cssi/SciSciGPT-SciSciNet huggingface dataset:
Validation of ultrasonography for non-invasive assessment of diaphragm function in muscular dystrophy.

Key points Duchenne muscular dystrophy (DMD) is a severe, degenerative muscle disease that is commonly studied using the mdx mouse. The mdx diaphragm muscle closely mimics the pathophysiological changes in DMD muscles. mdx diaphragm force is commonly assessed ex vivo, precluding time course studies. Here we used ultrasonography to evaluate time-dependent changes in diaphragm function in vivo, by measuring diaphragm movement amplitude. In mdx mice, diaphragm amplitude decreased with age and values were much lower than for wild-type mice. Importantly, diaphragm amplitude strongly correlated with ex vivo specific force values. Micro-dystrophin administration increased mdx diaphragm amplitude by 26% after 4 weeks. Diaphragm amplitude correlated positively with ex vivo force values and negatively with diaphragm fibrosis, a major cause of DMD muscle weakness. These studies validate diaphragm ultrasonography as a reliable technique for assessing time-dependent changes in mdx diaphragm function in vivo. This technique will be valuable for testing potential therapies for DMD. Abstract Duchenne muscular dystrophy (DMD) is a severe, degenerative muscle disease caused by dystrophin mutations. The mdx mouse is a widely used animal model of DMD. The mdx diaphragm muscle most closely recapitulates key features of DMD muscles, including progressive fibrosis and considerable force loss. Diaphragm function in mdx mice is commonly evaluated by specific force measurements ex vivo. While useful, this method only measures force from a small muscle sample at one time point. Therefore, accurate assessment of diaphragm function in vivo would provide an important advance to study the time course of functional decline and treatment benefits. Here, we evaluated an ultrasonography technique for measuring time-dependent changes of diaphragm function in mdx mice. Diaphragm movement amplitude values for mdx mice were considerably lower than those for wild-type, decreased from 8 to 18 months of age, and correlated strongly with ex vivo specific force. We then investigated the time course of diaphragm amplitude changes following administration of an adeno-associated viral vector expressing Flag-micro-dystrophin (AAV-μDys) to young adult mdx mice. Diaphragm amplitude peaked 4 weeks after AAV-μDys administration, and was 26% greater than control mdx mice at this time. This value decreased slightly to 21% above mdx controls after 12 weeks of treatment. Importantly, diaphragm amplitude again correlated strongly with ex vivo specific force. Also, diaphragm amplitude and specific force negatively correlated with fibrosis levels in the muscle. Together, our results validate diaphragm ultrasonography as a reliable technique for assessing time-dependent changes in dystrophic diaphragm function in vivo, and for evaluating potential therapies for DMD.
Mixed Methods Study of the Effectiveness of Intensive Family Finding Services with Youth in Congregate Care

ABSTRACTHelping youth in congregate care form healthy relationships and achieve stability is an ongoing concern among child welfare stakeholders. The purpose of this mixed methods study was to examine the effectiveness of a family finding intervention with youth with a history of congregate care placement and to explore factors related to the achievement of relational and physical permanency. Results from a logistic regression indicated that for youth previously in congregate care, intensive family finding increased the odds of achieving relational permanency, but not physical permanency. Qualitative analyses identified several themes surrounding successes and challenges to achieving relational and physical permanency.
Polyelectrolyte Coacervates Deposited as High Gas Barrier Thin Films

Multilayer coatings consisting of oppositely charged polyelectrolytes have proven to be extraordinarily effective oxygen barriers but require many processing steps to fabricate. In an effort to prepare high oxygen barrier thin films more quickly, a polyelectrolyte complex coacervate composed of polyethylenimine and polyacrylic acid is prepared. The coacervate fluid is applied as a thin film using a rod coating process. With humidity and thermal post-treatment, a 2 µm thin film reduces the oxygen transmission rate of 0.127 mm poly(ethylene terephthalate) by two orders of magnitude, rivalling conventional oxygen barrier technologies. These films are fabricated in ambient conditions using low-cost, water-based solutions, providing a tremendous opportunity for single-step deposition of polymeric high barrier thin films.
The experiences of a biochemist in the evolving world of G protein-dependent signaling.

Preface This review describes how a biochemist and basic researcher (i.e. myself) came to make a career in the area of receptor-coupled signal transduction and the roles cellular signaling activities play both in normal physiology and in disease. Much of what has been the best part of this research life is due to the time I spent with Bob Lefkowitz (1982–1985), during an extraordinary period in the emerging field of G-protein-coupled receptors. Among my laboratory colleagues were some truly outstanding scientists including Marc Caron, the late Jeffrey Stadel, Berta Strulovici, Jeff Benovic, Brian Kobilka, and Henrik Dohlman, as well as many more. I came to Bob's laboratory after being trained as a physical biochemist and enzymologist. Bob and his laboratory exposed me to a research style that made it possible to connect the kinds of fundamental biochemical and mechanistic questions that I loved to think about with a direct relevance to disease. Indeed, I owe Bob a great deal for having imparted a research style and philosophy that has remained with me throughout my career. Below, I describe how this has taken me on an interesting journey through various areas of cellular signaling, which have a direct relevance to the actions of one or another type of G-protein
Practice and philosophy of climate model tuning across six US modeling centers

Model calibration (or "tuning") is a necessary part of developing and testing coupled ocean-atmosphere climate models regardless of their main scientific purpose. There is an increasing recognition that this process needs to become more transparent for both users of climate model output and other developers. Knowing how and why climate models are tuned and which targets are used is essential to avoiding possible misattributions of skillful predictions to data accommodation and vice versa. This paper describes the approach and practice of model tuning for the six major U.S. climate modeling centers. While details differ among groups in terms of scientific missions, tuning targets and tunable parameters, there is a core commonality of approaches. However, practices differ significantly on some key aspects, in particular, in the use of initialized forecast analyses as a tool, the explicit use of the historical transient record, and the use of the present day radiative imbalance vs. the implied balance in the pre-industrial as a target.
Text Message Intervention (TEACH) Improves Quality of Life and Patient Activation in Celiac Disease: A Randomized Clinical Trial

Objective To determine the impact of the Text Message Educational Automated Compliance Help (TEACH) text message intervention as a pragmatic approach for patient engagement among adolescents with celiac disease (CD) as measured by gluten-free diet (GFD) adherence, patient activation, and quality of life (QOL). Study design Randomized controlled trial with patient recruitment at a pediatric, university-based hospital and through social media; 61 participants ages 12-24 years with CD diagnosed at least 1 year were enrolled. The TEACH intervention cohort received 45 unique text messages over a 3-month study period while the control group received standard of care treatment. Primary outcome measures included objective markers of GFD adherence included serum tissue transglutaminase IgA and deamidated gliadin peptide IgA levels. Secondary patient-reported outcomes collected via online survey included the Celiac Dietary Adherence Test, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Global Short Form measure of QOL, Celiac Symptom Index, and Patient Activation Measure. All measures were assessed at enrollment and after the 3-month study period. Statistical analysis performed using the 2-tailed paired Student t test. Results Among the TEACH intervention group, there was significant improvement comparing enrollment scores with 3-month follow-up scores in patient activation (Patient Activation Measure score 63.1 vs 72.5, P = .01) and QOL (NIH PROMIS Global Mental Health 50.8 vs 53.3, P = .01 and NIH PROMIS Global Physical Health 50.8 vs 57.7, P = .03). There was no statistically significant difference in patient-reported or objectively measured GFD adherence. Conclusions TEACH is an effective intervention among patients with CD to improve patient activation and QOL, even among a cohort with GFD adherence at baseline. Trial registration ClinicalTrials.gov : NCT02458898 .
TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity

Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other. However, there is little experimental evidence supporting this mechanism in TRP channels. Here, we combined high-throughput mutagenesis, functional screening, and deep sequencing to identify mutations from a total of ~7,300 TRPV1 random mutant clones. We found that strong decreases in hydrophobicity of amino acids are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation. Altogether, our work provides initial correlative support for a previously hypothesized temperature mechanism in TRP ion channels.
The Electrochemical Properties of Zinc-rich Paints

SummaryThe paper distinguishes between the electrochemical and chemical roles of zinc-rich paints. Use was made of a technique in which the zinc paint layer was insulated from the underlying steel surface. It was shown that the corrosion behaviour of artificial pores provided in such coatings was much less satisfactory than at similar pores in painted specimens from which insulating layers were omitted. Use of a micro-electrode also showed that a much more rapid rise in pH was experienced at the exposed steel surface in specimens of the second kind. This provides further evidence of a short period of cathode protection which, however, is essential if the protection due to subsequent precipitation of zinc salts is to prove adequate.
The appropriateness of 30-day mortality as a quality metric in colorectal cancer surgery.

Abstract Background Our study compares 30-day vs. 90-day mortality following colorectal cancer surgery (CRS), and examines hospital performance ranking based on this assessment. Methods Mortality rates were compared between 30 vs. 90 days following CRS for patients with stage I-III colorectal cancers from the National Cancer Database (2004–2012). Risk-adjusted hierarchical regression models evaluated hospital performance based on mortality. Hospitals were ranked into top (10%), middle (80%), and lowest (10%) performance groups. Results Among 185,464 patients, 90-day mortality was nearly double the 30-day mortality (4.4% vs. 2.5%). Following risk adjustment 176 hospitals changed performance ranking: 39% in the top 30-day mortality group changed ranking to the middle group; 37% of hospitals in the lowest 30-day group changed ranking to the middle 90-day group. Conclusions Evaluation of hospital performance based on 30-day mortality is associated with misclassification for 15% of hospitals. Ninety-day mortality may be a better quality metric in oncologic CRS.
Computer Animated Control Laboratory Emulation Modules

Abstract The importance of hands-on learning in undergraduate level control courses is indisputable. Unfortunately, a laboratory platform which allows multiple control methods to be applied to different systems can easily cost several tens of thousands of dollars per setup, making the development of a laboratory with several experimental stations prohibitively expensive for most universities. A more viable option is to use computers, which are fast, flexible, easy to use, and widely available on most campuses, to simulate the real world systems. This paper details such a system which has been developed using MATLAB, a numerical analysis package, to simulate and animate a variety of representative systems.
Regulation of S-Adenosylmethionine Synthesis in Human Lymphocytes

The biochemistry of S-adenosylmethionine (AdoMet) provides several possible strategies for drug design. One focuses on the ability of S-adenosylhomocysteine (AdoHcy) and its analogues to inhibit transmethylation reactions; and involves the design of agents that inhibit transmethylases directly, or inhibit AdoHcy hydrolase causing AdoHcy accumulation, or react intracellularly with homocysteine to form inhibitory analogues of AdoHcy.
The Economies of Israel’s Neighbors

Naturally one must begin with the Phoenicians whose trade expansion reached its height during the eighth through mid-seventh centuries B.C.E.1 Phoenicia was famous for its fish2 but its most famous industry was the production of Tyrian purple, a prestigious substance distilled from two types of sea snails native to its coast, used to produce a color-fast dye for woolen goods. Much of the wool and textiles were probably obtained from Moab and Babylonia while the linen, which was woven, no doubt had its origin in Edom or Egypt or, perhaps, the Jericho area (see Josh. 2:6)3. The proximity of the coastal waters to the great cedar forests promoted the production and export of various wood products, ships, and lumber. The Phoenicians also possessed a glass industry4 and a toiletry industry, that respectively, exported polychrome glass beads and marble scent bottles. Further, making use of imported metals and ivory, they produced bronze and golden bowls and ivory carvings known and coveted throughout the ancient world. Smelters of iron and copper are mentioned on funerary stelae and metalworking tools are depicted. Needless to say, the Phoenicians also played an active role in the export and import of slaves (see, for instance, Amos 1:9). The typical Phoenician red-burnished pottery of the ninth-eighth centuries has been found at coastal sites including er-Retabeh in the Egyptian Delta, Bethpelet and er-Regeish near Gaza, and inland Israelite cities such as Hazor and Samaria.
Sauerstofftransport nach Herz-Lungen-Wiederbelebung

Hypoxamie, Hyperkapnie und metabolische Acidose werden haufig nach Herz-Lungen-Wiederbelebung beobachtet [3, 5, 6]. Die hier berichteten Ergebnisse an Patienten und im Tierexperiment zeigen, das die Acidose mit Natriumbikarbonat und Hyperkapnie durch Beatmung korrigiert werden konnen. Die Therapie der Hypoxamie ist jedoch oft problematisch.
Inspiring Types of Purpose

Sources of inspiring purpose in life are endless. People can be moved to serve their family, their God, their country, or their community. They may also find purpose in promoting a new kind of music, creating a novel art form, or advancing a line of scientific inquiry. Caring for others, teaching, or working on behalf of a personally meaningful cause can also imbue lives with purpose. The body of empirical work on different forms of purpose is surprisingly small, but more studies focus on sources of meaning. While meaning and purpose are not synonymous, research on meaning sheds light on potential kinds of purpose, and consequently, sources of meaning are primarily discussed in this chapter. Likewise, a discussion of the importance of studying different types of purpose along with an outline of some of the more significant challenges involved in doing so is also included. Finally, this chapter features illustrative examples of real people who exemplify distinct types of life purposes.
Predictive Process Design Kits

For nearly half a century, semiconductor technology has continued to deliver exponential growth in the number of transistors on a chip. Even in the 22 nm processes of today, with exponentially increasing costs of research and development, masks, and design, transistors are still cheaper and denser than in previous process nodes. However, the cracks are showing in the industry’s armor. Prior to 2005, each technology generation brought not only lower cost, but also more speed and less power consumption. Today, designers must be much more creative to balance the competing customer needs of cost, speed, and power. One size no longer fits all.
Calcium Oxalate Crystallization in Urothelial-Lined Systems

The liquid/solid interface is of fundamental importance in the crystallization of solutes from aqueous systems. Nucleation preferentially occurs at interfaces that inherently present energetically favored sites for the initiation of crystallization1,2. Most crystallization studies have dealt with the nature of the solute and/or the solvent2,4 and have usually ignored consideration of the containers and the nature of the solid surfaces enclosing the systems.
Not My Child

A popular consensus about the mandatory vaccination of schoolchildren against smallpox never existed. This chapter summarizes the diffuse antivaccination movement during the Progressive Era, especially the factors feeding it and organizational manifestations. One of them, the American Humane Association, expanded its agenda to oppose immunizations and use of children as test subjects. Before it became quiescent in the 1930s, the antivaccination campaign successfully lobbied many states to ban compulsory inoculations for school admissions.
Ethnic Disparities in Autism Spectrum Disorder Screening and Referral: Implications for Pediatric Practice.

ABSTRACT:Objective:Autism spectrum disorder (ASD) screening completion rates are often low despite their validity and influence on earlier intervention and positive treatment outcomes. This study sought to examine the use of one ASD screening tool, the Modified Checklist for Autism in Toddlers-Revis
The role of genomic profiling in identifying molecular phenotypes in obstructive lung diseases

Purpose of review The biology underlying asthma and chronic obstructive pulmonary disease (COPD) is heterogeneous. Targeting therapies to patient subgroups, or 'molecular phenotypes', based on their underlying biology is emerging as an efficacious treatment strategy. This review summarizes the role of airway sample gene expression profiling in understanding molecular phenotypes in obstructive lung disease. Recent findings Recent gene expression studies have reinforced the importance of Type two (T2) inflammation in asthma and COPD subgroups. Studies in asthma also suggest that the molecular phenotype with enhanced T2 inflammation is itself heterogeneous with a subgroup that has steroid-refractory inflammation. Other inflammatory pathways are also emerging as implicated in asthma and COPD molecular phenotypes, including Type one and Type 17 adaptive immune responses and proinflammatory cytokines, such as interleukin-6. Summary Genomic profiling studies are advancing our understanding of the complex biology contributing to asthma and COPD molecular phenotypes. Recent studies suggest that asthma and COPD subgroups may benefit from different treatment strategies than those currently in practice.
The Association between Paradoxical Vocal Fold Motion and Dysphonia in Adolescents

Objective Associations between dysphonia and paradoxical vocal fold motion (PVFM) have been previously reported in adults, but it is unclear whether similar associations exist for adolescents. The goals of this study were to identify the prevalence and severity of voice disorders in adolescent patients with PVFM, identify differences between those with and without clinician-identified dysphonia, and investigate what factors were associated with voice handicap in this population. Methods A retrospective review of eligible adolescent patients diagnosed with PVFM over a 1-year period at a single institution was undertaken. Data collected from the medical record included demographic background, medical history and workup, patient- and family-reported symptoms, and findings from the laryngeal examination. The presence or absence of clinician-diagnosed dysphonia was used to subdivide the sample for analysis. Results Forty-eight patients with PVFM were included. The sample was primarily female (73%) with a median age of 15 years. Few patients had voice complaints (5%), but clinician-diagnosed dysphonia was common (52%) and ranged from mild to moderate. Vocal hyperfunction was frequently observed (55%), but anatomic abnormalities associated with dysphonia were rare (6%). Adolescents with dysphonia were significantly older, more likely to have vocal hyperfunction on laryngoscopy, and more likely to return for therapy than those without dysphonia. No notable differences existed in the number of behavioral therapy sessions or in the likelihood of completing treatment between the two groups. The majority of participants (79%) had at least one "confounding factor" (i.e., were currently taking a medication for asthma, allergies, or reflux, or had a laryngeal abnormality) but this did not differ significantly between those with and without dysphonia. A minority of individuals (28%) had abnormal scores on the Voice Handicap Index (VHI). Age was positively correlated with dysphonia severity but no other significant associations were observed. Conclusion Although voice complaints are rare, dysphonia among adolescents with PVFM is common and can occur in the absence of laryngeal abnormalities and medical comorbidities, typically as a result of vocal hyperfunction. Dysphonia does not appear to be a barrier to PVFM treatment and may be a useful target in therapy.
The Xicana Sacred Space: A Communal Circle of Compromiso for Educational Researchers

The Xicana Sacred Space resulted from an effort to develop a framework that would center the complexities of Chicana ontology and epistemology as they relate to social action projects in our communities. Claiming indigenous roots and ways of knowing, the Xicana Sacred Space functions as a decolonizing tool by displacing androcentric and Western linear notions of research in favor of a Mestiza consciousness (Anzaldua, 1999). Organically born, the space proved to be an important source of knowledge, strength, inspiration, and reflexivity for the authors in their journey as graduate students. Here the authors explain how the space evolved and detail its promise as a tool for raising consciousness, gaining strength, cultivating cultural intuition (Delgado Bernal, 1998), examining positionalities and standpoints, and achieving intellectual growth among those interested in conducting decolonial, emancipatory, and feminist research and action projects.
Fatigue Crack Growth Behavior in Al-7075 Under In-Plane Biaxial Loading with Mixed-Mode Overloads

Fatigue crack behavior in cruciform specimens of Al 7075-T6 under in-plane biaxial loading with mix-mode overloads is investigated. Tests were performed to characterize the fatigue behavior at four different levels of mode-mixity, and for each value of mode-mixity, overloads were applied at three different crack lengths as crack propagated under biaxial tensile loading. A significant change in the fatigue life and the crack growth behavior of the specimen was observed with change in mode-mixity of the applied overload. Although there was an increase in fatigue life for all the cases of mix-mode overloads, the maximum increase was observed for the pure shear overload and the minimum increase was observed for tensile dominant overload. When the shear component in the mix-mode overload was comparable but higher than the tensile component, an increase in mode-mixity value did not always show the increase in the fatigue life of the specimen, which indicates that the increase in fatigue life is not only governed by the combined effect of shear and tensile component of loading but also it is impacted differently by shear and tensile loading.
Using a Cooperative Hands-On General Chemistry Laboratory Framework for a Virtual General Chemistry Laboratory

Rising cases of COVID-19 caused St. John’s University to transition to an online educational model in the spring 2020 semester. As a result, an in-person Cooperative Learning advanced general chemi...
Formal Verification of Safety Critical Autonomous Systems via Bayesian Optimization

As control systems become increasingly more complex, there exists a pressing need to find systematic ways of verifying them. To address this concern, there has been significant work in developing test generation schemes for black-box control architectures. These schemes test a black-box control architecture's ability to satisfy its control objectives, when these objectives are expressed as operational specifications through temporal logic formulae. Our work extends these prior, model based results by lower bounding the probability by which the black-box system will satisfy its operational specification, when subject to a pre-specified set of environmental phenomena. We do so by systematically generating tests to minimize a Lipschitz continuous robustness measure for the operational specification. We demonstrate our method with experimental results, wherein we show that our framework can reasonably lower bound the probability of specification satisfaction.
Image Processing-Based Supervised Learning to Predict Robot Intention for Multimodal Interactions Between a Virtual Human and a Social Robot

A humanoid robot and a virtual human with human-like appearance were developed, and various similar intelligence, functions, autonomy and interaction modalities were developed for them that were deemed necessary for their real-world collaboration. The virtual human was integrated with the robot through a common platform based on some control algorithms so that they were capable of cooperating with each other in a real-world task, which was the task of assisting each other in searching for a hidden object in a homely environment. One important activity for such dynamic collaboration was the virtual human’s ability to predict the robot’s intention so that the virtual human could plan to collaborate with the robot, and vice versa. To address this problem, three representative robot behaviors such as hand shaking, hand pointing and hand waving were analyzed using supervised learning-based algorithms associated with image processing to help the virtual human learn robot behaviors so that the learned behaviors could help the virtual human predict the robot’s intention during their intended social interactions. In the training phase, the robot showed each of the three behaviors separately for 500 times. Images of each type of behaviors were taken separately, and the properties of the images were extracted following the image processing method. Then, each robot behavior extracted through image processing was labeled properly. Then, the supervised learning algorithm was developed that classified three different robot behaviors into three different classes. In the testing phase, the robot showed each of its three behaviors to the virtual human randomly for 100 times, the images were taken in real-time, and sent to the image processing-based machine learning algorithm. It was monitored whether the virtual human was able to recognize the robot behavior properly. The results showed that the virtual human was able to recognize robot behaviors and thus predict the robot’s intention with above 95% accuracy level.
Competing Visions of Angst Among Elite Lawyers

This review essay contrasts the explanations provided in two recent books for the existential anxiety suffered by many lawyers in top national law firms. Jean Stefancic and Richard Delgado's How Lawyers Lose Their Way: A Profession Fails Its Creative Minds, and Milton Regan's Eat What You Kill: The Fall of a Wall Street Lawyer, provide provocative case studies of different aspects of schizoid alienation at the highest rungs of the legal profession. Stefancic and Delgado explore the complex relationship between elite attorney Archibald MacLeish and Imagist poet Ezra Pound to demonstrate that top lawyers have struggled for many decades with the conflict between the demands of corporate law and the desire for self-fulfillment. Regan provides a riveting account of the downfall of John Gellene, a leading bankruptcy specialist in a top New York corporate law firm. While Stefancic and Delgado locate the core of the spiritual malaise among top corporate lawyers in the ideological cage resulting from the conceptual blinders of legal formalism, Regan takes a more economic-based perspective, portraying the hypercompetitive elite law firm as a soul destroying work environment.
‘Statistical Irreproducibility’ Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research

Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the ‘reproducibility of statistical results or direction of the effects’. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person–person differences and personalized medicine.
Accounting for heterogeneity in wild adult samples to measure insecticide resistance in Anopheles malaria vectors

Background Systematic, long-term, and spatially representative monitoring of insecticide resistance in mosquito populations is urgently needed to quantify its impact on malaria transmission, and to combat failing interventions when resistance emerges. Resistance assays on wild-caught adult mosquitoes (known as adult-capture) offer an alternative to the current protocols, and can be done cheaply, in a shorter time frame, and in the absence of an insectary. However, quantitative assessments of the performance of these assays relative to the gold standard, which involves rearing larvae in an insectary, are lacking. Methodology/Principal findings We developed a discrete-time deterministic mosquito lifecycle model to simulate insecticide resistance assays from adult-captured mosquito collection in a heterogeneous environment compared to the gold standard larval capture methods, and to quantify possible biases in the results. We incorporated non-lethal effects of insecticide exposure that have been demonstrated in laboratory experiments, spatial structure, and the impact of multiple exposure to insecticides and natural ageing on mosquito death rates during the assay. Using output from this model, we compared the results of these assays to true resistance as measured by the presence of the resistance allele. In simulated samples of 100 test mosquitoes, reflecting WHO-recommended sample sizes, we found that compared to adult-captured assays (MSE = 0.0059), larval-captured assays were a better measure of true resistance (MSE = 0.0018). Using a correction model, we were able to improve the accuracy of the adult-captured assay results (MSE = 0.0038). Bias in the adult-capture assays was dependent on the level of insecticide resistance rather than coverage of bed nets or spatial structure. Conclusions/Significance Using adult-captured mosquitoes for resistance assays has logistical advantages over the standard larval-capture collection, and may be a more accurate sample of the mosquito population. These results show that adult-captured assays can be improved using a simple mathematical approach and used to inform resistance monitoring programs.
Opportunism vs. specialization: the evolution of dispersal strategies in fleshy-fruited plants

In this paper we address two questions concerning the interaction between fleshy-fruited plants and their seed dispersers: (1) What determines optimal disperser coterie size (designated as Ĉ) and (2) Why does disperser specialization occur along taxonomic lines? We review factors that affect the evolution of Ĉ and conclude that seed size and disperser quality (designated as Q) are especially important. We present a simple graphical model for determining Ĉ based on Q and conclude that Ĉ will be small (i.e. a specialized disperser strategy) when Q declines rapidly with increasing coterie size; Ĉ will be large when Q declines slowly with increasing coterie size. We construct a model based on fitness set theory to predict that specialization on particular vertebrate taxa (e.g. birds or mammals) will be favored when different disperser taxa are perfectly substitutable or antagonistic (sensu Tilman 1982); mixed-taxa coteries are favored when different disperser taxa are complementary. Finally, we predict that when conditions favor taxonomic specialization, plants will evolve bird fruits more often than bat or primate fruits because of the greater species richness of birds compared with bats and primates.
ICT4ICTD: Computational Social Science for Digital Development

While the ICT for Development (ICTD) community is well aware about the far-reaching changes introduced by the digital age, it is remarkably slowly getting used to the idea that digital tools also revolutionize its very own core business: research. Information and communication technology (ICT) is currently transforming the way knowledge is created and insights are obtained. This applies to inductive empirical inquiry (i.e. 'Big data'), as well as deductive theoretical scholarship (i.e. 'agent-based computer simulations'). This article explores best practices of the application of such Computational Social Science in the field of development and contributes an informed perspective to intensify an outstanding discussion within the ICTD community. ICT should not only be used for development (ICTD), but also for the constant updating of our understanding of digital development, in order to fine-tune policies and project designs: 'ICT4ICTD'. On the one hand, the article shows that the consideration of this double role of ICT has the potential to significantly increase the impact of ICTD. On the other hand, developing countries and the ICTD community face important challenges when applying these tools, which should never be adopted uncritically.
EFFECT OF CULTURAL CONDITIONS ON GROWTH AND METABOLITE UPTAKE BY SERINE-GLYCINE AUXOTROPHS OF ESCHERICHIA COLI

Levine, Elliot M. (Yale University, New Haven, Conn.) and Sofia Simmonds. Effect of cultural conditions on growth and metabolite uptake by serine-glycine auxotrophs of Escherichia coli. J. Bacteriol. 84:683-693. 1962.-A study was made of the effect of environmental conditions on the growth and metabolite uptake by Escherichia coli strain S/G (a serine-glycine auxotroph) and strain S (a serine-glycine auxotroph lacking a normal transport system for glycine). The induction in strain S of the glycine transport system, which occurs during growth in a glycine-containing medium, was prevented by l-asparagine; the "repression" appeared to result from the endogenous formation of glycine from asparagine (through homoserine and threonine) via a pathway in which serine was not an obligatory intermediate. The response of both strains to glycine appeared to be determined by the amount of l-serine or glycine present in the media (containing asparagine) in which the cells were grown prior to testing. Preliminary growth in the presence of low concentrations of exogenous glycine, which should produce cells with small endogenous "glycine-serine pools," favored the induction of a functional glycine transport system in cells of strain S. Cells of strain S/G grown under similar conditions subsequently showed an enhanced ability to take up C(14)-labeled glycine. With both strains, preliminary growth conditions leading to the formation of large endogenous "glycine-serine pools" (e.g., growth in the presence of high concentrations of exogenous serine) produced cells exhibiting a glycine uptake rate that was not commensurate with the rate at which these cells grew on glycine. The growth response apparently depends not only on the ability of the cells to transport glycine but also on the size of the endogenous "glycine-serine pools"; inocula composed of cells having a limited capacity to accumulate labeled glycine showed significant growth in glycine-containing media if the cells had large "glycine-serine pools." The growth and uptake responses to glycylglycine appear to be governed, in part, by the same factors that control the responses to free glycine.
Complement fixation reaction for the diagnosis of type II avian (Marek's) leukosis.

The present study was designed to find a complement fixation (CF) reaction for the diagnosis of type II lymphoid leukosis, to learn some of the characteristics of the CF antigen, and to investigate the development of CF antibody response to this infection. JM virus-specific antigen was demonstrated in tumorous chicken tissue, in JM virus-infected chick embryo material, in JM virus-infected chicken kidney, and in duck embryo fibroblast tissue culture by using JM virus-immune rabbit serum. This CF antigen did not show cross-reactivity with Rous sarcoma virus or with RIF-type viruses. It was partially heat-labile. The CF activity was restored at —70 C for 10 months and was resistant to intermittent freeze-thaw treatment. The CF antigen may be denatured by ethyl alcohol, but no significant deleterious effects were noted after ether or chloroform treatment. JM virus-specific CF antibody could not be demonstrated by the direct complement dilution method or by the indirect or inhibition form of the CF test in infected or immunized chicken sera.
Oscillating field stimulation for complete spinal cord injury in humans: a Phase 1 trial

Object. An electrical field cathode (negative pole) has trophic and tropic effects on injured spinal cord axons in in vitro and in vivo models of sea lamprey, rodent, and canine spinal cord injury (SCI) and it improves functional outcome. A human oscillating field stimulator (OFS) was built, a Food and Drug Administration (FDA) exemption number was obtained, and institutional review board approval was given for a Phase 1 trial to study 10 humans with complete motor and sensory SCI. Methods. Entry criteria were complete SCI between C-5 and T-10 in patients 18 to 65 years of age and no transection demonstrated on magnetic resonance imaging. All participants received the National Acute Spinal Cord Injury Study (NASCIS) III methylprednisilone protocol. Cord compression and/or vertebral instability was treated before study entry. After treatment complete SCI (according to the American Spinal Injury Association [ASIA] score) remained in all patients with no somatosensory evoked potentials (SSEPs) below the injury level after surgery or for 48 hours. All patients underwent implantation of the OFS within 18 days. Patients underwent evaluation every 2 weeks postimplantation; the OFS was explanted at 15 weeks. Independent neurological status was assessed based on the ASIA score, visual analog scale (VAS) pain score, and SSEPs at 6 weeks, 6 months, and 1 year. Statistical analyses were performed using the two-tailed Wilcoxon test and analysis of variance (ANOVA). There were no complications at insertion of the OFS; there was one case of wound infection after explantation (5% infection rate). One patient was lost to follow up after 6 months. In all 10 patients the mean VAS pain score was 8 at implantation, 2 at 6 months, and in the nine attending follow up for 1 year it remained 2. At 1 year, the mean improvement in light touch was 25.5 points (ANOVA p , 0.001, Wilcoxon test p = 0.02), the mean improvement in pinprick sensation was 20.4 points (ANOVA p , 0.001, Wilcoxon test p = 0.02), and the mean improvement in motor status was 6.3 points (ANOVA p , 0.01, Wilcoxon test p = 0.02). Of five cases involving cervical cord injuries, bilateral upper-extremity SSEPs were normal in one, unilateral upper-extremity SSEPs were recovered in four, bilateral upper-extremity SSEPs were recovered in one, and abnormal lower-extremity SSEPs resolved in one case. In one of the five cases involving thoracic injuries an abnormal lower-extremity SSEP resolved. Conclusions. The use of OFS treatment in patients with SCI is safe, reliable, and easy. Compared with the outcomes obtained in compliant NASCIS III plegic patients, the results of the present study indicate efficacy, and the FDA has given permission for enrollment of 10 additional patients.
Modeling the three–dimensional structure of the monocyte chemo–attractant and activating protein MCAF/MCP-1 on the basis of the solution structure of interleukin-8

A model of the three-dimensional structure of the monocyte chemo-attractant and activating protein MCAF/MCP-1 is presented. The model is predicted based on the previously determined solution structure of interleukin-8 (IL-8/NAP-1) [Clore, G.M., Appella, E., Yamada, M., Matsushima, K. and Gronenborn, A.M. (1990) Biochemistry 29, 1689-1696]. Both proteins belong to a superfamily of cytokine proteins involved in cell-specific chemotaxis, host defense and the inflammatory response. The amino acid sequence identity between the two proteins is 24%. It is shown that the regular secondary structure elements of the parent structure can be retained in the modeled structure, such that the backbone hydrogen bonding pattern is very similar in the two structures. The polypeptide backbone is superimposable with an atomic r.m.s. difference of 0.9 A and all side chains can be modeled by transferring the parent side chain conformation to the new structure. Thus, the deduced structure, like the parent one, is a dimer and consists of a six-stranded antiparallel beta-sheet, formed by two three-stranded Greek keys, one from each monomer, upon which lie two symmetry-related antiparallel alpha-helices, approximately 24 A long and separated by approximately 14 A. All amino acid sequence changes can be accommodated within the parent polypeptide framework without major rearrangements. This is borne out by the fact that the IL-8/NAP-1 and modeled MCAF/MCP-1 structures have similar non-bonding energies. These results strongly suggest that both proteins and all other members of the superfamily most likely have the same tertiary structure.(ABSTRACT TRUNCATED AT 250 WORDS)
Two new water-soluble derivatives of 1,3,5-triaza-7-phosphaadamantane (PTA): Synthesis, characterization, X-ray analysis and solubility studies of 3,7-diformyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane and 1-pyridylmethyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane bromide

Abstract Two water-soluble phosphines, 3,7-diformyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane ( 1 , DFPTA) and 1-pyridylmethyl-3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1]decane bromide ( 2 , [pymePTA]Br), have been respectively, prepared by reacting 1,3,5-triaza-7-phosphaadamantane (PTA) with formic anhydride and bromomethylpyridine. Compound 1 is only the second acyl derivative of PTA to be prepared while 2 is only the second derivative of PTA reported that contains an aromatic appendage. Both compounds were characterized by elemental analysis, FAB-MS, 1 H, 13 C, and 31 P NMR spectroscopy, and single crystal X-ray diffraction. This analysis showed that the formamide groups of 1 were in an anti confirmation in solution but in a syn confirmation in the solid state. The solubilities of 1 and 2 were examined in common organic solvents and water. It was found that 1.1 M aqueous solutions of 1 could be prepared while 2.4 M solutions of 2 were produced. The greater solubility of 2 was likely due to its ionic nature.
Altruism, malice and public goods

Abstract Using the economic theory of public goods, this article demonstrates that kin selection cannot be used to explain altruism outside of the direct parent—child link. The same argument also indicates that what is normally called spite—and here is somewhat broadened and redefined as malice—would be confined to special circumstances.
The development of an explicit thermochemical nonequilibrium algorithm and its application to compute three dimensional AFE flowfields

This study presents a three-dimensional explicit, finite-difference, shock-capturing numerical algorithm applied to viscous hypersonic flows in thermochemical nonequilibrium. The algorithm employs a two-temperature physical model. Equations governing the finite-rate chemical reactions are fully-coupled to the gas dynamic equations using a novel coupling technique. The new coupling method maintains stability in the explicit, finite-rate formulation while allowing relatively large global time steps. The code uses flux-vector accuracy. Comparisons with experimental data and other numerical computations verify the accuracy of the present method. The code is used to compute the three-dimensional flowfield over the Aeroassist Flight Experiment (AFE) vehicle at one of its trajectory points.
MDA5 assembles into a polar helical filament on dsRNA

Melanoma differentiation-associated protein 5 (MDA5) detects viral dsRNA in the cytoplasm. On binding of RNA, MDA5 forms polymers, which trigger assembly of the signaling adaptor mitochondrial antiviral-signaling protein (MAVS) into its active fibril form. The molecular mechanism of MDA5 signaling is not well understood, however. Here we show that MDA5 forms helical filaments on dsRNA and report the 3D structure of the filaments using electron microscopy (EM) and image reconstruction. MDA5 assembles into a polar, single-start helix around the RNA. Fitting of an MDA5 homology model into the structure suggests a key role for the MDA5 C-terminal domain in cooperative filament assembly. Our study supports a signal transduction mechanism in which the helical array of MDA5 within filaments nucleates the assembly of MAVS fibrils. We conclude that MDA5 is a polymerization-dependent signaling platform that uses the amyloid-like self-propagating properties of MAVS to amplify signaling.