gebhart/patrepeval huggingface dataset:
Generation of Protease-Deficient Strains and Their Use in Heterologous Protein Expression (1998)

In optimizing expression of heterologous protein, the issue of proteolysis is often an important factor, since many peptides and proteins are susceptible to degradation by proteases produced in the host organism. In such cases even if the protein product is expressed at high levels, overall yield can be drastically reduced through proteolysis, which not only reduces the amount of intact material but also complicates the recovery process. The use of protease-deficient strains has been shown to be a successful approach to improve the yield of fully active, expressed proteins in both Saccharomyces cerevisiae and Escherichia coli (1,2). Proteolysis can occur during expression or during the first stages of purification. Certainly, expression of intracellular proteins, which requires cell lysis for purification, will result in their exposure to proteases. Similarly, secreted proteins will be exposed to vacuolar proteases through cell lysis that occurs during growth in the fermentor. Consequently, production of many proteins, particularly heterologously expressed proteins, depends on the amount of proteolytic activity they are exposed to during expression and purification, and the use of strains that are deficient in proteases can significantly improve overall yields.
Disruption of TPS2, the gene encoding the 100‐kDa subunit of the trehalose‐6‐phosphate synthase/phosphatase complex in Saccharomyces cerevisiae, causes accumulation of trehalose‐6‐phosphate and loss of trehalose‐6‐phosphate phosphatase activity (1993)

Preparations of the trehalose-6-phosphate synthase/phosphatase complex from Saccharomyces cerevisiae contain three polypeptides with molecular masses 56, 100 and 130 kDa, respectively. Recently, we have cloned the gene for the 56-kDa subunit of this complex (TPS1) and found it to be identical with CIF1, a gene essential for growth on glucose and for the activity of trehalose-6-phosphate synthase. Peptide sequencing of the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex (TPS2) revealed one sequence to be 100% identical with the deduced amino acid sequence of the upstream region of PPH3 on the right arm of chromosome IV. This sequence was used to clone an upstream region of PPH3 containing an open reading frame of 2685 nucleotides, predicted to encode a polypeptide of 102.8 kDa. The N-terminal sequence, as well as three internal amino acid sequences, obtained from peptide sequencing of the 100-kDa subunit, were identical with specific regions of the deduced amino acid sequence. Thus, the sequence cloned represents TPS2, the gene encoding the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex. Interestingly, a stretch of about 500 amino acids from the first part of TPS2 was 33% identical with the entire TPS1 sequence. Disruption of TPS2 had no effect on trehalose-6-phosphate synthase activity but caused complete loss of trehalose-6-phosphate phosphatase activity, measured in vitro, and accumulation of excessive amounts of trehalose-6-phosphate instead of trehalose upon heat shock or entrance into stationary phase in vivo. These results suggest that TPS2 codes for the structural gene of the trehalose-6-phosphate phosphatase. Heat shock induced an increase in trehalose-6-phosphate phosphatase activity and this was preceded by an accumulation in TPS2 mRNA, suggesting that the trehalose-6-phosphate phosphatase is subjected to transcriptional control under heat-shock conditions.
Rein oder nicht rein? (2010)

Lange Zeit ging man davon aus, dass Hahnemanns Arzneimittellehre im Wesentlichen Prüfungssymptome von hoher Zuverlässigkeit enthalte. Durch neuere medizinhistorische Forschungsergebnisse ist es möglich geworden, die unterschiedlichen Quellen dieser umfangreichen Symptomensammlung nicht nur quantitativ, sondern auch qualitativ genauer zu untersuchen. Dabei wurden 5 Hauptquellen identifiziert, aus denen Hahnemann seine Arzneimittellehre schöpfte.
Cutting Edge: Proangiogenic Properties of Alternatively Activated Dendritic Cells (2005)

Angiogenesis plays an important role in tissue remodeling and repair during the late phase of inflammation. In the present study, we show that human dendritic cells (DC) that matured in the presence of anti-inflammatory molecules such as calcitriol, PGE2, or IL-10 (alternatively activated DC) selectively secrete the potent angiogenic cytokine vascular endothelial growth factor (VEGF) isoforms VEGF165 and VEGF121. No VEGF production was observed in immature or classically activated DC. Also, the capacity to produce VEGF was restricted to the myeloid DC subset. When implanted in the chick embryo chorioallantoic membrane, alternatively activated DC elicit a marked angiogenic response, which is inhibited by neutralizing anti-VEGF Abs and by the VEGFR-2 inhibitor SU5416. Therefore, alternatively activated DC may contribute to the resolution of the inflammatory reaction by promoting VEGF-induced angiogenesis.
A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome (2003)

A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus.
Transient ectopic expression as a method to detect genes conferring drug resistance (2008)

Ectopic expression provides an alternative to RNAi to conduct functional genomic screens. We have determined whether transient expression can be used to identify genes which confer drug resistance. We constructed a bigenic vector that allows high throughput cloning and which also encodes a red fluorescent protein to monitor transfection. Assay conditions were optimized to allow detection of changes in sensitivity to carboplatin or paclitaxel. Following transient expression of MDR-1 and MCJ, changes in the sensitivity of Sk-Ov-3 cells to paclitaxel were detected whereas expression of Src, Bcl-2 and Bcl-X(L) decreased the sensitivity of Sk-Ov-3 cells to carboplatin. This approach may potentially be used as an independent screen or as a method to help rank hit identified in screens utilizing methods such as RNAi.
Signal Sequence Recognition and Protein Targeting to the Endoplasmic Reticulum Membrane (1994)

STRUCTURE OF THE SRP AND SRP RECEPTOR . NOlllelleiatllre . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SRP RNA SRP Structllre alld Assembly . SRP Proteill SlIbllllits . . . . . . .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SRP Receptor .
Influence of GATC sequences on Escherichia coli DNA mismatch repair in vitro (1987)

The effect of the number and position of DNA adenine methylation (dam) sites, i.e., d(GATC) sequences, on mismatch repair in Escherichia coli was investigated. The efficiency of repair was measured in an in vitro assay which used an f1 heteroduplex containing a G/T mismatch within the single EcoRI site. Both an increase in the number of dam sites and a shortened distance between dam site and mismatched site increased the efficiency of mismatch repair. The sequences adjacent to d(GATC) also affected the efficiency of methylation-directed mismatch repair. Furthermore, heteroduplexes with one extra dam site located close to either the 5' or 3' end of the excised base increased the repair efficiency to about the same extent. The findings suggest that the mismatch repair pathway has no preferred polarity.
Cysteine-Rich Secretory Protein 2 Binds to Mitogen-Activated Protein Kinase Kinase Kinase 11 in Mouse Sperm1 (2007)

Cysteine-rich secretory protein (CRISP) 2 (previously TPX1) is a testis-enriched member of the CRISP family, and has been localized to both the sperm acrosome and tail. Like all members of the mammalian CRISP family, its expression pattern is strongly suggestive of a role in male fertility, but functional support for this hypothesis remains limited. In order to determine the biochemical pathways within which CRISP2 is a component, the putative mature form of CRISP2 was used as bait in a yeast two-hybrid screen of a mouse testis expression library. One of the most frequently identified interacting partners was mitogen-activated protein kinase kinase kinase 11 (MAP3K11). Sequencing and deletion experiments showed that the carboxyl-most 20 amino acids of MAP3K11 interacted with the CRISP domain of CRISP2. This interaction was confirmed using pull-down experiments and the cellular context was supported by the localization of CRISP2 and MAP3K11 to the acrosome of the developing spermatids and epididymal spermatozoa. Interestingly, mouse epididymal sperm contained an approximately 60-kDa variant of MAP3K11, which may have been a result of proteolytic cleavage of the longer 93-kDa form seen in many tissues. These data raise the possibility that CRISP2 is a MAP3K11-modifying protein or, alternatively, that MAP3K11 acts to phosphorylate CRISP2 during acrosome development.
Plectin-1 as a Novel Biomarker for Pancreatic Cancer (2010)

Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging.
Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication (1992)

By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1.
On the Deformation and Recrystallization of (001)[110] Single Crystals of Pure Tungsten Rolled at 200&deg;C and Tantalum at 100&deg;C (1975)

The deformation and recrystallization of (001)[110] single crystals of pure W rolled at 200°C and Ta at 100°C were studied. The main experimental results obtained are as follows:(1) The widening of W crystals increased with increasing rolling reduction, but no widening was observed in Ta crystals rolled to a reduction of 60%.(2) Recrystallization of rolled W and Ta crystals always took place from the strip edge regions.(3) The ratios of the recrystallization temperature to the melting point were found to be very high in both W and Ta crystals rolled to 60% reduction.(4) The recrystallized textures observed in both W and Ta crystals were not so sharp. The axes for rotation relationship between successfully grown grains and rolled matrix were nearly 〈111〉 and 〈110〉 in W crystals and random in Ta crystals.(5) The spontaneously recrystallized textures were remarkably different from the artificially recrystallized ones in both W and Ta crystals.
Intraocular Pressure Reduction With PhXA34, a New Prostaglandin Analogue, in Patients With Ocular Hypertension (1992)

In a randomized, double-masked, parallel study, one drop of 0.003% (1 microgram; n = 9) or 0.01% (3 micrograms; n = 10) PhXA34, a new phenyl-substituted prostaglandin F2 alpha analogue (13,14-dihydro-15[R,S]-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), or its vehicle (n = 10) was applied topically twice daily for 6 days to one eye in each of 29 patients with ocular hypertension. Compared with either baseline, contralateral, or vehicle control values, PhXA34 caused a significant (P < .001) dose-dependent reduction of intraocular pressure. The reduction lasted at least 12 hours after each drop and 24 to 48 hours after the last drop, with a significant (P < .0001) mean +/- SEM reduction of as much as 10 +/- 1 mm Hg (40%). Conjunctival hyperemia was not produced by 0.003% PhXA34, but was noted in some eyes treated with 0.01% PhXA34, and after repeated tonometry with either concentration. The prostaglandin analogue did not produce clinically obvious miosis, anterior chamber flare or cellular response, or any subjective adverse effects. PhXA34 is a potent, effective, and well-tolerated ocular hypotensive agent based on our results in this small, short-term study. Its potential as a new drug for glaucoma therapy warrants further investigation in long-term, larger studies.
Advances in diabetes for the millennium: understanding insulin resistance. (2004)

Type 2 diabetes is a heterogeneous disorder in which both insulin resistance and impaired insulin secretion play important roles. Studies in monozygotic twins in which one is discordant for type 2 diabetes and studies of first-degree relatives of patients with type 2 diabetes who still have normal glucose tolerance indicate that impaired insulin secretion can be detected before insulin resistance, suggesting that impaired beta-cell function may be the primary genetic defect. The insulin resistance found in most individuals with impaired glucose tolerance and/or type 2 diabetes appears to be largely acquired and can be accounted for by obesity, physical inactivity, and glucose and lipotoxicity. Progressive deterioration in beta-cell function as demonstrated in the United Kingdom Prospective Diabetes Study (UKPDS) and/or worsening of insulin resistance leads to deterioration in glucose tolerance and to secondary failure of oral antidiabetic drugs. Therefore, agents that improve beta-cell function (such as sulfonylureas and meglitinides) and insulin sensitizers (such as metformin and thiazolidinediones) both are useful alone or in combination for treating type 2 diabetes.
14C-2-deoxyglucose uptake in the ground squirrel brain during entrance to and arousal from hibernation (1990)

Neuronal activity underlying various phases of the mammalian hibernation cycle was investigated using the 14C-2-deoxyglucose (2DG) method. Relative 2DG uptake (R2DGU) values were computed for 96 brain regions across 7 phases of the hibernation cycle: euthermia, 3 body temperature (Tb) intervals during entrance into hibernation, stable deep hibernation, and 2 Tb intervals during arousal from hibernation. Multivariate statistical techniques were employed to identify objectively groups of brain regions whose R2DGU values showed a similar pattern across all phases of hibernation. Factor analysis revealed that most of the variability in R2DGU values for the 96 brain regions across the entire cycle could be accounted for by 3 principal factors. These factors could accurately discriminate the various phases of hibernation on the basis of the R2DGU values alone. Three hypothalamic and 3 cortical regions were identified as possibly mediating the entrance into hibernation because they underwent a change in R2DGU early in entrance into hibernation and loaded strongly on one of the principal factors. Another 4 hypothalamic regions were similarly identified as possibly causally involved in the arousal from hibernation. These results, coupled with characteristic changes in ordinal rank of the 96 brain regions in each phase of hibernation, support the concept that mammalian hibernation is an active, integrated orchestration of neurophysiological events rather than a state entered through a passive process.
Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma (2011)

The tumour-suppressor miRNAs let-7 and mir-101 target MYCN and inhibit proliferation and clonogenic growth of MYCN-amplified neuroblastoma cells.
Functionalization of Carbon Nanotubes by Electrochemical Reduction of Aryl Diazonium Salts:  A Bucky Paper Electrode (2001)

Small-diameter (ca. 0.7 nm) single-wall carbon nanotubes are predicted to display enhanced reactivity relative to larger-diameter nanotubes due to increased curvature strain. The derivatization of these small-diameter nanotubes via electrochemical reduction of a variety of aryl diazonium salts is described. The estimated degree of functionalization is as high as one out of every 20 carbons in the nanotubes bearing a functionalized moiety. The functionalizing moieties can be removed by heating in an argon atmosphere. Nanotubes derivatized with a 4-tert-butylbenzene moiety were found to possess significantly improved solubility in organic solvents. Functionalization of the nanotubes with a molecular system that has exhibited switching and memory behavior is shown. This represents the marriage of wire-like nanotubes with molecular electronic devices.
SIRT3, a human SIR2 homologue, is an NAD- dependent deacetylase localized to mitochondria (2002)

The SIR2 (silent information regulator 2) gene family has diverse functions in yeast including gene silencing, DNA repair, cell-cycle progression, and chromosome fidelity in meiosis and aging. Human homologues, termed sirtuins, are highly conserved but are of unknown function. We previously identified a large imprinted gene domain on 11p15.5 and investigated the 11p15.5 sirtuin SIRT3. Although this gene was not imprinted, we found that it is localized to mitochondria, with a mitochondrial targeting signal within a unique N-terminal peptide sequence. The encoded protein was found also to possess NAD(+)-dependent histone deacetylase activity. These results suggest a previously unrecognized organelle for sirtuin function and that the role of SIRT3 in mitochondria involves protein deacetylation.
Opioid growth factor inhibition of a human squamous cell carcinoma of the head and neck in nude mice: Dependency on the route of administration (2004)

Opioid growth factor (OGF), [Met5]-enkephalin, interacts with the OGF receptor (OGFr) to inhibit the growth of human squamous cell carcinoma of the head and neck (SCCHN) in vitro. Administration of OGF by daily intraperitoneal injection (i.p.) to animals with xenografts of CAL-27, a poorly differentiated SCCHN, is known to repress tumorigenic events. In this study, the ubiquity of OGF action on SCCHN was investigated by examination of OGF activity on SCC-1 tumors; this human cell line is well-differentiated and highly invasive. Mice receiving daily i.p. injections (10 mg/kg) of OGF had more than a 3-day delay in tumor appearance, and decreases in tumor volume ranging from 51 to 64% in comparison to controls throughout the experimental period. Receptor binding analysis for OGFr showed that binding capacity (Bmax) was 2.2-fold greater than control values, but binding affinity (Kd) was comparable. Plasma OGF levels did not vary between OGF and control groups. Mice receiving OGF by continuous infusion using minipumps, or by daily intratumoral injection, had characteristics of tumorigenicity similar to their corresponding control animals, although the OGF levels in mice receiving the OGF by minipump were elevated 18-fold greater than the control group. These data indicate that: i) the inhibitory action of OGF may be ubiquitous for SCCHN, ii) OGF treatment alters the characteristics of the OGF receptor but not of plasma OGF levels, and iii) the magnitude of effects of OGF on SCCHN is dependent on the route of administration.
Programming by example (1984)

Programming by example is a way of programming a software system in its own user interface. The user of the system writes a program by giving an example of what the program should do. The system records the sequence of actions, and can perform it again. Programming by example allows a user to create programs without doing conventional programming. Programming by example was incorporated into a simulation of an office information system. As the system evolved, it became clear that the basic concept of programming by example needed to be extended: certain aspects of program creation are better done by program modification than by using the programming-by-example mechanism. The final system includes a static program representation that is easy to understand, a mechanism for describing data, and a method of adding control structure. A user operates on certain data while creating a program by example, but does not necessarily tell the system why that data was selected. The user can supply this missing information by using data descriptions, which are program operands that specify how to choose the data to be used when the program is run. The system automatically supplies reasonable default data descriptions while recording a program; if necessary the user can modify the descriptions later to reflect his or her true intentions. Since programming by example is best at recording sequential user actions, rather than branching or iteration, control structure that alters program flow is specified by program editing. The operands in iterations and the predicates in conditional control structures are built from data descriptions. Real users have learned to use the system quickly and with little difficulty. The techniques used in this system can be applied to other systems as well. This research has demonstrated that programming by example is a practical method for creating programs. This document is a slightly corrected version of a dissertation submitted to the Department of Electrical Engineering and Computer Sciences, Computer Science Division, University of California, Berkeley, in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Computer Science. A nearly identical version of this document was also published by the Office Systems Division, Systems Development Department, Xerox Corporation, as technical report OSD-T8402, December, 1984. An online version of this document was recreated by the author in March, 1999. For more information, contact the author at halbert@world.std.com halbert@halwitz.org. Copyright © 1984 by Daniel Conrad Halbert. All rights reserved.
Prior immunologic experience potentiates the subsequent antibody response when Salmonella strains are used as vaccine carriers (1991)

Prior immunologic experience with homologous and heterologous serotype Salmonella strains potentiated the subsequent antibody response when the same strains were used as vaccine carriers of foreign antigens. This potentiation was positively correlated with the appearance of antibody directed against the lipopolysaccharide of the carrier strain. Both serum and mucosal antibody responses against the foreign antigen increased over time. Antibody responses in sera of animals primed with either the homologous or heterologous serotype strain were not statistically significantly different, while animals primed with the homologous serotype strain developed significantly better mucosal antibody responses against the foreign antigen.
Global Effect of PEG-IFN- α and Ribavirin on Gene Expression in PBMC In Vitro (2004)

Using oligonucleotide microarrays, we have examined the expression of 22,000 genes in peripheral blood cells treated with pegylated interferon-α2b (PEG-IFN-α) and ribavirin. Treatment with ribavirin had very little effect on gene expression, whereas treatment with PEG-IFN-α had a dramatic effect, modulating the expression of approximately 1000 genes (at p < 0.001). In addition to genes previously reported to be induced by type I or type II IFNs, many novel genes were found to be upregulated, including transcription factors, such as ATF3, ATF4, properdin, a key regulator of the complement pathway, a homeobox gene (HESX1), and an RNA editing enzyme (apobec3). Chemokines CXCL10 and CXCL11 were upregulated, whereas CXCL5 was downregulated. Cytokines interleukin-15 (IL-15) and IL-18 were also significantly induced, whereas IL-1α and IL-1β were downregulated. Most other interleukins were not affected. The results of the microarrays were confirmed by kinetic real-time PCR. These data indicate that IFN treatment causes upregulation of genes associated with the stress response, apoptosis, and signaling, and an equal number of genes are downregulated, including those associated with protein synthesis, specific cytokines and chemokines and other biosynthetic functions.