cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of mixed proximal and distal topogenic signals on the topological sensitivity of a membrane protein to the lipid environment

The final topology of membrane proteins is thought to be dictated primarily by the encoding sequence. However, according to the Charge Balance Rule the topogenic signals within nascent membrane proteins are interpreted in agreement with the Positive Inside Rule as influenced by the protein phospholipid environment. The role of long-range protein-lipid interactions in establishing a final uniform or dual topology is unknown. In order to address this role, we determined the positional dependence of the potency of charged residues as topological signals within Escherichia coli sucrose permease (CscB) in cells in which the zwitterionic phospholipid phosphatidylethanolamine (PE), acting as topological determinant, was either eliminated or tightly titrated. Although the position of a single or paired oppositely charged amino acid residues within an extramembrane domain (EMD), either proximal, central or distal to a transmembrane domain (TMD) end, does not appear to be important, the oppositely charged residues exert their topogenic effects separately only in the absence of PE. Thus, the Charge Balance Rule can be executed in a retrograde manner from any cytoplasmic EMD or any residue within an EMD most likely outside of the translocon. Moreover, CscB is inserted into the membrane in two opposite orientations at different ratios with the native orientation proportional to the mol % of PE. The results demonstrate how the cooperative contribution of lipid-protein interactions affects the potency of charged residues as topological signals, providing a molecular mechanism for the realization of single, equal or different amounts of oppositely oriented protein within the same membrane.
Dietary Stress and Animal Resource Use at the Postclassic Maya city, Mayapan (Mexico)

ABSTRACTEnvironmental changes resulting in drought and reductions in the availability of animal resources during the Late Classic Maya have been linked with the Maya ‘collapse’. Decreases in availability of dietary staples such as artiodactyls, and particularly white-tailed deer, during the Late Classic period would have placed food stress on populations during later periods. To test this hypothesis, here bone breakage patterns are examined at the Postclassic Maya city, Mayapan, to assess whether artiodactyl bones were being intensively processed for bone fats (marrow and grease). Fragmentation morphology, size and surface markings, along with skeletal part representation and distribution of large mammal bones were recorded for bone assemblages from several houselots. Evidence suggests the Maya were likely utilising bone marrow from artiodactyls but not intensively and they were not extracting bone grease. These results indicate that decreased accessibility to artiodactyls during the Postclassic was not c...
Blocking CRMP2 SUMOylation reverses neuropathic pain

Collapsin response mediator proteins 1−5 (CRMPs1−5) are a family of cytosolic proteins that coordinate neuronal migration, axonal guidance, dendritic organization, dendritic spine development and synaptic plasticity (reviewed in Khanna et al.1and Quach et al.2). Members of the CRMP family are reported to be involved in the pathogenesis of various neuronal disorders. For instance, proteomic, genomic and translational approaches linked the CRMP1 gene with chronic, negative symptoms of schizophrenia and severe major depression.3 Mice lacking CRMP1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition behavioral abnormalities related to schizophrenia.4 Genetic association and linkage studies pointed to CRMP2 as a liability gene for schizophrenia, autism, alcohol dependence, depression and bipolar disorders.5, 6, 7, 8, 9, 10 Mice with brain-specific Crmp2 deletion exhibited behavioral deficits in locomotor activity, sensorimotor gating, social behavior, and spatial learning and memory.11 Maternal autoantibodies against CRMP1 and CRMP2 were found in children with autism spectrum disorders that displayed core deficits in communication and reciprocal social interaction as well as repetitive or stereotypical behaviors.12 CRMP3-deficient mice display significant decreases in dendritic length and branching points, and an abnormal undulation of apical primary dendrites; these findings are recapitulated in the brain of Down syndrome where the expression of CRMP3 gene is also impaired.13 Little is known about the relationship between CRMP4 and neuropsychiatric disorders. However, mice lacking CRMP4 manifest impaired olfactory function and hyperactivity in the olfactory bulb and have increased levels of ionotropic glutamate receptors GluRs 1 and 2, which have been implicated in autism spectrum disorders and schizophrenia.14 CRMP5 knockout mice implicate this protein in dendritic development and synaptic plasticity in cerebellar purkinje cells,15 and CRMP5 autoantibodies were reported in patients with paraneoplastic neurological syndrome characterized by cerebellar ataxia and chorea. Therefore, understanding CRMP signaling has significant clinical implications.
The relationship between child welfare financing, screening, and substantiation

Abstract This study examines the relationship between state-level child welfare spending and two important decision points in the child welfare system: the decision to screen out a referral and the decision to substantiate. The model is estimated using a pooled fractional probit estimator that controls for year effects and state-level clustering. The findings suggest that decreases in state-level child welfare expenditures predict increases in the proportion of referrals that are screened out and decreases in the proportion of maltreatment claims that are substantiated. The results are robust to the inclusion of caseload and federal spending as control variables, to the exclusion of states known to have changed their screening or funding practices during the sample period, and to the use of combined state and local child welfare expenditures as an explanatory variable in lieu of state-level child welfare expenditures. The findings imply that the amount of money a state spends on child welfare may influence important decisions in the child welfare process.
The further rise of the career politician

Political careers have changed dramatically in the last 50 years. Still, political science research has yet to fully quantify this development. Building on existing literature on career politicians, this study uses a handful of indicators introduced by King (Br J Polit Sci 11(3):249–285, 1981), a new variable (pre-parliamentary occupations), and an original data set compiled by the author. The paper’s contribution to the literature is threefold. Firstly, using the variables introduced by King, it observes that a plateau in the number of career politicians has been reached. Secondly, when looking at the occupational background of politicians, the data show a further rise in career politicians. Thirdly, this development is especially prevalent among cabinet ministers.
Article Commentary: Alcohol policy research and the grey literature:

This commentary is a tale of two international surveys dealing with alcohol policy. One was conducted by an international public health agency, the World Health Organization, the other by a “social...
Weighted estimating equations for additive hazards models with missing covariates

This paper presents simple weighted and fully augmented weighted estimators for the additive hazards model with missing covariates when they are missing at random. The additive hazards model estimates the difference in hazards and has an intuitive biological interpretation. The proposed weighted estimators for the additive hazards model use incomplete data nonparametrically and have close-form expressions. We show that they are consistent and asymptotically normal, and are more efficient than the simple weighted estimator which only uses the complete data. We illustrate their finite-sample performance through simulation studies and an application to study the progression from mild cognitive impairment to dementia using data from the Alzheimer's Disease Neuroimaging Initiative as well as an application to the mouse leukemia study.
A framework for annotating OpenStreetMap objects using geo-tagged tweets

Recent years have witnessed an explosion of geospatial data, especially in the form of Volunteered Geographic Information (VGI). As a prominent example, OpenStreetMap (OSM) creates a free editable map of the world from a large number of contributors. On the other hand, social media platforms such as Twitter or Instagram supply dynamic social feeds at population level. As much of such data is geo-tagged, there is a high potential on integrating social media with OSM to enrich OSM with semantic annotations, which will complement existing objective description oriented annotations to provide a broader range of annotations. In this paper, we propose a comprehensive framework on integrating social media data and VGI data to derive knowledge about geographical objects, specifically, top relevant annotations from tweets for objects in OSM. We first integrate geo-tagged tweets with OSM data with scalable spatial queries running on MapReduce. We propose a frequency based method for annotating boundary based geographic objects (a polygon), and a probability based method for annotating point based geographic objects (Latitude and Longitude), with consideration of noise. We evaluate our methods using a large geo-tagged tweets corpus and representative geographic objects from OSM, which demonstrates promising results through ground-truth comparison and case studies. We are able to produce up to 80% correct names for geographical objects and discover implicitly relevant information, such as popular exhibitions of a museum, the nicknames or visitors’ impression to a tourism attraction.
Cows, Cookstoves, and Climate Change: A Non-Anthropocentric View of Household Energy Use in the Rural Indian Himalayas

Household air pollution in the form of smoke from cookstoves in low-income homes is a serious threat to the health of women and children in the global South, and a contributor to global climate change. Many development actors have attempted to intervene in rural kitchens, by facilitating an energy transition to new technologies and fuels. Based on research in the rural Indian Himalayas, this paper will demonstrate how efforts to promote improved cookstoves bring different visions of stoves together in rural kitchens – as a technology meant to generate heat for cooking food, and as a device at the heart(h) of energy and mass flows between people, their livestock, and their fields. Drawing on eighteen months of fieldwork conducted between 2013-17 in rural Himachal Pradesh in India, this paper will examine the effect that human-animal relationships have on household energy decisions, ultimately affecting individual health and the environment. This approach expands existing scholarship in energy studies, which has historically been anthropocentric.
SPECIAL CLINICAL CONCERNS/ PROBLEMS IN THE MANAGEMENT OF MDS AND SEDONDARY ACUTE MYELOID LEUKEMIAS

Management of patients with myelodysplastic syndromes (MDS) and acute myeloid leukemias arising from pre-existing MDS (Secondary AML, sAML) presents many unique problems to the treating physician. These patients are often elderly and are at high risk for life threatening complications of treatment. Recurrent infections and a history of multiple blood product transfusions complicate the clinical management and compromise their ability to tolerate therapy. Drug resistance and the frequent occurrence of cytogenetic abnormalities result in lower remission rates and decreased long term responses. This chapter will review these unique aspects of management of these patients.
[18F]Lansoprazole and [11C]N-methyl lansoprazole: High affinity radiotracers for imaging tau pathology

322 Objectives The high affinities of lansoprazole (Ki = 2.5 nM) and N-methyl lansoprazole (Kd = 700 pM) for heparin induced tau make radiolabeled versions attractive candidates for PET imaging of tau pathology in Alzheimer’s disease and related tauopathies. We recently reported initial pre-clinical evaluation of [11C]N-methyl lansoprazole (Shao et al., ACS Med Chem Lett, 2012). However, reflecting issues associated with the short half-life of carbon-11, it was important to prepare [18F]lansoprazole. Herein we report the first synthesis of [18F]lansoprazole (by radiolabeling the -CF3 group) and progress in the pre-clinical evaluation of both radiotracers. Methods [18F]Lansoprazole was prepared from the corresponding gem-difluoroalkene precursor on a GE TRACERlab FXFN module by adaptation of chemistry reported by Riss et al (Org Biomol Chem, 2012). [11C]N-Methyl lansoprazole was prepared as previously reported (ACS Med Chem Lett, 2012). Standard pre-clinical evaluation was conducted as follows: - Rodent and primate MicroPET imaging studies - Rodent metabolism and biodistribution studies - In vitro autoradiography / immunocytochemistry with human brain samples (tau positive, amyloid positive, and age matched healthy controls) using mouse anti-human monoclonal tau antibody - Determination of binding affinities for both tau and amyloid. Results Non-decay-corrected yields of [11C]N-methyl lansoprazole and [18F]lansoprazole were 7% (from 900 mCi of [11C]MeI, n= 15) and 7% (from 1.5 Ci of [18F]fluoride, n= 5), respectively. Doses passed all other quality control, confirming their suitability for future clinical PET imaging. Autoradiography and immunocuctochemistry confirmed co-localization of both radiotracers with tau (as globose tangles) in brain samples from PSP patients. MicroPET imaging showed pharmacokinetics compatible with brain imaging applications. Conclusions [11C]N-Methyl lansoprazole and [18F]lansoprazole are radiotracers with high affinity for tau that have potential for in vivo imaging of tau pathology. Research Support Financial support of this work by the University of Michigan Office for the Vice President of Research (OVPR#6354) and NIBIB (T32EB005172-02) are gratefully acknowledged.
The Me and the Not-Me

Symbolic interactionists have long regarded identification of Self and Other as a key feature of social interaction (Blumer, 1962; Cooley, 1902; McCall & Simmons, 1978/1966; Mead, 1934). Establishment of one’s own identity to oneself is as important in interaction as to establis it for the other. One’s own identity in a situation is not absolutely given but is more or less problematic. (Foote, 1951, p. 18) For just such reasons, symbolic interactionists have similarly considered identity to be a key feature of the self. As Kuhn put it, “a person interiorizes his roles and statuses, and with these the expectations that significant others have of him” (Hickman & Kuhn, 1956, p. 242). Adding to this foundation a Cooley-esque emphasis on imagination, (1978/1966) proposed that “a role-identity is his imaginative view of himself as he likes to think of himself being and acting as an occupant” of a particular social position. These components remain central to the concept today, as (2001) stated that “identities are internalized role expectations” (p. 286) and that “self-meanings develop in the context of meanings of roles and counter roles” (p. 287).
Self Reflections: The Origins of an Attribution Theorist

The attainment of an award provides the occasion for self-reflection, a time to be self-indulgent, and even perhaps the opportunity to provide guidance to others striving for accomplishment and recognition. Hence, at this time I would like to think back autobiographically and reconstruct some of the past to explain, in my own biased way, what events might have been responsible for the receipt of this award.
Accuracy of ultrasound-guided versus palpation-based carpometacarpal joint injections: A randomized pilot study in cadavers.

ObjectiveTo determine the accuracy of ultrasound guidance compared to palpation in performing carpometacarpal joint injections in cadavers.DesignIn all, 36 carpometacarpal joints were randomized to...
O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response

Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms. Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations. Whether and how O-GlcNAc modification regulates HSR remains unclear. Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region. Without O-GlcNAc modification, the preferential translation of stress mRNAs is impaired. Unexpectedly, stress mRNAs are entrapped within stress granules (SGs) that are no longer dissolved during stress recovery. Mechanistically, we show that stress-induced eIF4GI O-GlcNAcylation repels poly(A)-binding protein 1 and promotes SG disassembly, thereby licensing stress mRNAs for selective translation. Using various eIF4GI mutants created by CRISPR/Cas9, we demonstrate that eIF4GI acts as a translational switch via reversible O-GlcNAcylation. Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
Community-based palliative care utilization in elderly pancreatic cancer patients.

10108Background: Community-based Palliative Care (CBPC) has shown to stabilize symptoms, alleviate psychological and spiritual burdens, satisfy care preferences, and improve quality of life among c...
Quantifying amide proton exchange rate and concentration in chemical exchange saturation transfer imaging of the human brain

Abstract Current chemical exchange saturation transfer (CEST) neuroimaging protocols typically acquire CEST-weighted images, and, as such, do not essentially provide quantitative proton-specific exchange rates (or brain pH) and concentrations. We developed a dictionary-free MR fingerprinting (MRF) technique to allow CEST parameter quantification with a reduced data set. This was accomplished by subgrouping proton exchange models (SPEM), taking amide proton transfer (APT) as an example, into two-pool (water and semisolid macromolecules) and three-pool (water, semisolid macromolecules, and amide protons) models. A variable radiofrequency saturation scheme was used to generate unique signal evolutions for different tissues, reflecting their CEST parameters. The proposed MRF-SPEM method was validated using Bloch-McConnell equation-based digital phantoms with known ground-truth, which showed that MRF-SPEM can achieve a high degree of accuracy and precision for absolute CEST parameter quantification and CEST phantoms. For in-vivo studies at 3 T, using the same model as in the simulations, synthetic Z-spectra were generated using rates and concentrations estimated from the MRF-SPEM reconstruction and compared with experimentally measured Z-spectra as the standard for optimization. The MRF-SPEM technique can provide rapid and quantitative human brain CEST mapping.
Contrast-induced coronary no-flow phenomenon: during diagnostic coronary angiography.

A 55-year-old man presented with episodes of severe nonexertional chest pressure that radiated to his left arm. Results of exercise technetium-99m sestamibi single-photon-emission computed tomographic myocardial perfusion imaging were unremarkable; however, the exercise electrocardiogram showed significant inferior and anterolateral ST-segment depression consistent with ischemia. Coronary angiography was performed. The left main stem was engaged with a 4F Judkins left diagnostic catheter, and iopamidol contrast medium was injected. No flow was seen in the left anterior descending coronary artery (LAD) beyond its proximal part, which tapered; very slow flow in the ramus intermedius and left circumflex coronary artery ceased toward the end of the test, with stagnation of contrast medium (Fig. 1A). The patient became hemodynamically unstable, with blood pressure of 45/40 mmHg, widespread ST-segment elevation, and a pulse rate of 35 beats/min. The operator recognized severe epicardial and microvascular contrast-induced spasm. Despite the profound hypotension, he injected 200 μg of intracoronary nitroglycerin and 1 mg of atropine intravenously. The patient's blood pressure rapidly returned to normal and the ST-segment elevation resolved. Repeat angiography showed restored coronary flow (Fig. 1B). The patient was transferred to the medical intensive care unit for observation and was started on oral diltiazem. He remained in stable condition overnight with no allergic reactions and no elevation of cardiac markers, and he was discharged from the hospital the next day. Fig. 1 Coronary angiography. A) No flow is seen in the left anterior descending coronary artery (LAD) beyond its proximal part; very slow flow in the ramus intermedius and left circumflex coronary artery ceases toward the end of the angiographic run, ...
What Influences Sustainment and Nonsustainment of Facilitation Activities in Implementation? Analysis of Organizational Factors in Hospitals Implementing TeamSTEPPS:

Implementation processes are often long and complex, requiring sustained facilitation efforts. Drawing on organizational and implementation literature, we examined the influence of senior management support (SMS), middle management support (MMS), facilitator team time availability (TIME) and team continuity (CONTINUITY) on sustainment of internal facilitation activities. For 2 years, we followed 10 small rural hospitals implementing TeamSTEPPS, a patient safety program, and conducted quarterly interviews with key informants. We coded, calibrated, and analyzed the data using the fuzzy-set qualitative comparative analysis. We found that five hospitals sustained facilitation activities and the combination of SMS, MMS, and CONTINUITY (i.e., presence of all three factors) was a sufficient condition for sustainment. Five other hospitals did not sustain facilitation activities and they either lacked MMS or lacked both TIME and CONTINUITY. In follow-up analyses, we found that team leadership continuity also influenced sustainment patterns. We discussed the implications for research and practice.
Metal-organic frameworks for capture and degradation of organic pollutants

Abstract The accumulation of hazardous organic pollutants in the environment severely threatens the health of human beings as well as the safety of ecosystems. Efficient removal of organic pollutants has become a hot research topic with great importance, and the search for superior methods still continues in science today. In this chapter, we introduce the recent progress that has been made for the treatment of organic pollutants using metal-organic frameworks (MOFs). First, a brief summary of the methods for MOFs synthesis, postmodification, and composite fabrication will be introduced. Considering the practical use in environmental science, the stability of MOFs in water will be specially discussed. Moreover, the multiple roles MOFs play in the removal of organic pollutants are highlighted. Owing to their unique properties such as the inorganic–organic hybrid nature, high surface area, and versatile functionality, MOFs have shown great promise in detection, capture, and degradation of organic pollutants.
Age-dependency of molecular diffusion in the human anterior lens capsule assessed using fluorescence recovery after photobleaching.

Purpose To quantify the partition coefficient and the diffusion coefficient of metal-carrier proteins in the human lens capsule as a function of age. Methods Whole lenses from human donors were incubated overnight in a solution of fluorescently labeled transferrin, albumin, or ceruloplasmin. In the central plane of the capsule thickness, fluorescence recovery after photobleaching (FRAP) experiments were conducted to measure the diffusion of the protein within the lens capsule. The anterior portion of the lens was recorded before the FRAP experiments to locate the boundaries of the anterior lens capsule and to measure the partition coefficient of the labeled proteins. The partition coefficient (P), the time to half maximum recovery of the fluorescent intensity (τ1/2), and the diffusion coefficient (D) for each protein were analyzed as a function of donor age. Results There was no statistically significant relationship between the half maximum recovery time or the diffusion coefficient and age for transferrin (molecular weight [MW]=79.5 kDa, τ1/2=17.26±4.840 s, D=0.17±0.05 μm2/s), serum albumin (MW=66.5 kDa, τ1/2=18.45±6.110 s, D=0.17±0.06 μm2/s), or ceruloplasmin (MW=120 kDa, τ1/2=36.57±5.660 s, D=0.08±0.01 μm2/s). As expected, the larger protein (ceruloplasmin) took longer to recover fluorescent intensity due to its slower movement within the lens capsule. The partition coefficient statistically significantly increased with age for each protein (Palbumin: 0.09-0.71, Pceruloplasmin: 0.42-0.95, Ptransferrin: 0.19-1.17). Conclusions The diffusion of heavy-metal protein carriers within the anterior lens capsule is not dependent on age, but it is dependent on the size of the protein. The permeability of the lens capsule to these heavy-metal protein carriers increases with age, suggesting that there will be a higher concentration of heavy metals in the older lens. This behavior may favor the formation of cataract, because heavy metals enhance protein oxidation through the Fenton reaction.
MARS: Machine learning based Adaptable and Robust Network Management for Software-defined Networks

Traditional networks were initially designed to scale fast, but in turn are harder to monitor and manage. The rise in the Internet of Things (IoT) has caused an increase in the number of mobile nodes and thus the topology changes constantly. This compels researchers to explore more efficient methods to monitor and manage the network. Software Defined Networking (SDN) have become the primary focus of the research community due to the flexibility it enables by the separation of the data and the control plane. However, the centralized nature of SDN causes a scalability and a single point of failure problems. To combat this problem, we propose an adaptable and robust network management approach using machine learning while considering the control plane architecture for software-defined networks. Our system aims to enhance the network resource utilization and increase the SDN's scalability by using multiple controllers and assigning the switches among them autonomously, based on network traffic patterns.
The Implications of Brain Tumors on Aggressive Behavior and Suicidality: A Review

Abstract The medical side effects of brain tumors have been studied rather extensively for the development of accurate diagnosis and effective treatments; however, the psychological implications of the various tumor types are vastly understudied. There has been mixed literature surrounding the impacts of tumors on personality changes. Some research, primarily case studies and few quantitative studies, have suggested that brain tumors in the frontal lobe, limbic system, and cerebellum are most associated with personality changes related to aggression. This aggression has been noted to be directed outwards towards others, as well as inward in the form of suicidal ideation, attempts, and deaths by suicide. Furthermore, research has indicated that some of the indicated methods of treatment for brain tumors are associated with side effects that further perpetuate the behavior changes, particularly in terms of aggression. Unfortunately, to date, there is a dearth of research into identifying the psychiatric profiles of different brain tumors.
SUBOPTIMIZATION IN ACCOUNTING EDUCATION AND THE SUBJECTIVE THEORY OF VALUE: SOME SUGGESTIONS FOR CHANGE

The subjective theory of value -- the theory that something is worth whatever someone is willing to pay for it -- has been around for more than 100 years. Yet the people who determine what accounting students must study ignore this basic fact when they construct accounting degree requirements. The result is suboptimization -- an accounting program that is necessarily of lower quality than would otherwise be the case. Applying the subjective theory of value to graduate accounting and tax curricula in the United States makes it clear that, in order to offer higher quality programs, it is necessary to giv e students a choice. Rather than dictating from above what courses must be taken to receive a degree, students must be free to choose for themselves what courses they, in their own subjective judgment, place the highest value on. Any curriculum that does not maximize student choice must,
Design and Implementation of Estimating Algorithm for Foreign Object Location in Wireless Charging EV Systems

Foreign object detection(FOD) is crucial in wireless power transfer architectures. The impact level of the foreign object(FO) is dependent on its location within the charging area. Therefore, location estimation of foreign objects on the transmitter and receiver pads is of great importance due firstly to the inaccessibility of the buried transmitter pad, and secondly to invisibility of the receiver pad attached underneath the car. This paper presents a theoretical formulation for location estimation of foreign object inside an inductive power transfer (IPT) system using resonant frequency and current deviation. An experimental set up of a self-tuning IPT system with a foreign object located on the primary coil as well as the ferrite bars is presented. The results show that for the same resonance frequency deviation caused by two foreign objects with different size, the one located on the primary coil surface relatively affects primary resonant current more than the one placed on ferrite bars. This difference in current can be used to characterize a current deviation profile which will enable the location of the FO to be accurately pin pointed within the IPT system.
Intellectual Property as a Determinant of Health

Public health literature has long recognized the existence of determinants of health, a set of socio-economic conditions that affect health risks and health outcomes across the world. The World Health Organization defines these determinants as “forces and systems” consisting of “factors combin[ing] together to affect the health of individuals and communities.” Frameworks relying on determinants of health have been widely adopted by countries in the global South and North alike, as well as international institutional players, several of which are direct or indirect players in transnational intellectual property (IP) policymaking. Issues raised by the implementation of IP policies, however, are seldom treated as an integral part of analyses using these frameworks, even though IP bears direct effects on the dynamics of several determinants of health, such as access to health goods and health services. This article conceptualizes post-TRIPs IP as a contributing element to the literature on the socio-economic determinants of health. IP norms and policies have long been understood as playing a role in outcomes that closely align with determinants frameworks, but interventions inspired by institutions relying on determinants frameworks routinely fail to consider the role of international IP regimes. The article explores two consequences of this dissociation: first, it argues that TRIPs-implemented IP materially affects several determinants of health, both at the social and economic levels; and second, it argues that IP should be regarded on equal footing with other canonically recognized determinants of health. While taking steps towards the development of an IP framework that can be articulated with, and incorporated by, literature on the determinants of health, the article presents three short case studies on pharmaceutical and agricultural technologies—HIV prophylactic drugs (Truvada); drugs and vaccines needed for epidemic and pandemic preparedness (Ebola vaccines and COVID-19 treatments like remdesivir); and genetically modified rice crops.
Augmenting patient safety through participation by design – An assessment of dual monitors for patients in the outpatient clinic

Abstract Background Patients and physicians engaging together in the electronic health record (EHR) during clinical visits may provide opportunities to both improve patient understanding and reduce medical errors. Objective To assess the potential impact of a patient EHR display intervention on patient quality and safety. We hypothesized that if patients had a dedicated display with an explicit invitation to follow clinicians in the EHR that this would identify several opportunities to engage patients in their care quality and safety. Material and methods Physician-patient outpatient encounters (24 patients and 8 physicians) were videotaped. Encounters took place in a hospital-based general internal medicine outpatient clinic where physicians and patients had their respective EHR monitors. Following the visits, each patient and physician was interviewed for 30 min to understand their perception of the mirrored-screen setting. Results The following 7 themes were identified (a) curiosity, (b) opportunity to ask questions, (c) error identification, (d) control over medications, (e) awareness, (f) shared understanding & decision-making, (g) data privacy. These themes collectively comprised a conceptual model for how patient engagement in electronic health record use, through a dedicated second screen or an explicitly shared screen, relates to safety and quality opportunities. Therefore, the double EHR screen provides an explicit invitation for patients to join the process to influence safety. Conclusion Desired outcomes include real-time error identification and better-shared understanding and decision-making, leading to better downstream follow-through with care plans.
Exploring the Subgraph Density-Size Trade-off via the Lovaśz Extension

Given an undirected graph, the Densest-k-Subgraph problem (DkS) seeks to find a subset of k vertices such that the sum of the edge weights in the corresponding subgraph is maximized. The problem is known to be NP-hard, and is also very difficult to approximate, in the worst-case. In this paper, we present a new convex relaxation for the problem. Our key idea is to reformulate DkS as minimizing a submodular function subject to a cardinality constraint. Exploiting the fact that submodular functions possess a convex, continuous extension (known as the Lovasz extension), we propose to minimize the Lovasz extension over the convex hull of the cardinality constraints. Although the Lovasz extension of a submodular function does not admit an analytical form in general, for DkS we show that it does. We leverage this result to develop a highly scalable algorithm based on the Alternating Direction Method of Multipliers (ADMM) for solving the relaxed problem. Coupled with a pair of fortuitously simple rounding schemes, we demonstrate that our approach outperforms existing baselines on real-world graphs and can yield high quality sub-optimal solutions which typically are a posteriori no worse than65-80%of the optimal density.
Using Portfolio Returns to Estimate the Probability of Large Jumps

Sudden jumps in the stock market have a significant impact on consumers’ wealth. A market crash, in particular, can devastate lives and destabilize the entire economy. Therefore, it would be desirable if consumers, policy makers, and financial intermediaries could better anticipate such events. Unfortunately, it is difficult to infer market crashes, in part because they occur so infrequently. This paper proposes the use of portfolio returns as an additional tool for gauging the probability of market jumps. Sophisticated investors (such as hedge funds) incorporate the probability of such jumps in their asset allocation. Thus, the returns of optimally performing portfolios include this forward-looking information in a way that market returns do not. Portfolio returns allow the econometrician to infer the probability of jumps faster and more accurately than using market returns alone. Indeed, I find that, using portfolio returns, the asymptotic variance of jump estimators can converge to zero.
Identify challenges in vibration measurements for rotating tyres using a finite element model

In the current paper, the measurements from a tyre testing on a dynamometer are replicated using a finite element analysis to identify the feasibility of obtaining mode shapes using rotating tyre data. Performing vibration analysis using computer-aided engineering (CAE) reduces the human effort of executing the complex experimental setup and performing the tests. Furthermore, it provides test engineers with an understanding of the dynamic performance of tyres. In this work, an explicit finite element analysis was performed on the rolling tyre. Using the data from the simulation, an operational modal analysis was performed to extract the modal parameters of the tyre in the rolling condition. The results are analysed with those obtained from the experimentation of the Kettering Formula SAE (FSAE) tyre.
Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties.

Sangivamycin is a nucleoside analog that is well-tolerated by humans and broadly active against phylogenetically distinct viruses, including arenaviruses, filoviruses, and orthopoxviruses. Here, we show that sangivamycin is a potent antiviral against multiple variants of replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with half-maximal inhibitory concentration (IC50) in the nanomolar range in several cell types. Sangivamycin suppressed SARS-CoV-2 replication with greater efficacy than remdesivir (another broad-spectrum nucleoside analog). When we investigated sangivamycin's potential for clinical administration, pharmacokinetic, ADME (absorption, distribution, metabolism, and excretion), and toxicity properties were found to be favorable. When tested in combination with remdesivir, efficacy was additive rather than competitive against SARS-CoV-2. The proven safety in humans, long half-life, potent antiviral activity (compared to remdesivir), and combinatorial potential suggest that sangivamycin is likely to be efficacious alone or in combination therapy to suppress viremia in patients. Sangivamycin may also have the ability to help combat drug-resistant or vaccine-escaping SARS-CoV-2 variants since it is antivirally active against several tested variants. Our results support the pursuit of sangivamycin for further preclinical and clinical development as a potential coronavirus disease 2019 (COVID-19) therapeutic.
Spatial distribution, localization, and speciation of arsenic in the hyperaccumulating fern Pteris vittata L.

Abstract This study is concerned with the distribution, localization, and speciation of arsenic (As) in the hyperaccumulating fern Pteris vittata L. Sections across an intact pinnae, stipe, and root were taken from plants grown in soil treated with 1% or 200 ppm As. Arsenic distribution and speciation in plant material were examined with micro-focused X-rays and X-ray absorption near-edge structure (XANES). In the pinnae, As was confined to the midrib and minor veins, especially those in close proximity to the blade margins. Very little As was detected in the cellular compartments of fresh root or stipe sections, whereas in cryosections of the pinnae, As was localized in epidermal cells, mesophyll cells, and xylem tissues. XANES showed that As occurred predominantly as arsenite [As(III), the most toxic form] in all tissues. Analysis of xylem sap showed that As was present as arsenate (As(V)) and reduced to arsenite (As(III)) in the fronds. P. vittata may adapt to As-rich soils by translocating As as As(V) and then compartmentalizing it as As(III) in the shoot system. Such information could be very valuable for the successful implementation of phytoremediation strategy as well as proper disposal of toxic waste generated after phytoremediating As-contaminated soils.
A teaching prototype for educating IT security engineers in emerging environments

Many enterprises today do not have an information security program or anyone on staff who can help them manage the escalating security risks. Computer science, information technology (IT) and information systems see an urgent need to train students in Internet security but have limited or untrained resources available to enhance their curricula. Perceiving that students best learn information security by doing it, the IT program at Brigham Young University elected to initiate a security emphasis in its instruction by creating security courses and an experimental security laboratory. Students collaboratively prepare lectures and labs as part of an IT security teaching model. Their enthusiasm in using the security lab as a playground follows a pedagogical approach of active learning and persistent student-led teams. Students have architected, administered and operated two lab concepts, namely, (a) an isolated Sandbox security tab, and (b) a prototype network that could serve as a simple model for a small university and which does have external Internet connectivity that offers features for extensive wired and wireless deployment. Students created the security best practices and student security team used to manage this on-going, active experimental environment that served as the test-bed for evaluating security projects that deal with network hardening, vulnerability and intrusion prevention issues. This security teaching model served, and continues to serve, as a prototype for facilitating the education and preparation of urgently needed security engineers in emerging environments worldwide.
Rapid Eye Movement Sleep Behavior Disorder

Rapid eye movement sleep behavior disorder (RBD) is a rapid eye movement (REM) parasomnia in which the normal muscle atonia of REM sleep is absent. The lack of muscle atonia may lead to motor activation and the appearance of dream-related behaviors. Dream content during RBD is vivid and often has aggressive themes, such as being threatened, chased, or attacked. During an episode, both the patient with RBD and their bed partner are at risk for serious injuries (e.g., bruises, lacerations, and bone fractures). Diagnosis of RBD currently requires the presence of established clinical criteria, but polysomnography is recommended to confirm the diagnosis and differentiate it from other sleep disorders, including sleep apnea. Controlled trials are lacking; yet, clonazepam has been effective in treating symptoms in up to 90% of patients with RBD. Other treatment approaches are dopaminergic agonists, antiepileptic agents, α-adrenergic agonists, acetylcholinesterase inhibitors, and melatonin. RBD is frequently associated with synucleinopathies, such as multiple system atrophy, dementia with Lewy bodies, and Parkinson’s disease. In these patients, RBD symptoms may precede motor symptoms by months to years. Abnormalities in central dopaminergic mechanisms have been postulated.
William Morris & Edward Burne-Jones: Interlacings by Caroline Arscott

This book is a radical modification of the monographic project. To give two artists equal significance; to consider their relationship while paying full attention to the specific qualities of each ...
NUMERICAL INVESTIGATION OF CARRIER TRANSPORT IN DOUBLE HETEROSTRUCTURE: AlGaAs/GaAs PNPN Bistable Device

Numerical device simulation is developed to study the steady‐state and transient current‐voltage characteristics of double heterostructure AlGaAs/GaAs PNPN electro‐photonic device when its performance is influenced by the presence of interface and bulk recombination mechanism. The simulation results show that the holding current and voltage and the breakover point are strongly affected by varying the minority carrier lifetime at outer heterojunctions. Numerical results also indicate that shortening the minority carrier lifetime in the inner PN homojunction region only increases the OFF‐state current. These results are in agreement with experimental data on AlGaAs/GaAs PNPN devices. The numerical modelling approach taken in this study is shown to be essential in the design and optimization of PNPN switch.
Irritable Bowel Syndrome

Irritable Bowel Syndrome (IBS) is a chronic and fluctuating functional gastrointestinal disorder characterized by abdominal pain and discomfort and accompanying altered bowel habit. The prevalence of IBS is estimated at about 10–13% in the United States. The etiology of IBS is poorly understood, but the relations noted between stress, heightened sensitivity to stimuli and gastrointestinal symptoms has been labeled by gastroenterologists and psychologists alike as the “brain-gut axis,” and has increasingly allowed for the acceptance of psychological interventions for IBS. This chapter attempts to offer the clinician some general, evidence-based guidelines for the assessment and treatment of irritable bowel syndrome. Special emphasis is given to the use of hypnotherapy and cognitive-behavioral therapy in treating these disorders.
Large Hadron collider tests of the little Higgs model.

The little Higgs model provides an alternative to traditional candidates for new physics at the TeV scale. The new heavy gauge bosons predicted by this model should be observable at the Large Hadron Collider (LHC). We discuss how the LHC experiments could test the little Higgs model by studying the production and decay of these particles.
How Calcium Enhances Plant Salt Tolerance

For their normal function, plants take up potassium salts and exclude sodium, a process that becomes more difficult in arid, salty soils. In his commentary, Epstein describes the physiological experiments that established that this selective accumulation depends on the presence of another salt, calcium, and how results in this issue by Liu et al. reveal the molecular basis of the calcium dependence.
The Application of Ecological Principles and Fermentable Fibers to Manage the Gastrointestinal Tract Ecosystem

Because diet can influence the structure and functions of the gastrointestinal tract, there are opportunities for using diet as a management tool to affect the resident microbiota. Fermentable fibers increase the densities of beneficial bacteria and stimulate growth and functions of the healthy intestine. Recent findings show that after acute diarrhea, the use of an oral electrolyte solution with the fermentable fiber oligofructose accelerates recovery of beneficial bacteria, reduces the relative abundance of detrimental bacteria, stimulates mucosal growth and enhances digestive and immune functions. This review will focus on how the principles of stream ecology can be applied to better understand the distribution of bacteria along the length of the gastrointestinal tract, the effect of diarrhea on the gastrointestinal ecosystem and how fermentable fibers can be used as a management tool to promote gastrointestinal health in normal states and during recovery from diarrhea.
CT scanning and computerized reconstructions of the inner ear of multituberculate mammals

ABSTRACT The inner-ear structure of four multituberculate petrosals from the Late Cretaceous and Early Paleocene of North America was examined with computerized tomography (CT). Transverse CT scan images of these petrosals were digitized to produce a three-dimensional reconstruction of the acousto-vestibular spaces of multituberculates. Our investigation shows that the acousto-vestibular spaces of multituberculates are characterized by a straight cochlear canal and an extraordinarily enlarged vestibular cavity. Comparison of multituberculate inner-ear structures with those in other major mammalian clades suggests that the cochlea of multituberculates, which is similar to that of Morganucodon, is more derived than the cochlea of non-mammalian therapsids but more primitive than the coiled cochlea of therian and monotreme mammals. The extraordinary inflation of the vestibule of multituberculates is a uniquely derived character of most Cretaceous and Tertiary multituberculates, and it may be the synapomorphy ...