cssi/SciSciGPT-SciSciNet huggingface dataset:
A phosphoethanolamine transferase specific for the outer 3-deoxy-D-manno-octulosonic acid residue of Escherichia coli lipopolysaccharide. Identification of the eptB gene and Ca2+ hypersensitivity of an eptB deletion mutant.

Abstract Addition of a phosphoethanolamine (pEtN) moiety to the outer 3-deoxy-d-manno-octulosonic acid (Kdo) residue of lipopolysaccharide (LPS) in WBB06, a heptose-deficient Escherichia coli mutant, occurs when cells are grown in 5–50 mm CaCl2 (Kanipes, M. I., Lin, S., Cotter, R. J., and Raetz, C. R. H. (2001) J. Biol. Chem. 276, 1156–1163). A Ca2+-induced, membrane-bound enzyme was responsible for the transfer of the pEtN unit to the Kdo domain. We now report the identification of the gene encoding the pEtN transferase. E. coli yhjW was cloned and overexpressed, because it is homologous to a putative pEtN transferase implicated in the modification of the β-chain heptose residue of Neisseria meningitidis lipo-oligosaccharide (Mackinnon, F. G., Cox, A. D., Plested, J. S., Tang, C. M., Makepeace, K., Coull, P. A., Wright, J. C., Chalmers, R., Hood, D. W., Richards, J. C., and Moxon, E. R. (2002) Mol. Microbiol. 43, 931–943). In vitro assays with Kdo2-4′-[32P]lipid A as the acceptor showed that YhjW (renamed EptB) utilizes phosphatidylethanolamine in the presence of Ca2+ to transfer the pEtN group. Stoichiometric amounts of diacylglycerol were generated during the EptB-catalyzed transfer of pEtN to Kdo2-lipid A. EptB is an inner membrane protein of 574 amino acid residues with five predicted trans-membrane segments within its N-terminal region. An in-frame replacement of eptB with a kanamycin resistance cassette rendered E. coli WBB06 (but not wild-type W3110) hypersensitive to CaCl2 at 5 mm or higher. Ca2+ hypersensitivity was suppressed by excess Mg2+ in the medium or by restoring the LPS core of WBB06. The latter was achieved by reintroducing the waaC and waaF genes, which encode LPS heptosyl transferases I and II, respectively. Our data demonstrate that pEtN modification of the outer Kdo protected cells containing heptose-deficient LPS from damage by high concentrations of Ca2+. Based on its sequence similarity to EptA(PmrC), we propose that the active site of EptB faces the periplasmic surface of the inner membrane.
Anemia and Transfusion in Critical Care: Physiology and Management

Objective:The objective of this report is to review the physiology and management of anemia in critical care. Selected publications on physiology and transfusion related to anemia and critical care...
Anomalous Westerlies, El Niño, and the Colonization of Polynesia

The west to east migration of the Polynesians and their Lapita predecessors was not accomplished by tacking against the prevailing southeast trade winds, but by using periodic westerly wind reversals to sail eastward. Data on equatorial westerlies and associated ocean current effects, including those gathered during recent El Nino events, are presented to indicate how these canoe voyagers were able to migrate so far into the Pacific.
Assessing the diagnostic accuracy of a sequence of tests.

We consider the assessment of the overall diagnostic accuracy of a sequence of tests (e.g. repeated screening tests). The complexity of diagnostic choices when two or more continuous tests are used in sequence is illustrated, and different approaches to reducing the dimensionality are presented and evaluated. For instance, in practice, when a single test is used repeatedly in routine screening, the same screening threshold is typically used at each screening visit. One possible alternative is to adjust the threshold at successive visits according to individual-specific characteristics. Such possibilities represent a particular slice of a receiver operating characteristic surface, corresponding to all possible combinations of test thresholds. We focus in the development and examples on the setting where an overall test is defined to be positive if any of the individual tests are positive ('believe the positive'). The ideas developed are illustrated by an example of application to screening for prostate cancer using prostate-specific antigen.
What Can You Do with That Degree?: College Major and Occupational Status of College Graduates over Time

While income inequality among college graduates is well documented, inequality in occupational status remains largely unexplored. We examine whether and how occupational specificity of college majors is related to college graduates' transition into the labor market and their subsequent occupational trajectories. Analyses of NLSY79 indicate that occupationally specific degrees are beneficial at the point of entry into the labor market but have the lowest growth in occupational status over time. Students earning credentials focusing on general skills, in contrast, begin in jobs with low occupational status but subsequently report the greatest growth. These findings illuminate specific ways in which educational and occupational systems interact and provide a novel approach for understanding inequality in labor market outcomes among college graduates.
Effect of disorder on the superfluid transition in two-dimensional systems

In recent experiments on thin {sup 4}He films absorbed to rough surfaces Luhman and Hallock [Phys. Rev. Lett. 93, 086106 (2004)] attempted to observe Kosterlitz-Thouless (KT) features of the superfluid-normal transition of this strongly disordered two-dimensional (2D) bosonic system. It came as a surprise that while peak of dissipation was measured for a wide range of surface roughness there were no indications of the theoretically expected universal jump of the areal superfluid density for the strongly disordered samples. We test the hypothesis that this unusual behavior is a manifestation of finite-size effects by numerical study of the corresponding 2D bosonic model with strong diagonal disorder. We demonstrate that the discontinuous features of the underlying KT transition are severely smoothed out for finite system sizes (or finite frequency measurements). We resolve the universal discontinuity of the areal superfluid density by fitting our data to the KT renormalization group equations for finite systems. In analogy to our simulations, we suggest that in experiments on strongly disordered 2D bosonic systems the very existence of the KT scenario can and should be revealed only from a proper finite-size scaling of the data (for {sup 4}He films finite-size scaling can be effectively controlled by themore » scaling of finite frequency of measurements). We also show relevance of our conclusions for a wider class of systems, such as superconducting granular films, Josephson junction arrays, and ultracold atomic gases, where similar difficulties appear in experiments designed to verify KT transition (especially in disordered cases)« less
Recent Changes in Climate and Forest Ecosystems

In recent decades, gradual warming over the long term has been punctuated by droughts that facilitate widespread ecological disturbances. Although no single event can be attributed to climate change, it is reasonable to infer that a permanently warmer climate will escalate disturbances, causing a much faster change in ecosystem structure and function than a gradual increase in warming. Various species of pine beetles have spread across large land areas in Alaska, the western United States, and southern United States, in some cases attacking tree species that have not experienced previous outbreaks. Area burned by wildfire has been especially high during the 2000s. A reduction in the quantity and persistence of snow in mountainous regions is affecting the hydrology of forest ecosystems and downstream water supply. Interactions of multiple disturbances and stressors may result in new combinations of species and ecosystem conditions for which there is no precedent in historical or paleoecological records. Rapid shifts in climate and disturbance may strain both the resilience of forest ecosystems and the capacity of social systems and management institutions. In the future, shifting the management focus from restoring systems to building resilience will be a more viable strategy for retaining key ecological functions and ecosystem services.
Vision loss after spinal fusion for scoliosis in a child with spinal cord injury.

Background: Vision loss after spinal surgery is a rare and devastating complication. Risk factors include patient age, operative time, estimated blood loss, and intraoperative fluid management. Chi...
Diagnosis and Management of Intra-abdominal Sepsis

Intra-abdominal infections are commonly encountered in the general medical/surgical intensive care unit (ICU). Perhaps the largest group of these patients has recently undergone or will shortly undergo some form of interventional procedure. There have been important advances in supportive care, diagnostic tools, anti-infective therapy, and interventional techniques; resulting in both improved care and new controversies in the management of these critically ill patients. Most notable is the role of routine non-invasive imaging for suspected intra-abdominal infections, its use in monitoring success of therapy, and the role of percutaneous or laparoscopic intervention to replace formal laparotomy. The continuing development of antibiotics has provided a novel opportunity for tailoring therapy to the requirements of the individual.
High Mobility Group Box 1 (HMGB1) Phenotypic Role Revealed with Stress

High mobility group box 1 (HMGB1) is an evolutionarily ancient protein that is present in one form or another in all eukaryotes. It fundamentally resides in the nucleus but translocates to the cytosol with stress and is subsequently released into the extracellular space. HMGB1 global knockout mice exhibit lethal hypoglycemia, whereas tissues and cells from conditional knockout or knock-in mice are born alive without apparent significant functional deficit. An aberrant response to targeted stress in the liver, pancreas, heart or myeloid cells is consistent with a protective role for HMGB1 in sustaining nuclear homeostasis and enabling other stress responses, including autophagy. Under some conditions, HMGB1 is not required for liver and heart function. Many challenges remain with respect to understanding the multiple roles of HMGB1 in health and disease.
Factors contributing to the integration of computer technology in classroom instruction

The purpose of this study was to determine what factors contribute to and what factors inhibit the integration of computer technology in classroom instruction in the middle school setting at selected schools in a central Virginia public school system. Information derived from this study may be used to assist in the planning and decision making process by central office and building level administrators. The population for this study included teachers from three middle schools in a central Virginia public school system. This school system has demonstrated through the Virginia Standards of Learning test scores, an even distribution of results regardless of demographics. A pilot study was conducted in the same school system. Participants completed a questionnaire, and a sample of participants was interviewed. The results were coded and chunked for the purpose of establishing an emerging theme or themes. There has been a wealth of quantitative data with regard to student to computer ratio and computer to classroom ratio over the last several years. However, there is scant data from a qualitative perspective that may allow for in-depth answers to questions regarding the factors that come into play as to the reasons for the use or non-use of available technology. Findings indicate that respondents appear to use computer technology for a range of personal reasons, yet are reluctant to use and integrate that technology into classroom instruction. In addition, thematic analysis revealed that time, access, and support appear to be major factors that inhibit the use and integration of computer technology in classroom instruction.
Synthesis, crystal structure and electrical properties of the tetrahedral quaternary chalcogenides CuM 2 InTe 4 (M=Zn, Cd)

Abstract Quaternary chalcogenides form a large class of materials that continue to be of interest for energy-related applications. Certain compositions have recently been identified as possessing good thermoelectric properties however these materials typically have the kesterite structure type with limited variation in composition. In this study we report on the structural, optical and electrical properties of the quaternary chalcogenides CuZn2InTe4 and CuCd2InTe4 which crystallize in the modified zinc-blende crystal structure, and compare their properties with that of CuZn2InSe4. These p-type semiconductors have direct band gaps of about 1 eV resulting in relatively high Seebeck coefficient and resistivity values. This work expands on the research into quaternary chalcogenides with new compositions and structure types in order to further the fundamental investigation of multinary chalcogenides for potential thermoelectrics applications.
Abstract 1794: Cross-regulation of polycomb group protein BMI1 and WNT inhibitors.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Polycomb group (PcG) proteins are evolutionarily conserved gene silencers, which determine cell fate decisions during development. These proteins are often aberrantly expressed in cancer cells. In particular, BMI1 and EZH2 are known to be overexpressed in a number of human malignancies including breast and prostate cancers. In vitro models of cancer development strongly support oncogenic role of overexpressed BMI1 in cancer and metastasis. BMI1 is known to be required for self-renewal of neural, hematopoietic, intestinal and mammary stem cells. In addition, BMI1 is downregulated in senescent cells, and this downregulation may contribute to age-related pathologies. BMI1 is also suspected to play a role in cancer stem cell development and increase stem cell-ness of tumors to promote drug resistance. Despite its role in cancer, stem cell phenotype, development and aging, very little is known about the signaling pathways that regulate the expression of BMI1. Here we report that BMI1 activates WNT pathway and upregulates its target genes such as Cyclin D1 and c-Myc. Using promoter-reporter assays, quantitative RT-PCR and Western blot analyses, we show that BMI1 auto-activates its expression via an E-box present in its promoter. Because auto-activation of BMI1 depends on E-box sequences present in its promoter, we hypothesized that BMI1 may regulate expression of c-Myc directly or indirectly via activation of WNT pathway. Indeed, our data suggest that BMI1 upregulated expression of c-Myc via activation of WNT pathway. Further dissection of this regulation revealed that BMI1 represses expression of WNT inhibitors, in particular DKK family of proteins such as DKK1, DKK2 and DKK3. Interestingly, we also found that DKK1 inhibits expression of BMI1, which also depends on E-box present in BMI1 promoter. Thus BMI1 and WNT inhibitors such as DKK1 cross-regulate each other's expression. We speculate that such regulation might favor BMI1 overexpression in cancer cells via increased WNT activity and c-Myc expression. On the other hand, increased expression of WNT inhibitors such as DKK1 might favor BMI1 downregulation in senescent and aged tissues. Thus, a fine tuned positive feedback loop controls BMI1 expression via WNT signaling pathway, and this feedback loop may be relevant to the role of BMI1 in cancer, stem cells and senescence. Citation Format: Joon-Ho Cho, Manjari Dimri, Goberdhan P. Dimri. Cross-regulation of polycomb group protein BMI1 and WNT inhibitors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1794. doi:10.1158/1538-7445.AM2013-1794
Palmitate metabolism and norepinephrine sensitivity in brown adipose, liver, and white adipose tissues of Zucker rats.

AbstractInterscapular brown adipose tissue (BAT) in vitro utilization of palmitate (0.5 mM) and glucose (5.0 mM) were examined at 0, 0.1, 1.0, and 10.0 μg norepinephrine-bitartrate (NE)/ml. With increasing NE concentrations, in vitro palmitate oxidation was stimulated and glucose oxidation was inhibited in BAT of nonobese rats. This characterization of BAT metabolism provided the constraints for our analysis of fatty acid utilization and norepinephrine sensitivity at submaximal response concentrations in BAT of lean and obese Zucker rats. Liver and inguinal white adipose were used for tissue comparisons. In comparison to its lean littermates, it was demonstrated that the obese rat: (i) had heavier interscapular BAT pads, (ii) oxidized a similar amount of palmitate to CO2 per 100 mg of BAT, (iii) oxidized more palmitate in response to NE stimulation of BAT, and (iiii) had slower rates of hepatic ketogenesis and palmitate oxidation. Altered palmitate oxidation or NE sensitivity in BAT was not contributing t...
Photoinduced Charge Transfer and Polaron Dynamics in Polymer and Hybrid Photovoltaic Thin Films: Organic vs Inorganic Acceptors

We use photoinduced absorption (PIA) spectroscopy to study charge generation and recombination in a series of bulk heterojunction blends relevant to organic and hybrid solar cells. We compare both organic and inorganic electron acceptors, including the fullerene, phenyl-C61-butyric acid methyl ester (PCBM), oxides such as ZnO and TiO2, and colloidal quantum dots, including CdSe and PbS nanocrystals. We use a variety of donor host polymers, including poly(3-hexylthiophene) (P3HT), poly[2-methoxy-5-(3′,7′-dimethyloctyloxy)-p-phenylenevinylene] (MDMO-PPV), and poly(2,3-bis(2-hexyldecyl)quinoxaline-5,8-diyl-alt-N-(2-hexyldecyl)-dithieno[3,2-b:2′,3′-d]pyrrole) (PDTPQx-HD). In every case, we measure longer average carrier lifetimes in blends with the inorganic acceptors as compared to blends with PCBM. The PIA data also suggest that the internal electric fields are attenuated in the inorganic blends, consistent with increased screening between the photogenerated carriers due to the higher dielectric constants o...
A Dynamic Model for Quantifying Rail–Highway Grade Crossing Roughness

Annually, more than 2,000 rail-highway crossing crashes in the United States result in nearly 300 fatalities. Crossing roughness is a concern for the motoring public from a comfort and vehicle maintenance perspective, and to highway authorities from a maintenance perspective. Roughness may even increase the risk of crossing crashes. However, with 216,000 rail-highway grade crossings in the United States, maintenance management is a large undertaking. Crossings deteriorate over time, sometimes rapidly, and life-cycle costs increase without preventive maintenance. However, though methods are available to quantify highway roughness, no method exists to quantitatively assess the condition of rail crossings. Because conventional inspection relies on qualitative judgment based on an inspector's perception of the crossing, effect on different vehicles and perception by other drivers are unknown. Further, roughness may be due to as-built geometry, deterioration, or a combination of both. A quantifiable and extensible procedure is thus desired. The article details the use of 3D surface models and a customized vehicle dynamic model to predict accelerations experienced by highway vehicles using the crossing. The model is validated with field-measured accelerations. RESULTS indicate good agreement between modeled and measured accelerations for a test vehicle at several speed ranges at two different locations. Language: en
SETI as a science

Interviews with pioneers in the search of extraterrestrial intelligence clarify questions about the nature of the search. Despite its ‘far out’ objective, it shares characteristics with other, more conventional activities which are considered to be “science”.
Effects of Volume, Pitch, and Phonation Type on Oscillation Initiation and Termination Phases Investigated With High-speed Videoendoscopy.

Summary Objectives This study aimed to investigate the effects of varying volume, pitch, and phonation types on the initiation and termination phases of vocal fold oscillation using high-speed digital videoendoscopy. Specifically, it addressed the effects of the variation of volume, pitch, and phonation type (normal, pressed, and breathy) on the transient duration of the vibrating glottal length (length transient duration, T len ), the transient duration of the glottal area waveform (area transient duration, T area ), the time offset between the beginning (or the end) of the full-length vibration and the full-amplitude vibration, T Δ , and the variation of the fundamental frequency during the vocal fold oscillation initiation and termination segments (pitch instability, %PI). Methods A female subject with no voice problem produced voices with varying pitch and loudness, including comfortable pitch and comfortable loudness, normal pitch loud, high pitch and comfortable loudness, and high pitch and loud. Breathy and pressed phonations were also recorded. Each of the six phonation types was recorded six times, which resulted in 72 transient segments (each recording included both initiation and termination phases). Mixed model statistical analyses were employed to the five objective high-speed digital videoendoscopy parameters. Results Preliminary findings demonstrated significant findings for voice type effects for the length and area transient durations for the oscillation initiation segment but not for the oscillation termination segment. Conclusions This study demonstrates that voice types appear to influence vibration initiation patterns more than the vibration termination patterns.
The route of administration influences the effect of estrogen on insulin sensitivity in postmenopausal women

Objective To determine the effect of transdermal estrogen on insulin sensitivity in postmenopausal women and to compare this effect with changes observed with oral conjugated equine estrogens. Design Fourteen postmenopausal women were randomized to receive a transdermal E 2 patch, 0.1mg, for 25days each month (n=7) or transdermal E 2 with added medroxyprogesterone acetate (MPA), 10mg, from days 16 to 25 each month (n=7). An insulin tolerance test (ITT) was performed at baseline and between days 23 and 25 during the 2nd month of treatment to assess insulin sensitivity. Values for the disappearance of glucose (K itt ) were calculated and compared with values obtained from women receiving 1.25mg of oral equine estrogens (n=8). Setting University Clinical Research Center. Patients Healthy postmenopausal women not receiving hormonal replacement. Intervention Insulin tolerance tests before and after treatment. Main Outcome Measure Disappearance of glucose and insulin (K itt ) before and after treatment. Results Women receiving transdermal E 2 alone demonstrated improved insulin sensitivity. The K itt glucose values increased by 13.2%, compared with a 23.9% decrease in K itt values observed with 1.25mg of conjugated equine estrogen. The group treated with transdermal E 2 and MPA had a reduction in insulin sensitivity. Insulin clearance was enhanced only with transdermal estrogen and was significantly delayed (blunted clearance) with the addition of MPA to transdermal E 2 and with oral estrogen. Conclusion We previously demonstrated a bimodal effect of oral equine estrogens on insulin sensitivity with an improvement occurring with the lower dose of 0.625mg but with a deterioration with the dose of 1.25mg. Here we suggest that this effect may be related to a first-pass hepatic-portal effect in that transdermal E 2 (0.1mg), which may be equated more closely with the larger dose of oral estrogen (1.25mg), improved insulin sensitivity. Progestin, however, appeared to attenuate the beneficial effects of transdermal estrogen and may alter the clearance of insulin.
The effects of pyridinolcarbamate on induced atherosclerosis in cynomolgus monkeys (Macaca ira).

Abstract Atherosclerosis was induced in cynomolgus monkeys ( Macaca iya ) fed on a semipurified diet containing 0.5% cholesterol. No differences in the extent of aortic or coronary atherosclerosis were observed when pyridinolcarbamate (2–6 pyridine-dimethanol-bis ( N -methylcarbamate)), was added to the diet at concentrations ranging from 400–2000 mg/kg food.
Team Emergence Leadership Development and Evaluation: A Theoretical Model Using Complexity Theory

This paper presents a leadership development model that is designed to utilise the self-organising, self-managing, and self-regulating functions found in teams and small groups. This theoretical paper presents the Team Emergence Leadership Development and Evaluation Model as a new dynamic leadership development model designed to function in complex and non-predictive environments. Complexity theory, complexity leadership theory, and emergence were utilised to connect this theoretical model to leadership development, team cognition and learning, and knowledge management. This new theoretical model provides a new way of viewing leadership development, by incorporating naturally occurring team processes as a means of replicating the characteristics traditionally viewed as being related to leadership development. Emergent events occur through distributed leadership among various agents and are defined by levels of meaning, providing new knowledge to the agents, and allowing for the collective to move onto the...
Comparing two periphyton collection methods commonly used for stream bioassessment and the development of numeric nutrient standards

Periphyton is an important component of stream bioassessment, yet methods for quantifying periphyton biomass can differ substantially. A case study within the Arkansas Ozarks is presented to demonstrate the potential for linking chlorophyll-a (chl-a) and ash-free dry mass (AFDM) data sets amassed using two frequently used periphyton sampling protocols. Method A involved collecting periphyton from a known area on the top surface of variably sized rocks gathered from relatively swift-velocity riffles without discerning canopy cover. Method B involved collecting periphyton from the entire top surface of cobbles systematically gathered from riffle-run habitat where canopy cover was intentionally avoided. Chl-a and AFDM measurements were not different between methods (p = 0.123 and p = 0.550, respectively), and there was no interaction between method and time in the repeated measures structure of the study. However, significantly different seasonal distinctions were observed for chl-a and AFDM from all streams when data from the methods were combined (p < 0.001 and p = 0.012, respectively), with greater mean biomass in the cooler sampling months. Seasonal trends were likely the indirect results of varying temperatures. Although the size and range of this study were small, results suggest data sets collected using different methods may effectively be used together with some minor considerations due to potential confounding factors. This study provides motivation for the continued investigation of combining data sets derived from multiple methods of data collection, which could be useful in stream bioassessment and particularly important for the development of regional stream nutrient criteria for the southern Ozarks.
FAS expression inversely correlates with the expression of PTEN and an Akt inhibitor synergizes with FAS siRNA to induce apoptosis in prostate cancer cells

2260 Fatty Acid Synthase (FAS), a key enzyme of the fatty acid biosynthetic pathway, has been shown to be overexpressed in various types of human cancer, and is therefore, considered to be an attractive target for anti-cancer therapy. However, relatively little is known about the regulatory mechanisms of the FAS gene in human tumor, and understanding these mechanisms is of paramount interest to design intervention of the FAS enzymatic pathway. Thus far, several factors including androgen, epidermal growth factor (EGF), PTEN and p53 have been demonstrated to modulate the expression of the FAS gene in vitro , however, none of these results have been validated in the clinical setting. In the present study, by immunohistochemical analysis of 81 prostate cancer specimens, we demonstrate that expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression in vivo . Furthermore, we used siRNA to inhibit the PTEN gene expression in vitro and found that knocking down the PTEN gene leads to overexpression of FAS in vitro . Together, these results suggest that the tumor suppressor gene, PTEN, negatively regulates the expression of the FAS gene. Our immunohistochemical analysis followed by Cox regression analysis also revealed that the combination of PTEN and FAS gene expression was an independent prognostic marker for prostate cancer. These data underscore the prognostic importance of combination of the FAS and PTEN genes, and also point toward the clinical relevance of the PTEN-FAS pathway in prostate tumorigenesis. As an initial trial for therapeutic targeting, we also used siRNA specific to the FAS gene in vitro . Our results indicated that the treatment of prostatic tumor cells with FAS siRNA leads to growth inhibition followed by apoptosis. Furthermore, in order to explore the possibility that the PTEN signaling pathway can be utilized to synergize the FAS siRNA mediated apoptosis, we introduced FAS siRNA and PI3K inhibitor into prostate cancer cells, and found that the PI3K inhibitor indeed synergized the effect of siRNA leading to tumor cell death. These results provide a strong rationale for exploring the therapeutic use of an inhibitor of the PTEN signaling pathway in conjunction with the FAS siRNA to inhibit prostate tumor growth.
Two-Element Transcriptional Regulation in the Canonical Wnt Pathway

The canonical Wnt pathway regulates numerous fundamental processes throughout development and adult physiology and is often disrupted in diseases [1; 2; 3 ; 4]. Signal in the pathway is transduced by β-catenin, which in complex with Tcf/Lef regulates transcription. Despite the many processes that the Wnt pathway governs, β-catenin acts primarily on a single cis element in the DNA, the Wnt-responsive element (WRE), at times potentiated by a nearby Helper site. In this study, working with Xenopus, mouse, and human systems, we identified a cis element, distinct from WRE, upon which β-catenin and Tcf act. The element is 11 bp long, hundreds of bases apart from the WRE, and exhibits a suppressive effect. In Xenopus patterning, loss of the 11-bp negative regulatory elements (11-bp NREs) broadened dorsal expression of siamois. In mouse embryonic stem cells, genomic deletion of the 11-bp NREs in the promoter elevated Brachyury expression. This reveals a previously unappreciated mechanism within the Wnt pathway, where gene response is not only driven by WREs but also tuned by 11-bp NREs. Using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP), we found evidence for the NREs binding to β-catenin and Tcf—suggesting a dual action by β-catenin as a signal and a feedforward sensor. Analyzing β-catenin ChIP sequencing in human cells, we found the 11-bp NREs co-localizing with the WRE in 45%–71% of the peaks, suggesting a widespread role for the mechanism. This study presents an example of a more complex cis regulation by a signaling pathway, where a signal is processed through two distinct cis elements in a gene circuitry.
Metallic nanoislands on graphene: a metamaterial for chemical, mechanical, optical, and biological applications

Graphene decorated with metallic nanoparticles exhibits electronic, optical, and mechanical properties that neither the graphene nor the metal possess alone. These composite films have electrical conductivity and optical properties that can be modulated by a range of physical, chemical, and biological signals. Such properties are controlled by the morphology of the nanoisland films, which can be deposited on graphene using a variety of techniques, including in situ chemical synthesis and physical vapor deposition. These techniques produce non-random (though loosely defined) morphologies, but can be combined with lithography to generate deterministic patterns. Applications of these composite films include chemical sensing and catalysis, energy storage and transport (including photoconductivity), mechanical sensing (using a highly sensitive piezroresistive effect), optical sensing (including so-called “piezoplasmonic” effects), and cellular biophysics (i.e. sensing the contractions of cardiomyocytes and myoblasts).
The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project:

Objectives:Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emer...
Racial and Sexual Objectification of Asian American Women: Associations with Trauma Symptomatology, Body Image Concerns, and Disordered Eating

Sexism and racism often imbue Asian American women’s socialization experiences. Operating from an objectification theory framework, the present article (a) examines the conceptual relevance of raci...
Consequences of tuning network function by tonic and phasic locus coeruleus output and stress: Regulating detection and discrimination of peripheral stimuli.

Abstract Flexible and adaptive behaviors have evolved with increasing complexity and numbers of neuromodulator systems. The neuromodulatory locus coeruleus-norepinephrine (LC-NE) system is central to regulating cognitive function in a behaviorally-relevant and arousal-dependent manner. Through its nearly ubiquitous efferent projections, the LC-NE system acts to modulate neuron function on a cell-by-cell basis and exert a spectrum of actions across different brain regions to optimize target circuit function. As LC neuron activity, NE signaling, and arousal level increases, cognitive performance improves over an inverted-U shaped curve. Additionally, LC neurons burst phasically in relation to novel or salient sensory stimuli and top-down decision- or response-related processes. Together, the variety of LC activity patterns and complex actions of the LC-NE system indicate that the LC-NE system may dynamically regulate the function of target neural circuits. The manner in which neural networks encode, represent, and perform neurocomputations continue to be revealed. This has improved our ability to understand the optimization of neural circuits by NE and generation of flexible and adaptive goal-directed behaviors. In this review, the rat vibrissa somatosensory system is explored as a model neural circuit to bridge known modulatory actions of NE and changes in cognitive function. It is argued that fluid transitions between neural computational states reflect the ability of this sensory system to shift between two principal functions: detection of novel or salient sensory information and detailed descriptions of sensory information. Such flexibility in circuit function is likely critical for producing context-appropriate sensory signal processing. Nonetheless, many challenges remain including providing a causal link between NE mediated changes in sensory neural coding and perceptual changes, as well as extending these principles to higher cognitive functions including behavioral flexibility and decision making.
Characterization of Lubricating Oils by Differential Scanning Calorimetry

The oxidative stability of formulated lubricating oils, and virgin and re-refined lubricating base stocks, have been determined by high pressure differential scanning calorimetry. Data on the response of re-refined and virgin base stocks to fixed quantities of an additive have been obtained. They are indicative of the wide diversity of the substances in question. The results of these studies indicate that the induction period measurements yield important information on the response of base stocks to additive treatment which could be used in quality control for formulating lubricating oils. Further studies are, however, needed to obtain more definite conclusions.
The structure of SDS22 provides insights into the mechanism of heterodimer formation with PP1.

Protein phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets by associating with nearly 200 regulatory proteins to form highly specific holoenzymes. The vast majority of regulators are intrinsically disordered proteins (IDPs) and bind PP1 via short linear motifs within their intrinsically disordered regions. One of the most ancient PP1 regulators is SDS22, a protein that is conserved from yeast to mammals. Sequence analysis of SDS22 revealed that it is a leucine-rich repeat (LRR) protein, suggesting that SDS22, unlike nearly every other known PP1 regulator, is not an IDP but instead is fully structured. Here, the 2.9 A resolution crystal structure of human SDS22 in space group P212121 is reported. SDS22 adopts an LRR fold with the horseshoe-like curvature typical for this family of proteins. The structure results in surfaces with distinct chemical characteristics that are likely to be critical for PP1 binding.
Nonverbal synchrony as a behavioural marker of patient and physician race-related attitudes and a predictor of outcomes in oncology interactions: protocol for a secondary analysis of video-recorded cancer treatment discussions.

Introduction Racial disparities in cancer treatment contribute to racial disparities in mortality rates. The quality of patient–physician communication during clinical interactions with black patients and non-black physicians (racially discordant) is poorer than communication quality with white patients (racially concordant). Patient and physician race-related attitudes affect the quality of this communication. These attitudes are likely expressed through subtle non-verbal behaviours, but prior research has not examined these behaviours. Nonverbal synchrony, the coordination of physical movement, reflects the preinteraction attitudes of participants in interactions and predicts their postinteraction perceptions of and affect towards one another. In this study, peer reviewed and funded by the National Institute of Minority Health and Health Disparities (R21MD011766), we will investigate non-verbal synchrony in racially concordant and discordant interactions to better understand racial disparities in clinical communication. Methods and analysis This secondary analysis includes racially concordant (n=163) and racially discordant (n=68) video-recorded oncology interactions, patient and oncologist self-reported race-related attitudes, perceptions of the interaction and observer ratings of physician patient-centred communication and patient and physician affect and rapport. In aim 1, we will assess and compare non-verbal synchrony between physicians and patients in racially concordant and discordant interactions. In aim 2, we will determine the influence of non-verbal synchrony on patient and physician affect and communication. In aim 3, we will examine possible causes (ie, race-related attitudes) and consequences (ie, negative perceptions) of non-verbal synchrony in racially discordant interactions. In aim 4, we will develop and test a mediational model linking physician and patient race-related attitudes to non-verbal synchrony and, in turn, interaction outcomes. Ethics and dissemination The parent and current studies were approved by the Wayne State University Institutional Review Board. Since only archival data will be used, ethical or safety risks are low. We will disseminate our findings to relevant conferences and journals.
The Risk of Regional Governance: Cultural Theory and Interlocal Cooperation

Creating metropolitan regions that are more efficient, equitable, and sustainable depends on the willingness of local officials to work together across municipal boundaries to solve large-scale problems. How do these local officials think? Why do they only sometimes cooperate? What kind of governance do they choose in the face of persistent problems? The Risk of Regional Governance offers a new perspective on these questions. Drawing on theory from sociology and anthropology, it argues that many of the most important cooperative decisions local officials make—those about land use planning and regulation—are driven by heuristic, biased reasoning driven by cultural values. The Risk of Regional Governance builds a sociocultural collective action framework, and supports it with rich survey and interview data from hundreds of local elected officials serving in the suburbs of Detroit and Grand Rapids, Michigan. It is a story of the Rust Belt, of how local officials think about their community and the region, and—most importantly—of how we might craft policies that can overcome biases against regional governance.
Effects of Parental Opioid Use: Outcomes of Children of Parents in Medication-Assisted Treatment Compared to Healthy Controls

Background Opioid use is a significant national crisis impacting individuals struggling with addiction and their families. The majority of individuals who abuse opioids are of child-rearing age, and critical knowledge gaps remain regarding how this abuse impacts their offspring. Fortunately, treatment for opioid use disorders is available. The primary goal of this study was to evaluate both physical and psychiatric diagnoses of children who have at least 1 parent participating in a buprenorphine-assisted treatment program. Methods This retrospective study is based on chart review (January 1, 2010, through June 30, 2018). Children with parents receiving care in a buprenorphine clinic were identified and matched on sex, race, and age in a ratio of 1:5 with controls from the general pediatric clinic population. Data related to health outcomes were extracted from the medical records. Results Compared to controls (n = 120), children of parents receiving buprenorphine-assisted treatment (n = 24) were more likely to have been born premature (odds ratio [OR] = 3.3, P = .035), had jaundice after birth (OR = 2.7, P = .034), had enuresis/encopresis (P < .001), and had been the victims of abuse or neglect (OR = 19.7, P = .0005). Children of parents with opioid use disorders were also more likely to utilize emergency services (ie, being seen in the emergency department for fussiness; OR = 4.0, P = .046) and were less likely to be covered by private insurance compared to state-funded insurance (OR = 0.2, P = .0013). Conclusions Parental opioid use disorder impacts children. More research is needed to better describe long-term effects of treatment of parental opioid use on their offspring and to help design addiction treatment programs to support whole family units.
Multiinstitutional U.S. Academic Radiology Perspectives on Inpatient Diagnostic Imaging of Patients With Coronavirus Disease (COVID-19) and Persons Under Investigation.

OBJECTIVE. This article presents the perspectives of radiologists in different sub-specialties at three institutions across the United States regarding inpatient imaging of patients confirmed to ha...
Radiculomedullary arterial contributions to the thoracolumbar spinal cord: an angiographic study.

Background Anterior and posterior spinal arteries (ASA, PSA) receive vital collateral flow from radiculomedullary arteries (RM). The purpose of this study was to review a series of spinal angiograms in order to characterize normal RM arterial anatomy. Methods The reports of digital subtraction spinal angiograms from consecutive patients from our institution from 2002-2019 were retrospectively reviewed. The RM contributions to both the ASA and PSA were characterized by noting laterality, spinal level and multiplicity. Results 336 spinal angiograms from 336 patients were included. Regarding RM input to the ASA, 328 patients (97.6%) had at least one RM contribution to the ASA. 46 patients (46/328 = 14.1%) had multiple RM ASA contributions. 381 total RM with input to the ASA were visualized. 95 RM of the ASA (95/381 = 24.9%) were located on the right, 286 (75.1%) on the left. 324 RM arteries (85.0%) arose between T8 and L2: 246 (64.5% overall) were located on the left, and 78 (20.5%) on the right. 61 patients (18.2%) had at least one visualized RM contribution to the PSA: 16 patients (16/61 = 26.2%) had more than one RM contribution to the PSA. 87 total RM contributions to the PSA were visualized. 81 (93.1%) RM arose between T6 and L1, 52 of which (59.8% overall) were from the left, and 29 (33.3%) from the right. Conclusions Radiculomedullary anastomoses with both the ASA and PSA most-commonly originate from the left-sided T6-L2 spinal levels. Multiple RM contributions to the ASA or PSA are less common.
Extraction of ground clutter return interference from downward-looking UWB radar signal

Ultra-wideband (UWB) ground-penetrating radar (GPR) technology has been widely employed for detecting targets that range from buried explosive devices such as landmines, improvised explosive devices (IEDs), to underground utilities and tunnels, etc. However, the backscatter signals from the ground surface pose a critical challenge for downward-looking GPR systems since (i) these ground return signals have significant power compared to the backscatter signal from subsurface targets, and (ii) the ground return and target signals completely overlap in both the time and frequency domains. Many techniques have been proposed to date; however, they all have limitations in mitigating the adverse effects of the very high power ground return interference (GRI) signals. This paper presents a novel technique for reconstructing and extracting the GRI signals from downward-looking UWB GPR signals. Our proposed technique performs an estimation of the return signal from the ground surface. This signal estimation, together with the estimated scatter center of the ground surface, is used to construct a dictionary that represents the ground return signal subspace. Finally, we employ a sparsity-driven optimization algorithm to reconstruct the GRI signals and then extract them from the received radar signals. All information used to construct the dictionary is completely derived from the data. Our technique performs this GRI extraction directly in the phase history data domain prior to synthetic aperture radar (SAR) image formation. Thus, it can be implemented as an additional step, completely independent from all other steps, in the pre-processing stage. Recovery results from simulated data set illustrate the robustness and effectiveness of our proposed technique.
Obesity as a Risk Factor for Severe Illness From COVID-19 in the Pediatric Population

In this current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many studies have been published to determine the spectrum of illness, risk factors, prevention, and treatment strategies. Due to relatively fewer cases among children as compared to adults, there is a paucity of clinical data available to fully understand the risk factors and disease course in the pediatric population. Our understanding is evolving with limited data showing an increased risk of severe or critical disease in children less than one year of age and those with certain underlying medical conditions. Recognition of emerging risk factors for morbidity and mortality is now paramount, to anticipate and provide appropriate clinical care specific to the pediatric population. Obesity has only recently been identified as a risk factor for severe COVID-19 disease in children. Case reports such as this are essential in understanding the pathophysiologic association, associated disease severity, and clinical outcome attributed to obesity and COVID-19 infections in children.