gebhart/patrepeval huggingface dataset:
The Multisubstrate Adapter Gab1 Regulates Hepatocyte Growth Factor (Scatter Factor)–c-Met Signaling for Cell Survival and DNA Repair (2001)

Hepatocyte growth factor (scatter factor) (HGF/SF) is a pleiotrophic mediator of epithelial cell motility, morphogenesis, angiogenesis, and tumorigenesis. HGF/SF protects cells against DNA damage by a pathway from its receptor c-Met to phosphatidylinositol 3-kinase (PI3K) to c-Akt, resulting in enhanced DNA repair and decreased apoptosis. We now show that protection against the DNA-damaging agent adriamycin (ADR; topoisomerase IIalpha inhibitor) requires the Grb2-binding site of c-Met, and overexpression of the Grb2-associated binder Gab1 (a multisubstrate adapter required for epithelial morphogenesis) inhibits the ability of HGF/SF to protect MDCK epithelial cells against ADR. In contrast to Gab1 and its homolog Gab2, overexpression of c-Cb1, another multisubstrate adapter that associates with c-Met, did not affect protection. Gab1 blocked the ability of HGF/SF to cause the sustained activation of c-Akt and c-Akt signaling (FKHR phosphorylation). The Gab1 inhibition of sustained c-Akt activation and of cell protection did not require the Gab1 pleckstrin homology or SHP2 phosphatase-binding domain but did require the PI3K-binding domain. HGF/SF protection of parental MDCK cells was blocked by wortmannin, expression of PTEN, and dominant negative mutants of p85 (regulatory subunit of PI3K), Akt, and Pak1; the protection of cells overexpressing Gab1 was restored by wild-type or activated mutants of p85, Akt, and Pak1. These findings suggest that the adapter Gab1 may redirect c-Met signaling through PI3K away from a c-Akt/Pak1 cell survival pathway.
Next-generation microchannel coolers (2008)

A next-generation microchannel cooler has been developed for packaging laser diode arrays that eliminates many of the problems associated with typical copper-based cooling designs. The coolers are built on well-established Low-Temperature Cofired Ceramic technology and provide excellent thermal performance. They do not require the use of deionized water. This work highlights the strengths of the new cooler technology. The results of a long-term, high-flow-rate test which demonstrates the excellent erosion resistance of these coolers are presented. Three devices have been tested for 2500 hours at a flow rate of 0.25 GPM and show minimal signs of erosion. This data is compared to a similar test conducted with copper coolers. Several design parameters are also addressed for the ceramic coolers. The available form and fit characteristics are addressed, as is the custom-configurable nature of the devices.
Fast and scalable pattern matching for content filtering (2005)

High-speed packet content inspection and filtering devices rely on a fast multi-pattern matching algorithm which is used to detect predefined keywords or signatures in the packets. Multi-pattern matching is known to require intensive memory accesses and is often a performance bottleneck. Hence specialized hardware-accelerated algorithms are being developed for line-speed packet processing. While several pattern matching algorithms have already been developed for such applications, we find that most of them suffer from scalability issues. To support a large number of patterns, the throughput is compromised or vice versa.We present a hardware-implementable pattern matching algorithm for content filtering applications, which is scalable in terms of speed, the number of patterns and the pattern length. We modify the classic Aho-Corasick algorithm to consider multiple characters at a time for higher throughput. Furthermore, we suppress a large fraction of memory accesses by using Bloom filters implemented with a small amount of on-chip memory. The resulting algorithm can support matching of several thousands of patterns at more than 10 Gbps with the help of a less than 50 KBytes of embedded memory and a few megabytes of external SRAM. We demonstrate the merit of our algorithm through theoretical analysis and simulations performed on Snort's string set.
Electrode discrimination and speech recognition in postlingually deafened adult cochlear implant subjects (1997)

This study investigated the relationship between electrode discrimination and speech recognition in 11 postlingually deafened adult cochlear implant subjects who were implanted with the Nucleus/Cochlear Corporation multichannel device. The discriminability of each electrode included in a subject's clinical map was measured using adaptive and fixed-level discrimination tasks. Considerable variability in electrode discriminability was observed across subjects. Two subjects could discriminate all electrodes, and discrimination performance by the remaining nine subjects varied from near perfect to very poor. In these nine subjects, the results obtained from the discrimination tasks were used to create a map that contained only discriminable electrodes, and subjects' performance on speech recognition tasks using this experimental map was measured. Four different speech recognition tests were administered: a nine-choice closed-set medial vowel recognition task, a 14-choice closed-set medial consonant recognition task, the NU6 Monosyllabic Words Test [T. W. Tillman and T. Carhart, Tech. Rep. No. SAM-TR-66-55, USAF School of Aerospace Medicine, Brooks Air Force Base, Texas (1966)] scored for both words and phonemes correct, and the Central Institute for the Deaf (CID) Everyday Sentences test [H. Davis and S. R. Silverman, Hearing and Deafness (Holt, Rinehart, and Winston, New York, 1978)]. Seven of the nine subjects tested with the experimental map showed significant improvement on at least one speech recognition measure, even though the experimental map contained fewer electrodes than the original map. Three subjects' scores improved significantly on the CID Everyday Sentences test, three subjects' scores improved significantly on the NU6 Monosyllabic Words test, and five subjects' scores improved significantly on the NU6 Monosyllabic Words test scored for phonemes correct. None of the subjects' scores improved significantly on either the vowel or consonant tests. No significant correlation was observed between electrode discrimination ability and speech recognition scores or between electrode discrimination ability and improvement in speech recognition scores when programmed with the experimental map. The results of this study suggest that electrode discrimination tasks may be used to improve speech recognition of some cochlear implant subjects, and that each electrode site does not necessarily provide perceptually distinct information.
The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. (1997)

The purine nucleoside adenosine (9-beta-D-ribofuranosyladenine) inhibits a number of lymphocyte functions in vitro, including the ability of activated T lymphocytes and natural killer cells to adhere to and kill tumor targets. Solid tumors, such as adenocarcinomas of the lung and colon, are frequently hypoxic and are, therefore, likely to exhibit increased adenine nucleotide breakdown through the 5'-nucleotidase pathway, yielding adenosine. We examined whether the concentration of adenosine in the extracellular fluid of such tumors is adequate to cause immunosuppression. Murine tumors grown in syngeneic hosts or human tumors grown in immunodeficient nu/nu mice were subjected to microdialysis, and adenosine levels in the microdialysate were measured by high-performance liquid chromatography. Treatment of the tumor microdialysates with adenosine deaminase eliminated the adenosine peak. Recovery of adenosine ranged from 15 to 29%, depending on the microdialysis probe, and concentrations of adenosine in tumors ranged from 0.2 to 2.4 microM with a mean of 0.5 microM. In contrast, the adenosine concentration measured s.c. at the same location was 30 +/- 5 nM (mean +/- SE). Inclusion of the adenosine deaminase inhibitor coformycin (10 microM) and the adenosine kinase inhibitor 5'-iodotubercidin (0.1 microM) in the microdialysis perfusion buffer increased extracellular adenosine concentration in tumors to as high as 13 microM. These data show that extracellular adenosine levels in solid tumors are sufficient to suppress the local antitumor immune response and that interference with pathways of adenosine metabolism causes marked increases in tumor extracellular adenosine concentration.
Molecular Recognition at Crystal Interfaces (1991)

Nucleation, growth, and dissolution of crystals have been studied by stereochemical approach involving molecular recognition at interfaces. A methodology is described for using ;;tailor-made'' additives designed to interact stereospecifically with crystal surfaces during growth and dissolution. This procedure was instrumental in controlling crystal morphology and in revising the concept of the structure and symmetry of solid solutions. Consequently, it was applied to the transformation of centrosymmetric single crystals into solid solutions with polar arrangement displaying second-harmonic generation and to the performance of asymmetric synthesis of guest molecules inside centrosymmetric host crystals. The method has led to a discovery of a new ;;relay'' mechanism explaining the effect of solvent on crystal growth. Finally, it allowed for the design of auxiliary molecules that act as promoters or inhibitors of crystal nucleation that can be used to resolve enantiomers and crystallize desired polymorphs.
Expression of complementary DNA and genomic clones for carcinoembryonic antigen and nonspecific cross-reacting antigen in Chinese hamster ovary and mouse fibroblast cells and characterization of the membrane-expressed products. (1990)

Complementary DNA clones coding for both carcinoembryonic antigen (CEA), a well characterized colonic tumor marker, and nonspecific cross-reacting antigen (NCA), a related antigen, were expressed in Chinese hamster ovary (CHO) cells and L-cells (mouse fibroblasts). A genomic clone coding for CEA was also expressed in CHO cells. Positive clones were identified by fluorescence flow cytometry and enzyme-linked immunosorbent assay. Membrane location of the recombinant CEA and NCA was confirmed by indirect immunofluorescence labeling of the transfectants, followed by visualization under a fluorescence microscope. The apparent molecular weight of the expressed CEA and NCA were 180,000 and 96,000, respectively, for both cell lines, as determined by immunoblot analysis. The CEA and NCA expressed on CHO cells were sensitive to treatment with phosphatidylinositol-specific phospholipase C (PI-PLC), whereas the CEA and NCA proteins on L-cells were resistant to removal by PI-PLC. Unlike NCA, which contains three methionine residues, the only methionine in CEA is in the C-terminal hydrophobic domain. This domain in CEA was shown to be removed and replaced by a phosphatidylinositol glycan (PI-G) anchor (Hefta et al., Proc. Natl. Acad. Sci. USA, 85: 4648-4652, 1988). The recombinant CEA from both CHO cells and L-cells could be labeled with [3H]-ethanolamine (a component of the PI-G anchor) but not with [35S] methionine, whereas the recombinant NCA could be labeled with both [3H]ethanolamine and [35S]methionine. The labeling studies and PI-PLC treatment results are consistent with the CEA and NCA expressed on CHO cells possessing a PI-G anchor. The CEA expressed on the L-cell transfectants may contain a PI-G anchor which is resistant to cleavage by PI-PLC. In addition, the membrane-bound and secreted levels of CEA from the CHO and L-cell transfectants were determined.
Heat Shock RNA Levels in Brain and Other Tissues After Hyperthermia and Transient Ischemia (1990)

A number of studies have demonstrated increased synthesis of heat shock proteins in brain following hyperthermia or transient ischemia. In the present experiments we have characterized the time course of heat shock RNA induction in gerbil brain after ischemia, and in several mouse tissues after hyperthermia, using probes for RNAs of the 70-kilodalton heat shock protein (hsp70) family, as well as ubiquitin. A synthetic oligonucleotide selective for inducible hsp70 sequences proved to be the most sensitive indicator of the stress response whereas a related rat cDNA detected both induced RNAs and constitutively expressed sequences that were not strongly inducible in brain. Considerable polymorphism of ubiquitin sequences was evident in the outbred mouse and gerbil strains used in these studies when probed with a chicken ubiquitin cDNA. Brief hyperthermic exposure resulted in striking induction of hsp70 and several-fold increases in ubiquitin RNAs in mouse liver and kidney peaking 3 h after return to room temperature. The oligonucleotide selective for hsp70 showed equivalent induction in brain that was more rapid and transient than observed in liver, whereas minimal induction was seen with the ubiquitin and hsp70-related cDNA probes. Transient ischemia resulted in 5- to 10-fold increases in hsp70 sequences in gerbil brain which peaked at 6 h recirculation and remained above control levels at 24 h, whereas a modest 70% increase in ubiquitin sequences was noted at 6 h. These results demonstrate significant temporal and quantitative differences in heat shock RNA expression between brain and other tissues following hyperthermia in vivo, and indicate that hsp70 provides a more sensitive index of the stress response in brain than does ubiquitin after both hyperthermia and ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of granulocyte-macrophage colony-stimulating factor receptor on the blast cells of acute myeloblastic leukemia (1990)

Iodinated granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to document the specific binding of GM-CSF to all acute myeloblastic leukemia (AML) samples examined in the present study. There was some heterogeneity in the number of GM-CSF binding sites per cell. To determine whether the low level of binding to some patient samples may be attributed to receptor occupancy by an endogenous source of GM-CSF, we devised an acid wash procedure that could remove surface-bound GM-CSF without affecting receptor properties. We thus document that GM-CSF specific binding to AML blasts before or after acid wash was the same, indicating that the observed heterogeneity in binding is not the result of receptor occupancy by an endogeneous source of GM-CSF. Saturation analyses are in favor of the presence of two classes of binding sites on AML blasts: a high-affinity receptor that binds GM-CSF with a dissociation constant (kd) of 3 to 73 pmol/L and a second class of low-affinity receptor that binds GM-CSF with a kd of 1 to 10 nmol/L. Binding studies with two established cell lines KG-1, and IRCM-8 also showed the presence of two classes of binding sites with high and low affinities. Analysis of GM-CSF titration curves in culture indicate that the median effective concentration required for stimulation of blast colony formation (EC50 = 5-36 pmol/L) were in the range of the kd of the high-affinity binding site, suggesting that this high-affinity binding site mediates the proliferative response.
Study of the Filamentary Growth of Silicon Crystals from the Vapor (1964)

The preparation from vapor and the structure of filamentary crystals of silicon have been studied in detail. It was found by chemical etching, by examination for a twist associated with a screw dislocation, and by observations in the electron microscope, that both ribbons and needles of small dimensions are free of dislocations and imperfections. Certain impurities such as gold, nickel, or platinum, however, are essential for the growth of filamentary crystals. The growth of micron size and larger whisker crystals from the vapor takes place in two stages. The first is a rapid extension in length of a leader-like crystal of small cross section; the second, a slow thickening of the leader through deposition on lateral faces. Initial growth is associated with impurities and does not require an axial screw dislocation. Subsequent growth may be explained by classical nucleation at a step and lateral translation of the step.
Volumetric absorptive microsampling (VAMS) coupled with high-resolution, accurate-mass (HRAM) mass spectrometry as a simplified alternative to dried blood spot (DBS) analysis for therapeutic drug monitoring of cardiovascular drugs (2018)

Here, volumetric absorptive microsampling (VAMS), used for the measurement of cardiovascular drugs, is compared against conventional dried blood spot (DBS) card sampling to evaluate adherence to prescribed medication. Volumetric absorptive microsampling (VAMS) is an attractive alternative to plasma sampling for routine drug monitoring and potentially overcomes haematocrit issues associated with quantitative bioanalysis of conventional dried blood spots. A quantitative VAMS-based LC-HRAM MS assay for atenolol, lisinopril, simvastatin and valsartan was developed and validated. The assay demonstrated acceptable linearity, selectivity, accuracy, precision, recovery and insignificant matrix effects with no impact of haematocrit on assay accuracy. Volunteers provided both VAMS and DBS 903 card samples (the current standard) to allow comparison of the two methods and demonstrate the potential utility of VAMS. Analysis of VAMS samples correctly identified drugs in volunteers known to be adherent, and found no false positives from volunteers known to be taking no medication. There was a strong correlation between the two sampling systems confirming the utility of VAMS. Therapeutic drug monitoring (TDM) can assist clinicians in deciding how to proceed with treatment in the event of poor improvement in patient health. VAMS could offer a potentially more efficient method of sample collection, with fewer rejected samples than the DBS approach.
Chemistry of thienopyridines. XVIII. Lithiation as a route to 2‐ and 3‐substituted thieno[2,3‐b]pyridines (1974)

Abstract Treatment of thieno[2,3‐ b ]pyridine (1a) with n ‐butyllithium in hexane‐tetramethylethylene‐diamine at −70° plus subsequent addition of dimethylformamide produced 2‐formyl‐Ia (66%). Halogen‐metal exchange between 3‐bromothieno[2,3‐ b ]pyridine and n ‐butyllithium was effected in ether at −70. Further reaction of the 3‐lithio‐Ia intermediate with a variety of carbonyl compounds gave 3‐substituted thieno[2,3‐ b ]pyridines bearing formyl (77%), acetyl, benzoyl, chloroacetyl, ethoxycarbonyl, N ‐phenylcarbamyl, and diphenyl hydroxymethyl groups. Common characteristics of these derivatives in pmr and mass spectra are noted.
Analysis of operating mechanism in semiconductor optical modulator with electron‐depleting absorption control (1996)

Abstract The optical absorption mechanism of a semiconductor optical modulator with electron‐depletion absorption control was theoretically and experimentally investigated. In the doped direct transition semiconductor material, optical absorption increased when electrons were depleted. In the region where electrons are depleted, the number of electrons in the conduction band and holes in the valence band decrease, the impurity energy level shifts due to the decrease of the screening effect and the internal electric field strength increases. Because of these phenomena, the band‐to‐band electron transition probability increases. As a result, the optical absorption increases in the modulator.
Classic Selective Sweeps Were Rare in Recent Human Evolution (2011)

Efforts to identify the genetic basis of human adaptations from polymorphism data have sought footprints of "classic selective sweeps" (in which a beneficial mutation arises and rapidly fixes in the population).Yet it remains unknown whether this form of natural selection was common in our evolution. We examined the evidence for classic sweeps in resequencing data from 179 human genomes. As expected under a recurrent-sweep model, we found that diversity levels decrease near exons and conserved noncoding regions. In contrast to expectation, however, the trough in diversity around human-specific amino acid substitutions is no more pronounced than around synonymous substitutions. Moreover, relative to the genome background, amino acid and putative regulatory sites are not significantly enriched in alleles that are highly differentiated between populations. These findings indicate that classic sweeps were not a dominant mode of human adaptation over the past ~250,000 years.
The Theory and Practice of Industrial Pharmacy (1970)

The theoty and Practice of Industrial Pharmacy , The theoty and Practice of Industrial Pharmacy , کتابخانه دیجیتال جندی شاپور اهواز
Bovine Spleen, a Convenient Source for Purifying a Type I Interferon Receptor (1987)

Bovine spleen was investigated for the presence of receptors for radioiodinated human interferon-alpha 2 (125I-labeled HuIFN-alpha 2). Membranes were prepared by homogenization and differential centrifugation and analyzed for labeled IFN binding with recently developed tissue membrane assays. The characteristics of IFN binding included an affinity constant (Ka) of 3.1 +/- 0.99 X 10(10) M-1 and a receptor content of 8.4 +/- 0.74 fmoles/mg (wet weight) of bovine spleen membranes. The labeled IFN-receptor complex on these membranes was chemically cross-linked with 1.0 mM ethylene glycol bis(succinimidyl succinate (EGS), and subjected to SDS-PAGE and autoradiography. The formation of a 137-kD complex observed on autoradiographs was inhibited in a dose-dependent manner by unlabeled HuIFN-alpha 2 at concentrations that inhibited the binding of labeled IFN to the membranes. The products of the cross-linking reaction were purified by gel filtration on a column of Ultragel AcA34 in the presence of SDS and examined by SDS-PAGE and autoradiography. In addition to the 137-kD complex, several low-molecular-weight species were observed in the column profile of radioactivity which migrated to the bottom of 10% polyacrylamide gels. The fractions containing the 137-kD complex were pooled, concentrated, and utilized as a substrate for endoglycosidase digestion assays. Endoglycosidase H (EndoH) had no affect on the migration of the 137-kD complex while peptide:N-glycosidase F (PNGase F) increased the migration of the 137-kD band to a position with an Mr of 105 kD.(ABSTRACT TRUNCATED AT 250 WORDS)
Ado-trastuzumab Emtansine (T-DM1): An Antibody–Drug Conjugate (ADC) for HER2-Positive Breast Cancer (2014)

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the antitumor properties of the humanized anti-human epidermal growth factor receptor 2 (HER2) antibody, trastuzumab, with the maytansinoid, DM1, a potent microtubule-disrupting agent, joined by a stable linker. Upon binding to HER2, the conjugate is internalized via receptor-mediated endocytosis, and an active derivative of DM1 is subsequently released by proteolytic degradation of the antibody moiety within the lysosome. Initial clinical evaluation led to a phase III trial in advanced HER2-positive breast cancer patients who had relapsed after prior treatment with trastuzumab and a taxane, which showed that T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine. In 2013, T-DM1 received FDA approval for the treatment of patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane, separately or in combination, the first ADC to receive full approval based on a randomized study.