gebhart/patrepeval huggingface dataset:
The preservation of poliomyelitis vaccine with stabilized merthiolate. (1956)

Abstract 1.1. Solutions of Merthiolate are stable to prolonged periods of heating when traces of cupric ion are removed. 2.2. Trivalent poliomyelitis virus vaccine produced in monkey kidney tissue culture may be satisfactorily preserved with Merthiolate if the trisodium salt of ethylene diamine tetra-acetic acid is added. 3.3. The protective antigenicity of the vaccine against the three types of virus is maintained in accelerated aging tests at 37 ° C. for two weeks. 4.4. The antibacterial and antifungal actions of this preservative are not diminished by the addition of EDTA.
Growth Hormone Stimulates Longitudinal Bone Growth Directly (1982)

Local administration of human growth hormone in vivo to the cartilage growth plate of the proximal tibia of hypophysectomized rats resulted in accelerated longitudinal bone growth. This finding suggests that growth hormone directly stimulates the cells in the growth plate, and does not support the theory that the increase in the plasma concentration of somatomedin that follows growth hormone administration is the cause of this stimulation.
Informativity assessment for biallelic single nucleotide polymorphisms (1999)

Common single nucleotide polymorphisms (SNPs) have the potential to provide a widely used means of simple and robust kinship testing. Suitable measures of polymorphism informativity are therefore required in order to guide the search for the most efficient combinations of SNPs. In the context of kinship testing, such measures should preferably be related to Z, the power of excluding false paternity in trios comprising mother, child and alleged father. Since the bulk of SNPs is expected to be biallelic, a Z-related measure of informativity can be defined for SNPs in a particularly elegant manner: allele frequency vectors of sets of n biallelic SNPs that give rise to the same Z value approximate to an n-dimensional sphere around (1/2,...,1/2). Owing to this relationship, it can be shown that the number N of maximally informative SNPs (i.e., of SNPs with allele frequencies 1/2), providing the same Z value as a given set of n SNPs, approximates to 2n times the average gene diversity of the latter. Linear regression analysis of a large number of simulated SNP sets reveals that only a minor linear correction of Nis required for large n. Since Z= 1-(13/16)N, Ncan also be calculated easily for multiallelic markers with known Z. The "equivalent number of maximally informative SNPs", N, is therefore suggested as a measure of marker informativity in the context of kinship testing.
Protein topology determines binding mechanism (2003)

Protein recognition and binding, which result in either transient or long-lived complexes, play a fundamental role in many biological functions, but sometimes also result in pathologic aggregates. We use a simplified simulation model to survey a range of systems where two highly flexible protein chains form a homodimer. In all cases, this model, which corresponds to a perfectly funneled energy landscape for folding and binding, reproduces the macroscopic experimental observations on whether folding and binding are coupled in one step or whether intermediates occur. Owing to the minimal frustration principle, we find that, as in the case of protein folding, the native topology is the major factor that governs the choice of binding mechanism. Even when the monomer is stable on its own, binding sometimes occurs fastest through unfolded intermediates, thus showing the speedup envisioned in the fly-casting scenario for molecular recognition.
The sheep metallothionein gene family (1988)

Southern blot analysis of the sheep genome revealed a metallothionein gene family with at least nine members. Two overlapping cosmid clones spanning approximately 67 kb and containing five metallothionein genes have been isolated. DNA sequence analysis reveals that one of these is a metallothionein II variant, three are metallothionein I variants and one is a truncated metallothionein pseudogene containing only the first exon. The predicted amino acid sequence was compared with previously reported amino acid composition data of sheep metallothioneins [Whanger, P. D., Oh, S.-H. & Deagen, J. T. (1981) J. Nutr. 111, 1207-1215], and this suggests that we have isolated the genes encoding the major protein isoforms found in the sheep liver. The promoter regions of these genes contain many conserved elements, among them metal-regulatory elements and putative glucocorticoid-responsive elements. However, there are a number of differences between these genes in the arrangement of these elements. Sequence comparisons indicate that the multiple metallothionein I genes and the pseudogene appear to have resulted from sequential duplication events, and a larger cluster of metallothionein I genes may have been disrupted leading to the formation of the pseudogene.
Prognostic meta-signature of breast cancer developed by two-stage mixture modeling of microarray data (2004)

The mixture modeling approach unifies disparate gene expression data on a common probability scale allowing for robust, inter-study validated prognostic signatures to be obtained. With the emerging utility of microarrays for cancer prognosis, it will be important to establish paradigms to meta-analyze disparate gene expression data for prognostic signatures of potential clinical use.
Oil-Based Muds for Reservoir Drilling: Their Performance and Cleanup Characteristics (2001)

Summary This paper evaluates the performance of a standard oil-based mud (OBM) to drill horizontal wellbores, concentrating on its formationdamage characteristics and the flow-initiation pressures (FIP's) required for production to flow through the filter cake. For heterogeneous reservoirs, damage is relatively low in low-permeability rocks, but the FIP is high. Conversely, for high-permeability rocks, the FIP is low but formation damage is relatively high. If the drawdown pressure available from the reservoir is low, the scenario exists where inflow will occur predominantly from the higher-permeability formations, which could be damaged badly, but little inflow will occur from relatively undamaged lower-permeability rocks. In terms of maximizing production, this is obviously a less-than-optimal scenario. Evaluations of cleanup fluids were conducted to gauge their effect on lowering the FIP of OBM filter cakes. Various fluids were screened for their mud-removal performance, which would indicate potentially good OBM "chemical breakers." Mud parameters such as oil:water (O:W) ratio, base-oil type, and emulsifier content all affected the efficiency of the cleanup fluids. The best cleanup fluids were used then in a series of core tests to evaluate their effectiveness in reducing the filter-cake FIP. Reductions between 25 and 40% were possible, although parameters such as soak time and overbalance pressure were critical to their success.
Epidermal expression of interleukin-6 and tumour necrosis factor-alpha in normal and immunoinflammatory skin states in humans. (1992)

The in vivo presence of cytokines in human skin was examined by ABC- and IF-techniques, and by using antisera to human rIL-6, rIL-1-alpha, rIL-1-beta, rTNF-alpha and an antiserum to crude supernatants of Staph. albus activated human blood monocytes (anti-MK-antiserum) before and after absorption with rIL-6. The following normal and immunoinflammatory human skin states were examined: Normal skin. Examination of biopsies from 9 healthy individuals and single cell preparations from 3 healthy individuals revealed a granular intercellular/membrane associated staining for IL-6 and TNF-alpha in the upper epidermal layers. A cytoplasmic staining was also detected, most pronounced using the anti-rIL-6 antiserum. Membrane associated IL-6 and TNF-alpha were detected in epidermal single cell preparations, but CD1 positive LC failed to express any of the cytokines examined. Psoriasis skin. Biopsies from lesional and unaffected skin of 11 patients with chronic, nummular/plaque type psoriasis were investigated for IL-6, and in addition 5 of these, moreover, for TNF-alpha. Biopsies from lesional psoriatic skin continually revealed increased staining for IL-6 compared with non-lesional skin, where the staining was similar to that observed in healthy individuals. Epidermal TNF-alpha expression did not differ from that observed in normal skin. AIDS related Kaposi's sarcom. Epidermal staining patterns were similarly increased for IL-6 and TNF-alpha in biopsies obtained from nodular KS tumours compared with unaffected skin of 6 homosexual male AIDS patients, whereas the endotheloid cell of the tumour did not stain for any of the cytokines. Staining of unaffected skin was similar to that observed in healthy individuals. The allergic and irritant patch test reaction. Investigation of biopsies from 5 patients with positive APR and 5 healthy individuals with IPR disclosed increased epidermal staining for IL-6, but not for TNF-alpha, in both reactions, while staining from petrolatum tested and non-tested skin was similar to that observed in normal individuals. CD1 positive LC remained negative in all biopsies when stained for IL-6 and TNF-alpha. In vivo UV-irradiated skin. Using anti-MK and anti TNF-alpha antisera skin biopsies from 5 healthy subjects 24 h after UVB irradiation revealed markedly increased epidermal staining for both cytokines compared with non-irradiated skin. Furthermore, a gradual decrease in epidermal staining for IL-6 was observed in specimens from lesional skin of 6 patients with psoriasis taken before and during PUVA therapy, while staining of non-lesional skin remained unchanged.
Physical reasons for secondary structure stability: α‐Helices in short peptides (1991)

It was recently found that some short peptides (including C- and S-peptide fragments of RNase A) can have considerable helicity in solution, which was considered to be surprising. Does the observed helicity require a new explanation, or is it consistent with previous understanding? In this work we show that this helicity is consistent with the physical theory of secondary structure based on an extension of the conventional Zimm-Bragg model. Without any special modifications, this theory explains reasonably well almost all the experimentally observed dependencies of helicity on pH, temperature, and amino acid replacements. We conclude that the observed "general level" of helicity of C- and S-peptides (5-30% at room temperature and 10-50% near 0 degrees C) is "normal" for short peptides consisting mainly of helix-forming and helix-indifferent residues. The helicity is modified by a multitude of weak specific side chain interactions, many of which are taken into account by the present theory; some discrepancies between the theory and experiment can be explained by weak side-chain-side chain interactions that were neglected. A reasonable coincidence of the theory with experiment suggests that it had been used to investigate the role of local interactions in the formation of alpha-helical "embryos" in unfolded protein chains.
Insights into the initiation of type 2 immune responses (2011)

Type 2 immune responses, characterized by the differentiation of CD4+ T helper type 2 (Th2) cells and the production of the type 2 cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, are associated with parasitic helminth infections and inflammatory conditions such as asthma and allergies. Until recently the initiating factors associated with type 2 responses had been poorly understood. This review addresses the recent advances in identifying the diverse range of antigens/allergens associated with type 2 responses and the function, expression and sources of type-2-initiating cytokines (thymic stromal lymphopoietin, IL-25 and IL-33). We also discuss the latest findings regarding innate lymphoid cells, such as nuocytes, as early sources of type 2 cytokines and their importance in protective immunity to helminth infections. These developments represent major breakthroughs in our understanding of type 2 immunity, and highlight the increased complexity existing between the innate and adaptive arms of these responses. These additional steps in the type 2 immune pathway also offer potential targets for therapeutic intervention.
Surfection: a new platform for transfected cell arrays (2004)

Efficient high-throughput expression of genes in mammalian cells can facilitate large-scale functional genomic studies. Towards this aim, we developed a simple yet powerful method to deliver genes into cells by cationic polymers on the surface of substrates. Transfection can be achieved by directly contacting nucleic acid-cell mixtures with the cationic substrates, e.g. polyethylenimine/collagen-coated wells. This single-step matrix-surface- mediated transfection method, termed 'surfection', can efficiently deliver multiple plasmids into cells and can successfully assay siRNA-mediated gene silencing. This technology represents the easiest method to transfer combinations of genes in large-scale arrays, and is a versatile tool for live-cell imaging and cell-based drug screening.
Osthole improves alcohol‐induced fatty liver in mice by reduction of hepatic oxidative stress (2010)

The aim of our study was to examine the therapeutic effect of osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, on alcohol-induced fatty liver in mice and investigate its potential mechanisms of treatment. A mouse alcoholic fatty liver model was established by feeding 52% alcohol for 4 weeks. These experimental mice were then treated with osthole 10, 20 and 40 mg/kg for 6 weeks. The levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and hepatic tissue contents of TC, TG and malondialdehyde (MDA) in osthole-treated groups were significantly decreased, while the level of superoxide dismutase (SOD) was significantly increased compared with the model group. Moreover, the cytochrome P450 (CYP) 2E1 and diacylglycerol acyltransferase (DGAT) mRNA expressions in mouse liver were significantly decreased, and the carnitine palmitoyltransferase (CPT) 1A mRNA expression was increased by osthole treatment. Importantly, the histological evaluation of liver demonstrated that osthole dramatically decreased lipid accumulation. It was concluded that osthole was effective in treating mouse alcoholic fatty liver, and its main mechanisms might be related to reduction of hepatic oxidative stress, including the inhibition of reactive oxygen species (ROS) production, enhancement of antioxidative enzyme activity, and reduction of lipid accumulation and peroxidation.
Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization (1991)

An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to combretastatins, were highly cytotoxic in all five cell lines and these were also found to be active as inhibitors of tubulin polymerization. The most active compounds also inhibited the binding of colchicine to tubulin. The most potent of the new compounds, both as a tubulin polymerization inhibitor and as a cytotoxic agent, was (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene (5a). This substance was almost as potent as combretastatin A-4 (1a), the most active of the combretastatins, as a tubulin polymerization inhibitor. Compound 5a was found to be approximately 140 times more cytotoxic against HT-29 colon adenocarcinoma cells and about 10 times more cytotoxic against MCF-7 breast carcinoma cells than combretastatin A-4. However, 5a was found to be about 20 times less cytotoxic against A-549 lung carcinoma cells, 30 times less cytotoxic against SKMEL-5 melanoma cells, and 7 times less cytotoxic against MLM melanoma cells than combretastatin A-4. The relative potencies 5a greater than 8a greater than 6a for the cis, dihydro, and trans compounds, respectively, as inhibitors of tubulin polymerization are in agreement with the relative potencies previously observed for combretastatin A-4 (1a), dihydrocombretastatin A-4 (1c), and trans-combretastatin A-4 (1b). The relative potencies 5a greater than 8a greater than 6a were also reflected in the results of the cytotoxicity assays. Structure-activity relationships of this group of compounds are also discussed.
A general method for maximizing the expression of a cloned gene. (1979)

We present a method, utilizing a combination of restriction endonuclease cleavage and digestion with Escherichia coli exonuclease III and Aspergillus orizae nuclease S1, that allows us to position a restriction fragment bearing the promoter of the lacZ gene of E. coli at virtually any distance in front of any cloned gene. In particular, we have used this method to examine the effect on protein production of gene-promoter separation for the cro gene of phage lambda and to produce plasmids that, upon transformation into appropriate E. coli hosts, direct the synthesis of up to 190,000 cro protein monomers per cell.
The Androgen Axis in Recurrent Prostate Cancer (2004)

Testosterone and dihydrotestosterone occur in recurrent prostate cancer tissue at levels sufficient to activate androgen receptor. Novel therapies for recurrent prostate cancer should target androgen receptor directly and prevent the formation of androgens within prostate cancer tissue.
Route packets, not wires: on-chip interconnection networks (2002)

Using on-chip interconnection networks in place of ad-hoc global wiring structures the top level wires on a chip and facilitates modular design. With this approach, system modules (processors, memories, peripherals, etc...) communicate by sending packets to one another over the network. The structured network wiring gives well-controlled electrical parameters that eliminate timing iterations and enable the use of high-performance circuits to reduce latency and increase bandwidth. The area overhead required to implement an on-chip network is modest, we estimate 6.6%. This paper introduces the concept of on-chip networks, sketches a simple network, and discusses some challenges in the architecture and design of these networks.
Inverse Thinking about Double Mutants of Enzymes (2004)

The quantitative effect of a second damaging mutation on a mutated enzyme may be additive, partially additive, synergistic, antagonistic, or absent, in the double mutant. Each of these five possible types of interactions has its own mechanistic explanation [Mildvan, A. S., Weber, D. J., and Kuliopulos, A. (1992) Arch. Biochem. Biophys. 294, 327-340]. Additive effects indicate independent functioning of the two residues in the process being studied, such as catalysis (k(cat)) or substrate binding (K(S)). Departures from additivity reflect interaction of the two residues. Thus, partial additivity indicates cooperativity, synergy indicates anticooperativity, and antagonism indicates opposing structural effects of the two mutations. No additional effects represent limiting cases of either partial additivity or antagonism. A significant conceptual simplification is achieved by applying inverse thinking, namely, by using the parameters of the double mutant rather than those of the wild-type enzyme as the reference point. To explain partially additive effects on k(cat), inverse thinking starts with the k(cat) of the double mutant. Restoring only one residue increases k(cat) by the factor A. Restoring only the other residue increases k(cat) by the factor B. Restoring both residues is shown to increase k(cat) by a factor greater than A x B, with the excess directly measuring the cooperativity. Similarly, inverse thinking provides simpler and more intuitive explanations of synergistic and antagonistic effects, as illustrated by specific examples.
Design and performance of scalable high-performance programmable routers (2002)

The flexibility to adapt to new services and protocols without changes in the underlying hardware is and will increasingly be a key requirement for advanced networks. Introducing a processing component into the data path of routers and implementing packet processing in software provides this ability. In such a programmable router, a powerful processing infrastructure is necessary to achieve a level of performance that is comparable to custom silicon-based routers and to demonstrate the feasibility of this approach. This work aims at the general design of such programmable routers and, specifically, at the design and performance analysis of the processing subsystem. The necessity of programmable routers is motivated, and a router design is proposed. Based on the design, a general performance model is developed and quantitatively evaluated using a new network processor benchmark. Operational challenges, like scheduling of packets to processing engines, are addressed, and novel algorithms are presented. The results of this work give qualitative and quantitative insights into this new domain that combines issues from networking, computer architecture, and system design.
Facet preparation of SOI waveguides by etching and cleaving compared to dicing and polishing (2005)

We compared two different techniques of facet preparation of silicon-on-insulator (SOI) waveguides: The conventional by dicing and polishing and our proposed by dry etching the facets and cleaving along anisotropically etched cleaving grooves.
A Novel cis -Acting Element Required for Lipopolysaccharide-Induced Transcription of the Murine Interleukin-1β Gene (1995)

Regulatory elements important for transcription of the murine interleukin-1 beta (IL-1 beta) gene lie within a DNase I-hypersensitive region located > 2,000 bp upstream from the transcription start site. We have identified within this region a novel positive regulatory element that is required for activation of an IL-1 beta promoter-chloramphenicol acetyltransferase (CAT) fusion gene in the murine macrophage line RAW264.7. Electrophoretic mobility shift analysis of the 3' portion (-2315 to -2106) of the hypersensitive region revealed at least two nuclear factor binding sites, one of which is located between positions -2285 and -2256. Competitive inhibition studies localized the binding site to a 15-bp sequence between -2285 and -2271. Nuclear factor binding was lost by mutation of the 6-bp sequence from -2280 to -2275. The specific retarded complex formed with RAW264.7 nuclear extract was not detected under similar conditions with nuclear extracts from RLM-11, a murine T-cell line which does not express IL-1 beta RNA. Mutation of the 6-bp sequence (-2280 to -2275) in the chimeric IL-1 beta promoter -4093 +I CAT plasmid virtually eliminated the activation of this reporter gene by lipopolysaccharide (LPS) in transfected RAW264.7 cells. Multimerization of the 15-bp sequence containing the core wild-type 6-bp sequence 5' of minimal homologous or heterologous promoters in CAT reporter plasmids resulted in significant enhancement of CAT expression compared with parallel constructs containing the mutant 6-bp core sequence. This element was LPS independent and position and orientation dependent. The multimerized 15-bp sequence did not enhance expression in RLM-11 cells. Methylation interference revealed contact residues from -2281 to -2271, CCAAAAAGGAA. Because a search of the NIH TFD data bank with the 11-bp binding site sequence found no homology to known nuclear factor binding sites, we have designated this sequence the IL1 beta -upstream nuclear factor 1 (IL1 beta -UNF1) target. UV cross-linking and sodium dodecyl sulfate-polyacrylamide electrophoresis identified an IL1 beta -UNF1-specific binding factor approximately 85 to 90 kDa in size.