cssi/SciSciGPT-SciSciNet huggingface dataset:
Shiga Toxin Therapeutics: Beyond Neutralization

Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal failure in otherwise healthy children, resulting in a mortality rate of 10% and a chronic morbidity rate near 25%. There are currently no available therapeutics to prevent or treat HUS in STEC patients despite decades of work elucidating the mechanisms of Shiga toxicity in sensitive cells. The preclinical development of toxin-targeted HUS therapies has been hindered by the sporadic, geographically dispersed nature of STEC outbreaks with HUS cases and the limited financial incentive for the commercial development of therapies for an acute disease with an inconsistent patient population. The following review considers potential therapeutic targeting of the downstream cellular impacts of Shiga toxicity, which include the unfolded protein response (UPR) and the ribotoxic stress response (RSR). Outcomes of the UPR and RSR are relevant to other diseases with large global incidence and prevalence rates, thus reducing barriers to the development of commercial drugs that could improve STEC and HUS patient outcomes.
Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription

Viruses are completely dependent upon cellular machinery to support replication and have therefore developed strategies to co-opt cellular processes to optimize infection and counter host immune defenses. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode a relatively small number of genes. Viruses with limited genetic content often encode multifunctional proteins that function at multiple stages of the viral replication cycle. In this review, we discuss the functions of HIV-1 regulatory (Tat and Rev) and accessory (Vif, Vpr, Vpu, and Nef) proteins. Each of these proteins has a highly conserved primary activity; however, numerous additional activities have been attributed to these viral proteins. We explore the possibility that HIV-1 proteins leverage their multifunctional nature to alter host transcriptional networks to elicit a diverse set of cellular responses. Although these transcriptional effects appear to benefit the virus, it is not yet clear whether they are strongly selected for during viral evolution or are a ripple effect from the primary function. As our detailed knowledge of these viral proteins improves, we will undoubtedly uncover how the multifunctional nature of these HIV-1 regulatory and accessory proteins, and in particular their transcriptional functions, work to drive viral pathogenesis.
Making a measurable difference in advanced Huntington disease care

Neurologists' role in the care of people with advanced Huntington disease (HD) (total functional capacity <7), often limited by a lack of clinical research to support good practice, includes the following: (1) provide comprehensive health records to an interdisciplinary care staff before admission to a more intense care setting (home health services, day program, assisted living, group home, long-term skilled nursing facility, palliative care); (2) consult with and refer to rehabilitation (occupational therapy, physical therapy, speech and language pathology), behavioral and psychiatric professionals for problem-solving strategies, which must be reviewed with direct care staff before implementation; (3) encourage and support qualitative and quantitative interdisciplinary research studies, and randomized controlled studies of nonpharmacologic interventions; and (4) assist in the development of meaningful measures to further document what works to provide a good quality of life for the patient and family and a comfortable thoughtful approach to a good death. Collaborative models of care depend on: (1) clear communication; (2) ongoing education and support programs; with (3) pharmacologic and rehabilitation interventions, always in the context of respect for the person with HD, a preservation of the individuals' dignity, autonomy, and individual preferences.
Regulation of Signal Transduction by DJ-1

The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson’s disease.
Taking up iodide in breast tissue.

Both thyroid and breast cells take up iodide, and it seems that the same molecule is responsible. This molecule is expressed in lactating and cancerous breast tissues, a result that may reopen the discussion about the usefulness of iodide transport for detecting or treating breast cancer.
Preclinical Evidence for Combined Use of Aromatase Inhibitors and NSAIDs as Preventive Agents of Tobacco-Induced Lung Cancer

Abstract Introduction A hormonal role in NSCLC development is well documented. We previously showed that the aromatase inhibitor (AI) anastrozole decreased development of tobacco carcinogen-induced lung tumors in a murine lung cancer prevention model and that aromatase and estrogen receptor were expressed in pulmonary inflammatory cells. Methods We utilized a tobacco carcinogen–induced lung tumor mouse model by treatment with 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), to determine whether an AI combined with nonsteroidal anti-inflammatory drugs results in greater lung tumor prevention effects compared to single-agent treatment. Results Combination of anastrozole (0.1 mg/kg/d) with aspirin (25 mg/kg/d) after NNK exposure resulted in significantly fewer and smaller lung tumors than did single-agent treatments and was accompanied by maximum decreases in circulating β-estradiol (E2) and interleukin-6, tumor-infiltrating macrophages, and tumoral Ki67, phospho–mitogen-activated protein kinase, phospho–signal transducer and activator of transcription 3, and interleukin-17A expression. Preneoplasia arising after combination treatment showed the lowest Sox-2 expression, suggesting an inhibitory effect on proliferative capacity in the airways by blocking both E2 and inflammation. Anastrozole combined with ibuprofen instead of aspirin also showed enhanced antitumor effects. Moreover, male mice treated with NNK that received E2 in their drinking water showed greater levels of pulmonary macrophages and inflammatory markers than did the control, confirming an E2 effect on inflammation in the microenvironment. Conclusions Our results suggest a benefit to joint targeting of the estrogen and inflammatory pathways for NSCLC prevention. Combining AIs with nonsteroidal anti-inflammatory drugs reduces circulating E2, proinflammatory cytokines, and macrophage recruitment in the lung microenvironment after tobacco exposure. This strategy could be particularly effective in women who have underlying pulmonary inflammatory diseases.
Life cycle analysis of a combined CO2 capture and conversion membrane reactor

Abstract This paper reports a life cycle analysis of a combined CO2 capture and conversion “all-in-one” membrane reactor system. The reactor is composed of a high-temperature mixed electronic and carbonate-ion conductor (MECC) membrane for CO2 capture and a solid oxide electrolysis cell (SOEC) for CO2/H2O co-reduction. The results show that the parasitic energy (PE) using MECC membrane to capture CO2 is 321 kJ for every kilogram CO2 captured, less than half of the consumption of the stat-of the-art MEA plant. The energy efficiency of the combined system can reach 82%. A cost analysis further shows that the cost of electricity dictates the price of synthetic fuel produced by the reactor at a lower SOEC area (lower capital cost), while both electricity cost and SOEC capital cost play an important role for higher SOEC area (higher capital cost). Finally, the synthetic fuel produced from Ag-based MECC and NiO-based MECC capture/conversion systems are comparable to that of biomass derived liquids (carbon neutral) when the electricity cost is
Preliminary Interactions of Human-Robot Trust, Cognitive Load, and Robot Intelligence Levels in a Competitive Game

This paper presents a pilot study in which we examine the interactions between human-robot teammate trust, cognitive load, and robot intelligence levels. In particular, we attempt to assess these interactions during a competitive game of capture the flag played between a human and a robot. We present results while the human plays against robots of different intelligence levels and determines their level of trust of each robot as a potential teammate through a post experiment questionnaire. We also present our exploration of heart rate measures as approximations of cognitive load. It is our goal to determine guidelines for future autonomy and interaction designers such that their systems will reduce cognitive load and increase the level of trust in robot teammates. This is an initial experiment that uses the least amount of vehicles yet still gathers competitive data on the water. Future experiments will increase in complexity to many opponents and many teammates.
Diverse landscapes, diverse risks: synthesis of the special issue on climate change and adaptive capacity in a hotter, drier Southwestern United States

Assessing regional-scale vulnerability of agricultural systems to climate change and variability is vital in securing food and fiber systems, as well as sustaining rural livelihoods. Farmers, ranchers, and forest landowners rely on science-based, decision-relevant, and localized information to maintain production, ecological viability, and economic returns. This paper synthesizes the collection of research on the future of agricultural production in the Southwestern United States. A variety of assessment methods indicate the diverse impacts and risks across the Southwest, often related to water availability, which drives adaptive measures in this region. Sector- or species-specific adaptive measures have long been practiced in this region and will continue to be necessary to support agricultural production as a regional enterprise. Diversification of crop selection and income source imparts climate resilience. Building upon biophysical vulnerability through incorporating social and economic factors is critical to future adaptation planning efforts. The persistence and adaptive capacity of agriculture in the water-limited Southwest serves as an instructive example for producers outside the region expecting drier and warmer conditions and may offer solutions to reduce future climate impacts.
Differentiating between Affine and Perspective-Based Models for the Geometry of Visual Space Based on Judgments of the Interior Angles of Squares

This paper attempts to differentiate between two models of visual space. One model suggests that visual space is a simple affine transformation of physical space. The other proposes that it is a transformation of physical space via the laws of perspective. The present paper reports two experiments in which participants are asked to judge the size of the interior angles of squares at five different distances from the participant. The perspective-based model predicts that the angles within each square on the side nearest to the participant should seem smaller than those on the far side. The simple affine model under our conditions predicts that the perceived size of the angles of each square should remain 90°. Results of both experiments were most consistent with the perspective-based model. The angles of each square on the near side were estimated to be significantly smaller than the angles on the far side for all five squares in both experiments. In addition, the sum of the estimated size of the four angles of each square declined with increasing distance from the participant to the square and was less than 360° for all but the nearest square.
Retrospective evaluation of fidaxomicin versus oral vancomycin for treatment of Clostridium difficile infections in allogeneic stem cell transplant

Abstract Objective/background Clostridium difficile infection (CDI) is a potential complication during hematopoietic stem cell transplantation (HSCT), and no specific recommendations exist regarding treatment of CDI in allogeneic SCT patients. Use of metronidazole and oral vancomycin has been associated with clinical failure. Fidaxomicin has previously been found noninferior to the use of oral vancomycin for the treatment of CDI, and no studies have compared the use of oral vancomycin with fidaxomicin for the treatment of CDI in allogeneic SCT. Methods This retrospective chart review included 96 allogeneic SCT recipients who developed CDI within 100 days following transplantation. Participants were treated with oral vancomycin (n = 52) or fidaxomicin (n = 44). The primary outcome was clinical cure, defined as no need for further retreatment 2 days following completion of initial CDI treatment. Secondary outcomes were global cure, treatment failure, and recurrent disease. Results No differences in clinical cure were observed between patients receiving oral vancomycin or fidaxomicin (75% vs. 75%, p = 1.00). Secondary outcomes were similar between oral vancomycin and fidaxomicin in regards to global cure (66% vs. 67%, p = .508), treatment failure (28% vs. 27%, p = .571), and recurrent disease (7% vs. 5%, p = .747). In a subanalysis of individuals that developed acute graft-versus-host disease following CDI, the difference in mean onset of acute graft-versus-host disease was 21.03 days in the oral vancomycin group versus 32.88 days in the fidaxomicin group (p = .0031). Conclusion The findings of this study suggest that oral vancomycin and fidaxomicin are comparable options for CDI treatment in allogeneic SCT patients within 100 days following transplant.
Synthesis for Management

Among the first and most densely settled of estuaries in the United States, Long Island Sound presents a trajectory of change common to many estuarine and coastal ecosystems. The challenges to managing this ecosystem for the future also are mirrored in other coastal systems. Improving management of Long Island Sound requires synthesis and integration of the underlying science. The implications of such insights to the ecosystem, including changes that may be driven by broader climate patterns, must be incorporated into regulatory and management approaches. To demonstrate the utility of this analysis, key advancements in the science of the Long Island Sound ecosystem are summarized. To support integration with management, we present essential elements of the Clean Water Act, providing specific examples of current program policies in synchrony or in conflict with the principles of ecosystem-based management. We then recommend a general framework and specific actions to support ongoing management of Long Island Sound.
How Do Franchisors Evaluate Foreign Markets

This article has suggested a macro environmental model of international franchising which divides the host country factors into economic, demographic, distance and political dimensions. By specifying the macro environmental variables that are responsible for choosing a host country for a franchise concept, this article can help international franchising researchers build empirical models. Furthermore, the resulting model can help franchisors evaluate and rate international locations and can produce cumulative scores that can be used as references for comparing and contrasting competing environments.
Near Rational Powers of n

Those with experience in random graphs should not be surprised that the Zero-One Law does not hold when p = n -1/3. Take a strictly balanced H with e edges, υ vertices and υ/ e = 1/3 — more specifically, take H = K 7. The number X of copies of K 7 has E [ X ] = ( n 7 ) p 21 → 1/7! . From Janson’s Inequality 5.0.4, or even the original methods of Erdos and Renyi, Pr[X = 0] → e –1/7!. Here X = 0 is the first order ¬∃K 7 and e -1/7! is certainly neither zero nor one. One might expect (as, indeed, this author once conjectured) that for any first order A lim n→ ∞ Pr [G(n, n -1/3) ⊨ A] would exist and one might even hope for a description of the limiting probabilities as in Section 3.6. We shall see in this chapter that very much the opposite is true, that there are first order A for which Pr [A] behaves very strangely at and near n -1/3.
Fatigue in a Dynamic Neural Network

The addition of neural fatigue, due to adaptive membrane currents, can greatly expand the computational repertoire of recurrent (Hopfield-type) networks to include the rich, dynamical behavior of real biological neu-ronal networks such as the production of rythmic oscillations, central pattern generators, and the storage and retreival of temporal sequences of memories. Numerical simulations of a simple model of a recurrent network with neural fatigue, described by a lattice of coupled, 2-D nonlinear maps, shows that temporal sequences of memories can be reliably stored and retrieved using only fixed asymmetric weights and that memories with overlapping representations can be sequentially retrieved in a process resembling “free association”.
The Degradation of Talent

Let me get something straight. I am glad Schindler’s Listwas made;I am glad it exists. Except for the last ten minutes or so, when Spielberg faces the same problem as Bertolucci in 1900 (how do I bring this sort of thing to a close? So he doesn’t, and the thing goes on and on, and risks becoming its own caricature), this is a decent movie about the Holocaust, and we can use movies like that, just as we could use The Killing Fields or Little Big Man or The Mission or other popular illustrations of major historical tragedies. Nor do I buy the“ Who needs yet another movie about the Holocaust?” line: we need to be reminded of these events constantly, to constantly meditate on their significance. Some of us still need to learn about them; my own children, for example, who got a powerful set of images from this movie and will have to live, and somehow deal, with them. So, to paraphrase a line from Ben Kingsley in the movie, I believe Schindler’s List is good. Not great, however, which is where my problem lies. A problem that has nothing to do with the Holocaust, but a lot to do with Steven Spielberg.
1026. Trends in Infective Endocarditis During the Substance Use Disorder Epidemic at an Academic Medical Center

Background In many areas of the United States, substance use disorders (SUD) have increased dramatically over the past decade. Overdose deaths have increased as well, and Kentucky ranks among the nation’s leaders in deaths per 100,000 population. Infective endocarditis (IE) is a well-known complication of intravenous drug use, contributing to significant morbidity and mortality, but few studies have evaluated the effect of the current SUD epidemic on rates and demographics of IE. We sought to examine the trends in IE and IE with SUD at our institution.
Collaborating to Connect the Underserved With Patient Portals

Abstract This chapter introduces a library-led project to engage underserved patients with patient portal systems. It provides a background of the project, including the institutional context, a summary of the literature supporting patient portal implementation, as well as the national policies driving uptake. It highlights the unique challenges underserved patients and their health-care systems face in effectively engaging with patient portal systems. It describes the interdisciplinary project team and efforts to increase patient engagement in hospital and clinic settings. The chapter describes research funded by the National Library of Medicine to develop, test, and share video-based patient portal curricula. Finally, the chapter concludes with reflections on the benefits of the project from Library, physician, researcher, and patient perspectives and offers recommendations for other health sciences libraries considering similar projects.
CHAPTER 24 – Absorption, Distribution, and Pharmacokinetics

This chapter includes a general discussion of absorption, distribution, and pharmacokinetics of chemicals, especially pesticides. It also discusses the factors that influence the transfer of chemicals across biological membranes. Human exposure to pesticides is typically by oral, dermal, and inhalation routes. Whereas, occupational exposure to pesticides is likely to occur by inhalation or dermal contact, exposure of small children is more likely to be by oral and/or dermal routes. Absorption generally occurs from gastrointestinal tract and respiratory tract. Once in the bloodstream, the chemical is available for distribution throughout and elimination from the body. Factors that influence the rate and extent of distribution of a chemical to a particular tissue include blood flow to the tissue the mass of the tissue, the ability of the chemical to cross membranes, and the affinity of the chemical for the tissue relative to blood. The rate of distribution of a chemical from blood to tissues can be perfusion- or diffusion-rate- limited. Pharmacokinetics is the modeling and mathematical description of the time course of chemical disposition. Pharmacokinetic models typically describe the change in blood concentration of the chemical with time. There are two basic approaches to characterizing the pharmacokinetics of a chemical in the body: compartmental and noncompartmental.
An innovative resident-driven mortality case review curriculum to teach and drive system-based practice improvements in the United States

Purpose Traditionally, Morbidity and Mortality Conference (M&MC) are forums where medical errors are discussed. Though M&MC can lead to identification of opportunities for system wide improvements, there is little in the literature to describe the use for this purpose, particularly in residency training programs. This paper describes the use of M&MC case review as a quality improvement activity that teaches systems-based practice and can engage residents in improving systems of care. Methods Internal medicine residents at a tertiary care academic medical center reviewed 347 consecutive mortalities from March 2104 to September 2017. Residents used case review worksheets to categorize and track causes of mortality. The residents then debriefed with a faculty member. Selected cases were then presented at a larger interdepartmental meeting and action items were implemented. Descriptive statistics and thematic analysis were used to analyze the results. Results The residents identified a diagnosis mismatch from admission to death in 54.5 % (n=189) of cases and possible need for improvement in management in 48.0% cases. Three 'management failure' themes were identified including failures to plan, failure to communicate and failure to rescue, consisting of 21.9%, 10.7 %, and 10.1% of cases respectively. Following the reviews, quality improvement initiatives proposed by residents lead to system-based changes. Conclusion A resident-driven mortality review curriculum can lead to improvement in systems of care. This type of novel curriculum can teach systems-based practice. The recruitment of teaching faculty with expertise in quality improvement and mortality case analyses is essential for such a project.
Awareness of and experience with online outsourcing journalism labor markets: A benchmark study of freelance journalists

Online outsourcing markets (OOMs), those sites that connect buyers and sellers of digital labor, have grown dramatically, attracting a global cadre of freelance workers. Journalism OOMs are beginning to have an impact on the buying and selling of freelance journalism. This paper is an exploration of early effects, reporting findings of a survey ( n =453) of freelance journalists who use OOMs and those who don’t, or don’t yet. The paper reviews recent scholarship on OOMs and freelance journalists. Freelance journalists were asked about their awareness of and experience with journalism OOMs. Considering OOMs only recently started diffusing, analysis shows a relatively high level of awareness and use of OOMs, plus perceptions about their value for obtaining work, working conditions and monetary and intrinsic rewards.
Gregory Interpolation: A Trick for Problem Solvers from Out of the Past.

As different as they may seem, all these problems belong to a very large class of problems all of which can be solved or par tially solved by the easily applied Gregory interpolation formula. To explain the for mula we first introduce the notion of a dif ference table and also that of an arithmetic sequence of order m. Consider the sequence 1, 5, 14, 30, 55,_In an effort to discover a possible rule of formation, we form a difference table using the numbers in the sequence, their differences, the differences of their dif ferences, and so on. We then obtain
Telling Tales The Transactional Lawyer as Storyteller

Transactional documents, whether employment contracts or lease agreements, encapsulate the wishes, hopes, and fears of the transacting parties. The documents share a series of events, identify the key actors in the event, and anticipate particular outcomes. In other words, the transactional documents are narratives. The transactional lawyer is thus more than a transactional intermediary. The transactional lawyer is the narrative agent or storyteller. Equating a transactional lawyer to Aesop, the Brothers Grimm, and Scheherazade may appear to be an ill-fitting comparison. Yet, the comparison is surprisingly apt. Transactional lawyers weave together provisions and clauses to craft documents that will promote, guide, and control the relationship of those parties. This article shares five strategies to demonstrate how narratology can be used by transactional lawyers to draft documents that more effectively tell their client’s stories.
Point-of-care HIV viral load in pregnant women without prenatal care: a cost-effectiveness analysis.

Background Routine cesarean delivery has been shown to decrease mother-to-child-transmission of HIV in women with high viral load greater than 1000 copies/mL; however, women presenting late in pregnancy may not have viral load results before delivery. Objective Our study investigated the costs and outcomes of using a point-of-care HIV RNA viral load test to guide delivery compared with routine cesarean delivery for all in the setting of unknown viral load. Study Design A decision-analytic model was constructed using TreeAge software to compare HIV RNA viral load testing vs routine cesarean delivery for all in a theoretical cohort of 1275 HIV-positive women without prenatal care who presented at term for delivery, the estimated population of HIV-positive women without prenatal care in the United States annually. TreeAge Pro software is used to build decision trees modeling clinical problems and perform cost-effectiveness, sensitivity, and simulation analysis to identify the optimal outcome. The average cost per test was $15.22. To examine the downstream impact of a cesarean delivery and because most childbearing women in the United States will deliver 2 children, we incorporated a second pregnancy and delivery in the model. Primary outcomes were mother-to-child transmission, delivery mode, cesarean delivery–related complications, cost, and quality-adjusted life years. Model inputs were derived from the literature and varied in sensitivity analyses. The cost-effectiveness threshold was $100,000/quality-adjusted life year. Results Measuring viral load resulted in more HIV-infected neonates than routine cesarean delivery for all due to viral exposure during more frequent vaginal births in this strategy. There were no observed maternal deaths or differences in cesarean delivery–related complications. Quantifying viral load increased cost by $3,883,371 and decreased quality-adjusted life years by 63 compared with routine cesarean delivery for all. With the threshold set at $100,000/quality-adjusted life year, the viral load test is cost-effective only when the vertical transmission rate in women with high viral load was below 0.68% (baseline: 16.8%) and when the odds ratio of vertical transmission with routine cesarean delivery for all compared with vaginal delivery was above 0.885 (baseline: 0.3). Conclusions For HIV-infected pregnant women without prenatal care, quantifying viral load to guide mode of delivery using a point-of-care test resulted in increased costs and decreased effectiveness when compared with routine cesarean delivery for all, even after including downstream complications of cesarean delivery.
The psychological burden of baby weight: Pregnancy, weight stigma, and maternal health

Weight stigma is increasingly prevalent, highly distressing, and associated with an array of negative health and psychological outcomes. Many of the known correlates - depression, stress, and weight gain - have the potential to be particularly harmful in the context of pregnancy and the postpartum, a life phase in which women's social roles, body weights, and body meanings are in particular flux. Yet, there is little literature connecting the experiences of weight stigma to the wellbeing of pregnant and postpartum women. 501 pregnant (n = 143) and postpartum (n = 358) women in the United States were surveyed between August and November of 2017. They answered questions about their experiences with weight stigma and standardized scale measures of depressive symptoms, perceived stress, maladaptive dieting behavior, emotional eating behavior, gestational weight gain, and postpartum weight retention. Regression analyses revealed that women experiencing weight stigma from more sources reported more depressive symptoms, maladaptive dieting behavior and perceived stress when controlling for pre-pregnancy BMI, parity, weeks of pregnancy or months since birth, and demographic covariates. Weight-stigmatizing experiences were also associated with more emotional eating behavior in pregnant participants and greater postpartum weight retention in postpartum participants. This preliminary study suggests that experiencing weight stigma may contribute to unfavorable physical and mental health outcomes for pregnant and postpartum women. These findings reflect the powerful negative social meanings of weight gain faced in pregnancy and often unachievable social standards of "dropping the baby weight" as new mothers.
The effects of developmental alcohol exposure on the neurobiology of spatial processing

The consumption of alcohol during gestation is detrimental to the developing central nervous system. One functional outcome of this exposure is impaired spatial processing, defined as sensing and integrating information pertaining to spatial navigation and spatial memory. The hippocampus, entorhinal cortex, and anterior thalamus are brain regions implicated in spatial processing and are highly susceptible to the effects of developmental alcohol exposure. Some of the observed effects of alcohol on spatial processing may be attributed to changes at the synaptic to circuit level. In this review, we first describe the impact of developmental alcohol exposure on spatial behavior followed by a summary of the development of brain areas involved in spatial processing. We then provide an examination of the consequences of prenatal and early postnatal alcohol exposure in rodents on hippocampal, anterior thalamus, and entorhinal cortex-dependent spatial processing from the cellular to behavioral level. We conclude by highlighting several unanswered questions which may provide a framework for future investigation.
The transmembrane domain of DWORF activates SERCA directly; P15 and W22 residues are essential

The Ca-ATPase isoform 2a (SERCA2a) re-sequesters cytosolic Ca2+ into the sarcoplasmic reticulum (SR) of cardiac myocytes, enabling muscle relaxation during diastole. A central factor in heart failure is abnormally high cytosolic [Ca2+], resulting in pathophysiology and decreased cardiac performance. Therefore, augmentation of the SERCA2a Ca2+ transport activity is a promising therapeutic approach. A novel transmembrane peptide, dwarf open reading frame (DWORF), is proposed to enhance SR Ca2+ uptake and myocyte contractility by displacing the protein phospholamban (PLB) from its inhibitory site on SERCA2a. In the present study, we have developed several cell-based FRET biosensor systems for time-resolved FRET (TR-FRET) measurements of the protein-protein interactions and structural changes in SERCA2a complexes with PLB and/or DWORF. To test the hypothesis that DWORF competes with PLB to occupy the putative SERCA2a binding site, we transiently transfected DWORF into a stable cell line expressing SERCA2a labeled with green fluorescent protein (GFP, the FRET donor) and PLB labeled with red fluorescent protein (RFP, the FRET acceptor). We observed a significant decrease in FRET efficiency, consistent with a decrease in the fraction of SERCA2a bound to PLB. Functional analysis demonstrates that DWORF activates SERCA in both the presence and absence of PLB. Furthermore, using site-directed mutagenesis, we generated DWORF variants that do not activate SERCA, thus identifying residues that are necessary for functional SERCA2a-DWORF interactions. This work advances our mechanistic understanding of the regulation of SERCA2a by small transmembrane proteins and sets the stage for future therapeutic development in heart failure research.
On the atomic structure of Pt(1 1 1)/γ-Al2O3(1 1 1) interfaces and the changes in their interfacial energy with temperature and oxygen pressure

Abstract Metal/metal-oxide interfaces are important in many applications including metal coatings, sensing, and catalysis. Here we investigate and predict the structure and chemical bonding of the interface between γ-Al2O3 and Pt using density functional theory. Previous high-resolution transmission electron microscopy studies showed atomically flat interfaces between the (1 1 1) planes of Pt and γ-Al2O3; this interfacial orientation is studied herein. A simulated temperature–pressure equilibrium configuration diagram shows how the stability of the interfaces changes with temperature and oxygen pressure. Of the three interfacial terminations (O, Al, Al2) the oxygen-terminated γ-Al2O3 (1 1 1) is the most stable at atmospheric conditions. The stability of this interface is attributed to the strong electrostatic interaction between the Pt and the oxygen atoms at the oxygen-terminated interface. This work provides essential insights into the atomic structure and the origins of the interactions at the interface between transition metals and metal-oxides, as well as interfacial configuration at a range of conditions.
Phase-sensitive γ-encoded recoupling of heteronuclear dipolar interactions and 1H chemical shift anisotropy.

Abstract γ-encoded recoupling sequences are known to produce strong amplitude modulations that lead to sharp doublets when Fourier transformed. These doublets depend very little on the recoupled tensor asymmetry and thus enable for the straightforward determination of dynamic order parameters. It can, however, be difficult to measure small anisotropies, or small order parameters, using such sequences; the resonances from the doublet may overlap with each other, or with the zero-frequency glitch. This limitation has prevented the widespread use of 1H chemical shift anisotropy (CSA) for the measurement of dynamics, particularly for CH protons which typically have CSAs of only a few ppm when immobile. Here, we introduce a simple modification to the traditional 1H CSA and proton-detected local field pulse sequences that enables the acquisition of a hypercomplex dataset and the removal of the uncorrelated magnetization that results in the zero-frequency glitch. These new sequences then yield a frequency shift in the indirect dimension, rather than a splitting, which is easily identifiable even in cases of weak interactions.
Synthetic Aperture Radar

The previous discussions of this A.S.I. of target scattering and effects of the atmosphere upon microwave propagation are extended to the problem of imaging by synthetic aperture radar (SAR). The foundation for discussion of SAR system performance has been given by Corless [1]. A SAR system generates an image of the reflectivity distribution of the surface being observed, as it appears at the wavelength employed by the radar. Differences in gross reflectivity, shadowing, texture, and shape of the illuminated terrain features are analyzed to yield information required for specific applications. These may include mapping, agricultural land use, ice surveillance, and measurement of ocean waves. The implications of terrain scattering for imaging radar system performance and initial applications of a dual-wavelength, dual-polarization SAR are discussed. The influence of atmospheric turbulence on SAR is then examined.
Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats

Dieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effects of increasing leptin levels in the hypothalamus using gene therapy with conventional caloric restriction on weight gain, food consumption, serum leptin and adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (n = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for leptin (rAAV-Lep), and maintained on standard rat chow for 18 weeks. A second group (n = 15) was calorically-restricted to match the weight of the rAAV-Lep group. Both approaches prevented weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue Ucp-1 mRNA expression than rAAV-Lep rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum leptin and adiponectin levels, and higher marrow adiposity. Caloric restriction and hypothalamic leptin gene therapy, while equally effective in preventing weight gain, differ in their effects on energy intake, energy expenditure, adipokine levels, and body composition.
Optimal Control and Architecture Design Optimization for Hydraulic Drive Train of a Compact Track Loader

Hydrostatic transmission (HST) is a common hydraulic drive train transmission used in track loaders and other high power off-road vehicles. While reliable, traditional HST with fixed-displacement motors has relatively poor efficiencies. In this paper, alternative HST and series hybrid drive train architectures are proposed to replace the traditional HST to allow the implementation of optimal control and optimization methods for better vehicle fuel efficiency. Besides the optimal control methods applied to minimize fuel consumption, the proposed architectures are also optimized for the best configuration in terms of component sizing. Backward-facing (acausal) simulation models were developed to estimate the fuel efficiency of each architecture. Finally, each architecture is compared for optimized performance and fuel saving relative to the traditional HST as baseline.
Patient-Reported Outcome Measures Modestly Enhance Prediction of Readmission in Patients with Cirrhosis.

Background & Aims Patients with cirrhosis have high rates of hospital readmission, but prediction models are suboptimal and have not included important patient-reported outcome measures (PROMs). In a large prospective cohort, we examined the impact of PROMs on prediction of 30-day readmissions. Methods We performed a prospective cohort study of adults with cirrhosis admitted to a tertiary center between June 2014 and March 2020. We collected clinical information, socioeconomic status, and PROMs addressing functional status and quality of life. We used hierarchical competing risk time-to-event analysis to examine the impact of PROMs on readmission prediction. Results A total of 654 patients were discharged alive, and 247 (38%) were readmitted within 30 days. Readmission was independently associated with cerebrovascular disease, ascites, prior hospital admission, admission via the emergency department, lower albumin, higher Model for End-Stage Liver Disease, discharge with public transportation, and impaired basic activities of daily living and quality-of-life activity domain. Reduced readmission was associated with cancer, admission for infection, children at home, and impaired emotional function. Compared with a model including only clinical variables, addition of functional status and quality-of-life variables improved the area under the receiver-operating characteristic curve from 0.72 to 0.73 and 0.75, with net reclassification indices of 0.22 and 0.18, respectively. Socioeconomic variables did not significantly improve prediction compared with clinical variables alone. Compared with a model using electronically available variables only, no models improved prediction when examined with integrated discrimination improvement. Conclusions PROMs may marginally add to the prediction of 30-day readmissions for patients with cirrhosis. Poor social support and disability are associated with readmissions and may be high-yield targets for future interventions.
Cell-cell Adhesion Impacts Epithelia Response to Substrate Stiffness: Morphology and Gene Expression

Abstract Monolayer epithelial cells interact constantly with the substrate they reside on and their surrounding neighbors. As such, the properties of epithelial cells are profoundly governed by the mechanical and molecular cues that arise from both the substrate and contiguous cell neighbours. While both cell-substrate and cell-cell interactions have been studied individually, these results are difficult to apply to native confluent epithelia, in which both jointly regulate the cell phenotype. Specifically, it remains poorly understood about the intertwined contributions from intercellular adhesion and substrate stiffness on cell morphology and gene expression, two essential microenvironment properties. Here, by adjusting the substrate modulus and altering the intercellular adhesion within confluent kidney epithelia, we found that cell-substrate and cell-cell interactions can mask each other’s influence. For example, we found that epithelial cells exhibit an elongated morphological phenotype only when the substrate modulus and intercellular adhesions are both reduced, whereas their motility can be upregulated by either reduction. These results illustrate that combinatorial changes of the physical microenvironment are required to alter cell morphology and gene expression.
Towards a hybrid relational and XML benchmark for loosely-coupled distributed data sources

Designed heterogeneous data sources for a hybrid version of the TPC-H enterprise.Developed hybrid LINQ queries over the relational and XML data sources.Evaluated the hybrid benchmark for loosely-coupled distributed data sources.Assessed query performance for two database products with various options. There are known benchmarks for the performance evaluation of relational and XML databases. However, there is an increasing demand for database applications that require access to heterogeneous loosely-coupled distributed data sources. This paper presents a hybrid benchmark based on TPC-H where the data sources are heterogeneous. Specifically, the paper describes the design of the relational and XML data sources as well as the query redesign in the LINQ query language, which supports queries over heterogeneous data sources. The results of a performance evaluation of the hybrid benchmark over various database products is included for untyped and typed XML with and without clearing the database cache.
Maternal and fetal disorders in pregnancies of mothers of twins

Abstract A study of pregnancy data on 329 mothers of twins indicates that certain maternal and fetal disorders, e.g., Rh erythroblastosis fetalis and cardiac malformations, were significantly more prevalent preceding twin conceptions compared to the singleton pregnancies of control mothers. In addition, mothers of twins more frequently had offspring with hypospadias or enlarged clitoris than mothers with only singleton pregnancies. I conclude that there may be maternal factors common to twinning and genital abnormalities and that certain disorders in other pregnancies are associated with twinning. The possible influence of maternal and pregnancy conditions on the reproductive physiology of offspring is discussed, and the potential effect on twinning rate is considered.
MPDM: Multipolicy decision-making in dynamic, uncertain environments for autonomous driving

Real-world autonomous driving in city traffic must cope with dynamic environments including other agents with uncertain intentions. This poses a challenging decision-making problem, e.g., deciding when to perform a passing maneuver or how to safely merge into traffic. Previous work in the literature has typically approached the problem using ad-hoc solutions that do not consider the possible future states of other agents, and thus have difficulty scaling to complex traffic scenarios where the actions of participating agents are tightly conditioned on one another. In this paper we present multipolicy decision-making (MPDM), a decision-making algorithm that exploits knowledge from the autonomous driving domain to make decisions online for an autonomous vehicle navigating in traffic. By assuming the controlled vehicle and other traffic participants execute a policy from a set of plausible closed-loop policies at every timestep, the algorithm selects the best available policy for the controlled vehicle to execute. We perform policy election using forward simulation of both the controlled vehicle and other agents, efficiently sampling from the high-likelihood outcomes of their interactions. We then score the resulting outcomes using a user-defined cost function to accommodate different driving preferences, and select the policy with the highest score. We demonstrate the algorithm on a real-world autonomous vehicle performing passing maneuvers and in a simulated merging scenario.
Lessons from Canada: Crisis-Proofing a National Financial System

The Article compares the financial institutions and financial regulation of the United States and Canada with regard to ten key factors: 1) Financial institution asset size and market concentration; 2) Capital requirements for financial institutions; 3) Prudential regulation structures and policies; 4) Regulatory oversight of the federal Financial Consumer Agency of Canada (FCAC) and the stringency of consumer financial protection measures compared with no separate federal consumer financial protection agency in the U.S. until passage of the Dodd-Frank bill; 5) Real estate market issues, including price trends and foreclosure rates; 6) Mortgage lending policies; 7) Secondary mortgage market structures; 8) Tax policy issues, including the non-deductibility of mortgage interest in Canada; 9) Monetary policy issues, including interest rate policy; and 10) Budget and trade balances. In reviewing these ten factors, the Article shows that the Canadian financial system typically demonstrates a lower risk-appetite, more prudent business practices, and more conservative regulation as compared with that in the U.S..