gebhart/patrepeval huggingface dataset:
Future Treatment of Bone Metastases (2006)

All bone surfaces are periodically remodeled by the coupled and balanced action of osteoclasts and osteoblasts, of which the activities are regulated by a variety of cytokines and growth factors. Patients with cancer metastatic to the skeleton often develop osteolytic bone lesions, in which the actions of osteoclasts and osteoblasts remain coupled, but become imbalanced in sites adjacent to the tumor. The result is net bone loss. Many cancers secrete osteoclast-stimulating cytokines, which increase bone resorption by osteoclasts. In turn, factors released from the bone matrix during osteolysis can stimulate tumor growth. In this so-called "vicious cycle," there are multiple sites that are targets for new bone-directed therapies. A variety of new agents for the treatment and prevention of osteolytic bone metastasis are currently being developed. These include new agents that inhibit osteoclast differentiation, bone adhesion, and osteoclast function. These new strategies have evolved from a better understanding of the interaction between tumor cells and cells in the bone marrow microenvironment. There is great promise that these new bone-targeted therapies can decrease the frequent skeletal-related events that greatly diminish quality of life of patients with bone metastases.
Introduction to Protein Structure Prediction (2010)

This chapter contains sections titled: Introduction to Protein Structures Protein Structure Prediction Methods References
I-TAC/CXCL11 is a natural antagonist for CCR5 (2004)

The selective CXC chemokine receptor 3 (CXCR3) agonists, monokine induced by interferon-gamma (IFN- gamma)/CXC chemokine ligand 9 (CXCL9), IFN-inducible protein 10/CXCL10, and IFN-inducible T cell alpha chemoattractant (I-TAC)/CXCL11, attract CXCR3+ cells such as CD45RO+ T lymphocytes, B cells, and natural killer cells. Further, all three chemokines are potent, natural antagonists for chemokine receptor 3 (CCR3) and feature defensin-like, antimicrobial activities. In this study, we show that I-TAC, in addition to these effects, acts as an antagonist for CCR5. I-TAC inhibited the binding of macrophage-inflammatory protein-1alpha (MIP-1alpha)/CC chemokine ligand 3 (CCL3) to cells transfected with CCR5 and to monocytes. Furthermore, cell migration evoked by regulated on activation, normal T expressed and secreted (RANTES)/CCL5 and MIP-1beta/CCL4, the selective agonist of CCR5, was inhibited in transfected cells and monocytes, respectively. In two other functional assays, namely the release of free intracellular calcium and actin polymerization, I-TAC reduced CCR5 activities to minimal levels. Sequence and structure analyses indicate a potential role for K17, K49, and Q51 of I-TAC in CCR5 binding. Our results expand on the potential role of I-TAC as a negative modulator in leukocyte migration and activation, as I-TAC would specifically counteract the responses mediated by many "classical," inflammatory chemokines that act not only via CCR3 but via CCR5 as well.
Empirical research on target cost setting method and authority of target cost allocation in the alternative organizations of product development (2000)

This paper investigates how the causal relationship among (1) the alternativeorganizations of product development, (2) the alternative methods for settingtarget cost and (3) the alternative decision authority positions in allocation oftarget cost will effect the cost-reduction performance, through questionnairesurvey for the Japanese companies listed on the Tokyo Stock Exchange.We apply the log-linear model to test this relationship. This model willestimate the effects of each factor as well as the combinations among factors.In this research, we found that the relationship between product developmentorganizations and management's decisionauthority in the allocation of producttarget cost among various parts will affect the target-costing performance.Firstly, the decision for allocating target cost of a product to its various partsmade by the product manager will bring good cost-reduction performance underthe organization of “product group center”. Also, the decision for allocatingtarget cost made by both of product manager and parts designers will have thesame results under this organization.On the other hand, the decision of allocating target cost made by the partsdesigners will have a good performance in cost reduction under the “matrixorganization” of product development.As a result, it can be featured that the former is the top-down decision makingin target costing system under the organization of product group center; and thelatter is the bottom-up decision making in target costing system under thematrix organization of product development.
Credentials for privacy and interoperation (1995)

We consider the problem of providing secure, private access to applications and data in a world-wide distributed client-server environment such as the Internet of the future. In such a system, the set of potential users of a service may extend far beyond the local community knowable to the application providing the service. Applications will not generally have prior knowledge of the individual making a request upon which an access control decision can be baed and furthermore, knowledge of an individual's identity may not be directly useful. We frame our discussion in the context of supporting credentials which are submitted with a request, and propose a list of desiderata for such credentials. We evaluate several well-known proposals for credentials, focusing on issues related to privacy and scalability, and then point out the research issues that remain before such schemes can be deployed in a world-wide environment with strong privacy guarantees.
Hydrogen adsorption and cohesive energy of single-walled carbon nanotubes (1999)

Hydrogen adsorption on crystalline ropes of carbon single-walled nanotubes (SWNT) was found to exceed 8 wt. %, which is the highest capacity of any carbon material. Hydrogen is first adsorbed on the outer surfaces of the crystalline ropes. At pressures higher than about 40 bar at 80 K, however, a phase transition occurs where there is a separation of the individual SWNTs, and hydrogen is physisorbed on their exposed surfaces. The pressure of this phase transition provides a tube-tube cohesive energy for much of the material of 5 meV/C atom. This small cohesive energy is affected strongly by the quality of crystalline order in the ropes.
Emerging mobile and personal communication systems (1995)

The market demand for wireless communications has been demonstrated by the rapid growth of different second-generation wireless technologies that are optimized for particular applications and environments. Obvious examples include: digital cellular systems like GSM, ADC, PDC,and DCS1800 for widespread vehicular and pedestrian services, and cordless telecommunication systems based on CT2, DECT, and PHS standards for residential, business, and public cordless access applications. Efforts are also underway to consolidate the various radio environments and applications under a single standard for third generation wireless, i.e., FPLMTS. In the area of personal mobility, with the recent availability of "personal" numbers in various countries (e.g., 500 numbers in the United States), many fixed network operators are starting to offer such personal mobility services as "personal number service" and "number portability". These services represent initial stages of full personal mobility that will be provided by UPT in both wireline as well as wireless environments. The expected heavy demand for PCS in the United States and the underlying market/regulatory forces are driving the standardization and business activity. A number of air interface standards for the 1900 MHZ PCS band are being considered, which are based on TDMA, CDMA, and FDMA technologies singly or in combination. Many are variations of existing digital cellular and cordless telecommunications technologies. PCS networking standards are also being developed; both for standalone systems and for systems that will utilize public switched network capabilities.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Fructosamine or glycated haemoglobin as a measure of diabetic control? (1988)

Glycated haemoglobin A1 (HbA1c), fructosamine, and total serum proteins were measured in 30 normal and 61 diabetic children. The normal range for HbA1c was 4.7-8.8% and for fructosamine was 0.98-1.88 mmol/l. These were similar to adult normal ranges and there were no significant age differences during childhood. There was a highly significant correlation between HbA1c and fructosamine in the diabetic children but this was lost when only concentrations within the established normal ranges were considered. Adjustment of concentrations of fructosamine for total serum proteins made no difference to the results. Changes in HbA1c and fructosamine were followed in three newly diagnosed patients and in one whose diabetes was getting worse. HbA1c decayed with a half life of 28.7 days and fructosamine decayed with a half life of 16.5 days. Fructosamine concentrations were lower than expected in the patients who were improving and higher than expected in the patient who was deteriorating. It is suggested that while fructosamine is not a direct substitute for HbA1c it may be a useful adjunct in determining whether a patient is worsening or improving in the short term. A change from HbA1c to fructosamine for routine assessment of diabetes while retaining HbA1c on selected occasions would result in some cost savings while retaining the advantages of having both assays available.
Lipophilic 5'-alkyl phosphate esters of 1-.beta.-D-arabinofuranosylcytosine and its N4-acyl and 2,2'-anhydro-3'-O-acyl derivatives as potential prodrugs (1982)

Lipophilic 5'-(alkyl phosphate) esters of 1-beta-D-arabinofuranosylcytosine (ara-C) and several N4-acyl and 3'-O-acyl-2,2'-anhydro derivatives of ara-C were synthesized as potential prodrugs of ara-C 5'-monophosphate (ara-CMP). Alkylphosphorylation of ara-C, N4-palmitoyl-ara-C, and N4-stearoyl-ara-C was achieved in a single continuous operation by allowing the nucleoside to react with POCl3 in trimethyl or triethyl phosphate and adding the appropriate anhydrous alcohol directly to the intermediate phosphorodichloridate without isolation. Similar reaction of cytidine yielded cytidine 5'-(alkyl phosphate) esters, which on treatment with myristoyl or palmitoyl chloride in the presence of boron trifluoride gave 3'-O-acyl-2,2'-anhydro-ara-C 5'-(alkyl phosphate) esters. Ara-C 5'-(n-butyl phosphate) (1b), N4-palmitoyl-ara-C 5'-(n-butyl phosphate) (1h), and 2,2'-anhydro-3'-O-palmitoyl-ara-C 5'-(n-butyl phosphate) (2h) were tested against L1210/ara-C leukemia in mice in the hope that this kinase-deficient tumor would respond to treatment with these "prephosphorylated" derivatives, but no activity was observed. Of the simple 5'-(alkyl phosphate) esters tested in culture against l1210 leukemic cells, only ara-C 5'-(glyceryl phosphate) (1g) showed toxicity comparable to ara-CMP (ID50 = 0.35 and 0.65 microM, respectively), suggesting that beta-hydroxyalkyl phosphate esters may be worthwhile to examine further as prodrugs of ara-CMP.
Agkistrodon piscivorus piscivorus platelet aggregation inhibitor: a potent inhibitor of platelet activation. (1989)

Applaggin (Agkistrodon piscivorus piscivorus platelet aggregation inhibitor) is a potent inhibitor of platelet activation. The protein is isolated from the venom of the North American water moccasin snake in three steps, including gel filtration, cation exchange, and reverse-phase HPLC procedures. The purified protein migrates as a 17,700-Da polypeptide by SDS/PAGE under nonreducing conditions and as a 9800-Da peptide in the presence of thiol. The behavior of applaggin on SDS/PAGE would indicate that the protein is a disulfide-linked dimer. Applaggin has been completely sequenced by Edman degradation and consists of 71 amino acids. The sequence is rich in cysteine and contains Arg-Gly-Asp at residues 50-52. Applaggin blocks platelet aggregation induced by ADP, collagen, thrombin, or arachidonic acid with IC50 values ranging from 12 to 128 nM (0.2-2.3 micrograms/ml) depending on the agonist and its concentration. This inhibition is found to correlate with inhibition of thromboxane A2 generation and of dense granule release of serotonin. Inhibition by applaggin of serotonin release induced by ADP, gamma-thrombin, and collagen was monitored in plasma under stirred conditions with [3H]serotonin-loaded platelets, and IC50 values for inhibition are found to range from less than 10 to 145 nM. At saturating concentrations, 125I-labeled applaggin (125I-applaggin) binds to 28,500 sites per unstimulated, washed platelet with a Kd of 1.22 x 10(-7) M. Binding of 125I-applaggin to platelets is inhibited by the synthetic undecapeptide Arg8-Gly-Asp-Val at 200 microM.
Mild Palladium-Catalyzed Selective Monoarylation of Nitriles (2005)

Two new palladium-catalyzed procedures for the arylation of nitriles under less basic conditions than previously reported have been developed. The selective monoarylation of acetonitrile and primary nitriles has been achieved using alpha-silyl nitriles in the presence of ZnF2. This procedure is compatible with a variety of functional groups, including cyano, keto, nitro, and ester groups, on the aryl bromide. The arylation of secondary nitriles occurred in high yield by conducting reactions with zinc cyanoalkyl reagents. These reaction conditions tolerated base-sensitive functional groups, such as ketones and esters. The combination of these two methods, one with alpha-silyl nitriles and one with zinc cyanoalkyl reagents, provides a catalytic route to a variety of benzylic nitriles, which have not only biological significance but utility as synthetic intermediates. The utility of these new coupling reactions has been demonstrated by a synthesis of verapamil, a clinically used drug for the treatment of heart disease, by a three-step route from commercial materials that allows convenient variation of the aryl group.
Sharpening of Frequency Tuning by Inhibition in the Thalamic Auditory Nucleus of the Mustached Bat (1997)

Unlike the quasitriangular frequency-tuning curves of peripheral neurons, pencil- or spindle-shaped frequency-tuning curves (excitatory areas) have been found in the central auditory systems of many species of animals belonging to different classes. Inhibitory tuning curves (areas) are commonly found on both sides of such "level-tolerant" sharp frequency-tuning curves. However, it has not yet been examined whether sharpening of frequency tuning takes place in the medial geniculate body (MGB). We injected an inhibitory transmitter antagonist, bicuculline methiodide (BMI), into the MGB of the mustached bat to examine whether frequency tuning is sharpened by inhibition in the MGB and whether this sharpening, if any, occurs in addition to that performed in prethalamic auditory nuclei. Thirty-seven percent of thalamic Doppler-shifted constant frequency (DSCF) neurons mostly showing a level-tolerant frequency-tuning curve had an inhibitory area or areas. BMI changed the inhibitory areas of these neurons into excitatory areas, so that their excitatory frequency-tuning curves became broader. However, the BMI-broadened excitatory frequency-tuning curves were still much narrower than those of peripheral neurons. Our results indicate that level-tolerant frequency tuning of thalamic DSCF neurons is mostly created by prethalamic auditory nuclei and that it is further sharpened in 37% of thalamic DSCF neurons by lateral inhibition occurring in the MGB. The comparisons in sharpness (quality factors) of frequency-tuning curves between peripheral, thalamic, and cortical DSCF neurons indicate that the skirt portion of tuning curves is sharper in the above order, and that their tip portion is not significantly different between the peripheral and thalamic DSCF neurons, but significantly sharper in the cortical DSCF neurons than in the thalamic DSCF neurons. Therefore the central auditory system has inhibitory mechanisms for the progressive sharpening of frequency tuning. DSCF neurons in the primary auditory cortex were recently found to show facilitative responses to paired sounds. That is, they are combination sensitive. In the present studies, we found that thalamic DSCF neurons also showed facilitative responses to paired sounds. The responses of thalamic DSCF neurons to acoustic stimuli consisted of a slow and a fast component. BMI mainly increased the slow component and an excitatory transmitter antagonist, D-2-amino-5-phosphonovalerate mainly suppressed the slow component. Therefore the response pattern of these thalamic neurons is shaped by both gamma-aminobutyric acid-mediated inhibition and N-methyl-D-aspartate-mediated facilitation.
Dynamic Sag Instabilities in Long Underground Belt Conveyors (1991)

The transportation of coal in high volumes from underground long wall mining systems is becoming more widespread. Throughput demands of up to 4000 T/hr., over distances of 3 to 4 km., places severe strain on the traditional fabric conveyor belting and its support structure. Panel conveyors can be very long and suffer dynamic effects on starting and stopping and the type of pre-tensioning system employed is now becoming a key issue in the design stability. Main gate conveyors with a retreating tail-end suffer more extreme problems of tensioning and if the introduction of a booster drive is required special operating difficulties may occur. The selection of take-up devices and their location will be discussed in terms of the dynamic and static sag conditions that lead to unstable operation. It is shown that high belt sag becomes a critical factor in conveyor system dynamic stability.
Plasma Stromal Cell–Derived Factor (SDF)‐1 Levels, SDF1‐3′A Genotype, and Expression of CXCR4 on T Lymphocytes: Their Impact on Resistance to Human Immunodeficiency Virus Type 1 Infection and Its Progression (2002)

Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A polymorphism, and CXCR4(+) T lymphocytes in relation to resistance to human immunodeficiency virus (HIV)-1 infection and its progression were investigated in a study of HIV-positive patients, exposed but uninfected (EU) subjects, and healthy control subjects, all lacking CCR5 Delta 32 homozygosity. SDF1-3'A homozygosity was associated with low plasma SDF-1 levels in uninfected persons and was not related to long-term nonprogression. HIV-1 infection involved increased plasma SDF-1 levels, which were not attributable to any kind of chronic viral infection, because all EU hemophiliacs were hepatitis C virus-positive but had normal SDF-1 levels. High plasma SDF-1 levels and low CXCR4 expression on T lymphocytes was associated with long-term nonprogression, whereas in advancing disease expression of CXCR4 increased, accompanied by a decrease in plasma SDF-1 during the more advanced stages of HIV-1 infection. EU subjects with sexual exposure to HIV-1, but not EU hemophiliacs, showed an underpresentation of SDF1-3'A allele frequency, which was coupled with high plasma SDF-1 levels and low CXCR4 expression.
Lysine‐Specific Demethylase 1‐Selective Inactivators: Protein‐Targeted Drug Delivery Mechanism (2013)

Drug drop off: Given that lysine-specific demethylase 1 (LSD1) could be potently and selectively inactivated by delivering phenylcyclopropylamine (PCPA), a weak and nonselective LSD1 inhibitor, directly to the enzyme's active site, a novel series of LSD1 inactivators (1) were designed. Biological and mechanistic studies indicate that 1 inhibits LSD1 potently and selectively. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Technical Debt (2015)

We report here on the Sixth International Workshop on Managing Technical Debt, collocated with the International Conference on Software Maintenance and Evolution (ICSME 2014). The major themes of discussion this year indicate a growing maturity in this area of investigation and the desire to move beyond definitional issues to impact.
Amelioration of Diabetes Mellitus in Partially Depancreatized Rats by Poly(ADP-ribose) Synthetase Inhibitors: Evidence of Islet B-Cell Regeneration (1984)

Ninety percent depancreatized rats received daily intraperitoneal injection of 0.5 g/kg nicotinamide and 0.05 g/kg 3-aminobenzamide, potent inhibitors of islet poly(ADP-ribose) synthetase. One to three months after the partial pancreatectomy, urinary and plasma glucose levels in nicotinamide- and 3-aminobenzamide-treated rats were markedly lower than those in saline-treated control rats. Morphologic examination of the remaining pancreata revealed that islets in the poly(ADP-ribose) synthetase inhibitor-treated rats were markedly enlarged and consisted largely of B-cells. These results suggest that poly(ADP-ribose) synthetase inhibitors induce islet B-cell regeneration, thereby preventing or improving diabetes mellitus in partially depancreatized rats.
Solid‐Phase Synthesis of Aryl‐Alkylamine Derivatives Using Protected Aminoalcohol Building Blocks on SynPhaseTM Lanterns (2006)

Abstract A series of aryl‐alkylamine carboxamide and sulfonamide derivatives were synthesized on a BAL linker using SynPhase TM Lanterns. All the reaction steps were performed on a solid support. The key stage was on‐resin substitution of TBDPSi‐protected aminoalcohols with various amines, which circumvented the multistep solution‐phase synthesis of alkylamine building blocks. The chemistry applied allows building up focused libraries targeted on CNS receptors.
A clinical staging system for multiple myeloma correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival (1975)

The presenting clinical features of 71 patients with multiple myeloma were correlated with myeloma cell mass (myeloma cells X 10(12)/m2 of body surface area) determined from measurements of monoclonal immunoglobulin (M-component) synthesis and metabolism. Bivariate correlation and multivariate regression analyses showed that myeloma cell mass could be accurately predicted from A) extent of bone lesions, B) hemoglobin level, C) serum calcium level, and D) M-component levels in serum and urine. Analyses of response to chemotherapy and survival indicated significant correlation with measured myeloma cell burden. The results were synthesized to produce a very reliable and useful clinical staging system with three tumor cell mass levels (Table 7). For clinical research purposes, multivariate regression equations were developed to predict optimally the exact myeloma cell mass. Thus, initial staging can be quantitatively related to followup using tumor cell mass changes calculated from changes in M-component production. Use of the clinical staging system sould provide better initial assessment and followup of individual patients, and should lead to improved study design and analysis in large clinical trials of therapy for multiple myeloma.