gebhart/patrepeval huggingface dataset:
Characterization of the Estrogenic Properties of a Nonsteroidal Estrogen, Equol, Extracted from Urine of Pregnant Macaques1 (1984)

Recent reports of substantial urinary levels of equol in pregnant macaques and humans pose a concern, because equol poisoning in the ovine is characterized by an often permanent failure of reproductive processes. Equol (Fig. 1), a metabolite of phytoestrogens, is thought to act through estrogen receptors. The present study made a direct comparison of the estrogenic activity of equol from macaque urine, (+/-) equol and 17 beta-estradiol (E2) in vitro and in vivo. Relative binding affinity of equol for rat uterine receptor was 1% that of E2, and the dissociation rate of equol from the receptor was very high. Consistent with equol's binding properties in vitro, it was ineffective in stimulating rat uterine weight gain and possessed limited ability to increase progesterone receptor. Uterine nuclear receptors after doses of equol sufficient to produce depletion and replenishment of cytosol estrogen receptor were not measurable by exchange assay. No antiestrogenic activity of equol could be demonstrated. Equol's weak potency and lack of antiestrogenic activity are difficult to reconcile with its ability to induce ovine infertility. We conclude species differences at some level other than classical estrogen receptor as defined in the rat model are responsible for variability in equol's impact.
Development of a Multi‐DOF Electromyography Prosthetic System Using the Adaptive Joint Mechanism (2006)

This paper describes an electrically powered prosthetic system controlled by electromyography (EMG) signal detected from the skin surface of the human body. The research of electrically powered prosthetic systems is divided into two main subjects. One is the design of the joint mechanism. We propose the use of an adaptive joint mechanism based on the tendon‐driven architecture. This mechanism includes mechanical torque–velocity converters and a mechanism to assist the proximal joint torque by distal actuators. The other subject is the recognition of the EMG signal. For the discrimination of many patterns and nonlinear properties of the EMG signal, we propose a controller based on a simple pattern recognition information process. The system also drives 12 servomotors to move the adaptive joint mechanism. In this paper, we show the proposed system and describe the mechanical design of the prosthetic hand. The experimental results show that the electrically powered devices can be controlled using the proposed method.
A case for redundant arrays of inexpensive disks (RAID) (1988)

Increasing performance of CPUs and memories will be squandered if not matched by a similar performance increase in I/O. While the capacity of Single Large Expensive Disks (SLED) has grown rapidly, the performance improvement of SLED has been modest. Redundant Arrays of Inexpensive Disks (RAID), based on the magnetic disk technology developed for personal computers, offers an attractive alternative to SLED, promising improvements of an order of magnitude in performance, reliability, power consumption, and scalability. This paper introduces five levels of RAIDs, giving their relative cost/performance, and compares RAID to an IBM 3380 and a Fujitsu Super Eagle.
A Sense Phosphorothioate Oligonucleotide Directed to the Initiation Codon of Transcription Factor NF-κ-B Causes Sequence-Specific Immune Stimulation (1993)

Antisense oligonucleotides have proved effective in achieving targeted inhibition of gene expression. In such experiments, sense oligonucleotides have frequently been used as a control for nonspecific effects, but the results have been variable, raising questions about the reliability of sense oligomers as a control. It is possible that some of the effects of sense oligonucleotides may be specific. We have shown that phosphorothioate antisense oligonucleotides to the p65 subunit of NF-kappa B, a transcription factor, cause a block in cell adhesion. In our efforts to test the efficacy of NF-kappa B p65 oligonucleotides in vivo, we unexpectedly observed that the control p65-sense, but not the p65-antisense, oligonucleotides caused massive splenomegaly in mice. In the current study we demonstrate a sequence-specific stimulation of splenic cell proliferation, both in vivo and in vitro, by treatment with p65-sense oligonucleotides. Cells expanded by this treatment are primarily B-220+, sIg+ B cells. The secretion of immunoglobulins by the p65-sense oligonucleotide-treated splenocytes is also enhanced. In addition, the p65-sense-treated splenocytes, but not several other cell lines, showed an upregulation of NF-kappa B-like activity in the nuclear extracts, an effect not dependent on new protein or RNA synthesis. These results demonstrate that phosphorothioate oligonucleotides can exert sequence-specific effects in vivo, irrespective of sense or antisense orientation.
IL-18 Is Produced by Articular Chondrocytes and Induces Proinflammatory and Catabolic Responses (1999)

IL-18, a cytokine originally identified as IFN-gamma-inducing factor, is a member of the IL-1 family of proteins. Because IL-1alpha and IL-1beta are important mediators in the pathogenesis of arthritis, the present study addresses the expression of IL-18 and its role in regulating in articular chondrocytes. IL-18 mRNA was induced by IL-1beta in chondrocytes. Chondrocytes produced the IL-18 precursor and in response to IL-1 stimulation secreted the mature form of IL-18. Studies on IL-18 effects on chondrocytes showed that it inhibits TGF-beta-induced proliferation and enhances nitric oxide production. IL-18 stimulated the expression of several genes in normal human articular chondrocytes including inducible nitric oxide synthase, inducible cyclooxygenase, IL-6, and stromelysin. Gene expression was associated with the synthesis of the corresponding proteins. Treatment of normal human articular cartilage with IL-18 increased the release of glycosaminoglycans. These finding identify IL-18 as a cytokine that regulates chondrocyte responses and contributes to cartilage degradation.
Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis-activated myelin basic protein kinase (1991)

Synthetic peptides have been used to define the consensus amino acid sequence for substrate recognition by the meiosis-activated myelin basic protein (MBP) kinase (p44mpk), which was purified from maturing sea star oocytes. This protein kinase shares many properties with the mitogen-activated microtubule-associated protein-2 kinase (p42mapk) in vertebrates. Recently, Thr-97 in the tryptic fragment KNIVTPRTPPPSQGK of bovine MBP was identified as the major site of phosphorylation by p44mpk (Sanghera, J. S., Aebersold, R., Morrison, H. D., Bures, E. J., and Pelech, S. L. (1990) FEBS Lett. 273, 223-226). Synthetic peptides modeled after this sequence revealed that the presence of a proline residue C-terminal (+1 position) to the phosphorylatable threonine (or serine) residue was critical for recognition by p44mpk. Although not essential, a proline residue located at the -2 position enhanced the Vmax of peptide phosphorylation. Basic, acidic, and non-polar residues were equally tolerated at the -1 position. The presence of an amino acid residue at position -3 also increased peptide phosphorylation. Thus, the optimum consensus sequence for phosphorylation by p44mpk was defined as Pro-X-(Ser/Thr)-Pro, where X is a variable amino acid residue, but ideally not a Pro. Peptides that included this sequence were phosphorylated by p44mpk with Vmax values approaching 1 mumol.min-1.mg-1 and with apparent Km values of approximately 1 mM). Pseudosubstrate peptides in which the phosphorylatable residue was replaced by valine or alanine were weak inhibitors of p44mpk (apparent Ki values of approximately 3 mM). Over 40 distinct protein kinases contain Pro-X-(Ser/Thr)-Pro sequences including the human receptors for insulin and epidermal growth factor, and kinases encoded by the human proto-oncogenes abl, neu, and raf-1, and Schizosaccharomyces pombe cell cycle control genes ran-1 and wee-1. Multiple putative sites were also identified in rat microtubule-associated protein-2, human retinoblastoma protein, human tau protein, and Drosophila myb protein and RNA polymerase II.
Exploring the limits of early register release (2009)

Register pressure in modern superscalar processors can be reduced by releasing registers early and by copying their contents to cheap back-up storage. This article quantifies the potential benefits of register occupancy reduction and shows that existing hardware-based schemes typically achieve only a small fraction of this potential. This is because they are unable to accurately determine the last use of a register and must wait until the redefining instruction enters the pipeline. On the other hand, compilers have a global view of the program and, using simple dataflow analysis, can determine the last use. This article evaluates the extent to which compiler analysis can aid early releasing, explores the design space, and introduces commit and issue-based early releasing schemes, quantifying their benefits. Using simple compiler analysis and microarchitecture changes, we achieve 70% of the potential register file occupancy reduction. By adding more hardware support, we can increase this to 94%. Our schemes are compared to state-of-the-art approaches for varying register file sizes and are shown to outperform these existing techniques.
Existence and Failure of T-Cell Homeostasis Prior to AIDS Onset in HIV-Infected Injection Drug Users (1996)

Prior studies, based on populations of homosexual men, have shown that during HIV infection, levels of total circulating T-cells (CD3+ lymphocytes) remain constant for long periods of time after seroconversion. This suggested homeostatic phenomenon was observed to break down about 18 months prior to AIDS diagnosis with a quick loss of T-cells. The objective of this study was to determine whether (a) total T-cells are maintained at a constant level for long periods of time among HIV-infected injection drug users (IDUs) and (b) total T-cells decline before AIDS onset in this risk group and, if so, by how long. The design and setting was prospective follow-up, with semiannual clinic visits, of 646 HIV-infected IDUs who participate in the ALIVE study (Baltimore, MD). Among AIDS cases, T-cell levels remained quite stable at about 1500 cells/microl up to approximately 24 months prior to AIDS. However, a steep decline in CD3+ cell levels began approximately 24 months prior to AIDS diagnosis and was -17.5% per 6 months in the last 18 months before AIDS. Among seropositive IDUs without AIDS, a gradual decline of less than -4% per 6 months was observed. These trends remained virtually unchanged after accounting for current injection drug use, smoking, and HIV-related medications. IDUs, like homosexual men, exhibited T-cell homeostasis following HIV infection, as well as failure of this homeostasis about 2 years before AIDS. Although the mechanisms for the maintenance and later failure of the homeostasis of T-lymphocytes are not well understood, the observation has a potentially important prognostic value as well as biological interest.
Contact pressure dependence of wear rates of ultra high molecular weight polyethylene (1979)

Wear rates of orthopaedic polyethylene in 37 degrees C water are not very contact stress dependent below 1000 psi (6.9 MPa) but above that level they accelerate substantially. The pressure dependence overall follows an exponential function. Creep in the contact pressure range of 3--17 MPa and above is a much larger factor than wear in indentation effects. For accurate measurement of wear rates by depth measurements it is necessary to permit creep to proceed under static load until it ceases before beginning the wear test.
Compact Isolated High Frequency DC/DC Converters Using Self-Driven Synchronous Rectification (2003)

In the early 1990's, with the boom of the Internet and the advancements in telecommunications, the demand for high-speed communications systems has reached every corner of the world in forms such as, phone exchanges, the internet servers, routers, and all other types of telecommunication systems. These communication systems demand more data computing, storage, and retrieval capabilities at higher speeds, these demands place a great strain on the power system. To lessen this strain, the existing power architecture must be optimized.\nWith the arrival of the age of high speed and power hungry microprocessors, the point of load converter has become a necessity. The power delivery architecture has changed from a centralized distribution box delivering an entire system's power to a distributed architecture, in which a common DC bus voltage is distributed and further converted down at the point of load. Two common distributed bus voltages are 12 V for desktop computers and 48 V for telecommunications server applications. As industry strives to design more functionality into each circuit or motherboard, the area available for the point of load converter is continually decreasing. To meet industries demands of more power in smaller sizes power supply designers must increase the converter's switching frequencies. Unfortunately, as the converter switching frequency increases the efficiency is compromised. In particular, the switching, gate drive and body diode related losses proportionally increase with the switching frequency.\nThis thesis introduces a loss saving self-driven method to drive the secondary side synchronous rectifiers. The loss saving self-driven method introduces two additional transformers that increase the overall footprint of the converter. Also, this thesis proposes a new magnetic integration method to eliminate the need for the two additional gate driver magnetic cores by allowing three discrete power signals to pass through one single magnetic structure. The magnetic integration reduces the overall converter footprint.
Chemoprevention of experimental mammary carcinogenesis by the synthetic organoselenium compound, benzylselenocyanate, in rats (1989)

The effect of the dietary organoselenium compound, benzylselenocyanate (BSC) along with its sulphur analogue, benzylthiocynanate (BTC) and sodium selenite (Na2SeO3), on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis was examined in female Sprague-Dawley rats during the initiation phase of carcinogenesis. Semipurified diets containing 25 p.p.m. of BSC and 25 p.p.m. BTC, and 4 p.p.m. Selenium as Na2SeO3 in drinking water were given to 5-week-old rats for 3 weeks starting 2 weeks before, during and until 1 week after carcinogen treatment. At 7 weeks of age animals were given a single dose of DMBA (10 mg) in 1 ml olive oil by oral intubation. One week after DMBA treatment, the groups receiving BSC- and BTC-supplemented diets were transferred to the unsupplemented standard diets and the group of rats receiving Na2SeO3 in drinking water was transferred to regular tap water for the duration of the experiment. The results indicate that the rats receiving BSC in their diet showed a highly significant inhibition of tumor incidence and tumor multiplicity as well as a prolonged latency period when compared to the group fed the control diet. Neither BTC nor Na2SeO3 had any effect on the subsequent development of mammary tumors. These results indicate that dietary BSC inhibits mammary tumor incidence during the initiation phase of carcinogenesis and is a considerably more potent inhibitor than its sulphur analogue BTC and inorganic selenium. This is the first report that demonstrates the inhibition of mammary carcinogenesis by a synthetic organoselenium compound.
Contraction to big endothelin‐1, big endothelin‐2 and big endothelin‐3, and endothelin‐converting enzyme inhibition in human isolated bronchi (2000)

All three endothelin precursor peptides, i.e. big endothelin-1 (big ET-1), big endothelin-2 (big ET-2) and big endothelin-3 (big ET-3), produced contractile responses in human isolated bronchi, demonstrating the presence of functional endothelin-converting enzyme (ECE) in this tissue. The maximal contractile responses were equal to 108.4+/-8.0% (0.1 microM big ET-1; n=4), 85.2+/-11.8% (0.1 microM big ET-2; n=7) and 43.0+/-7.2% (0.1 microM big ET-3; n=5) of the reference response to acetylcholine (1 mM). The response to big ET-1 (0.1 microM), but not endothelin-1 (ET-1, 0.1 microM), was diminished after overnight storage of the tissue at 4 degrees C, demonstrating instability of the enzyme. The responses to all three big-endothelins were significantly inhibited, by the ECE inhibitors CGS 26393 and CGS 26303, in a concentration-related manner. The responses to the mature peptides ET-1, endothelin-2 (ET-2), and endothelin-3 (ET-3) were unaffected by CGS 26393 and CGS 26303. Phosphoramidon (10 microM) also produced an inhibition of the response to big ET-1 that was equivalent to that produced by CGS 26393 (10 microM). Combination of CGS 26393 (10 microM) and phosphoramidon (10 microM) did not produce an additive inhibition. These results demonstrate the presence of functional ECE for all three big endothelins in human bronchus and inhibition of the enzyme by newly developed orally active ECE inhibitors, as well as phosphoramidon. British Journal of Pharmacology (2000) 129, 170 - 176
Controlled Formation of Silica Particles from Tetraethyl Orthosilicate in Nonionic Water-in-Oil Microemulsions (1997)

The formation of silica particles by the ammonia-catalyzed hydrolysis of tetraethyl orthosilicate (TEOS) in nonionic water-in-oil microemulsions was investigated as a function of the molecular structure of the surfactant, the type of oil, and the concentrations of surfactant and water. Three types of nonionic surfactants and two oils, heptane and cyclohexane, were used. Microemulsion solutions were characterized using photon correlation spectroscopy, electrical conductivity measurement, and titration of phase separation points. The hydrolysis of TEOS and the size of synthesized silica particles were measured by FTIR spectroscopy and transmission electron microscopy measurements, respectively. It was found that the size distribution of silica particles correlates well with the size, connectivity, and stability of microemulsion droplets. This correlation indicates that the final size distribution of silica particles is predetermined in the silica particle's nucleation stage. In this stage, hydrolyzed (monomeric and polymeric) silica reacting species undergo interdroplet dynamic exchanges to contact one another and grow into nuclei. The results of this study showed that the nucleation of silica particles is enhanced (as to result in smaller final particles) by increasing the number of microemulsion droplets that compartmentalize reacting species in solutions or by increasing the strength of surfactant films in sterically hindering the dynamic exchange of reacting species between droplets. The effect of each variable described above on the formation of silica particles in microemulsions is detailed in the paper.
Regulation of postendocytic trafficking of the epidermal growth factor receptor through endosomal retention. (1994)

Little is known about the regulation of EGF receptor (EGF-R) trafficking following endocytosis. We investigated this by using a series of EGF-R with altered cytoplasmic tails and comparing their ability to undergo recycling and lysosomal targeting in both the occupied and empty state. We found that 2-3% of empty EGF-R are internalized each minute, but rapidly recycle (t1/2 approximately 5 min). This constitutive internalization and recycling of empty receptors was independent of cytoplasmic receptor sequences. Occupied EGF-R, in contrast, displayed a much slower rate of recycling (t1/2 between 10-23 min) due to retention within recycling endosomes. Endosomal retention of different EGF-R correlated with lysosomal targeting of EGF. Intrinsic receptor tyrosine kinase activity had no discernible effect on postendocytic trafficking of EGF. Although sequences within the cytoplasmic tail of the EGF-R appear to be required for occupancy-dependent endosomal retention, they are distinct from those required for ligand-induced endocytosis. Our studies indicate that intracellular trafficking of the EGF-R is regulated by endosomal components that preferentially recognize occupied receptors. Down-regulation of the EGF-R thus involves two distinct regulatory processes: one at the level of internalization and one at the level of recycling.
Robust and Accurate Single Nucleotide Polymorphism Genotyping by Dynamic Allele-Specific Hybridization (DASH): Design Criteria and Assay Validation (2001)

We recently introduced a generic single nucleotide polymorphism (SNP) genotyping method, termed DASH (dynamic allele-specific hybridization), which entails dynamic tracking of probe (oligonucleotide) to target (PCR product) hybridization as reaction temperature is steadily increased. The reliability of DASH and optimal design rules have not been previously reported. We have now evaluated crudely designed DASH assays (sequences unmodified from genomic DNA) for 89 randomly selected and confirmed SNPs. Accurate genotype assignment was achieved for 89% of these worst-case-scenario assays. Failures were determined to be caused by secondary structures in the target molecule, which could be reliably predicted from thermodynamic theory. Improved design rules were thereby established, and these were tested by redesigning six of the failed DASH assays. This involved reengineering PCR primers to eliminate amplified target sequence secondary structures. This sophisticated design strategy led to complete functional recovery of all six assays, implying that SNPs in most if not all sequence contexts can be effectively scored by DASH. Subsequent empirical support for this inference has been evidenced by approximately 30 failure-free DASH assay designs implemented across a range of ongoing genotyping programs. Structured follow-on studies employed standardized assay conditions, and revealed that assay reproducibility (733 duplicated genotypes, six different assays) was as high as 100%, with an assay accuracy (1200 genotypes, three different assays) that exceeded 99.9%. No post-PCR assay failures were encountered. These findings, along with intrinsic low cost and high flexibility, validate DASH as an effective procedure for SNP genotyping.
Genomic Sequence of C 1 , the First Streptococcal Phage (2003)

C(1), a lytic bacteriophage infecting group C streptococci, is one of the earliest-isolated phages, and the method of bacterial classification known as phage typing was defined by using this bacteriophage. We present for the first time a detailed analysis of this phage by use of electron microscopy, protein profiling, and complete nucleotide sequencing. This virus belongs to the Podoviridae family of phages, all of which are characterized by short, noncontractile tails. The C(1) genome consists of a linear double-stranded DNA molecule of 16,687 nucleotides with 143-bp inverted terminal repeats. We have assigned functions to 9 of 20 putative open reading frames based on experimental substantiation or bioinformatic analysis. Their products include DNA polymerase, holin, lysin, major capsid, head-tail connector, neck appendage, and major tail proteins. Additionally, we found one intron belonging to the HNH endonuclease family interrupting the apparent lysin gene, suggesting a potential splicing event yielding a functional lytic enzyme. Examination of the C(1) DNA polymerase suggests that this phage utilizes a protein-primed mechanism of replication, which is prominent in the phi29-like members of Podoviridae. Consistent with this evidence, we experimentally determined that terminal proteins are covalently attached to both 5' termini, despite the fact that no homology to known terminal proteins could be elucidated in any of our open reading frames. Likewise, comparative genomics revealed no close evolutionary matches, suggesting that the C(1) bacteriophage is a unique member of the Podoviridae.