gebhart/patrepeval huggingface dataset:
Transcriptional repression by the orphan steroid receptor RVR/Rev-erb beta is dependent on the signature motif and helix 5 in the E region: functional evidence for a biological role of RVR in myogenesis (1996)

RVR/Rev-erb beta/BD73 is an orphan steroid receptor that has no known ligand in the "classical' sense. RVR binds as a monomer to an element which consists of an A/T-rich sequence upstream of the consensus hexameric half-site. However, RVR does not activate transcription and blocks transactivation of this element by ROR/RZR. The mechanism of RVR action remains obscure, hence we used the GAL4 hybrid system to identify and characterize an active transcriptional silencer in the ligand binding domain (LBD) of RVR. Rigorous deletion and mutational analysis demonstrated that this repressor domain is encoded by amino acids 416-449 of RVR. Furthermore, we demonstrated that efficient repression is dependent on the so-called LBD-specific signature motif, (F/W)AKxxxxFxxLxxxDQxxLL (which spans loop3-4 and helix 4) and helix 5 (H5; identified in the crystal structures of the steroid receptor LBDs). Although RVR is expressed in many adult tissues, including skeletal muscle, and during embryogenesis, its physiological function in differentiation and mammalian development remains unknown. Since other 'orphans', e.g. COUP-TF II and Rev-erbA alpha, have been demonstrated to regulate muscle and adipocyte differentiation, we investigated the expression and functional role of RVR during mouse myogenesis. In C2C12 myogenic cells, RVR mRNA was detected in proliferating myoblasts and was suppressed when the cells were induced to differentiate into post-mitotic, multinucleated myotubes by serum withdrawal. This decrease in RVR mRNA correlated with the appearance of muscle-specific markers (e.g. myogenin mRNA). RVR 'loss of function' studies by constitutive over-expression of a dominant negative RVR delta E resulted in increased levels of p21Cip1/Waf1 and myogenin mRNAs after serum withdrawal. Time course studies indicated that expression of RVR delta E mRNA results in the precocious induction and accumulation of myogenin and p21 mRNAs after serum withdrawal. In addition, we demonstrated that over-expression of the COUP-TF II and Rev-erbA alpha receptors in C2C12 cells completely blocked induction of p21 mRNA after serum withdrawal. In conclusion, our studies identified a potent transcriptional repression domain in RVR, characterized critical amino acids within the silencing region and provide evidence for the physiological role of RVR during myogenesis.
Characterization of Solid State Fermentation Culture Conditions for Growth and Mananase Production by Aspergillus niger USM F4 on Rice Husk in Tray System (2012)

Aim: The study evaluated various fermentation conditions for the production of mannanase. Place and Duration of Study: Industrial Biotechnology Research Laboratory (IBRL), School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia between May 2009 and September 2010. Methodology: Solid substrate fermentation was carried out in a shallow aluminum tray system (16 cm x 16 cm x 5 cm) for maximum mannanase production by Aspergillus niger USM F4 using rice husk as a substrate. Results: The maximum mannanase activity of 119.91 U/g substrate was achieved on the 6 days of cultivation when the optimized physical parameters were used (substrate thickness of 1.6 cm or equivalent to 80 g of 0.75 mm rice husk, moisture content to substrate ratio of 1:1 (w/v), cultivation temperature at room temperature (28±2oC), inoculum size of 6x10 spores/ml and in static condition (no mixing during the Research Article British Biotechnology Journal, 2(3): 133-145, 2012 134 fermentation process). The results showed an increment of about 30.79% of mannanase activity after the optimization (119.91 U/g substrate) compared to before optimization (91.68 U/g substrate). Conclusion: The results obtained from this study revealed that rice husk can be used as a substrate for mannanase production in solid state fermentation process.
High-Yield, Radical-Initiated Oxidative Functionalization of Ethane by Perfluorocarboxylic Acid Anhydrides. Role of Metal Ions in Catalytic Alkane Oxidations in the Presence of Perfluorocarboxylic Acid Anhydrides (1997)

Hydrogen peroxide and a trace of either ethene or propene initiated the conversion of ethane to propionic acid and its mixed anhydride (CH3CH2CO2H + CH3CH2COOCOCF3) and trifluoromethyl ethyl ketone, CH3CH2COCF3, by trifluoroacetic anhydride at 80 °C. For a fixed amount of H2O2, the amount of products formed increased with increasing amount of trifluoroacetic anhydride employed and was always higher than the amount of H2O2 added. These products were also obtained when H2O2 was replaced by other radical initiators: m-chloroperbenzoic acid, azobisisobutyronitrile, and PbEt4. With PbEt4, ethene or propene was not required for product formation and close to 500 equiv of products was formed for every equivalent of PbEt4 employed! Longer chain perfluorocarboxylic acid anhydrides reacted analogously; however, as the Rf group increased in length, a corresponding increase in mixed anhydride to ketone selectivity was observed. Methane gave very little product under the reaction conditions whereas propane underwent simple stoichiometric oxidation to 2-propanol and acetone by H2O2. The addition of (CF3CO2)2Pd to the ethane reaction resulted in simple oxidation to ethanol and acetaldehyde in amounts lower than that corresponding to the H2O2 present. In complete contrast to the ethane reaction, the yield of products from methane increased significantly (although less than the H2O2 added) upon the addition of (CF3CO2)2Pd, with methanol being the principal product.
Steroid hormone receptors and endocrine response of prostatic carcinoma. (1987)

In this study 63 open prostatectomies were performed and studied for steroid receptor content. There were 23 prostatic carcinoma (PC) and 40 benign prostatic hyperplasia (BPH). All grades and stages of cancer were represented. Androgen (AR), estrogen (ER), and progesterone (PR) receptors were assayed in the same cytosols prepared from the BPH and PC patients. Nuclear AR was also assayed in some specimens from PC patients. All receptor assays were performed before therapy was given to PC patients. Two distinct binding sites for estrogen with two different affinities and capacities were found in the cytosol fractions of BPH and PC tissues. The mean values for the high affinity site (Kd approximately 0.1 nM) were 4-fold greater in PC than BPH (P less than 0.05), while the mean values for the low affinity estrogen binding site (Kd greater than 2 nM) were slightly lower in PC than BPH. There was no significant difference in PR content between PC and BPH. AR content in PC was approximately 2-fold greater than BPH (P less than 0.05). Higher amounts of high affinity estrogen binding sites and/or high androgen receptor content in tumor tissues appear to be potential markers to predict the response of PC patients to endocrine therapy. Simultaneous measurement of nuclear AR with cytosolic AR increased the predictability of endocrine response.
Resonance Raman spectra and quantum chemical vibrational analysis of the C7H7⋅ and C7D7⋅ benzyl radicals (1994)

Time-resolved resonance Raman (RR) spectra of the benzyl radical and its perdeutero isotopomer are presented. The radicals are created by laser flash photolysis (λ=266 nm) of benzylchloride in solution. The spectra are excited at a wavelength of 315 nm, in resonance with the intense D3(2 2A2)←D0(1 2B2) transition. Twenty Raman bands, both polarized and depolarized, are observed. The RR spectra are analyzed through quantum chemical force field for π electrons (QCFF/PI) and ab initio calculations of equilibrium geometries, vibrational frequencies, Franck–Condon factors, and vibronic interactions. Polarized intense bands are assigned to totally symmetric a1 modes, and a number of depolarized bands to fundamentals of b1 modes. The observed activity of b1 modes suggests vibronic coupling, which is confirmed theoretically by calculations of vibronic interactions between the D3(2 2A2) and D5(4 2B2) states. The results from semiempirical and ab initio calculations are compared with experiment. The contributions of the different internal coordinates to the normal modes are calculated together with the changes in the molecular structure upon electronic excitation from D0 to D3 and D5.
Risk-Adjusting the Doughnut Hole to Improve Efficiency and Equity (2011)

An important goal of consumer cost-sharing in health insurance is to increase incentives for cost containment. A relatively new cost-sharing phenomenon is the "doughnut hole": a gap in coverage starting at a predefined level of medical expenses. An important question is where to locate the starting point to achieve the strongest incentives for cost containment. We argue that the answer depends on an individual's health status. Using data from a Dutch insurer, this paper illustrates that using a risk-adjusted starting point results in both stronger incentives for cost containment and more equity than a uniform starting point.
Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure (2002)

Despite similar clinical endpoints, heart failure resulting from dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) appears to develop through different remodeling and molecular pathways. Current understanding of heart failure has been facilitated by microarray technology. We constructed an in-house spotted cDNA microarray using 10,272 unique clones from various cardiovascular cDNA libraries sequenced and annotated in our laboratory. RNA samples were obtained from left ventricular tissues of precardiac transplantation DCM and HCM patients and were hybridized against normal adult heart reference RNA. After filtering, differentially expressed genes were determined using novel analyzing software. We demonstrated that normalization for cDNA microarray data is slide-dependent and nonlinear. The feasibility of this model was validated by quantitative real-time reverse transcription-PCR, and the accuracy rate depended on the fold change and statistical significance level. Our results showed that 192 genes were highly expressed in both DCM and HCM (e.g., atrial natriuretic peptide, CD59, decorin, elongation factor 2, and heat shock protein 90), and 51 genes were downregulated in both conditions (e.g., elastin, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase). We also identified several genes differentially expressed between DCM and HCM (e.g., alphaB-crystallin, antagonizer of myc transcriptional activity, beta-dystrobrevin, calsequestrin, lipocortin, and lumican). Microarray technology provides us with a genomic approach to explore the genetic markers and molecular mechanisms leading to heart failure.
Combined constrained and error control coding in suppression of intrachannel fiber nonlinearities (2005)

A combined constrained-iterative FEC scheme for high-speed long-haul transmission is proposed. It can operate in the presence of strong intrachannel nonlinearities when even advanced FEC schemes would be overwhelmed with errors, and provides the coding gain of 12 dB at BER of 10-9. (2 pages)
CMOS-like logic in defective, nanoscale crossbars (2004)

We present an approach to building defect-tolerant, nanoscale compute fabrics out of assemblies of defective crossbars of configurable FETs and switches. The simplest structure, the complementary/symmetry array, can implement AND-OR-INVERT functions, which are powerful enough to implement general computation. These arrays can be combined to create logic blocks capable of implementing sum-of-product functions, and still larger computations, such as state machines, can be obtained by adding additional routing blocks. We demonstrate the defect tolerance of such structures through experimental studies of the compilation of a small microprocessor onto a crossbar fabric with varying defect rates and compiler mapping parameters.
Control of microtubule assembly by extracellular matrix and externally applied strain (2001)

A number of studies have suggested that externally applied mechanical forces and alterations in the intrinsic cell-extracellular matrix (ECM) force balance equivalently induce changes in cell phenotype. However, this possibility has never been directly tested. To test this hypothesis, we directly investigated the response of the microtubule (MT) cytoskeleton in smooth muscle cells to both mechanical signals and alterations in the ECM. A tensile force that resulted in a positive 10% step change in substrate strain increased MT mass by 34 +/- 10% over static controls, independent of the cell adhesion ligand and tyrosine phosphorylation. Conversely, a compressive force that resulted in a negative 10% step change in substrate strain decreased MT mass by 40 +/- 6% over static controls. In parallel, increasing the density of the ECM ligand fibronectin from 50 to 1,000 ng/cm(2) in the absence of any applied force increased the amount of polymeric tubulin in the cell from 59 +/- 11% to 81 +/- 13% of the total cellular tubulin. These data are consistent with a model in which MT assembly is, in part, controlled by forces imposed on these structures, and they suggest a novel control point for MT assembly by altering the intrinsic cell-ECM force balance and applying external mechanical forces.
Plasma and rectal adenosine in inflammatory bowel disease: Effect of methotrexate (2007)

In animal models, the antiinflammatory mechanism of action of methotrexate has been attributed to elevation of the extracellular concentration of the endogenous autocoid, adenosine. Our goal was to determine if methotrexate elevates adenosine concentrations in plasma and at the site of disease in patients with inflammatory bowel disease. In 10 patients with Crohn's disease or ulcerative colitis, rectal adenosine and plasma adenosine concentrations were measured before and immediately after a subcutaneous injection of methotrexate, 15 or 25 mg. The mean predose rectal adenosine concentration of 2.4 μmol/l was not significantly different from the postdose concentration of 2.1 μmol/l, p = 0.17, (paired two-tailed t test). Rectal adenosine concentration tended to correlate with rectal endoscopic disease activity, r = 0.59, p = 0.067 (Spearman rank order correlation). After methotrexate injection, neither the mean daily plasma adenosine concentration, nor the plasma adenosine at any individual time point, were significantly different from preinjection values. In patients with inflammatory bowel disease, an injection of methotrexate in the clinically effective dose range does not raise rectal or plasma adenosine concentrations. A role for adenosine as the mediator of the antiinflammatory action of methotrexate is not supported.
Mathematics through Art - Art through Mathematics (2000)

Computer software can be used for artistic design and as a means to facilitate the understanding of mathematical concepts. We discuss some of the issues that arise when we use computers in this way, and some of our own experiences teaching both art and mathematics students using software that can assist in the design and coloring of symmetric images.
Limitations of the Three-Microphone Signal Enhancement Technique (2007)

The so-called three-microphone method is a signal enhancement method that allows one to educe a signal buried in extraneous noise using the coherence between each pair of microphones in a three microphone system. This method holds considerable promise for separating core noise from jet-mixing noise provided the limitations of the three-microphone method are well understood. A detailed uncertainty analysis of the three-microphone method is carried out in order to determine error bands for calculated data. The behavior of the method when multiple correlated sources are present is studied via numerical simulations and model-scale experimentation in anechoic facilities. Results from this numerical-simulation and model-scale testing form the backbone of this paper. Conclusions concerning the practical usage of the limitations of the three-microphone technique are drawn.
Physical Derivatives: Computing policy gradients by physical forward-propagation (2022)

Model-free and model-based reinforcement learning are two ends of a spectrum. Learning a good policy without a dynamic model can be prohibitively expensive. Learning the dynamic model of a system can reduce the cost of learning the policy, but it can also introduce bias if it is not accurate. We propose a middle ground where instead of the transition model, the sensitivity of the trajectories with respect to the perturbation of the parameters is learned. This allows us to predict the local behavior of the physical system around a set of nominal policies without knowing the actual model. We assay our method on a custom-built physical robot in extensive experiments and show the feasibility of the approach in practice. We investigate potential challenges when applying our method to physical systems and propose solutions to each of them.
A microphysiological model of the human placental barrier (2016)

During human pregnancy, the fetal circulation is separated from maternal blood in the placenta by two cell layers - the fetal capillary endothelium and placental trophoblast. This placental barrier plays an essential role in fetal development and health by tightly regulating the exchange of endogenous and exogenous materials between the mother and the fetus. Here we present a microengineered device that provides a novel platform to mimic the structural and functional complexity of this specialized tissue in vitro. Our model is created in a multilayered microfluidic system that enables co-culture of human trophoblast cells and human fetal endothelial cells in a physiologically relevant spatial arrangement to replicate the characteristic architecture of the human placental barrier. We have engineered this co-culture model to induce progressive fusion of trophoblast cells and to form a syncytialized epithelium that resembles the syncytiotrophoblast in vivo. Our system also allows the cultured trophoblasts to form dense microvilli under dynamic flow conditions and to reconstitute expression and physiological localization of membrane transport proteins, such as glucose transporters (GLUTs), critical to the barrier function of the placenta. To provide a proof-of-principle for using this microdevice to recapitulate native function of the placental barrier, we demonstrated physiological transport of glucose across the microengineered maternal-fetal interface. Importantly, the rate of maternal-to-fetal glucose transfer in this system closely approximated that measured in ex vivo perfused human placentas. Our "placenta-on-a-chip" platform represents an important advance in the development of new technologies to model and study the physiological complexity of the human placenta for a wide variety of applications.
Target nanomaterials at CERN-ISOLDE: synthesis and release data (2016)

Five different nanostructured target materials were tested and operated at ISOLDE in the year of 2014, three of them being carbon-based nanocomposites. In most cases such target materials have higher radioisotope intensities than standard targets and with apparently longer release characteristics. Here, an isotope release profile from a standard calcium oxide (CaO) powder target is compared to the nanostructured one. For all target materials, the synthesis is the key process since it determines the material characteristics and maximum operation temperature which, in turn, defines the final isotope yields (especially for exotic isotopes). An unexpected release of Ar isotopes from a nanometric CaO powder target, with its oven set to room temperature is described and a release mechanism is proposed: spallation recoil momentum from the nat Ca(p,x) 35 Ar reaction.
Automated, High-Throughput Screening of Hybrid Elastin-like Polypeptide/Polysaccharide Multilayer Film Deposition (2023)

The self-assembled layer-by-layer technique has attracted a great deal of attention as a method for engineering bio-functional surfaces under mild chemical conditions. The production of multilayer films, starting from newly designed building blocks, may be laborious, considering the inherent limitations for anticipating how minimal changes in the macromolecular composition may impact both film deposition and performance. This paper presents an automated, high-throughput approach to depositing polyelectrolyte multilayers (PEMs) in multiwell plates, enabling the screening of nearly 100 film formulations in the same process. This high-throughput layer-by-layer (HT-LbL) method runs in an affordable, fully commercial platform using Python-coded routines that can be easily adapted for the materials science lab settings. The HT-LbL system was validated by investigating the deposition of polysaccharide-based films in multiwell plates, probing the absorbance signal of ionically stained polyelectrolyte multilayers (PEMs) prepared in one single batch. The HT-LbL method was also used to investigate the deposition of PEMs with a small library of genetically engineered elastin-like polypeptides (ELPs) with different levels of ionizable and hydrophobic amino acid residues. The deposition of ELP/chitosan films was assessed based on the signal of fluorescently labeled species (chitosan or ELP-mCherry), demonstrating that both electrostatic and hydrophobic residues are essential for film buildup. The growth and surface properties of ELP-mCherry/chitosan films also seemed susceptible to the assembly pH, forming a higher film growth and a rougher and more hydrophobic surface for both polyelectrolytes deposited under a low ionization degree. Overall, this study illustrates the challenge of predicting the growth and properties of multilayer films and how the HT-LbL can accelerate the development of multilayer films that demand high levels of testing and optimization.
Effect of maternal age and conditions of fertilization on programmed cell death during murine preimplantation embryo development (1998)

One of the major morphological anomalies observed in many human pre-embryos is extensive cellular fragmentation. Previously we confirmed that embryo fragmentation seemed to be associated with the activation of programmed cell death (PCD). The purpose of our experiments was to establish a rate for murine embryo fragmentation in vivo after hormonal stimulation in young versus older females and to compare it with the rate of embryo fragmentation during in-vitro fertilization (IVF). While murine maternal age beyond 40 weeks increased the rate of embryo fragmentation following in-vivo fertilization (P = 0.001), oocytes from females of all ages had a uniformly high rate of fragmentation when fertilized in vitro (33%). None of the fragmented murine embryos proceeded further in development. In the mouse, fragmentation occurs exclusively during the first cell cycle. Furthermore, IVF significantly reduced the rate of blastocyst formation (P = 0.0001) and decreased the mean cell number at the blastocyst stage in comparison with embryos produced in vivo (P < 0.0001). The cell death index was significantly affected by both maternal age (P = 0.005) and IVF (P = 0.0001). Identification of specific factors which trigger PCD, especially those associated with IVF, may enable us to lower the rates of fragmentation in preimplantation embryos and thereby increase pregnancy rates after human IVF.
Vemurafenib resistance reprograms melanoma cells towards glutamine dependence (2015)

Our study is a proof-of-concept for the potential of targeting glutamine metabolism as an alternative strategy to suppress acquired MAPKi-resistance in melanoma.