cssi/SciSciGPT-SciSciNet huggingface dataset:
In vitro studies of cross-resistance mutations against two hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061.

VX-950 is a potent, small molecule, peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3·4A serine protease and has recently been shown to possess antiviral activity in a phase I trial in patients chronically infected with genotype 1 HCV. In a previous study, we described in vitro resistance mutations against either VX-950 or another HCV NS3·4A protease inhibitor, BILN 2061 (Lin, C., Lin, K., Luong, Y.-P., Rao, B. G., Wei, Y.-Y., Brennan, D. L., Fulghum, J. R., Hsiao, H.-M., Ma, S., Maxwell, J. P., Cottrell, K. M., Perni, R. B., Gates, C. A., and Kwong, A. D. (2004) J. Biol. Chem. 279, 17508-17514). Single amino acid substitutions that conferred drug resistance (distinct for either inhibitor) were identified in the HCV NS3 serine protease domain. The dominant VX-950-resistant mutant (A156S) remains sensitive to BILN 2061. The major BILN 2061-resistant mutants (D168V and D168A) are fully susceptible to VX-950. Modeling analysis suggested that there are different mechanisms of resistance for these mutations induced by VX-950 or BILN 2061. In this study, we identified mutants that are cross-resistant to both HCV protease inhibitors. The cross-resistance conferred by substitution of Ala156 with either Val or Thr was confirmed by characterization of the purified enzymes and reconstituted replicon cells containing the single amino acid substitution A156V or A156T. Both cross-resistance mutations (A156V and A156T) displayed significantly diminished fitness (or replication capacity) in a transient replicon cell system.
Telemedicine in a global context.

Telemedicine is part of the most recent revolution in healthcare. It will be most impactful to the developing world. The rapid advance of technology has made the entry into the telemedicine field much faster and cheaper. Telemedicine helps provide patient-centered care, reduce healthcare cost, save lives and improve patient’s health.
Population Screening for Biological and Environmental Properties of the Human Metabolic Phenotype: Implications for Personalized Medicine

Adoption of metabolic screening into routine health care has the potential to support Personalized Medicine; however, before informed decisions can be made on the basis of metabolic phenotyping, heterogeneity and confounding factors will have to be understood. This can only be accomplished through a data-driven approach, particularly when considering dietary and environmental influences. Identification of how phenotypic and lifestyle traits contribute to definition of an individual’s metabolic phenotype is required for meaningful interpretation of metabolic associations. In this chapter, we discuss the feasibility of metabolomics as a tool for population screening and for defining the human metabolic phenotype. Inherent factors contributing to the metabolic phenotype, including circadian rhythm, gender, age, and disease status, are reviewed. Because of the all-encompassing influence of human–environment interactions, we also discuss how environmental factors affect the metabolic phenotype and the use of metabolomics for broad-spectrum chemical biomonitoring. We close with a case study identifying biological responses to insecticide exposure in a healthy population.
Determinants of prognosis in late chronic-phase chronic myelogenous leukemia.

PURPOSESince interferon alfa (IFN-A) became an established treatment in chronic myelogenous leukemia (CML), more patients are referred to tertiary centers in late chronic phase (ie, > 12 months after diagnosis). Trials conducted in this phase cannot be evaluated precisely unless the features that determine prognosis in late chronic-phase CML are identified. The purpose of this study is to define the prognostic determinants of late chronic-phase CML.PATIENTS AND METHODSFrom 1980 to 1997,257 consecutive CML patients referred in late chronic phase were studied. Their clinical characteristics at the time of referral and their association with survival were investigated. A staging model was designed.RESULTSThe median survival from time of referral was 43 months. Pretreatment characteristics associated with worse outcome included older age, poor performance status, splenomegaly, low albumin level, high percentage of blasts or basophils in peripheral blood (PB) or bone marrow, longer duration of chronic phase, a...
Coordination Ring-Opening Copolymerization of Naturally Renewable α-Methylene-γ-butyrolactone into Unsaturated Polyesters

Reported herein is the first coordination–insertion ring-opening copolymerization of α-methylene-γ-butyrolactone (MBL) and e-caprolactone (e-CL) catalyzed by f-block lanthanide (Ln) catalysts, Ln[N(SiMe3)2]3, that produce exclusively an unsaturated copolyester PMBL-co-PCL without coproducing any homopolymer PMBL. Accomplishing such synthesis requires effective strategies to meet two key challenges: ring-opening of the γ-butyrolactone (γ-BL) ring in MBL—the five-membered lactone well recognized for its nonpolymerizability—and shutting down the vinyl-addition pathway via conjugate addition across the double bond—the exocyclic C═C moiety in MBL known for its high reactivity toward vinyl addition. Remarkably, the current Ln coordination catalyst system, coupled with judiciously chosen reaction conditions (relatively nonpolar solvent and low temperature, 0 or −20 °C), effectively copolymerizes MBL and e-CL to produce the ring-opening copolyester PMBL-co-PCL, with the MBL incorporation up to 40 mol % and withou...
Sanitary test results of public articles in hotels of Baodi District of Tianjin City

[Objective]To understand the sanitary status of public articles in hotels of Baodi District of Tianjin City from 2010-2012,and provide evidence for further strengthening disinfection management,improving health conditions of public places.[Methods]Sampling and testing was based on"Technical Specifications for Health Monitoring in Public Places"and"Hygiene Standards Monitoring Methods in Public Places".[Results] From 2010-2012,a total of 1 622 public articles were collected from hotels and tested in Baodi District,1 535(94.64%) were qualified.The qualified rate of hotels with 2 stars and above(98.48%) was better than the hotels with 2 stars below(92.78%).Of all articles,bedclothes had the lowest qualified rate(87.79%),while tableware had the highest(97.85%).The unqualified rate of public articles was highest in summer,with significant difference between seasons.[Conclusion]The general condition of hotels is well in Baodi District.The sanitary status of low-grade hotel is much lower than that of the high-grade hotel,with safety risks.It is necessary to strengthen the health inspection on the low-grade hotels in Baodi District.
The Massive Transfusion Score as a decision aid for resuscitation: Learning when to turn the massive transfusion protocol on and off.

BACKGROUNDPrevious work proposed a Massive Transfusion Score (MTS) calculated from values obtained in the emergency department to predict likelihood of massive transfusion (MT). We hypothesized the MTS could be used at Hour 6 to differentiate who continues to require balanced resuscitation in Hours
Onco-Cardiology for Breast Cancer

The purpose of this chapter is to underline the importance of cardiotoxicity, to identify the patients at risk for cardiotoxicity, and to outline strategies for the management of cardiac adverse events in patients with breast cancer undergoing systemic therapy. Several trials have suggested that regular assessment of cardiac function and parameters, including serum lipids that might be affected by adjuvant therapy, the management of hypertension, and weight control are important to minimize cardiovascular risks, especially in women aged >65 years, who constitute >50 % of the breast cancer population. The decision to use one specific cancer treatment regime should depend on its toxicity and efficacy profile. Reducing the severity and frequency of adverse cardiac events may improve the quality of life for patients undergoing systemic therapy for breast cancer and offer continuation of the well-documented and beneficial therapies. Management approaches should consider risk management plans to support the use of life-saving systemic therapeutics agents and avoid the interruption of their use due to the mismanagement of side effects. Cancer patients are vulnerable to many conditions; they can be protected from adverse events with better therapy regimens and regular assessment.
Combining Uncaging Techniques with Patch-Clamp Recording and Optical Physiology

Patch-clamp recording is a powerful approach to monitoring membrane electrical activity with high temporal resolution. However, the spatial resolution of patch-clamp recording in a distributed structure such as a neuron or a brain slice is limited by the fact that each electrode records from just one point, making recording from more than a very small number of points impractical. An approach that allows biological signals to be monitored and manipulated with high spatial resolution is the use of optical methods. For the monitoring of signals, a powerful approach is the use of activity-dependent fl uorescent dyes. In this type of recording, one or more cells are loaded with a fl uorescent dye that is sensitive to some change of interest, such as intracellular calcium or membrane voltage. Loading can be done by including the dye in the patch pipette, by bulk loading of many cells at once with acetoxymethyl (AM) ester dyes (Garaschuk et al., 2006; Sullivan et al., 2005; Tsien, 1999) or voltage-sensitive dyes (Djurisic et al., 2003; Grinvald and Hildesheim, 2004), or by expression of an activity-dependent fl uorescent protein (Bozza et al., 2004; Wang et al., 2003). Regardless of the means of loading, biological signals lead to variations in fl uorescence that can be detected by high-speed fl uorescence microscopy. The combination of electrophysiological and fl uorimetric recording thus allows monitoring of biochemical and electrical signals simultaneously with high temporal and spatial resolution.
A Sociopolitical Analysis of Black Enrollment

This chapter examines the findings produced from bivariate correlations, multivariate regression, and path analysis. The bivariate coefficients provide the basis for confirming/disconfirming the hypotheses about the relationships between the variables. Regression and path analysis are used as empirical tests of the propositions in the structural models or formal equations. A discussion of the statistics and research methods used to analyze the data provides verification for the reliability of the analyses. The political variables used for the analyses are Black voter Turnout and Registration, Black Legislators and Black Elected Officials. The socioeconomic variables are Black High school graduation rates and Black family Income levels.
Social Competition and the Evolution of Fluid Intelligence

The human brain is three times larger than that of our australopithecine ancestors and our closest living relatives. The pressures that drove the evolution of the hominid brain are debated and include climatic, ecological, and social factors. The thread that ties these models together is the ability to anticipate and cope with novelty and change. Geary presents a model of the evolution of mental models for coping with change and integrates this with cognitive and neuroscience research.
Targeting algorithms for online social advertising markets

Advertisers in online social networks (OSNs) like Facebook and LinkedIn have some preferred set of users they wish to reach by showing their ads. OSNs offer fine-grained sets of user characteristics — including their career, wealth, education information, etc — that advertisers can specify for targeting their audience, and each of these characteristics requires different amounts of money for targeting. The problem we address is what we call the targeting problem, that is, given a set S T characteristics of interest to an advertiser (that is, the advertiser wishes to reach users who have these characteristics, i.e. U(S T )) and a budget b 0 he wishes to spend, how to split the budget among the user characteristics so that they can reach the most number of users in U(S T )? • OSN-perspective. OSNs have complete knowledge of each user and their characteristics. In this case, we propose a polynomial time algorithm for the targeting problem and prove that it is an 1-1/e approximation to the targeting that gets the optimal number of users. We define the marginal increment and iteratively maximize it. • Advertiser-perspective. No single advertiser has the mapping of users to their characteristics or the distribution of users over the characteristics, and hence they cannot use the algorithm from above. We show through empirical data analysis that the strategy of targeting subsets U(S) ⊆ U(S T ) is their only feasible approach (in other words, targeting U(S) ⊈ U(S T ) will be arbitrarily worse than the direct solution). For evaluation, we crawl and analyze more than one million suggested bids from Facebook and LinkedIn. Further, we propose a fast greedy algorithm for the targeting problem based on targeting subsets, that in empirical analysis, increases the number of reached preferred users by nearly 40% over directly targeting the characteristics of interest, and for a moderate budget, it increases the number of reached preferred users by nearly 20%.
Integrative Analysis and Refined Design of CRISPR Knockout Screens

Genome-wide CRISPR-Cas9 screen has been widely used to interrogate gene functions. However, the analysis remains challenging and rules to design better libraries beg further refinement. Here we present MAGeCK-NEST, which integrates protein-protein interaction (PPI), improves the inference accuracy when fewer guide-RNAs (sgRNAs) are available, and assesses screen qualities using information on PPI. MAGeCK-NEST also adopts a maximum-likelihood approach to remove sgRNA outliers, which are characterized with higher G-nucleotide counts, especially in regions distal from the PAM motif. Using MAGeCK-NEST, we found that choosing non-targeting sgRNAs as negative controls lead to strong bias, which can be mitigated by sgRNAs targeting the 9safe harbor9 regions. Custom-designed screens confirmed our findings, and further revealed that 19nt sgRNAs consistently gave the best signal-to-noise separation. Collectively, our method enabled robust calling of CRISPR screen hits and motivated the design of an improved genome-wide CRISPR screen library.
Medical Care Expenditures for Individuals with Prediabetes: The Potential Cost Savings in Reducing the Risk of Developing Diabetes

Abstract The United States has 86 million adults with prediabetes. Individuals with prediabetes can prevent or delay the development of type 2 diabetes through lifestyle modifications such as parti...
Uncovering Structural Diversity of Unsaturated Fatty Acyls in Cholesteryl Esters via Photochemical Reaction and Tandem Mass Spectrometry

Mass spectrometry analysis of cholesteryl esters (CEs) faces several challenges, with one of them being the determination of the carbon–carbon double bond (C=C) locations within unsaturated fatty acyl chains. Paternὸ-Buchi (PB) reaction, a photochemical reaction based on the addition of acetone to C=C, is capable of C=C location determination when coupled with tandem mass spectrometry (MS/MS). In this study, the PB reaction conditions were tailored for CEs and subsequent nanoelectrospray ionization (nanoESI). A solvent system containing acetone/methanol/dichloromethane/water (40/30/20/10, volume ratios) and 100 μM LiOH was determined to be optimal, resulting in reasonable PB reaction yield (~30%) and good ionization efficiency (forming lithium adduct of CEs). Collision-induced dissociation (CID) of the PB reaction products produced characteristic fragment ions of CE together with those modified by the PB reactions, such as lithiated fatty acyl ([FA + Li]+) and its PB product ([FA – PB + Li]+). MS3 CID of [FA – PB + Li]+ led to abundant C=C diagnostic ion formation, which was used for C=C location determination and isomer quantitation. A PB-MS3 CID approach was developed and applied for CE analysis from human plasma. A series of unsaturated CEs was identified with specific C=C locations within fatty acyl chains. Absolute quantitation for each CE species was achieved including coexisting C=C location isomers, such as Δ9 and Δ11 isomers of CE 18:1 and ω-6 and ω-3 isomers of CE 18:3. These results show that PB-MS/MS is useful in uncovering structural diversity of CEs due to unsaturation in fatty acyls, which is often undetected from current lipid analysis approach.
Memory Compression Techniques for Network Address Management in MPI

MPI allows applications to treat processes as a logical collection of integer ranks for each MPI communicator, while internally translating these logical ranks into actual network addresses. In current MPI implementations the management and lookup of such network addresses use memory sizes that are proportional to the number of processes in each communicator. In this paper, we propose a new mechanism, called AV-Rankmap, for managing such translation. AV-Rankmap takes advantage of logical patterns in rank-address mapping that most applications naturally tend to have, and it exploits the fact that some parts of network address structures are naturally more performance critical than others. It uses this information to compress the memory used for network address management. We demonstrate that AV-Rankmap can achieve performance similar to or better than that of other MPI implementations while using significantly less memory.
Neurological Complications of Chemotherapy

One of the most common complications of conventional chemotherapy is neurotoxicity, including both the central nervous system (CNS) and peripheral nervous systems (PNS). These toxicities can manifest in many ways, including neuropathy, encephalopathy, seizures, headache, vision changes, cerebellar dysfunction, and spinal cord damage with myelopathy. The severity of the neurotoxicity may significantly vary from patient to patient and may be predictable based route of administration or cumulative dose or idiosyncratic and unpredictable in some cases. The vinca alkaloids, taxanes, platinums and proteasome inhibitors are known to cause peripheral neurotoxicity mainly manifesting as a sensory peripheral neuropathy. Antimetabolite drugs such as methotrexate, 5-fluorouracil, and cytarabine are most likely to cause central neurotoxicity. Intra-arterial administration significantly increases the neurotoxicity of some chemotherapeutic agents including cisplatin and nitrosoureas (e.g. BCNU). High dose ifosfamide therapy is likely to cause central neurotoxicity due to a metabolite of the medication. Other alkylating agents such as busulfan, cyclophosphamide, procarbazine, and temozolomide are better tolerated in terms of neurotoxicity at moderate doses. The retinoid drugs are known to cause severe headaches at high doses and l-asparaginase can induce an encephalopathy syndrome and cerebrovascular complications such as stroke.
Reduced-Order multi-modal model of SEI layer growth for management and control of lithium-ion batteries

Battery-management systems (BMS) seek to maximize battery-pack performance while extending life by optimizing dynamic operational power limits. To do so in a meaningful way, the BMS must have computationally simple yet accurate models of degradation to use in the optimization. As the growth of a solid-electrolyte interphase (SEI) layer on negative-electrode particles in lithium-ion cells is the dominant aging mechanism leading to capacity loss and resistance rise, we propose a reduced-order model of diffusion-or kinetics-limited SEI growth that could be used in an embedded optimization framework. This model approximates a full-order partial-differential-equation (PDE) model in the literature with less than 1 % relative error, at a speedup of more than 19 000 : 1.
Partnerships for Active Children in Elementary Schools (PACES): First year process evaluation.

Abstract Movement integration (MI) is a strategy within comprehensive school physical activity programs (CSPAP). School-university partnerships are recommended to leverage teachers’ capacity to use MI. A mixed method process evaluation was conducted of the first year of implementing Partnerships for Active Children in Elementary Schools (PACES). Classroom teachers (N = 12) from four schools participated. Data were collected in Fall 2014 (baseline) and Spring 2015 (∼ four months of intervention) using the System for Observing Student Movement in Academic Routines and Transitions and semi-structured interviews. There were no significant differences between intervention classrooms and control classrooms MI promotion. Differences approaching significance (U = 5, p = 0.04, d = 1.2) were observed when comparing classrooms that received two (community of practice, community-based participatory research) or three components (two components plus service learning) of the intervention and classrooms that received one (community of practice) or no components. Qualitative findings revealed that teachers in classrooms that were more successful responded more favorably to the intervention components than teachers in classrooms that were less successful. Quantitative and qualitative results supported the effectiveness of community-based participatory research as a component of PACES. This study provides information about MI process variables in the context of a CSPAP intervention.
Values of Participants in Behavioral Accounting Research: A Comparison of the M-Turk Population to a Nationally Representative Sample

ABSTRACT The external validity of conclusions from behavioral accounting experiments is in part dependent upon the representativeness of the sample compared to the population of interest. Researche...
Unexplained fever after pancreas transplantation

Background Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. Methods We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. Results Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post-transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. Conclusion UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.
Correction to: Multiple levers for overcoming the recalcitrance of lignocellulosic biomass.

Following publication of the original article [1], the authors reported that the omission of author name.
Precision Medicine in the Intensive Care Unit: Identifying Opportunities and Overcoming Barriers

Is precision medicine really precise? Precision in medicine can only be achieved with precision diagnostics. Unfortunately, barriers such as access to clean electronic medical data, accurate and precise laboratory tests, and a propensity to over simplify complex pathophysiology hinders this transformation to achieve the ‘four Ps’ of precision medicine: Personalized, Preventive, Predictive, and Participatory.
In Situ Time-Resolved Phase Evolution and Phase Transformations in U-6 Wt Pct Nb

In situ time-resolved synchrotron X-ray diffraction experiments were conducted to study the fine-scale phase evolution of U-6Nb. Upon rapid heating from 125 °C to 400 °C, a reverse martensitic transformation sequence, α″ → γo → γs, was observed in less than 4 seconds, which represents the first direct observation of the γo → γs transformation in diffraction-based measurements. Consistent with previous ex situ metallography experiments, our isothermal hold experiments at 526 °C, 530 °C and 565 °C reveal two distinct reactions for the phase separation, γs → α-U + γ1 (general precipitation) followed by (α-U + γ1) → α-U + γ1-2 (discontinuous precipitation). For the first-stage precipitation, the incubation time is determined to be ~ 50 and 100 seconds, respectively, for the isothermal aging at 526-530 °C and 565 °C. At this stage, the phase transformation is characterized by the simultaneous growth of α-U and γ1 at the expense of γs. As expected from the Arrhenius equation for the reaction rate, the determined times (~ 23 minutes) for the completion of the first-stage reaction at 526 ± 3 °C and 530 ± 3 °C are nearly twice longer than that at 565 ± 4 °C (~ 13 minutes). Over these periods of time, the Nb contents derived from a Vegard’s-type relationship for γ1 are in the 30.2 to 32.1 and 29.2 to 30.6 at. pct ranges, and the kinetics of the precipitation at 565 ± 4 °C can be described by the classic Avrami rate equation and one-dimensional growth of a surface or grain-boundary nucleation. During the second-stage precipitation, the γ1 phase continues to enrich in Nb as it gradually evolves toward the α + γ1-2 metastable state (up to 47 at. pct over a period of 172 minutes at 530 °C). These new and time-resolved measurements can be used to better constrain the time–temperature–transformation diagram, solute (Nb) redistribution, and transformation kinetics during the early stages of the diffusional phase transformation.
Fluid-induced metamorphism and anatexis of refractory Ni-Co-Cu sulphides in subduction-related rocks

The role of metamorphism on refractory sulfides is not well constrained. Although experiments have displayed the effectiveness of high grade metamorphism, namely granulite facies metamorphism, on sulfide anatexis, its role in the presence of other variables is still poorly understood. Rocks from the Bay Islands Accretionary Complex in Honduras and the Ildeus-Lucha Complex in Russia exhibit extensive metamorphism. Sulfide mineralization is prolific in these rocks suggesting that metamorphism has played an important role in re-concentrating these sulfides during amphibolite and granulite facies metamorphism.
PART I: The role of public health nursing in addressing health care needs of children in foster care.

AIMS AND OBJECTIVES The purpose of this study was to describe the role of Public Health Nurses (PHN) addressing the needs of children and adolescents in foster care. BACKGROUND Children in foster care have more physical, mental, dental, developmental health problems than the general pediatric population. National data indicate that between 30%-80% of children come into foster care with at least one physical health problem. DESIGN An online survey was developed to describe PHN day-to day activities, PHN funding, case load and case management responsibilities. METHOD Thirty-nine PHNs completed the survey (72% response rate). RESULTS Nurses described the most important needs as being mental and emotional health services, self-esteem/self-worth and dental care. Care coordination, case management and monitoring/oversight of psychotropic medications were the top responsibilities. CONCLUSION The study demonstrated that public health nursing expertise is an essential part of the child welfare team in addressing medical, dental, mental and developmental needs of children in foster care. RELEVANCE TO CLINICAL PRACTICE There is an expanding role of Public Health Nurses in non-health care settings to intervene at the system level of the Intervention Wheel that includes policy development and enforcement, community organizing, and coalition building.
DELVE FOR THE VALVE MASS: A CASE OF PULMONARY FIBROELASTOMA MIMICKING ENDOCARDITIS

Cardiac papillary fibroelastoma (PFE) are rare and benign tumors of endocardium accounting for 7% of all cardiac tumors. Aortic and mitral valve area are the most common sites of its occurrence and rarely they involve pulmonary valve (PV) area and are typically found incidentally during a open heart
Evoked and intrinsic brain network dynamics in children with autism spectrum disorder.

Abstract Objective Brain dynamics underlie flexible cognition and behavior, yet little is known regarding this relationship in autism spectrum disorder (ASD). We examined time-varying changes in functional co-activation patterns (CAPs) across rest and task-evoked brain states to characterize differences between children with ASD and typically developing (TD) children and identify relationships with severity of social behaviors and restricted and repetitive behaviors. Method 17 children with ASD and 27 TD children ages 7–12 completed a resting-state fMRI scan and four runs of a non-cued attention switching task. Metrics indexing brain dynamics were generated from dynamic CAPs computed across three major large-scale brain networks: midcingulo-insular (M-CIN), medial frontoparietal (M-FPN), and lateral frontoparietal (L-FPN). Results Five time-varying CAPs representing dynamic co-activations among network nodes were identified across rest and task fMRI datasets. Significant Diagnosis × Condition interactions were observed for the dwell time of CAP 3, representing co-activation between nodes of the M-CIN and L-FPN, and the frequency of CAP 1, representing co-activation between nodes of the L-FPN. A significant brain-behavior association between dwell time of CAP 5, representing co-activation between nodes of the M-FPN, and social abilities was also observed across both groups of children. Conclusion Analysis of brain co-activation patterns reveals altered dynamics among three core networks in children with ASD, particularly evident during later stages of an attention task. Dimensional analyses demonstrating relationships between M-FPN dwell time and social abilities suggest that metrics of brain dynamics may index individual differences in social cognition and behavior.
Evolutionary trajectory of fish Piscine novirhabdovirus (=Viral Hemorrhagic Septicemia Virus) across its Laurentian Great Lakes history: Spatial and temporal diversification.

Piscine novirhabdovirus = Viral Hemorrhagic Septicemia Virus (VHSV) first appeared in the Laurentian Great Lakes with large outbreaks from 2005 to 2006, as a new and novel RNA rhabdovirus subgenogroup (IVb) that killed >30 fish species. Interlude periods punctuated smaller more localized outbreaks in 2007, 2010, and 2017, although some fishes tested positive in the intervals. There have not been reports of outbreaks or positives from 2018, 2019, or 2020. Here, we employ a combined population genetics and phylogenetic approach to evaluate spatial and temporal evolutionary trajectory on its G-gene sequence variation, in comparison with whole-genome sequences (11,083 bp) from a subset of 44 individual isolates (including 40 newly sequenced ones). Our results show that IVb (N = 184 individual fish isolates) diversified into 36 G-gene haplotypes from 2003 to 2017, stemming from two originals ("a" and "b"). G-gene haplotypes "a" and "b" differed by just one synonymous single-nucleotide polymorphism (SNP) substitution, remained the most abundant until 2011, then disappeared. Group "a" descendants (14 haplotypes) remained most prevalent in the Upper and Central Great Lakes, with eight (51%) having nonsynonymous substitutions. Group "b" descendants primarily have occurred in the Lower Great Lakes, including 22 haplotypes, of which 15 (68%) contained nonsynonymous changes. Evolutionary patterns of the whole-genome sequences (which had 34 haplotypes among 44 isolates) appear congruent with those from the G-gene. Virus populations significantly diverged among the Upper, Central, and Lower Great Lakes, diversifying over time. Spatial divergence was apparent in the overall patterns of nucleotide substitutions, while amino acid changes increased temporally. VHSV-IVb thus significantly differentiated across its less than two decades in the Great Lakes, accompanied by declining outbreaks and virulence. Continuing diversification likely allowed the virus to persist at low levels in resident fish populations, and may facilitate its potential for further and future spread to new habitats and nonacclimated hosts.
Protocol for determining zinc-dependent β cell-selective small-molecule delivery in mouse pancreas.

Summary Targeted drug delivery to pancreatic islet β cells is an unmet clinical need. β cells possess a uniquely high Zn2+ concentration, and integrating Zn2+-binding activity into a small molecule can bias drug accumulation and activity toward β cells. This protocol can be used to evaluate a molecule’s capacity to chelate islet Zn2+, accumulate in islets, and stimulate β cell-selective replication in mouse pancreas. One obstacle is establishing an LC-MS/MS-based method for compound measurement. Limitations include target compound ionizability and the time-sensitive nature of some experimental assay steps. For complete details on the use and execution of this protocol, please refer to Horton et al. (2019) .
FINDING THE PROPER MEASURE:THE VALUE OF MONEY VERSUS HIGHER VALUES

In our consumerist world, our values center around the possession of money and the possi­bility of buying things we have never imagined we need. Shopping has become our lifestyle to the extent that our sense of freedom seems to be reduced to a choice between brands. I ex­amine this state of affairs from three perspectives: apologetic, critical, and one attempting to balance our obsession with money and shopping with a proper understanding of higher values. Following Nicolai Hartmann, I develop the last of these standpoints. We should not be too concerned about our love for shopping, nor is there anything wrong with convincing people to buy things they had never imagined they needed. But it is problematic when we spend more time shopping than with our children and reorganize our schools as if they are corporations created to make profit. The problem of our age is that we place money, shop­ping, and economic values in a position that is inappropriately high: we see the highlights of our lives in shopping and the acquisition of new things, while their values are far lower. The central task of our age is to find the right balance between low and strong material val­ues and high and weak personal values.
Application of U-Nets for the automatic segmentation of immune cells in high-dimensional microscopy images of kidney biopsies

Lupus nephritis (LuN) is an inflammatory kidney disease characterized by the infiltration of immune cells into the kidney, including T-cells, B-cells, and dendritic cells. Here, we combine high-dimensional immunofluorescence microscopy with computer vision to identify and segment multiple populations of cells. A U-Net was trained to segment CD4+ T-cells in high-resolution LuN biopsy images and subsequently used to make CD4+ T-cell predictions on a test-set from a lower-resolution, high-dimensional LuN dataset. This produced higher precision, but lower recall and intersection over union for cells in the low-resolution dataset. Further application of U-Nets to immune cell segmentation will be discussed.
The Musculoskeletal System

Dr. Heberden, remembered by the eponymous name of osteophytic spurs involving the distal interphalangeal joints often seen in patients with degenerative joint disease, lamented the lack of specificity in describing various sorts of musculoskeletal diseases. What would he have thought of aromatase inhibitor-induced arthralgia, statin-associated myalgia, cell phone thumb, and wiiitis?
Analysis of Formation and Growth of the δ Phase in Additively Manufactured Functionally Graded Materials

This study focuses on the formation of the σ phase in three functionally graded material (FGM) systems made by additive manufacturing (AM): stainless steel 420 (SS420) to V to Ti-6Al-4V, Ti-6Al-4V to V to stainless steel 304L (SS304L), and SS420 to V. Directly joining Ti-6Al-4V and stainless steel may result in the formation of brittle Fe-Ti intermetallics. This study investigates the potential use of V as an intermediate element between terminal alloys of Ti-6Al-4V and stainless steel. Experimental analysis of the elemental and phase composition revealed that different amounts of σ phase were present in the three FGM systems at locations with similar elemental compositions. Computational studies were performed to simulate the thermal history, phase transformation kinetics, and σ phase growth within these FGMs. The computations suggested that, at the conditions studied, the σ phase should nucleate faster and grow to a larger volume fraction in the SS420-V alloy than the SS304L-V alloy, contrasting with experimental observations. Instead, experimental analysis confirmed that the disparate growth of σ phase in the FGMs was due differences in cracking during fabrication, resulting in different amounts of time spent at the elevated temperatures conducive to σ phase growth in each of the samples.
Teotihuacan

Teotihuacan in the northeastern Basin of Mexico was an unusually large and influential early city and state. This article reviews recent research trends in Teotihuacan from its founding and explosive growth ca. 100 BC into the largest city in Mesoamerica. Biogenetics provide details of how immigration fueled the city’s growth and shaped its multiethnic composition and link Teotihuacan to other parts of the central highlands and more distant regions. Urban theory highlights the importance of neighborhoods and how their composition changed. Collective aspects of irrigation, markets, warfare and the military, and ideology encouraged the development of Teotihuacan’s corporate governance. Although Teotihuacan politically dominated central Mexico, its control over the regional economy was not as centralized. Beyond its hinterland, Teotihuacan’s foreign relations were a mosaic of trade diasporas, diplomatic exchanges, pilgrimages, emulation, and strategic direct interventions of limited duration. As its foreign influence retracted, Teotihuacan faced challenges from its hinterlands and intermediate elites and factions that culminated in the burning and desecration of the urban center. The Epiclassic saw the change from Teotihuacan’s regional state to city-states and confederations. Although much reduced in size, Postclassic Teotihuacan retained an enormous legacy that subsequent states sought for their historical validation.
Out-of-Pocket Spending for Asthma-Related Care Among Commercially Insured Patients, 2004-2016.

Background Out-of-pocket (OOP) health care costs can cause financial burden and deferred care for many Americans. Little is known about OOP spending for asthma-related care among the commercially insured. Objectives To analyze OOP spending for asthma-related care overall, across types of care, and by income. Methods Using enrollment, claims, and geocoded census tract data on income from a large US commercial health plan from 2004 to 2016, we measured inflation-adjusted OOP spending for individuals with asthma ages 4 to 64 years (n = 1,986,769). We estimated annual asthma-related OOP spending over time, and average total, asthma-related, asthma type of care, and asthma medication spending by income. We measured trends in median OOP cost per medication. Linear regression models were adjusted for patient covariates and deductible level. Results Asthma-related OOP spending decreased over time both for patients enrolled in high-deductible health plans and for those in traditional plans. High-deductible plan enrollment increased from 7% to 54%. Compared with patients living in high-income areas, patients in the lowest-income areas had similar annual total and asthma-related OOP spending, but spent 30% less on controller medications and a higher proportion of their asthma-related OOP spending on inpatient and emergency care (10% vs 3%; P Conclusions Patients with asthma living in the lowest-income areas have greater cost burden, lower spending on controller medications, and greater spending on high-acuity care than higher-income counterparts.
The Challenges Educators Face in Virtually Creating High Quality LMX with Students and Colleagues

One of the fundamental pieces to educational success is for teachers to actively engage students in the learning environment. Covid-19 has fundamentally altered how instruction is delivered in public high schools and how secondary teachers are able to engage and interact with high school students and colleagues. Given that students are more apt to engage and succeed academically when they have positive relationships with teachers, secondary teachers had to adapt to a new virtual learning environment and a new way of establishing meaningful connections with students. This shift from in-person instruction to virtual instruction creates a need for new ways of engaging in a Leader-Member Exchange Theory (LMX) that could result in high quality exchanges that increase student learning and active participation. Further, teachers, themselves, must engage in their own professional learning communities virtually, as well, removing an important component of face-to-face collaboration with colleagues that promotes student growth and achievement. The purpose of this conceptual paper is to develop recommendations based upon a literature review of LMX and Secondary and Virtual Learning Pedagogies.
Molecular Recognition of HIV Glycans by Antibodies

Human immunodeficiency virus 1 (HIV-1) currently infects over 34 million people across the world and remains one of the greatest global public health burdens despite the development of highly active antiretroviral therapy. An effective prophylactic vaccine is therefore greatly needed but remains elusive due to HIV-1’s ability to evade the immune system. The isolation of potent, broadly neutralizing antibodies (bnAb) from infected individuals suggests a vaccine might in principle be possible. Structural characterization of such antibodies in complex with component pieces of the heavily glycosylated envelope glycoprotein gp160 (Env) is providing information critical for the design of more effective immunogens. Recently, a number of glycan-dependent bnAbs have been isolated that are very potent. Four of these bnAbs have been structurally characterized in complex with their glycosylated antigens. In this chapter, we describe the different binding modes of these glycan-dependent antibodies and how they define novel sites of vulnerability that can be used for design of a new generation of glycosylated immunogens.
Regulation of acetylcholine muscarinic receptors by embryonic septal grafts showing cholinergic innervation of host hippocampus.

Publisher Summary This chapter describes whether cholinergic innervation by embryonic septal or striatal grafts would result in the regulation of muscarinic receptors in the denervated hippocampus using quantitative autoradiography. The evidence indicates that the cholinergic input from the grafted embryonic septum also makes muscarinic synapses, as the electrophysiological responses are atropine sensitive and in aged rats transplantinduced behavioral recovery is atropine sensitive. Combined pharmacological and electrophysiological studies have shown that cholinergic synapses in the normal hippocampus are of the muscarinic type. The septo-hippocampal cholinergic projection is a particularly useful model for studying the capacity of the transplant to reinnervate the host region. Regulation of muscarinic sites after destruction of the cholinergic system innervating the cortex has been difficult to show. The results show an increase of muscarinic receptors that are shown as down regulated with appropriate cholinergic innervation by grafts of embryonic septal or striatal tissue. This work provides further evidence that the synaptic contacts made by these grafts are functional.
Reactions of the 3' terminus of transfer ribonucleic acid. VI. Properties of the poly(C) polymerase activity associated with rabbit liver transfer ribonucleic acid nucleotidyltransferase.

Abstract The properties of the poly(C) polymerase activity associated with rabbit liver tRNA nucleotidyltransferase were examined. The anomalous activity co-purified with tRNA nucleotidyltransferase throughout a 25,000-fold purification and was associated with both forms of the latter enzyme. Both activities also co-migrated during isoelectric focusing, and had similar, but not identical, heat inactivation profiles. The poly(C) polymerase reaction was identical with the normal CMP-incorporating activity of tRNA nucleotidyltransferase with regard to pH and temperature optima, requirements for a divalent cation and an RNA acceptor, and nonlinear double reciprocal plots with respect to varying CTP concentrations. However, the poly(C) polymerase activity also differed in several properties, including its response to divalent cations, ATP, salt, and organic solvents. Normal CMP incorporation into tRNA-C was most active with Mg2+, was stimulated by ATP and salt, and was inhibited by a variety of organic solvents. In contrast, the poly(C) polymerase reaction was most active with Mn2+, was inhibited by ATP and salt, and was stimulated by organic solvents. The poly(C) polymerase activity utilized intact tRNA-C-C-A, tRNA-C-C, 5 S RNA, and rRNA as acceptors for CMP incorporation. In the presence of Mg2+ the rate of the anomalous reaction was generally only a few per cent of CMP incorporation into the presumed normal acceptor, tRNA-C, although 5 S RNA was 15% as active. In all cases, the poly(C) polymerase reaction was stimulated 2- to 3-fold by 1 mm Mn2+ and the normal reaction was inhibited, so that under these conditions the best substrate was 5 S RNA. Extended nucleotide incorporation into tRNA-C-C-A or rRNA was found only in the presence of CTP, whereas incorporation of AMP and UMP was limited or nonexistent. These data indicate that liver tRNA nucleotidyltransferase, like several other enzymes which synthesize phosphodiester bonds, can also act as a homopolymer polymerase. The relation of this activity to other known poly(C) polymerases and its possible mechanism of action are also discussed.
Evaluating Online Real-Time Reference in an Academic Library: Obstacles and Recommendations

Summary Online real-time or “chat” reference, while still in its infancy when compared to traditional reference services is beginning to come of age. The time has come to move beyond the earlier challenges and issues debated at length in the library profession and begin to consider how to evaluate real-time reference. This article will consider obstacles to evaluating chat reference and present practical recommendations. These obstacles are presented in four basic areas including; organizational structure, scarcity of resources, newness of the service, and difficulty developing techniques of assessment or applying existing methodology.
On-Demand Node Reclamation and Replacement for Guaranteed Area Coverage in Long-Lived Sensor Networks

To achieve required sensing coverage for a very long period of time is an important and challenging problem in sensor network design. Recently, Tong et al. have proposed a node replacement and reclamation (NRR) strategy, and designed an adaptive rendezvous-based two-tier scheduling (ARTS) scheme. However, the ARTS scheme only considers point coverage but not area coverage, which is required in many applications. To address this limitation, we propose in this paper a new implementing scheme for the NRR strategy based on a novel staircase-based scheduling model. Extensive simulations have been conducted to verify that the proposed scheme is effective and efficient.