gebhart/patrepeval huggingface dataset:
Development of HIV fusion inhibitors (2005)

In the past 25 years, the worldwide AIDS epidemic has grown such that roughly 38 million people were estimated to be living with the disease worldwide at the end of 2003. The introduction of antiretroviral-based therapies, beginning in 1987, has enabled many to live with HIV as a chronic, rather than terminal, disease. However, the emergence and spread of drug-resistant strains highlights the continued need for new therapies with novel modes of action. In 2003, the FDA and EMEA approved enfuvirtide (Fuzeon), a 36 amino acid peptide derived from the natural gp41 HR2 sequence, as the first HIV fusion inhibitor. T-1249, a 39 amino acid fusion inhibitor, is active against viruses that develop resistance to enfuvirtide. The development of FIs and the processes to manufacture enfuvirtide and T-1249 on an unprecedented scale for peptide therapeutics are presented. Synthetic routes based on a combination of solid phase peptide synthesis and solution phase fragment condensation as well as the analytical controls necessary to insure a robust process are discussed.
Fast secondary transforms for scalable video coding (2013)

In this paper, we present a secondary transform scheme for inter-layer prediction residue in scalable video coding (SVC). Efficient prediction of the co-located blocks from the base layer (BL) can significantly improve the enhancement layer (EL) coding in SVC, especially when the temporal information from previous EL frames is less correlated than the co-located BL information. Previously, Guo et al. showed that because of the peculiar frequency characteristics of EL residuals, the conventional DCT Type-2 transform is suboptimal and is often outperformed by either the DCT Type-3, or DST Type-3 when these transforms are applied to the EL residuals. However, their proposed technique requires upto 8 additional transform cores, two of which are of size 32×32. Here, in this work, we propose a low-complexity secondary transform scheme, where the proposed transform is applied only to the lower frequency coefficients after DCT. Our proposed transform scheme requires at most only 2 additional cores. We also present a fast implementation for a class of 4×4 secondary transforms, which actually is a cascade of two DCT Type-2 using only 6 multiplications. Simulation results show that our proposed scheme provides significant BD-Rate improvement over the conventional DCT-based coding scheme in the ongoing scalable extensions of HEVC standardization.
A Model-Based Controller for A Three-Phase Four-Wire Shunt Active Filter With Compensation of the Neutral Line Current (2007)

This paper presents a model-based controller for a three-phase four-wire shunt active filter, which uses a three-leg split-capacitor topology to implement the voltage source inverter. The controller is aimed to compensate reactive power and harmonic distortion in the general case of distorted and unbalanced source voltages and load currents, including distorted loads connected between a phase and the neutral line. In addition, the controller is able to compensate for the homopolar component of the load current, that is, the current flowing to the source via the neutral line can be considerably reduced without modifying the actual topology. The complete model in (fixed frame) alphabetagamma-coordinates is presented. Special attention is given to the homopolar component (referred here as the gamma-component) of the line current, source voltage and control input, which are instrumental for the control design purpose. Experimental results in a 2 kVA prototype are provided to illustrate the benefits of the proposed solution.
Hyaluronan-binding protein in endothelial cell morphogenesis. (1992)

Previous studies from several laboratories have provided evidence that interaction of hyaluronan (HA) with the surface of endothelial cells may be involved in endothelial cell behavior. We have recently characterized a mAb, mAb IVd4, that recognizes and neutralizes HA-binding protein (HABP) from a wide variety of cell types from several different species (Banerjee, S. D., and B. P. Toole. 1991. Dev. Biol. 146:186-197). In this study we have found that mAb IVd4 inhibits migration of endothelial cells from a confluent monolayer after "wounding" of the monolayer. HA hexasaccharide, a fragment of HA with the same disaccharide composition as polymeric HA, also inhibits migration. In addition, both reagents inhibit morphogenesis of capillary-like tubules formed in gels consisting of type I collagen and basement membrane components. Immunocytology revealed that the antigen recognized by mAb IVd4 becomes localized to the cell membrane of migrating cells, including many of their lamellipodia. Treatment with high concentrations of HA hexamer causes loss of immunoreactivity from these structures. We conclude that HABP recognized by mAb IVd4 is involved in endothelial cell migration and tubule formation.
Automated prostate cancer detection using <i>T</i>2‐weighted and high‐<i>b</i>‐value diffusion‐weighted magnetic resonance imaging (2015)

Purpose: The authors propose a computer‐aided diagnosis (CAD) system for prostate cancer to aid in improving the accuracy, reproducibility, and standardization of multiparametric magnetic resonance imaging (MRI). Methods: The proposed system utilizes two MRI sequences [ T 2‐weighted MRI and high‐ b ‐value ( b = 2000 s/mm 2 ) diffusion‐weighted imaging (DWI)] and texture features based on local binary patterns. A three‐stage feature selection method is employed to provide the most discriminative features. The authors included a total of 244 patients. Training the CAD system on 108 patients (78 MR‐positive prostate cancers and 105 benign MR‐positive lesions), two validation studies were retrospectively performed on 136 patients (68 MR‐positive prostate cancers, 111 benign MR‐positive lesions, and 117 MR‐negative benign lesions). Results: In distinguishing cancer from MR‐positive benign lesions, an area under receiver operating characteristic curve (AUC) of 0.83 [95% confidence interval (CI): 0.76–0.89] was achieved. For cancer vs MR‐positive or MR‐negative benign lesions, the authors obtained an AUC of 0.89 AUC (95% CI: 0.84–0.93). The performance of the CAD system was not dependent on the specific regions of the prostate, e.g., a peripheral zone or transition zone. Moreover, the CAD system outperformed other combinations of MRI sequences: T 2W MRI, high‐ b ‐value DWI, and the standard apparent diffusion coefficient (ADC) map of DWI. Conclusions: The novel CAD system is able to detect the discriminative texture features for cancer detection and localization and is a promising tool for improving the quality and efficiency of prostate cancer diagnosis.
VII.C.4 Low Pt Loading Fuel Cell Electrocatalysts (2005)

Objectives • Improve the activity of Pt monolayer electrocatalysts for O2 reduction (PtML/Pd/C). • Demonstrate the stability of Pt monolayer electrocatalysts in fuel cell tests. • Improve the syntheses of electrocatalysts with ultra-low or no Pt content (Pt/AuNi/C and Pd2Co/C), and test the electrocatalysts in fuel cells. • Explore a novel class of electrocatalysts for O2 reduction consisting of mixed monolayers of Pt and late transition metals.
Choline Dehydrogenase Polymorphism rs12676 Is a Functional Variation and Is Associated with Changes in Human Sperm Cell Function (2012)

Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh(-/-) males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm.
A study on robust utterance verification for connected digits recognition (1997)

Utterance verification represents a key technology in the design of a user-friendly speech recognition system. One essential element when designing such a system is the ability to maintain a uniform performance over a wide range of acoustic conditions. An acoustic mismatch between training and testing conditions often results in an undesirable performance degradation. This paper addresses the issue of robustness in utterance verification of a speech recognition system. Two techniques, namely signal bias removal (SBR) and on-line adaptation, are studied. The SBR algorithm is used to deal with global mismatch conditions caused by handset and channel differences. The on-line adaptation algorithm is used to adjust verification threshold at runtime for achieving a desirable trade-off between false rejection and false alarm in new test conditions. Various on-line adaptation schemes are investigated. We show that both supervised or unsupervised adaptation can effectively adjust the verification threshold to achieve a desirable performance trade-off irrespective of the initial setting of the threshold. We report on connected digit recognition/verification results for matched and mismatched training and testing conditions. At a 5% digit string rejection rate, the proposed robust utterance verification system gives a reduction in string error rate between 32% and 35% over the conventional system, while still correctly rejects over 99.9% of nonvocabulary utterances.
Cellulose Nanofibers Prepared by TEMPO-Mediated Oxidation of Native Cellulose (2007)

Never-dried and once-dried hardwood celluloses were oxidized by a 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated system, and highly crystalline and individualized cellulose nanofibers, dispersed in water, were prepared by mechanical treatment of the oxidized cellulose/water slurries. When carboxylate contents formed from the primary hydroxyl groups of the celluloses reached approximately 1.5 mmol/g, the oxidized cellulose/water slurries were mostly converted to transparent and highly viscous dispersions by mechanical treatment. Transmission electron microscopic observation showed that the dispersions consisted of individualized cellulose nanofibers 3-4 nm in width and a few microns in length. No intrinsic differences between never-dried and once-dried celluloses were found for preparing the dispersion, as long as carboxylate contents in the TEMPO-oxidized celluloses reached approximately 1.5 mmol/g. Changes in viscosity of the dispersions during the mechanical treatment corresponded with those in the dispersed states of the cellulose nanofibers in water.
Development of a biocompatible and biodegradable hybrid hydrogel platform for sustained release of ionic drugs (2014)

In this study, we reported the development of a new drug encapsulation strategy and a robust hybrid hydrogel platform for controlled and sustained release of small and large molecule ionic drugs. A biodegradable, biocompatible and temperature stimuli responsive hybrid hydrogel platform was fabricated from arginine based unsaturated poly(ester amides) (Arg-UPEAs), Pluronic diacrylate (Pluronic-DA) and alginate by the UV photo-crosslinking method, combining the favorable properties of a hydrogel and a polyelectrolyte complex. The hydrogels were systematically characterized, including the swelling mechanics, mechanical properties, biodegradation and interior morphologies. In vitro biocompatibility study showed that the hydrogels could support the cell attachment and proliferation well. Some model drugs, such as hydrochloride salts of hydralazine, insulin and interleukin-12, were encapsulated into the hydrogels and the drug release behavior was investigated using HPLC, LC-MS, BCA assay and ELISA assay. The obtained release profiles indicated that the Pluronic/Arg-UPEA/alginate hybrid hydrogels could release ionic drugs over weeks in vitro via a sustained manner. The structure-function study of hydrogels indicated that the polymer structure, hydrogel composition and environmental temperature had strong effects on the hydrogel properties and their drug release profiles.
Identification of differentially expressed mRNA in prokaryotic organisms by customized amplification libraries (DECAL): The effect of isoniazid on gene expression in <i>Mycobacterium tuberculosis</i> (1998)

Understanding the effects of the external environment on bacterial gene expression can provide valuable insights into an array of cellular mechanisms including pathogenesis, drug resistance, and, in the case of Mycobacterium tuberculosis, latency. Because of the absence of poly(A)+ mRNA in prokaryotic organisms, studies of differential gene expression currently must be performed either with large amounts of total RNA or rely on amplification techniques that can alter the proportional representation of individual mRNA sequences. We have developed an approach to study differences in bacterial mRNA expression that enables amplification by the PCR of a complex mixture of cDNA sequences in a reproducible manner that obviates the confounding effects of selected highly expressed sequences, e.g., ribosomal RNA. Differential expression using customized amplification libraries (DECAL) uses a library of amplifiable genomic sequences to convert total cellular RNA into an amplified probe for gene expression screens. DECAL can detect 4-fold differences in the mRNA levels of rare sequences and can be performed on as little as 10 ng of total RNA. DECAL was used to investigate the in vitro effect of the antibiotic isoniazid on M. tuberculosis, and three previously uncharacterized isoniazid-induced genes, iniA, iniB, and iniC, were identified. The iniB gene has homology to cell wall proteins, and iniA contains a phosphopantetheine attachment site motif suggestive of an acyl carrier protein. The iniA gene is also induced by the antibiotic ethambutol, an agent that inhibits cell wall biosynthesis by a mechanism that is distinct from isoniazid. The DECAL method offers a powerful new tool for the study of differential gene expression.
Thermodynamics of Solute Partitioning into Immobilized Artificial Membranes (1995)

The solute retention mechanism on immobilized artificial membranes (IAMs) was studied using three different IAM.PC phases. IAMs were prepared by immobilizing either single-chain or double-chain phosphatidylcholine (PC) ligands. Solute affinity for the single-chain IAM.PC columns (with a ligand density of 127 mumol of PC/g of IAM) was 3-fold lower compared to solute affinity on the double-chain IAM.PC column (with a ligand density of 98 mumol of PC/g of IAM). This suggests that the solute retention on IAMs is dominated by a solute partitioning mechanism. Temperature-dependent studies indicated that the thermodynamics of solute partitioning is similar on both the single-chain and double-chain IAM.PC surfaces. For a set of phenol derivatives, the partitioning into IAM.PC surfaces is both enthalpy and entropy driven. For beta-blockers, the partitioning into IAM.PC surfaces is entropy driven. The free energy of solute partitioning into IAMs correlates very well with the free energy of solute partitioning into liposomes.
Decision support system for treatment selection: <i>Application of a statistical expert advisor to the problem of prostate cancer treatment selection</i> (1993)

Abstract For clinical cases with difficult combinations of patient parameter values, treatment selection may be complex or controversial and require considerable time. Treatment selection may be affected by a clinician's experience with a disease and expertise with a treatment, existing protocols, capabilities of local medical facilities, and patient preference. We discuss the concepts and clinical applications of an interactive statistical package (isp) software shell which can create systems that reproduce the judgment of one or more expert clinicians in the management of a patient. An isp system can 1) be taught, verified, updated, and tailored to local facilities quickly and easily by an individual clinician, 2) compute and rank treatment selection probabilities for a presented case in accord with the treatment preferences of its human teacher and explain to a clinician the logical and statistical basis of each step of the decision process, 3) identify sensitive variables of a case for additional verification and to allow questions of the type “what would be the treatment preferences if the value of this variable were changed?”, 4) accumulate statistics for unusual cases (rare combinations of patient parameter values), and 5) continue to learn and achieve further (statistical) insight by recognizing variable combinations (joint variables) whose values are more sensitive to the selection of a particular treatment. An isp system can be used for 1) second opinions, by estimating the treatment preferences of one or more clinical experts for a particular case, 2) allowing patient involvement in the treatment decision in cases for which several treatment options may provide the same outcome, 3) quality assurance, by helping a clinician to identify and review critical patient parameter values and pivotal questions, and to check a treatment decision with his own isp system and those of colleagues, 4) avoiding unnecessary diagnostic tests, by identifying parameters that do not affect the treatment selection for a case, 5) documenting the decision factors of a case, 6) finding the reasons for differences among experts in treatment selection for different types of cases, and 7) teaching residents. The concepts and clinical application of an isp system are discussed. © 1993 Wiley‐Liss, Inc.
Transparent Conductive Oxide Layer-Less Three Dimensional Dye Sensitized Solar Cells: Fabrication of Ionic Path in Three Dimensional Ti Electrode (2009)

A transparent conductive oxide-less dye-sensitized solar cell (TCO-less DSC) consisting of a thick and porous Ti electrode is reported. The Ti electrode was contacted with the back of a stained porous titania layer. A thick Ti electrode prepared by conventional sputtering prevented ionic diffusions through the Ti electrode and decreased photovoltaic performance. Tetrapod-shaped ZnO crystals were used to prepare straight and continuous nanopores in the Ti electrode to maintain the ionic diffusion. 8% efficiency of the TCO-less DSC is also reported.
Abstract B254: Extended target-coverage by selective Chk1 inhibitors enhances pharmacodynamic inhibition of Chk1 signaling and antitumor activity <i>in vivo</i> (2009)

Abstract Loss of coordination between cell cycle checkpoints and DNA damage repair is a fundamental feature tumor cells rely on for unregulated growth and developing chemotherapeutic resistance. The protein kinase Checkpoint kinase 1 (Chk1) is a sentinel molecule essential for cell cycle arrest at the S and G2M checkpoints, as well as regulating homologous recombination DNA repair. In tumor cells exposed to chemotherapy, Chk1 inhibition overrides cell cycle arrest and DNA repair functions, effectively driving tumor cells into a state of mitotic catastrophe and, ultimately, cell death. We have previously reported in schedule-dependence studies, using Chk1 inhibitors and irinotecan (CPT-11), that oral administration of Chk1 inhibitors allows for multi-day target-coverage, and thus continuous inhibition of Chk1 for a finite period of time, which maximizes anti-tumor efficacy. Here, we extend these studies and investigate the pharmacodynamic relationship to efficacy, as well as the specific biomarkers that are predictive of an anti-tumor effect, when Chk1 inhibitors are administered on a multi-day dosing schedule. Utilizing potent (IC50=24–27nM), selective, and orally bio-available small molecule Chk1 inhibitors of which Chk1-A and Chk1-C are representative, we find only modest inhibition of the functional biomarker phospho-cdc2, following a single dose of a Chk1 inhibitor. Alternatively, on multi-day Chk1 inhibitor dose schedules, we find dose-related pharmacodynamic inhibition of Chk1 signaling that is maximized at doses where we see significant tumor growth inhibition in efficacy experiments. Furthermore, multi-day dosing of Chk1 inhibitors induces marked inhibition of phospho-cdc2 and Rad51 protein levels, suggesting tumoricidal activity related to Chk1 inhibition is due to both checkpoint override and impairment of DNA damage repair. In human tumor xenografts administered combination therapy with gemcitabine, an orally-delivered Chk1 inhibitor dosed on a multi-day schedule shows superior efficacy over an IV administered compound. Taken together, our findings show a clear correlative relationship between pharmacodynamic target inhibition and anti-tumor activity that is exclusively achieved on multi-day dose schedules. These results demonstrate the need for prolonged Chk1 inhibition to provide robust pharmacodynamic inhibition and maximal anti-tumor efficacy. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B254.
Measurement of compressed breast thickness by optical stereoscopic photogrammetry (2009)

The determination of volumetric breast density (VBD) from mammograms requires accurate knowledge of the thickness of the compressed breast. In attempting to accurately determine VBD from images obtained on conventional mammography systems, the authors found that the thickness reported by a number of mammography systems in the field varied by as much as 15 mm when compressing the same breast or phantom. In order to evaluate the behavior of mammographic compression systems and to be able to predict the thickness at different locations in the breast on patients, they have developed a method for measuring the local thickness of the breast at all points of contact with the compression paddle using optical stereoscopic photogrammetry. On both flat (solid) and compressible phantoms, the measurements were accurate to better than 1 mm with a precision of 0.2 mm. In a pilot study, this method was used to measure thickness on 108 volunteers who were undergoing mammography examination. This measurement tool will allow us to characterize paddle surface deformations, deflections and calibration offsets for mammographic units.
Defective Interfering Influenza Virus RNAs: Time To Reevaluate Their Clinical Potential as Broad-Spectrum Antivirals? (2014)

Defective interfering (DI) RNAs are highly deleted forms of the infectious genome that are made by most families of RNA viruses. DI RNAs retain replication and packaging signals, are synthesized preferentially over infectious genomes, and are packaged as DI virus particles which can be transmitted to susceptible cells. Their ability to interfere with the replication of infectious virus in cell culture and their potential as antivirals in the clinic have long been known. However, until now, no realistic formulation has been described. In this review, we consider the early evidence of antiviral activity by DI viruses and, using the example of DI influenza A virus, outline developments that have led to the production of a cloned DI RNA that is highly active in preclinical studies not only against different subtypes of influenza A virus but also against heterologous respiratory viruses. These data suggest the timeliness of reassessing the potential of DI viruses as a novel class of antivirals that may have general applicability.