gebhart/patrepeval huggingface dataset:
Epidermal Langerhans cells from normal human skin bind monomeric IgE via Fc epsilon RI. (1992)

Human epidermal Langerhans cells (LC) bearing IgE are found in disease states associated with hyperimmunoglobulinemia E. When studying the mechanism(s) underlying this phenomenon, immunohistology revealed that a majority of epidermal LC from normal skin of healthy individuals can specifically bind monomeric IgE. IgE binding to LC could neither be prevented by preincubation of the tissue with monoclonal antibodies (mAb) against either Fc epsilon RII/CD23 or Fc gamma RII/CD32, nor by the addition of lactose. However, binding could be entirely abrogated by preincubation with the anti-Fc epsilon RI alpha mAb 15-1, which interferes with IgE binding to Fc epsilon RI alpha gamma transfectants. These observations indicated that IgE binding to epidermal LC is mediated by Fc epsilon RI rather than by CD23, CD32, or the D-galactose-specific IgE-binding protein. This assumption gained support from our additional findings that: (a) the majority of LC exhibited distinct surface immunolabeling with the anti-Fc epsilon RI alpha mAbs 15-1 and 19-1, but not with any of eight different anti-Fc epsilon RII/CD23 mAbs; and (b) transcripts for the alpha, beta, and gamma chains of Fc epsilon RI could be amplified by polymerase chain reaction from RNA preparations of LC-enriched, but not of LC-depleted, epidermal cell suspensions. In view of the preeminent role of Fc epsilon RI crosslinking on mast cells and basophils in triggering the synthesis and release of mediators of allergic reactions, the demonstration of this receptor on epidermal LC may have important implications for our understanding of allergic reactions after epicutaneous contact with allergens.
Detection of Solder Bump Defects in Electronic Packages Using Local Temporal Coherence Analysis of Laser Ultrasonic Signals (2009)

Microelectronics packaging technology has evolved from through-hole and bulk configurations to surface-mount and small-profile configurations. Surface mount devices, such as flip chip packages, chip scale packages, and ball grid arrays, use solder bump interconnections between them and substrates/printed wiring boards. Solder bumps, which are hidden between the device and the substrate/board, are difficult to inspect. A solder bump inspection system was developed using laser ultrasound and interferometric techniques. This system has been successfully applied to detect solder joint/bump defects, including missing, misaligned, open, and cracked solder joints/bumps in flip chips, chip scale packages, and multilayer ceramic capacitors. This system uses a pulsed Nd:YAG laser to induce ultrasound in the electronic packages in the thermoelastic regime; it then measures the transient out-of-plane displacement response on the package surface using the interferometric technique. This paper presents a local temporal coherence (LTC) analysis of laser ultrasound signals and compares it to previous signal-processing methods, including error ratio and correlation coefficient methods. The results showed that LTC analysis increased measurement accuracy and sensitivity for inspecting solder bump defects in electronic packages. Laser ultrasound inspection results are also compared with X-ray and C-mode scanning acoustic microscopy results. In particular, this paper discusses defect detection for 6.35×6.35×0.6 mm3 flip chips and flip chips (“SiMAF;” Siemens AG) with lead-free solder bumps.
Purification and Characterization of A Cytostatic Factor With Anti-Viral Activity From The Bitter Melon (1983)

Abstract We have previously reported -that a crude aqueous extract of the bitter melon (Momordica charantia) has both cytostatic and cytotoxic active ties 1,2, and is a competitive inhibitor of guanylate cyclase activity3. This crude preparation kills human leukemic lymphocytes in a dose-dependent manner while not affecting the viability of normal human lymphocytes at these same doses1. In this report we describe the purification and characterization of one of these cytostatic factors which also exhibits anti-viral activity. The partially purified factor was both cytostatic to BHK-21 cells and inhibitory to VSV plaque formation in a dose-dependent manner. This preparation was inhibitory to both viral and host cell RNA and protein synthesis as early as 30 min after addition to these samples. As determined by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), this purified factor is a single component with a molecular weight corresponding to 40,000 daltons. The factor is sensitive to boiling and to pre-treatments with trypsin, but not ribonuclease (RNAse), or deoxyribonuclease (DNAse). As determined by radioactive precursor uptake and incorporation studies, the purified factor inhibits both RNA and protein synthesis in intact tissue culture cells and inhibits protein synthesis in a cell-free wheat germ system. DNA synthesis was slightly stimulated. The purified factor is cytostatic for both BHK-21 and for the IM9 leukemic cell lines for at least 120 h. The cytostatic component had no effect on cellular cyclic CMP metabolism.
Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy? (2008)

Induction of apoptosis in tumor cells by direct activation of the Bcl-2-regulated apoptosis pathway by small molecule drugs carries high hopes to overcome the shortcomings of current anticancer therapies. This novel therapy concept builds on emerging insights into how Bcl-2-like molecules maintain mitochondrial integrity and how pro-apoptotic BH3-only proteins lead to its disruption. Means to unleash the pro-apoptotic potential of BH3-only proteins in tumor cells, or to bypass the need for BH3-only proteins by directly blocking possible interactions of Bcl-2-like pro-survival molecules with Bax and/or Bak, constitute interesting options for the design of novel anticancer therapies. For the optimization and clinical implementation of these novel anticancer strategies, a detailed understanding of the role of individual BH3-only proteins in cell death signaling in healthy cells and during tumor suppression is required. In this review, we will touch on the latest findings on BH3-only protein function and attempts to define the molecular properties of the so-called 'BH3 mimetics,' a novel class of anticancer agents, able to prompt apoptosis in tumor cells, regardless of their p53 or Bcl-2 status.
Pancreatic duct inflammatory infiltration in the nonobese diabetic (NOD) mouse. (1994)

The pancreatic duct system during the early stages of type 1 diabetes was examined in 8-wk-old female nonobese diabetic (NOD) mice. Infiltration was seen to involve the smaller ducts while the larger ducts were usually free from ductulitis. The infiltration affected ducts both close to and remote from the islets of Langerhans. In the former situation, infiltration of the islet and that of the duct were not separable. A strong positivity for both Ia and ICAM-1 molecules was observed in all infiltrated ducts, indicating that this infiltrating process is due to the same elements as are involved in the islet inflammation and that also mononuclear cells infiltrating the nonislet ducts express adhesive mechanisms. At the ultrastructural level, endocrine cells that were mainly of the 'closed' type were observed intermingled with the ductular epithelial cells and infiltrating mononuclear cells were detected either in the connective layer or among the epithelial cells of the affected ducts.
Human Telomerase Reverse Transcriptase Gene Expression and the Surgical Management of Suspicious Thyroid Tumors (2004)

Abstract Purpose: Patients with a preoperative cytologic diagnosis of a suspicious thyroid nodule present a therapeutic dilemma because surgery differs for benign and malignant lesions. To address this issue, several molecular markers, including human telomerase reverse transcriptase (TERT), have been tested as markers of thyroid cancer. Because most studies select cases falling into well-defined categories to test new markers, they may overestimate their discriminatory power when applied to samples that are difficult to classify. Fine-needle aspirates (FNAs) of the thyroid with indeterminate cytology are an example of such cases. Experimental Design: We examined whether assessing TERT mRNA by reverse transcription-PCR could have improved the surgical management in a cohort of 100 patients undergoing thyroidectomy for indeterminate FNA results. Results: Ninety percent of 48 cancers were TERT positive, as were 35% of 52 benign lesions. When 10 cases with concomitant lymphocytic thyroiditis were excluded, the overall sensitivity of TERT was 91% (95% confidence interval, 80–98%) and specificity was 79% (64–90%). No clinical or tumor variable contributed to the predictive ability of TERT except for tumor size, which added only marginally. Basing the surgical approach on the TERT assay alone would have reduced lobectomies performed for malignant disease from 11 to 4 cases and reduced total thyroidectomies for benign lesions from to 15 to 9, an overall 50% reduction in suboptimal treatment. Conclusions: The overall performance of preoperative differential diagnosis for thyroid tumors with indeterminate FNA results can be substantially improved by the inclusion of molecular markers such as TERT.
CRISPR-Cas9/Cas12a biotechnology and application in bacteria (2018)

CRISPR-Cas technologies have greatly reshaped the biology field. In this review, we discuss the CRISPR-Cas with a particular focus on the associated technologies and applications of CRISPR-Cas9 and CRISPR-Cas12a, which have been most widely studied and used. We discuss the biological mechanisms of CRISPR-Cas as immune defense systems, recently-discovered anti-CRISPR-Cas systems, and the emerging Cas variants (such as xCas9 and Cas13) with unique characteristics. Then, we highlight various CRISPR-Cas biotechnologies, including nuclease-dependent genome editing, CRISPR gene regulation (including CRISPR interference/activation), DNA/RNA base editing, and nucleic acid detection. Last, we summarize up-to-date applications of the biotechnologies for synthetic biology and metabolic engineering in various bacterial species.
Ray casting on shared-memory architectures: memory-hierarchy considerations in volume rendering (1998)

To improve ray casting frame rates on shared memory architectures, the authors explore memory hierarchy effects and their interaction with parallel partitioning and load balancing. With their optimizations, a 16-processor Power Challenge machine renders a 1-Gbyte data set at a frame per second-faster than previously reported for a data set this large.
MicroRNAs: novel regulators in cardiac development and disease (2008)

MicroRNAs (miRNAs) are endogenous, small ribonucleotides regulating the translation of target messenger RNAs that have been shown to be involved in orchestrating growth, development, function, and stress responses of various organs, including the heart. Muscle miRNAs are mainly controlled by a network of myogenic transcription factors, and throughout cardiac development they fine-tune regulatory protein levels in a spatiotemporal manner. Recent profiling studies revealed that miRNA expression patterns are derailed in both human cardiac disease and animal models of cardiac hypertrophy and failure. Modulation of miRNA expression in vitro as well as in vivo has revealed an important role of miRNAs in regulating heart function, particularly cardiac growth and conductance. Here, we overview the recent findings on miRNAs in cardiac development and disease and report the latest advances in the identification and validation of miRNA targets, which are important for a comprehensive understanding of cardiac miRNA function. Finally, we focus on the development and use of miRNA antagonists (antagomirs) to target miRNAs in vivo, which may translate into novel therapeutic strategies for heart disease in the future.
Nitrous oxide (N 2 O) processing for silicon oxynitride gate dielectrics (1999)

The gas-phase chemistry of silicon oxynitridation in N <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O has been investigated. From an evaluation of available kinetic data, we have developed a model for the thermal decomposition of gaseous N <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O. To quantify heat transfer between the N <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O gas and the wall of the furnace, we introduce the concept of referencing to an N <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> gas-temperature profile, measured in an oxidation furnace. Using this model, we can account for the increase with flow rate and temperature of the NO concentration in the N <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O decomposition product, and the self-heating during decomposition, for furnace processing. This change in gaseous NO concentration translates to a higher nitrogen content and lower growth rate for the silicon oxynitride. For rapid thermal and other short-gas-residence-time systems, we show that atomic oxygen is present at the Si wafer, and that this removes previously incorporated nitrogen.
Verifiable Secret Redistribution (2001)

We present a new protocol for verifiably redistributing secrets from an (m, n) threshold sharing scheme to an (m # , n # ) scheme. Our protocol guards against dynamic adversaries. We observe that existing protocols either cannot be readily extended to allow redistribution between different threshold schemes, or have vulnerabilities that allow faulty old shareholders to distribute invalid shares to new shareholders. Our primary contribution is that in our protocol, new shareholders can verify the validity of their shares after redistribution between different threshold schemes.
Dual-gate organic thin-film transistors (2005)

A dual-gate organic thin-film transistor is realized using solution-processed organic semiconductor and insulator layers. Electrodes are made from gold. Compared to conventional single-gate transistors, this device type has a higher on current and steeper subthreshold slope. We show that the improved performance is the result of a nonconstant threshold voltage rather than formation of a second accumulation channel. Formation of a second accumulation channel does occur but the field-effect mobility associated with this channel is a factor 104 lower than the primary channel due to the relatively rough insulator-semiconductor interface.
The cancer‐related protein SSX2 interacts with the human homologue of a Ras‐like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP (2002)

The SSX gene family is composed of at least five functional and highly homologous members, SSX1 to SSX5, that are normally expressed in only the testis and thyroid. SSX1, SSX2, or SSX4 may be fused to the SYT gene as a result of the t(X;18) translocation in synovial sarcoma. In addition, the SSX1, SSX2, SSX4, and SSX5 genes were found to be aberrantly expressed in several other malignancies, including melanoma. The SSX proteins are localized in the nucleus and are diffusely distributed. In addition, they may be included in polycomb-group nuclear bodies. Other studies have indicated that the SSX proteins may act as transcriptional repressors. As a first step toward the elucidation of the cellular signaling networks in which the SSX proteins may act, we used the yeast two-hybrid system to identify SSX2-interacting proteins. By doing so, two novel human proteins were detected: RAB3IP, the human homolog of an interactor of the Ras-like GTPase Rab3A; and a novel protein, SSX2IP. RAB3IP did not interact with either SSX1, SSX3, or SSX4 in the yeast two-hybrid system, whereas SSX2IP interacted with SSX3 but not with either SSX1 or SSX4. Further analysis of deletion mutants showed that both RAB3IP and SSX2IP interact with the N-terminal moiety of the SSX2 protein. Immunofluorescence analyses of transfected cells revealed that the RAB3IP protein is normally localized in the cytoplasm. However, coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus. Likewise, the SSX2IP protein was found to be colocalizing with SSX2 in the nucleus. By performing glutathione-S-transferase pull-down assays, we found that both RAB3IP and SSX2IP interact directly with SSX2 in vitro. These newly observed protein/protein interactions may have important implications for the mechanisms underlying normal and malignant cellular growth.
Water and Ion Permeation of Aquaporin-1 in Planar Lipid Bilayers (2001)

The aquaporin-1 (AQP1) water channel protein is known to facilitate the rapid movement of water across cell membranes, but a proposed secondary role as an ion channel is still unsettled. Here we describe a method to simultaneously measure water permeability and ion conductance of purified human AQP1 after reconstitution into planar lipid bilayers. Water permeability was determined by measuring Na(+) concentrations adjacent to the membrane. Comparisons with the known single channel water permeability of AQP1 indicate that the planar lipid bilayers contain from 10(6) to 10(7) water channels. Addition of cGMP induced ion conductance in planar bilayers containing AQP1, whereas cAMP was without effect. The number of water channels exceeded the number of active ion channels by approximately 1 million-fold, yet p-chloromethylbenzenesulfonate inhibited the water permeability but not ion conductance. Identical ion channel parameters were achieved with AQP1 purified from human red blood cells or AQP1 heterologously expressed in Saccharomyces cerevisae and affinity purified with either N- or C-terminal poly-histidine tags. Rp-8-Br-cGMP inhibited all of the observed conductance levels of the cation selective channel (2, 6, and 10 pS in 100 mm Na(+) or K(+)). Deletion of the putative cGMP binding motif at the C terminus by introduction of a stop codon at position 237 yielded a truncated AQP1 protein that was still permeated by water but not by ions. Our studies demonstrate a method for simultaneously measuring water permeability and ion conductance of AQP1 reconstituted into planar lipid bilayers. The ion conductance occurs (i) through a pathway distinct from the aqueous pathway, (ii) when stimulated directly by cGMP, and (iii) in only an exceedingly small fraction of AQP1 molecules.
Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor. (1991)

Clones encoding the type 1 (p80) and type 2 (p60) forms of the murine receptors for tumor necrosis factor (TNF) were isolated by cross-hybridization using probes derived from the cloned human TNF receptors. Each of the murine receptors shows strong sequence homology to the corresponding human receptor (approximately 65% amino acid identity) throughout the molecule but only modest homology, limited to ligand-binding domains, between themselves. The ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs: both receptor types bind TNF-alpha and -beta with multiple affinity classes, and the ligands cross-compete. Analysis of the murine transcripts encoding these receptors revealed the presence of RNAs for one or both forms of the receptors in all cells examined. It was also demonstrated that for both types of human TNF receptor, variably sized transcripts are observed in different cells. The murine cDNAs were further used to determine the chromosomal locations of the TNF receptor genes. They are not linked, in contrast to the ligands, and map to chromosomes 4 (type 1) and 6 (type 2).
Studies on quinoline derivatives and related compounds. 1. A new synthesis of 1‐alkyl‐1,4‐dihydro‐4‐oxo‐3‐quinolinecarboxylic acids (1971)

Abstract A novel preparative method for 1‐alkyl‐1,4‐dihydro‐4‐oxo‐3‐quinolinecarboxylic acids was developed. The key process is the cyclization of N ‐alkylanilinomethylenemalonales, which was effected successfully in the presence of polyphosphoric acid, polyphosphate ester, boron tri‐fluoride or a mixture of acetic anhydride and sulfuric acid. With phosphorus oxychloride, N ‐alkylanilinomethylenemalonates yielded 1‐alkyl‐4‐chloro‐3‐carbethoxyquinolinium salts which were hydrolyzed readily to ethyl 1‐alkyl‐1,4‐dihydro‐4‐oxo‐3‐quinolineearboxylates or their acids. By means of this novel method several new 1‐alkyl‐1,4‐dihydro‐4‐oxo‐3‐quinolineearboxylic acids were prepared.
Studies on cardiovascular agents. 6. Synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to heterocyclic systems (1980)

The synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to pyrrole, thiophene, pyran, pyridine, and pyridazine are described. Among these compounds, 8-tert-butyl-7,8-dihydro-5-methyl-6H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine (23) was found to be the most promising potential cardiovascular agent, having been shown to be more potent in coronary vasodilating activity than trapidil [7-diethylamino)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine] and approximately equipotent to guanethidine sulfate in antihypertensive activity.
SVM Model for Virtual Screening of Lck Inhibitors (2009)

Lymphocyte-specific protein tyrosine kinase (Lck) inhibitors have treatment potential for autoimmune diseases and transplant rejection. A support vector machine (SVM) model trained with 820 positive compounds (Lck inhibitors) and 70 negative compounds (Lck noninhibitors) combined with 65 142 generated putative negatives was developed for predicting compounds with a Lck inhibitory activity of IC(50) < or = 10 microM. The SVM model, with an estimated sensitivity of greater than 83% and specificity of greater than 99%, was used to screen 168 014 compounds in the MDDR and was found to have a yield of 45.8% and a false positive rate of 0.52%. The model was also able to identify novel Lck inhibitors and distinguish inhibitors from structurally similar noninhibitors at a false positive rate of 0.27%. To the best of our knowledge, the SVM model developed in this work is the first model with a broad applicability domain and low false positive rate, which makes it very suitable for the virtual screening of chemical libraries for Lck inhibitors.
Disulfide Cross-Linked Polyethylenimines (PEI) Prepared via Thiolation of Low Molecular Weight PEI as Highly Efficient Gene Vectors (2008)

Ring-opening reaction of low molecular weight polyethylenimine with an Mw of 800 Da (800 Da PEI) with methylthiirane produced thiolated polyethylenimine (PEI-SHX ). The thiolation degree X, which is the average number of thiol groups on a PEI molecule, was readily adjusted by the methylthiirane/PEI ratio. Oxidation of the thiolated PEIs with DMSO afforded disulfide cross-linked PEIs (PEI-SSX ). The molecular weights of PEI-SS X were estimated by viscosity measurement to be 7100, 8000, and 8400 for X=2.6, 6.5, and 9.4, respectively. The PEI-SSX series can bind and condense plasmid DNAs effectively forming nanosized polyplexes. The size of dry polyplexes is less than 100 nm on the TEM pictures. In solution, the size of the polyplexes was measured by DLS to be about 400 nm. In vitro experiments showed that the PEI-SS X series have a lower cytotoxicity and higher gene transfection efficiency compared with the high molecular weight PEI with Mw of 25 KDa. The presence of fetal bovine serum did not decrease the transfection efficiency. The results proved the hypothesis that reductively degradable disulfide-containing PEIs could possesses simultaneously higher gene transfection efficiency and lower cytotoxicity than the nondegradable ones.