gebhart/patrepeval huggingface dataset:
MIR21-induced loss of junctional adhesion molecule A promotes activation of oncogenic pathways, progression and metastasis in colorectal cancer (2021)

Junctional adhesion molecules (JAMs) play a critical role in cell permeability, polarity and migration. JAM-A, a key protein of the JAM family, is altered in a number of conditions including cancer; however, consequences of JAM-A dysregulation on carcinogenesis appear to be tissue dependent and organ dependent with significant implications for the use of JAM-A as a biomarker or therapeutic target. Here, we test the expression and prognostic role of JAM-A downregulation in primary and metastatic colorectal cancer (CRC) (n = 947). We show that JAM-A downregulation is observed in ~60% of CRC and correlates with poor outcome in four cohorts of stages II and III CRC (n = 1098). Using JAM-A knockdown, re-expression and rescue experiments in cell line monolayers, 3D spheroids, patient-derived organoids and xenotransplants, we demonstrate that JAM-A silencing promotes proliferation and migration in 2D and 3D cell models and increases tumour volume and metastases in vivo. Using gene-expression and proteomic analyses, we show that JAM-A downregulation results in the activation of ERK, AKT and ROCK pathways and leads to decreased bone morphogenetic protein 7 expression. We identify MIR21 upregulation as the cause of JAM-A downregulation and show that JAM-A rescue mitigates the effects of MIR21 overexpression on cancer phenotype. Our results identify a novel molecular loop involving MIR21 dysregulation, JAM-A silencing and activation of multiple oncogenic pathways in promoting invasiveness and metastasis in CRC.
Reactive etching of polycrystalline CdS and ZnS films by electron cyclotron resonance hydrogen plasma (1991)

The reactive etching effect of polycrystalline CdS and ZnS films in electron cyclotron resonance (ECR) hydrogen discharge has been studied. The etch rates were strongly dependent on the material itself, the substrate temperature, and the microwave power. The activation energy for the CdS and ZnS etching was estimated to be 1.0 and 1.3 eV, respectively, and high-rate etching at the rates of 18 μm/min for the CdS and 7 μm/min for the ZnS was demonstrated. The optical emission spectral observation emitted from ECR hydrogen plasma revealed that the etch rates closely correlated with the emission intensity from the hydrogen radical and suggested that the removal process of the one molecule required three hydrogen radicals at the same time.
Arabidopsis ROCK1 transports UDP-GlcNAc/UDP-GalNAc and regulates ER protein quality control and cytokinin activity (2014)

The formation of glycoconjugates depends on nucleotide sugars, which serve as donor substrates for glycosyltransferases in the lumen of Golgi vesicles and the endoplasmic reticulum (ER). Import of nucleotide sugars from the cytosol is an important prerequisite for these reactions and is mediated by nucleotide sugar transporters. Here, we report the identification of REPRESSOR OF CYTOKININ DEFICIENCY 1 (ROCK1, At5g65000) as an ER-localized facilitator of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) transport in Arabidopsis thaliana. Mutant alleles of ROCK1 suppress phenotypes inferred by a reduced concentration of the plant hormone cytokinin. This suppression is caused by the loss of activity of cytokinin-degrading enzymes, cytokinin oxidases/dehydrogenases (CKXs). Cytokinin plays an essential role in regulating shoot apical meristem (SAM) activity and shoot architecture. We show that rock1 enhances SAM activity and organ formation rate, demonstrating an important role of ROCK1 in regulating the cytokinin signal in the meristematic cells through modulating activity of CKX proteins. Intriguingly, genetic and molecular analysis indicated that N-glycosylation of CKX1 was not affected by the lack of ROCK1-mediated supply of UDP-GlcNAc. In contrast, we show that CKX1 stability is regulated in a proteasome-dependent manner and that ROCK1 regulates the CKX1 level. The increased unfolded protein response in rock1 plants and suppression of phenotypes caused by the defective brassinosteroid receptor bri1-9 strongly suggest that the ROCK1 activity is an important part of the ER quality control system, which determines the fate of aberrant proteins in the secretory pathway.
Selective growth of GaN nanocolumns on predeposited Al patterns by rf‐plasma‐assisted molecular‐beam epitaxy (2008)

Abstract The selective area growth of GaN nanocolumns was performed on a Si (111) substrate using predeposited Al nanopatterns by rf‐plasma‐assisted molecular‐beam epitaxy. The nanopatterns consisted of Al dots with 20‐65 nm diameter and 9‐27 nm thickness that were arranged in a 300‐nm‐period triangular lattice array and prepared by electron‐beam lithography and a liftoff process. The shape of the Al pattern tended to change during the growth process before nanocolumn growth, but its significant deformation was suppressed by nitridation at temperatures below 860 °C. The configuration of the GaN nanocolumns grown on the nitrided Al patterns depended on the pattern configuration; a sufficient volume of nitrided Al was required for nanocolumns to grow perpendicular to the substrate surface. (© 2008 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Localization of Bombesin‐like Peptides in Tumors (1988)

The localization of bombesin gene products in neuroendocrine tumors was achieved by a number of techniques used in combination. These included immunocytochemistry, radioimmunoassay, and chromatographic procedures using a variety of region-specific antibodies recognizing separate portions of probombesin. In situ hybridization using cRNA probes was employed to analyze bombesin gene expression at a cellular level. A novel procedure using a divalent form of bombesin and gold-labeled monoclonal antibodies for the localization of bombesin binding sites at the ultrastructural level was employed in this study. Antibodies to neuron-specific enolase and electron microscopy were employed for the determination of neuroendocrine differentiation. Surgical samples of pulmonary (n = 250) and nonpulmonary (n = 28) small cell carcinomas, 49 carcinoids, and 62 atypical lung carcinoids were investigated and compared with 169 control tumors, including lymphomas, adenocarcinomas, squamous cell carcinomas, and non-small-cell undifferentiated tumors. Cell lines cultured from pulmonary small cell carcinoma and smear preparations of pleural effusions from patients with small cell carcinoma of the lung were also investigated. Strong immunostaining for neuron-specific enolase was noted in all neuroendocrine tumors investigated, and no immunoreactivity was noted in control cases. Electron-dense neurosecretory granules were abundant in carcinoid tumors, scattered in small cell carcinoids, and absent in control cases. Immunostaining for bombesin was particularly strong in benign carcinoids, whereas the more malignant neuroendocrine tumors (e.g., small cell carcinomas) stained best with antibodies to the carboxyl-terminal flanking portion of human probombesin (proGRP). These findings were further validated by radioimmunoassay and chromatography of tissue extracts. Specific binding sites for bombesin were demonstrated on the surface of small cell carcinoma cells maintained in culture. In situ hybridization demonstrated mRNA for preprobombesin in all small cell carcinomas investigated, including surgical samples, cytological preparations, and cell lines. Hybridization reactions varied in intensity, with some cells in autoradiograms almost masked by silver grains and others showing much lighter deposits.
In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models (2022)

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs' suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in <i>S. mansoni</i>-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.
Utility of Rat Liver S9 Fractions to Study Skin-Sensitizing Prohaptens in a Modified KeratinoSens Assay (2013)

Prohaptens are chemicals, which may cause skin sensitization after being converted into electrophilic molecules by skin enzymes. Aroclor-induced rat liver S9 fractions represent the metabolic activation system most commonly used in in vitro toxicology. This system contains much higher enzyme activities compared with those reported in skin, but it may still serve as a surrogate system to study the potential of chemicals to act as prohaptens. To test this concept, the luciferase induction in KeratinoSens reporter cells treated with chemicals in presence and absence of S9 fractions was measured. Suspected prohaptens such as methyl isoeugenol, eugenol, or trans-anethole gave no, or only weak, ge ne induction in absence of S9 fractions, and a significantly enhanced luciferase induction in presence of S9, proving their prohapten status. Direct-acting haptens like 2,4-dinitrochlorobenzene or cinnamic aldehyde gave a reduced response in presence of S9. We evaluated whether this metabolic activation assay might be implemented in a tiered screening strategy to counter-screen negatives in the KeratinoSens assay to enhance sensitivity. To this aim, all chemicals classified negative were retested with this activation step. Among the 77 chemicals found as correct-negatives, 73 were also negative in presence of metabolic activation, thus this counterscreen would reduce specificity only slightly. However, this comprehensive screening showed that only a small fraction of the known skin sensitizers need activation by the S9 system. Therefore, the KeratinoSens-S9 assay appears useful for the in vitro evaluation of specific classes of potential prohaptens and to mechanistically rationalize their prohapten status.
Layout Considerations of Logic Designs Using an N-layer 3D Nanofabric Process Flow (2020)

In the past few years, novel fabrication schemes such as parallel and monolithic 3D integration have been proposed to keep sustaining the need for more powerful integrated circuits. By stacking several devices, wafers, or dies, the footprint, delay, and power can be decreased when compared to traditional 2D implementations. While parallel 3D does not enable very fine-grained vertical connections, monolithic 3D currently only offers a limited number of transistor tiers due to the high cost of the additional masks and processing steps, limiting the benefits of using the third dimension. In this paper, we introduce an innovative planar circuit netlist and layout approach, which enables a new 3D integration flow called 3D Nanofabric. The flow, consisting of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$N$</tex> identical vertical tiers, is aimed at single instruction multiple data processor Arithmetic Logic Units (ALUs). By using a single metal routing layer for each vertical tier, the process flow is significantly simplified since multiple vertical layers can potentially be patterned at once, similar to the 3D NAND flash process. In our study, we thoroughly investigate the layout constraints arising from the Nanofabric flow and the unique metal layer rule and propose several ways to overcome them. We then show that by stacking 32 layers to build a 32-bit ALU, the footprint is reduced by <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$8.7\times$</tex> when compared to a conventional 7nm FinFET implementation.
Facts and Figures on Materials Science and Nanotechnology Progress and Investment (2021)

As the twenty-first century unfolds, nanotechnology is no longer just a buzzword in the field of materials science, but rather a tangible reality. This is evident from the surging number of commercial nanoproducts and their corresponding revenue generated in different industry sectors. However, it is important to recognize that sustainable growth of nanotechnology is heavily dependent on government funding and relevant national incentive programs. Consequently, proper analyses on publicly available nanotechnology data sets comprising information on the past two decades can be illuminating, facilitate development, and amend previous strategies as we move forward. Along these lines, classical statistics and machine learning (ML) allow processing large data sets to scrutinize patterns in materials science and nanotechnology research. Herein, we provide an analysis on nanotechnology progress and investment from an unbiased, computational vantage point and using orthogonal approaches. Our data reveal both well-established and surprising correlations in the nanotechnology field and its actors, including the interplay between the number of research institutes-industry, publications-patents, collaborative research, and top contributors to nanoproducts. Overall, data suggest that, supported by incentive programs set out by stakeholders (researchers, funding agencies, policy makers, and industry), nanotechnology could experience an exponential growth and become a centerpiece for economical welfare. Indeed, the recent success of COVID-19 vaccines is also likely to boost public trust in nanotechnology and its global impact over the coming years.
Creating a national lab shared storage infrastructure (2002)

Big science requires large research teams and huge amounts of data. The Internet 2 project provides the pipes, but where are the next generation buckets that will feed that network? The national labs require a storage infrastructure that is readily expandable, tightly integrated with the network, highly secure and cost-effective. This paper discusses a storage architecture that would meet these most stringent requirements.
Differential effects of CXCR4‐CXCL12‐ and CXCR7‐CXCL12‐mediated immune reactions on murine P0106–125‐induced experimental autoimmune neuritis (2013)

These data suggest differential and hierarchically ordered roles for CXCR4/CXCL12- vs. CXCR7/CXCL12-dependent effects during EAN: CXCR7/CXCL12 interaction is a gatekeeper for pathogenic cells, regardless of their CXCR4/CXCL12-dependent state of activation.
Abstract A261: In vitro characterization of AMG 900, an orally active small molecule inhibitor of aurora kinases in phase 1 clinical trials (2009)

Abstract Background: The aurora family of serine-threonine kinases (Aurora-A, -B, -C) regulate cell-cycle progression in mammalian cells. Aurora kinases A and B are essential for proper chromosome congression, segregation, and cytokinesis during mitosis, whereas aurora kinase C function appears restricted to male meiosis. Aurora kinase B is responsible for the direct phosphorylation of histone H3 on serine-10 (p-histone H3). Aurora kinase A and B expression is elevated in a variety of human cancers and is associated with advanced clinical staging and poor prognosis. The emergence of aurora kinases as key mitotic regulators and their potential role in tumorigenesis has focused substantial interest in developing selective small molecule inhibitors for the treatment of human cancers. Objective: The aim of this study was to characterize the in vitro effects of AMG 900 in tumor cell lines, including cell lines resistant to paclitaxel and three well-characterized aurora kinase inhibitors. Results: AMG 900 is a novel ATP competitive small molecule inhibitor that is highly potent and selective for aurora kinases A, B, and C. In cells, AMG 900 inhibits autophosphorylation of aurora kinases A and B as well as the phosphorylation of histone H3. The predominant cellular response of tumor cells to AMG 900 treatment is aborted cell division without a mitotic arrest, which leads to endoreduplication and cell death. The effect of AMG 900 was tested in a panel of 26 tumor cell lines to evaluate its potential to inhibit cell proliferation across multiple tumor types. AMG 900 inhibited the proliferation of tumor cell lines at low nanomolar concentrations (EC50 values 1–6 nM). Importantly, AMG 900 was equally potent against multidrugresistant (MDR) cell lines expressing ATP-binding cassette transporters (P-gp and BCRP1), whereas paclitaxel and three aurora kinase inhibitors (AZD1152, MK-0457, and PHA-739358) showed a loss of potency in these MDR-positive cell lines compared with matched parental cell lines. To further investigate potential mechanisms of resistance, an HCT116 cell line was adapted to grow in the presence of AZD1152, a selective inhibitor of aurora kinase B. The resulting AZD1152-resistant HCT116 subline harbors a mutation in one allele of the aurora kinase B gene (W221L substitution) and was negative for P-gp and BCRP1 expression. AMG 900 induced an accumulation of cells with ≥4N DNA content (EC50 value 5 nM) and inhibited colony formation in this AZD1152-resistant HCT116 subline. Conclusion: To our knowledge, AMG 900 is the first described inhibitor of aurora kinases A, B, and C that has uniform in vitro potency in MDR-positive tumor cell lines. AMG 900 is currently undergoing phase 1 clinical evaluation in patients with advanced solid tumors. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A261.
Convergence behavior of the normalized least mean fourth algorithm (2002)

The normalized least mean fourth (NLMF) algorithm is presented in this work and shown to have potentially faster convergence. Unlike the LMF algorithm, the convergence behavior of the NLMF algorithm is independent of the input data correlation statistics. Sufficient conditions for the NLMF algorithm convergence in the mean are obtained and the analysis of the steady-state performance is carried out using the feedback approach. Simulation results confirm the performance of the NLMF algorithm.
Perceptual studies of violin body damping and vibrato (2010)

This work explored how the perception of violin notes is influenced by the magnitude of the applied vibrato and by the level of damping of the violin resonance modes. Damping influences the "peakiness" of the frequency response, and vibrato interacts with this peakiness by producing fluctuations in spectral content as well as in frequency and amplitude. Initially, it was shown that thresholds for detecting a change in vibrato amplitude were independent of body damping, and thresholds for detecting a change in body damping were independent of vibrato amplitude. A study of perceptual similarity using triadic comparison showed that vibrato amplitude and damping were largely perceived as independent dimensions. A series of listening tests was conducted employing synthesized, recorded, or live performance to probe perceptual responses in terms of "liveliness" and preference. The results do not support the conclusion that liveliness results from the combination of the use of vibrato and a "peaky" violin response. Judgments based on listening to single notes showed inconsistent patterns for liveliness, while preferences were highest for damping that was slightly less than for a reference (real) violin. In contrast, judgments by players based on many notes showed preference for damping close to the reference value.
A trihydroxy acyclonucleoside series (1984)

An acyclonucleoside structure (Z) has been developed which possesses three hydroxymethyl groups attached to the carbon which is analogous to the 4′-carbon of natural nucleosides. The presence of the third hydroxymethyl group significantly reduces activity against herpesviruses as compared to the dihydroxymethyl (BIOLF-62) and monohydroxymethyl (acyclovir) models.
ChemInform Abstract: Synthesis of Geminal Bis(hydroxymethyl)pyrrolidine and Pyrrolizidine Imino Sugars. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Surgical treatment of tension pneumomediastinum in patients with covid-19 at the field hospital: a case series (2022)

Tension pneumomediastinum was a life-threatening complication in critically ill COVID-19 patients requiring mechanical ventilation. Surgical mediastinal decompression was the salvage procedure. The surgical technique of mediastinal drainage via suprasternal and subxiphoid incisions proved an advantage in tension relief, hemodynamic improvement and mortality reduction.
Gamma Knife radiosurgery for sellar and parasellar meningiomas: a multicenter study (2014)

Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients.
Regularizing and Optimizing LSTM Language Models (2017)

Recurrent neural networks (RNNs), such as long short-term memory networks (LSTMs), serve as a fundamental building block for many sequence learning tasks, including machine translation, language modeling, and question answering. In this paper, we consider the specific problem of word-level language modeling and investigate strategies for regularizing and optimizing LSTM-based models. We propose the weight-dropped LSTM which uses DropConnect on hidden-to-hidden weights as a form of recurrent regularization. Further, we introduce NT-ASGD, a variant of the averaged stochastic gradient method, wherein the averaging trigger is determined using a non-monotonic condition as opposed to being tuned by the user. Using these and other regularization strategies, we achieve state-of-the-art word level perplexities on two data sets: 57.3 on Penn Treebank and 65.8 on WikiText-2. In exploring the effectiveness of a neural cache in conjunction with our proposed model, we achieve an even lower state-of-the-art perplexity of 52.8 on Penn Treebank and 52.0 on WikiText-2.
Angiopoietin-1 and Pulmonary Hypertension (2003)

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