gebhart/patrepeval huggingface dataset:
Primary structure of human C-reactive protein. (1979)

The complete amino acid sequence has been derived for human C-reactive protein (CRP). The protein yielded a unique sequence containing 187 amino acids in a single polypeptide chain. The NH2-terminal residue of CRP is pyrrolidonecarboxylic acid and the COOH terminus is proline. The 2 half-cystine residues at positions 36 and 78 are involved in a disulfide bond. Based on the amino acid composition derived from the sequence data, a minimal molecular weight of 20,946 has been calculated for human CRP. This value agrees well with the molecular weight of 21,500 established by gel filtration of CRP in 5.0 M guanidine Cl (Gotschlich, E.C., and Edelman, G.M. (1965) Proc. Natl. Acad. Sci. U.S.A. 54, 558--566). The primary structure of human CRP has been examined for internal homology and compared to all known proteins whose structures were published before April, 1978 by two computer programs; program SEARCH and program RELATE (Dayhoff, M. O., ed (1976) in Atlas of Protein Sequence and Structure, Vol. 5, Suppl. 2, pp. 3--8, National Biomedical Research Foundation, Silver Spring, MD). The computer analyses showed no significant repeating sequences within the C-reactive protein molecule. This observation seems to rule out the possibility of gene duplication in the evolution of this protein. Distant homologies, which were statistically insignificant, have been noted to the CH2 domain of immunoglobulin G (IgG) and to C3a anaphylotoxin. The homologie noted are insufficient to support a common evolutionary origin of these proteins. No homology region in other heavy chains was observed. It is therefore preferable, at this point in time, to assign CRP and the protein known as 9.5 S alpha-glycoprotein, P component, and Clt to a new super family unrelated to any other proteins investigated. The homology between these proteins was demonstrated previously (Osmand, A.P., Friedenson, B., Gewurz, H., Painter, R.H., Hofmann, T., and Shelton, E. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 739--743) on the basis of sequence data on approximately 20 NH2-terminal residues of rabbit C-reactive protein, of Clt, and a cyanogen bromide fragment of human CRP.
Modification of Infectious Bovine Rhinotracheitis (IBR) Virus in Tissue Culture and Development of a Vaccine (1957)

Summary1. A modified IBR virus was produced by rapid passages and terminal dilutions in bovine embryo kidney tissue culture. Its avirulence was demonstrated by intramuscular and intranasal inoculation of susceptible cattle. 2. Modified virus inoculated intramuscularly elicits an immune response which protects cattle against challenge with virulent virus. 3. The virus did not spread from intramuscularly-inoculated cattle to susceptible contacts, and could not be reisolated from blood or nasal washings of vaccinated cattle. 4. This modified virus prepared in tissue culture can be successfully lyophilized, thus allowing its use as a vaccine for prevention of IBR disease.
Light Alloys : Metallurgy of the Light Metals (1981)

Light Alloys: From Traditional Alloys to Nanocrystals, Fifth Edition, covers the materials science, properties, manufacturing processes, and applications of key engineering metals in a single accessible volume. As use of these metals is now more widespread than ever, with routine use in motor vehicles and aircraft, this book includes materials characteristics and applications, heat treatment properties, fabrication, microstructure/property relationships, new applications, and processes. Provides a definitive, single volume overview on the light alloysPresents new material on the processing, characteristics, and applications of these essential metalsCovers the latest applications and processes in the auto and aero industries
Canister design for deep borehole disposal of nuclear waste (2006)

The objective of this thesis was to design a canister for the disposal of spent nuclear fuel and other high-level waste in deep borehole repositories using currently available and proven oil, gas, and geothermal drilling technology. The canister is suitable for disposal of various waste forms, such as fuel assemblies and vitrified waste. The design addresses real and perceived hazards of transporting and placing high-level waste, in the form of spent reactor fuel, into a deep igneous rock environment with particular emphasis on thermal performance. The proposed boreholes are 3 to 5 km deep, in igneous rock such as granite. The rock must be in a geologically stable area from a volcanic and tectonic standpoint, and it should have low permeability, as shown in recent data taken from a Russian deep borehole. Although deep granite should remain dry, water in flooded boreholes is expected to be reducing, but potentially corrosive to steel. However, the granite and plug are the containment barrier, not the canister itself. The canisters use standard oil drilling casings. The inner diameter is 315.32mm in order to accommodate a PWR assembly with a width of 214mm. At five meters tall, each canister holds one PWR assembly. The canister thickness is 12.19mm, with an outer diameter of 339.7mm. A liner can extend to the bottom of the emplacement zone to aid in retrievability. The liner has an outer diameter of 406.4mm and a thickness of 9.52mm. The standard drill bit used with a liner of this size has an outer diameter of 444.5mm.
Regulation of the expression and subcellular localization of the taurine transporter TauT in mouse NIH3T3 fibroblasts (2004)

The cellular level of the organic osmolyte taurine is a balance between active uptake and passive leak via a volume sensitive pathway. Here, we demonstrate that NIH3T3 mouse fibroblasts express a saturable, high affinity taurine transporter (TauT, Km = 18 microm), and that taurine uptake via TauT is a Na+- and Cl(-)-dependent process with an apparent 2.5 : 1 : 1 Na+/Cl-/taurine stoichiometry. Transport activity is reduced following acute administration of H2O2 or activators of protein kinases A or C. TauT transport activity, expression and nuclear localization are significantly increased upon serum starvation (24 h), exposure to tumour necrosis factor alpha (TNFalpha; 16 h), or hyperosmotic medium (24 h); conditions that are also associated with increased localization of TauT to the cytosolic network of microtubules. Conversely, transport activity, expression and nuclear localization of TauT are reduced in a reversible manner following long-term exposure (24 h) to high extracellular taurine concentration. In contrast to active taurine uptake, swelling-induced taurine release is significantly reduced following preincubation with TNFalpha (16 h) but unaffected by high extracellular taurine concentration (24 h). Thus, in NIH3T3 cells, (a) active taurine uptake reflects TauT expression; (b) TauT activity is modulated by multiple stimuli, both acutely, and at the level of TauT expression; (c) the subcellular localization of TauT is regulated; and (d) volume-sensitive taurine release is not mediated by TauT.
Public Health Assessment of Potential Biological Terrorism Agents (2002)

As part of a Congressional initiative begun in 1999 to upgrade national public health capabilities for response to acts of biological terrorism, the Centers for Disease Control and Prevention (CDC) was designated the lead agency for overall public health planning. A Bioterrorism Preparedness and Response Office has been formed to help target several areas for initial preparedness activities, including planning, improved surveillance and epidemiologic capabilities, rapid laboratory diagnostics, enhanced communications, and medical therapeutics stockpiling (1). To focus these preparedness efforts, however, the biological agents towards which the efforts should be targeted had to first be formally identified and placed in priority order. Many biological agents can cause illness in humans, but not all are capable of affecting public health and medical infrastructures on a large scale.

The military has formally assessed multiple agents for their strategic usefulness on the battlefield (2). In addition, the Working Group on Civilian Biodefense, using an expert panel consensus-based process, has identified several biological agents as potential high-impact agents against civilian populations (3–7). To guide national public health bioterrorism preparedness and response efforts, a method was sought for assessing potential biological threat agents that would provide a reviewable, reproducible means for standardized evaluations of these threats.

In June 1999, a meeting of national experts was convened to 1) review potential general criteria for selecting the biological agents that pose the greatest threats to civilians and 2) review lists of previously identified biological threat agents and apply these criteria to identify which should be evaluated further and prioritized for public health preparedness efforts. This report outlines the overall selection and prioritization process used to determine the biological agents for public health preparedness activities. Identifying these priority agents will help facilitate coordinated planning efforts among federal agencies, state and local emergency response and public health agencies, and the medical community.
Advantages and limitations of cytogenetic, molecular cytogenetic, and molecular diagnostic testing in mesenchymal neoplasms (2008)

Elucidation of the pathogenesis of bone and soft tissue tumors has been challenging because the genetic events are unique for the different mesenchymal tumor subtypes. However, enormous progress has been achieved with the advancement of cytogenetic and molecular genetic techniques. As a result, relevant oncogenes and tumor suppressor genes have been identified and localized, and new gene constructs and their protein products that result from translocations during sarcoma genesis have been determined. The identification of tumor-specific genetic markers for bone and soft tissue tumors, such as Ewing’s sarcoma, has added a new dimension to the formulation of a diagnosis and the resolution of cellular origin. Many of the genetic markers appear to have prognostic value, and studies to determine their potential applications as specific therapeutic targets are in progress. Three common genetic approaches used to identify mesenchymal tumorspecific abnormalities are conventional cytogenetic, molecular cytogenetic (fluorescence in situ hybridization, or FISH) and reverse transcription-polymerase chain reaction (RT-PCR) analyses. In this instructional lecture, emphasis is placed on the practical applications of each of these techniques, including their advantages and limitations. Certain case presentations are included to illustrate the integration of traditional histopathological and genetic approaches and serve as useful paradigms.
Controlled contamination of optics under 157-nm laser irradiation (2001)

Contamination rates of CaF2 substrates in the presence of trace levels of toluene vapor and oxygen under 157-nm irradiation have been studied to determine conditions which prevent contamination films from depositing on optical elements in lithographic projection systems. A 2 - 3 monolayer thick deposit, causing a 1 - 2% transmission drop per surface, can readily form over a range of contaminant levels in the sub-ppm range and typical background oxygen levels. In addition, stable partial surface coverage can be supported with either lower concentrations of contaminant or conversely much higher levels of oxygen. Contamination rates are also higher at lower fluences, and thus contamination effects are expected to impact the projection optics more severely than beam delivery and illumination components. Finally, a permanent degradation in transmission of coated optics has been observed on anti-reflective coatings exposed to sub-ppm levels of toluene. Taken together, the results suggest that even with hydrocarbon based contaminants, where oxygen can be introduced into the beam-line in trace levels (i.e. hundreds of ppb) without significantly degrading transmission, toluene contaminant levels will have to be maintained in the ppb range or below.
Drospirenone-containing hormone therapy for postmenopausal women. Perspective on current data. (2007)

A novel progestogen, drospirenone, in combination with 17beta-estradiol has been studied as hormone therapy (HT) for menopausal symptoms. In addition to providing effective and safe relief of menopausal symptoms, the combination has a beneficial effect on blood pressure and weight gain.
A new method of preparing gold probes for multiple-labeling cytochemistry. (1985)

A new method is described for preparing colloidal gold particles in any size between approximately 3 and 17 nm for electron microscopy. The gold particles are homogeneous in size (homodisperse). When bound to various proteins (e.g. IgG and protein A), the complexes were stable for long periods and suitable for affinity cytochemistry. We demonstrated the usefulness of the new gold probes bound to protein A for multiple labeling in a current immunocytochemical study on receptor mediated transport of IgA in human duodenal crypt cells. Other gold-protein complexes were useful for studying macromolecular arrangements at high resolution.
PF285 ZELLA‐101: PHASE 1 STUDY OF ALVOCIDIB FOLLOWED BY 7+3 INDUCTION IN NEWLY DIAGNOSED AML PATIENTS (2019)

Background: Alvocidib, a potent cyclin‐dependent kinase‐9 (CDK‐9) inhibitor, has been studied extensively in newly diagnosed and relapsed/refractory AML in a timed sequential combination with cytarabine and mitoxantrone (ACM) with promising activity. Inhibition of CDK‐9 leads to downregulation of BCL‐2 family member, MCL‐1, which in turn inhibits tumor growth. We hypothesized that alvocidib followed by 7+3 induction therapy would be safe and effective in newly diagnosed non‐favorable risk AML. Aims: To evaluate the safety and clinical activity of alvocidib, in combination with cytarabine and daunorubicin (7+3), in previously untreated AML Methods: We are conducting a multicenter, open‐label, dose‐escalation, safety and biomarker prediction study (Zella 101) of alvocidib given as timed sequential therapy prior to cytarabine and daunorubicin for adults with previously untreated AML. The key eligibility criteria are: ages 18–65 years; previously untreated AML; ECOG PS 0–2; and no major organ dysfunction. Treatment consisted of increasing dose levels of alvocidib starting at 20 mg/m 2 as a 30‐minute IV bolus followed by 30 mg/m 2 over 4 hours on days 1–3, cytarabine 100 mg/m 2 /day by continuous IV infusion on days 5–11, and daunorubicin 60 mg/m 2 IV on days 5–7. Dose escalation was assessed by standard 3+3 design. Reinduction therapy with alvocidib (same dose as induction) days 1–3, followed by cytarabine 100 mg/m 2 /day continuous IV days 5–9 and daunorubicin 45 mg/m 2 IV days 5–6 was recommended in patients with &gt;10% and &gt;5% cellularity and blasts, respectively. Results: A total of 13 patients have been enrolled to date with the median age of 59 years (Range: 31–65 years) (See Table 1). The maximum dose of alvocidib administered was 30 mg/m 2 as a 30‐minute IV bolus followed by 60 mg/m 2 over 4 hours on days 1–3 as previously given in prior studies. Overall, alvocidib was well tolerated. The most common NCI CTCAE ≥Grade 3 treatment emergent nonhematologic AEs noted in ≥3 patients in the safety population were device related infection (30.8%), diarrhea (30.8%) and lung infection (23.1%). Cytogenetics were reported on 7 patients, 5 were intermediate to high risk. Ten patients were evaluable with post baseline response assessments, two patients were too early for disease assessment, and one patient died prior to disease assessment due to septic shock. Nine of the 10 evaluable patients achieved CR (9/10, 90%). Summary/Conclusion: Alvocidib given as timed sequential therapy prior to cytarabine and daunorubicin (7+3) induction in newly diagnosed AML demonstrated an acceptable safety profile with an MTD (30 mg/m 2 IV bolus followed by 60 mg/m 2 infusion over 4 hours) similar to previously investigated timed sequential regimens of alvocidib. Future directions include a randomized phase 2 expansion comparing cytarabine and daunorubicin with or without preceding timed sequential alvocidib, and prospective BH3 profiling of AML patients. image
Spectroscopy and Electrochemistry of Cobalt(III) Schiff Base Complexes (1997)

The structural, spectroscopic, and electrochemical properties of cobalt(III) derivatives of acacen (H2acacen = bis(acetylacetone) ethylenediimine) and related ligands have been investigated. Electronic structure calculations indicate that the absorption between 340 and 378 nm in CoIII(acacen) spectra is attributable to the lowest π−π* intraligand charge-transfer transition. Equatorial ligand substitutions affect reduction potentials less than axial ligand changes, consistent with an electronic structural model in which dz2 is populated in forming cobalt(II). The crystal structure of [Co(3-Cl-acacen)(NH3)2]BPh4 has been determined: The compound crystallizes in the monoclinic space group P21/m (No. 11) with a = 9.720(2) Å, b = 18.142(4) Å, c = 10.046(2) Å, β = 100.11(3)°, Dc = 1.339 g cm-3, and Z = 2; the complex cation, [Co(3-Cl-acacen)(NH3)2]+, exhibits a slightly distorted octahedral coordination geometry. The distances between the cobalt atom and the two axial nitrogen donor atoms differ only slightly (1.960(6) and 1.951(6) Å) and are similar to Co−N distances found in cobalt−ammine complexes as well as the axial Co−N distances in [Co(acacen)(4-MeIm)2]Br·1.5H2O; the latter compound crystallizes in the triclinic space group P1̄ (No. 2) with a = 18.466(9) Å, b = 14.936(7) Å, c = 10.111(5)Å, α = 96.27(5)°, β = 94.12(5)°, γ = 112.78(5)°, Dc = 1.447 g cm-3, and Z = 4.
Obesity‐induced insulin resistance and hepatic steatosis are alleviated by ω‐3 fatty acids: a role for resolvins and protectins (2009)

Omega-3-polyunsaturated fatty acids (omega-3-PUFAs) have well-documented protective effects that are attributed not only to eicosanoid inhibition but also to the formation of novel biologically active lipid mediators (i.e., resolvins and protectins). In this study, we examined their effects on ob/ob mice, an obesity model of insulin resistance and fatty liver disease. Dietary intake of omega-3-PUFAs had insulin-sensitizing actions in adipose tissue and liver and improved insulin tolerance in obese mice. Genes involved in insulin sensitivity (PPARgamma), glucose transport (GLUT-2/GLUT-4), and insulin receptor signaling (IRS-1/IRS-2) were up-regulated by omega-3-PUFAs. Moreover, omega-3-PUFAs increased adiponectin, an anti-inflammatory and insulin-sensitizing adipokine, and induced AMPK phosphorylation, a fuel-sensing enzyme and a gatekeeper of the energy balance. Concomitantly, hepatic steatosis was alleviated by omega-3-PUFAs. A lipidomic analysis with liquid chromatography/mass spectrometry/mass spectrometry revealed that omega-3-PUFAs inhibited the formation of omega-6-PUFA-derived eicosanoids, while triggering the formation of omega-3-PUFA-derived resolvins and protectins. Moreover, representative members of these lipid mediators, namely resolvin E1 and protectin D1, mimicked the insulin-sensitizing and antisteatotic effects of omega-3-PUFAs and induced adiponectin expression to a similar extent that of rosiglitazone, a member of the thiazolidinedione family of antidiabetic drugs. Taken together, these findings uncover beneficial actions of omega-3-PUFAs and their bioactive lipid autacoids in preventing obesity-induced insulin resistance and hepatic steatosis.
Eph Family Receptors and Their Ligands Distribute in Opposing Gradients in the Developing Mouse Retina (1996)

The Eph family of receptor tyrosine kinases and their ligands can be divided into two specificity subclasses: the Eck-related receptors and their GPI-anchored ligands, and the Elk-related receptors and their transmembrane ligands. Previous reports demonstrated that Eck- and Elk-related receptors in the retina distribute in high temporal-low nasal and high ventral-low dorsal gradients, respectively. While others have focused on complementary ligand gradients in the retinal axon target, the tectum, we report that ligands from each subclass also distribute in gradients opposing those of their corresponding receptors within the retina itself. Moreover, ligand gradients in the retina precede ganglion cell genesis. These results support an intraretinal role for Eph family members in addition to their previously proposed role in the development of retinotectal topography. The distinct distributions of Eph family members suggest that each subclass specifies positional information along independent retinal axes.
Critical Role for the Second Extracellular Loop in the Binding of Both Orthosteric and Allosteric G Protein-coupled Receptor Ligands (2007)

The second extracellular (E2) loop of G protein-coupled receptors (GPCRs) plays an essential but poorly understood role in the binding of non-peptidic small molecules. We have utilized both orthosteric ligands and allosteric modulators of the M2 muscarinic acetylcholine receptor, a prototypical Family A GPCR, to probe possible E2 loop binding dynamics. We developed a homology model based on the crystal structure of bovine rhodopsin and predicted novel cysteine substitutions that should dramatically reduce E2 loop flexibility via disulfide bond formation and significantly inhibit the binding of both types of ligands. This prediction was validated experimentally using radioligand binding, dissociation kinetics, and cell-based functional assays. The results argue for a flexible "gatekeeper" role of the E2 loop in the binding of both allosteric and orthosteric GPCR ligands.
The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. (1995)

The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA. Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium. We recently demonstrated that AKA recognize human epidermal filaggrin. Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD. This protein is seen to be closely related to human epidermal (pro) filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules. These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro) filaggrin-related proteins of buccal epithelial cells. Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.
Circadian Rhythms, Jet Lag, and Chronobiotics: An Overview (1994)

This overview considers the origins of jet lag in terms of altered circadian rhythmicity. The properties required of a chronobiotic--an agent to cause phase adjustment of the body clock--are discussed, and an account is given of the major candidates at the present time: light, melatonin, activity, and benzodiazepines. It is concluded that current knowledge indicates that a combination of factors is likely to be most effective.