gebhart/patrepeval huggingface dataset:
Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation (2004)

Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo fibroblasts (MEFs) and white preadipocytes by expression of simian virus 40 large T antigen results in the expression of the brown fat-specific uncoupling protein 1 (UCP-1) in the adipose state. Retinoblastoma gene-deficient (Rb-/-) MEFs and stem cells, but not the corresponding wild-type cells, differentiate into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. pRB-deficient MEFs exhibit an increased expression of the Forkhead transcription factor Foxc2 and its target gene cAMP-dependent protein kinase regulatory subunit RIalpha, resulting in increased cAMP sensitivity. Suppression of cAMP-dependent protein kinase activity in Rb(-/-)MEFs blocked the brown adipocyte-like gene expression pattern without affecting differentiation per se. Immunohistochemical studies revealed that pRB is present in the nuclei of white but not brown adipocyte precursor cells at a developmental stage where both cell types begin to accumulate lipid and brown adipocytes express UCP-1. Furthermore, pRB rapidly undergoes phosphorylation upon cold-induced neodifferentiation and up-regulation of UCP-1 expression in brown adipose tissue. Finally, down-regulation of pRB expression accompanies transdifferentiation of white into brown adipocytes in response to beta3-adrenergic receptor agonist treatment. We propose that pRB acts as a molecular switch determining white vs. brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment and differentiation.
Discrete time adaptive control for a MEMS gyroscope (2005)

Abstract This paper presents a discrete time version of the observer‐based adaptive control system for micro‐electro‐mechanical systems gyroscopes, which can be implemented using digital processors. A stochastic analysis of this control algorithm is developed and it shows that the estimates of the angular rate and the fabrication imperfections are biased due to the signal discretization errors in the feedforward control path introduced by the sampler and holder. Thus, a two‐rate discrete time control is proposed as a compromise between the measurement biases and the computational burden imposed on the controller. The convergence analysis of this algorithm is also conducted and an analysis method is developed for determining the trade‐off between the controller sampling frequency and the magnitude of the angular rate estimate biased errors. All convergence and stochastic properties of a continuous time adaptive control are preserved, and this analysis is verified with computer simulations. Copyright © 2005 John Wiley & Sons, Ltd.
Fused Impurity P-N-P Junction Transistors (1952)

Fused impurity p-n-p junction transistors have been made which exhibit the useful circuit characteristics of high-gain, low-noise figure and alpha slightly less than unity. Such transistors are well adapted for application involving high ambient temperatures or high dissipation levels since alpha remains very nearly constant up to 120 degrees C and decreases somewhat above this temperature, permitting their stable use in emitter-grounded circuits at high temperatures. This is in contrast to junction transistors having high-resistivity collector regions, for which alpha often rises above unity at high temperatures leading to circuit instability. Satisfactory operation at several watts collector dissipation has been achieved.
A combined approach of array processing and independent component analysis for blind separation of acoustic signals (2002)

Two array signal processing techniques are combined with independent component analysis to enhance the performance of blind separation of acoustic signals in a reflective environment such as rooms. The first technique is the subspace method which reduces the effect of room reflection. The second technique is a method of solving the permutation, in which the coherency of the mixing matrix in adjacent frequencies is utilized.
ERP Correlates of Feedback and Reward Processing in the Presence and Absence of Response Choice (2004)

The feedback negativity is a component of the event-related brain potential that is elicited by feedback stimuli associated with unfavorable outcomes. The present research investigated whether this component reflects an evaluation of the valence of experienced outcomes or a process of learning about actions that led to those outcomes. The latter hypothesis predicts that the feedback negativity should be observed only when negative outcomes are experienced in relation to executed actions. Contrary to this prediction, feedback negativities were observed in simple monetary gambling tasks in which participants made no active choices (experiment 1) and no overt actions (experiment 2). However, the amplitude of the component was reduced in these tasks relative to a gambling task in which the outcomes appeared to be contingent upon participants' response choices. This reduction was correlated with changes in participants' subjective ratings of involvement in the tasks, suggesting that the evaluative process indexed by the feedback negativity is sensitive to the motivational significance of ongoing events.
Finding an Optimal Sequence by Dynamic Programming: An Extension to Precedence-Related Tasks (1978)

We discuss the dynamic programming approach to finding an optimal sequence of a set of tasks when the tasks are related by precedence restrictions. We describe how to use this approach in problems where no explicit precedence relations exist. Computer implementation considerations played an important role in its development. Computational results indicate that, when the curse of dimensionality can be dispelled, dynamic programming can be a useful procedure for large sequencing problems.
5G Mixed Mode: NR Multicast-Broadcast Services (2020)

This work presents a potential solution for enabling the use of multicast in the 5G New Radio Release 17, called 5G NR Mixed Mode. The proposed multicast/broadcast mode follows one of the two approaches envisaged in 3GPP, which enables a dynamic and seamless switching between unicast and multicast, both in the downlink and the uplink. This paper also provides a performance evaluation of several IMT-2020 KPIs, including available data rate and spectral efficiency, user and control plane latencies, energy efficiency, and mobility, highlighting the potential advantages of this solution over unicast in relevant scenarios. Finally, other multipoint-based KPIs such as coverage or packet loss rate are also evaluated by means of system level simulations.
Metabolic system alterations in pancreatic cancer patient serum: potential for early detection (2013)

The serum metabolome of PC patients is significantly altered. The utility of serum metabolite biomarkers, particularly PC-594, for identifying subjects with elevated risk of PC should be further investigated.
Development of high-affinity ligands and photoaffinity labels for the d-fructose transporter GLUT5 (2002)

The GLUT5 transporter catalyses the specific uptake of D-fructose and can accept this hexose in its furanose and pyranose ring forms. The transporter does not accept fructose epimers and has very limited tolerance of bulky groups substituted at the 2-, 3-, 4- and 5-OH positions [Tatibouët, Yang, Morin and Holman (2000) Bioorg. Med. Chem. 8, 1825-1833]. To further explore whether bulky groups can be tolerated at the primary OH positions, a D-fructose analogue with an allylamine group substitution to replace the 1-OH group was synthesized and was found to be quite well tolerated ( K (i)=27.1 mM). However, this analogue occurs in multiple ring forms. By contrast, 2,5-anhydro-D-mannitol is a symmetrical molecule that occurs only in a furanose ring form in which C-1 and C-6 are equivalent. We have therefore synthesized new 2,5-anhydro-D-mannitol analogues (substituted at the equivalent of the 6-OH of D-fructose) and from studies in Chinese hamster ovary cells expressing GLUT5 cells report that (i) the allylamine derivative of 2,5-anhydro-D-mannitol is well tolerated ( K (i)=2.66 mM); (ii) introduction of a di-nitrophenyl-substituted secondary amine group enhances affinity ( K (i)=0.56 mM); (iii) introduction of amide-linked biotinylated photolabel moieties is possible without loss of affinity relative to 2,5-anhydro-D-mannitol but a small secondary amine spacer between the biotinylated photolabelling moiety and the fructofuranose ring increases affinity (fructose photolabel 2; K (i)=1.16 mM); (iv) introduction of a hydrophilic tartarate spacer between biotin and the diazirine photoreactive groups can be accomplished without reduction in affinity and (v) photoactivation of biotinylated fructose photolabels leads to specific biotin tagging of GLUT5. These data suggest that substitution of a secondary amine group (-NH) to replace the C-6 (or C-1) -OH of 2,5-anhydro-D-mannitol results in compounds of high affinity; the affinity is enhanced over 10-fold compared with D-fructose.
Highly selective .kappa.-opioid analgesics. 2. Synthesis and structure activity relationships of novel N-(2-aminocyclohexyl)arylacetamide derivatives (1989)

This paper describes the chemical synthesis and the development of structure-activity relationships (SAR) for the kappa opioid receptor affinity and mu/kappa opioid receptor selectivity of novel N-[(2-aminocyclohexyl)aryl]acetamide derivatives. The SAR of this series are investigated by consideration of structural modifications made to the aromatic moiety, the amide linkage, and cyclohexane and the pyrrolidine ring substituents of the prototype kappa selective agonist, PD117302 (trans-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzo[b]thiophene-4- acetamide) (1). The kappa and mu opioid receptor binding affinities of 23 novel compounds are reported. It is observed that optimal mu/kappa receptor selectivity is obtained with a benzo[b]thiophene aromatic system attached via the C-4 position, which is discussed in terms of steric and electronic parameters. The amide linkage has been replaced with the reversed amide, an ester, an aminomethylene, a thioamide, and a secondary amide. The best of these isosteres is the N-methyl amide. Substitution of the pyrrolidine ring of PD117302 in the 3-position with a hydroxymethylene group increases the mu/kappa selectivity compared to the unsubstituted compound, e.g. compound 14, trans-(+/-)-N-methyl-N-[2-[3-(hydroxymethyl)-1-pyrrolidinyl] cyclohexyl]-4-benzo[b]furanacetamide monohydrochloride, mu/kappa receptor selectivity = 244. The cis fused, 4,5 dimethyl ether substituted cyclohexane analogue trans-(+/-)-N-methyl-N-[4,5-dimethoxy-2-(1-pyrrolidinyl) cyclohexyl]-benzo[b]thiophene-4-acetamide monohydrochloride (32) has high in vitro kappa opioid receptor affinity (Ki = 16 nM) and equipotent analgesic activity to morphine after iv administration in rats.
Fabrication of Precision Scaffolds Using Liquid-Frozen Deposition Manufacturing for Cartilage Tissue Engineering (2008)

The fused deposition manufacturing (FDM) system has been used to fabricate tissue-engineered scaffolds with highly interconnecting and controllable pore structure, although the system is limited to a few materials. For this reason, the liquid-frozen deposition manufacturing (LFDM) system based on an improvement of the FDM process was developed. Poly(D,L-lactide-co-glycolide) (PLGA) precision scaffolds were fabricated using LFDM from PLGA solutions of different concentrations. A greater concentration of PLGA solution resulted in greater mechanical strength but also resulted in less water content and smaller pore size on the surface of the scaffolds. LFDM scaffolds in general had mechanical strength closer to that of native articular cartilage than did FDM scaffolds. Neocartilage formation was observed in LFDM scaffolds seeded with porcine articular chondrocytes after 28 days of culture. Chondrocytes in LFDM scaffolds made from low concentrations (15-20%) of PLGA solution maintained a round shape, proliferated well, and secreted abundant extracellular matrix. In contrast, the FDM PLGA scaffolds had low cell numbers and poor matrix production because of heavy swelling. The LFDM system offered a useful way to fabricate scaffolds for cartilage tissue-engineering applications.
The surface coat of procyclic <i>Trypanosoma brucei:</i> Programmed expression and proteolytic cleavage of procyclin in the tsetse fly (2001)

Trypanosoma brucei, the protozoan parasite causing sleeping sickness, is transmitted by a tsetse fly vector. When the tsetse takes a blood meal from an infected human, it ingests bloodstream form trypanosomes that quickly differentiate into procyclic forms within the fly's midgut. During this process, the parasite loses the 10(7) molecules of variant surface glycoprotein that formed its surface coat, and it develops a new coat composed of several million procyclin molecules. Procyclins, the products of a small multigene family, are glycosyl phosphatidylinositol-anchored proteins containing characteristic amino acid repeats at the C terminus [either EP (EP procyclin, a form of procyclin rich in Glu-Pro repeats) or GPEET (GPEET procyclin, a form of procyclin rich in Glu-Pro-Glu-Glu-Thr repeats)]. We have used a sensitive and accurate mass spectrometry method to analyze the appearance of different procyclins during the establishment of midgut infections in tsetse flies. We found that different procyclin gene products are expressed in an orderly manner. Early in the infection (day 3), GPEET2 is the only procyclin detected. By day 7, however, GPEET2 disappears and is replaced by several isoforms of glycosylated EP, but not the unglycosylated isoform EP2. Unexpectedly, we discovered that the N-terminal domains of all procyclins are quantitatively removed by proteolysis in the fly, but not in culture. These findings suggest that one function of the protease-resistant C-terminal domain, containing the amino acid repeats, is to protect the parasite surface from digestive enzymes in the tsetse fly gut.
A Data-Centric Approach for Image Scene Localization (2018)

Due to the ubiquity of GPS-equipped cameras such as smartphones, more photos are getting automatically tagged with camera locations (referred to as geo-tagged images) so large-scale geo-tagged image datasets are available on the Web. And a significant portion of online images such as travel and surveillance may not be meaningful without their location information. Thus, image localization for untagged images has been studied. However, the point camera location of an image might be quite different from the location of the scene depicted in the image (referred to as scene location) rendering image localization inaccurate. To address this problem, we propose a data-centric framework for image scene localization using a CNN-based classification in three steps. First, the framework provides two mechanisms for constructing a reference image dataset tagged with scene locations. Second, a spatial-visual classification approach organizes a dataset spatially using R-tree to generate a set of geographical regions tightly bounding the image scene locations. Then, we train a classifier based on the classes of images corresponding to the generated regions. Finally, to enhance the classification accuracy, we train a set of hierarchical classification models utilizing the spatial hierarchical structure of the R-tree where the trained models enable learning the visual features of images at different geographical granularities. We evaluate our framework using a geo-tagged image dataset obtained from Google Street View and demonstrate that the utilization of scene locations enables localizing images far more accurately as compared with camera location based localization.
Histochemical Staining of <em>Arabidopsis thaliana</em> Secondary Cell Wall Elements (2014)

Arabidopsis thaliana is a model organism commonly used to understand and manipulate various cellular processes in plants, and it has been used extensively in the study of secondary cell wall formation. Secondary cell wall deposition occurs after the primary cell wall is laid down, a process carried out exclusively by specialized cells such as those forming vessel and fiber tissues. Most secondary cell walls are composed of cellulose (40-50%), hemicellulose (25-30%), and lignin (20-30%). Several mutations affecting secondary cell wall biosynthesis have been isolated, and the corresponding mutants may or may not exhibit obvious biochemical composition changes or visual phenotypes since these mutations could be masked by compensatory responses. Staining procedures have historically been used to show differences on a cellular basis. These methods are exclusively visual means of analysis; nevertheless their role in rapid and critical analysis is of great importance. Congo red and calcofluor white are stains used to detect polysaccharides, whereas Mäule and phloroglucinol are commonly used to determine differences in lignin, and toluidine blue O is used to differentially stain polysaccharides and lignin. The seemingly simple techniques of sectioning, staining, and imaging can be a challenge for beginners. Starting with sample preparation using the A. thaliana model, this study details the protocols of a variety of staining methodologies that can be easily implemented for observation of cell and tissue organization in secondary cell walls of plants.
Structure-Based Design of Novel Potent Nonpeptide Thrombin Inhibitors (2002)

The clinical syndromes of thromboembolism are evoked by an excessive stimulation of the coagulation cascade. In this context, the serine protease thrombin plays a key role. Considerable efforts have therefore been devoted to the discovery of safe, orally active inhibitors of this enzyme. On the basis of the X-ray crystal structure of the peptide-like thrombin inhibitor NAPAP complexed with bovine thrombin, we have designed a new structural class of nonpeptidic inhibitors employing a 1,2,5-trisubstituted benzimidazole as the central scaffold. Supported by a series of X-ray structure analyses, we optimized the activity of these compounds. Thrombin inhibition in the lower nanomolar range could be achieved although the binding energy mainly results from nonpolar, hydrophobic interactions. To improve in vivo potency, we increased the overall hydrophilicity of the molecules by introducing carboxylate groups. The very polar compound 24 (BIBR 953) exhibited the most favorable activity profile in vivo. This zwitterionic molecule was converted into the double-prodrug 31 (BIBR 1048), which showed strong oral activity in different animal species. On the basis of these results, 31 was chosen for clinical development.
Joint training of interpolated exponential n-gram models (2013)

For many speech recognition tasks, the best language model performance is achieved by collecting text from multiple sources or domains, and interpolating language models built separately on each individual corpus. When multiple corpora are available, it has also been shown that when using a domain adaptation technique such as feature augmentation [1], the performance on each individual domain can be improved by training a joint model across all of the corpora. In this paper, we explore whether improving each domain model via joint training also improves performance when interpolating the models together. We show that the diversity of the individual models is an important consideration, and propose a method for adjusting diversity to optimize overall performance. We present results using word n-gram models and Model M, a class-based n-gram model, and demonstrate improvements in both perplexity and word-error rate relative to state-of-the-art results on a Broadcast News transcription task.
Lipid metabolism in prostate cancer. (2014)

The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, α-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for β-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice.
On acoustic-echo cancellation implementation with multiple cascadable adaptive FIR filter chips (2003)

The implementation of an acoustic-echo canceler for a speakerphone using multiple cascadable adaptive FIR (finite impulse response) filter ICs (the DSP 56200) is described. Ideally, canceling acoustic echoes requires a delay line that provides a delay equal to the impulse response time of the echo. It is shown that it is feasible to use the 24-bit-coefficient precision of the DSP56200 to reduce the length of the delay line. Simulation results show that with only 256 taps an echo return loss enhancement (ERLE) greater than 10 dB can be achieved on an echo 1000 samples in length.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Simple Protocol for NMR Analysis of the Enantiomeric Purity of Chiral Hydroxylamines (2013)

A practically simple three-component chiral derivatization protocol for determining the enantiopurity of chiral hydroxylamines by (1)H NMR spectroscopic analysis is described, involving their treatment with 2-formylphenylboronic acid and enantiopure BINOL to afford a mixture of diastereomeric nitrono-boronate esters whose ratio is an accurate reflection of the enantiopurity of the parent hydroxylamine.