gebhart/patrepeval huggingface dataset:
Abstract 1809: Engineered destabilized ARE on the 3UTR of MYC degrades oncogenic c-MYC transcript and protein and induces apoptosis in multiple cancer types (2022)

Abstract The c-MYC oncogene is overexpressed in more than 18 human cancers, including triple negative breast cancer (TNBC), prostate cancer, and osteosarcoma, yet there is no clinically approved drug that targets this major oncogenic driver. We discovered that the 3’UTR of c-MYC in many cancers is enriched with stabilizing poly U tract sequences that can be destabilized with our novel engineered stabilizing AU Rich Elements (ARE), leading to degradation of c-MYC. We hypothesize that c-MYC destabilizing constructs will degrade c-MYC transcript and proteins across a range of cancers that overexpress this oncogene. We used heterogeneous panels of TNBC, prostate cancer, and osteosarcoma cell lines that are reflective of the heterogeneity of human cancers. We introduced our c-MYC destabilizing construct and assessed cell viability. We then performed immunofluorescence and western blot for assessment of c-MYC protein expression. Vector constructs were used as controls. Introduction of destabilizing elements achieved the degradation of both c-MYC transcript and proteins within four days, as well as a subsequent loss in cell viability. We observed that treated cells disintegrated from their nucleus, leading to increased active caspase 3/7 and cell death. Taken together, we have developed a novel technology that reliably targets and degrades the c-MYC oncogene across a range of highly aggressive and difficult to treat cancers Citation Format: Chidiebere Awah, Fu Dong, Yana Glemaud, Fayola Levine, Daniel Weiser, Olorunseun Ogunwobi. Engineered destabilized ARE on the 3UTR of MYC degrades oncogenic c-MYC transcript and protein and induces apoptosis in multiple cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1809.
Cortisol, obesity, and the metabolic syndrome: A cross‐sectional study of obese subjects and review of the literature (2013)

Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or MS.
Doubly-fluted tubes and enhanced tubes in confined crossflow. Annual report, August 1987-July 1988 (1989)

This report describes the results of an ongoing project to investigate the thermal hydraulic characteristics of spirally-enhanced tubes and annuli in heat-exchanger applications. Heat-transfer enhancement and pressure-drop increase data for the turbulent-flow regime available in the literature for over sixty spirally enhanced tubes fabricated by different manufacturers was analyzed. A geometric nondimensional parameter known as severity was used to collapse data for Nusselt number increase, friction factor increases, and enhancement efficiency for all these tubes.
NEURAL NETWORKS AS A MODEL FOR VISUAL PERCEPTION: WHAT IS LACKING? (1998)

A central mystery of visual perception is the classical problem of invariant object recognition: Different appearances of an object can be perceived as ``the same'', despite, e.g., changes in position or illumination, distortions, or partial occlusion by other objects. This article reports on a recent email discussion over the question whether a neural network can learn the simplest of these invariances, i.e. generalize over the position of a pattern on the input layer, including the author's view on what ``learning shift-invariance'' could mean. That definition leaves the problem unsolved. A similar problem is the one of learning to detect symmetries present in an input pattern. It has been solved by a standard neural network requiring some 70000 input examples. Both leave some doubt if backpropagation learning is a realistic model for perceptual processes. Abandoning the view that a stimulus-response system showing the desired behavior must be learned from scratch, yields a radically different solution. Perception can be seen as an active process that rapidly converges from some initial state to an ordered state, which in itself codes for a percept. As an example, I will present a solution to the visual correspondence problem, which greatly alleviates both problems mentioned above.
Role of the RNA polymerase α subunit in transcription activation (1992)

The N-terminal two-thirds of the alpha subunit of Escherichia coli RNA polymerase plays an essential role in the initiation of subunit assembly, by gathering two large subunits, beta and beta', together into a core-enzyme complex. One group of RNA polymerase mutants deficient in response to transcription activation carries mutations in the C-terminal region of the alpha subunit, indicating that the C-terminal region of the alpha subunit is involved in protein-protein contact in positive control of transcription. A set of activators (class I transcription factors) which make contact with this contact site I region on RNA polymerase alpha subunit bind in most cases to DNA upstream of the promoter -35 signal. Genetic fine mapping indicates that a cluster of subsites exists in the contact site I region, each interacting with a set of the class I factors and each consisting of a structure formed by only 5-10 amino acid residues.
Inhibition of the Plasma SCUBE1, a Novel Platelet Adhesive Protein, Protects Mice Against Thrombosis (2014)

We conclude that plasma SCUBE1 participates in platelet aggregation by bridging adjacent activated platelets in thrombosis. Blockade of soluble SCUBE1 might represent a novel antithrombotic strategy.
Using the PerioChip in treating adult periodontitis: an interim report. (2000)

Multicenter clinical trials have established that the adjunctive use of the subgingival controlled release of chlorhexidine, in the form of the PerioChip, significantly reduces pocket probing depth, improves probing attachment levels, and reduces bleeding on probing compared to scaling and root planing alone, for periods up to 9 months. The purpose of the present study was to report on the adjunctive use of the PerioChip for the long-term management of adult periodontitis for 2 years. A total of 836 patients with adult periodontitis from private dental offices were recruited into the trial. This interim report is on the first 72 patients to have completed the 2-year study. Treatments included initial definitive therapy followed by PerioChip placement in pocket sites with a pocket probing depth of > or = 5 mm after 1 month. Subsequently, the patients received routine periodontal maintenance therapy together with the placement of a PerioChip in pockets with pocket probing depths > or = 5 mm every 3 months. Results indicated that there was a continuous decrease in pocket probing depth over the 2 years (1.26 +/- 0.77 mm). This decrease in pocket probing depth was marked over the first 9 to 12 months, and then appeared to be less marked over the next 12 months. At 2 years, 60% of the patients had at least 2 pockets showing a reduction of 2 mm or more, and only 10% of the patients showed no change or increased pocket probing depth. The results indicate that adjunctive PerioChip use is a clinically effective treatment option for dental professionals and their patients for the long-term management of adult periodontitis.
a posteriori Error estimation for triangular and tetrahedral quadratic elements using interior residuals (1992)

Abstract A reliable and accurate a posteriori error estimator for quadratic triangular and tetrahedral elements is presented. Its application in an automated, adaptive finite element modelling system for elasticity problems demonstrates its ability to accurately estimate the error in the energy norm. A local version of this error estimator is also used to determine the multiple level h ‐refinement necessary to improve the finite element mesh.
Simultaneous Suppression of pi- and sigma- Transmission in pi-Conjugated Molecules (2020)

&lt;div&gt;&lt;div&gt;&lt;div&gt;&lt;p&gt;Molecular dielectric materials require ostensibly conflicting requirements of high polarizability and low conductivity. As previous efforts towards molecular insulators focused on saturated molecules, it remains an open question whether pi- and sigma-transport can be simultaneously suppressed in conjugated systems. Here, we demonstrate that there are conjugated molecules where the sigma-transmission is suppressed by destructive sigma-interference, while the pi-transmission can be suppressed by a localized disruption of conjugation. Using density functional theory, we study the Landauer transmission and ballistic current density, which allow us to determine how the transmission is affected by various structural changes in the molecule. We find that in para-linked oligophenyl rings the sigma-transmission can be suppressed by changing the remaining hydrogens to methyl groups due to the inherent gauche-like structure of the carbon backbone within a benzene ring, similar to what was previously seen in saturated systems. At the same time, the methyl groups fulfil a dual purpose as they modulate the twist angle between neighboring phenyl rings. When neighboring rings are orthogonal to each other, the transmission through both pi- and sigma-systems is effectively suppressed. Alternatively, breaking conjugation in a single phenyl ring by saturating two carbons atoms with two methyl substituents on each carbon, results in suppressed pi- and sigma-transport independent of dihedral angle. These two strategies demonstrate that methyl-substituted oligophenyls are promising candidates for the development of molecular dielectric materials.&lt;/p&gt;&lt;/div&gt;&lt;/div&gt;&lt;/div&gt;
Radar Target Detection via Deep Learning (2020)

This work proposes a Deep Learning based technique for radar target detection to replace standard radar signal processing techniques. The proposed technique comprises a Convolutional Neural Network (CNN) with the range-Doppler ambiguity function serving as its input. A radar simulator is developed to generate range-Doppler data for a single target with an isotropic antenna. The method is compared with the classical Cell-Averaging Constant False Alarm Rate (CA-CFAR) detector, and it is demonstrated that the proposed method outperforms CFAR approximately by a factor of 2 terms of probability of detection (PD) and by a factor of 100 in terms of probability of false alarm (PFA), at a minor cost of computational complexity.
The Brazilian Economy after the Global Crisis: An Assessment of the Economic Slowdown in 2011–2012 (2015)

The Brazilian economy grew only 1.8 percent per annum on average in 2011–2012, in contrast with growth of 3.6 percent per annum in 2001–2010. In spite of the change in the economic policy mix (notably a sharp reduction in the interest rate and currency devaluation) and a fiscal stimulus to manufacturing firms (including a reduction of the tax on some manufactured products and exemption of the payroll in various manufacturing sectors, etc.), economic growth dropped in 2012 (0.9 percent). Such a performance has given rise to some criticism from orthodox economists related to the efficacy of activist economic policy that seeks to to boost sustained growth in Brazil.
Novel elastase inhibitors from marine cyanobacteria: Structural diversity, target-bound crystal structures and cellular effects (2012)

We report the isolation and structure determination of six new dolastatin 13 analogs given the trivial names symplostatins 5–10, the molecular basis of their anti-proteolytic activity, and characterization of their cytoprotective effects. IC50 determination for symplostatin 5 against a panel of 26 serine proteases revealed potent and selective anti-proteolytic activity against elastase with low-nanomolar IC50, and to a lesser extent against chymotrypsin, while IC50s for the other serine proteases tested occurred only at high-micromolar concentrations. Crystallization of the elastase-inhibitor complex at 1.5 Å resolution offered insights on key pharmacophores for this class of serine protease inhibitor, with the 2-amino-butenoic acid (Abu) moiety being central, while other functionalities can be tuned to achieve further improvements in potency and selectivity. The structural basis of elastase inhibition was also corroborated by structure-activity relationship studies derived from in vitro enzyme inhibition assays. This family of compounds can also alleviate the effects of exogenous elastase on mammalian cells, and elastase-induced cell injury was attenuated with inhibitor treatment.
ARM Data File Standards Version: 1.0 (2014)

The Atmospheric Radiation Measurement (ARM) Climate Research Facility performs routine in situ and remote-sensing observations to provide a detailed and accurate description of the Earth atmosphere in diverse climate regimes. The result is a diverse data sets containing observational and derived data, currently accumulating at a rate of 30 TB of data and 150,000 different files per month (http://www.archive.arm.gov/stats/storage2.html). Continuing the current processing while scaling this to even larger sizes is extremely important to the ARM Facility and requires consistent metadata and data standards. The standards described in this document will enable development of automated analysis and discovery tools for the ever-growing volumes of data. It also will enable consistent analysis of the multiyear data, allow for development of automated monitoring and data health status tools, and facilitate development of future capabilities for delivering data on demand that can be tailored explicitly to user needs. This analysis ability will only be possible if the data follows a minimum set of standards. This document proposes a hierarchy that includes required and recommended standards.
Atypical Ductal Hyperplasia Presenting as Pseudomicrocalcifications (2003)

A 53-year-old white female on mammography had "suspicious" microcalcifications. Upon excision, these turned out to be pseudomicrocalcifications created by the intraductal cellular proliferations of atypical ductal hyperplasia so dense as to create radiodensities.
Heat Transfer and Cooling Techniques at Low Temperature (2014)

The first part of this chapter gives an introduction to heat transfer and cooling techniques at low temperature. We review the fundamental laws of heat transfer (conduction, convection and radiation) and give useful data specific to cryogenic conditions (thermal contact resistance, total emissivity of materials and heat transfer correlation in forced or boiling flow for example) used in the design of cooling systems. In the second part, we review the main cooling techniques at low temperature, with or without cryogen, from the simplest ones (bath cooling) to the ones involving the use of cryocoolers without forgetting the cooling flow techniques.
Physical-resource demands for scalable quantum computation (2003)

The primary resource for quantum computation is Hilbert-space dimension. Whereas Hilbert space itself is an abstract construction, the number of dimensions available to a system is a physical quantity that requires physical resources. Avoiding a demand for an exponential amount of these resources places a fundamental constraint on the systems that are suitable for scalable quantum computation. To be scalable, the number of degrees of freedom in the computer must grow nearly linearly with the number of qubits in an equivalent qubit-based quantum computer.
A phase I/II trial of clofarabine in patients with relapsed T-cell or NK-cell lymphomas. (2010)

8046 Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous and poor prognostic subset of non-Hodgkin's lymphoma. Clofarabine is a nucleoside analog which blocks DNA synthesis via inhibition of ribonucleotide reductase and DNA polymerases, and induces apoptosis. In early phase trials, complete responses (CR) were seen among patients with T/NK-cell lymphomas treated with clofarabine. Methods: In 2006, we began a phase I/II trial to examine the use of clofarabine in patients with relapsed and refractory T or NK lymphomas. The objective of the phase I portion was to identify the maximum tolerated dose (MTD) and determine its toxicities. The phase I portion started at a dose of 4 mg/m2 iv for 3 consecutive days every 3 weeks. The cohort was expanded at the MTD. Results: 29 patients (median age was 54; range, 23-82) have been enrolled. The trial will be closed to accrual in 2 months. The most common histologies include: PTCL-NOS (n=8), transformed mycosis fungoides (tMF) (n=5), ALK- anaplastic large cell lymphoma (n=4), angioimmunoblastic T-cell lymphoma (AITL) (n=4), HTLV-I associated lymphoma (n=4) and NK-lymphoma (n=3). Patients received a median of 3 (range, 1-12) prior chemotherapy regimens. Eleven patients had refractory disease and 12 had received pralatrexate. Pleural effusion (n=1) and prolonged thrombocytopenia (n=1) were seen at the 28 mg/m2 dose level. The 20 mg/m2 dose was then determined to be the MTD. 17% (5/29) of all patients and 21% (5/24) of evaluable patients responded. 2 pts had a CR and 3 had a PR. 7 pts had stable disease and 12 patients progressed. Two out of 4 pts with AITL had a CR. Responses were also seen in pts with NK lymphoma, PTCL, and tMF. Tumor reduction was observed at the following dose levels (mg/m2): 8, 13.2 and 20. Conclusions: Clofarabine can be administered to relapsed and refractory patients with T or NK-lymphoma at a dose of 20 mg/m2 using the schedule outlined above. Responses were seen in 17% of this heavily pretreated group. Clofarabine is tolerable in this patient population and produces responses in a group of patients with few options. No significant financial relationships to disclose.
The Rat Leukocyte Antigen MRC OX-44 Is a Member of a New Family of Cell Surface Proteins Which Appear To Be Involved in Growth Regulation (1991)

Moloney murine leukemia virus (MoMuLV)-induced rat T-cell lymphomas express discrete 1.8-, 2.2-, and 4-kb mRNA transcripts hybridizing under conditions of reduced stringency to a probe derived from a region upstream of the first exon of the Tpl-1/Ets-1 gene. Screening a cDNA library from one rat T-cell lymphoma with this genomic probe yielded 15 cDNA clones which were derived from 10 different genes. One of these genes, defined by the cDNA clone pRcT7a, was expressed as a 1.8-kb mRNA transcript in spleen and thymus but not in other normal rat tissues. Expression of the gene defined by the pRcT7a cDNA clone in a series of MoMuLV-induced rat T-cell lymphomas showed a perfect correlation with the expression of the rat leukocyte antigen MRC OX-44. Because of this observation, the pRcT7a clone was sequenced and it was shown to identify a gene coding for a 219-amino-acid protein. The homology between pRcT7a and the Tpl-1 probe used for its detection mapped within the 3' untranslated region of the pRcT7a cDNA clone. The pRcT7a protein, which exhibits four putative transmembrane regions and three putative glycosylation sites, contains a region which is nearly identical in sequence to a peptide derived from the rat leukocyte antigen MRC OX-44. This finding suggested that the pRcT7a cDNA clone defines the gene coding for OX-44. To confirm this finding, a pRcT7a construct in the retrovirus vector pZipNeo was introduced into the OX-44- T-cell lymphoma line 2788. Immunostaining with the MRC OX-44 monoclonal antibody followed by flow cytometry revealed that following gene transfer, the 2788 cells became OX-44+. Sequence comparisons revealed that pRcT7a/MRC OX-44 is a member of a family of genes which includes the melanoma-specific antigen ME491; the human leukocyte antigen CD37; the protein TAPA-1, which is expressed on the surface of human T cells and appears to be involved in growth regulation; the human gastrointestinal tumor antigen CO-029; and the Schistosoma mansoni-associated antigen Sm23.
pH-Dependent Gating in the Streptomyces lividans K+ Channel (1998)

Because of its size, high levels of expression, and unusual detergent stability, the small K+ channel from Streptomyces lividans (SKC1) is considered to be an ideal candidate for detailed structural analysis. In this paper, we have used planar lipid bilayers and radiotracer uptake experiments to study purified and reconstituted SKC1, in an attempt to develop a bulk assay for its functional characterization. In channels reconstituted into liposomes with external pH 3.5 and intravesicular pH 7.5, a time-dependent SKC1-catalyzed 86Rb+ uptake was observed. This cationic influx was blocked by Ba2+ ions with a Ki (external) of 0.4 mM and was shown to have the following selectivity sequence: K+ > Rb+ > NH4+ >> Na+ > Li+. In experiments with external pH 7.5 or in liposomes containing no channels, no 86Rb+ uptake was detected. When SKC1 was incorporated into planar lipid bilayers, we failed to observe significant single-channel activity at neutral pH but detected frequent multiple-channel openings a pH < 5.0. These results indicate that under these experimental conditions SKC1 behaves as a pH-gated K+ channel in which protonation of one or more residues promotes channel opening. At acidic pH and symmetrical 200 mM KCl solutions, SKC1 showed numerous brief openings with a main single-channel conductance of 135 pS and a subconductance state of 70 pS. Channel open probability showed a slight voltage dependence, with higher activities observed at negative potentials, a fact which may suggest that the protonation site lies within the transmembrane electrical field. Attempts to determine the pKa of channel activation were obscured by intrinsic limitations of the 86Rb+ flux assay. However, it appears to be lower than pH 4.0. Limited proteolysis experiments demonstrated that SKC1 reconstitutes vectorially, almost exclusively in the right-side-out configuration, indicating that the protonation site responsible for channel opening is located at the extracellular face of the channel. These results point toward a potentially novel gating mechanism for SKC1 and open the possibility of using transmembrane-driven radiotracer influx experiments as a reliable bulk functional assay for reconstituted SKC1.
Investigation of Simple Algorithms for Estimation of Delay-Spread and Angle-Spread (2012)

In this paper we describe two simple methods for estimation of delay-spread and angle-spread, re-spectively. The algorithms are simple in the sense that the transmitted signal may consist of only threesuperimposed CW tones -and the receiver need only two antennas. The algorithms are also simple in thesense that the computational cost is very low. We verify the algorithms by applying them to wideband andmulti-antenna measurement data, respectively.
Effects of lovastatin on biliary lipid secretion and bile acid metabolism in humans. (1991)

Lovastatin, an inhibitor of HMG-CoA reductase, lowers cholesterol saturation of bile. To determine the mechanism of this effect and further define the role of cholesterol synthesis in regulation of biliary lipid metabolism, we studied ten human volunteers in a control period and again after 5-6 weeks on lovastatin, 40 mg b.i.d. Mean sterol production from acetate in mononuclear leukocytes fell from 1.18 to 0.84 pmol/min per 10(6) cells on lovastatin (P less than 0.02). Concomitantly there was reduction in mean biliary secretion of cholesterol from 143 to 96 mumol/h (P less than 0.02). On lovastatin, mean pool size of bile acids by the Lindstedt method fell from 3193 to 2917 mumol (one-sided P = 0.05) and mean pool size by the one-sample method fell from 5158 to 4091 mumol (P less than 0.002). Lovastatin had no effect on mean fractional turnover rate of either cholic acid (0.77 vs. 0.74 day-1) or chenodeoxycholic acid (0.51 vs. 0.54 day-1). Mean total bile acid synthesis was lower on lovastatin (1443 vs. 1240 mumol/day), but the difference did not quite achieve statistical significance. In humans, inhibition of cholesterol synthesis by lovastatin lowers biliary cholesterol saturation by reducing cholesterol secretion into bile. Bile acid pool size, and perhaps bile acid synthesis, are also reduced by this inhibition.