cssi/SciSciGPT-SciSciNet huggingface dataset:
Human Integrin β3 Gene Expression: Evidence for a Megakaryocytic Cell-Specific cis-Acting Element

The human integrin β3 participates in a wide range of adhesive biologic functions and is expressed in a selected subset of tissues, but little is known about the cis -acting DNA elements or trans -acting factors responsible for this regulation. Using cell lines characterized for β3 expression, a number of upstream regulatory regions in the β3 gene were identified. (1) The three regions from −1159 to −584, −290 to −146, and −126 to −115 demonstrated positive, negative, and negative activity, respectively. (2) The region from −115 to +29 of the β3 gene was sufficient for cell-specific activity. Deletion of the sequence from −115 to −89 produced a 6- to 40-fold reduction in reporter gene activity in β3-expressing megakaryocytic cell lines (K562, Dami, and HEL), but only a 1.7- and 2.7-fold reduction, respectively, in β3-expressing endothelial and melanoma cell lines, and 1.3- and 2.8-fold reduction, respectively, in non–β3-expressing Chinese hamster ovary and 293 cell lines. This sequence also bound nuclear proteins in a cell-specific manner in electrophoretic mobility shift assays. Mutational analysis indicated that the sequence GAGGGG (positions −113 to −108) is a megakaryocytic cell line-specific cis -acting element. (3) The region from −89 to +29 promoted lower activity in all cell lines. We also provide evidence that a CCCACCC sequence at position −70 has transcriptional activity, most likely through the Sp1 transcription factor. These data supply the first detailed map of the transcriptional regulatory elements of the 5′ region of the β3 gene, define positive regulatory sequences with potent megakaryocyte preferential activity, and indicate that the ubiquitous transcription factor, Sp1, may augment β3 gene expression. © 1998 by The American Society of Hematology.
Breeding of a Photo-thermo Sensitive Genie Male Sterile Indica Rice Zhongzi S with a Purple-leaf Marker and the Hoterosis of Its Hybrid Rice Produced with It

Photo-thermo sensitive genie male sterile indica rice(PGMR) with leaf color marker is more advantageous than those without marker in hybrid seed production by two-lines method when abnormal summer low temperature occurs. An indica PGMR rice, Zhongzi S with purple-leaf marker was developed by incorporating a recessive gene controlling purple leaf into a ther-moperiod sensitive genie male sterile (TGMR) indica rice W6154S by backcrossing. It was shown that under natural condition of Hangzhou (30°05'N), Zhongzi S was completely male sterile for over 25 days in summer. Further study of Zhongzi S in phytotrons with 3 photoperiods (P)×3 temperture (T) treatmemts showed that under high temperature (30. 1 ℃ ) Zhongzi S had complete or high male sterility with all photoperiods (15. 0 h, 14. 0 h and 12. 5 h). Variance analysis of the seed setting of Zhongzi S indicated that its photoperiod (P) effect is not significant, but its temperature (T) and PXT effect is significant. F1 hybrids of Zhongzi S with 15 va- rieties of 3 types of indica, japonica and intermedicate showed that Zhongzi S has good combining ability.
GLI Transcription Factors Modulate IgM Secretion In Waldenström Macroglobulinemia

Elevated immunoglobulin (Ig) secretion by malignant cells is a characteristic feature of several malignancies including Waldenstrom macroglobulinemia (WM), where elevated IgM is associated with significant morbidity and poor prognosis. Thus, the identification and characterization of the mechanisms controlling Ig secretion are of great importance for the development of future therapeutic approaches for these diseases. Here, we defined a novel pathway involving the oncogenic GLI transcription factors modulating IgM secretion by WM malignant cells. Initial screening of molecules involved in Ig secretion identified components of the Hedgehog-GLI pathway as modulators of this cellular process. Inhibition of smoothened (SMO), the signaling component of the Hedgehog receptor, with the pharmacological inhibitor cyclopamine had no effect on cell proliferation by XTT assay. Cyclopamine inhibition had no effect on cell viability by Annexin V/Propidium Iodide staining, but had a modest in IgM secretion by ELISA in BCWM.1 but not in MWCL-1 and RPCI-WM1 cells. Interestingly, pharmacological inhibition of GLI proteins (GLI1, 2 and 3), downstream effectors of the pathway, using GANT61 reduced the expression of GLI1 and GLI2 and had no effect on cell proliferation or viability. However, it resulted in a significant reduction in IgM secretion (40-60%) in BCWM.1 (p=0.0030), MWCL (p=0.0206) and RPCI-WM1 (p=0.0303) cells. Validation of these results using RNAi showed that out of the three GLI transcription factors, only GLI2 knockdown impaired IgM secretion by BCWM.1 (p=0.0415) and MWCL-1 (p=0.0075) cells. To further characterize the mechanism of regulation of IgM secretion by GLI2, we screened for pathways that are known to modulate Ig secretion. We identified the IL-6 receptor (IL-6R) alpha subunit as a potential mechanism mediating GLI2-IgM axis. Treatment of B-cells with GANT61 resulted in reduced IL-6R expression. Furthermore, overexpression of GLI2 in B-cells increased IL-6R expression. Conversely, GLI2 knockdown reduced IL-6R expression suggesting the involvement of IL-6R in GLI2 mediated regulation of IgM secretion. Taken together, these results identify a novel role for GLI proteins, particularly GLI2, as modulators of IgM secretion by malignant B-cells. Therefore therapies targeting this signaling axis may provide efficacy in patients with Ig-mediated diseases. Disclosures: No relevant conflicts of interest to declare.
Development of a Mouse Model for the Study of Human Purine Metabolism

Patients with Down syndrome are known to be hyperuricemic and this condition is thought to result from the over-production of purines (Pant et al., 1968). Only one purine metabolism gene is located on human chromosome 21 in the critical region associated with Down syndrome. This gene encodes for the trifunctional protein composed of phosphoribosylglycinamide synthetase (GARS), phosphoribosylglycinamide transformylase (GART) and phosphoribosylaminoimidazole synthetase (AIRS). Increased levels of this protein, known collectively as GART, have also been observed in the cultured fibroblasts of Down Syndrome patients (Scoggin et al., 1980) It is therefore highly likely that the increased levels of purines described in these patients is directly due to their over-expression of the GART trifunctional protein.
Synthesizing Compound Words for Machine Translation

Most machine translation systems construct translations from a closed vocabulary of target word forms, posing problems for translating into languages that have productive compounding processes. We present a simple and effective approach that deals with this problem in two phases. First, we build a classifier that identifies spans of the input text that can be translated into a single compound word in the target language. Then, for each identified span, we generate a pool of possible compounds which are added to the translation model as “synthetic” phrase translations. Experiments reveal that (i) we can effectively predict what spans can be compounded; (ii) our compound generation model produces good compounds; and (iii) modest improvements are possible in end-to-end English‐German and English‐Finnish translation tasks. We additionally introduce KomposEval, a new multi-reference dataset of English phrases and their translations into German compounds.
Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4

Aquaporin-4 (AQP4)-specific T cells are expanded in neuromyelitis optica (NMO) patients and exhibit Th17 polarization. However, their pathogenic role in CNS autoimmune inflammatory disease is unclear. Although multiple AQP4 T-cell epitopes have been identified in WT C57BL/6 mice, we observed that neither immunization with those determinants nor transfer of donor T cells targeting them caused CNS autoimmune disease in recipient mice. In contrast, robust proliferation was observed following immunization of AQP4-deficient (AQP4-/-) mice with AQP4 peptide (p) 135-153 or p201-220, peptides predicted to contain I-Ab-restricted T-cell epitopes but not identified in WT mice. In comparison with WT mice, AQP4-/- mice used unique T-cell receptor repertoires for recognition of these two AQP4 epitopes. Donor T cells specific for either determinant from AQP4-/-, but not WT, mice induced paralysis in recipient WT and B-cell-deficient mice. AQP4-specific Th17-polarized cells induced more severe disease than Th1-polarized cells. Clinical signs were associated with opticospinal infiltrates of T cells and monocytes. Fluorescent-labeled donor T cells were detected in CNS lesions. Visual system involvement was evident by changes in optical coherence tomography. Fine mapping of AQP4 p201-220 and p135-153 epitopes identified peptides within p201-220 but not p135-153, which induced clinical disease in 40% of WT mice by direct immunization. Our results provide a foundation to evaluate how AQP4-specific T cells contribute to AQP4-targeted CNS autoimmunity (ATCA) and suggest that pathogenic AQP4-specific T-cell responses are normally restrained by central tolerance, which may be relevant to understanding development of AQP4-reactive T cells in NMO.
Genomic analysis of exceptional responders to radiotherapy reveals somatic mutations in ATM.

// Jennifer Ma 1 , Jeremy Setton 1 , Luc Morris 2 , Pedro Blecua Carrillo Albornoz 1 , Christopher Barker 1 , Benjamin H. Lok 1 , Eric Sherman 3 , Nora Katabi 4 , Kathryn Beal 1 , Ian Ganly 2 , Simon N. Powell 1 , Nancy Lee 1 , Timothy A. Chan 1, 5 , Nadeem Riaz 1 1 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 2 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA 3 Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 4 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 5 Human Oncology and Pathogenesis, Memorial Sloan Kettering Cancer Center, New York, NY, USA Correspondence to: Nadeem Riaz, email: riazn@mskcc.org Timothy A. Chan, email: chant@mskcc.org Keywords: somatic ATM mutations, radiation therapy Received: May 24, 2016 Accepted: November 30, 2016 Published: December 31, 2016 ABSTRACT Radiation therapy is a mainstay of cancer treatment, yet the molecular determinants of clinical response are poorly understood. We identified exceptional responders to radiotherapy based on clinical response, and investigated the associated tumor sequencing data in order to identify additional patients with similar mutations. Among head and neck squamous cell cancer patients receiving palliative radiotherapy at our institution, we identified one patient with documented complete metabolic response. Targeted sequencing analysis of the tumor identified a somatic frame-shift mutation in ATM , a gene known to be associated with radio-sensitivity in the germline. To validate the association of somatic ATM mutation with radiotherapy response, we identified eight patients with ATM truncating mutations who received radiotherapy, all of whom demonstrated excellent responses with a median local control period of 4.62 years. Analysis of 22 DNA repair genes in The Cancer Genome Atlas (TCGA) data revealed mutations in 15.9% of 9064 tumors across 24 cancer types, with ATM mutations being the most prevalent. This is the first study to suggest that exceptional responses to radiotherapy may be determined by mutations in DNA repair genes. Sequencing of DNA repair genes merits attention in larger cohorts and may have significant implications for the personalization of radiotherapy.
In vivo three-photon activity imaging of GCaMP6-labeled neurons in deep cortex and the hippocampus of the mouse brain

We demonstrate that three-photon microscopy (3PM) with 1300-nm excitation enables functional imaging of GCaMP6s labeled neurons beyond the depth limit of two-photon microscopy (2PM) with 920-nm excitation. We quantitatively compared 2PM and 3PM imaging of calcium indicator GCaMP6s by measuring correlation between activity traces, absolute signal level, excitation attenuation with depth, and signal-to-background ratio (SBR). Compared to 2PM imaging of GCaMP6s-labeled neurons, 3PM imaging has increasingly larger advantages in signal strength and SBR as the imaging depth increases in densely labeled mouse brain, given the same pulse energy, pulse width, and repetition rate at the sample surface. For example, 3PM has comparable signal strength as 2PM and up to two orders of magnitude higher SBR as 2PM in mouse cortex around 700-800um. We also demonstrate 3PM activity recording of 150 neurons in the hippocampal stratum pyramidale (SP) at 1mm depth, which is inaccessible to non-invasive 2PM imaging. Our work establishes 3PM as a powerful tool for calcium imaging at the depth beyond 2PM limits.
Role of receptor coupling to phosphoinositide metabolism in the therapeutic action of lithium.

Lithium is one of the most effective psychopharmacological treatments for affective illness and offers a potential avenue for furthering our understanding of the neurobiological components of this disorder. Among the most specific and potent actions of lithium is its ability to not only treat the acute episode of mania but also reduce the frequency and severity of recurrent episodes of mania and depression in bipolar patients and depression in unipolar patients (Bunney and Garland, 1984). Thus, the unique action of lithium appears to be its long-term ability to dampen pathological neurobiological oscillations in individuals vulnerable to profound cyclic affective disturbances.
A Novel Apremilast Nail Lacquer Formulation for the Treatment of Nail Psoriasis

The objective was to prepare a novel nail lacquer formulation to improve the ungual and trans-ungual delivery of apremilast for the potential treatment of nail psoriasis. Nail lacquer formulation was prepared using Eudragit® S 100 as a film-forming polymer and the mixture of ethanol, ethyl acetate, and water as a solvent system. As a result of high-throughput screening studies, dexpanthenol and salicylic acid were found to be the potential penetration enhancers. After 7 days of in vitro studies, the cumulative amount of apremilast delivered by the nail lacquer formulation across the nail plate was found to be ~3-fold (0.52 ± 0.07 μg/cm2) more compared to control (nail lacquer formulation without enhancers) (0.19 ± 0.02 μg/cm2). The cumulative amount of apremilast retained in the nail plate in the case of nail lacquer formulation was 1.26 ± 0.18 μg/mg which was found to be ~2-fold more compared to control (0.57 ± 0.07 μg/mg). Human subject studies were performed on the nails of thumb and index finger of six volunteers for 15 days. As a result, the cumulative amount of apremilast retained in the free distal edge of the nail plate in the case of nail lacquer was found to be ~2-fold (0.93 ± 0.14 μg/mg) more related to control (0.41 ± 0.04 μg/mg). As a conclusion, nail lacquer formulation was found to be capable of delivering a substantial amount of apremilast into the nail apparatus; thus, it can be a potential option for the treatment of nail psoriasis.
On Future Automated Ground Transport--Individual Vehicle Longitudinal Control

EXTRAIT La realisation d’un controle longitudinal sur et efficace est probablement le probleme technique le plus significatif en relation avec un vehicule automatique individuel, des systemes de transport tels que PRT, a double fonction, et avec la voierie publique automatique. Une structure de controle generale implequerait un controller central pour surveiller le fonctionnement du reseau, cela comprenant la coordination d’ordinateurs de secteur dont l’un superviserait et controlerait les vehicules fonctionnant dans le secteur qui lui est affecte. A ce niveau les trois facettes essentielles des operations sont: a) La determination de l’etat de chaque vehicule et quel rapport cet etat a avec l’etat desire; b) b) Les communications entre chaque vehicule controle et le controle de secteur; c) Le controle de chaque vehicule individuel. De recents progres concernant la conception, le developpement et l’experimentation de ces facettes seront decrits dans le contexte de la realisation d’un fonctionnement sur et efficace dans un court intervalle de temps (1-2 sec). Precisement, deux techniques ont ete mises au point en fournissant a un vehicule en marche des renseiqnements sur la position (ne permettant une marge d’erreur que de 20 cm ou moins), et sur la velocite (ou la marge d’erreur ne depasse pas 1.7%). D’autre part, un controller longitudinal de vehicule dont la marge d’erreur ne depasse pas 30 cm a l’arrivee de signaux de moindre et de grande intensite, reste insensible aux forces de perturbation et permet aussi aux passagers de jouir d’un trajet confortable, a ete concu, mis a l’epreuve et juge dans des conditions reelles de fonctionnaient.
Streptococcus azizii sp. nov., isolated from naïve weanling mice

Three isolates of a previously reported novel catalase-negative, Gram-stain-positive, coccoid, alpha-haemolytic, Streptococcus species that were associated with meningoencephalitis in naive weanling mice were further evaluated to confirm their taxonomic status and to determine additional phenotypic and molecular characteristics. Comparative 16S rRNA gene sequence analysis showed nearly identical intra-species sequence similarity (≥99.9 %), and revealed the closest phylogenetically related species, Streptococcus acidominimus and Streptococcuscuniculi, with 97.0 and 97.5 % sequence similarity, respectively. The rpoB, sodA and recN genes were identical for the three isolates and were 87.6, 85.7 and 82.5 % similar to S. acidominimus and 89.7, 86.2 and 80.7 % similar to S. cuniculi , respectively. In silico DNA–DNA hybridization analyses of mouse isolate 12-5202T against S. acidominimus CCUG 27296T and S. cuniculi CCUG 65085T produced estimated values of 26.4 and 25.7 % relatedness, and the calculated average nucleotide identity values were 81.9 and 81.7, respectively. These data confirm the taxonomic status of 12-5202T as a distinct Streptococcus species, and we formally propose the type strain, Streptococcus azizii 12-5202T (=CCUG 69378T=DSM 103678T). The genome of Streptococcus azizii sp. nov. 12-5202T contains 2062 total genes with a size of 2.34 Mbp, and an average G+C content of 42.76 mol%.
Characterizing human activity induced impulse and slip-pulse excitations through structural vibration

Abstract Many human activities induce excitations on ambient structures with various objects, causing the structures to vibrate. Accurate vibration excitation source detection and characterization enable human activity information inference, hence allowing human activity monitoring for various smart building applications. By utilizing structural vibrations, we can achieve sparse and non-intrusive sensing, unlike pressure- and vision-based methods. Many approaches have been presented on vibration-based source characterization, and they often either focus on one excitation type or have limited performance due to the dispersion and attenuation effects of the structures. In this paper, we present our method to characterize two main types of excitations induced by human activities (impulse and slip-pulse) on multiple structures. By understanding the physical properties of waves and their propagation, the system can achieve accurate excitation tracking on different structures without large-scale labeled training data. Specifically, our algorithm takes properties of surface waves generated by impulse and of body waves generated by slip-pulse into account to handle the dispersion and attenuation effects when different types of excitations happen on various structures. We then evaluate the algorithm through multiple scenarios. Our method achieves up to a six times improvement in impulse localization accuracy and a three times improvement in slip-pulse trajectory length estimation compared to existing methods that do not take wave properties into account.
Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer

Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells. Selective ablation of the cancer cells was achieved without significant off-target toxicity to the resident stem cells. Genomic, proteomic and multimodal imaging analyses revealed that the downregulation of CD49d, one of the dimeric protein targets of the nanomicelles, caused therapy resistance in small clusters of cancer cells. Similar treatment of a highly metastatic breast cancer model using human serum albumin-titanocene formulation significantly inhibited cancer growth. This strategy expands the use of phototherapy for treating previously inaccessible metastatic disease.
Adapted dorling cartogram on wage inequality in Portugal

Wage inequality in Portugal has been systematically around 27%. This paper describes a set of animated cartograms that show this inequality for several years. The visualization was designed for an exhibition setting, and instead of presenting the final cartograms, it shows the cartogram formation for each year as a way of reiterating the message. The model used is a modification of Dorling cartograms that visually appears as a set of contiguous amalgams of total wages earned by subregion. This aspect confers an organic tone to the artifact, as if liquids of different densities were being poured into the canvas without mixing, and depicting a tensionbased behavior where amalgams of men and women push among themselves to compete for the same space.
Abstract 456: Early Doxorubicin Exposure Upregulates P-STAT3 Expression in Adult Murine Model

Background: Anthracyclines such as doxorubicin (DOX) are a key component of chemotherapy treatments and also have cardiotoxic effects that can manifest decades after initial exposure. Long term survivors have a 15 times greater risk of heart failure than the general population. Previously, our lab has shown an increase in serum leptin in DOX treated animals 15 months after exposure. Altered p-STAT3 activation has been shown in patient and mouse models of heart failure and is downstream of leptin receptor activation. Our overall aim was to evaluate p- STAT3 levels in mice hearts of aged mice previously exposed to doxorubicin during development. Methods: C57/BL6J mice were injected weekly intraperitoneally with saline or 1 mg/kg, 3 mg/kg/ and 5mg/kg/ week of the DOX from 2 weeks to 6 weeks of age. At 7 weeks one cohort of mice were harvested. At 15 months a second cohort was harvested. Hearts were cut in half and one half paraffin sectioned. From the other half, heart lysates were prepared. P-STAT3 and STAT3 expression was evaluated by Immunohistochemistry and Western blots. Results and Conclusions: Western blot confirms a dose-dependent upregulation of p-STAT3 expression in DOX treated mice hearts at 80 weeks old compared to controls (1.13 VS. 0.04, p-STAT3/STAT3 ratio). In addition, p-STAT3 is increased by immunohistochemistry. This indicates that early exposure to DOX may produce changes in the heart that continue throughout life. These findings suggest that gene targets of activated p-STAT3 may drive the gradual progression to heart failure in patients exposed to anthracyclines during childhood. Future studies, may elucidate therapeutic targets to slow the progression of heart failure in these patients.
Anatomy of Failure: Why America Loses Every War It Starts

Harlan K. Ullman is an author with impressive credentials as a government and military “insider” with many years of relatively senior service in the US Navy and at the Pentagon. Ullman, who holds a...
Corrosion resistance of weldable Fe-Al alloys in reducing environments

Low aluminum Fe-Al alloys are being investigated for use as protective coatings in reducing environments. Intermetallic compositions have already demonstrated excellent high temperature corrosion resistance in both oxidation and sulfidation environments, however, they are limited in use due to low room temperature ductility and poor weldability arising from hydrogen embrittlement. Using Gas Tungsten Arc and Gas Metal Arc Welding process without the use of pre-heat and post weld heat treatments, a weldability regime below approximately 10 wt% Al in the overlay has been found. The high temperature sulfidation behavior of alloys located near this crack/no crack boundary (5 to 12.5 wt% Al) was examined using a thermogravimetric balance in a reducing gas mixture of O.l% H{sub 2}-1.0% H{sub 2}S-balance Ar gas at 700 C. Light optical microscopy, scanning electron microscopy, and energy dispersive spectroscopy were used to analyze the surface and cross-sectional morphologies. It was seen that the Fe-Al alloys exhibited lower weight gains than bare water wall tubes (carbon steel) and 309 stainless steel. Aluminum additions to the iron were found to extrinsically affect the iron sulfide reaction product morphology. Low carbon steel, with no aluminum, formed a continuous, and somewhat dense, iron sulfide scale that provided some protection.more » Small additions of aluminum (5--7.5 wt% Al) resulted in the growth of iron sulfide as nodules or a porous surface scale. Larger additions (above 10 wt%) were found to limit the growth of iron sulfide and significantly reduce corrosion rates. These results indicate that Fe-Al claddings containing 5 to 10 wt% Al show potential promise for applications requiring a combination of weldability and sulfidation resistance in moderately reducing environments.« less
Mutation, Mutagenese und Selektion

In einem fruheren Kapitel haben wir die Struktur der DNA behandelt. Ein Gen besteht aus einer spezifischen Folge von DNA-Nukleotiden: verschiedene Gene bestehen aus unterschiedlichen Nukleotidsequenzen. Mutationen sind Anderungen in der Basensequenz der DNA, wie etwa Transitionen und Transversionen, Insertionen und Deletionen. Man konnte zeigen, das die meisten Mutationen eines einzelnen Basenpaares reversibel sind. Die Folgen eines Mutationsereignisses hangen von seiner Lage im Gen ab: daher fuhren nicht alle Mutationen zu einem veranderten (Mutanten-) Phanotyp eines Organismus. Die Induktion von Mutationen wird Mutagenese, das Agens Mutagen genannt.
Synthesis and Properties of Biodegradable Polymers Used as Synthetic Matrices for Tissue Engineering

Organ or tissue failure remains a frequent, costly, and serious problem in health care despite advances in medical technology. The large number of patients suffering from tissue losses or organ failures is demonstrated by the approximately 8 million surgical procedures and 40 to 90 million hospital days required annually to treat these problems (Langer and Vacanti, 1993). Available treatments now include transplantation of organs from one individual to another, performing surgical reconstruction, use of mechanical devices (e.g., kidney dialyzer), and drug therapy. However, these treatments are not perfect solutions. Transplantation of organs is limited by the lack of organ donors, possible rejection, and other complications. For example, there are only 3000 donors available in contrast to 30,000 patients who die from liver failure each year (American Liver Foundation, 1988). Mechanical devices cannot perform all functions of an organ, e.g., kidney dialysis can only help remove some metabolic wastes from the body. Likewise, drugs can only replace limited biochemical functions of an organ or tissue, and physiologic control of drug levels comparable to the control systems of the body is difficult to achieve. For example, although diabetes can be partially treated by administration of insulin, it is still the leading cause of chronic renal failure and blindness (Chukwuma, 1995; Hoelscher et al, 1995; Sander and Wilson, 1993). This is partly due to difficulties in controlling the drug level in vivo (Levesque et al, 1992). Financially, the cost of surgical procedures is very high ($150,000 for a liver transplant). It is estimated that almost half of the United States $800 billion in annual health care costs are due to loss or malfunction of tissue or organs (Langer and Vacanti, 1993).
Medical faculty use of the journal literature, publishing productivity and the size of health sciences library journal collections

Abstract OBJECTIVES: This 1990-1991 study explored the relationship between the size of health sciences library journal collections and the number of different journals cited by medical school faculty in departments of biochemistry and medicine. METHODS: Two regression equations, including variables associated with a national stratified sample of 622 faculty who published articles during those two years, were used to explore factors correlated with variations in faculty use of the journal literature and faculty publishing productivity. RESULTS: Results suggest that, after controlling for other variables in the models, neither the number of different journals those faculty cited, nor the number of articles they published, had statistically significant correlations with the number of journals in the health sciences library collection. CONCLUSION: The traditional view that the size of an academic health sciences library's journal collection is a good measure of how well that library is positioned to support faculty research may not be entirely accurate.
Observing the tail of reionization: neutral islands in the z = 5.5 Lyman-α forest

Previous studies have noted difficulties in modeling the highest opacities of the $z>5.5$ Ly$\alpha$ forest, epitomized by the extreme Ly$\alpha$ trough observed towards quasar ULAS J0148+0600. One possibility is that the most opaque regions at these redshifts contain significant amounts of neutral hydrogen. This explanation, which abandons the common assumption that reionization ended before $z=6$, also reconciles evidence from independent observations of a significantly neutral Universe at $z=7.5$. Here we explore a model in which the neutral fraction is still $\approx 10\%$ at $z=5.5$. We confirm that this model can account for the observed scatter in Ly$\alpha$ forest opacities, as well as the observed Ly$\beta$ transmission in the J0148 trough. We contrast the model with a competing "earlier" reionization scenario characterized by a short mean free path and large fluctuations in the post-reionization ionizing background. We consider Ly$\alpha$ and Ly$\beta$ effective optical depths, their correlations, trough size distributions, dark pixel fractions, the IGM thermal history, and spatial distributions of Lyman-$\alpha$ emitters around forest sight lines. We find that the models are broadly similar in almost all of these statistics, suggesting that it may be difficult to distinguish between them definitively. We argue that improved constraints on the mean free path and the thermal history at $z>5$ could go a long way towards diagnosing the origin of the $z>5.5$ opacity fluctuations.
Demand Side Management- Literature Review and Performance Comparison

Several demand side management (DSM) techniques and algorithms used to show that by adopting DSM and Time-of-use (TOU) price tariffs, electricity cost significantly decreases, and optimum load scheduling is achieved. In the first part, this paper gives a comprehensive literature review on DSM’s that are related to load scheduling, Direct Load Control (DLC), and Demand Response (DR). In the second part, two algorithms are chosen to compare performance in terms of load consumption profile, Photovoltaic (PV) utilization efficiency, and power loss. These algorithms are implemented to find the optimal electric load consumption profile with presence of local PV generation. Furthermore, this paper aims to present two approaches for DSM for a residential home. These approaches can be used in response to changes in the price of electricity overtime and in the presence of PV generation to minimize the consumption cost and change the consumption pattern by shifting part of the load to off-peak hours. In addition, a case study of a single household with a single line is considered under the assumptions of its participation in a DSM program. Results show that the proposed scheduling algorithms can effectively reflect and affect user’s energy consumption behavior and achieve optimal time distribution of electricity usage. Numerical results show the impact of applying DSM algorithms on total power losses of the feeder. The proposed algorithms are implemented based on the Clonal Selection Algorithm (CSA).
Revolutionizing Tree Management via Intelligent Spatial Techniques

Tree management is becoming a big issue in a variety of societal domains. In recent years, historic wildfires and blackouts caused by failures in tree management have increased in both quantity and severity, resulting in many deaths and financial loses in the tens of billions of dollars. Many communities are also suffering from massive tree loss (e.g., in the millions) that affects the health and well-being of citizens. These problems are likely to worsen due to climate change, aging infrastructure and population growth. Tree management needs a revolution to deal with these urgent problems. This opens up new challenges and opportunities for the spatial community. This paper presents some of the open research problems from the perspectives of individual tree mapping and characterization as well as decision making and in-field intervention.
GENETIC INSIGHTS INTO CEREBROVASCULAR DISORDERS: A COMPREHENSIVE REVIEW

With the recent advances in genetic metic medicine, genome sequencing associated with clinical interpretation became more feasible for patients. Therefore, there is an increased focus on studying the molecular bases of multiple disorders, especially after the great advances in the gene-editing technologies like CRSPR. Since the cerebrovascular disorders represent a group of diseases with multiple anatomical, metabolic and multifactorial disorders, the study of the multiple genetic factirs responsible for these disorders represent a fertile field of clinical genetics. Continued advancement in the discovery of different genetic factors responsible for verebrovascular disorders will not only fascilitate an accurate diagnosis and prevension, but a possible future gene-modulation therapy for families found to inherit these disorders. This review, focuses on the latest dicoveries in the genetic bases of cerbrovascualr diseases, including the metabolic and anatomical malformations studied among affected individuals.
Strategies to Teach the National Council of State Boards of Nursing Clinical Judgment Model.

Background There is a growing concern that novice nurses who achieve licensure do not have the clinical judgment to practice safely. The National Council of State Boards of Nursing (NCSBN) began the Next Generation NCLEX (NGN) project to find methods to better assess entry-level competency. The NGN project is based on an integrative clinical judgment model (CJM) with 6 well-defined cognitive steps. Problem Teaching and assessing clinical judgment skills using the NCSBN-CJM will take faculty planning and commitment. Approach Clinical scenarios can be used to teach clinical judgment. Using prompts, instructors can deliberately lead students through the steps of recognizing cues, analyzing cues, prioritizing hypothesis, generating solutions, taking action, and evaluating outcomes. Conclusion Committing to integrating a CJM throughout the curriculum, using realistic clinical scenarios, and having students work through all the steps of a selected model are important ways educators can help students prepare for safe clinical practice.
Ulnar Artery Aneurysm as a Late Sequela of Marfan Syndrome

Marfan syndrome (MFS) is a connective tissue disorder caused by mutations of the FBN1 gene encoding fibrillin-1, which leads to overexpression of transforming growth factor-β, increased hyaluronan deposition, and matrix metalloproteinase activity in the media of the aorta and other muscular arteries. Marfan syndrome patients present with connective tissue laxity and aneurysmal changes to muscular arteries. Successful medical and surgical intervention has prolonged the life expectancy of MFS patients, which can allow atypical presentations of the syndrome to manifest. We present a case of a 49-year-old man with MFS who developed an ulnar artery aneurysm that was treated by excision and vein grafting.
The Role of Anxiety Sensitivity in terms of Weight-related Impairment and Fatigue Severity among Adults with Obesity and Chronic Low Back Pain.

Obesity and chronic low back pain often co-occur and are associated with psychosocial and physical impairments such as weight-related impairment and fatigue. Yet, there is little understanding of psychological factors that may be associated with weight-related impairment and fatigue (a psychosocial factor) among this vulnerable population. Thus, the current study examined the role of anxiety sensitivity as it relates to self-reported weight-related impairment and fatigue severity among persons with obesity and chronic low back pain. Participants included a nationally representative sample of adults (N = 616) with co-occurring obesity and chronic low back pain (77.3% female, Mage = 45.9 years, SD = 11.53). Results revealed that anxiety sensitivity was associated with greater levels of weight-related impairment and fatigue severity after controlling for age, sex, body mass index, pain interference, and perceived general health. The findings suggest that anxiety sensitivity may be a mechanistic target for better understanding and addressing weight-related impairment and fatigue severity among individuals with obesity and chronic low back pain.
Eltrombopag inhibits the proliferation of Ewing sarcoma cells via iron chelation and impaired DNA replication

The treatment of Ewing sarcoma, an aggressive bone and soft tissue sarcoma, is associated with suboptimal outcomes and significant side-effects. Consequently, there is an urgent need to identify novel therapies that will improve outcomes for children and adults with Ewing sarcoma tumors while also decreasing treatment-related toxicities. We analyzed data from the PRISM drug repurposing screen, which tested the activity of 4518 drugs across 578 cancer cell lines, to identify drugs that selectively inhibit the growth of Ewing sarcoma cell lines. We then tested the effects of a top hit from the screen on cell proliferation, cell cycle progression, and activation of the DNA damage pathway using Ewing sarcoma cell lines. We also used a CRISPR/Cas9 gene knockout approach to investigate the role of Schlafen 11 (SLFN11), a restriction factor for DNA replication stress that is overexpressed in Ewing sarcoma tumors, in mediating the sensitivity of Ewing sarcoma cells to the drug. We found that eltrombopag, an FDA-approved thrombopoietin-receptor agonist (TPO-RA) that is currently being evaluated as a treatment for chemotherapy-induced thrombocytopenia, inhibits the growth of Ewing sarcoma cell lines in vitro in proliferation and colony formation assays. However, from a mechanistic standpoint, the thrombopoietin receptor is not expressed in Ewing sarcoma cells and we show that eltrombopag impairs DNA replication and causes DNA damage in Ewing sarcoma cells by chelating iron, a known “off-target” effect of the drug. We also found that the sensitivity of Ewing sarcoma cells to eltrombopag is mediated, in part, by SLFN11, which regulates the cellular response to DNA replication stress. Ewing sarcoma cell lines are sensitive to eltrombopag and this drug could improve outcomes for patients with Ewing sarcoma tumors by both targeting the tumor, via chelation of iron and inhibition of DNA replication, and reducing chemotherapy-induced thrombocytopenia, via stimulation of the thrombopoietin receptor.
The Impact of COVID-19-Related Shutdown Measures on the Training Habits and Perceptions of Athletes in the United States: A Brief Research Report

The purpose of the current study was to examine the impact of COVID-19 government-enforced shutdown measures on the training habits and perceptions of athletes. A web-based electronic survey was developed and distributed online to athletes. The survey contained questions regarding currently available resources, changes in weekly training habits, and perceptions of training such as intensity, motivation, and enjoyment. A total of 105 (males: n = 31; females: n = 74) athletes completed the survey (mean ± SD age = 19.86 ± 2.13 years). Ninety-nine (94.3%) athletes continued to receive guidance from their primary sport coach or strength training staff. There was a significant (p < 0.001) decrease (mean ± SD) in self-reported participation time for strength training (-1.65 ± 4.32 h. week-1), endurance (-1.47 ± 3.93 h. week-1), and mobility (-1.09 ± 2.24 h. week-1), with the largest reduction coming from participation time in sport-specific activities (-6.44 ± 6.28 h. week-1) pre- to post-shutdown. When asked to rate their current state of emotional well-being using a visual analog scale of 0-100, with 100 being exceptional, the mean score was 51.6 ± 19.6 AU. Athletes experienced notable reductions in training frequency and time spent completing various training related activities. In the future, practitioners should have preparations in place in the event of another lockdown period or future pandemic to avoid or minimize significant disruptions in training. Special considerations may be needed when athletes are allowed to return to sport in the event of significant levels of detraining that may have occurred.
Flying Under the Radar? The State and the Enforcement of Labor Laws in Brazil

In recent years, developing countries have deregulated, privatized and liberalized their economies. Surprisingly, many of these countries have also retained or even strengthened their labor regulations. To understand how developing nations can ensure reasonable levels of labor protection without compromising the ability of domestic firms to compete in global markets, this paper examines how labor inspectors and prosecutors intervened in four troublesome industries in Brazil: charcoal; sugarcane; small-farming; and fireworks production. It finds that regulatory enforcement agents use their discretion and legal powers to realign incentives, reshape interests, and redistribute the risks, costs and benefits of compliance across an assemblage of public, private and non-profit agents adjacent to the violations. By doing so, they make compliance relatively easy, even desirable. Even more, as they perform this role, these agents become the foot-soldiers of a budding neo-developmental state.
Automatic Data Acquisition for Event Coreference Resolution

We propose to leverage lexical paraphrases and high precision rules informed by news discourse structure to automatically collect coreferential and non-coreferential event pairs from unlabeled English news articles. We perform both manual validation and empirical evaluation on multiple evaluation datasets with different event domains and text genres to assess the quality of our acquired event pairs. We found that a model trained on our acquired event pairs performs comparably as the supervised model when applied to new data out of the training data domains. Further, augmenting human-annotated data with the acquired event pairs provides empirical performance gains on both in-domain and out-of-domain evaluation datasets.
Distress and the Long-Stay Pediatric Intensive Care Unit Admission: A Longitudinal Study of Parents and the Medical Team

Prolonged critical illness in children has emotional consequences for both parents and providers. In this observational cohort study, we longitudinally surveyed anxiety and depression in parents and moral distress in pediatric intensive care unit (PICU) providers (attendings, fellows, and bedside registered nurses) and explored their trajectories and relationships. Anxiety/depression and provider moral distress were measured using the Hospital Anxiety and Depression Scale and the Moral Distress Thermometer, respectively. The relationships of parental and provider distress were evaluated using Spearman's correlations, and their trajectories and potentially associated variables were explored using quadratic random slope and intercept models. Predetermined associated factors included demographic and clinical factors, including parent psychosocial risk and intubation status. We found parental anxiety and depression decreased over their child's admission, and parental psychosocial risk was significantly associated with anxiety (coefficient = 4.43, p
How laser damage resistance of HfO2/SiO2 optical coatings is affected by embedded contamination caused by pausing the deposition process

Reducing contamination is essential for producing optical coatings with high resistance to laser damage. One aspect of this principle is to make every effort to limit long interruptions during the coating’s deposition. Otherwise, contamination may accumulate during the pause and become embedded in the coating after the deposition is restarted, leading to a lower laser-induced damage threshold (LIDT). However, pausing a deposition is sometimes unavoidable, despite our best efforts. For example, a sudden hardware or software glitch may require hours or even overnight to solve. In order to broaden our understanding of the role of embedded contamination on LIDT, and determine whether a coating deposited under such non-ideal circumstances could still be acceptable, this study explores how halting a deposition overnight impacts the LIDT, and whether ion cleaning can be used to mitigate any negative effects on the LIDT. The coatings investigated are a beam splitter design for high reflection at 1054 nm and high transmission at 527 nm, at 22.5° angle of incidence in S-polarization. LIDT tests were conducted in the nanosecond regime.
Chronic mucocutaneous candidiasis as a surface expression of deep-seated abnormalities: Report of a syndrome of superficial candidiasis, absence of delayed hyper sensitivity and aminoaciduria

Abstract Three patients with chronic mucocutaneous candidiasis have been studied. In the first patient, who also had an extensive skin infection due to Trichophyton rubrum, aminoaciduria and absence of delayed hypersensitivity to test antigens including oidiomycin were found. The coexistence of aminoaciduria and an immunologie abnormality has not been reported previously in a patient with chronic superficial candidiasis. The second patient had the following abnormalities: candidiasis, primary Addison's disease, enlarged thymus, miniscule spleen devoid of lymphoid tissue and lymphocytic infiltration of the thyroid gland. The third patient represents an example of the rare syndrome of familial juvenile keratoconjunctivitis, primary hypoparathyroidism, primary Addison's disease and superficial candidiasis. The patient who was lymphopenic lacked the addisonian component of the syndrome but had a sister who had the combination of hypoparathyroidism. Addison's disease and ovarian failure without associated candidiasis. Conditions favoring the development and persistence of chronic mucocutaneous candidiasis are discussed, with a review of the pertinent literature.
Elections and Political Risk: New Evidence from Political Prediction Markets in Taiwan

We examine the effects of party platforms on the economic opportunities of firms using a unique data set from a political prediction market in Taiwan, a country with two dominant parties whose political cleavage derives mainly from a single issue: the “One China Principle”. We find that during the 2008 Presidential campaign, the share price of Taiwanese firms with investments in the mainland responded strongly and positively to a positive electoral outlook for the KMT, the party which advocates lifting caps on cross-strait investment in mainland China. The response is strongest for those firms who have already hit their caps.