gebhart/patrepeval huggingface dataset:
Aberrations and retinal image quality of the normal human eye (1997)

We have constructed a wave-front sensor to measure the irregular as well as the classical aberrations of the eye, providing a more complete description of the eye's aberrations than has previously been possible. We show that the wave-front sensor provides repeatable and accurate measurements of the eye's wave aberration. The modulation transfer function of the eye computed from the wave-front sensor is in fair, though not complete, agreement with that obtained under similar conditions on the same observers by use of the double-pass and the interferometric techniques. Irregular aberrations, i.e., those beyond defocus, astigmatism, coma, and spherical aberration, do not have a large effect on retinal image quality in normal eyes when the pupil is small (3 mm). However, they play a substantial role when the pupil is large (7.3-mm), reducing visual performance and the resolution of images of the living retina. Although the pattern of aberrations varies from subject to subject, aberrations, including irregular ones, are correlated in left and right eyes of the same subject, indicating that they are not random defects.
A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection (2012)

We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic hepatitis C (CHC). This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR) rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents.
Selective Frequency Invariant Uniform Circular Broadband Beamformer (2010)

Frequency-Invariant (FI) beamforming is a well known array signal processing technique used in many applications. In this paper, an algorithm that attempts to optimize the frequency invariant beampattern solely for the mainlobe, and relax the FI requirement on the sidelobe is proposed. This sacrifice on performance in the undesired region is traded off for better performance in the desired region as well as reduced number of microphones employed. The objective function is designed to minimize the overall spatial response of the beamformer with a constraint on the gain being smaller than a pre-defined threshold value across a specific frequency range and at a specific angle. This problem is formulated as a convex optimization problem and the solution is obtained by using the Second Order Cone Programming (SOCP) technique. An analysis of the computational complexity of the proposed algorithm is presented as well as its performance. The performance is evaluated via computer simulation for different number of sensors and different threshold values. Simulation results show that, the proposed algorithm is able to achieve a smaller mean square error of the spatial response gain for the specific FI region compared to existing algorithms.
Methylation Subtypes and Large-Scale Epigenetic Alterations in Gastric Cancer (2012)

Epigenetic alterations are fundamental hallmarks of cancer genomes. We surveyed the landscape of DNA methylation alterations in gastric cancer by analyzing genome-wide CG dinucleotide (CpG) methylation profiles of 240 gastric cancers (203 tumors and 37 cell lines) and 94 matched normal gastric tissues. Cancer-specific epigenetic alterations were observed in 44% of CpGs, comprising both tumor hyper- and hypomethylation. Twenty-five percent of the methylation alterations were significantly associated with changes in tumor gene expression. Whereas most methylation-expression correlations were negative, several positively correlated methylation-expression interactions were also observed, associated with CpG sites exhibiting atypical transcription start site distances and gene body localization. Methylation clustering of the tumors revealed a CpG island methylator phenotype (CIMP) subgroup associated with widespread hypermethylation, young patient age, and adverse patient outcome in a disease stage-independent manner. CIMP cell lines displayed sensitivity to 5-aza-2'-deoxycytidine, a clinically approved demethylating drug. We also identified long-range regions of epigenetic silencing (LRESs) in CIMP tumors. Combined analysis of the methylation, gene expression, and drug treatment data suggests that certain LRESs may silence specific genes within the region, rather than all genes. Finally, we discovered regions of long-range tumor hypomethylation, associated with increased chromosomal instability. Our results provide insights into the epigenetic impact of environmental and biological agents on gastric epithelial cells, which may contribute to cancer.
Clonotypic B Cells Circulate in Hodgkin’s Lymphoma (HL). (2006)

Abstract Reed-Sternberg (RS) cells, the hallmark of HL, are clonal B lineage cells generally characterized by their co-expression of CD15 and CD30. RS cells also occasionally express the plasma cell (PC) cell surface antigen CD138 (syndecan-1), and we thus hypothesized that RS may represent aberrant PC differentiation. We found that RS cells from the L428 HL cell line exhibited an expression profile similar to normal PC and those from multiple myeloma (MM): high expression of the PC transcription factor Blimp-1 and low expression of the germinal center B cell markers Pax-5 and Bcl-6. We recently demonstrated that CD138+ MM PC, like their normal counterparts, have limited replicative potential; rather, self-renewing CD138neg clonotypic B cells appear to be responsible for the initiation and maintenance of MM, giving rise to the differentiated CD138+ MM PC (Matsui et al Blood103: 2332–2336, 2004). To determine if RS cells similarly were differentiated progeny of rare HL cancer stem cells, we studied HL cell lines (L428, KM-H2) and found that each line contained a small (&amp;lt;5%) subpopulation of cells that did not express the RS markers CD15 and CD30 present on most of the cells. This small subpopulation instead resembled memory B cells (CD19+CD20+CD27+) and in addition possessed most of the clonogenic capacity of the HL cell lines; this suggested that RS cells, similar to the neoplastic PC in MM, are not the cells responsible for the growth and maintenance of HL. Using Aldefluor, a fluorescent aldehyde that is a substrate for aldehyde dehydrogenase (ALDH), we previously showed that ALDH is highly expressed in both normal and MM stem cells. The clonogenic subpopulation within the HL cell lines also expressed high ALDH activity, while the predominant RS cells exhibited low ALDH activity. To determine if clonotypic memory B cells were similarly present in HL patients, CD19+ cells were isolated from the marrow or blood of 5 HL patients. The bulk CD19+ cells, as well as those that were ALDHlow, isolated from the HL patients were a mixture of non-clonal naive and memory B cells. However, the ALDHhigh CD19+ cells were a highly enriched population of immunoglobulin (Ig) light chain-restricted CD27+ memory B cells that represented 0.7 to 3% of the circulating CD19+ cells, in 4/5 patients (none with evidence of marrow involvement) studied. These ALDHhigh CD19+ cells also displayed clonal Ig gene rearrangement by polymerase chain reaction (PCR) amplification. In two of these patients, CD15+CD30+ RS cells were isolated from a fresh diagnostic lymph node and contained the same clonal Ig gene rearrangement as the circulating ALDHhigh CD19+ B cells. Thus, clonotypic memory B cells can be found in both HL cell lines and patients. These data suggest that these clonotypic memory B cells circulate in relatively high numbers even in early stage patients, and may represent the HL stem cells. Our results also suggest that therapies, such as rituximab, that target these putative HL stem cells may have clinical activity in HL patients.
Hepatitis B virus X protein produced in Escherichia coli is biologically functional (1990)

The hepatitis B virus X gene product trans activates transcription from a variety of viral and cellular regulatory elements. We expressed the complete, nonfused X protein in Escherichia coli and showed it to be active in trans activating a human immunodeficiency virus long terminal repeat-linked chloramphenicol acetyltransferase reporter gene.
X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease (2021)

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M<sup>pro</sup>), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M<sup>pro</sup> In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.
Effects of Drug Solubility, Drug Loading, and Polymer Molecular Weight on Drug Release from Polyox® Tablets (1998)

This study investigated the effects of polymer molecular weight, drug solubility, addition of a water-soluble excipient, and drug loading on zero-order release kinetics and elucidated the release mechanism of a drug from directly compressed tablets. Directly compressed tablets consisting of polyethylene oxides (PEO) (MW = 0.9, 2.0 and 4.0 x 10(6)) and drugs (solubility ranging from 290 to 25,000 mg/l) were formulated with or without a water-soluble excipient (lactose). For PEO tablets (MW = 0.9 x 10(6)), drug release is primarily swelling/erosion controlled for drugs for which solubility is below 1%, resulting in zero-order release kinetics. For PEO tablets (MW = 4.0 x 10(6)), drug release is controlled at a zero-order rate by the dissolution rate of the drug at high loading (39%). At low loading (20%), drug diffusion through the swollen gel layer becomes the governing release mechanism. For a highly water-soluble drug (e.g., diclofenac Na), drug diffusion is the controlling mechanism regardless of the molecular weight of the PEOs. Zero-order release kinetics can be achieved with PEO tablets (MW = 0.9 x 10(6)) for drugs for which solubility is below 1%. PEO tablets (MW = 2.0 x 10(6)) provided zero-order release for poorly water-soluble drugs (below 0.2%) at 39% drug loading. It is possible to attain zero-order release kinetics with PEO tablets (MW = 4.0 x 10(6)) using a drug which has a solubility of less than 0.1%.
Coenzyme Q Protects Cells Against Serum Withdrawal-Induced Apoptosis by Inhibition of Ceramide Release and Caspase-3 Activation (2000)

Coenzyme Q10 (CoQ10) is a component of the antioxidant machinery that protects cell membranes from oxidative damage and decreases apoptosis in leukemic cells cultured in serum-depleted media. Serum deprivation induced apoptosis in CEM-C7H2 (CEM) and to a lesser extent in CEM-9F3, a subline overexpressing Bcl-2. Addition of CoQ10 to serum-free media decreased apoptosis in both cell lines. Serum withdrawal induced an early increase of neutral-sphingomyelinase activity, release of ceramide, and activation of caspase-3 in both cell lines, but this effect was more pronounced in CEM cells. CoQ10 prevented activation of this cascade of events. Lipids extracted from serum-depleted cultures activated caspase-3 independently of the presence of mitochondria in cell-free in vitro assays. Activation of caspase-3 by lipid extracts or ceramide was prevented by okadaic acid, indicating the implication of a phosphatase in this process. Our results support the hypothesis that plasma membrane CoQ10 regulate the initiation phase of serum withdrawal-induced apoptosis by preventing oxidative damage and thus avoiding activation of downstream effectors as neutral-sphingomyelinase and subsequent ceramide release and caspase activation pathways.
Joint IP networking and radio architecture for vehicular networks (2011)

An attempt is made at jointly describing IP addressing/routing and radio architecture for vehicular networks. Since this relates very different communications layers (PHY/MAC/Network), the effective results are only roughly identified; yet the traits of a common perspective do develop, thanks to identifying common aspects of the vehicular networks topologies. We introduce first models of IP vehicular network topologies, representing a typical highway, vehicles and radio cells. Then we describe an IP addressing model for three types of vehicles and six types of IP topologies, followed by a description of frequency allocation and power control for cells; as an addition, we present an algorithm for IP route exchange and its model of route propagation in a particular topology used for multi-body vehicle applications. The concepts described in this paper are guidelines for further protocol development work towards a complete solution for IP networking and radio architecture for vehicular networks.
Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions (2018)

Autoantibody-mediated diseases are currently treated with intravenous immunoglobulin, which is thought to act in part via blockade of Fc gamma receptors, thereby inhibiting autoantibody effector functions and subsequent pathology. We aimed to develop recombinant molecules with enhanced Fc receptor avidity and thus increased potency over intravenous immunoglobulin. Here we describe the molecular engineering of human Fc hexamers and explore their therapeutic and safety profiles. We show Fc hexamers were more potent than IVIG in phagocytosis blockade and disease models. However, in human whole-blood safety assays incubation with IgG1 isotype Fc hexamers resulted in cytokine release, platelet and complement activation, whereas the IgG4 version did not. We used a statistically designed mutagenesis approach to identify the key Fc residues involved in these processes. Cytokine release was found to be dependent on neutrophil FcγRIIIb interactions with L234 and A327 in the Fc. Therefore, Fc hexamers provide unique insights into Fc receptor biology.
The role of superoxide in the destruction of erythrocyte targets by human neutrophils. (1980)

Human neutrophils exposed to the soluble stimulus, phorbol myristate acetate, generate a flux of O2.- which can destroy human erythrocyte targets. Under optimal conditions, each neutrophil was capable of lysing almost 10 erythrocyte targets. Hemolysis was inhibited by exogenous copper-zinc or iron superoxide dismutase while neither heat-denatured enzyme nor albumin inhibited cytotoxicity. Although neutrophils can also generate H2O2, neither catalase nor a glutathione-glutathione peroxidase system inhibited hemolysis. Hemolysis was prevented by conversion of the hemoglobin to carbon monoxyhemoglobin, suggesting an intracellular mechanism of cytotoxicity. Conversion of hemoglobin to methemoglobin by nitrite treatment did not impair neutrophil-mediated hemolysis. However, nitrite-treated targets were not protected by superoxide dismutase, while exogenous catalase inhibited cytotoxicity, suggesting a potential role for H2O2 and methemoglobin. H2O2 and methemoglobin are known to interact to form an oxidant complex whose cytotoxic potential was underlined by the marked sensitivity of nitrite-treated cells to commercial H2O2. It is proposed that neutrophil-derived O2.- oxidizes oxyhemoglobin to generate methemoglobin and H2O2 which interact to form a cytotoxic complex capable of hemolyzing the erythrocyte target.
Defined Oligonucleotide Tag Pools and PCR Screening in Signature-Tagged Mutagenesis of Essential Genes from Bacteria (1999)

We describe a fast and simple method for signature-tagged mutagenesis (STM) using defined oligonucleotides for tag construction into mini-Tn5 and PCR instead of hybridization for rapid screening of bacterial mutants in vivo. A collection of 12 unique 21-mers were synthesized as complementary DNA strands to tag bacterial mutants constructed by insertional mutagenesis using pUTmini-Tn5Km2 plasmids. Tags were tested in a combination of assays by PCR and compared to hybridization for specificity and for large-scale screening. Each defined tag has the same melting temperature, an invariable region to optimize PCRs and a variable region for specific amplification by PCR. A series of "suicide" plasmids carrying mini-Tn5s, each with a specific tag, were transferred into Pseudomonas aeruginosa, giving 12 libraries of mutants; groups of 12 mutants were pooled and arrayed into 96-well microplates, representing approximately one-sixth of the P. aeruginosa 5.9-Mb genome. This simple STM method can be adapted to any bacterial system and used for genome scanning in various growth conditions.
A laser/EMAT system for thickness monitoring applications using shear and L-S mode-converted waves (2001)

A laser/EMAT system is described for non-contact monitoring of metal thickness. In a B-scan imaging configuration, quantitative time-of-flight analysis of laser-generated shear waves and longitudinal-shear mode-converted waves can be used as an effective method for thickness monitoring. Q-switched Nd:YAG laser pulses with energies of ∼ 18 mJ were delivered to the material surface via an optical fibre and focused to a line source by a cylindrical lens. Transient acoustic waves propagated through the plate to be reflected from the far surface. Waves returning to the surface, including L-S mode-converted waves, were detected using an EMAT sensitive to in-plane motion. B-scans were generated as the sensor head was moved along the material's surface, forming a 2D intensity profile that made changes in plate thickness easy to visualize. The L-S and S-L mode-converted waves provided a method of simultaneously monitoring two different points on the far surface, enabling and changes in the material thickness to be clearly identified.
The Effect of Pipette Tip Roughness on Giga-seal Formation (2009)

Abstract — Reported is a study of applying nanofabrication technology to improve the surface roughness of micro glass pipettes to achieve giga ohm seal resistance in patch clamping processes. The surface roughness of pipette tips was first measured by 3D reconstruction of pipette tips using stereo imaging technique based on high resolution SEM images. Both the SEM images and the reconstructed images show that micro glass pipettes have rough and uneven tips which could be one of the causes of leakage in patch clamping. Then focused ion beam system was used to cut across the very end of the tip, producing a smooth and flat new tip. The average surface roughness Ra of a milled pipette tip was within a few nanometres. Patch clamping experiments were carried out using the polished pipettes on human umbilical vein endothelial cells (HUVEC), which were well known for their extremely flat shape making them very difficult to patch. The results show that above 3 Giga ohm seals were achieved in 60 % of the experiments, as opposed to 1.5-2.0 GΩ in average with the conventional pipettes. The highest seal resistance achieved with a focused ion beam polished pipette was 9 GΩ, well above the 3 GΩ resistance, the usually best result achieved with a conventional pipette. The leakage current in single channel recording afterwards was found 0.3 pA, significantly smaller than 2-3 pA usually achieved using conventional pipettes. The research results demonstrate that the surface roughness of a pipette has a significant effect on the giga-seal formation of a patch clamping process.
The bovine mannose 6-phosphate/insulin-like growth factor II receptor. The role of arginine residues in mannose 6-phosphate binding. (1993)

The extracytoplasmic region of the bovine cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) consists of 15 homologous repeating domains, each of which is approximately 147 residues in length. The receptor contains two high affinity mannose 6-phosphate (Man-6-P) binding sites and our recent studies (Westlund, B., Dahms, N. M., and Kornfeld, S. (1991) J. Biol. Chem. 266, 23233-23239) have localized these two binding sites to domains 1-3 and 7-11. To further define the location of the Man-6-P binding sites and to determine the role of specific arginine residues in Man-6-P binding, site-directed mutagenesis was utilized to create truncated soluble forms of the M6P/IGF-II receptor in conjunction with either conservative (Lys) or nonconservative (Ala) replacement of arginine residues. These mutants were expressed transiently in COS-1 cells and assayed for their ability to bind phosphomannosyl residues by affinity chromatography. Analysis of the ligand binding activity of carboxyl-terminal truncated forms of the receptor's extracytoplasmic region demonstrated that the second Man-6-P binding site is contained within domains 7-9. Substitution of Arg435 in domain 3 of the amino-terminal binding site and Arg1334 in domain 9 of the second binding site results in a dramatic loss of ligand binding activity. However, substitutions at positions 435 and/or 1334 did not affect the secretion, glycosylation, or immunoreactivity of these truncated proteins. Taken together, these results indicate that Arg435 and Arg1334 are essential components of the M6P/IGF-II receptor's high affinity Man-6-P binding sites.
.beta.-Adrenoceptor antagonist activity of bivalent ligands. 1. Diamide analogs of practolol. (1987)

Two series of bivalent ligands (P-X-P) containing the (R,S)-3-[(4-aminoaryl)oxy]-1-(isopropylamino)propan-2-ol pharmacophore and a connecting alpha,omega-dicarbonylpoly(methylene) [X = -OC(CH2)nCO-] or alpha,omega-N,N'-bis(carbonylmethylene) polymethylenediamine [X = -OCCH2NH(CH2)nNHCH2CO-] spanner were synthesized and evaluated for beta-adrenoceptor antagonist activity in rat heart and lung membrane preparations. The target compounds were obtained as a mixture of stereoisomers in modest yields by using a three to four step sequence beginning with N-benzylpractolol. The results from the competitive binding studies indicated that binding affinity increased by a factor of up to 160 by increasing the length of the group spanning the pharmacophore moieties. Modest increases in cardioselectivity were also obtained. The data suggest that further increases in spanner length and lipophilicity and optical resolution may improve the potential of a labeled bivalent beta 1-adrenoceptor antagonist to function as a myocardial imaging agent.
A mixed-signal decision-feedback equalizer that uses a look-ahead architecture (1997)

A mixed-signal decision-feedback equalizer (DFE) that uses a look-ahead architecture is described. The parallelism in the look-ahead DFE (LA DFE) achieves an increase in the data rate over a conventional DFE with a small increase in area. Fully differential analog circuits perform the convolution operation in the LA DFE, and the coefficient adaption is carried out by digital circuits. The LA DFE occupies 23 mm/sup 2/ in a 2-/spl mu/m CMOS process and operates at 50 Mb/s while dissipating 260 mW.