gebhart/patrepeval huggingface dataset:
Sequence requirements for proteolytic processing of glycoprotein B of human cytomegalovirus strain Towne (1990)

Truncated versions of the human cytomegalovirus (CMV) strain Towne glycoprotein B (gB) gene were stably expressed in CHO cell lines. The calcium-specific ionophore A23187 inhibited proteolytic cleavage of C-terminal-truncated gB expressed by cell line 67.77. These inhibition studies also showed that the 93-kilodalton cleavage product most likely represents the N-terminal cleavage fragment of gB. The ionophore carboxyl cyanide m-chlorophenyl-hydrazone was used to show that proteolytic cleavage of gB did not occur in the endoplasmic reticulum. Two-dimensional polyacrylamide gel electrophoresis demonstrated that the N- and C-terminal cleavage products of gB remained associated by disulfide linkages after cleavage. Expression studies using constructs in which 80% or all of the N terminus was deleted demonstrated that the N terminus was required for secretion of the gB molecule. The amino acid sequence at the site of cleavage was shown to be critical for cleavage by a cellular protease. Our results indicate that an arginine-to-threonine change at either amino acid 457 or 460, a lysine-to-glutamine change at amino acid 459, or all three substitutions together block gB cleavage. The effect on proteolysis of the arginine-to-threonine amino acid change at residue 457 (position -4 relative to the cleavage site) demonstrated that a basic pair of amino acids at the endoproteolytic processing site is not the only requirement in cis for gB cleavage.
A new family of growth factor‐like peptides ‘Trefoil’ disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins) (1989)

Four peptides present in completely different biological sources have been shown to exhibit a large degree of structural similarity. The peptides include: (i) a 60 amino acid residue breast cancer associated pS2 peptide isolated from human gastric juice and the culture media of the human breast cancer cell line MCF-7; (ii) a 106 amino acid residue pancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas and pancreatic juice; and (iii) a 49 and 50 amino acid residue peptide predicted from a cDNA isolated from the skin of the frog, Xenopus laevis. These peptides are characterized by having one (pS2 and the frog peptides) or two (PSP) domains of a highly conserved 38-39 amino acid residue consensus sequence not found in any other known peptides or proteins. The domain sequences contain 6 cysteine residues in nearly the same positions and it is suggested that these 6 residues are linked by 3 disulphide bonds to form a characteristic 'trefoil' disulphide loop structure common in all four peptides. From the sources of which the peptides have been isolated and from experiments showing that PSP has a growth factor stimulatory effect on MCF-7 cells, it is further suggested that these peptides may represent members of a new family of growth factors.
Disulfiram treatment of alcoholism. A Veterans Administration cooperative study. (1986)

We conducted a controlled, blinded, multicenter study of disulfiram treatment of alcoholism in 605 men randomly assigned to 250 mg of disulfiram (202 men); 1 mg of disulfiram (204 men), a control for the threat of the disulfiram-ethanol reaction; or no disulfiram (199 men), a control for the counseling that all received. Bimonthly treatment assessments were done for one year. Relative/friend interviews and blood and urine ethanol analyses were used to corroborate patients' reports. There were no significant differences among the groups in total abstinence, time to first drink, employment, or social stability. Among the patients who drank and had a complete set of assessment interviews, those in the 250-mg disulfiram group reported significantly fewer drinking days (49.0 +/- 8.4) than those in the 1-mg (75.4 +/- 11.9) or the no-disulfiram (86.5 +/- 13.6) groups. There was a significant relationship between adherence to drug regimen and complete abstinence in all groups. We conclude that disulfiram may help reduce drinking frequency after relapse, but does not enhance counseling in aiding alcoholic patients to sustain continuous abstinence or delay the resumption of drinking.
2.5-THz GaAs monolithic membrane-diode mixer (1999)

A novel GaAs monolithic membrane-diode (MOMED) structure has been developed and implemented as a 2.5-THz Schottky diode mixer. The mixer blends conventional machined metallic waveguide with micromachined monolithic GaAs circuitry to form, for the first time, a robust, easily fabricated, and assembled room-temperature planar diode receiver at frequencies above 2 THz. Measurements of receiver performance, in air, yield at T/sub receiver/ of 16500-K double sideband (DSB) at 8.4-GHz intermediate frequency (IF) using a 150-K commercial Miteq amplifier. The receiver conversion loss (diplexer through IF amplifier input) measures 16.9 dB in air, yielding a derived "front-end" noise temperature below 9000-K DSB at 2514 GHz. Using a CO/sub 2/-pumped methanol far-infrared laser as a local oscillator at 2522 GHz, injected via a Martin-Puplett diplexer, the required power is /spl ap/5 mW for optimum pumping and can be reduced to less than 3 mW with a 15% increase in receiver noise. Although demonstrated as a simple submillimeter-wave mixer, the all-GaAs membrane structure that has been developed is suited to a wide variety of low-loss high-frequency radio-frequency circuits.
CCI-779 Wyeth. (2002)

Wyeth Research (formerly Wyeth-Ayerst Research) is developing the sirolimus (rapamycin) analog CCI-779 as a potential treatment for various cancers [320924]. By November 2001, phase III trials had been initiated [428972], [429576]. In October 2001, Raymond James predicted filing in 2003, with a potential launch in 2005 [426718]. In March 2002, CCI-779, was designated for fast-track development by the FDA for the treatment of renal cell carcinoma after failure of initial therapy [442535]; at this time phase III trials for renal cell carcinoma and phase II trials for various solid tumors were ongoing [444030]. In March 2002, Wyeth revealed that filing was anticipated for 2004/2005 [443491]. In June and August 2001, Lehman Brothers predicted sales of US $40 million ($20 million in the US) in 2003, rising to US $75 million ($38 million in the US) in 2004 [418901], [420809]. In October 2001, analysts at Raymond James expected potential sales of the product at US $250 million [426718]. In May 2002, a patent (WO-00240000) was published claiming CCI-779 to be useful for the treatment of cancers of various origins, including renal, breast, cervical, uterine, head and neck, lung, prostate, pancreatic, ovarian, colon, lymphoma and melanoma.
Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a “paraptosis”-induced pathway that promotes systemic immunity against intracranial T9 gliomas (2002)

Cloned T9-C2 glioma cells transfected with membrane macrophage colony-stimulating factor (mM-CSF) never formed subcutaneous tumors when implanted into Fischer rats, whereas control T9 cells did. The T9-C2 cells were completely killed within 1 day through a mechanism that resembled paraptosis. Vacuolization of the T9-C2 cell's mitochondria and endoplasmic reticulum started within 4 hours after implantation. By 24 hours, the dead tumor cells were swollen and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive. Bcl2-transduced T9-C2 cells failed to form tumors in rats. Both T9 and T9-C2 cells produced cytokine-induced neutrophil chemoattractant that recruited the granulocytes into the tumor injection sites, where they interacted with the tumor cells. Freshly isolated macrophages killed the T9-C2 cells in vitro by a mechanism independent of phagocytosis. Nude athymic rats treated with antiasialo GM1 antibody formed T9-C2 tumors, whereas rats treated with a natural killer cell (NK)-specific antibody failed to form tumors. When treated with antipolymorphonuclear leukocyte (anti-PMN) and antimacrophage antibodies, 80% of nude rats formed tumors, whereas only 40% of the rats developed a tumor when a single antibody was used. This suggests that both PMNs and macrophages are involved in the killing of T9-C2 tumor cells. Immunocompetent rats that rejected the living T9-C2 cells were immune to the intracranial rechallenge with T9 cells. No vaccinating effect occurred if the T9-C2 cells were freeze-thawed, x-irradiated, or treated with mitomycin-C prior to injection. Optimal tumor immunization using mM-CSF-transduced T9 cells requires viable tumor cells. In this study optimal tumor immunization occurred when a strong inflammatory response at the injection of the tumor cells was induced.
Developmental regulation of a cyclin-dependent kinase inhibitor controls postembryonic cell cycle progression in Caenorhabditis elegans (1998)

C. elegans cki-1 encodes a member of the CIP/KIP family of cyclin-dependent kinase inhibitors, and functions to link postembryonic developmental programs to cell cycle progression. The expression pattern of cki-1::GFP suggests that cki-1 is developmentally regulated in blast cells coincident with G1, and in differentiating cells. Ectopic expression of CKI-1 can prematurely arrest cells in G1, while reducing cki-1 activity by RNA-mediated interference (RNAi) causes extra larval cell divisions, suggesting a role for cki-1 in the developmental control of G1/S. cki-1 activity is required for the suspension of cell cycling that occurs in dauer larvae and starved L1 larvae in response to environmental signals. In vulva precursor cells (VPCs), a pathway of heterochronic genes acts via cki-1 to maintain VPCs in G1 during the L2 stage.
Continuous-wave two-photon excitation of individual CdS nanocrystallites (2001)

By use of low-temperature confocal microscopy, continuous-wave two-photon fluorescence images are obtained of individual CdS nanocrystallites embedded in a polymer matrix. The quadratic dependence of the emission rate on the applied laser power proves that the observed fluorescence originates from the simultaneous absorption of two photons. From the experimental data the two-photon absorption cross-section σ(2) could be determined, resulting in a value smaller than that known from literature. The work presented is a first step towards high-resolution fluorescence-excitation spectroscopy on the electronic states in the band edge, inaccessible by conventional one-photon spectroscopy.
Trace-based compilation in execution environments without interpreters (2010)

Trace-based compilation is a technique used in managed language runtimes to detect and compile frequently executed program paths. The goal is to reduce compilation time and improve code quality by only considering hot parts of methods for compilation. Trace compilation is well suited for interpreter-based execution environments because the control flow of an application program is highly visible and recordable. In this paper, we show that trace compilation is also feasible and beneficial in runtime environments without interpreters where it is more difficult to monitor the control flow of an application.We present the implementation of Maxpath, a trace-based Java just-in-time compiler for the meta-circular Maxine virtual machine. Maxine uses a tiered compilation strategy where methods are first compiled with a non-optimizing just-in-time compiler in order to collect profiling information, and then recompiled with an optimizing compiler for long-term efficient execution. We record traces by dynamically inserting instrumentation code in non-optimized methods. Execution traces are first collected into trace regions, after which they are compiled, optimized and linked to non-optimized methods for efficient execution. We show that trace-based compilation is an effective way to focus scarce compilation resources on performance critical application regions.
Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. (1994)

Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-related protein-1 (gp75) were evaluated for recognition by HLA-A2-restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.
C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation (2017)

Hexanucleotide repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we demonstrate that the repeat-associated non-AUG (RAN) translation of (GGGGCC) <sub>n</sub> -containing RNAs into poly-dipeptides can initiate in vivo without a 5'-cap. The primary RNA substrate for RAN translation of C9ORF72 sense repeats is shown to be the spliced first intron, following its excision from the initial pre-mRNA and transport to the cytoplasm. Cap-independent RAN translation is shown to be upregulated by various stress stimuli through phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF2α), the core event of an integrated stress response (ISR). Compounds inhibiting phospho-eIF2α-signaling pathways are shown to suppress RAN translation. Since the poly-dipeptides can themselves induce stress, these findings support a feedforward loop with initial repeat-mediated toxicity enhancing RAN translation and subsequent production of additional poly-dipeptides through ISR, thereby promoting progressive disease.
Synthese und Reaktionen neuer Thiazol‐ und Triazol‐Abkömmlinge (1983)

Abstract Der Dimethylester 1 reagiert mit 2 und 5 bzw. mit primären oder sekundären Aminen zu den Abkömmlingen 4 , 7 , 8a – f , 9a , b und 10 . Cyclisierung von 8a – d mit Thioglycolsäure‐methylester bzw. von 8b – e mit Methylhydrazin liefert die Thiazolderivate 11a – d bzw. die Triazolderivate 12a – d/13a – d . Acylierung von 11b und 13c führt zu 14 bzw. 15 . Die Isomerengemische 12/13 werden zu den Azomethinen 16a – g , 17a – e und Thioharnstoffen 18a – f umgesetzt. Acylisothiocyanate reagieren mit 13c zu 19a , b und die Thioharnstoffe 18a , d – f ergeben mit Oxalylchlorid die Imidazolidindione 20a – d . — Von 12a und 20c wurden Röntgenstrukturanalysen angefertigt.
Control of Translation in Adenovirus-Infected Cells (1990)

The initiation of protein synthesis in adenovirus-infected cells is regulated during the late phase in two ways, which may be related. The overall translation rate is maintained by a small viral RNA, VA RNAI, which prevents the phosphorylation of initiation factor eIF-2 by a double-stranded RNA-activated protein kinase, DAI. In addition, the relative efficiency of translation of host cell and viral mRNA populations is regulated in the infected cell during the late phase such that viral mRNAs are selectively utilized. Three viral elements have been implicated in this process: the 5' leader present on most late viral mRNAs; the late protein, 100K; and VA RNA. This article reviews the mechanisms underlying these translational control phenomena.
Surface-Enhanced Raman Scattering Based Nonfluorescent Probe for Multiplex DNA Detection (2007)

To provide rapid and accurate detection of DNA markers in a straightforward, inexpensive, and multiplex format, an alternative surface-enhanced Raman scattering based probe was designed and fabricated to covalently attach both DNA probing sequence and nonfluorescent Raman tags to the surface of gold nanoparticles (DNA-AuP-RTag). The intensity of Raman signal of the probes could be controlled through the surface coverage of the nonfluorescent Raman tags (RTags). Detection sensitivity of these probes could be optimized by fine-tuning the amount of DNA molecules and RTags on the probes. Long-term stability of the DNA-AuP-RTag probes was found to be good (over 3 months). Excellent multiplexing capability of the DNA-AuP-RTag scheme was demonstrated by simultaneous identification of up to eight probes in a mixture. Detection of hybridization of single-stranded DNA to its complementary targets was successfully accomplished with a long-term goal to use nonfluorescent RTags in a Raman-based DNA microarray platform.
Proteinglycosylierung, konserviert von der Bäckerhefe bis zum Menschen: Ein Modellorganismus hilft bei der Aufklärung menschlicher Erbkrankheiten (2006)

Abstract Proteinmodifikationen durch Saccharide sind in großer Zahl bekannt. Der vorliegende Aufsatz konzentriert sich auf zwei Typen von Modifikationen, die Protein‐ N ‐Glycosylierung und die Protein‐ O ‐Mannosylierung, die mit wenigen Ausnahmen von Hefe bis Mensch im Laufe der Evolution konserviert geblieben sind. Sie sind dadurch gekennzeichnet, dass die Glycosylierungsprozesse im endoplasmatischen Reticulum der Zellen beginnen und im Golgi‐Apparat fortgesetzt werden und dass die Anfangsschritte über dolicholaktivierte Vorstufen verlaufen. In der gentechnisch einfach handhabbaren Bäckerhefe Saccharomyces cerevisiae sind die beiden Prozesse molekularbiologisch am besten untersucht worden. Dies ist der Hauptgrund dafür, dass zahlreiche genetisch bedingte, schwerwiegende Entwicklungsstörungen bei Kindern, wie das CDG (Congenital Disorder of Glycosylation) und die kongenitalen Muskeldystrophien mit neuronalen Migrationsdefekten, mithilfe der Hefe aufgeklärt werden konnten.
Targeting the c-Met Signaling Pathway in Cancer (2006)

On binding to the cell surface receptor tyrosine kinase (TK) known as c-Met, hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets including, epithelial and endothelial cells, hematopoietic cells, neurons, melanocytes, and hepatocytes. These pleiotropic actions are fundamentally important during development, homeostasis, and tissue regeneration. HGF signaling also contributes to oncogenesis and tumor progression in several human cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. Our present understanding of c-Met oncogenic signaling supports at least three avenues of pathway selective anticancer drug development: antagonism of ligand/receptor interaction, inhibition of TK catalytic activity, and blockade of intracellular receptor/effector interactions. Potent and selective preclinical drug candidates have been developed using all three strategies, and human clinical trials in two of the three areas are now under way.
Effects of long‐term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis (2010)

Etanercept treatment, with or without methotrexate, may contribute to the restoration of normal growth in children with JIA.
Genetic transformation assays for identification of strains of Moraxella urethralis (1977)

Studies of 31 strains of Moraxella urethralis have shown that 20 of them are competent for genetic transformation. This finding has led to the development of transformation assays for identification of newly isolated strains of this organism. Crude deoxyribonucleic acid (DNA) samples from all strains of M. urethralis readily transform auxotrophic mutants of competent strains to prototrophy, whereas DNA samples from unrelated bacteria such as Acinetobacter, Moraxella, and Neisseria species uniformly fail to elicit positive transformation of mutant tester strains. One of the competent strains of M. urethralis investigated is a naturally occurring mutant defective in its ability to utilize citrate as a carbon and energy source. DNA samples from 29 of the 30 remaining strains of utilization; the one nonreacting strain is citrate negative and probably possesses the same genetic lesion as the citrate-negative mutant. Three organisms originally identified as strains of M. urethralis, because of their phenotypic properties, are probably incorrectly designated, since DNA samples from these strains failed to transform any of the tester mutant strains used in the present study. The transformation assay for M. urethralis is very simple and can be performed readily in a clinical laboratory. The entire procedure can be carried out in less than 24 h.
The aliasing problem in computer-synthesized shaded images. (1976)

This paper describes work toward improving the quality of computer-synthesized shaded images. Current (practical) hidden-surface algorithms produce an image whose precision is strictly limited by the number of picture elements. Problems caused by this limitation are described and explained in the text. Other image production media such as television and screen printing processes exhibit the same problems, but to a far lesser extent. Therefore, current image production media are surveyed and compared to computer-synthesized images with a view toward establishing a criterion for acceptable image quality. The problems to be seen in computer-synthesized images are predominantly caused by a phenomenon known as aliasing. Aliasing is an artifact of the process of producing an image made of discrete dots. A well known cure for aliasing is motivated and explained in the text. The notions of sampling and convolutional filtering are introduced to assist the explanation. Based on these techniques, an algorithm for computing the intensity of a single dot of an image is developed. The algorithm is applied to a test pattern which serves as a worst case for the problems caused by aliasing.
Engineering Conformational Flexibility in the Lactose Permease of Escherichia coli:  Use of Glycine-Scanning Mutagenesis To Rescue Mutant Glu325→Asp (2000)

Lactose/H(+) symport by lactose permease of Escherichia coli involves interactions between four irreplaceable charged residues in transmembrane helices that play essential roles in H(+) translocation and coupling [Glu269 (helix VIII) with His322 (helix X) and Arg302 (helix IX) with Glu325 (helix X)], as well as Glu126 (helix IV) and Arg144 (helix V) which are obligatory for substrate binding. The conservative mutation Glu325-->Asp causes a 10-fold reduction in the V(max) for active lactose transport and markedly decreased lactose-induced H(+) influx with no effect on exchange or counterflow, neither of which involves H(+) symport. Thus, shortening the side chain may weaken the interaction of the carboxyl group at position 325 with the guanidino group of Arg302. Therefore, Gly-scanning mutagenesis of helices IX and X and the intervening loop was employed systematically with mutant Glu325-->Asp in an effort to rescue function by introducing conformational flexibility between the two helices. Five Gly replacement mutants in the Glu325-->Asp background are identified that exhibit significantly higher transport activity. Furthermore, mutant Val316-->Gly/Glu325-->Asp catalyzes active transport, efflux, and lactose-induced H(+) influx with kinetic properties approaching those of wild-type permease. It is proposed that introduction of conformational flexibility at the interface between helices IX and X improves juxtapositioning between Arg302 and Asp325 during turnover, thereby allowing more effective deprotonation of the permease on the inner surface of the membrane [Sahin-Tóth, M., Karlin, A., and Kaback, H. R. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 10729-10732.