (in building argument structures), thereby restricting the possibility of using this formal mechanism to the domain of sentential syntax (building of sentences). Argument structures are thus built in a cyclic and directional way, and without recursion.
Creative Genius as Causal Agent in History: William James's 1880 Theory Revisited and Revitalized:

Near the onset of his illustrious career, the psychologist William James proposed a theory of how individual genius can exert a unique and enduring causal impact on the history of civilization. Aft...
Transcriptome profiling of induced susceptibility effects on soybean-soybean aphid (Hemiptera: Aphididae) interaction.

Soybean aphid (Aphis glycines Matsumura; SBA) is the most economically damaging insect of soybean (Glycine max) in the United States. One previous study demonstrated that avirulent (biotype 1) and virulent (biotype 2) biotypes could co-occur and interact on resistant (i.e., Rag1) and susceptible soybean resulting in induced susceptibility after 11 days of feeding. The main objective of this research was to employ RNA sequencing (RNA-seq) technique to compare the induced susceptibility effect of biotype 2 on susceptible and resistant soybean at day 1 and day 11 (i.e., both susceptible and resistant soybean were initially challenged by biotype 2 and the effect was monitored through biotype 1 populations). We investigated susceptible and Rag1 transcriptome response to SBA feeding in soybean plants colonized by biotype 1 in the presence or absence of an inducer population (i.e., biotype 2). Ten RNA datasets are reported with 266,535,654 sequence reads (55.2 GB) obtained from pooled samples derived from the leaves collected at day 1 and day 11 post SBA infestation. A comprehensive understanding of these transcriptome data will enhance our understanding of interactions among soybean and two different biotypes of soybean aphids at the molecular level.
Synthesis and Structure of an Octasila[4.4]betweenallene

Highly strained, symmetrical betweenallenes would be of considerable interest owing to the fact that the theoretically predicted relief of strain in small cyclic allenes by concomitant bending and twisting is rendered impossible. Thus strained symmetrical betweenallenes can gain no strain relief by bending, since what is gained in one ring is lost in the other, and therefore only twisting, as defined as a reduction in the normal allene dihedral angle of 90[degree], is available for relief of strain. We report here the synthesis, structure, and thermal behavior of the first highly strained betweenallene. 15 refs., 2 figs., 1 tab.
A Novel Part of Speech Tagging Framework for NLP Based Business Process Management

Natural Language Processing (NLP) is a key technique to automate Business Process Management (BPM) at different levels. The performance of existing NLP based BPM methods suffer from the limited accuracy of Part of Speech (POS) tagging, which is a key step in NLP pipelines. Note that the performance of POS tagging highly depends on the domain of annotated training data. However, most state-of-the-art POS taggers are trained from corpus in newswire domain which usually have different syntax features with business process description (BPD). The syntax features of BPD domain include usually starting with an imperative verb and containing numerous out-of-vocabulary (OOV) words. In this paper, we propose a novel POS tagging framework to tackle these problems. The main idea is that syntax feature of starting with imperative verb could be studied by enhancing the proportion of correctly POS-annotated imperative sentences in the training data. The trained POS tagger could reduce the overall POS tagging error by nearly 12% compared with newswire trained POS tagger. For verbs which are key words in BPD, the tagging precision could be increased by 27%. The lexical ambiguity caused by OOV words is solved by extracting local contextual knowledge out of images which are attached to help users understand the process better. Experimental results show that the overall POS tagging accuracy could be increased by nearly 10% with contextual OOV knowledge.
Strategies for Acute Stress Reactions and Acute Stress Disorder (ASD)

This chapter deals entirely with acute posttraumatic responses. It begins by describing acute stress reactions, normal reactions to traumatic events both in civilian and military contexts. Issues such as resilience and prevention are addressed with respect to such acute responses, with specific attention to Psychological First Aid for civilians and Forward Psychiatry for military personnel in a war zone. Acute Stress Disorder (ASD) is presented with respect to how it differs from both normal reactions and from PTSD. The DSM-5 diagnostic criteria for ASD are presented in detail. Treatment for ASD is presented with specific attention to CBT approaches.
Body Dissatisfaction of Ethnically Diverse Gay, Straight Men and the Proliferation of Social Media and Fashion Magazines

Mass media is considered the most pervasive cause of body dissatisfaction. The current research takes a more focused look at ethnic minority gay men and their body dissatisfaction. The objective of this study was to examine the effects of social and entertainment media (fashion magazines) exposure on BD, social comparison and thin-ideal internalization of diverse gay and straight men. This study replicated results that find gay men are more dissatisfied with their bodies than straight men. This then may affect their choices of clothing, as gay may were found more likely to hide their bodies with loose clothing. Increased exposure to social and entertainment media (fashion magazines) affected BD in young diverse males. Entertainment media (fashion magazines) should focus on presenting more realistic, more diverse and more types of male bodies in general. Since young people use SNS so frequently, these sites should be a focus of media literacy programs.
Expression of Separate Foreign Proteins from the Rotavirus NSP3 Genome Segment Using a Translational 2A Stop-Restart Element

The segmented 18.5-kB dsRNA genome of rotavirus expresses 6 structural and 6 nonstructural proteins. We investigated the possibility of using the recently-developed plasmid-based rotavirus reverse genetics (RG) system to generate recombinant viruses that express a separate foreign protein, in addition to the 12 viral proteins. To address this, we replaced the NSP3 open-reading-frame (ORF) of the segment 7 (pT7/NSP3) transcription vector used in the RG system with an ORF encoding NSP3 fused to a fluorescent reporter protein (i.e., UnaG, mRuby, mKate, or TagBFP). Inserted at the fusion junction was a teschovirus 2A-like self-cleaving element designed to direct the separate expression of NSP3 and the fluorescent protein. Recombinant rotaviruses made with the modified pT7/NSP3 vectors were well growing, generally genetically stable, and expressed NSP3 and a separate fluorescent protein detectable by live cell imaging. NSP3 made by the recombinant viruses was functional, inducing nuclear accumulation of cellular poly(A)-binding protein. Further modification of the NSP3 ORF showed that it was possible to generate recombinant viruses encoding 2 foreign proteins (mRuby and UnaG) in addition to NSP3. Our results demonstrate that, through modification of segment 7, the rotavirus genome can be increased in size to at least 19.8 kB and can be used to produce recombinant rotaviruses expressing a full complement of viral proteins and multiple foreign proteins. The generation of recombinant rotaviruses expressing fluorescent proteins will be valuable for the study of rotavirus replication and pathogenesis by live cell imagining and suggest that rotaviruses may prove useful as expression vectors.
Analysis of traditional and modern image encryption algorithms under realistic ambience

Cryptography (encryption/decryption) is one of the prevailing mechanisms for protection of information (data or image) in the growing era of computerized exchange. It is the art of securing data/image by changing it into an unreadable format, called cipher text/image. Encryption mechanism is said to be efficient if it offers high security and robustness against attacks, and endow with very low correlation value between cipher and the original information. Enormous techniques and corresponding survey papers are available in literature considering only a few methods or parameters into account, but there is a stern need of investigation, which thoroughly considers vast variety of techniques and compares them in the light of numerous performance metrics under the influence of wide variety of probable threats. In view of the fact, this paper has taken account of almost all traditional, modern, chaotic, and quantum-chaotic based methods under the influence of prevalent intimidation and does a comprehensive investigation based on various performance metrics. To measure the efficacy, all the mechanisms are implemented in MATLAB-2014. Chaos and Quantum based algorithms are the superlative in comparison to others presented in literature under most of the extensive threats (attacks, noises etc.) and can resist brute force attacks due to large key space. In addition, suggestions for future scope have been given.
Increased Hepatic Stiffness in Young Adults After Biventricular Repair of Congenital Heart Disease.

Background This study evaluated hepatic stiffness by shear wave elastography to investigate subclinical hepatic changes in a cohort of patients with congenital biventricular heart disease (BHD). Methods The BHD patients and age-matched healthy controls were prospectively recruited for hepatic ultrasonography and shear wave elastography. Real-time B-mode imaging with Doppler was performed for celiac axis, superior mesenteric artery, and main portal vein, and hepatic shear wave elastography was assessed. Vascular Doppler indices included peak velocities; velocity time integral, resistive, pulsatility, and acceleration indices; and portal vein volumetric flow. One-way analysis of variance was used for comparisons between controls, BHD, and a cohort of Glenn and Fontan patients. Results In all, 66 subjects were included. Thirty-six subjects were in the BHD group (male, 25; female, 11; mean age 27.4 ± 4.6 years; mean weight 76.8 ± 18.5 kg), and 30 were healthy controls (male, 11; female, 23, mean age 27.4 ± 3.8 years; mean weight 70 ± 17.2 kg). Shear wave elastography was increased in BHD (8.11 ± 2.07 kPa) compared with controls (5.44 ± 1.18 kPa; P Conclusions Increased hepatic stiffness was observed in young adults with repaired BHD. Although cause is not established, possibilities include hepatic congestion early in life or elevated central venous pressures due to right heart burden. Further research is required to determine whether these patients will ultimately have clinically relevant liver disease.
502 The co-expression of two immune complex molecules, VISTA and TIGIT, define a dysfunctional cytotoxic T cell subset

Background Cancer immunotherapies have proven, over the last decade, to be of extreme importance for long term survival of patients. Specifically, immune checkpoint inhibitors such as anti-CTLA-4 and anti-PD-1/PD-L1 have had tremendous clinical success treating many cancers including melanoma, lung, breast, colon, and bladder cancer. The low response rate (~30%) of these drugs suggest a mechanism of resistance within the tumor microenvironment, and it demonstrates the immense need to study and develop alternative routes to long-term anti-tumor immunity.1V-domain Immunoglobulin Suppressor of T-cell Activation (VISTA) has been shown to be a suppressive molecule in the tumor microenvironment in preclinical models and VISTA’s expression is correlated with poor patient outcome across several cancers.2T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) is a functional receptor expressed on NK cells and T cells that contributes to a suppressive tumor microenvironment by acting on T cells, NK cells, and antigen presenting cells.3 Methods We use flow cytometry to visualize single cell expression of VISTA and TIGIT on CD8+ tumor infiltrating lymphocytes in pre-clinical models. Functional studies include cytotoxic assays as well as intracellular cytokine staining after cell sorting. Results Here we show the expression of these two immune checkpoint molecules, VISTA and TIGIT, across several pre-clinical models, and how their co-expression subsets a distinctly dysfunctional population of cytotoxic T cells. Conclusions Our data provides foundation to study the rejuvenation of this subset of T cells to restore cytotoxic function and therefore, anti-tumor immunity. Trial Registration NA Ethics Approval All in vivo studies were reviewed and approved by Institutional Animal Care and Use Committee (Approval number 2019-2142). Consent NA References Fares CM, Allen EMV, Drake CG, Allison JP & Hu-Lieskovan S. Mechanisms of resistance to immune checkpoint blockade: why does checkpoint inhibitor immunotherapy not work for all patients?American Society of Clinical Oncology Educational Book 2019;147–164. Xu W, Hieu T, Malarkannan S. & Wang L. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol 2018;15:438–446. Manieri NA, Chiang EY & Grogan JL. TIGIT: A Key Inhibitor of the Cancer Immunity Cycle. Trends Immunol 2017;38:20–28.
Incorporation of Integral Membrane Proteins into Liposomes

One of the most intriguing features of biological membranes is their asymmetry. A variety of techniques has shown that most membrane components are not randomly distributed, but specifically oriented with respect to the two membrane surfaces (1,2). In the case of the mitochondrial inner membrane, cytochromes c and cl are localized on the outer side (C-side) and the mitochondrial ATPase F1 on the inner or matrix side (M-side) of the membrane (2). Cytochrome c oxidase spans the membrane (3–5) so that some subunits of this oligomeric enzyme are situated on the outer side, some on the inner side and some in the interior of the membrane (4). We are beginning to understand how this asymmetric architecture determines the various vectorial functions of biological membranes but we know next to nothing about how this asymmetry arises in vivo. For example, it would be interesting to know to what extent the asymmetric transmembranous orientation of cytochrome oxidase is caused by an asymmetry in the enzyme itself, or by specific properties such as charge, curvature, phospholipid asymmetry or protein composition of the receptor membrane.
A New Start down an Old Road Toward Substantive Voter Equality for People with Disabilities

As the June 2020 state primary election in Pennsylvania approached, Joseph Drenth, who is legally blind, faced an untenable choice: vote by mail and sacrifice the ability to cast a private and independent vote, or continue to vote privately and independently at a polling location and sacrifice the health and safety of himself and his family due to the COVID-19 pandemic? Fortunately, a preliminary injunction ordering the state to implement a remote accessible vote-by-mail system ultimately made such a choice unnecessary for Mr. Drenth. Unfortunately, voters with disabilities in many other jurisdictions throughout the country were not so lucky. Even as the threat of COVID-19 hopefully moves to our rearview mirrors in the coming year, Mr. Drenth’s successful lawsuit highlights a critical but underutilized legal tool for ensuring that voters with disabilities are afforded an equal voting experience—including the ability to cast a private and independent ballot—as compared to other voters. This article proceeds in three parts. Part I summarizes the history and current state of voting with a disability in the United States. In doing so, it outlines the main federal statutory provisions related to voting rights for individuals with disabilities. Part II explains how federal courts initially narrowed the guarantee of the ADA and the Rehabilitation Act to mere technical equality in voting in a way that denied equal dignity and treatment when voting with a disability. It then analyzes a more recent line of cases that backs away from this early case law to expand the reach of the ADA and Rehabilitation Act to also ensure substantive equality and a fuller, more robust right to vote with a disability. Part III then speculates about broader adherence to a mandate of substantive equality throughout the federal judiciary.
Testing the Giles hypothesis using geometric morphometrics.

OBJECTIVES The Giles hypothesis posits that differences in the cranial morphology of Pan troglodytes and Gorilla gorilla are largely the result of allometric scaling. However, previous support for the Giles hypothesis was based on bivariate plots of linear measurements. This investigation uses geometric morphometric methods to retest this hypothesis and its prediction that extending the ontogenetic trajectory of a chimpanzee would produce an adult gorilla-like cranial morphology. MATERIALS AND METHODS Forty-three 3D cranial landmarks were collected from an ontogenetic series of 76 Pan troglodytes and 58 Gorilla gorilla specimens. Ontogenetic trajectories of cranial shape change were computed via multivariate regression of Procrustes aligned coordinates against LnCS (size vector) and molar eruption stage (developmental vector). These two vectors were then used in developmental simulations to extend the ontogenetic trajectories of adult chimpanzees. Allometric trajectories of chimpanzees and gorillas were also directly compared using Procrustes ANOVA. RESULTS Pan and Gorilla significantly differ in their allometric trajectories, and none of the Pan developmental simulations resembled actual adult gorillas. Additionally, the more the Pan developmental vector was extended, the more morphologically distinct the simulations became from actual adult gorillas. DISCUSSION Taken together, these results do not support the Giles hypothesis that allometric scaling is primarily responsible for observed morphological differences between chimpanzee and gorilla crania. This investigation demonstrates that neither "growing" a chimpanzee to the size of a gorilla, nor extending a chimpanzee's developmental shape trajectory will result in an adult gorilla-like cranial morphology as they differ in their patterns of allometry.
Exploring the lengthiest ambulatory breast surgery clinic appointments: is the patient the problem?

Background Prolonged outpatient clinic appointments can disrupt schedules, impacting patients and providers. We sought to define features of the longest ambulatory appointments in a breast surgery clinic, and to ascertain whether patients attending these appointments consistently have protracted appointments. Methods A single-institution retrospective cohort study was conducted of breast surgery clinic patients, January 2017 to May 2019, and the longest 1% of appointments identified using a real-time patient tracking system. A primary chart review was performed, and data abstracted. Other appointments attended by these patients were identified, and the ratio of appointments >75th percentile duration (protracted appointments) to the total appointments during the study period was calculated, enabling comparison for patients with consistently protracted (ratio >50%) vs. sporadically protracted appointments (≤50%). Descriptive analysis was performed, and results reported as medians with inter-quartile ranges. Results A total of 15,265 clinic appointments were identified, and the longest 148 (exceeding 244 minutes) analyzed. Median appointment length was 264 minutes (inter-quartile range: 253-290). 70% were new patient appointments, and 54% of patients underwent a test/investigation that day. A minority were obese (39%), smokers (41%), diagnosed with a psychiatric comorbidity (34%), had a genetic cancer syndrome (22%), or received unexpected news at their appointment (16%). Of 118 patients with multiple appointments, 26% had consistently protracted appointments and 74% sporadically protracted appointments. Conclusions The lengthiest appointments are usually newly diagnosed cancer patients. Only a minority of patients have consistently protracted appointments, implying that a patient's previously prolonged appointment may not predict future long appointments.
Intercalation of Water in Kaolinite (Al2Si2O5(OH)4) at Subduction Zone Conditions: Insights from Raman Spectroscopy

Kaolinite (Al2Si2O5(OH)4) is produced by weathering of continental rocks and is an important constituent of terrigenous sediment flux in subduction zone. It helps in transporting water into the Ear...
Letermovir conversion after valganciclovir treatment in cytomegalovirus high-risk abdominal solid organ transplant recipients may promote development of cytomegalovirus-specific cell mediated immunity.

Purpose To evaluate the association of conversion from valganciclovir to letermovir on cytomegalovirus-specific cellular immunity METHODS: Adult patients were included if they received a kidney or liver transplant between 8/1/2018-12/31/20, developed symptomatic, high-level CMV viremia and were converted to letermovir 480 mg daily as monotherapy after treatment with ganciclovir-derivatives for a minimum of 4 weeks and had subsequent CMV cell-mediated immunity (CMI) testing via ICS assay by flow cytometry (Viracor Eurofins T Cell Immunity Panel). Results Seven patients met inclusion criteria; 87.5% were male and recipients of a kidney transplant. All patients were CMV high risk (D+/R-). Mean time from transplant to CMV disease was 200±91 days. Peak viral load (VL) during CMV treatment was 540,341±391,211 IU/mL. Patients received a mean of 30±24 weeks (range:4-78 weeks) of therapy with ganciclovir-derivatives at induction doses prior to letermovir introduction. The median absolute lymphocyte count (ALC) at letermovir initiation was 400/uL (IQR 575) and the median VL was 51.6 (range: ND-490) IU/mL. Most patients (n = 5/7, 71.4%) experienced an increase in VL 1 and/or 2 weeks after conversion to letermovir. All patients had positive CMI per ICS assay after conversion. Patients received a mean of 10.3±6.9 weeks of letermovir prior to having a positive result. Median ALC at positivity was 900/uL. Immunosuppression was not further reduced from initiation of letermovir to demonstration of CMV CMI. No patient had progressive replication or breakthrough disease while maintained on letermovir and 3 patients (42.9%) underwent antiviral withdrawal without recurrence at last follow up. Conclusion In this case series of abdominal transplant recipients with severe or persistent CMV infection, patients developed CMV-specific CMI after conversion to letermovir monotherapy. This data suggests that using letermovir in place of valganciclovir for secondary prophylaxis may address the lack of efficacy previously seen with this approach, as well as the issues that plague antiviral withdrawal with systematic monitoring. Future prospective studies are needed to evaluate this effect in a more controlled research environment with serial CMI testing to elucidate the optimal duration of letermovir when used in this way This article is protected by copyright. All rights reserved.