Search

Introduction: Social support is important for many youth but may be particularly important for English learners (ELs) with disabilities, a population that has historically faced barriers accessing resources to meet their educational needs. The current study investigates social support from parents, peers, teachers, and schools in a nationally representative sample of adolescents. Method: Data from the National Longitudinal Transition Study 2012 was used to evaluate potential group differences in social support among participants that included ELs with (n = 440) and without disabilities (n = 100) and non‐ELs with (n = 4890) and without disabilities (n = 1090). A multivariate analysis of covariance was conducted to evaluate potential between‐group variations in social support among these student groups after controlling for variations in background demographic characteristics. Results and Conclusions: Results showed between group differences in parental support and peer connectedness but not in teacher or school support. Parents of students with disabilities reported the highest levels of support, whereas parents of ELs without disabilities reported the lowest levels of support. Students with disabilities reported the lowest levels of peer connectedness among the four groups. Overall, levels of teacher and school supports were high across all four groups of students. These patterns contribute to our understanding of the social support network of ELs with disabilities in comparison to other students. Further investigation is needed to examine the mechanisms that contribute to these differences. [ABSTRACT FROM AUTHOR]

Teacher–student relationships have been studied with increasing intensity during the past three decades, but the majority of this study has focused on young children and has relied on teacher perceptions of these relationships. The current study was designed to add to this growing body of research by exploring the factor structure, reliability, and validity of an instrument designed to measure adolescents' perceptions of their own relationships with teachers. Participants included 687 high school students, half of whom were students with diagnosed disabilities and the other half were students considered at risk of academic failure due to placement in dropout retrieval programs. All youth completed a self‐report instrument of teacher–student relationships along with multidimensional measures of school engagement. Findings from a confirmatory factor analysis of the Inventory of Teacher–Student Relationships indicated that the three hypothesized factors (i.e., Communication, Trust, and Alienation) had robust factor loadings, adequate internal consistency, and were associated with multiple measures of school engagement. These findings align with previous research linking teacher–student relationships with school engagement and support the need for continued research on the importance of teacher–student relationships among adolescents who are at‐risk of experiencing difficulties in school. Highlights: The Inventory of Teacher–Student Relationships had robust factor loadings, adequate internal consistency, and linked with multiple measures of school engagement.Participants included 687 high school students, half were students with diagnosed disabilities and half were students considered at risk of academic failure due to placement in dropout retrieval programs.Teacher–student relationships accounted for approximately 40% of the variance in school bonding and cognitive engagement, and approximately one‐fifth of the variance in behavioral engagement. [ABSTRACT FROM AUTHOR]

SF3B1 is the most frequently mutated RNA splicing factor in cancer, including in ~25% of myelodysplastic syndromes (MDS) patients. SF3B1-mutated MDS, which is strongly associated with ringed sideroblast morphology, is characterized by ineffective erythropoiesis, leading to severe, often fatal anemia. However, functional evidence linking SF3B1 mutations to the anemia described in MDS patients harboring this genetic aberration is weak, and the underlying mechanism is completely unknown. Using isogenic SF3B1 WT and mutant cell lines, normal human CD34 cells, and MDS patient cells, we define a previously unrecognized role of the kinase MAP3K7, encoded by a known mutant SF3B1-targeted transcript, in controlling proper terminal erythroid differentiation, and show how MAP3K7 missplicing leads to the anemia characteristic of SF3B1-mutated MDS, although not to ringed sideroblast formation. We found that p38 MAPK is deactivated in SF3B1 mutant isogenic and patient cells and that MAP3K7 is an upstream positive effector of p38 MAPK. We demonstrate that disruption of this MAP3K7-p38 MAPK pathway leads to premature down-regulation of GATA1, a master regulator of erythroid differentiation, and that this is sufficient to trigger accelerated differentiation, erythroid hyperplasia, and ultimately apoptosis. Our findings thus define the mechanism leading to the severe anemia found in MDS patients harboring SF3B1 mutations. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the predictive power of spirituality and religiousness in terms of well-being. Spirituality and religiousness were measured by the ASPIRES Scale. Participants in this study were 171 middle-aged Vietnamese-born American Catholics. Results indicated that both resilience and stress significantly related to Prayer Fulfillment, Religious Involvement, and Religious Crisis, and Universality related significantly to resilience. A series of hierarchical multiple regressions examined the incremental predictive validity of spirituality and religiousness over gender, religious status, and personality. Results demonstrated that spirituality and religiousness incrementally predicted stress overload and resilience in midlife over these other variables (ΔR2 scores ranged from.02 to.06). These findings provided further support for the hypothesis that spirituality and religiousness are important resources for managing stress and maintaining resilience for middle-aged Vietnamese-born American immigrants. [ABSTRACT FROM AUTHOR]

Based on findings from an interpretative phenomenological study, this article reports the lived experiences of religiosity and stress among six middle-aged Vietnamese-born American Catholic immigrants. The findings indicate how midlife is defined; types of midlife stressors; how participants coped with midlife stressors; religious strategies for coping with midlife stressors; and wisdom related to midlife. Implications for both clinical and congregational practice with Vietnamese American Catholic immigrants are outlined and include insights regarding how religious beliefs and practices can promote healthy coping with midlife stressors and facilitate resilience. Clinical implications and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Provides information on a study that used computer simulation to construct random structures of monosized spherical particles with various interactions among the particles. Computational method used; Details on the constructoin and characterization of structures; Results and discussion; Conclusion.

Amazon Mechanical Turk (MTurk) has increasingly attracted the attention of researchers as a convenient method to gather human subjects due to its efficiency, low cost, and ease of use in securing data samples. The current study provides a meta-analytic review across three separate MTurk samples. Participants were 1707 US citizens (774 males and 933 females, aged 18–77 years) recruited from Amazon's MTurk system. Results indicated that across three MTurk samples, demographic characteristics of workers closely approximated the general US population on gender and race but differed on religious affiliation given the very high number of Atheists and Agnostics (38.3%). Across the three samples, significant mean level differences were observed for 14 of the 15 study scales; however, effect sizes were small (eta2 ranged from.01 to.04). Results suggested that individuals working in the fields of personality and spirituality need to be aware that using an MTurk sample may introduce sample bias in their data. [ABSTRACT FROM AUTHOR]

In facilitating prosocial identity formation and preventing recidivism among adjudicated youth upon reentry to school and community, one key issue to address is the confidentiality of juvenile records. Educators can support young offenders by teaching youth to problem-solve the disclosure of past juvenile involvements. This article discusses two lessons that aim to help adjudicated youth take responsibility for past mistakes, use discretion when discussing their history, and communicate future goals to potential employers. [ABSTRACT FROM AUTHOR]

Objectives: "Heart sparing" refers to prominent antegrade fetal coronary artery (CA) blood flow readily visualized by color Doppler and is a harbinger of poor outcome in growth restricted fetus, but little is known of the features and presentation of heart sparing in normally grown fetuses. Our objective was to describe heart sparing effects in normally grown fetuses, and compare the presentation and outcome of heart sparing between fetuses with growth restriction and those who were normally grown. Methods: In a series of fetuses with prominent antegrade CA flow, we assessed Doppler flow profiles in the aortic isthmus, ductus venosus (DV), umbilical vein (UV), umbilical artery (UA) and middle cerebral artery (MCA). We calculated MCA and UA systolic/diastolic ratios and the cerebral placental ratio, and measured fetal biometry. We evaluated cardiac function using the myocardial performance index (MPI) and the cardiovascular profile score (CVPS). Results: Ten fetuses with heart sparing had normal DV flow at 24-36.6 (mean 30.9) weeks of gestation. Five had growth restriction (Group 1); 4/5 had normal MPI and CVPS, and one died. Five were normally grown (Group 2); 5/5 had elevated MPI and decreased CVPS, of these 2 died in utero and one died immediately after birth despite urgent delivery. Coronary arteries were normal after birth or autopsy. Conclusions: Heart sparing confers a poor prognosis in fetal growth restriction and in normally grown fetuses with cardiac dysfunction. We suggest CA flow be assessed in all high-risk fetuses. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to α-ketoglutarate (αKG). IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here we provide an overview of the function of normal and mutated IDH, discuss the role of IDH mutations in tumorigenesis and progression and review the key clinical considerations when treating IDH-mutated tumors based on emerging clinical data from mutant IDH1/2 inhibitor trials. IDH1 and IDH2 mutations confer neomorphic activity in the mutant protein, resulting in the conversion of αKG to the oncometabolite, D-2-hydroxyglutarate (2-HG). The subsequent accumulation of 2-HG results in epigenetic dysregulation via inhibition of αKG-dependent histone and DNA demethylases, and a block in cellular differentiation. There is growing preclinical and clinical evidence suggesting that IDH mutations are involved in neoplasia. Furthermore, preclinical studies assessing small molecule inhibitors of mutant IDH1/2 enzymes have provided proof of concept that this approach decreases intracellular 2-HG levels, reverses epigenetic dysregulation and induces cellular differentiation. Phase I studies of mutant IDH inhibitors are currently ongoing in patients with IDH-mutant hematologic and solid tumors, with early data in hematologic tumors suggesting a manageable safety profile as well as clinical benefit, with a mechanism of action based on differentiation of malignant cells. Inhibition of mutant IDH shows promise as a treatment approach in hematologic malignancies, with further development ongoing in solid tumors and glioma. The mutant IDH inhibitors may have clinical utility both as single agents and in combination strategies that target additional oncogenic pathways. [ABSTRACT FROM AUTHOR]

This exploratory study investigated linkages between parent, peer, teacher, and mentor relationships and adjustment among adolescents with disabilities. The sample included 228 high school students with disabilities (65% male, 50% White) across four states. Overall findings indicate that students’ social relationships were significantly associated with life satisfaction, problem behaviors, and school bonding and that teacher–student relationships contributed significant unique variance to these outcomes over and above influences of parents and peers. An analysis of specific dimensions of relationships indicated that trust and alienation in teacher–student relationships were particularly strong predictors of adjustment. Mentors also contributed significantly to the life satisfaction of youth. Collectively, our findings indicate that nonfamilial adults significantly contributed to the overall well-being of youth with disabilities. [ABSTRACT FROM AUTHOR]

Serine/arginine-rich splicing factor 2 (SRSF2) is an RNA-binding protein that plays important roles in splicing of mRNA precursors. SRSF2 mutations are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how these mutations affect SRSF2 function has only begun to be examined. We used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease to introduce the P95H mutation to SRSF2 in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (<1% of total). Of these events, 374 involved the inclusion of cassette exons, and the inclusion was either increased (206) or decreased (168). We detected a specific motif (UCCA/UG) enriched in the more-included exons and a distinct motif (UGGA/UG) in the more-excluded exons. RNA gel shift assays showed that a mutant SRSF2 derivative bound more tightly than itswild-type counterpart to RNA sites containing UCCAG but bound less tightly to UGGAG sites. Thus in most cases the pattern of exon inclusion or exclusion correlated with stronger or weaker RNA binding, respectively. We further show that the P95H mutation does not affect other functions of SRSF2, i.e., protein-protein interactions with key splicing factors. Our results thus demonstrate that the P95H mutation positively or negatively alters the binding affinity of SRSF2 for cognate RNA sites in target transcripts, leading to misregulation of exon inclusion. Our findings shed light on the mechanism of the disease-associated SRSF2 mutation in splicing regulation and also reveal a group of misspliced mRNA isoforms for potential therapeutic targeting. [ABSTRACT FROM AUTHOR]

Abstract: Existing measures of help-seeking focus on assessing attitudes and beliefs, rather than specific behaviors, toward help-seeking. This study described the development of a self-report measure of informal help-seeking behaviors (HSB). Participants were 228 high school students (148 males, 80 females) with disabilities from four states. Factor analyses revealed three underlying factors, each addressing a different source of help: parent, peer, and teacher. The HSB had good internal reliability and moderate validity. Results from regression analyses suggested that help-seeking behaviors toward parents and teachers contributed uniquely to students' self-ratings of school bonding, life satisfaction, and career outcome expectations. Help-seeking behaviors toward peers was a negative predictor of career outcome expectations. The value of the HSB as a research instrument was discussed. [Copyright &y& Elsevier]

Summary: We report that diffuse large B cell lymphoma (DLBCL) commonly fails to express cell-surface molecules necessary for the recognition of tumor cells by immune-effector cells. In 29% of cases, mutations and deletions inactivate the β2-Microglobulin gene, thus preventing the cell-surface expression of the HLA class-I (HLA-I) complex that is necessary for recognition by CD8+ cytotoxic T cells. In 21% of cases, analogous lesions involve the CD58 gene, which encodes a molecule involved in T and natural killer cell-mediated responses. In addition to gene inactivation, alternative mechanisms lead to aberrant expression of HLA-I and CD58 in >60% of DLBCL. These two events are significantly associated in this disease, suggesting that they are coselected during lymphomagenesis for their combined role in escape from immune-surveillance. [ABSTRACT FROM AUTHOR]

Abstract: The three-dimensional (3D) biochips prepared in this study are composed of a glass microscopy slide arrayed with amino aerogel dots. The amino aerogel was produced using the sol–gel process, with an ionic liquid as the template followed by a solvent extraction to remove the template and build a three-dimensional mesoporous structure. The FTIR spectrum verified that the major template was removed and the 29Si solid-state NMR spectra recognized the cross-linkages in the SiO2 network structure. SEM images measured the particles at around 100 nm. After grinding, the BET analysis confirmed that the nano-size amino aerogel powders had exhibited specific surface area of 188 m2/g, pore volume of 0.83 cm3/g, and average pore size of 16.2 nm. The as-prepared amino aerogel surface contained amino functional groups capable of performing a sandwich immunoassay. The primary antibody was immobilized on the internal surface of the arrayed amino aerogel to capture its affinity antigen. On the top of the captured antigen, the report antibody was read its labeling fluorescent dye. In comparison to the corresponding two-dimensional (2D) biochip, the 3D amino aerogel biochips were observed to amplify signal intensities more effectively due to their remarkable capturing capability. [Copyright &y& Elsevier]

The discovery of somatic mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone event in cancer biology. The nature of the heterozygous, point mutations mapping to arginine residues involved in the substrate binding inspired several research teams to investigate their impact on the biochemical activity of these enzymes. Soon, it became clear that the mutations identified impaired the ability of IDH1 and IDH2 to catalyze the conversion of isocitrate to α-ketoglutarate (αKG), whereas conferring a gain of a novel enzymatic activity leading to the reduction of αKG to the metabolite D2-hydroxyglutarate (D-2HG). Across glioma as well as several hematologic malignancies, mutations in IDH1 and IDH2 have shown prognostic value. Several hypotheses implicating the elevated levels of D-2HG and tumorigenesis, and the therapeutic potential of targeting mutant IDH enzymes will be discussed. [ABSTRACT FROM AUTHOR]

Mechanical disuse will bias bone marrow stromal cells towards adipogenesis, ultimately compromising the regenerative capacity of the stem cell pool and impeding the rapid and full recovery of bone morphology. Here, it was tested whether brief daily exposure to high-frequency, low-magnitude vibrations can preserve the marrow environment during disuse and enhance the initiation of tissue recovery upon reambulation. Male C57BL/6J mice were subjected to hindlimb unloading (HU, n = 24), HU interrupted by weight-bearing for 15 min/d (HU+SHAM, n = 24), HU interrupted by low-level whole body vibrations (0.2 g, 90 Hz) for 15 min/d (HU+VIB, n = 24), or served as age-matched controls (AC, n = 24). Following 3 w of disuse, half of the mice in each group were released for 3 w of reambulation (RA), while the others were sacrificed. RA+VIB mice continued to receive vibrations for 15 min/d while RA+SHAM continued to receive sham loading. After disuse, HU+VIB mice had a 30% greater osteogenic marrow stromal cell population, 30% smaller osteoclast surface, 76% greater osteoblast surface but similar trabecular bone volume fraction compared to HU. After 3 w of reambulation, trabecular bone of RA+VIB mice had a 30% greater bone volume fraction, 51% greater marrow osteoprogenitor population, 83% greater osteoblast surfaces, 59% greater bone formation rates, and a 235% greater ratio of bone lining osteoblasts to marrow adipocytes than RA mice. A subsequent experiment indicated that receiving the mechanical intervention only during disuse, rather than only during reambulation, was more effective in altering trabecular morphology. These data indicate that the osteogenic potential of bone marrow cells is retained by low-magnitude vibrations during disuse, an attribute which may have contributed to an enhanced recovery of bone morphology during reambulation. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSCs) have a unique capacity to undergo self-renewal and multi-lineage differentiation to provide a lifetime supply of mature blood cells. By using conditional knockout technology, we disrupted the c-myb proto-oncogene specifically in adult bone marrow (BM) to demonstrate that this transcription factor is a regulator of self-renewal and multi-lineage differentiation of adult HSCs. Targeted disruption of the c-myb gene resulted in a critical depletion of the HSC pool. In addition, BM hematopoiesis in adult mice was impaired, resulting in profound reductions of various hematopoletic lineages including neutrophilic, monocytic, B lymphoid, erythroid, and, unexpectedly, megakaryocytic cells. Serial BM transplantation into lethally irradiated recipient mice indicated an essential role for c-myb in the self-renewal process. Furthermore, in vitro functional assays demonstrated that deletion of the c-myb gene leads to a slightly reduced proliferative capacity and an aberrant and accelerated differentiation of HSCs. In addition to long-term HSCs, functional studies also show that c-myb plays a critical role in shortterm HSCs and multi-potential progenitors. Collectively, our data indicate a critical role for c-myb in adult BM hematopoiesis and in self-renewal and multi-lineage differentiation of adult HSCs. [ABSTRACT FROM AUTHOR]

Pluripotent mesenchymal stem cells (MSCs) are considered ideal therapeutic targets in regenerative medicine, as they hold the capacity to differentiate into higher order connective tissues. The potential to harness MSCs for disease treatment and acceleration of repair will ultimately depend on an improved understanding of how physical and/or chemical signals regulate their activity, and the ability of exogenous stimuli to enhance MSC proliferation and define MSC fate. Recent appreciation that bone marrow osteoprogenitors are inversely proportional to adipocyte precursors suggests that their shared progenitor, the MSC, will commit to one lineage at the cost of the other. This interrelationship may contribute to the phenotype of sedentary subjects who have more fat and less bone, while conversely, to the outcome of exercise being less fat and more bone. Mechanical biasing of MSC lineage selection suggests that physical signals may influence the quantity of both fat and bone through developmental, as well as metabolic or adaptive pathways. Considered with the recent finding that low magnitude mechanical signals (LMMS) suppress the development of subcutaneous and visceral fat without elevating energy expenditure, this indicates that MSCs are ideally positioned as mechanosensitive elements central to musculoskeletal adaptation, but that the signals needn't be large to be influential. The biasing of MSC differentiation by mechanical signals represents a unique means by which adiposity can be inhibited while simultaneously promoting a better skeleton, and may provide the basis for a safe, non-invasive, non-pharmacologic strategy to prevent both obesity and osteoporosis, yet uniquely — without targeting the resident fat or bone cell. [ABSTRACT FROM AUTHOR]

We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes. The patient presented with severe skeletal muscular weakness and respiratory failure. He also had a history of two OHTs, the first one for severe HCM and the second for allograft rejection. The patient’s myopathy was initially presumed to be exclusively related to steroid-induced “critical care myopathy.” However, further evaluation with a thigh muscle biopsy revealed autophagic vacuoles with sarcolemnal features suggestive of a lysosomal storage disorder. DNA analysis ultimately identified a previously unreported hemizygous IVS6+3_+6delGAGT splice site deletion mutation in the LAMP-2 gene located within the 5′ splice site of intron 6, consistent with Danon disease. [ABSTRACT FROM AUTHOR]

Reversible addition fragmentation chain transfer (RAFT) polymerization of methyl methacrylate (MMA) can be carried out in the presence of cyanoisopropyl methyl trithiocarbonate CH3SC(S)SC(CH3)2CN and scandium triflate Sc(OTf)3to provide simultaneous RAFT-controlled (reversible addition-fragmentation chain transfer controlled) molecular weight and molecular weight distribution (w/n< 1.3 at >95% conversion), Lewis acid-controlled tacticity (mm:mr:rr12:44:44 for a mole ratio Sc(OTf)3/MMA 1:8.5 at 60 °C) and an enhanced rate of polymerization. The tacticities observed for poly(methyl methacrylate) (PMMA) are similar to those observed with scandium triflate in the absence of the RAFT agent. The stability of dithiobenzoate RAFT agents ZC(S)SR in the presence of scandium triflate is strongly dependent on both the Z and R substituent. 2-(ethoxycarbonyl)prop-2-yl dithiobenzoate PhC(S)SC(CH3)2CO2CH3and the polymeric RAFT agent PhC(S)S−(CH3)(CO2CH3)CH2−PMMA appear relatively stable. However, cumyl PhC(S)SC(CH3)2Ph and cyanoisopropyl dithiobenzoate PhC(S)SC(CH3)2CN are rapidly degraded and are therefore not appropriate for direct use in this application. These RAFT agents may, however, be used to synthesize stereoblock copolymers where the RAFT agent is first transformed to an oligomeric or polymeric RAFT agent in the absence of a Lewis acid. Cyanoisopropyl 1H-pyrrole-1-carbodithioate (C4H4N)C(S)SC(CH3)2CN is stable to Lewis acid-induced decomposition but slowly homolyzes at 60 °C (even in the absence of the Lewis acid) to initiate the RAFT polymerization of MMA. [ABSTRACT FROM AUTHOR]

The removal of thiocarbonylthio groups from polymers synthesized by radical polymerization with reversible addition−fragmentation chain transfer (RAFT) by radical-induced reduction has been studied. The efficiency of reduction is strongly dependent on the H-donor and the polymer. The effectiveness of the H atom donors studied increases in the series toluene 2-propanol < triethylsilane < triphenylsilane tris(trimethylsilyl)silane ∼ N-ethylpiperidine hypophosphite < tributylstannane. The end groups of the (meth)acrylic polymers, e.g., poly(butyl acrylate) and poly(methyl methacrylate), are more readily reduced than those of polystyrene. With poor H-donors such as toluene or 2-propanol radical−radical reaction between propagating radicals competes with reduction even when they are used in vast excess as a solvent for the process. Thiocarbonylthio groups of polymers prepared with dithiobenzoate or trithiocarbonate RAFT agents can be replaced by hydrogen by radical-induced reduction with hypophosphite salts, in particular, N-ethylpiperidine hypophosphite. Their use overcomes issues of reagent toxicity and ease of workup associated with the use of stannane and silane H-donors. [ABSTRACT FROM AUTHOR]

Previous reports have suggested that the protooncogene c-myb participates in T cell development in the thymus and mature T cell proliferation. We have generated two T cell-specific c-myb knockout mouse models, myb/Lckcre and myb/CD4Cre. We have demonstrated that c-myb is required for the development of thymocytes at the DN3 stage, for survival and proliferation of double-positive thymocytes, for differentiation of single-positive CD4 and CD8 T cells, and for the proliferative responses of mature T cells. In addition, our data show that c-myb is directly involved in the formation of double-positive CD4+CD8+CD25+, CD4+CD25+, and CD8+CD25+ T cells, developmental processes that may imply a role for c-myb in autoimmune dysfunction. [ABSTRACT FROM AUTHOR]

The successful incorporation and sustained release of a hydrophilic antibiotic drug (Mefoxin®, cefoxitin sodium) from electrospun poly(lactide-co-glycolide) (PLGA)-based nanofibrous scaffolds without the loss of structure and bioactivity was demonstrated. The morphology and density of the electrospun scaffold was found to be dependent on the drug concentration, which could be attributed to the effect of ionic salt on the electrospinning process. The drug release behavior from the electrospun scaffolds and its antimicrobial effects on Staphylococcus aureus cultures were also investigated. In all tested scaffolds, the maximum dosage of drug was released after 1 h of incubation in water at 37 °C. The usage of the amphiphilic block copolymer (PEG-b-PLA) reduced the cumulative amount of the released drug at earlier time points and prolonged the drug release rate at longer times (up to a 1-week period). The antibiotic drug released from these electrospun scaffolds was effective in their ability to inhibit Staphylococcus aureus growth (>90%). The combination of mechanical barriers based on non-woven nanofibrous biodegradable scaffolds and their capability for local delivery of antibiotics increases their desired utility in biomedical applications, particularly in the prevention of post-surgical adhesions and infections. [Copyright &y& Elsevier]

It is impossible to obtain a representative anatomical documentation of an entire body using classical X-ray methods, they subsume three-dimensional bodies into a two-dimensional level. We used the novel multislice-computed tomography (MSCT) technique in order to evaluate a case of homicide with putrefaction of the corpse before performing a classical forensic autopsy. This non-invasive method showed gaseous distension of the decomposing organs and tissues in detail as well as a complex fracture of the calvarium. MSCT also proved useful in screening for foreign matter in decomposing bodies, and full-body scanning took only a few minutes. In conclusion, we believe postmortem MSCT imaging is an excellent vizualisation tool with great potential for forensic documentation and evaluation of decomposed bodies. [Copyright &y& Elsevier]

A spatial diversity reception assisted multiuser code-division multiple-access detector based on genetic algorithms (GAs) is proposed. Two different GA-based individual-selection strategies are considered. In our first approach, the so-called individuals of the GA are selected for further exploitation, based purely on the sum of their corresponding figures of merit evaluated for the individual antennas. According to our second strategy, the GA's individuals are selected based on the concept of the so-called Pareto optimality, which uses the information from the individual antennas independently. Computer simulations showed that the GAs employing the latter strategy achieve a lower bit-error rate as compared to the former strategy. For a 15-user GA-assisted system employing a spreading factor of 31, a complexity reduction factor of 81 was achieved at a performance identical to that of the optimum multiuser detector using full search. [ABSTRACT FROM AUTHOR]

Examines the changes in the coenzyme A profile and the possible effects of carnitine supplementation in the genetic disorders of the mitochondrial beta-oxidation in rat hepatocytes. Effects of methylenecyclopropaneacetic acid (MCPA) on hepatocyte CoA profiles; Effects of L-carnitine on ketogenesis and CoA profile in isolated mitochondria.

Determines the effects of enzymatic blocks in intramitochondrial acyl-CoA oxidation on CoA profiles in liver cells and the ability of carnitine to prevent these effects. CoA profiles induced by methylenecyclopanacetic acid (MCPA); Inability of carnitine supplementation to correct ketogenesis suppression; Implications to fatty acid oxidation.

Abstract: Introduction: This study aims to investigate anaerobic capacity with Wingate test of 11 elite male and seven elite female Taiwanese Taekwondo athletes, including Olympic gold- and silver-medalists. Synthesis of facts: The peak power, mean power, and fatigue index were 8.42±0.86 (mean±S.D.) W/kg, 6.56±0.60 W/kg, and 42.17±9.02%, respectively, in males, and 6.64±0.42, 5.45±0.88 W/kg, and 42.54±19.73%, respectively, in females. The two medalists showed relatively high peak and mean power with low fatigue index. Conclusion: Taiwanese Taekwondo athletes may need to improve anaerobic capacity. [Copyright &y& Elsevier]

Unlabelled: A male newborn presented with congenital chylous ascites, the treatment of which is difficult and complicated due to persistent loss of chyle. The primary therapeutic goal is to reduce the lymph flow and to allow the leakage to heal naturally. Usually, conservative management--enteric rest with total parental feeding or an enteral diet with medium-chain triglycerides--can achieve this. A new treatment option is the use of octeotride, a somatostatin analogue. Both therapies failed in our patient, and surgical ligation of the leaking lymphatic duct was successful.Conclusion: The success of the surgical treatment depends on localizing the leaking lymphatic duct. Lymphatic imaging with lymphoscintigraphy and pre-operative administration of lipophilic dye can assist the surgeon. [ABSTRACT FROM AUTHOR]

The Canadian Domestic Substances List (DSL) contains chemicals that have not been tested for genotoxicity as their use pre-dates regulatory requirements. In the present study, (quantitative) structure-activity relationships ((Q)SAR) model predictions and in vitro tests were conducted for genotoxicity assessment of 13 data-poor chemicals from the DSL (i.e. CAS numbers 19286-75-0, 13676-91-0, 2478-20-8, 6408-20-8, 74499-36-8, 26694-69-9, 29036-02-0, 120-24-1, 84696-48-9, 4051-63-2, 5718-26-3, 632-51-9, and 600-14-6). First, chemicals were screened by (Q)SAR models in Leadscope® and OASIS TIMES; two chemicals were excluded from (Q)SAR as they are complex mixtures. Six were flagged by (Q)SAR as potentially mutagenic and were subsequently confirmed as mutagens using the Ames assay. Of nine chemicals with clastogenic (Q)SAR flags, eight induced micronuclei in TK6 cells. Benchmark dose analysis was used to evaluate the potency of the chemicals. Four chemicals were bacterial mutagens with similar potencies. Three chemicals were more potent in micronuclei induction than the prototype alkylating agent methyl methanesulfonate and three were equipotent to the mutagenic carcinogen benzo[ a ]pyrene in the presence of rat liver S9. Overall, 11 of the 13 DSL chemicals demonstrated at least one type of genotoxicity in vitro. This study demonstrates the application of genotoxic potency analysis for prioritizing further investigations. Image 1 • In silico and in vitro genotoxicity tests were performed on 13 data-poor chemicals. • QSAR flags for bacterial mutagenicity were comparable to Ames data. • 11 out of 13 chemicals demonstrated at least one type of in vitro genotoxicity. • Benchmark doses (from Ames and MN data) compared potency between compounds. • Three chemicals were equipotent to BaP and three were more potent than MMS. [ABSTRACT FROM AUTHOR]

Background: A new form of congenital hyperinsulinism characterized by hypoglycemia and hyperammonemia was described recently. We hypothesized that this syndrome of hyperinsulinism and hyperammonemia was caused by excessive activity of glutamate dehydrogenase, which oxidizes glutamate to α-ketoglutarate and which is a potential regulator of insulin secretion in pancreatic beta cells and of ureagenesis in the liver. Methods: We measured glutamate dehydrogenase activity in lymphoblasts from eight unrelated children with the hyperinsulinism–hyperammonemia syndrome: six with sporadic cases and two with familial cases. We identified mutations in the glutamate dehydrogenase gene by sequencing glutamate dehydrogenase complementary DNA prepared from lymphoblast messenger RNA. Site-directed mutagenesis was used to express the mutations in COS-7 cells. Results: The sensitivity of glutamate dehydrogenase to inhibition by guanosine 5'-triphosphate was a quarter of the normal level in the patients with sporadic hyperinsulinism–hyperammonemia syndrome and half the normal level in patients with familial cases and their affected relatives, findings consistent with overactivity of the enzyme. These differences in enzyme insensitivity correlated with differences in the severity of hypoglycemia in the two groups. All eight children were heterozygous for the wild-type allele and had a mutation in the proposed allosteric domain of the enzyme. Four different mutations were identified in the six patients with sporadic cases; the two patients with familial cases shared a fifth mutation. In two clones of COS-7 cells transfected with the mutant sequence from one patient, the sensitivity of the enzyme to guanosine 5'-triphosphate was reduced, findings similar to those in the child's lymphoblasts. Conclusions: The hyperinsulinism–hyperammonemia syndrome is caused by mutations in the glutamate dehydrogenase gene that impair the control of enzyme activity. (N Engl J Med 1998;338:1352-7.) [ABSTRACT FROM AUTHOR]

Abstract: Heat shock protein (Hsp) 90 is a key component of the super-chaperone complex that maintains functionally active conformation of various client proteins. Many of these client proteins regulate important nodal points in multiple signalling pathways that promote cancer cell growth and survival. Inhibitors of Hsp90, therefore, have the potential of functioning as anti-cancer agents with pleiotropic effects. Identification of novel Hsp90 inhibitors with more favourable pharmacological properties is a priority in cancer therapy. To achieve this goal, we screened a compound library using a biochemical assay based on refolding of denatured firefly luciferase. The assay revealed high sensitivity, reliability and reproducibility with a Z-factor of 0.81±0.17. Six Hsp90 inhibitory compounds identified by this screening with IC50 values between 1.0 and 6μM were further characterised for anti-proliferative activity by Cell Titer-Blue Cell Viability Assay using multiple tumour cell lines. Of particular interest was ONO4140 with lowest GI50 values in three different cancer cell lines viz; DU-145, BT-474 and K562 cell lines. This study also revealed that short-term exposure of tumour cells with ONO4140 is sufficient to inhibit the catalytic activity of Hsp90, evaluated through disruption of Hsp90-p23 association by immunoprecipitation. This short term exposure appears to initiate events like degradation of Hsp90 client proteins such as ErbB2/Her-2 and Akt with concomitant inhibition of survival signalling leading to the apoptotic death of tumour cells as seen by western blotting and Caspase Glow-3,7 assay. The study also reveals that apoptosis following Hsp90 inhibition with ONO4140 occurs via Caspase9–Caspase3 intrinsic apoptotic pathway, a process that is likely triggered by inactivation of Akt. In conclusion, we have identified a novel class of synthetic compounds which show potent Hsp90 inhibitory action in preclinical studies. The discovery of this novel class of synthetic Hsp90 inhibitors with simple chemical backbone allows us to conduct further structural modifications to improve their potency and pharmacokinetic properties for use in cancer therapy. [Copyright &y& Elsevier]

The B-myb (MYBL2) gene is a member of the MYB family of transcription factors and is involved in cell cycle regulation, DNA replication, and maintenance of genomic integrity. However, its function during adult development and hematopoiesis is unknown. We show here that conditional inactivation of B-myb in vivo results in depletion of the hematopoietic stem cell (HSC) pool, leading to profound reductions in mature lymphoid, erythroid, and myeloid cells. This defect is autonomous to the bone marrow and is first evident in stem cells, which accumulate in the S and G2/M phases. B-myb inactivation also causes defects in the myeloid progenitor compartment, consisting of depletion of common myeloid progenitors but relative sparing of granulocyte-macrophage progenitors. Microarray studies indicate that B-myb-null LSK+ cells differentially express genes that direct myeloid lineage development and commitment, suggesting that B-myb is a key player in controlling cell fate. Collectively, these studies demonstrate that B-myb is essential for HSC and progenitor maintenance and survival during hematopoiesis. [ABSTRACT FROM AUTHOR]

Bacteria within biofilms are protected from multiple stresses, including immune responses and antimicrobial agents. The biofilm-forming ability of bacterial pathogens has been associated with increased antibiotic resistance and chronic recurrent infections. Although biofilms have been well studied for several gut pathogens, little is known about biofilm formation by anaerobic gut species. The obligate anaerobe Clostridium difficile causes C. difficile infection (CDI), a major health care-associated problem primarily due to the high incidence of recurring infections. C. difficile colonizes the gut when the normal intestinal microflora is disrupted by antimicrobial agents; however, the factors or processes involved in gut colonization during infection remain unclear. We demonstrate that clinical C. difficile strains, i.e., strain 630 and the hypervirulent strain R20291, form structured biofilms in vitro, with R20291 accumulating substantially more biofilm. Microscopic and biochemical analyses show multiple layers of bacteria encased in a biofilm matrix containing proteins, DNA, and polysaccharide. Employing isogenic mutants, we show that virulence-associated proteins, Cwp84, flagella, and a putative quorum-sensing regulator, LuxS, are all required for maximal biofilm formation by C. difficile. Interestingly, a mutant in Spo0A, a transcription factor that controls spore formation was defective for biofilm formation, indicating a possible link between sporulation and biofilm formation. Furthermore, we demonstrate that bacteria in clostridial biofilms are more resistant to high concentrations of vancomycin, a drug commonly used for treatment of CDI. Our data suggest that biofilm formation by C. difficile is a complex multifactorial process and may be a crucial mechanism for clostridial persistence in the host. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the parapharyngeal space venous plexus and marrow of the skull base bones are anatomic landmarks of the potential routes for the spread of disease for Stage I-III (American Joint Commission on Cancer 1997 staging system) nasopharyngeal carcinoma (NPC).Methods and materials: A total of 364 patients with NPC were enrolled in this study. The selection criteria were Stage I-III disease and primary radiotherapy at our hospital between 1990 and 2001. All patients had undergone MRI to evaluate the head-and-neck tumors. Patients who had undergone inadequate radiotherapy at a dose of <60 Gy and/or preradiotherapy chemotherapy before the imaging evaluation were excluded from the study.Results: Of the 364 patients treated between 1990 and 2001, 163 (44.8%) had low-risk Stage I-III NPC (without parapharyngeal space extension or T3 disease). The 5-year distant metastasis-free survival rate, with and without adjuvant chemotherapy, was 97% and 96%, respectively. The remaining 201 patients had Stage II-III with parapharyngeal space extension or T3 disease. Their 5-year recurrence-free survival rate, with and without adjuvant chemotherapy, was 76.8% and 53.2% (p = 0.01), respectively.Conclusion: Our findings suggest that the risk of distant metastasis in Stage I-III NPC patients without parapharyngeal space extension or T3 disease is extremely low. Invasion into the parapharyngeal space venous plexus and marrow of the skull base bones is associated with distant metastasis, and involvement of these anatomic sites is considered a potential route for hematogenous disease spread in patients with Stage I-III NPC. [Copyright &y& Elsevier]

Facial cellulitis caused by odontogenic bacterial infection is frequently encountered; however, facial cellulitis caused by Candida albicans infection is rarely found. A patient with oral submucous fibrosis (OSF) and unknown diabetes mellitus (DM) was treated in our out-patient dental clinic by biweekly submucosal injection of 40 mg triamcinolone acetonide into bilateral buccal mucosae plus forced mouth opening performed by the two hands of the clinician. The interincisal distance of the patient improved from 28 to 48 mm after four times of steroid injection. The symptoms and signs of OSF also improved markedly. Unfortunately, facial candidal cellulitis occurred 2 months after the last time of steroid injection treatment. The infection was cured by incision and drainage, intravenous administration of amphotericin B (100 mg once a day for a week), and an appropriate medical control of DM. No recurrence of facial cellulitis was found during the follow-up period of 18 months. To prevent the occurrence of facial cellulitis after a high-dose steroid therapy, some prophylactic procedures should be taken before the initiation of the steroid treatment. J Oral Pathol Med (2004) 33: 243–5 [ABSTRACT FROM AUTHOR]

We report on the development of a polarization-sensitive dichroic (150/220 GHz) detector array for the Cosmology Large Angular Scale Surveyor (CLASS) delivered to the telescope site in June 2019. In concert with existing 40 and 90 GHz telescopes, the 150/220 GHz telescope will make observations of the cosmic microwave background over large angular scales aimed at measuring the primordial B-mode signal, the optical depth to reionization, and other fundamental physics and cosmology. The 150/220 GHz focal plane array consists of three detector modules with 1020 transition edge sensor bolometers in total. Each dual-polarization pixel on the focal plane contains four bolometers to measure the two linear polarization states at 150 and 220 GHz. Light is coupled through a planar orthomode transducer fed by a smooth-walled feedhorn array made from an aluminum–silicon alloy (CE7). In this work, we discuss the design, assembly, and in-laboratory characterization of the 150/220 GHz detector array. The detectors are photon-noise limited, and we estimate the total array noise-equivalent power to be 2.5 and 4 aW s for 150 and 220 GHz arrays, respectively. [ABSTRACT FROM AUTHOR]

SF3B1 , which encodes an essential spliceosomal protein, is frequently mutated in myelodysplastic syndromes (MDS) and many cancers. However, the defect of mutant SF3B1 is unknown. Here, we analyzed RNA sequencing data from MDS patients and confirmed that SF3B1 mutants use aberrant 3′ splice sites. To elucidate the underlying mechanism, we purified complexes containing either wild-type or the hotspot K700E mutant SF3B1 and found that levels of a poorly studied spliceosomal protein, SUGP1, were reduced in mutant spliceosomes. Strikingly, SUGP1 knockdown completely recapitulated the splicing errors, whereas SUGP1 overexpression drove the protein, which our data suggest plays an important role in branchsite recognition, into the mutant spliceosome and partially rescued splicing. Other hotspot SF3B1 mutants showed similar altered splicing and diminished interaction with SUGP1. Our study demonstrates that SUGP1 loss is a common defect of spliceosomes with disease-causing SF3B1 mutations and, because this defect can be rescued, suggests possibilities for therapeutic intervention. • SF3B1 disease mutations disrupt SF3B1 interaction with SUGP1 in the spliceosome • SUGP1 depletion completely recapitulates mutant SF3B1 splicing defects • SUGP1 G-patch domain mutant also reproduces mutant SF3B1 splicing defects • SUGP1 overexpression partially rescues the mutant SF3B1 spliceosome Zhang et al. report that SF3B1 mutations found in myelodysplastic syndromes and many cancers disrupt interaction with splicing factor SUGP1 during branchsite recognition, leading to aberrant use of upstream branch points and cryptic 3′ splice sites during RNA splicing. This defect in splicing due to cancer-causing SF3B1 mutations is rescuable. [ABSTRACT FROM AUTHOR]

The design of a two-dimensional spatial beam-combining network employing a parallel-plate superconducting waveguide filled with a monocrystalline silicon dielectric substrate is presented. This component uses arrays of magnetically coupled antenna elements to achieve high coupling efficiency and full sampling of the intensity distribution while avoiding diffractive losses in the multimode waveguide region. These attributes enable the structure’s use in realizing compact far-infrared spectrometers for astrophysical and instrumentation applications. If unterminated, reflections within a finite-sized spatial beam combiner can potentially lead to spurious couplings between elements. A planar meta-material electromagnetic absorber is implemented to control this response within the device. This broadband termination absorbs greater than 0.99 of the power over the 1.7:1 operational band at angles ranging from normal to near-parallel incidence. The design approach, simulations and applications of the spatial power combiner and meta-material termination structure are presented. [ABSTRACT FROM AUTHOR]

Micro-Spec (µ-Spec) is a direct-detection spectrometer which integrates all the components of a diffraction-grating spectrometer onto a ∼ 10-cm2 chip through the use of superconducting microstrip transmission lines on a single-crystal silicon substrate. A second-generation µ-Spec is being designed to operate with a spectral resolution of 512 in the submillimeter (500-1000 µm, 300-600 GHz) wavelength range, a band of interest for several spectroscopic applications in astrophysics. High-altitude balloon missions would provide the first test bed to demonstrate the µ-Spec technology in a space-like environment and would be an economically viable venue for multiple observation campaigns. This work reports on the current status of the instrument design and will provide a brief overview of each instrument subsystem. Particular emphasis will be given to the design of the spectrometer’s two-dimensional diffractive region, through which the light of different wavelengths is focused on the detectors along the focal plane. An optimization process is employed to generate geometrical configurations of the diffractive region that satisfy specific requirements on spectrometer size, operating spectral range, and performance. An optical design optimized for balloon missions will be presented in terms of geometric layout, spectral purity, and efficiency. [ABSTRACT FROM AUTHOR]

Objectives This study correlated immunohistochemical studies with fluorodeoxyglucose ( FDG) uptake on positron emission tomography-computed tomography ( PET- CT) and identified prognostic factors for radiotherapy ( RT)-based treatment outcomes in patients with squamous cell carcinoma of the oropharynx and hypopharynx. Methods Genomic data from pre-treatment biopsy specimens ( Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met and p16) of 76 patients were analysed using tissue microarrays. FDG uptake was evaluated using the maximum standardised uptake value ( SUVmax), metabolic tumour volume ( MTV) and total lesion glycolysis ( TLG). Results The overexpression of Glut1 positively associated with increased values of the SUVmax, MTV and TLG, whereas VEGF and HIF-1α expression with the MTV and TLG, respectively. A VEGF immunoreactive score ( IRS) >2 ( P = 0.001, hazard ratio [ HR] = 3.94) and an MTV defined by an SUV of 2.5 ( MTV2.5) >14.5 mL ( P = 0.004, HR = 3.31) were prognostic factors for low cause-specific survival, whereas a VEGF IRS >2 ( P = 0.02, HR = 2.83) for low primary relapse-free survival. Conclusion The overexpression of Glut1, VEGF and HIF-1α associated with increased FDG uptake. For patients with pharyngeal cancer requiring RT, the treatment outcome can be stratified by VEGF and MTV2.5. [ABSTRACT FROM AUTHOR]

The article provides information regarding the study on radical polymerization. Researchers define the reversible addition - fragmentation chain transfer (RAFT) polymerization as a versatile process in conferring living characteristics and at the same time as a reversible deactivation polymerization. It notes that the RAFT process can control the polymerization of most monomers polymerized by radical polymerization. Details of related to the study of RAFT agents for polymerization are presented.

Characterization of the minute cosmic microwave background polarization signature requires multi-frequency, high-throughput precision instrument systems. We have previously described the detector fabrication of a 40 GHz focal plane and now describe the fabrication of detector modules for measurement of the CMB at 90 GHz. The 90 GHz detectors are a scaled version of the 40 GHz architecture where, due to smaller size detectors, we have implemented a modular (wafer level) rather than the chip-level architecture. The new fabrication process utilizes the same design rules with the added challenge of increased wiring density to the 74 TES's as well as a new wafer level hybridization procedure. The hexagonally shaped modules are tile-able, and as such can be used to form the large focal planes required for a space-based CMB polarimeter. The detectors described here will be deployed in two focal planes with seven modules each in the Johns Hopkins University led ground-based Cosmology Large Angular Scale Surveyor (CLASS) telescope. [ABSTRACT FROM AUTHOR]