cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanistic characterization of the 5'-triphosphate-dependent activation of PKR: lack of 5'-end nucleobase specificity, evidence for a distinct triphosphate binding site, and a critical role for the dsRBD.

The protein kinase PKR is activated by RNA to phosphorylate eIF-2α, inhibiting translation initiation. Long dsRNA activates PKR via interactions with the dsRNA-binding domain (dsRBD). Weakly structured RNA also activates PKR and does so in a 5′-triphosphate (ppp)–dependent fashion, however relatively little is known about this pathway. We used a mutant T7 RNA polymerase to incorporate all four triphosphate-containing nucleotides into the first position of a largely single-stranded RNA and found absence of selectivity, in that all four transcripts activate PKR. Recognition of 5′-triphosphate, but not the nucleobase at the 5′-most position, makes this RNA-mediated innate immune response sensitive to a broad array of viruses. PKR was neither activated in the presence of γ-GTP nor recognized NTPs other than ATP in activation competition and ITC binding assays. This indicates that the binding site for ATP is selective, which contrasts with the site for the 5′ end of ppp-ssRNA. Activation experiments reveal that short dsRNAs compete with 5′-triphosphate RNAs and heparin for activation, and likewise gel-shift assays reveal that activating 5′-triphosphate RNAs and heparin compete with short dsRNAs for binding to PKR's dsRBD. The dsRBD thus plays a critical role in the activation of PKR by ppp-ssRNA and even heparin. At the same time, cross-linking experiments indicate that ppp-ssRNA interacts with PKR outside of the dsRBD as well. Overall, 5′-triphosphate-containing, weakly structured RNAs activate PKR via interactions with both the dsRBD and a distinct triphosphate binding site that lacks 5′-nucleobase specificity, allowing the innate immune response to provide broad-spectrum protection from pathogens.
Assessment of deterioration in epoxy/mica machine insulation

Long-time accelerated aging tests in a laboratory environment have been conducted on generator stator insulation to identify meaningful diagnostic measures for the assessment of degradation and identification of aging mechanisms. A plurality of techniques are investigated and diagnostic parameter, the dynamic stagnation voltage, which appears to be correlated with delimination in the epoxy-mica structure, is proposed. The results provide a basis for an online interpretation method for insulation condition. >
Induction of Resistance in Staphylococcus aureus and Klebsiella pneumoniae by Exposure to Cephalothin and Cefoxitin

Six strains each of Staphylococcus aureus and Klebsiella pneumoniae were exposed to subinhibitory, but serially incremental, concentrations of cephalothin and cefoxitin in a totally defined liquid culture medium. After exposure to cephalothin, the level of resistance to both drugs increased; the gain was greater against cephalothin and among the strains of K. pneumoniae. After exposure to cefoxitin, resistance to both drugs developed; this resistance was greater against cefoxitin and among the strains of K. pneumoniae. Acquired resistance was not lost after serial subculture in drug-free medium. Qualitative tests revealed no cephalosporinase activity in the resistant straphylococci and in four of the strains of K. pneumoniae. Two strains of K. pneumoniae, which had been isolated from a patient before and after failure of treatment with cephalothin, respectively, had no demonstrable cephalosporinase activity as isolated but developed activity after exposure to cephalothin in vitro. Bacteria may resist the action of 3-lactam antimicrobics either through enzyme-mediated hydrolysis of the 3-lactam ring ((3-lactamases; i.e., penicillinases, cephalosporinases) or through as yet undefined, undestructive mechanisms (indifference; i.e., intrinsic, native resistance). The availability of a 13-lactamase-resistant cephalosporanic acid derivative, cefoxitin, made it feasible to examine acquired resistance in an effort to learn whether (1) the gained resistance resulting from exposure to cephalothin extended also to cefoxitin; (2) the gained resistance resulting from exposure to cefoxitin extended also to cephalothin; and (3) the gained resistance was destructive ((3-lactamase-mediated) or undestructive (intrinsic) in nature. Six isolates each of Staphylococcus aureus and Klebsiella pneumoniae were studied. Susceptibility to cephalothin and cefoxitin was measured before and after multiple exposure in vitro to incremental, but subinhibitory, concentrations of these drugs. Overall, resistance to both drugs resulted from exposure to either antimicrobic. The resistance was intrinsic in nature with the
Information processing in the mental workspace is fundamentally distributed

The brain is a complex, interconnected information processing network. In humans, this network supports a mental workspace that enables high-level abilities such as scientific and artistic creativity. Do the component processes underlying these abilities occur in discrete anatomical modules, or are they distributed widely throughout the brain? How does the flow of information within this network support specific cognitive functions? Current approaches have limited ability to answer such questions. Here, we report novel multivariate methods to analyze information flow within the mental workspace during visual imagery manipulation. We find that mental imagery entails distributed information flow and shared representations throughout the cortex. These findings challenge existing, anatomically modular models of the neural basis of higher-order mental functions, suggesting that such processes may occur at least in part at a fundamentally distributed level of organization. The novel methods we report may be useful in studying other similarly complex, high-level informational processes.
Minimal Surfaces in CR Geometry

Abstract The k-Hessian is the k-trace, or the kth elementary symmetric polynomial of eigenvalues of the Hessian matrix. When k ≥ 2, the k-Hessian equation is a fully nonlinear partial differential equations. It is elliptic when restricted to k-admissible functions. In this paper we establish the existence and regularity of k-admissible solutions to the Dirichlet problem of the k-Hessian equation. By a gradient flow method we prove a Sobolev type inequality for k-admissible functions vanishing on the boundary, and study the corresponding variational problems. We also extend the definition of k-admissibility to non-smooth functions and prove a weak continuity of the k-Hessian operator. The weak continuity enables us to deduce a Wolff potential estimate. As an application we prove the Holder continuity of weak solutions to the k-Hessian equation. These results are mainly from the papers [CNS2, W2, CW1, TW2, Ld] in the references of the paper.
Rapid quantitative T2 mapping of the prostate using three-dimensional dual echo steady state MRI at 3T

Purpose To develop and evaluate a rapid three-dimensional (3D) quantitative T2 mapping method for prostate cancer imaging using dual echo steady state (DESS) MRI at 3T. Methods In simulations, DESS-T2 mapping in the presence of T1 and B1+ variations was evaluated. In a phantom and in healthy volunteers (n = 4), 3D DESS-T2 mapping was compared with a two-dimensional turbo spin echo (TSE) approach. In volunteers and a pilot patient study (n = 29), quantitative T2 in normal prostate anatomical zones and in suspected cancerous lesions was evaluated. Results The simulated bias for DESS-T2 was < 2% (5%) for typically observed T1 ( B1+) variations. In phantoms and in vivo, high correlation of DESS-T2 and TSE-T2 (r2 = 0.98 and 0.88, P < 0.001) was found. DESS-T2 in the normal peripheral zone and transition zone was 115 ± 26 ms and 64 ± 7 ms, respectively, in healthy volunteers and 129 ± 39 ms and 83 ± 12 ms, respectively, in patients. In suspected cancerous lesions, DESS-T2 was 72 ± 14 ms, which was significantly decreased from the normal peripheral zone (P < 0.001) but not from the transition zone. Conclusion Rapid 3D T2 mapping in the entire prostate can be performed in 1 min using DESS MRI. Magn Reson Med 76:1720–1729, 2016. © 2016 International Society for Magnetic Resonance in Medicine
Electromagnetic field limits set by the V-Curve.

When emitters of electromagnetic energy are operated in the vicinity of sensitive components, the electric field at the component location must be kept below a certain level in order to prevent the component from being damaged, or in the case of electro-explosive devices, initiating. The V-Curve is a convenient way to set the electric field limit because it requires minimal information about the problem configuration. In this report we will discuss the basis for the V-Curve. We also consider deviations from the original V-Curve resulting from inductive versus capacitive antennas, increases in directivity gain for long antennas, decreases in input impedance when operating in a bounded region, and mismatches dictated by transmission line losses. In addition, we consider mitigating effects resulting from limited antenna sizes.
Late-Onset Glioma with Neurofibromatosis Type 1

The frequency of symptomatic nonoptic pathway brain tumors in adolescents and adults known to have neurofibromatosis type 1 (NF1) was determined from the National Neurofibromatosis Foundation International Database (NNFFID) in a study at Washington University School of Medicine, St Louis, MO.
Hybrid Pulmonary Artery Stenting at the Bidirectional Glenn or Fontan Operation in Patients With Single Ventricle Congenital Heart Disease

Background:Stenosis of the retroaortic pulmonary artery is common in patients with single ventricle heart disease. Intraoperative hybrid stenting at the bidirectional Glenn or Fontan operation can treat this lesion and avoid a complex surgical arterioplasty.Methods:Patients who underwent intraoperative stent implantation to the retroaortic pulmonary artery during the bidirectional Glenn or Fontan operation at our center between January 2005 and July 2014 were retrospectively identified.Results:Thirteen patients were included with a median weight of 8 kg (5.6-14.4 kg) and age of 6 months (4 months-3.8 years). All had undergone Norwood operation, and eight (62%) had hypoplastic left heart syndrome. Eight (62%) underwent stent placement during bidirectional Glenn and five (38%) during Fontan operation. Ten patients had one stent placed, and three had two overlapping stents. The median diameter of the stenotic vessel was 3 mm (2.0-5.5 mm) and diameter of the balloon used for stent expansion was 7 mm (5-10 mm)...
Physics: Material to meaning

Robert P. Crease assesses Sean Carroll's attempt to construct morality out of quantum field theory.
Stabilizing selection in Drosophila melanogaster

Stabilizing selection operates on egg length in Drosophila melanogaster. The percentage of eggs hatching decreases with departure from the population mean size; this effect cannot be explained by the model of neutral variation in a quantitative character. The finding of stabilizing selection agrees with expectations for a character inherited primarily through additive effects.
Twenty-four-hour progesterone and luteinizing hormone profiles in the midluteal phase of the infertile patient: correlation with other indicators of luteal phase insufficiency

Abstract The authors have further analyzed women diagnosed as having luteal phase insufficiency in hope of determining the value of specific screening tests as well as determining the degree of heterogeneity of pathophysiologic mechanisms involved in the disorder. Twelve women with the disorder were identified, 6 with two consecutive midluteal serum progesterone (P) levels
Macrolides, inflammation and the lung microbiome: untangling the web of causality

In the past decade, our understanding of the microbiology of the respiratory tract has been revolutionised by the introduction of culture-independent techniques of microbial identification.1 The lungs, once considered sterile in the absence of infection, have been consistently shown to contain diverse microbial communities, even in health.2 One consistent observation in the field is that in virtually every comparison to date, lung microbiota of healthy subjects differ from the lung microbiota of patients with acute and chronic lung disease. Yet, the field faces a crucial and challenging question: Are bacterial communities in the lung altered because of respiratory disease, or are our patients' lungs diseased because of their altered bacterial communities? Sorting out cause and effect here is an intimidating task: the microbiome and the host response are so tightly entwined that trying to isolate the effects of each is difficult, both practically and conceptually. Most studies to date in the nascent lung microbiome field have been retrospective and descriptive, replete with provocative correlations, but silent on the direction of causality. Few longitudinal studies have provided the means of determining temporally whether dysbiosis arises before lung disease or vice versa. Given the long chronicity and unpredictability of many lung diseases, prospective cohort studies would need to be impractically large and lengthy to determine temporal precedence. Though animal models hold promise to help unravel mechanisms of pathogenesis3 ,4 characterising the lung microbiota of small animals is technically challenging, and the relevance of animal-associated microbiota to human respiratory health is far from obvious. Some innovative recent studies have attempted ‘lung microbiome transplants’ between diseased and non-diseased animals4 ,5 though it has not been established how much of the effect of this exposure is attributable to transferred microbiota and …
Virtual infrastructure mapping in software-defined elastic optical networks

Software-defined networking (SDN) enables efficient and scalable network virtualization, which allows infrastructure resources such as computing and networking resources to be abstracted and outsourced as a service. The SDN technologies can be extended to the optical transport networks to achieve an intelligent and flexible resource management, thus achieving high-capacity, low-cost, and long-reach optical transport networks. In this paper, we introduce an architecture for software-defined elastic optical networks and study the virtual infrastructure (VI) mapping problem with the objective of minimizing the blocking probability. We propose a set of efficient heuristic algorithms, among which the Network followed by Compute Load Balancing (NCLB) algorithm is a novel attempt to solve the VI mapping problem by provisioning the networking resource first followed by allocating the computing resource. Furthermore, we propose a modified version of NCLB, called Network Depth-based NCLB (ND-NCLB), which confines the VI mapping assignment in a small-range sub-network to further optimize the physical network resource consumption. Through comprehensive simulations in various scenarios, we demonstrate that the proposed ND-NCLB algorithm achieves the best performance in terms of blocking probability compared to the other algorithms in this work.
Smoothened (SMO), a G-Protein-Coupled Receptor (GPCR) Activated by Hedgehog Ligands, Modulates the Activity Levels of PI3K/AKT and NF-Kβ in Diffuse Large B-Cell Lymphoma,

Abstract Abstract 3483 Activated Hedgehog (HH) signaling was identified in our laboratory to contribute to cell survival, proliferation and chemotolerance of diffuse large B-cell lymphoma (DLBCL) (Leukemia 2010;24:1025 & Oncogene 2011, in press). The HH receptor complex is integrated by two main proteins, smoothened (SMO) and patched-1 (PTCH1). SMO is a seven-transmembrane G protein-coupled receptor that transduces HH signal to the cytoplasm and has glioma-associated oncogene homologue (GLI) proteins as major signaling transcription effectors. PTCH1 is a 12 transmembrane protein that inhibits SMO in the absence of HH ligands. Here, we investigated potential cross talk between SMO with the activation status of PI3K/AKT and NF-kB, two relevant oncogenic pathways in DLBCL. Using a small interfering (si)RNA approach and DLBCL cell lines of germinal center (GC) and activated B-cell (ABC) type we found that the expression levels of SMO modulate the activation status of AKT and canonical NF-KB pathways in DLBCL cells of GC type and mainly AKT in those of ABC type. In DLBCL cells of GC cell type, silencing SMO resulted in decrease of the phosphorylation levels of ser473p-AKT and ser536p-P65 and silencing PTCH1 resulted in increase of the phosphorylation levels of both proteins. The same silencing experimental approach in DLBCL cells of ABC type resulted in similar modulation in the activation status of the AKT but not, or to less extent, in the activation of NF-kB pathway. The modulation of the activation status of the NF-KB pathway was also confirmed using protein nuclear extracts and DNA binding ELISA assays. In cells of both DLBCL subtypes, silencing of the SMO transcriptional effector GLI1 showed no changes in the activation status of both pathways. The modulation in the activation status of AKT and NF-KB was also detected using SMO inhibitors, cyclopamine-KAAD and HhAntag (Genentech Inc) or activators, purmorphamine and recombinant HH protein. Combinatorial treatments with increasing concentrations of SMO inhibitors (cyclopamine and HhAntag [1.6, 3.2 and 4.8 μM]) with minimal lethal doses of Ly294002 (PI3K inhibitor) or BAY-11 (NF-KB inhibitor) were also performed. Using cell viability, and apoptosis (Annexin-V) assays, we found that combined treatments of PI3K or NF-KB inhibitors with a SMO inhibitor resulted in an additive/synergistic decrease of cell viability and increase of apoptosis in comparison to the treatments with SMO inhibitors alone. Taken together, our data shed novel light on the contribution of SMO on the activation of PI3K/AKT and NF-kB pathways in DLBCL. Our data also provide a rationale to use SMO inhibitors in combination with inhibitors of other oncogenic pathways such as PI3K/AKT and/or NF-KB for the treatment of patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.
Human Induced Pluripotent Stem Cell-Derived Endothelial Cells for Three-Dimensional Microphysiological Systems

Microphysiological systems (MPS), or "organ-on-a-chip" platforms, aim to recapitulate in vivo physiology using small-scale in vitro tissue models of human physiology. While significant efforts have been made to create vascularized tissues, most reports utilize primary endothelial cells that hinder reproducibility. In this study, we report the use of human induced pluripotent stem cell-derived endothelial cells (iPS-ECs) in developing three-dimensional (3D) microvascular networks. We established a CDH5-mCherry reporter iPS cell line, which expresses the vascular endothelial (VE)-cadherin fused to mCherry. The iPS-ECs demonstrate physiological functions characteristic of primary endothelial cells in a series of in vitro assays, including permeability, response to shear stress, and the expression of endothelial markers (CD31, von Willibrand factor, and endothelial nitric oxide synthase). The iPS-ECs form stable, perfusable microvessels over the course of 14 days when cultured within 3D microfluidic devices. We also demonstrate that inhibition of TGF-β signaling improves vascular network formation by the iPS-ECs. We conclude that iPS-ECs can be a source of endothelial cells in MPS providing opportunities for human disease modeling and improving the reproducibility of 3D vascular networks.
State of urgency: Surveillance, power, and algorithms in France’s state of emergency:

The recent terrorist attacks and ongoing state of emergency in France have brought questions of police surveillance into the public spotlight, making it increasingly important to understand how pol...
Dietary fat intake reduction for patients with resected breast cancer.

In early 1994, a clinical trial has been initiated to definitively address, for the first time, whether a dietary fat intake reduction program can influence the clinical course of patients with breast cancer. This study, the Women’s Intervention Nutrition Study (WINS) is based on a hypothesis which is directly supported by laboratory, animal and epidemiological observations.1-3 In addition, the feasibility of prospectively testing this hypothesis has been established by a series of pilot clinical studies. 2,4-8 These results represent a culmination of over a decade of research activity and are outlined in more detail below.
Use of Protective Behavioral Strategies among Young Adult Veteran Marijuana Users

Young adult veterans are at risk for problematic marijuana use and associated consequences, which is partially due to their high rates of Posttraumatic Stress Disorder (PTSD), depression, and problematic substance use. Veterans tend to endorse more severe and chronic mental health symptoms compared to their civilian counterparts and they identify marijuana use as a method to cope with their symptoms. Given the prevalence of marijuana use among veterans in the community and in clinical settings, it is important to explore the factors that may help minimize harm associated with use for those that choose to use the drug. The present study sought to examine the impact of protective behavioral strategies on the relationship between mental health symptoms and marijuana use and consequences in a sample of 180 young adult veteran marijuana users. Participants were recruited via social media advertisements and completed measures of marijuana use and consequences, protective behavioral strategies, and PTSD and depression symptoms. Findings indicated that more frequent use of protective behavioral strategies was associated with less marijuana use and consequences. Participants who screened positive for PTSD or depression reported more marijuana consequences than did those not positive on these screeners. Regression analyses revealed protective strategies moderated the relationship between PTSD and marijuana consequences such that young veterans who endorsed more PTSD symptoms and infrequent use of protective strategies reported the most marijuana consequences. No moderating effects were found for the relationship between depression and marijuana consequences. Findings have clinical implications for working with young veterans.
Flame Propagation in Microchannels

Combustion at small scales (micro- and mesoscales) is gaining increasing attention these days due to the wide spectrum of potential applications in sensors, actuators, portable electronic devices, rovers, robots, unmanned air vehicles, thrusters, industrial heating devices, and, furthermore, heat and mechanical backup power sources for air-conditioning equipment in hybrid vehicles and direct ignition (DI) engines as well [1–3]. Combustion of hydrocarbon fuels is more attractive to manufacturers of miniature power devices because the energy density of hydrocarbons is several times higher than modern batteries [4]. Microscale combustion physics is quite different from those at larger length scales. For example, flame propagation through narrow channels has unique characteristics, e.g., the increasing effects of flame–wall interaction and molecular diffusion [5–10]. In small-scale combustion systems, the surface-to-volume (S/V) ratio is large, which leads to more heat loss and thus causes flame extinction more easily.
Quantum spin models for measurement-based quantum computation

Measurement-based quantum computation is different from other approaches for quantum computation, in that everything needs to be done is only local measurement on a certain entangled state. It thus uses entanglement as the resource that drives computation. We give a pedagogical treatment on the basics, and then review some selected developments beyond graph states, including Affleck–Kennedy–Lieb–Tasaki states and more recent 2D symmetry-protected topological states. We point out some open questions along the way.
Cancer Metabolism: Current Understanding and Therapies

Dysregulation of cancer cell metabolism contributes to abnormal cell growth, the biological end point of cancer. We review here numerous affected oncogenes and metabolic pathways common in cancer and how they contribute to cancer pathogenesis and malignancy. This review also discusses various pharmacological manipulations that take advantage of these metabolic abnormalities and the current targeted therapies that have arisen from this research.
Late Andean Hunting-Collecting

relative time period: Follows the Early Andean Hunting-Collecting and precedes the Early Highland Andean Archaic.
Magnetic and Gravity Anomalies in the Central Red Sea

Marine magnetic and gravity profile results over the hot brine area (21°30′N, 38°E) and axial trough of the Red Sea between 25°N and 18°N latitudes confirm previous hypotheses that dense, strongly magnetic rocks underlie these areas. The gravity and magnetic anomalies in the immediate vicinity of the hot brine area appear to be part of broad, regional anomaly trends subparallel to the axial trough. It is unlikely that the heavy metal deposits of the hot brine area contribute significantly to the observed anomalies. Model studies show the configuration of bodies which could account for the axial trough anomalies to be compatible with a rifting origin associated with seafloor spreading. There appear to be at least two distinct zones of active seafloor spreading in the axial trough. One region is located beneath the hot brine area; its spreading axis trends about N70°E with an apparent rate of 1.5cm/yr. The other zone, extending between 20°N and 16°N, has its spreading axis trending about N35°E near 18°N, 40°E with an apparent rate of 1.0cm/yr. Assuming a nearly N-S direction of separation for Africa and Arabia, the true spreading rates are 1.6 and 1.7cm/yr, respectively. The location of the hot brine area over the northern seafloor spreading center (near 21°30′N) and the known volcanism associated with seafloor spreading zones on other mid-ocean ridges strongly suggest the heavy metal deposits and hot brine waters result from submarine volcanic emanations.
Contaminant/Natural Background Values: Timing and Processes

Natural geochemical background concentrations have been taken in the past as average crustal contents (Table 5–1). This is not compatible with environmental geochemistry research on specific pollution problems because of the great variation in composition of the rock types comprising the crustal surface (Table 2–1). This leads to variations in soil and other overburden chemistry. Chemical variations among flora and fauna likely reflect their growing and feeding in an area of varying geology. Added to this are the chemical changes rock materials undergo during weathering and from diagenesis. Natural background varies with other factors such as the sample used (Table 6–1), the size fraction or organism part analysed, and the analytical methodology employed.
Business Aspects of Telemental Health in Private Practice

Technological advancements and declining costs have led many traditional mental health practices to consider the use of telemedicine as a means of increasing their patients’ access to care and a way to change their professional and personal lifestyle balance. Mental health providers are now looking for specific answers to questions of licensure, risks, malpractice coverage, and other legal and regulatory issues regarding telemental health practice. The goal of this chapter is to provide a directed review of the literature and to share professional experiences relevant to meeting the unique challenges to establishing a successful telemental health private practice. This chapter walks readers through the decision-making process regarding whether to start an independent telemental health practice or to join an established group telemental health practice. This is followed by a discussion of the different models of telemental health care that range from consultation to direct ongoing treatment. Specific practical considerations such as licensure, liability coverage, staffing, billing, and sharing of records are addressed. Additional sections address decisions regarding the choice of technology and obtaining adequate support. Practical suggestions for growing a telemental health business and joining a community of telemental health providers are discussed. Ultimately, the transition to a telemental health practice is based more on flexibility and adaptation rather than a completely novel style of practice. This transition can be aided by cultivating an understanding of how the relative risks and benefits of the many practice options available will impact a given provider.
Sport psychology in a virtual world: Considerations for practitioners working in eSports

Recent technological advances have steadily led to the increased popularity of videogames. With computers more readily accessible, videogames have become more popular than ever (Murphy, 2009). As t...
Computing with Matrix and Basic Algebras

This is a survey of my lecture delivered at the Southern Regional Algebra Conference in March 2017. It is meant to demonstrate some of the methods and technology that can be used to investigate examples in the theory of representations of groups and algebras. The concentration is on using computational methods to determine the structure of a matrix algebra as in the theorems of Wedderburn and investigating homological properties of the algebra by way of its basic algebra. For every split finite-dimensional associative algebra, there is a basic algebra, one whose simple modules have dimension one, that has the same representation theory. In the computational setting, it is usually much more practical to first find the basic algebra when studying representation theory.
Mapping the energy performance gap of dwelling stock at high-resolution scale: Implications for thermal comfort in Portuguese households

Abstract An aging building stock and low-efficiency heating, ventilation and air conditioning (HVAC) systems may be preventing the adequate energy performance (EP) of Portuguese dwellings. This study aims to estimate and analyze the EP gap of the occupied main residence Portuguese residential dwelling stock, for thermal comfort attainment, at high geographical resolution scale, i.e. for every civil parish. A building typology approach was applied to estimate the heating and cooling (H&C) theoretical final energy consumption (TFEC) for thermal comfort. An energy consumption statistics-based approach was used to estimate the H&C real final energy consumption (RFEC). The EP gap is the percentual difference between the TFEC and RFEC. Three scenarios were tested, looking deeper into southern European space H&C patterns, considering varied conditioned areas and occupancy schedules. This study provides a methodological framework for zooming in the assessment of the dwelling stock EP for a whole country, allowing for a comparative analysis between regions, as the different regional EP gap drivers are identified. For nominal conditions, every civil parish has an EP gap higher than 60%, for both H&C, related to poor energy efficiency of the building stock and low H&C energy consumptions. The scenarios demonstrated a bridging of several civil parishes’ EP gap, possibly resulting from temporal space climatization patterns. High remaining EP gaps suggest the civil parishes in the north and center inland regions are the most vulnerable in the winter and summer seasons, potentially due to significant energy poverty levels.
CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South-East and East Asian populations: A systematic review.

What is known and objective Genetic polymorphism is one of the most important factors responsible for interindividual and interethnic variability in drug response. Studies in major populations, ie, Caucasians, Asians, and Africans, have provided evidence of differences in the genotype frequencies of major drug-metabolizing enzyme cytochrome P450 (CYP). This study aimed to review systematically, all relevant articles related to the genetic polymorphisms in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in South-East and East Asian (SEEA) populations. Methods Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database. Results and discussions A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%-99.1%), *1/*3 (2.3%-20.1%) and *3/*3 (0%-2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%-88.07%), *1/*2 (21.5%-86.46%), *1/*3 (0.8%-15.8%), *2/*2 (3.4%-14.5%), *2/*3 (0%-7.3%) and *3/*3 (0%-10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%-69.6%), *1/*1 (0%-61.21%) and *1/*10 (0%-62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%-71.4%), *1/*3 (16.0%-57.1%) and *1/*1 (0%-82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer). What is new and conclusion Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South-East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South-East Asian countries which will assist in establishing the databases for SEEA populations.
Emergence of B-immunoblastic sarcoma in patients with multiple myeloma: a clinicopathologic study of 10 cases

Immunologic and histologic studies were performed in 10 cases of myeloma that showed progression to a more aggressive proliferation, designated as immunoblastic sarcoma of B-cell type (B-IBS). Several patterns of clinical presentation were observed: eight patients showed typical multiple myeloma, four developed B-IBS within the bone marrow, and four developed B-IBS in multiple extramedullary sites; the remaining two patients had relatively localized myeloma, but also showed development of extramedullary B-IBS. The implications of these findings are discussed with regard to their prognostic import and their relationship to current concepts of plasma cell development.
The role of nucleic acid sensors and type I IFNs in patient populations and animal models of autoinflammation

A spectrum of human autoinflammatory conditions result from defects in cytosolic nucleic acid clearance or overexpression of the nucleic acid sensor STING. These patients often develop severely debilitating lesions and invariably show robust IFN signatures that have been attributed to the cGAS/STING signaling cascade and type I IFN. However, murine models that recapitulate major features of these syndromes have now shown that autoinflammation is more likely to depend on type II IFN/IFNgamma or type III IFN/IFNlambda, and further revealed a critical role for Th1 cells in tissue damage and the persistence of inflammation. These studies provide important insights about the types of IFNs, and the interplay of the innate and adaptive immune systems mediated by these IFNs, that can initiate and maintain the corresponding human diseases. They further point to type II/III IFNs and effector T cells as targets for more effective therapeutic strategies in the treatment of these patient populations.
LIV-4: A novel model for predicting transplant-free survival in critically ill cirrhotics.

Background Critically ill patients with cirrhosis, particularly those with acute decompensation, have higher mortality rates in the intensive care unit (ICU) than patients without chronic liver disease. Prognostication of short-term mortality is important in order to identify patients at highest risk of death. None of the currently available prognostic models have been widely accepted for use in cirrhotic patients in the ICU, perhaps due to complexity of calculation, or lack of universal variables readily available for these patients. We believe a survival model meeting these requirements can be developed, to guide therapeutic decision-making and contribute to cost-effective healthcare resource utilization. Aim To identify markers that best identify likelihood of survival and to determine the performance of existing survival models. Methods Consecutive cirrhotic patients admitted to a United States quaternary care center ICU between 2008-2014 were included and comprised the training cohort. Demographic data and clinical laboratory test collected on admission to ICU were analyzed. Area under the curve receiver operator characteristics (AUROC) analysis was performed to assess the value of various scores in predicting in-hospital mortality. A new predictive model, the LIV-4 score, was developed using logistic regression analysis and validated in a cohort of patients admitted to the same institution between 2015-2017. Results Of 436 patients, 119 (27.3%) died in the hospital. In multivariate analysis, a combination of the natural logarithm of the bilirubin, prothrombin time, white blood cell count, and mean arterial pressure was found to most accurately predict in-hospital mortality. Derived from the regression coefficients of the independent variables, a novel model to predict inpatient mortality was developed (the LIV-4 score) and performed with an AUROC of 0.86, compared to the Model for End-Stage Liver Disease, Chronic Liver Failure-Sequential Organ Failure Assessment, and Royal Free Hospital Score, which performed with AUROCs of 0.81, 0.80, and 0.77, respectively. Patients in the internal validation cohort were substantially sicker, as evidenced by higher Model for End-Stage Liver Disease, Model for End-Stage Liver Disease-Sodium, Acute Physiology and Chronic Health Evaluation III, SOFA and LIV-4 scores. Despite these differences, the LIV-4 score remained significantly higher in subjects who expired during the hospital stay and exhibited good prognostic values in the validation cohort with an AUROC of 0.80. Conclusion LIV-4, a validated model for predicting mortality in cirrhotic patients on admission to the ICU, performs better than alternative liver and ICU-specific survival scores.
Viscoelastic Characterization in Muscle using Group Speed Analysis and Volumetric Shear Wave Elasticity Imaging

Shear wave elasticity imaging (SWEI) typically assumes a homogeneous, isotropic, elastic material to relate shear wave speed (SWS) to stiffness; however muscle is anisotropic and viscoelastic (VE). To characterize this complex tissue, we combine 3D SWEI (accumulated with an axially rotating transducer performing 2D SWEI acquisitions) with a novel variant of our previously published robust group SWS dispersion analysis method. We evaluated this system in isotropic elastic and VE phantoms, and in human muscle in vivo. We determined the group SWS of the particle velocity maxima (peak SWS) and minima (trough SWS) at each transducer rotation angle, fit an ellipse to both the peak and trough SWS, and determined the major and minor ellipse axes. A look up table was generated to relate the peak and trough SWS at the principal axes to VE parameters assuming a linear attenuation model characterized by the phase velocity (c) and dispersion slope (c') at a reference frequency of 200 Hz. The results from the isotropic phantoms are isotropic, demonstrate dispersion in the VE phantom, and agree with previous measurements. Our preliminary in vivo data indicate slower speeds across muscle fibers than along the fibers and minor dispersion in both directions. The 3D SWEI method allows for repeatable SWS measurements across multiple in vivo acquisitions.
Antimicrobial effects in oral microenvironments by a novel herbal toothpaste.

Abstract Objective This clinical study compared the antibacterial effects after brushing with a novel herbal toothpaste incorporating zinc [test] to a control fluoride toothpaste on anaerobic organisms, gram-negative bacteria and malodor bacteria of dental plaque, tongue scrapings and cheek surfaces. Methods This double-blind, two-cell study enrolled 44 adults [age range 19–63 years]. Subjects completed a 1-week washout and provided baseline oral samples i.e. dental plaque, tongue and cheek scrapings for microbiological analysis. Diluted samples for microbiological analyses were plated on agar to enumerate anaerobic organisms, gram-negative bacteria and malodor bacteria representing functional groups of organisms. Subjects were randomized to brush their teeth with either the test or control with the first brushing conducted under supervision in the dental clinic. Post-treatment samples were collected 12 h after 21 day hygiene with assigned toothpaste. After providing these samples, subjects brushed in the dental clinic with additional samples collected 4 h after brushing. Statistical analyses were conducted separately for each organism collected from each oral niche by t-test for within-treatment assessments and analysis of covariance (ANCOVA) for between-treatment comparisons. Results Treatment groups demonstrated no significant differences at baseline for anaerobic organisms, gram-negative bacteria and malodor bacteria in any oral niche (p > 0.05). The test demonstrated reductions between 42 and 68% for anaerobic bacteria in oral niches, 12 h after brushing with reductions increasing to 46–80%, 4 h after brushing. Similarly, the test demonstrated reductions between 49 and 61% for gram-negative bacteria of oral niches that increased to 54–69% at the 4 h post-brushing evaluation. Reductions in malodor organisms of 22–42% were noted 12 h after brushing that increased to 60–72%, 4 h after brushing. Conclusions In comparison to control, brushing with a novel herbal toothpaste demonstrated significant reductions in functional bacterial groups from distinct oral niches 12 h after brushing with additional microbial reductions 4 h after brushing.
Racial/Ethnic Disparities in Screening for and Awareness of High Cholesterol Among Pregnant Women Receiving Prenatal Care.

Background Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality among women, with younger women being disproportionately affected by traditional cardiovascular risk factors such as dyslipidemia. Despite recommendations for lipid screening in early adulthood and the risks associated with maternal dyslipidemia during pregnancy, many younger women lack access to and utilization of early screening. Accordingly, our objective was to assess the prevalence of and disparities in lipid screening and awareness of high cholesterol as an atherosclerotic cardiovascular disease risk factor among pregnant women receiving prenatal care. Methods and Results We invited 234 pregnant women receiving prenatal care at 1 of 3 clinics affiliated with the University of Pennsylvania Health System to complete our survey. A total of 200 pregnant women (86% response rate) completed the survey. Overall, 59% of pregnant women (mean age 32.2 [±5.7] years) self-reported a previous lipid screening and 79% of women were aware of high cholesterol as an atherosclerotic cardiovascular disease risk factor. Stratified by racial/ethnic subgroups, non-Hispanic Black women were less likely to report a prior screening (43% versus 67%, P=0.022) and had lower levels of awareness (66% versus 92%, P<0.001) compared with non-Hispanic White women. Non-Hispanic Black women were more likely to see an obstetrician/gynecologist for their usual source of non-pregnancy care compared with non-Hispanic White women (18% versus 5%, P=0.043). Those seeing an obstetrician/gynecologist for usual care were less likely to report a prior lipid screening compared with those seeing a primary care physician (29% versus 63%, P=0.007). Conclusions Significant racial/ethnic disparities persist in lipid screening and risk factor awareness among pregnant women. Prenatal care may represent an opportunity to enhance access to and uptake of screening among younger women and reduce variations in accessing preventive care services.
Low-Level Viremia Is Associated With Cumulative Adherence to Antiretroviral Therapy in Persons With HIV.

The drivers of low-level viremia (LLV) between 20 and 200 copies/mL remain unclear. In 1042 person-visits from 497 persons with HIV on tenofovir disoproxil fumarate-containing antiretroviral therapy (ART), the association between LLV and cumulative antiretroviral adherence (quantified using tenofovir diphosphate [TFV-DP] in dried blood spots) was assessed. Lower TFV-DP levels were associated with higher odds of LLV. As TFV-DP (fmol/punch) categories decreased from >1650 to 800-1650; 800-1650 to 1650 to <800, the adjusted odds ratios for LLV vs HIV VL <20 copies/mL were 2.0 (95% CI, 1.2-3.1), 2.4 (95% CI, 1.1-5.0), and 4.6 (95% CI, 2.2-9.9), respectively. This suggests that adherence could impact LLV.
First principles analysis of impurities in silicon carbide grain boundaries

Abstract Silicon carbide is an important structural and electronic ceramic material that finds many uses in a wide variety of applications that require stability at extreme conditions. In this study, we provide a detailed investigation of the formation energies of point defects and the stability of a wide variety of dopants in bulk cubic silicon carbide (3C-SiC) and in 3C-SiC grain boundaries (GBs) using first principles methods and a detailed charge distribution analysis. We also determine the driving force (segregation energies) of these dopants towards GBs. Our results show that smaller, more electronegative elements such as oxygen and nitrogen occupy carbon substitutional sites whereas larger transition metals such as molybdenum and rare earth elements such as cesium, substitute for silicon sites in SiC. Such dopants tend to migrate to more open spaces as provided in the Σ9 GB. This suggests that Σ9 GB is more effective in pinning the defect centers as compared to Σ3 GB. These findings provide the chemical landscape for defect engineering through which doped 3C-SiC can be designed for targeted materials development purposes.
Option-Implied Downside Risk Premiums

This article examines downside risk premiums using S&P 500 index (SPX) options. Portfolios are constructed using the index options to replicate the downside risk factors and their average excess returns provide estimates of downside risk premiums. We show that all the market risk premium comes from the downside. The mimicking portfolio returns also show that most of the downside risk premium is associated with large market-level losses that are rarely observed. In contrast, investors seem to require little excess return for bearing moderate market-level losses. Therefore, the downside risk premium is largely a tail risk premium. We compare the downside risk premiums measured from stocks and the options to examine whether the risk is priced consistently across the two markets. Our evidence raises several concerns about the downside risk premium measures from the stock market. Overall, we find no robust evidence that downside risks are priced in the stock market in the same way as in the options market.