gebhart/patrepeval huggingface dataset:
Nonspecific immunostimulant activities of synthetic trehalose-6,6'-diesters (lower homologs of cord factor) (1978)

Mycobacterial cord factors (6,6'-diesters of trehalose with mycolic acids ranging from C80 to C90) have been shown to protect mice effectively against infection with Klebsiella pneumoniae or with Listeria monocytogenes. Our present findings indicate that the low-molecular-weight cord factor of Corynebacterium diphtheriae (with corynomycolic acids ranging from C28 PTO C36) is equally active. Moreover, its synthetic analog (with synthetic C32 mycolic acid) has the same activity. Two lower synthetic 6,6'-diesters of trehalose with C22 acids, which are described here for the first time, as well as dipalmitate and a dioleate of sucrose, were found inactive. The synthetic C76 trehalose diesters, which are capable of enhancing nonspecific resistance to infection, increase the immune response in mice, even when injected in metabolizable oil. They induce in the injected paws an inflammatory process weaker and more transient than the natural cord factor.
Human humoral immunity to hsp70 during Trypanosoma cruzi infection. (1990)

Immunologic screening of cDNA expression libraries has been widely used for the identification of DNA sequences encoding the immunologically relevant proteins of many pathogenic microorganisms. For reasons that are not entirely clear, sequences encoding 70-kDa heat shock and related proteins (hsp70), which are among the most highly conserved proteins known, have routinely been identified by this approach. Consequently, hsp70 proteins have been proposed to be involved in the autoimmune processes thought responsible for the pathogenesis of the diseases caused by some of these organisms, e.g., chronic Trypanosoma cruzi infection (Chagas' disease). Therefore, we investigated whether hsp70 might be a specific target of the human humoral immune response to T. cruzi infection, and, if so, whether humoral autoimmunity to hsp70 might play a role in pathogenesis. We found that hsp70 is indeed a major polypeptide Ag in Chagas' disease, but that the antibodies to T. cruzi hsp70 do not react with human hsp70--even though the proteins display 73% amino acid sequence identify. These results indicate that self-tolerance to hsp70 is maintained during chronic T. cruzi infection and strongly argue against a role for humoral autoimmunity to hsp70 in the pathogenesis of Chagas' disease.
.alpha.- And .beta.-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure (1990)

Protein phosphatase 2A (polycation-stimulated protein phosphatase L) was purified from porcine kidney and skeletal muscle. The 36-kDa catalytic and the 65-kDa putative regulatory (hereafter termed PR65) subunits of protein phosphatase 2A2 were separated by reverse-phase HPLC. Partial amino acid sequence data (300 residues) was obtained for PR65. Molecular cloning showed that two distinct mRNAs (termed alpha and beta) encoded the PR65 subunit. The cDNA encoding the alpha-isotype spanned 2.2 kilobases (kb) and contained an open reading frame of 1767 bases predicting a protein of 65 kDa, which was in good agreement with the size of the purified protein. The cDNAs encoding the beta-isotype contained an open reading frame of size similar to that of alpha-form but lacked an initiator ATG. Northern analysis, using RNA isolated from several human cell lines, indicated that the alpha-isotype was encoded by a mRNA of 2.4 kb that was much more abundant than the beta mRNA of 4.0 kb. Comparison of the predicted amino acid sequences of the two isotypes revealed 87% identity. The deduced protein sequences of the alpha- and beta-isotypes were found to be made up of 15 imperfect repeating units consisting of 39 amino acids. This repeating structure was conserved between species.
In vivo recovery with products of very high purity — assay discrepancies (1998)

In view of reports of FVIII assay discrepancies in post-infusion plasma samples depending on methods used, we compared FVIII results run by each of four different methods following infusion of rFVIII (Kogenate). Nine persons with haemophilia A were infused with each of two lots of product. Plasma samples were obtained at baseline, and at 10 min, 30 min, 1, 2, 4, 8, 12, 14, 30 and 48 h post-infusion for measurement of FVIII. FVIII assay methods were chromogenic, and one-stage APTT using three different types of activators: micronized, silica, ellagic acid, and kaolin. The same reference plasma standard was used throughout. Results demonstrated a consistent difference in FVIII values, with chromogenic assays being considerably higher than those run by one-stage assays. The discrepancy was greatest when kaolin was the activator. These results point out the problems in attempting to determine the "correct" FVIII level in patient plasma samples following infusion of high purity FVIII preparations. Potential "pitfalls" include the standard used for defining product potency, the methods, reagents, instrumentation and standards used in assaying plasma samples and, in some instances, the characteristics of the product itself. This situation has considerable cost implications, potential impact on patient care, and makes it difficult to compare results between laboratories.
Inhibition of Mammalian Legumain by Some Cystatins Is Due to a Novel Second Reactive Site (1999)

We have investigated the inhibition of the recently identified family C13 cysteine peptidase, pig legumain, by human cystatin C. The cystatin was seen to inhibit enzyme activity by stoichiometric 1:1 binding in competition with substrate. The Ki value for the interaction was 0.20 nM, i.e. cystatin C had an affinity for legumain similar to that for the papain-like family C1 cysteine peptidase, cathepsin B. However, cystatin C variants with alterations in the N-terminal region and the "second hairpin loop" that rendered the cystatin inactive against cathepsin B, still inhibited legumain with Ki values 0.2-0.3 nM. Complexes between cystatin C and papain inhibited legumain activity against benzoyl-Asn-NHPhNO2 as efficiently as did cystatin C alone. Conversely, cystatin C inhibited papain activity against benzoyl-Arg-NHPhNO2 whether or not the cystatin had been incubated with legumain, strongly indicating that the cystatin inhibited the two enzymes with non-overlapping sites. A ternary complex between legumain, cystatin C, and papain was demonstrated by gel filtration supported by immunoblotting. Screening of a panel of cystatin superfamily members showed that type 1 inhibitors (cystatins A and B) and low Mr kininogen (type 3) did not inhibit pig legumain. Of human type 2 cystatins, cystatin D was non-inhibitory, whereas cystatin E/M and cystatin F displayed strong (Ki 0.0016 nM) and relatively weak (Ki 10 nM) affinity for legumain, respectively. Sequence alignments and molecular modeling led to the suggestion that a loop located on the opposite side to the papain-binding surface, between the alpha-helix and the first strand of the main beta-pleated sheet of the cystatin structure, could be involved in legumain binding. This was corroborated by analysis of a cystatin C variant with substitution of the Asn39 residue in this loop (N39K-cystatin C); this variant showed a slight reduction in affinity for cathepsin B (Ki 1.5 nM) but >>5,000-fold lower affinity for legumain (Ki >>1,000 nM) than wild-type cystatin C.
Estrogen receptor‐β: Implications for the prostate gland (1999)

Estrogens can have profound effects on prostate growth and differentiation. These effects were thought to be mediated by the classical estrogen receptor; however, the discovery of a second estrogen receptor has redefined the estrogen signaling pathway and may have broad implications on estrogen-responsive tissues, including the prostate. The new estrogen receptor, named estrogen receptor-β (ERβ), is preferentially expressed in the prostate and maintains some characteristics that are different from ERα. Establishing the distribution and function of ERβ in the various estrogen-responsive tissues is critical to defining its pharmacological and physiological impact. Differential expression of ERβ may facilitate development of tissue-specific estrogen agonists and antagonists, a goal in the treatment of diseases in estrogen-sensitive tissues such as breast cancer. This article reviews the current knowledge on ERβ and its potential impact on the prostate. Prostate 40:115–124, 1999. © 1999 Wiley-Liss, Inc.
<title>On-chip analog-to-digital conversion for cooled infrared detector arrays</title> (2000)

As CMOS technology evolves, more and more functions can be integrated on the infrared focal plane array (FPA). This paper presents a study on the integration of analog to digital (A/D) conversion onto the FPA. A possible application for this is high-resolution (640 X 480 pixels) quantum well infrared photodetector (QWIP) FPAs operating at 70K. Operation at liquid nitrogen temperatures and below gives both advantages and disadvantages. CMOS transistors are performing better at these temperatures: increased transconductance and no leakage currents. On the other hand power dissipation needs to be limited to prevent a high load on the cooling system. The system aspects will ultimately determine the requirements for the A/D converters on the FPA. Some of the most stringent requirements are on: power dissipation, number of bits, die area and throughput. An FPA lends itself very well for the utilization of parallelism, so a trade-off can be made between sample rate per A/D converter and number of converters. With all these parameters in mind, an overview of state-of-the-art A/D converters at room temperature will be given. Trends will be identified and different architectures like delta/sigma and successive approximation will be evaluated. Also different implementation technologies such as switched current and switched capacitor will be reviewed with respect to their applicability in our application.
Differential Modulation of Apoptosis Sensitivity in CD95 Type I and Type II Cells (1999)

We have recently identified two different pathways of CD95-mediated apoptosis (Scaffidi, C., Fulda, S., Srinivasan, A., Feng, L., Friesen, C., Tomaselli, K. J., Debatin, K.-M., Krammer, P. H., and Peter, M. E. (1998) EMBO J. 17, 1675-1687). CD95-mediated apoptosis in type I cells is initiated by large amounts of active caspase-8 formed at the death-inducing signaling complex (DISC) followed by direct cleavage of caspase-3. In contrast, in type II cells very little DISC and small amounts of active caspase-8 sufficient to induce the apoptogenic activity of mitochondria are formed causing a profound activation of both caspase-8 and caspase-3. Only in type II cells can apoptosis be blocked by overexpressed Bcl-2 or Bcl-x(L). We now show that a number of apoptosis-inhibiting or -inducing stimuli only affect apoptosis in type II cells, indicating that they act on the mitochondrial branch of the CD95 pathway. These stimuli include the activation of protein kinase C, which inhibits CD95-mediated apoptosis resulting in a delayed cleavage of BID, and the induction of apoptosis by the ceramide analog C(2)-ceramide. In addition, we have identified the CD95 high expressing cell line Boe(R) as a CD95 apoptosis-resistant type II cell that can be sensitized by treatment with cycloheximide without affecting formation of the DISC. This also places the effects of cycloheximide in the mitochondrial branch of the type II CD95 pathway. In contrast, c-FLIP was found to block CD95-mediated apoptosis in both type I and type II cells, because it acts directly at the DISC of both types of cells.
Proteins, radicals, isotopes, and mutants in photosynthetic oxygen evolution. (1993)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Ontario familial colon cancer registry: methods and first-year response rates. (2000)

The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that collects family history information, epidemiologic data, blood samples and tumour specimens from a population-based sample of colorectal cancer patients and their families. Families are classified as either high familial risk, intermediate familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high response rates in genetic family studies is especially challenging because of both the time commitment required and issues of confidentiality. The first-year response rate was 61%, resulting in 1,395 participating probands. In an attempt to assess potential response bias, we compared participants with non-participants. The age and sex of participants did not differ from non-participating probands; however, cases in rural areas were somewhat more likely to participate. To date, 57% of 1,587 relatives participated; females were more likely to participate, and relatives of low familial risk were least likely to participate. The OFCCR is an excellent resource that will facilitate the study of genetic and environmental factors associated with colorectal cancer.
Use of Inducible Feedback-Resistant N -Acetylglutamate Synthetase ( argA ) Genes for Enhanced Arginine Biosynthesis by Genetically Engineered Escherichia coli K-12 Strains (1998)

The goal of this work was to construct Escherichia coli strains capable of enhanced arginine production. The arginine biosynthetic capacity of previously engineered E. coli strains with a derepressed arginine regulon was limited by the availability of endogenous ornithine (M. Tuchman, B. S. Rajagopal, M. T. McCann, and M. H. Malamy, Appl. Environ. Microbiol. 63:33-38, 1997). Ornithine biosynthesis is limited due to feedback inhibition by arginine of N-acetylglutamate synthetase (NAGS), the product of the argA gene and the first enzyme in the pathway of arginine biosynthesis in E. coli. To circumvent this inhibition, the argA genes from E. coli mutants with feedback-resistant (fbr) NAGS were cloned into plasmids that contain "arg boxes," which titrate the ArgR repressor protein, with or without the E. coli carAB genes encoding carbamyl phosphate synthetase and the argI gene for ornithine transcarbamylase. The free arginine production rates of "arg-derepressed" E. coli cells overexpressing plasmid-encoded carAB, argI, and fbr argA genes were 3- to 15-fold higher than that of an equivalent system overexpressing feedback-sensitive wild-type (wt) argA. The expression system with fbr argA produced 7- to 35-fold more arginine than a system overexpressing carAB and argI genes on a plasmid in a strain with a wt argA gene on the chromosome. The arginine biosynthetic capacity of arg-derepressed DH5 alpha strains with plasmids containing only the fbr argA gene was similar to that of cells with plasmids also containing the carAB and argI genes. Plasmids containing wt or fbr argA were stably maintained under normal growth conditions for at least 18 generations. DNA sequencing identified different point mutations in each of the fbr argA mutants, specifically H15Y, Y19C, S54N, R58H, G287S, and Q432R.
Environmental aspects of the Anthony power development (1991)

This paper outlines the environmental procedures and practices established by the Hydro-Electric Commission Tasmania for planning, design and construction of the Anthony Power Development in an uninhabited region of Western Tasmania. Much of the project lies within a designated conservation area having significant tourist potential because of its outstanding scenic quality and access provided by the project roads. Some unusual procedures were adopted because of the urgency to proceed with construction following the stoppage of work on the Lower Gordon hydro project.
Sub-Nyquist Sampling of Short Pulses: Part I (2010)

Despite the increasing importance of the Canadian elk industry, the veterinary literature concerning diseases of elk is sparse, in particular for the neonatal period. This study summarizes necropsy findings in 111 farmed elk calves, up to 30 days of age, submitted to the diagnostic laboratory of the Western College of Veterinary Medicine over a 9-year period (990 to 1998). Causes of mortality fit into 3 categories: infectious disease, noninfectious disease, and undetermined. Organisms causing disease included Escherichia coli, Listeria monocytogenes, and Cryptosporidium sp. Starvation, including dehydration, was also a significant cause of mortality. Necropsy records are a useful source of information, but their scope is limited. There is a need for research that determines the prevalence of neonatal elk diseases and identifies risk factors for morbidity and mortality.
Circulating insulin: the proinsulin-like properties of “big” insulin in patients without islet cell tumors (1971)

When plasma is filtered on Sephadex G-50, insulin immunoreactivity is recovered in two peaks. "Big" insulin, the higher molecular weight component, and "little" insulin, the lower molecular weight component, have elution volumes that correspond to those of proinsulin-(125)I and insulin-(125)I respectively. When plasma was extracted with acid ethanol and filtered in 1.0 M acetic acid, the patterns and proportions of "big" and "little" insulin were indistinguishable from those obtained by filtration of whole plasma in neutral buffer. When "big" insulin was isolated from plasma and mixed with a tracer of porcine proinsulin-(125)I, trypsin converted the "big" insulin immunoreactivity to the gel filtration pattern of "little" insulin in the same way that it converted the proinsulin radioactivity. More than 90% of both "big" insulin and proinsulin were converted at optimal trypsin concentrations. Our present guinea pig anti-insulin serum failed to distinguish "big" from "little" but a porcine proinsulin anti-serum, under appropriate conditions of assay, reacted strongly with "big" insulin but not at all with "little." When tested on isolated fat cells, "little" insulin had the same bioactivity as porcine insulin, whereas "big" insulin had the same low activity as porcine proinsulin. These studies suggest that "big" insulin represents either single-chain proinsulin and/or a proinsulin intermediate that has similar low bioactivity.
Cobalt Chloride in the Treatment of Refractory Anaemia in Patients undergoing long‐term Haemodialysis (1975)

The effect of oral cobalt chloride on the anaemia of patients undergoing long-term haemodialysis therapy was investigated in 14 patients taking 25 mg then 50 mg daily. After eight weeks of treatment the mean haematocrit increase in 11 patients completing the trial was 23% of the original level and the 51Cr-red cell volume had increased by 20%. The 51Cr red half-life lengthened after treatment in six patients and the 59Fe plasma half-time shortened in ten patients. After treatment, evidence of increased erythropoietic activity was seen in the bone marrow of five patients. No evidence was found of thyroid of liver dysfunction but three patients developed transient loss of hearing demonstrated by audiometry. Cobalt chloride appears to be helpful in the management of some uraemic patients with refractory anaemia.
Risk management using behavior based attack graphs (2004)

Security administration is an uphill task to implement in an enterprise network providing secured corporate services. With the slew of patches being released by Microsoft, HP and other vendors, system administrators require a barrage of tools for analyzing the risk due to these vulnerabilities. In addition to this, criticalities in patching some end hosts (e.g., in hospitals) raises serious security issues about the network to which the end hosts are connected. In this context, it would be imperative to know the risk level of all critical resources (e.g., Oracle Server in HR department) keeping in view the everyday emerging new vulnerabilities. We hypothesize that sequence of network actions by an attacker depends on the social behavior (e.g., skill level, tenacity, financial ability). By verifying our hypothesis on hacker email communications, we extended this methodology and calculated risk level for a small network. Towards this goal, we formulated a mechanism to estimate the risk level of critical resources that may be compromised based on attacker behavior. This estimation is accomplished using behavior based attack graphs. These graphs represent all the possible attack paths to all the critical resources. Based on these graphs, we calculate the risk level of a critical resource using Bayesian methodology and periodically update the subjective beliefs about the occurrence of an attack. Such a calculated risk level would be a measure of the vulnerability of the resource and it forms an effective basis for a system administrator to perform suitable changes to network configuration. Thus suitable vulnerability analysis and risk management strategies can be formulated to efficiently curtail the risk from different types of attacker (script kiddies, hackers, criminals and insiders).
Multiplex Polymerase Chain Reaction for Rapid Detection of Atypical Mycobacteria and Mycobacterium tuberculosis Complex (1998)

A three-step polymerase chain reaction (PCR) method was developed for the detection and typing of mycobacterial DNA in clinical samples and fixed tissue specimens. The first step was to rule out or prove the presence of DNA of Mycobacterium tuberculosis complex. An amplified fragment from the insertion sequence (IS) 6110 was used for this purpose. Patients negative for IS 6110 were evaluated for a fragment of the 65 kDa-antigen, present in all mycobacteria. In positive patients, a multiplex PCR was performed for M. gordonae, M. avium, M. kansasii, M. fortuitum, and M. malmoense, combined in one PCR run. As another control, to prove mycobacterial DNA, PCR was used for the gene coding for the 16S ribosomal RNA also found in all mycobacteria. Appropriate negative controls were included. Different clinical samples were compared for an efficient amplification of these different mycobacterial DNA fragments. Different mycobacteria can be identified within one day in either unfixed cytologic and bacteriologic samples, or formalin-fixed paraffin-embedded tissue samples. Therefore, this method is a quick, cost efficient, and reliable tool to identify mycobacteria other than the tuberculosis complex.
Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults (2012)

The author panel reviewed 284 abstracts, which ultimately yielded 29 Class I or Class II articles that are reviewed herein. Divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol, and timolol are effective for migraine prevention and should be offered to patients with migraine to reduce migraine attack frequency and severity (Level A). Frovatriptan is effective for prevention of menstrual migraine (Level A). Lamotrigine is ineffective for migraine prevention (Level A).
Oxidative Stress Mediates Tumor Necrosis Factor-α–Induced Mitochondrial DNA Damage and Dysfunction in Cardiac Myocytes (2003)

The intimate link between TNF-alpha, ROS, and mtDNA damage might play an important role in myocardial remodeling and failure.