cssi/SciSciGPT-SciSciNet huggingface dataset:
A MATHEMATICAL PROGRAMMING APPROACH TO SENSITIVITY ANALYSIS IN SINGLE‐STAGE DECISION MAKING

This paper presents sensitivity analyses for a single-stage decision problem where an action which will maximize the expected payoff must be chosen from a finite number of actions given the states of nature, their probabilities, and the payoffs corresponding to each action and state of nature. Three types of sensitivity analysis are developed: (1) sensitivity analysis on the probabilities keeping the payoff numbers fixed, (2) sensitivity analysis on the payoffs keeping the probabilities fixed, and (3) joint sensitivity analysis on the payoffs and the probabilities. The approach is illustrated with an example. Quite often the sensitivity analysis can be conducted by solving an appropriate linear or quadratic programming problem.
Compartmentalization of Synaptic Tagging and Capture

Testing of the synaptic tagging and capture (STC) hypothesis has produced remarkable work on the understanding of how a single neuron undergoes spatial and temporal encoding of information. Central to this work is the notion that STC processes can be compartment specific. Formed by activation of synaptic plasticity mechanisms and extending along confined dendritic domains, these compartments can work as the neuron’s information integration units. Association or dismissal of incoming information would depend on the plasticity-driven functional state of the compartment. With multiple streams of neural activity arriving at distinct synapses of a neuron, compartmentalization emerges as a key strategy to organize this information and enhance the neuron’s computing capability.
Epilepsy and Mental Decline

Experience with prolonged seizures in animal models and humans teaches that cellular injury and cognitive impairment can occur in epilepsy. Status epilepticus probably causes cerebral injury and cognitive dysfunction if it is of long duration; however, studies of electroconvulsive therapy do not support the idea that repeated seizures alone produce a decline in cognitive function. Although many factors related to seizures may correlate with cognitive impairment in certain groups of patients with epilepsy, prospective studies do not support the premise that cognitive impairment develops or progresses in a population of epilepsy patients. When impairment is present, its origin appears to be multifactorial. In addition to the seizures and associated seizure variables (including anticonvulsant medications), interictal epileptiform discharges and the perceptions of the patients and others also may play major roles.
Cationic polymerization — Iodonium and sulfonium salt photoinitiators

Diaryliodonium, triarylsulfonium, dialkylphenacylsulfonium and dialkyl-4-hydroxyphenylsulfonium salts are versatile new classes of photoinitiators of cationic polymerization which have been reported in the last few years. These photoinitiators fall into two basic types based on the mechanisms of their photolysis. The first class comprises diaryliodonium and triarylsulfonium salts which undergo photoinduced fragmentations to generate aryl radicals and either aryliodinium or diarylsulfinium cation-radicals. On the other hand, dialkylphenacylsulfonium and dialkyl-4-hydroxyphenylsulfonium salts generate ylides and Bronsted acids by a reversible photolysis. Both classes of onium salts can be photosensitized to respond to long wavelength UV and visible light. Photosensitization occurs chiefly by an electron transfer process. Photogenerated free radicals can also be employed to induce the decomposition of diaryliodonium and certain triarylsulfonium salts by a chain reaction. Modifications within the cations and anions of the above onium salts have a marked influence on the course of the cationic polymerizations which are initiated using these photoinitiators. The structure of the cations exerts a dominant role in the photochemistry and determines the rate at which initiator fragments are produced. The reactivity and propensity of the initiator fragments to undergo termination are controlled by the nature of the anion. Photoinitiated cationic polymerizations using iodonium and sulfonium salts are currently finding use in a number of commercial applications including coatings, adhesives, inks and novel photoresists.
Navarette: Bedeviling Courts for a Long Time to Come

The legal community continually evaluates emerging decisions of the United States Supreme Court for guidance. When those decisions refine or clarify rules for applying legal tests they aid lawyers as well as citizens in understanding the rights and duties society confers to its members. Occasionally, however, the Court blunders, instead muddying the waters that were previously clear. This is particularly true when the tests for a particular issue are well understood and easy to apply in the first place. In its decision in Navarette v. California, the Court has created confusion and chaos in exactly that way with regard to stops and seizures based upon an anonymous tip from an unidentified caller. Courts at all levels have exhibited confusion, from the rulings on suppression motions by trial courts to opinions from courts of appeal and even the federal courts. In one case, justices on a state’s highest court put their confusion on public display when they debated among themselves the proper application of Navarette in competing opinions. This Article concludes that the level of confusion stemming from Navarette is palpable and unacceptable, and that there is a critical need for clarification from the highest court to clarify how anonymous tip analysis is to be viewed relative to 4th Amendment stops and seizures.
Yoga as an Intervention for PTSD: a Theoretical Rationale and Review of the Literature

There is evidence to suggest that yoga may reduce PTSD symptoms. It is unclear at this point, however, whether or not yoga reduces PTSD symptoms any more than a non-specific intervention given inconsistent findings and methodological limitations. Nonetheless, additional research in this area is important because of the high level of interest in and acceptability of yoga. Ultimately, yoga may be most effective when taught using trauma-sensitive guidelines and within a framework that helps the practitioner to apply the experience to coping with symptoms.
A Comparison Study of Nonlinear Kernels.

In this paper, we compare 5 different nonlinear kernels: min-max, RBF, fRBF (folded RBF), acos, and acos-$\chi^2$, on a wide range of publicly available datasets. The proposed fRBF kernel performs very similarly to the RBF kernel. Both RBF and fRBF kernels require an important tuning parameter ($\gamma$). Interestingly, for a significant portion of the datasets, the min-max kernel outperforms the best-tuned RBF/fRBF kernels. The acos kernel and acos-$\chi^2$ kernel also perform well in general and in some datasets achieve the best accuracies. One crucial issue with the use of nonlinear kernels is the excessive computational and memory cost. These days, one increasingly popular strategy is to linearize the kernels through various randomization algorithms. In our study, the randomization method for the min-max kernel demonstrates excellent performance compared to the randomization methods for other types of nonlinear kernels, measured in terms of the number of nonzero terms in the transformed dataset. Our study provides evidence for supporting the use of the min-max kernel and the corresponding randomized linearization method (i.e., the so-called "0-bit CWS"). Furthermore, the results motivate at least two directions for future research: (i) To develop new (and linearizable) nonlinear kernels for better accuracies; and (ii) To develop better linearization algorithms for improving the current linearization methods for the RBF kernel, the acos kernel, and the acos-$\chi^2$ kernel. One attempt is to combine the min-max kernel with the acos kernel or the acos-$\chi^2$ kernel. The advantages of these two new and tuning-free nonlinear kernels are demonstrated vias our extensive experiments.
Hypochlorous acid inhibits Ca2+-ATPase from skeletal muscle sarcoplasmic reticulum

Favero, Terence G., David Colter, Paul F. Hooper, and Jonathan J. Abramson. Hypochlorous acid inhibits Ca2+-ATPase from skeletal muscle sarcoplasmic reticulum. J. Appl. Physiol. 84(2): 425–430, 199...
Dissemination of Myxomycete Spores Through The Feeding Activities (Ingestion-Defecation) of an Acarid Mite

(1978). Dissemination of Myxomycete Spores Through The Feeding Activities (Ingestion-Defecation) of an Acarid Mite. Mycologia: Vol. 70, No. 6, pp. 1239-1241.
Bison Ecology and Bison Diplomacy: The Southern Plains from 1800 to 1850

In bright spring light on the Great Plains of two centuries ago, governorJuan Bautista de Anza failed in the last of the three crucial tasks that his superiors had set him as part of their effort to reform New Mexico's Comanche policy. Over half a decade, Anza had followed one success with another. He had brilliantly defeated the formidable Comanche nomnekaht (war leader) Cuerno Verde in 1779, and as a consequence in 1786, he had personally fashioned the long-sought peace between New Mexico and the swelling Comanche population of the Southern Plains. His third task was to persuade the Comanches to settle in permanent villages and to farm.' But the New Mexico governor found the third undertaking impossible. Observers of Plains Indian life for 250 years and committed to encouraging agriculture over hunting, the Spaniards were certain that the culture of the horse Indians was ephemeral, that the bison on which they depended were an exhaustible resource. Thus Anza pleaded with the tribes to give up the chase. The Comanches thought him unconvincing. Recently liberated by horse culture and by the teeming wildlife of the High Plains, their bands found the Arkansas River pueblo the governor built for them unendurable. They returned to the hunt with the evident expectation that their life as buffalo hunters was an endless cycle. And yet Anza proved to be a prophet. Within little more than half a century, the Comanches and other tribes of the Southern Plains were routinely suffering from starvation and complaining of shortages of bison. What had happened?2 Environmental historians and ethnohistorians whose interests have been environmental topics have in the two past decades been responsible for many of our most valuable recent insights into the history of native Americans since their contact with
Explaining the results of examinations to patients. 2.

Part 1 of this discussion published last month described the kinds of information which physicians should include or withhold in offering explanations to patients of their conditions. The present article offers suggestions about how to give explanations.
Analysis of results of surveillance of soil-transmitted nematodiasis in Baisha county of Hainan province from 2010 to 2012

Objective To analyze the infection status and grasp the epidemic regularity of soil- transmittednematodiasis in Baisha county of Hainan province from 2010 to 2012,and to provide scientific basis for evaluation of soil-transmitted nematode control effect and development of effective prevention and control measures.Methods The Kato-Katz's thick smears and adhesive tape test were used to investigate the infection status of soil-transmitted nematodes among thelocal residents. Results A total of 3 045 people were examined from 2010 to 2012,including 1 556 males and1 489 females.The infection rates of roundworm,whipworm and hookworm were 0.45%,11.31% and 9.70% in males and0.54%,10.41%,and 13.70% in females respectively.The total infection rates of soil-transmitted nematodes from 2010 to 2012 were 25.69%,22.61% and 17.06%,respectively. The infection rates of roundworm,whipworm,hookworm and pinworm in 2010 were 0.60%,12.30%,14.98 and 34.21%,respectively. The infection rates of roundworm,whipworm,hookworm and pinworm in2011 were 0.87%,11.79%,10.72% and 38.78%. The infection rates of roundworm,whipworm,hookworm and pinworm in 2012 were 0.00%,8.48%,9.28%and 36.31%,respectively. Conclusion The monitoring in 2010-2012 revealed a decreasing soiltransmitted nematodes prevalence but showed a relatively high infection rate of pinw orm in the children.
Zulu grandmothers’ socialization of granddaughters

Qualitative exploratory research among Zulu grandmothers and granddaughters was carried out in 199S in KwaZulu-Natal. Preliminary analysis of data from interviews and participant observation is briefly reported here. This analysis suggests that older women continue to have important roles in Zulu families, including teaching granddaughters about work and respectful behaviour. At the same time, there are tensions and stresses between the generations and between Zulu ideas about women's roles and transformations of women's roles in contemporary South Africa. Interviewees' perceptions of critical junctures of these interpersonal and sociocultural tensions focussed on premarital sexual behaviour and pregnancies, respect between the generations, and education and its effects on the roles of Zulu women (and more broadly, gender relations), and women's possibilities for success in the formal economy and modern world. Aware of these tensions and problems, grandmothers are not giving up their mission to socialise granddaughters into Zulu culture, even when there are failures such as a granddaughters falling pregnant. At the same time, they are looking for ways to enhance their granddaughters' life chances through formal education.
κ Agonists as a novel therapy for menopausal hot flashes.

Objective The etiology of postmenopausal hot flashes is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing kisspeptin, neurokinin B and dynorphin-called KNDy neurons-are located adjacent to the thermoregulatory center. KNDy neurons regulate pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Dynorphin may inhibit this system by binding κ opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. Methods A double-blind, cross-over, placebo-controlled pilot study evaluated the effects of a κ agonist. Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate to severe hot flashes (aged 48-60 y) were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all three interventions: placebo, standard-dose pentazocine/naloxone (50/0.5 mg), or low-dose pentazocine/naloxone (25/0.25 mg). In an inpatient research setting, each participant received the three interventions, in randomized order, on three separate days. On each day, an intravenous catheter was inserted for LH blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. Results The mean (SEM) hot flash frequency 2 to 7 hours after therapy initiation was lower than that for placebo (standard-dose κ agonist, 4.75 [0.67] hot flashes per 5 h; low-dose κ agonist, 4.50 [0.57] hot flashes per 5 h; placebo, 5.94 [0.78] hot flashes per 5 h; P = 0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some--but not all--women. Conclusions This pilot study suggests that κ agonists may affect menopausal vasomotor symptoms.
Shall This Too Pass? Education Reform in the Obama Era and Beyond

What does the 2016 presidential election say about the Obama education agenda? Will that agenda stick, or face erosion? We will address this in this, the closing chapter. As we write, after former Texas Governor Rick Perry and immediately after Wisconsin Governor Scott Walker pulled out of the presidential race, there are still an astonishing 14 GOP candidates running. The numbers reflect a GOP resurgence and the difficulty any party, in this case the Democrats, has winning three consecutive presidential races. This makes the Republican nomination a much sought-after commodity. We can broadly characterize the 14 remaining GOP presidential candidates as local education libertarians and business-driven modernizers.
Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.
A simple proof of some generalized principal ideal theorems

Using symmetric algebras we simplify (and slightly strengthen) the Bruns-Eisenbud-Evans “generalized principal ideal theorem” on the height of order ideals of nonminimal generators in a module. We also obtain a simple proof and an extension of a result by Kwiecinski, which estimates the height of certain Fitting ideals of modules having an equidimensional symmetric algebra.
Assisting Discovery in Public Health

Several public health (PH) researchers have lately been arguing that big data can play a profound role in scientific discovery. Leveraging the vast amount of population-level data collected by public agencies and other organizations, could lead to important discoveries that were not necessarily suspected to be true. However, they also warn about the pitfalls of data-driven discovery: The large amount of data can easily lead to information overload for the researchers. Additionally, data-driven studies that make a lot of tests in the search for important discoveries have the potential to lead to discoveries that seem important but are in fact random.We show that data-driven studies can be effective and yet avoid the potential pitfalls by keeping the researchers in the loop of the discovery process. To this end, we propose PHD; an interactive visual discovery system that allows public health researchers to gain interesting insights from large datasets. PHD generalizes the current workflow of PH researchers by facilitating the major analytics tasks involved in PH discovery, such as calculating important associations based on the standard notions of odds rations and confidence intervals, controlling for the effect of other variables and discovering interesting compounding effects. More importantly however, it leverages user interaction and the semantics of the domain to make sure that this workflow scales to large datasets, while avoiding information overload and random discoveries.
A new hypertragulid (Mammalia, Ruminantia) from the early Chadronian of Wyoming and Texas

aParitragulus priscus, a new genus and species of the family Hypertragulidae, is described from early Chadronian (early Oligocene) deposits of Wyoming and Texas. It differs from the other genera of the family mainly in the complexity of its premolar teeth, and the crown height of its molar teeth. Parvitragulus may be ancestral to some of the species of Nanotragulus (e.g., N. loomisi), though this possibility is rendered uncertain by the long time interval separating the two genera (early Chadronian to Arikareean), and the scarcity and fragmentary nature of possible intermediates. Some species now referred to Nanotragulus may be more appropriately referred to Hypertragulus. If Parvitragulus is not ancestral to Nanotragulus, it probably has no known descendants.
The Role of Surface-Bound Dihydropyridine Analogues in Pyridine-Catalyzed CO2 Reduction over Semiconductor Photoelectrodes

We propose a general reaction mechanism for the pyridine (Py)-catalyzed reduction of CO2 over GaP(111), CdTe(111), and CuInS2(112) photoelectrode surfaces. This mechanism proceeds via formation of a surface-bound dihydropyridine (DHP) analogue, which is a newly postulated intermediate in the Py-catalyzed mechanism. Using density functional theory, we calculate the standard reduction potential related to the formation of the DHP analogue, which demonstrates that it is thermodynamically feasible to form this intermediate on all three investigated electrode surfaces under photoelectrochemical conditions. Hydride transfer barriers from the intermediate to CO2 demonstrate that the surface-bound DHP analogue is as effective at reducing CO2 to HCOO– as the DHP(aq) molecule in solution. This intermediate is predicted to be both stable and active on many varying electrodes, therefore pointing to a mechanism that can be generalized across a variety of semiconductor surfaces, and explains the observed electrode depe...
Weight Beliefs and Messages: Mindsets Predict Body-Shame and Anti-Fat Attitudes via Attributions

In two samples (N = 247, N = 291), we examined the link between beliefs and messages about the changeable (incremental theory) vs. fixed (entity theory) nature of weight, attributions for weight, and body shame. We recruited participants using online sampling, employing a correlational design in Study 1 and an experimental design in Study 2. Across both studies, we found evidence for the stigma-asymmetry effect—incremental, relative to entity beliefs/messages of weight predicted both (a) stronger onset responsibility attributions, indirectly increasing body shame and (b) stronger offset efficacy attributions, indirectly decreasing body shame. Study 2 replicated the stigma-asymmetry effect with anti-fat attitudes. We discuss implications for public health obesity messages with the goal of reducing stigma.
Radical S-Adenosylmethionine Enzymes Involved in RiPP Biosynthesis.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) display a diverse range of structures and continue to expand as a natural product class. Accordingly, RiPPs exhibit a wide array of bioactivities, acting as broad and narrow spectrum growth suppressors, antidiabetics, and antinociception and anticancer agents. Because of these properties, and the complex repertoire of post-translational modifications (PTMs) that give rise to these molecules, RiPP biosynthesis has been intensely studied. RiPP biosynthesis often involves enzymes that perform unique chemistry with intriguing reaction mechanisms, which attract chemists and biochemists alike to study and re-engineer these pathways. One particular type of RiPP biosynthetic enzyme is the so-called radical S-adenosylmethionine (rSAM) enzyme, which utilizes radical-based chemistry to install several distinct PTMs. Here, we describe the rSAM enzymes characterized over the past decade that catalyze six reaction types from several RiPP biosynt...
State-Mandated Nutrition, Physical Activity, and Screen Time Policies in Child Care Centers

Background. The child care center (CCC) environment presents opportunities for healthy weight promotion in preschoolers. Our study examined the current state of CCC adherence to nutrition, physical...
Bolivian Economic Policies: An Assessment

The Sanchez de Lozada administration’s plan to export Bolivian natural gas using a Chilean port ignited a bloody social unrest which resulted in the resignations of two presidents, thus ending the neoliberal period that had begun in August 1985. Bolivians elected Evo Morales, the candidate of Movimiento hacia el Socialismo (MAS). Mr. Morales, an indigenous Aymara, won the election with 54% of the popular vote in December of 2005. This paper argues that the Morales administration‘s Decrees of nationalizations and land redistribution are indications of return to the interventionist statism. Part II presents a succinct narrative of the experience of some productive industries and land reform. Part III presents an assessment of the policies of the Morales administration during its first year in power followed by our Conclusions.
Expanding the Reach of Effective PTSD Treatment Into Primary Care: Prolonged Exposure for Primary Care

Posttraumatic stress disorder (PTSD) is a costly mental health issue in the United States and throughout the world. Effective treatments are available; however, most people with PTSD never access t...
CRISPR/Cas9-mediated modulation of splicing efficiency reveals short splicing isoform of Xist RNA is sufficient to induce X-chromosome inactivation

Alternative splicing of mRNA precursors results in multiple protein variants from a single gene and is critical for diverse cellular processes and development. Xist encodes a long noncoding RNA which is a central player to induce X-chromosome inactivation in female mammals and has two major splicing variants: long and short isoforms of Xist RNA. Although a differentiation-specific and a female-specific expression of Xist isoforms have been reported, the functional role of each Xist RNA isoform is largely unexplored. Using CRISPR/Cas9-mediated targeted modification of the 5' splice site in Xist intron 7, we create mutant female ES cell lines which dominantly express the long- or short-splicing isoform of Xist RNA from the inactive X-chromosome (Xi) upon differentiation. Successful execution of CRISPR/Cas-based splicing modulation indicates that our CRISPR/Cas-based targeted modification of splicing sites is a useful approach to study specific isoforms of a transcript generated by alternative splicing. Upon differentiation of splicing-mutant Xist female ES cells, we find that both long and short Xist isoforms can induce X-chromosome inactivation normally during ES cell differentiation, suggesting that the short splicing isoform of Xist RNA is sufficient to induce X-chromosome inactivation.
Current and future therapeutic approaches for osteosarcoma

ABSTRACTIntroduction: Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a...
A Review of the Cell to Graphene-Based Nanomaterial Interface

The area of cellular interactions of nanomaterials is an important research interest. The sensitivity of cells toward their extracellular matrix allows researchers to create microenvironments for guided stem cell differentiation. Among nanomaterials, graphene, often called the “wonder material,” and its derivatives are at the forefront of such endeavors. Graphene’s carbon backbone, paired with its biocompatibility and ease of functionalization, has been used as an enhanced method of controlled cell proliferation. Graphene’s honeycomb nature allows for compatibility with polymers and biological material for the creation of nanocomposite scaffolds that help differentiation into cell types that have otherwise been proven difficult. Such materials and their role in guiding cell growth can aid the construction of tissue grafts where shortages and patient compatibility create a low success rate. This review will bring together novel studies and techniques used to understand and optimizes graphene’s role in cell growth mechanisms.
Linked oppression: Connecting animal and gender attitudes:

Ecofeminists and animal rights advocates have posited a connection between the oppression of women and the oppression of animals. Although male/female comparisons regarding attitudes toward animals have frequently been considered, only limited research has focused on gender roles and animal attitudes. We therefore examined the relation between gender roles and animal attitudes with undergraduate students (260 males, 484 females) at a public university in Texas. Participants responded to an online Qualtrics survey that assessed their attitudes toward animals, gender norms, and several forms of sexism. The survey also presented participants with questions about their justifications for meat consumption. As hypothesized, pro meat-eating justifications were positively related to sexist attitudes as well as traditional gender roles and negatively related to gender role transcendent attitudes. On the other hand, pro-animal attitudes were positively correlated with gender role transcendent attitudes and negative...
Principal-Agent Models of Political Control of Bureaucracy

In the March 1988 issue of this Review, B. Dan Wood invoked a principal-agent perspective to establish the importance of democratic hierarchies in shaping the outputs of public bureaucracies. He tested the model with air pollution enforcements of the Environmental Protection Agency (EPA) between 1977 and 1985. His results suggested some limitations on bureaucracies' responsiveness to elected political institutions, consistent with a principal-agent perspective with emphasis on the agent. Brian J. Cook challenges features of the design and empirical testing of Wood's hierarchical model. He questions the accuracy of Wood's characterization of the extent of EPA autonomy and power. Cook argues that a proper model requires recognition of the multiple principal nature of the U.S. system, and he advocates consideration of the normative foundations of principal-agent theory. Wood responds to both the substantive and methodological issues raised and suggests an eclectic approach in future research.
Genetic Approaches to the Study of Eukaryotic Ribosomes

The ribosome is an object of ancient beauty and function. As we seek to understand the ribosome and its place in the physiology of the cell, we must use every technique in our armamentarium. One of these is genetics. Amongst the eukaryotes, the yeast Saccharomyces cerevisiae has proved particularly useful for the application of genetics to the study of ribosome function and biosynthesis. This paper, which we dedicate to the memory of Prof. H.-G. Wittmann, describes our recent work on genetic approaches to the S. cerevisiae ribosome.
IMPACT OF MOISTURE ON REGIONAL-SCALE NUMERICAL MODEL SIMULATIONS

Regional-scale atmospheric simulation models with domains ranging from 2.5 × 10 5 km 2 to 4 × 10 6 km 2 with grid intervals varying from 30 km to 140 km are currently being tested and used in both research and operational modes. Examples of these models and their sensitivity to the magnitude and scale-resolution of the initial moisture distribution are presented. These examples demonstrate the influence of the moisture on both the developing model dynamics as well as on the forecast quantitative precipitation amounts.
A qualitative assessment of health behaviors and experiences during menopause: A cross-sectional, observational study.

Abstract Objectives A qualitative research study was performed to assess the health and lifestyle behaviors of middle-aged women during the menopause transition, as well as to inform the development of interventions designed to combat menopause symptoms and improve quality of life during and after menopause. Study design Data were collected from 1611 women via a 21-item questionnaire distributed electronically. Only women who self-reported age ≥40 years and who were either peri-menopausal or post-menopausal were included in the analyses. Outcome measures Women responded to questions about their health behaviors and experiences during menopause, including use of hormone replacement therapy (HRT), symptom ratings, and use of diet/lifestyle, exercise, and holistic remedies to relieve menopause symptoms. Results More than 80% of women were interested in a structured lifestyle program to alleviate menopause symptoms, with 72% of these women wanting targeted strategies for weight loss or weight maintenance. Insomnia and hot flashes were the most severe symptoms reported. Although HRT is a well-established treatment of menopausal symptoms, more than 60% of women denied use of HRT, stating that they ‘never considered HRT’ as a treatment option or ‘preferred to not take HRT’. Most women (65%) did not feel prepared for menopause. Conclusions Women do not feel prepared for menopause and report interest in a structured lifestyle program containing weight-loss and weight-maintenance strategies to combat menopause symptoms.
Evolution of damage and failure in an additively manufactured 316L SS structure: experimental reinvestigation of the third Sandia fracture challenge

The third Sandia Fracture Challenge (SFC3) was a benchmark problem for comparing experimental and simulated ductile deformation and failure in an additively manufactured (AM) 316L stainless steel structure. One surprising observation from the SFC3 was the Challenge-geometry specimens had low variability in global load versus displacement behavior, attributed to the large stress-concentrating geometric features dominating the global behavior, rather than the AM voids that tend to significantly influence geometries with uniform cross-sections. This current study reinvestigates the damage and failure evolution of the Challenge-geometry specimens, utilizing interrupted tensile testing with micro-computed tomography (micro-CT) scans to monitor AM void and crack growth from a virgin state through complete failure. This study did not find a correlation between global load versus displacement behavior and AM void attributes, such as void volume, location, quantity, and relative size, which incidentally corroborates the observation from the SFC3. However, this study does show that the voids affect the local behavior of damage and failure. Surface defects (i.e. large voids located on the surface, far exceeding the nominal surface roughness) that were near the primary stress concentration affected the location of crack initiation in some cases, but they did not noticeably affect the global response. The fracture surfaces were a combination of classic ductile dimples and crack deviation from a more direct path favoring intersection with AM voids. Even though the AM voids promoted crack deviation, pre-test micro-CT scan statistics of the voids did not allow for conclusive predictions of preferred crack paths. This study is a first step towards investigating the importance of voids on the ductile failure of AM structures with stress concentrations.
The Design and Build of a Zoom Telescope Utilizing Additive Manufacturing

Developers of optical systems are seeking lighter, cheaper, and rapidly- developed systems. Design, fabrication, and testing a 10x dual-focus telescope is presented utilizing additive manufacturing, active alignment, and image correction algorithms.
Transcriptome analysis reveals nutrition‐ and age‐related patterns of gene expression in the fat body of pre‐overwintering bumble bee queens

Many diapausing insects undergo a nutrient storage period prior to their entry into diapause. Bumble bee queens diapause as adults in the winter preceding their spring nest initiation period. Before diapause, they sequester glycogen and lipids, which they metabolize during the overwintering period. We used RNA sequencing to examine how age and nectar diet (specifically, the concentration of sucrose in nectar) impact gene expression in the pre-overwintering bumble bee queen fat body, the "liver-like" organ in insects with broad functions related to nutrient storage and metabolism. We found that diet on its own, and in combination with age, impacts the expression of genes involved in detoxification. Age was also a strong driver of gene expression, especially at earlier ages (up to 3 days). In addition to these molecular correlates of diet and age, we also found a putative molecular signature of diapause entry or preparation in adult queens in the oldest age group (12 days) fed the most sucrose-rich diet, based on comparisons between our data set and another transcriptome data set from bumble bee queens. This transcriptomic pattern suggests that preparation for (or entry into) diapause might be in part mediated by nutritional state in bumble bee queens. Collectively, these findings show that there are molecular processes in the fat body that are responsive to sucrose levels in the diet and/or associated with age-related maturational changes. A better understanding of these processes may shed light on important aspects of bumble bee biology, such as queen responses to nutritional and other forms of stress, and the factors that regulate their entrance into diapause.
P2Y12 inhibitors with oral anticoagulation for percutaneous coronary intervention with atrial fibrillation: a systematic review and meta-analysis

Objective This study aimed to compare the safety and efficacy of third-generation P2Y12 inhibitors versus clopidogrel in combination with oral anticoagulation (OAC) with or without aspirin in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Methods We performed a systematic review including both prospective and retrospective studies that compared dual and triple antithrombotic regimens for bleeding and major adverse cardiac events (MACE) in patients with AF undergoing PCI. We analysed rates of bleeding and MACE by P2Y12 inhibitor choice. Risk ratio (RR) 95% CIs were measured using the Mantel-Haenszel method. Where study heterogeneity was low (I2 Results A total of 22 014 patients were analysed from the seven studies included. Among patients treated with both OAC and P2Y12 inhibitor with or without aspirin, 90% (n=9708) were treated with clopidogrel, 8% (n=830) with ticagrelor, and 2% (n=191) with prasugrel. When compared with clopidogrel, use of ticagrelor (RR 1.36; 95% CI 1.18 to 1.57) and prasugrel (RR 2.11; 95% CI 1.34 to 3.30) were associated with increased rates of bleeding. Compared with clopidogrel, there were no significant differences in rates of MACE with ticagrelor (RR 1.03; 95% CI 0.65 to 1.62) or prasugrel (RR 1.49; 95% CI 0.69 to 3.24). Conclusion Based on this meta-analysis, the use of clopidogrel is associated with a lower rate of bleeding compared with ticagrelor or prasugrel in patients with AF on OAC undergoing PCI.
Outreach and Inreach Strategies for Colorectal Cancer Screening Among Latinos at a Federally Qualified Health Center: A Randomized Controlled Trial, 2015-2018.

Objectives. To compare usual care, inreach consisting of one-on-one education, mailed outreach offering a fecal immunochemical test (FIT), and a combination of outreach and inreach for promoting co...
srcClone: Detecting Code Clones via Decompositional Slicing

Detecting code clones is an established method for comprehending and maintaining systems. One important but challenging form of code clone detection involves detecting semantic clones, which are those that are semantically similar code segments that differ syntactically. Existing approaches to semantic clone detection do not scale well to large code bases and have room for improvement in their precision and recall. In this paper, we present a scalable slicing-based approach for detecting code clones, including semantic clones. We determine code segment similarity based on their corresponding program slices. We take advantage of a lightweight, publicly available, and scalable program slicing approach to compute the necessary information. Our approach uses dependency analysis to find and measure cloned elements, and provides insights into elements of the code that are affected by an entire clone set/class. We have implemented our approach as a tool called srcClone. We evaluate it by comparing it to two semantic clone detectors in terms of clones, performance, and scalability; and perform recall and precision analysis using established benchmark scenarios. In our evaluation, we illustrate our approach is both relatively scalable and accurate. srcClone can also be used by program analysts to run on non-compilable and incomplete source code, which serves comprehension and maintenance tasks very well. We believe our approach is an important advancement in program comprehension that can help improve clone detection practices and provide developers greater insights into their software.
Maps in History: Fighting Epidemics

The first anniversary of COVID-19 warrants a look on medical cartography and how maps contributed to keep such devastating pandemics at bay. Infections have threatened mankind since its cradle, but...
Abstract PO043: Layer-by-layer nanoparticles for non-toxic delivery of interleukin 12 to disseminated syngeneic ovarian tumors

Ovarian cancer presents a notable challenge for cancer immunotherapy with less than a 10% objective response rate to checkpoint inhibitors (CPI). One strategy to augment the impact of checkpoint therapy is to initiate the infiltration of leukocytes into the tumor prior to CPI using pro-inflammatory cytokines. One particularly potent and promising cytokine is interleukin-12 (IL-12) – the hallmark Th-1 cytokine known to drive an influx of antigen presenting cells, expansion of cytotoxic T-cells, and NK-cell activation in a variety of solid tumors. Unfortunately, IL-12 has been hampered clinically by toxicity issues when administered systemically – a necessity for disseminated tumors such as advanced ovarian cancer. We have previously shown that nanoparticles engineered for cytokine delivery target human ovarian tumors in mouse models and that delivery of IL-12 using those particles enables the non-toxic delivery of IL-12 when given intratumorally to syngeneic tumors. In this study we demonstrate that these particles given systemically continue to limit IL-12 toxicity, accumulate within syngeneic, orthotopic models of ovarian tumors, induce tumor regressions, and reshape the immune microenvironment within those tumors. IL-12 was loaded onto the surface of negatively charged liposomes using the Ni-His interaction. The layer-by-layer process was then used to add layers of poly-L-arginine and poly-L-glutamine producing a final diameter of 120 nm and zeta potential of -60 mV. These layered nanoparticles (LNPs) preferentially accumulated in intraperitoneal HM-1 ovarian tumor nodules when given intravenously and intraperitoneally with a 30% increase in concentration over unlayered nanoparticles (ULNPs) as measured via fluorescence. IL-12 accumulation measured using ELISA was shown to correlate with NP accumulation for LNPs but not ULNPs. LNPs were non-toxic (via weight loss) at doses deemed toxic with ULNPs or free IL-12. Intraperitoneal treatment with LNPs extended survival and caused tumor regression in 30% of mice at a dose deemed toxic for free IL-12 or ULNPs (10 µg IL-12 given once daily for 5 days). Flow cytometry revealed a marked increase in memory T-cells and a decrease in granulocytes. The LNPs also induced substantial upregulation of exhaustion markers in the infiltrating T-cells – especially the TIM3+TIGIT+PD1+ highly exhausted phenotype suggesting potential for future combination therapies. Citation Format: Sean G. Smith, Antonio E. Barberio, Ivan S. Pires, Mariane Melo, Darrell J. Irvine, Paula T. Hammond. Layer-by-layer nanoparticles for non-toxic delivery of interleukin 12 to disseminated syngeneic ovarian tumors [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO043.
Cine MRI characterizes HFpEF and HFrEF in post-capillary pulmonary hypertension.

Abstract Purpose To test the hypothesis that cine MRI can be used to characterize features of left and right ventricles in post-capillary pulmonary hypertension (PH) caused by heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Methods With the approval of institution review board (IRB), 28 consecutive post-capillary PH patients (11 males, 62.1 ± 13.4 years old, range 39–89 years old) underwent cine MRI scans. Cine MRI-derived left ventricular (LV) ejection fraction (LVEF) and other function, motion, and deformation indices (acquired with heart deformation analysis [HDA]) were compared between PH-HFpEF (defined as LVEF ≥ 50 %]) and PH-HFrEF (LVEF Results Totally 19 patients (68 %, 95 % confident interval [CI] 49 %–86 %) were assigned to PH-HFpEF group while 9 (32 %) was assigned to the PH-HFrEF group. There were differences of LV and right ventricular (RV) global functional indices, LV mass, LV displacement, velocity, strain and strain rate between the two patient groups. Cine MRI-derived LV indices had broad associations with RV indices and RHC measurements. LVEF was negatively correlated with pulmonary capillary wedge pressure (PCWP) (r = -0.5, p = 0.007). LV cardiac index (LVCI) was associated with systolic pulmonary artery pressure (sPAP) (r = 0.443, p = 0.018). Conclusions PH-HFpEF and PH-HFrEF patients present dissimilar function, motion and deformation features in LV and RV. Cine MRI-derived LV measures are correlated with hemodynamic abnormalities of PH.
Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations

Abstract Background ATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. Aim We aimed to describe the manifestations of early onset severe ATP1A2-related epileptic encephalopathy and its underlying mutations in a cohort of seven patients. Methods A retrospective chart review of a cohort of seven patients was conducted. Response to open-label memantine therapy, used off-label due to its NMDA receptor antagonist effects, was assessed by the Global Rating Scale of Change (GRSC) and Clinical Global Impression Scale of Improvement (CGI-I) methodologies. Molecular modeling was performed using PyMol program. Results Patients (age 2.5–20 years) had symptom onset at an early age (6 days–1 year). Seizures were either focal or generalized. Common features were: drug resistance, recurrent status epilepticus, etc., severe developmental delay with episodes of acute severe encephalopathy often with headaches, dystonias, hemiplegias, seizures, and developmental regression. All had variants predicted to be disease causing (p.Ile293Met, p.Glu1000Lys, c.1017+5G>A, p.Leu809Arg, and 3 patients with p.Met813Lys). Modeling revealed that mutations interfered with ATP1A2 ion binding and translocation sites. Memantine, given to five, was tolerated in all (mean treatment: 2.3 years, range 6 weeks–4.8 years) with some improvements reported in all five. Conclusions Our observations describe a distinctive clinical profile of seven unrelated probands with early onset severe ATP1A2-related epileptic encephalopathy, provide insights into structure–function relationships of ATP1A2 mutations, and support further studies of NMDAR antagonist therapy in ATP1A2-encephalopathy.
Modeling cyclic plasticity of additively manufactured alloy Mar-M-509 using a high-performance spectral-based micromechanical model

Abstract A high-performance full-field spectral crystal plasticity model referred to as MPI-ACC-EVPCUFFT is adapted to study the deformation behavior of additively manufactured Mar-M-509® cobalt-based superalloy. The model features a dislocation density-based hardening law for the evolution of slip resistance, a barrier effect induced by grain morphology to influence the slip resistance, and a slip system-level back-stress law for adjusting the driving force to slip. The model is used to interpret and predict strength of the alloy in tension, compression, load reversal, and low-cycle fatigue as a function of initial microstructure. The initial microstructure varied from sample-to-sample to represent the effects of build orientation and heat treatment. Results show that the model successfully reproduces phenomena pertaining to monotonic and cyclic deformation including the non-linear unloading, Bauschinger effect, and cyclic hardening/softening using a single set of model parameters. Moreover, the model offers insights into fluctuations of mechanical fields and strain partitioning.