cssi/SciSciGPT-SciSciNet huggingface dataset:
Reduced HIV-1 integrase flexibility as a mechanism for raltegravir resistance.

Abstract HIV-1 integrase is an essential enzyme necessary for the replication of the HIV virus as it catalyzes the insertion of the viral genome into the host chromosome. Raltegravir was the first integrase inhibitor approved by the FDA for antiretroviral treatment. HIV patients on raltegravir containing regimens often develop drug resistance mutations at residue 140 and 148 in the catalytic 140’s loop resulting in a 5–10 fold decrease in susceptibility to raltegravir. Obtaining crystallographic structure information on the Q148H/R, G140S/A primary and secondary mutations has been elusive. Using 10 ns molecular dynamics simulations, we present a detailed analysis of the structural changes induced by these mutations. The formation frequency of a transient helix in the catalytic 140’s loop is increased and the length of this helix is extended from 3-residues to 4 in the mutants relative to the wild type. This helix causes reduced flexibility in the protein active site and therefore serves as a gating mechanism restricting the access of raltegravir to the integrase binding pocket. These results suggest that resistance to raltegravir occurs through a common mechanism of altering the formation frequency of transient secondary structures such as α2 and β5 in addition to the conformational changes in the 140’s loop therefore decreasing the flexibility of the HIV-1 integrase protein. The reduced integrase flexibility serves as a mechanism of resistance to raltegravir.
Certified safe farm: identifying and removing hazards on the farm.

This article describes the development of the Certified Safe Farm (CSF) on-farm safety review tools, characterizes the safety improvements among participating farms during the study period, and evaluates differences in background variables between low and high scoring farms. Average farm review scores on 185 study farms improved from 82 to 96 during the five-year study (0-100 scale, 85 required for CSF certification). A total of 1292 safety improvements were reported at an estimated cost of $650 per farm. A wide range of improvements were made, including adding 9 rollover protective structures (ROPS), 59 power take-off (PTO) master shields, and 207 slow-moving vehicle (SMV) emblems; improving lighting on 72 machines; placing 171 warning decals on machinery; shielding 77 moving parts; locking up 17 chemical storage areas, adding 83 lockout/tagout improvements; and making general housekeeping upgrades in 62 farm buildings. The local, trained farm reviewers and the CSF review process overall were well received by participating farmers. In addition to our earlier findings where higher farm review scores were associated with lower self-reported health outcome costs, we found that those with higher farm work hours, younger age, pork production in confinement, beef production, poultry production, and reported exposure to agrichemicals had higher farm review scores than those who did not have these characteristics. Overall, the farm review process functioned as expected, encouraging physical improvements in the farm environment, and contributing to the multi-faceted CSF intervention program.
Propagation through an elevated duct: Tradewinds III

In July and August of 1960, a joint Naval Research Laboratory-Naval Electronics Laboratory radio-meteorological program (Project Tradewinds III) was carried out between San Diego, Calif., and Opana, Hawaii. The purpose of this project was to evaluate the propagation characteristics of the duct formed by the tradewinds inversion which is generally found in this region. Two frequencies, 220 Mc and 445 Mc, were used and data concerning signal strength vs range from each terminal, height gain data at several points in the path, as well as the gross meteorological conditions which prevailed over the path were taken. This report attempts both to correlate the radio propagation data with the observed meteorology and to formulate a mechanism to explain the presence in the duct of signal power transmitted from a point well below the duct. In general, cloud heights and types serve as indicators of the stability of the tradewinds inversion and can be correlated with the altitude and strength of the inversion and consequently of the duct. By using both ray and scatter theories, a relation is developed which may be used to determine the signal losses expected in transmission through an elevated duct in which either or both terminals are well below the duct.
Sorting sequential files with limited auxiliary storage

This paper considers the problem of sorting files whose size exceeds main memory and for which only limited auxiliary memory resources are available.
Threshold Voltage Variation Effects on Aging-Related Hard Failure Rates

This paper quantifies the impact of threshold voltage variation on aging-related hard failure rates in a high-performance 65nm processor. Simulations show that threshold voltage variations can accelerate aging substantially, depending on the thermal resistance of the heatsink and the total leakage power of the processor before variation. For unfavorable values of these parameters, our models suggest that the time at which 1% of the processors have failed can decrease by about 60%.
Liquid Water Formation and Transport in the PEFC Anode

Transparent polymer electrolyte fuel cells PEFCs with parallel- and serpentine-channel flowfields have been developed to study liquid water formation and transport on the anode side. In situ observations reveal that liquid water in the anode channels results from condensation of water on cooler and more hydrophilic channel walls and that water available for condensation in the anode comes either from the cathode through membrane transport or from hydrogen consumption. No water droplets can be found on the anode gas diffusion layer GDL surface, in sharp contrast with the cathode side. Moreover, GDL wettability has much influence on water distribution in the anode for the cell operated at low current density 0.2 A/cm 2 . Using hydrophobic GDL at low current density, water is prone to condense on the channel surfaces rather than inside hydrophobic carbon paper GDL. The condensed water then accumulates and results in channel clogging in the anode. In contrast, by using untreated carbon paper as the anode GDL, it is found that channel clogging by liquid water is avoided under similar operating conditions. This finding implies that water distributions in the anode with hydrophilic and hydrophobic anode GDLs differ much from each other at low current density. Finally, experiments suggest that water condensation on the channel surfaces is a primary mechanism for liquid water formation and anode flooding and that elevating the anode plate temperature modestly is effective to avoid surface condensation and mitigate anode flooding.
Behavior and nutritional condition buffer a large‐bodied endotherm against direct and indirect effects of climate

Temporal changes in net energy balance of animals strongly influence fitness; consequently, natural selection should favor behaviors that increase net energy balance by buffering individuals against negative effects of environmental variation. The relative importance of behavioral responses to climate-induced variation in costs vs. supplies of energy, however, is uncertain, as is the degree to which such responses are mediated by current stores of energy. We evaluated relationships among behavior, nutritional condition (i.e., energy state), and spatiotemporal variation in costs vs. supplies of energy available to a large- bodied endotherm, the North American elk (Cervus elaphus), occupying two ecosystems with contrasting climates and energy landscapes: a temperate, montane forest and an arid, high- elevation desert. We hypothesized that during spring through autumn, behavioral responses to the energy landscape would be both context dependent (i.e., would vary as a function of the contrasting environmental conditions experienced by elk in the forest vs. the desert), and state dependent (i.e., would vary as a function of the energy balance of an individual). We tested several predictions derived from that hypothesis by combining output from a biophysical model of the thermal environment with data on forage quality, animal locations, and nutritional condition of individuals. At the population level, elk in the desert selected areas that reduced costs of thermoregulation over those that provided the highest-quality forage. In the forest, however, costs imposed by the thermal environment were less pronounced, and elk selected areas that increased access to high-quality forage over those that reduced costs of thermoregulation. At the individual level, nutritional condition did not influence strength of selection for low-cost areas or high-quality forage among elk in the forest. In the desert, however, strength of selection for low-cost areas (but not forage quality) was state dependent; individuals in the poorest condition at the end of winter showed the strongest selection for areas that reduced costs of thermoregulation during spring and summer, and also expended the least amount of energy on locomotion. Our results highlight the importance of understanding the roles of behavior and nutritional condition in buffering endotherms against direct and indirect effects of climate on fitness.
A new photographic-based system for the measurement of contrast sensitivity.

Abstract— A new photographic-based system has been developed for the measurement of contrast sensitivity in human vision. The system has several advantages over other photographic methods and is relatively easy and inexpensive to produce. This paper describes the design of the new system and the methods used in the production of the photographic prints. Preliminary tests show that full contrast sensitivity curves can be obtained with a small number of photographic prints and that these curves are very similar to those obtained using a carefully calibrated electronic pattern generator.
The Information Intermediary Role of Short Sellers

This paper examines the conditions under which the market responds to disclosures of significant increases in short selling, and whether proxies for earnings expectations and alternative information sources help explain this response. Our sample is based on firms that experience abnormal short interest increases (“short spikes”) during 1989–1998. We find that the mean abnormal return around short spike announcements is significantly more negative for firms with low analyst following, consistent with short sellers providing perceived value when there are limited alternative sources of guidance available. For firms with high analyst following we find the market response is dependent on earnings levels, consistent with investors viewing a short interest increase as providing information about the sustainability of earnings. Additional analyses reveal that these inferences are not affected by measures of firms' earnings quality or by the relative size of the short spike. We infer from our analyses that the in...
The Unfolded Protein Response in the Protozoan Parasite Toxoplasma gondii Features Translational and Transcriptional Control

The unfolded protein response (UPR) is an important regulatory network that responds to perturbations in protein homeostasis in the endoplasmic reticulum (ER). In mammalian cells, the UPR features translational and transcriptional mechanisms of gene expression aimed at restoring proteostatic control. A central feature of the UPR is phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF2) by PERK (EIF2AK3/PEK), which reduces the influx of nascent proteins into the ER by lowering global protein synthesis, coincident with preferential translation of key transcription activators of genes that function to expand the processing capacity of this secretory organelle. Upon ER stress, the apicomplexan parasite Toxoplasma gondii is known to induce phosphorylation of Toxoplasma eIF2α and lower translation initiation. To characterize the nature of the ensuing UPR in this parasite, we carried out microarray analyses to measure the changes in the transcriptome and in translational control during ER stress. We determined that a collection of transcripts linked with the secretory process are induced in response to ER stress, supporting the idea that a transcriptional induction phase of the UPR occurs in Toxoplasma. Furthermore, we determined that about 500 gene transcripts showed enhanced association with translating ribosomes during ER stress. Many of these target genes are suggested to be involved in gene expression, including JmjC5, which continues to be actively translated during ER stress. This study indicates that Toxoplasma triggers a UPR during ER stress that features both translational and transcriptional regulatory mechanisms, which is likely to be important for parasite invasion and development.
A Low-Supply-Voltage CMOS Sub-Bandgap Reference

A low-power (21 muW ) bandgap reference source that is operable from a nominal supply voltage of 1.4 V is described. The circuit provides an output voltage equal to the bandgap voltage having a low output resistance and allows resistive loading. It does not use resistors or operational amplifiers. Thus, the design is suitable for fabrication in any digital CMOS technology. The circuit uses a current conveyor and current mirrors to convert the proportional to absolute temperature voltage into a current using a MOSFET. The current is converted back to a voltage by using the functional inverse of the FET v-i characteristics. This makes the voltage gain linear and temperature independent. The absence of back-gate bias is the reason for achieving the low supply voltage of operation. Simulation results using the transistor models for the 0.18-mum TSMC process show that the voltage-variation over the temperature range 0 to 100degC is <1 mV.
Maximum Getis–Ord Statistic Adjusted for Spatially Autocorrelated Data

Local statistics test the null hypothesis of no spatial association or clustering around the vicinity of a location. To carry out statistical tests, it is assumed that the observations are independent and that they exhibit no global spatial autocorrelation. In this article, approaches to account for global spatial autocorrelation are described and illustrated for the case of the Getis–Ord statistic with binary weights. Although the majority of current applications of local statistics assume that the spatial scale of the local spatial association (as specified via weights) is known, it is more often the case that it is unknown. The approaches described here cover the cases of testing local statistics for the cases of both known and unknown weights, and they are based upon methods that have been used with aspatial data, where the objective is to find changepoints in temporal data. After a review of the Getis–Ord statistic, the article provides a review of its extension to the case where the objective is to choose the best set of binary weights to estimate the spatial scale of the local association and assess statistical significance. Modified approaches that account for spatially autocorrelated data are then introduced and discussed. Finally, the method is illustrated using data on leukemia in central New York, and some concluding comments are made.
Against Narrative: A Preface to Lyrical Sociology*

This article develops a concept of lyrical sociology, a sociology I oppose to narrative sociology, by which I mean standard quantitative inquiry with its “narratives” of variables as well as those parts of qualitative sociology that take a narrative and explanatory approach to social life. Lyrical sociology is characterized by an engaged, nonironic stance toward its object of analysis, by specific location of both its subject and its object in social space, and by a momentaneous conception of social time. Lyrical sociology typically uses strong figuration and personification, and aims to communicate its author's emotional stance toward his or her object of study, rather than to “explain” that object. The analysis considers many examples and draws on literary criticism, the philosophy of time, and the theory of emotion. It also addresses contemporary debates in ethnography.
Looking Beyond RevPAR: Productivity Consequences of Hotel Strategies

Decisions about a hotel's size, service orientation, strategic orientation, and ownership and management arrangements affect a number of labor- and capital-productivity measures.
The role of positron emission tomography imaging in movement disorders

PET imaging provides the means to study neurochemical, hemodynamic, or metabolic processes that underlie movement disorders in vivo. Because the extent of presynaptic nigrostriatal dopaminergic denervation can be quantified in PD even at an early or preclinical stage of the disease, PET imaging may allow the selection of at-risk subjects for neuroprotective intervention trials. These techniques may also provide markers to follow progression of disease or evaluate the effects of neurorestorative interventions in patients who have more advanced disease. PET is expected to play an increasing role in the selection of patients who have PD for deep brain stimulation. Dopaminergic studies may have a limited clinical role in the diagnosis of patients who have symptoms that suggestive of PD yet do not respond to typical dopaminergic drugs, such as patients who have vascular parkinsonism or ET with mild resting tremor who may have normal dopaminergic innervation. The differential diagnosis between PD and multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration is not yet clearly established by PET, but combined pre- and postsynaptic dopaminergic imaging may be able to distinguish early idiopathic PD from atypical parkinsonian disorders, in general. Huntington's chorea is characterized by more prominent striatal dopamine receptor loss, whereas nigrostriatal denervation is present to a lesser degree. Patients who have TS may have enhanced synaptic dopamine release in the putamen. Functional imaging studies have generally failed to demonstrate nigrostriatal denervation in essential tremor or idiopathic dystonia. Studies have shown striatal dopamine receptor loss in selected subtypes of dystonic patients. In conclusion, it is expected that PET will help us to better understand the pathophysiology of movement disorders, increase the diagnostic accuracy, allow preclinical diagnosis, monitor disease progression, and evaluate the efficacy of therapeutic agents. Pharmacologic radioligand displacement studies and the development of new nondopaminergic ligands may further aid in the unraveling of cerebral mechanisms that underlie movement disorders.
Correlates of cruelty to animals in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

Objective: To examine the sociodemographic, behavioral, and psychiatric correlates of cruelty to animals in the US. Materials and methods: Data were derived from a nationally representative sample of adults residing in the US Structured psychiatric interviews (N = 43,093) were completed by trained lay interviewers between 2001 and 2002. Personality, substance use, mood, and anxiety disorders and cruelty to animals were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule (DSM-IV) version. Results: The lifetime prevalence of animal cruelty in US adults was 1.8%. Men, African-Americans, NativeAmericans/Asians, native-born Americans, persons with lower levels of income and education and adults living the western region of the US reported comparatively high levels of cruelty to animals, whereas Hispanics reported comparatively low levels of such behavior. Cruelty to animals was significantly associated with all assessed antisocial behaviors. Adjusted analyses revealed strong associations between lifetime alcohol use disorders, conduct disorder, antisocial, obsessive–compulsive, and histrionic personality disorders, pathological gambling, family history of antisocial behavior, and cruelty to animals. Conclusions: Cruelty to animals is associated with elevated rates observed in young, poor, men with family histories of antisocial behavior and personal histories of conduct disorder in childhood, and antisocial, obsessive–compulsive and histrionic personality disorders, and pathological gambling in adulthood. Given these associations, and the widespread ownership of pets and animals, effective screening of children, adolescents and adults for animal cruelty and appropriate mental health interventions should be deployed.
Discrete point based signatures and applications to document matching

Document analysis often starts with robust signatures, for instance for document lookup from low-quality photographs, or similarity analysis between scanned books. Signatures based on OCR typically work well, but require good quality OCR, which is not always available and can be very costly. In this paper we describe a novel scheme for extracting discrete signatures from document images. It operates on points that describe the position of words, typically the centroid. Each point is extracted using one of several techniques and assigned a signature based on its relation to the nearest neighbors. We will discuss the benefits of this approach, and demonstrate its application to multiple problems including fast image similarity calculation and document lookup.
Simplified interpretative format for assessing test interference: studies with hemoglobin-based oxygen carrier solutions

Substances such as hemoglobin that interfere with analytical processes are recognized as a frequent source of error in laboratory medicine. Standard guidelines for assessment of test interferences assume that interference effects are not related to the concentration of the analyte being measured. However, previous investigations have demonstrated that interference effects can be markedly different, depending on the concentrations of interferent and analyte within the specimen. An experimental protocol for investigating these different types of interference effects has been developed. This protocol utilizes an orthogonally arranged matrix with progressively increasing concentrations of analyte and interferent. Evaluation of the measured analyte concentrations in specimens within the matrix using multiple regression analysis allows the magnitude, direction, and significance of each type of interference to be determined. Unfortunately, implementation of the interference data derived from the multiple regression analysis for judging the clinical acceptability of test results when an interferent is present is difficult. We describe a two-dimensional graphical format for evaluating the clinical acceptability of test results, based on criteria established under the Clinical Laboratory Improvement Amendments of 1988, in specimens containing hemoglobin-based oxygen carrier solutions.
Cimetidine Impairs Nitrazepam Clearance

The effect of cimetidine on hepatic clearance of the benzodiazepine derivative nitrazepam was evaluated in healthy subjects. Six received a single 5- or 10-mg oral nitrazepam dose in the drug-free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min/kg in the control state to 1.17 ml/min/kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t½ from 22.2 to 27.8 hr. Thus the ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction. Clinical Pharmacology and Therapeutics (1983) 34, 227–230; doi:10.1038/clpt.1983.157
Advances in microwave measurement science

With the recent impact of digital technology, a review of the subject of microwave measurements is timely. Following a brief summary of those features which make this a unique science, the current status of the so-called "basic standards" for microwave measurements is noted. This is followed by a review of the use of digital techniques, power equation concepts, connector problems, and related developments. Finally, certain projections for the future are made.
A Matter of Principle

School principals are often faced with difficult decisions that challenge both their moral beliefs and ethical behaviors. Personal relationships and political associations can create an even greater challenge and level of frustration for building level administrators when attempting to carry out duties as moral agents and acting in loco parentis. As the new principal of Davidson High School, Jeffrey Jones encounters a series of events that become further complicated in light of his personal and professional relationships.
Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions.

Lymphoplasmacytic lymphoma (LPL) is characterized by t(9;14)(p13;q32) in 50% of patients who lack paraproteinemia. Waldenstrom macroglobulinemia (WM), which has an immunoglobulin M (IgM) paraproteinemia, is classified as an LPL. Rare reports have suggested that WM sometimes is associated with 14q23 translocations, deletions of 6q, and t(11;18)(q21;q21). We tested for these abnormalities in the clonal cells of WM patients. We selected patients with clinicopathologic diagnosis of WM (all had IgM levels greater than 1.5 g/dL). Southern blot assay was used to detect legitimate and illegitimate IgH switch rearrangements. In addition to conventional cytogenetic (CC) and multicolor metaphase fluorescence in situ hybridization (M-FISH) analyses, we used interphase FISH to screen for t(9;14)(p13;q32) and other IgH translocations, t(11;18)(q21;q21), and 6q21 deletions. Genomic stability was also assessed using chromosome enumeration probes for chromosomes 7, 9, 11, 12, 15, and 17 in 15 patients. There was no evidence of either legitimate or illegitimate IgH rearrangements by Southern blot assay (n = 12). CC (n = 37), M-FISH (n = 5), and interphase FISH (n = 42) failed to identify IgH or t(11;18) translocations. Although tumor cells from most patients were diploid for the chromosomes studied, deletions of 6q21 were observed in 42% of patients. In contrast to LPL tumors that are not associated with paraproteinemia and that have frequent t(9;14)(p13;q32) translocations, IgH translocations are not found in WM, a form of LPL tumor distinguished by IgM paraproteinemia. However, WM tumor cells, which appear to be diploid or near diploid, often have deletions of 6q21.
Microsatellite variation and fine‐scale population structure in the wood frog (Rana sylvatica)

We investigated genetic population structure in wood frogs (Rana sylvatica) from a series of Prairie Pothole wetlands in the northern Great Plains. Amphibians are often thought to exist in demographic metapopulations, which require some movement between populations, yet genetic studies have revealed strong subdivision among populations, even at relatively fine scales (several km). Wood frogs are highly philopatric and studies of dispersal suggest that they may exhibit subdivision on a scale of approximately 1-2 km. We used microsatellites to examine population structure among 11 breeding assemblages separated by as little as 50 m up to approximately 5.5 km, plus one population separated from the others by 20 km. We found evidence for differentiation at the largest distances we examined and among a few neighbouring ponds, but most populations were strikingly similar in allele frequencies, suggesting high gene flow among all but the most distant populations. We hypothesize that the few significant differences among neighbouring populations at the finest scale may be a transient effect of extinction-recolonization founder events, driven by periodic drying of wetlands in this hydrologically dynamic landscape.
In-cell SHAPE reveals that free 30S ribosome subunits are in the inactive state

It was shown decades ago that purified 30S ribosome subunits readily interconvert between “active” and “inactive” conformations in a switch that involves changes in the functionally important neck and decoding regions. However, the physiological significance of this conformational change had remained unknown. In exponentially growing Escherichia coli cells, RNA SHAPE probing revealed that 16S rRNA largely adopts the inactive conformation in stably assembled, mature 30S subunits and the active conformation in translating (70S) ribosomes. Inactive 30S subunits bind mRNA as efficiently as active subunits but initiate translation more slowly. Mutations that inhibited interconversion between states compromised translation in vivo. Binding by the small antibiotic paromomycin induced the inactive-to-active conversion, consistent with a low-energy barrier between the two states. Despite the small energetic barrier between states, but consistent with slow translation initiation and a functional role in vivo, interconversion involved large-scale changes in structure in the neck region that likely propagate across the 30S body via helix 44. These findings suggest the inactive state is a biologically relevant alternate conformation that regulates ribosome function as a conformational switch.
Current Status of Medical Grand Rounds in Departments of Medicine at US Medical Schools

OBJECTIVE To assess the status of medical grand rounds (MGR) as an educational endeavor. METHODS A survey of 133 departments of medicine at US medical schools was performed from September 2003 to March 2004; the results were compared with those of a previous (1988) survey. RESULTS Ninety-nine departments (74%) responded to the survey; all 99 conducted MGR. Providing updates in diagnosis, treatment, and medical research, educating house staff and faculty, and promoting collegiality were the most important objectives of MGR. Regarding objectives, responses to the current survey differed significantly from the responses to the 1988 survey for providing updates in medical research ( P =.047), providing continuing medical education credit ( P P =.048), and educating faculty ( P CONCLUSIONS Departments of medicine regard MGR as an important educational and social endeavor. However, most departments use suboptimal teaching, planning, and evaluation methods, and many rely on industry to pay for MGR. Addressing these concerns and other challenges may enhance the value of MGR.
TGFβ-mediated BIM expression and apoptosis are regulated through SMAD3-dependent expression of the MAPK phosphatase MKP2

Transforming growth factor-b (TGFb) induces the expression of the pro-apoptotic protein BIM, and mediates apoptosis in hepatocytes and B lymphocytes. BIM is regulated through a post-translational mechanism involving ERK-dependent phosphorylation and ubiquitin-mediated proteasomal degradation. Here, we show that TGFb induces BIM through its rapid inhibition of ERK, thereby preventing the phosphorylation and degradation of BIM. TGFb, through a SMAD3-dependent mechanism, transcriptionally induces the mitogen-activated protein kinase (MAPK) phosphatase MKP2, encoded by an immediate early gene, to attenuate ERK and promote the accumulation of BIM protein. Overexpression of MKP2 in hepatocytes modulates ERK-mediated phosphorylation of BIM and apoptosis in the absence of TGFb, whereas its ablation in pro-B cells, derived from MKP2-deficient mice, protects cells from TGFb-mediated apoptosis, and blocks TGFb-induced ERK inhibition and BIM induction. Furthermore, in pro-B cells derived from SMAD3-deficient mice, induction of MKP2 by TGFb, inhibition of ERK, induction of BIM and apoptosis do not occur. Our results indicate that MKP2 mediates TGFb-dependent apoptosis by linking SMAD3 to the modulation of ERK activity and mitochondrial-mediated pro-apoptotic events.
Individual Flexibility in the Workplace A Spatial Perspective

During the past few decades, scholars have undertaken numerous studies to map various determinants of flexibility at various levels: organizational, group, and individual. However, limited attention has been paid to the role of context and spatiality in realizing individual flexibility. This article aims to fill this gap and seeks to inquire into links between flexibility and spatiality. More specifically, this article will explore how organizational spatial layouts affect individual flexibility as everyday work activities are undertaken in the production of services in two settings, namely, health care and financial services. The findings show that spatial layout is important to better understand and conceptualize individual and organizational flexibility. The findings also show how spatial layout affords various and unexpected outcomes and that layouts that unilaterally foster flexibility are difficult to achieve due to the polymorphous nature of flexibility.
A Review on Fat Necrosis of the Breast: The Dilemma of Differential Diagnosis with Cancer

Fat necrosis is a benign inflammatory process which can involve adipose tissue anywhere in the body. A previous history of trauma or surgery may or may not be present. Information about the clinical and radiological appearance of this lesion is very important because it can mimic breast cancer.In this article, we review the features of fat necrosis in different imaging modalities including mammography, ultrasound, and magnetic resonance imaging (MRI), and compare them with histopathologic findings; then, we try to provide a logical approach for fat necrosis management.The appearance of fat necrosis at imaging is variable from definitely benign type to highly suspicious for malignancy. The specificity of mammography is higher than that of ultrasonography; therefore, for a definite diagnosis of fat necrosis, emphasis should be mainly based on mammography rather than ultrasonography.Finally, fat necrosis is not a common disease; however, regarding unusual and atypical findings in different imaging modalities, differentiation from a cancer may be difficult, especially in patients with a previous history of malignancy. Therefore, a multimodality approach is required for a definite diagnosis.
Developmental Trajectories of Suicidal Thoughts and Behaviors From Adolescence Through Adulthood

Objective Little is known about the patterns among individuals in the long-term course of suicidal thoughts and behaviors (STBs). The objective of this study was to identify developmental trajectories of STBs from adolescence through young adulthood, as well as risk and protective covariates, and nonsuicidal outcomes associated with these trajectories. Method A total of 180 adolescents (ages 12–18 years at recruitment) were repeatedly assessed over an average of 13.6 years (2,273 assessments) since their psychiatric hospitalization. Trajectories were based on ratings of STBs at each assessment. Covariates included psychiatric risk factors (proportion of time in episodes of psychiatric disorders, hopelessness, trait anxiety, impulsivity, and aggression in adulthood, sexual and physical abuse, parental history of suicidal behavior), protective factors (survival and coping beliefs, social support in adulthood, parenthood), and nonsuicidal outcomes (social adjustment and functional impairment in adulthood, school drop-out, incarcerations). Results Using a Bayesian group-based trajectory model, 4 trajectories of STBs were identified: an increasing risk class (11%); a highest overall risk class (12%); a decreasing risk class (33%); and a low risk class (44%). The 4 classes were associated with distinct patterns of correlates in risk and protective factors and nonsuicidal outcomes. Conclusion Adolescents and young adults have heterogeneous developmental trajectories of STBs. These trajectories and their covariates may inform strategies for predicting STBs and targeting interventions for individuals at risk for suicidal behavior.
Lesion of the nodulus and ventral uvula abolish steady-state off-vertical axis otolith response

1. During rotations that dynamically activate utricular and saccular primary afferents, the otolith system centrally detects the velocity and direction of rotation of the head in space. This property is experimentally manifested as a steady-state compensatory nystagmus during constant velocity off-vertical axis rotations. The computational, physiological, and anatomic details of this response remain presently unknown. Here we report that surgical inactivation of the cerebellar nodulus and ventral uvula abolished the ability of the otolith system to generate steady-state nystagmus during constant velocity rotation and to improve the dynamics of the vestibuloocular reflex (VOR) during low-frequency sinusoidal oscillations about off-vertical axes in rhesus monkeys. These results suggest that the cerebellar nodulus and/or ventral uvula comprise part of the neural substrate that is involved in these computations.
African Intermediaries and the ‘Bargain’ of Collaboration

The goal of this chapter is to examine the wider range of roles Africans played in the making of colonial legal and political orders. We recognize that Africans were employed in a wide range of service roles, including menial workers and skilled artisans, but our focus will be on those Africans who served as interpreters and administrative intermediaries. We have discovered a rich historical vein of insight and detail into the colonial experience through our focus on African intermediaries. What these intermediaries had in common was not only their strategic positions within the colonial edifice, but their centrality in the flows and circuits of information. These intermediaries controlled information and intelligence through their cross-cultural brokerage roles, which depended upon their knowledge of European languages and European cognitive categories. We want to stress the differences here: it was not enough for intermediaries to know European languages or African lingua franca, such as Kiswahili, Hausa, or Malinke, but they needed to master European cultural and legal categories to translate African experiences into terms that made sense to Europeans. As such, African intermediaries and interpreters lived in social worlds that straddled both African and European universes. These two worlds provided opportunities and challenges to those who tried to navigate them.
Applied dynamic system modeling - Six degree-of-freedom simulation of forced unsteady maneuvers using recursive neural networks

Techniques have been developed to computationally simulate six-degree-of-freedom forced unsteady maneuvers for a real vehicle using recursive neural network (RNN) technologies. The approach taken was to develop RNN 6-DOF maneuvering simulations using existing free-flight radio controlled model maneuvers. A modular design strategy was adopted which was comprised of component subsystems coupled within the recursive neural network architecture. In particular, semi-empirical component models for the propulsion and plane forces were developed. These time-varying models of the component forces were then coupled directly within the RNN 6-DOF algorithm. The RNN techniques are described in detail, and results using the combination of semi-empirical component models and RNN 6-DOF simulation techniques are described. It is concluded that RNN 6-DOF maneuvering simulations can provide accurate predictions of vehicle maneuvers, including maneuvers which are dominated by forced unsteady fluid dynamics. Across large numbers of maneuvers, the results indicate that these techniques provide accurate predictions for both maneuvers used to develop the RNN 6-DOF simulation and for validation maneuvers comprised of novel control sequences. (Author)
Body and the Arts: The Need for Somaesthetics

This essay shall consider how somaesthetics is related to the field of fine arts, though the scope of somaesthetics is indeed wider, extending into all practices of life in which we can enhance our perception and performance through improved somatic self-use and self-knowledge. It begins by clarifying the idea of somaesthetics and how it is needed to counterbalance the strong tendencies in modern aesthetics, beginning with its founder Alexander Baumgarten, to neglect or reject the body's role in aesthetic experience. Hegel, a crucial figure in this tradition, will be critically examined, specially as to his ranking of the arts in terms of their relation to material embodiment. Using his classificatory scheme heuristically to highlight the body's wide-ranging role in the different arts, it is argued that somaesthetics can improve our understanding and performance of that role.
Chapter 19 - Viral Vaccines: Fighting Viruses with Vaccines

Vaccines are biological preparations that stimulate protective immune responses against pathogens. They have had a profound impact on human health: decreasing illness, extending life spans, and improving quality of life. This chapter is based on the premise that vaccine-induced protection can best be understood in the context of viral pathogenesis, which identifies potential steps in the infectious process where immunity might intervene to prevent disease. Importantly, the pathogenesis of a specific viral disease helps to determine the immunobiological requirements for a vaccine to protect against that particular infection. We first describe the major vaccine modalities, with their strengths and limitations, followed by an analysis of the mechanisms of vaccine-induced protection as exemplified by a few of the best-studied vaccines. Finally, we explore the utility of systems approaches to vaccine characterization and development.
Predictors of Adverse Events for Ankle Fractures: An Analysis of 6800 Patients

Ankle fractures are one of the most common injuries seen by orthopedic surgeons. It is therefore essential to understand the risks associated with their treatment. Using the American College of Surgeons National Surgical Quality Improvement Program(®) database from 2006 to 2013, the patient demographics, comorbidities, and 30-day complications were collected for 5 types of ankle fractures. A bivariate analysis was used to compare the patient demographics, comorbidities, and complications across all Common Procedural Terminology codes. A multivariable logistic regression model was then used to assess the odds of minor and major postoperative complications within 30 days after open treatment. A total of 6865 patients were included in the analysis. Of these patients, 2507 (36.5%) had bimalleolar ankle fractures. The overall rate of adverse events for ankle fractures was low. Bimalleolar fractures had the greatest rate of major (2.6%, n = 64), minor (3.8%, n = 94), and total (5.7%, n = 143) complications. When controlling for individual patient characteristics, bimalleolar fractures were associated with 4.92 times the odds (95% confidence interval 1.80 to 13.5; p = .002) of developing a complication compared with those with a medial malleolar fracture. The risk factors driving postoperative complications for all ankle fractures were age >65 years, obesity, diabetes, American Society of Anesthesiologists score >2, and functional status (p < .05). Although the overall rate of adverse events for ankle fractures was low, bimalleolar fractures were associated with 5 times the odds of developing a complication compared with medial malleolar fractures. Orthopedic surgeons must be aware of the risk factors that increase the rate of ankle fracture complications to improve patients' quality of care.
#BlackLivesMatter: A Call for Transformative Leadership.

Michael Pelligrino is a novice principal in a large urban high school. After a rocky yet somewhat successful first year as the principal of Hilltop High School, tensions in the school and surrounding community are at an all-time high. The deaths of unarmed Black men, women, and children by law enforcement agents nationwide have led hundreds of students to participate in community-led protests aligned with the #BlackLivesMatter movement. Pelligrino is conflicted. Should he respond to the needs of his school community or continue to focus on district mandates? This case study provides opportunities for aspiring school leaders to engage in critical reflection and transformative leadership practices.
Phenotypic plasticity of leaves enhances water-stress tolerance and promotes hydraulic conductivity in a tall conifer

3 PREMISE OF THE STUDY: Leaves respond to environmental signals and acclimate to local conditions until their ecological limits are reached. Understanding the relationships between anatomical variation in leaves and the availability of water and light improves our ability to predict ecosystem-level impacts of foliar response to climate change, as it expands our knowledge of tree physiology. METHODS: We examined foliar anatomy and morphology of the largest plant species, Sequoiadendron giganteum , from leafy shoot samples collected throughout crowns of trees up to 95 m tall and assessed the functionality of within-crown variation with a novel drought/recovery experiment. KEY RESULTS: We found phenotypic variation in response to water availability in 13 anatomical traits of Sequoiadendron leaves. Shoot expansion was con- strained by the hydrostatic gradient of maximum water potential, while functional traits supporting succulence and toughness were associated with sites of peak hydraulic limitation. Water-stress tolerance in experimental shoots increased dramatically with height. CONCLUSION: We propose a heat-sink function for transfusion tissue and uncover a suite of traits suggesting rapid hydraulic throughput and fl exibility in water-stress tolerance investments as strategies that help this montane species reach such enormous size. Responses to water stress alter the amount of carbon stored in foliage and the rate of the eventual release of carbon.
Expanding the Undergraduate Marketing Curriculum: A Course in Marketing and Public Policy

Generally, the mix of courses offered in the marketing curriculum has changed as knowledge of marketing has advanced. However, a course in marketing and public policy is absent from many curricula. This paper examines the response of marketing educators to the need for an undergraduate course in marketing and public policy and presents a framework and suggested course outline for teaching an elective course in this important area.
Medication Considerations in Hypercalcemia and Hyperparathyroidism

Hypercalcemia associated with hydrochlorothiazide is a well-known clinical entity, likely due to an increased renal tubular reabsorption of calcium. However, it is estimated that approximately two-thirds of patients with thiazide-associated hypercalcemia have underlying primary hyperparathyroidism (PHPT). Persistence of hypercalcemia after more than 2 years of thiazide use and higher serum calcium and parathyroid hormone (PTH) levels at diagnosis suggest PHPT. Many commonly used medications can also influence calcium and PTH measurement in patients with PHPT, including estrogen, raloxifene, calcium, and vitamin D. A number of other commonly used medications can influence PTH and calcium measurements in patients without PHPT including numerous antihypertensive agents, aromatase inhibitors, estrogen, tenofovir, and several osteoporosis therapies.