55 research outputs found

    Reconceptualizing the Achieving Success Everyday Group Counseling Model to Focus on the Strengths of Black Male Middle School Youth

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    Scholarship focused on Black male students in school counseling has been intermittent despite being well documented in the larger field of education and other disciplines. In this article, we conducted a systematic review of the school counseling literature that focused on Black male students. We used critical race theory (CRT) to examine the programs and interventions that have been published with Black male participants in school settings within the school counseling literature and examined the role that school counselors took when supporting Black male students’ academic, social emotional, college and career identity development. We reconceptualize the Achieving Success Everyday (ASE) group model (Steen et al., 2014) and call for others to use the ASE group model to combat racism and foster Black excellence

    AMR4NLI: Interpretable and robust NLI measures from semantic graphs

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    The task of natural language inference (NLI) asks whether a given premise (expressed in NL) entails a given NL hypothesis. NLI benchmarks contain human ratings of entailment, but the meaning relationships driving these ratings are not formalized. Can the underlying sentence pair relationships be made more explicit in an interpretable yet robust fashion? We compare semantic structures to represent premise and hypothesis, including sets of contextualized embeddings and semantic graphs (Abstract Meaning Representations), and measure whether the hypothesis is a semantic substructure of the premise, utilizing interpretable metrics. Our evaluation on three English benchmarks finds value in both contextualized embeddings and semantic graphs; moreover, they provide complementary signals, and can be leveraged together in a hybrid model.Comment: International Conference on Computational Semantics (IWCS 2023); v2 fixes an imprecise sentence below Eq.

    Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma

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    The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors

    Distinct latitudinal community patterns of Arctic marine vertebrates along the East Greenlandic coast detected by environmental DNA

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    Aim: Greenland is one of the places on Earth where the effects of climate change are most evident. The retreat of sea ice has made East Greenland more accessible for longer periods during the year. East Greenland fjords have been notoriously difficult to study due to their remoteness, dense sea ice conditions and lack of infrastructure. As a result, biological monitoring across latitudinal gradients is scarce in East Greenland and relies on sporadic research cruises and trawl data from commercial vessels. We here aim to investigate the transition in fish and marine mammal communities from South to Northeast Greenland using environmental DNA (eDNA). Location: South to Northeast Greenland. Methods: We investigated the transition in fish and marine mammal communities from South to Northeast Greenland using eDNA metabarcoding of seawater samples. We included both surface and mesopelagic samples, collected over approximately 2400 km waterway distance, by sampling from Cape Farewell to Ella Island in August 2021. Results: We demonstrate a clear transition in biological communities from south to northeast, with detected fish and mammal species matching known distributions. Samples from the southern areas were dominated by capelin (Mallotus villosus) and redfish (Sebastes), whereas northeastern samples were dominated by polar cod (Boreogadus saida), sculpins (Myoxocephalus) and ringed seal (Pusa hispida). We provide newly generated 12S rRNA barcodes from 87 fish species, bringing the public DNA database closer to full taxonomic coverage for Greenlandic fish species for this locus. Main Conclusions: Our results demonstrate that eDNA sampling can detect latitudinal shifts in marine biological communities of the Arctic region, which can supplement traditional fish surveys in understanding species distributions and community compositions of marine vertebrates. Importantly, sampling of eDNA can be a feasible approach for detecting northward range expansions in remote areas as climate change progresses

    Typing of Lymphogranuloma Venereum Chlamydia trachomatis Strains

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    We analyzed by multilocus sequence typing 77 lymphogranuloma venereum Chlamydia trachomatis strains from men who have sex with men in Europe and the United States. Specimens from an outbreak in 2003 in Europe were monoclonal. In contrast, several strains were in the United States in the 1980s, including a variant from Europe

    Engineering naturally occurring trans-acting non-coding RNAs to sense molecular signals

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    Non-coding RNAs (ncRNAs) are versatile regulators in cellular networks. While most trans-acting ncRNAs possess well-defined mechanisms that can regulate transcription or translation, they generally lack the ability to directly sense cellular signals. In this work, we describe a set of design principles for fusing ncRNAs to RNA aptamers to engineer allosteric RNA fusion molecules that modulate the activity of ncRNAs in a ligand-inducible way in Escherichia coli. We apply these principles to ncRNA regulators that can regulate translation (IS10 ncRNA) and transcription (pT181 ncRNA), and demonstrate that our design strategy exhibits high modularity between the aptamer ligand-sensing motif and the ncRNA target-recognition motif, which allows us to reconfigure these two motifs to engineer orthogonally acting fusion molecules that respond to different ligands and regulate different targets in the same cell. Finally, we show that the same ncRNA fused with different sensing domains results in a sensory-level NOR gate that integrates multiple input signals to perform genetic logic. These ligand-sensing ncRNA regulators provide useful tools to modulate the activity of structurally related families of ncRNAs, and building upon the growing body of RNA synthetic biology, our ability to design aptamer–ncRNA fusion molecules offers new ways to engineer ligand-sensing regulatory circuits

    What parameters affect left ventricular diastolic flow propagation velocity? in vitro studies using color m-mode doppler echocardiography

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    BACKGROUND: Insufficient data describe the relationship of hemodynamic parameters to left ventricular (LV) diastolic flow propagation velocity (Vp) measured using color M-mode Doppler echocardiography. METHODS: An in vitro LV model used to simulate LV diastolic inflow with Vp measured under conditions of varying: 1) Stroke volume, 2) heart rate (HR), 3) LV volume, 4) LV compliance, and 5) transmitral flow (TMF) waveforms (Type 1: constant low diastasis flow and Type 2: no diastasis flow). RESULTS: Univariate analysis revealed excellent correlations of Vp with stroke volume (r = 0.98), LV compliance (r = 0.94), and HR with Type 1 TMF (r = 0.97). However, with Type 2 TMF, HR was not associated with Vp. LV volume was not related to Vp under low compliance, but inversely related to Vp under high compliance conditions (r = -0.56). CONCLUSION: These in vitro findings may help elucidate the relationship of hemodynamic parameters to early diastolic LV filling

    Design Constraints on a Synthetic Metabolism

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    A metabolism is a complex network of chemical reactions that converts sources of energy and chemical elements into biomass and other molecules. To design a metabolism from scratch and to implement it in a synthetic genome is almost within technological reach. Ideally, a synthetic metabolism should be able to synthesize a desired spectrum of molecules at a high rate, from multiple different nutrients, while using few chemical reactions, and producing little or no waste. Not all of these properties are achievable simultaneously. We here use a recently developed technique to create random metabolic networks with pre-specified properties to quantify trade-offs between these and other properties. We find that for every additional molecule to be synthesized a network needs on average three additional reactions. For every additional carbon source to be utilized, it needs on average two additional reactions. Networks able to synthesize 20 biomass molecules from each of 20 alternative sole carbon sources need to have at least 260 reactions. This number increases to 518 reactions for networks that can synthesize more than 60 molecules from each of 80 carbon sources. The maximally achievable rate of biosynthesis decreases by approximately 5 percent for every additional molecule to be synthesized. Biochemically related molecules can be synthesized at higher rates, because their synthesis produces less waste. Overall, the variables we study can explain 87 percent of variation in network size and 84 percent of the variation in synthesis rate. The constraints we identify prescribe broad boundary conditions that can help to guide synthetic metabolism design

    Acid-evoked Ca2+ signalling in rat sensory neurones: effects of anoxia and aglycaemia

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    Ischaemia excites sensory neurones (generating pain) and promotes calcitonin gene-related peptide release from nerve endings. Acidosis is thought to play a key role in mediating excitation via the activation of proton-sensitive cation channels. In this study, we investigated the effects of acidosis upon Ca2+ signalling in sensory neurones from rat dorsal root ganglia. Both hypercapnic (pHo 6.8) and metabolic–hypercapnic (pHo 6.2) acidosis caused a biphasic increase in cytosolic calcium concentration ([Ca2+]i). This comprised a brief Ca2+ transient (half-time approximately 30 s) caused by Ca2+ influx followed by a sustained rise in [Ca2+]i due to Ca2+ release from caffeine and cyclopiazonic acid-sensitive internal stores. Acid-evoked Ca2+ influx was unaffected by voltage-gated Ca2+-channel inhibition with nickel and acid sensing ion channel (ASIC) inhibition with amiloride but was blocked by inhibition of transient receptor potential vanilloid receptors (TRPV1) with (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide (AMG 9810; 1 μM) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropryazine-1(2H)-carbox-amide (BCTC; 1 μM). Combining acidosis with anoxia and aglycaemia increased the amplitude of both phases of Ca2+ elevation and prolonged the Ca2+ transient. The Ca2+ transient evoked by combined acidosis, aglycaemia and anoxia was also substantially blocked by AMG 9810 and BCTC and, to a lesser extent, by amiloride. In summary, the principle mechanisms mediating increase in [Ca2+]i in response to acidosis are a brief Ca2+ influx through TRPV1 followed by sustained Ca2+ release from internal stores. These effects are potentiated by anoxia and aglycaemia, conditions also prevalent in ischaemia. The effects of anoxia and aglycaemia are suggested to be largely due to the inhibition of Ca2+-clearance mechanisms and possible increase in the role of ASICs
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