gebhart/patrepeval huggingface dataset:
Clinical course of thrombocytopenia in patients treated with imatinib mesylate for accelerated phase chronic myelogenous leukemia (2002)

We studied 28 patients with accelerated phase chronic myelogenous leukemia (CML) who were enrolled on the Novartis expanded access study 114. Diagnosis of accelerated phase CML was based on karyotypic evolution (n = 9) and hematologic criteria (n = 18). All patients were begun on 600 mg/day of imatinib mesylate. Dose reductions to 400 mg/day and then 300 mg/day were prescribed for an absolute neutrophil count (ANC) of <0.5/microl or a platelet count of <20,000/microl. Twenty-seven of the 28 patients continued treatment for a median of 34 weeks. Eleven patients developed thrombocytopenia following an average of 8.4 +/- 1.4 weeks of therapy. The onset of thrombocytopenia was associated with disease progression in one patient and a decline in bone marrow megakaryocytes in the other 10. Nine patients recovered to a platelet count of >20,000/microl after an average of 19.7 +/- 1.8 weeks. Patients who developed thrombocytopenia had a longer duration of disease (9.39 vs. 4.35 years; P < 0.01) and were more likely to be diagnosed with accelerated phase CML by hematologic criteria. Hematologic responses in patients with and without thrombocytopenia were comparable; however, 31.3% of patients without thrombocytopenia had a complete cytogenetic response compared to none of those with thrombocytopenia. Grade III-IV thrombocytopenia is common in accelerated phase CML and may be a marker for the inability to achieve cytogenetic response using single agent imatinib mesylate.
Image archival technologies. (1992)

A typical radiology department can create many gigabytes of image data per day and as much as 1 terabyte of data per year. Archiving and accessing this much data are substantial problems. One solution is data compression, which decreases data storage requirements and increases the rate of data transfer; however, standards are not yet available. Other solutions involve improvements in archival media. Jukebox subsystems allow automated access to multiple units. Digital magnetic tape, the standard medium, can store large amounts of information and enables easy updates or replacements; more practical technologies have been introduced in recent years. Digital videotape allows storage of digital video data and features a high rate of data transfer. Optical disks, now the preferred permanent archival medium, have a large storage capacity and provide excellent long-term stability. Optical tape is also being investigated as a solution to the archiving dilemma. Which technology to choose depends on many factors, including needs of the institution and the cost, stability, transfer time, and storage capacity of the system.
Inhibition of Inducible Nitric Oxide Synthase by Peroxisome Proliferator-Activated Receptor Agonists: Correlation with Induction of Heme Oxygenase 1 (1998)

Genetic knock-out in mice of peroxisome proliferator-activated receptor-alpha (PPAR alpha) can prolong inflammation in response to leukotriene B4. Although cyclooxygenase 2 has been shown to be induced by PPAR activation, the effect of PPAR agonists on the key inflammatory enzyme systems of nitric oxide synthase (NOS) and stress proteins has not been investigated. The effect on these of naturally occurring eicosanoid PPAR agonists (leukotriene B4 and 8(S)-hydroxyeicosatetraenoic acid, which are PPAR alpha selective; PGA2, PGD2, PGJ2, and delta12PGJ2, which are PPAR gamma selective) and the synthetic PPAR alpha agonist Wy14,643 was examined in activated RAW264.7 murine macrophages. Leukotriene B4 and 8(S)-hydroxyeicosatetraenoic acid stimulated nitrite accumulation, indicative of enhanced NOS activity. PGA2, PGD2, PGJ2, delta12PGJ2, and Wy14,643 reduced nitrite accumulation, with delta12PGJ2 being the most effective. The mechanism behind this reduction was examined using Western blotting. Inhibition of nitrite accumulation was associated with a fall in inducible NOS protein and an induction of heme oxygenase 1, correlating both dose dependently and temporally. Other proteins examined (cyclooxygenase 2, heme oxygenase 2, heat shock protein 70, and glucose-regulated protein 78) were unaffected. The data suggest that naturally occurring PPAR agonists can inhibit the inducible NOS enzyme pathway. This inhibition may be mediated by modulation of the stress protein, heme oxygenase 1. Thus, the generation of eicosanoid breakdown products during inflammation may contribute to its eventual resolution by activation of the PPAR system. This system may thus represent a novel target for therapeutic intervention in inflammatory disease.
Absolute Quantification of Proteins in Solutions and in Polyacrylamide Gels by Mass Spectrometry (2004)

A combination of nanoelectrospray tandem mass spectrometry and (18)O-labeled peptide internal standards was applied for the absolute quantification of proteins from their in-solution and in-gel tryptic digests. Although absolute quantification from in-solution digests was accurate, we observed that in-gel digestion compromised the quantification accuracy by affecting the recovery of individual peptides and, therefore, the provided estimates might be strongly influenced by the selection of reference peptides. Under optimized experimental conditions, it was possible to provide a semiquantitative estimate of the absolute amount of gel separated proteins within better than 50% error margin.
Attraction of Several Dipterous Insects to Aliphtic Esters : Diptera : Milichiidae, Chloropidae and Ceratopogonidae (1974)

The enticement of several dipterous insects to straight chain aliphatic esters was tested under field conditions by means of a filter paper trap permeated with an ascending flow of chemicals. The structurally related compounds were simultaneously exposed in a group and their activities were mutually compared by the numbers of trapped insects. Four insect species respectively gave a precise choice to chemical structures within a limited range, which shifted gradually from species to species; the favored comounds were hexyl butanoate for Neophyllomyza sp. (Milichiidae), octyl butanoate for Siphonella sp. (Chloropidae), hexyl hexanoate for Forcipomyia sp. A (Ceratopogonidae) and decyl hexanoae for Forcipomyia sp. B. The attracting activity of the compounds to the insect species varied, in different ways according to the responding species, wit respect to the total chain length as well as the length of either the alcohol or acid moiety and the position of the functional group in molecules of the same length. The results are discussed in the light of the current conception on the mechanism of insect olfaction.
Interaction and visualization techniques for volumetric data of various scalar modalities: integration of visualization and interaction (2013)

Over the last years, acquisition techniques have improved significantly in several areas such as oil minig industry, medicine, geophysics, weather predictions, etc. resulting in large volumetric data sets. Visualizing and exploring this kind of data introduces some questions: how to select the appropriate method for a particular case? how to represent more than 3 dimensions? How to guide the users to extract valuable information? The interaction with the final visualization is also crucial to gain insight and reach conclusions. Providing the different visualization techniques combined with appropriate methods of interaction seems to be the way to empower the final user. This paper present several visualization and interaction techniques used in volumetric data, as well as some aspects reagarding the integration of visualization and interaction.
A decentralised conflict and error detection and prediction model (2009)

The objective of this research is to study the performance of a newly developed decentralised conflict and error detection and prediction model (CEDPM) over different networks. In the CEDPM, conflict and error (CE) detection and prediction agents are deployed at each collaborative unit to detect and predict CEs, and exchange information with the support of a CE detection and prediction protocol. Two metrics, detection and prediction time and conflict severity, are defined to evaluate CEDPM and CE propagation, respectively, for linear, divergence, convergence, and parallel coordination networks in which different task dependences exist among collaborative units. Experiment results show that the CEDPM performs significantly better for networks with parallel activities. The conflict severity reflects network complexity and increases as the dependence between collaborative units increases. The findings are useful for the design of emerging prognostics systems-of-systems.
Psoriasis, from Pathogenesis to Therapeutic Strategies: IL-21 as a Novel Potential Therapeutic Target (2012)

Psoriasis is a common (1-3% of the population worldwide), multifactorial, immune-mediated chronic skin disease. In psoriasis pathogenesis an over-reaction of local innate immune response initiates inflammation with subsequent involvement of adaptive immune response leading to the production of a panel of cytokines, chemokines and growth factors leading to epidermal hyperplasia. Recently, IL-21 has been involved in this process as this cytokine is overexpressed in psoriatic skin and can cause epidermal hyperplasia and inflammation when injected intradermally into mice. Moreover blockade of IL-21 with a human antibody against IL-21 reduces the epidermal thickness and the expression of Th1 and Th17 genes in the well-characterized model of human psoriasis-xenograft mouse. Therefore, the inhibition of this cytokine may be therapeutically effective in the treatment of psoriasis. Here we will review recent data on psoriasis pathogenesis focusing on the role of IL-21 as novel therapeutic target.
Highly flexible transparent electrodes based on mesh-patterned rigid indium tin oxide (2018)

We developed highly bendable transparent indium tin oxide (ITO) electrodes with a mesh pattern for use in flexible electronic devices. The mesh patterns lowered tensile stress and hindered propagation of cracks. Simulations using the finite element method confirmed that the mesh patterns decreased tensile stress by over 10% because of the escaped strain to the flexible film when the electrodes were bent. The proposed patterned ITO electrodes were simply fabricated by photolithography and wet etching. The resistance increase ratio of a mesh-patterned ITO electrode after bending 1000 times was at least two orders of magnitude lower than that of a planar ITO electrode. In addition, crack propagation was stopped by the mesh pattern of the patterned ITO electrode. A mesh-patterned ITO electrode was used in a liquid-based organic light-emitting diode (OLED). The OLED displayed the same current density-voltage-luminance (J-V-L) curves before and after bending 100 times. These results indicate that the developed mesh-patterned ITO electrodes are attractive for use in flexible electronic devices.
Frequency, risk factors, anatomy, and course of unilateral neglect in an acute stroke cohort (2004)

This series confirms that hemispatial neglect may occur with damage to several supratentorial structures but is most common and persistent with lesions of the right temporoparietal cortex. Increasing age is associated with neglect, particularly after right brain lesions. Gender and handedness do not exert a marked effect on the likelihood of the occurrence of neglect.
Liberating the radicle: A case for softening-up (1996)

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A Double‐blind Placebo Controlled Study of Male Alcoholics Given a Subcutaneous Disulfiram Implantation (1987)

Summary Twenty‐one alcoholics participated in a double blind study to elicit information of the clinical effect of implanted disulfiram. They were randomized to either of two groups, 11 patients to the placebo group and 10 patients to the disulfiram group. Each patient was subjected to seven sessions of intravenous ethanol challenge, once before and six times during the first 20 weeks after implantation. The acute ethanol challenge did not result in any differences between the groups with respect to blood ethanol and acetaldehyde concentrations. No patient showed any clinical signs of disulfiram‐ethanol reaction. After a study period of 20 weeks no significant differences were found between the groups with regard to the reduction in average ethanol consumption, days from implantation to the first drink and number of abstinent weeks. Our results do not support the idea that a 1 g disulfiram implant has any pharmacological or clinical action.
Short crack growth and fatigue life in austenitic‐ferritic duplex stainless steel (2005)

ABSTRACT The kinetics of short crack growth has been studied in austenitic‐ferritic 2205 duplex stainless steel. Smooth cylindrical specimens and specimens with shallow notch were subjected to constant plastic strain amplitude loading. The crack growth was studied in notched specimens. The notch area has been mechanically and electrolytically polished to facilitate the observation of crack initiation and growth. The initiated cracks were observed in an SEM (scanning electron microscope). The crack growth was studied using long distance QUESTAR optical microscope equipped with high‐resolution camera. In constant plastic strain amplitude loading the microcracks were initiated and their growth kinetics has been studied. The characteristic features of the crack growth at different plastic strain amplitudes were recorded. Two approaches to analyse the crack growth rates were adopted. The comparison of the prediction of the fatigue life using the plastic‐strain‐dependent crack growth rate was compared with Manson–Coffin law and the relation between parameters of this law and parameters of the short crack growth law were established.
Expression of retrovirus-related, cytotoxic T lymphocyte- and transplantation-defined antigens in NIH/3T3 transfectants after a single passage in nude mice. (1989)

Transfection of T24c-Ha-ras oncogene into NIH/3T3 fibroblasts resulted in the establishment of a transformed cell line (pT) that was tumorigenic when injected s.c. both into Swiss outbred nude mice and normal NIH inbred mice. The passage into nude mice, however, led to the development of a tumor variant (pT-nude) able to subsequently grow into sublethally x-irradiated but not into immunocompetent NIH mice. NIH mice immunized with this tumor variant developed a strong specific CTL response against the immunizing cell line, whereas the parental transformed pT cell line was not lysed. Clones were derived by limiting dilution from anti-pT-nude bulk population and were tested on a panel of transformed NIH/3T3 lines before and after their growth as tumor into nude mice. All of these lines were lysed by the Lyt-2+ CTL clones as a sole consequence of one in vivo passage into nude mice. The cross-reactive Ag were shown to be related to endogenous retroviral products as assessed by 1) immunoprecipitations of gp70, p15E, and p30 viral proteins in the nude variants but not in parental lines, and 2) by the ability of retroviruses from irradiated pT-nude cells to infect NIH/3T3 or pT lines making them susceptible to lysis by anti-pT-nude CTL clones. These results show that a single passage in nude mice can induce retrovirus-related, cell-surface Ag in transplanted neoplastic cells.
Note on the Critical Bandwidth (1962)

Exceptionally small values of the critical bandwidth are found from masking thresholds of a tone in narrow bands of noise, when the test tone's frequency remains at the center of the band of noise components. Numerous other experiments—by no means limited to masking—have led to the conception of a markedly wider critical band. In this communication the evidence on this ambivalence. especially as regards masking at the central frequency of a noise band, is critically examined. It appears that the critical band cannot be expected to be accurately determined from central-masking experiments. The most important reason is that the effective power of masking noise is not the sole determinant of masking. The inherent fluctuations of random noise, becoming less rapid and more noticeable at small bandwidths, exert a considerable influence on the detection of tones. The extent of this effect can be evaluated from the intensity difference limen of narrow-band noise. It is to be concluded from the discussion that the larger values of the critical bandwidth are to be preferred, and that the smaller values should be rejected.
Peptide Inhibitors Identify Roles for SSB C-Terminal Residues in SSB/Exonuclease I Complex Formation (2009)

Bacterial single-stranded (ss) DNA-binding proteins (SSBs) facilitate DNA replication, recombination, and repair processes in part by recruiting diverse genome maintenance enzymes to ssDNA. This function utilizes the C-terminus of SSB (SSB-Ct) as a common binding site for SSB's protein partners. The SSB-Ct is a highly conserved, amphipathic sequence comprising acidic and hydrophobic elements. A crystal structure of Escherichia coli exonuclease I (ExoI) bound to a peptide comprising the E. coli SSB-Ct sequence shows that the C-terminal-most SSB-Ct Phe anchors the peptide to a binding pocket on ExoI and implicates electrostatic binding roles for the acidic SSB-Ct residues. Here, we use SSB-Ct peptide variants in competition experiments to examine the roles of individual SSB-Ct residues in binding ExoI in solution. Altering the C-terminal-most Pro or Phe residues in the SSB-Ct strongly impairs SSB-Ct binding to ExoI, confirming a major role for the hydrophobic SSB-Ct residues in binding ExoI. Alteration of N-terminal SSB-Ct residues leads to changes that reflect cumulative electrostatic binding roles for the Asp residues in SSB-Ct. The SSB-Ct peptides also abrogate SSB stimulation of ExoI activity through a competitive inhibition mechanism, indicating that the peptides can disrupt ExoI/SSB/ssDNA ternary complexes. Differences in the potency of the SSB-Ct peptide variants in the binding and nuclease inhibition studies indicate that the acidic SSB-Ct residues play a more prominent role in the context of the ternary complex than in the minimal ExoI/SSB-Ct interaction. Together, these data identify roles for residues in the SSB-Ct that are important for SSB complex formation with its protein partners.
Engineering of stable bispecific antibodies targeting IL-17A and IL-23 (2009)

Bispecific antibodies (bsAbs) present an attractive opportunity to combine the additive and potentially synergistic effects exhibited by combinations of monoclonal antibodies (mAbs). Current challenges for engineering bsAbs include retention of the binding affinity of the parent mAb or antibody fragment, the ability to bind both targets simultaneously, and matching valency with biology. Other factors to consider include structural stability and expression of the recombinant molecule, both of which may have significant impact on its development as a therapeutic. Here, we incorporate selection of stable, potent single-chain variable fragments (scFvs) early in the engineering process to assemble bsAbs for therapeutic applications targeting the cytokines IL-17A/A and IL-23. Stable scFvs directed against human cytokines IL-23p19 and IL-17A/A were isolated from a human Fab phage display library via batch conversion of panning output from Fabs to scFvs. This strategy integrated a step for shuffling V regions during the conversion and permitted the rescue of scFv molecules in both the V(H)V(L) and the V(L)V(H) orientations. Stable scFvs were identified and assembled into several bispecific formats as fusions to the Fc domain of human IgG1. The engineered bsAbs are potent neutralizers of the biological activity of both cytokines (IC(50) < 1 nM), demonstrate the ability to bind both target ligands simultaneously and display stability and productivity advantageous for successful manufacture of a therapeutic molecule. Pharmacokinetic analysis of the bsAbs in mice revealed serum half-lives similar to human mAbs. Assembly of bispecific molecules using stable antibody fragments offers an alternative to reformatting mAbs and minimizes subsequent structure-related and manufacturing concerns.
Mechanistic Studies of Ubiquitin C-Terminal Hydrolase L1 (2006)

Ubiquitin C-terminal hydrolases (UCHs) cleave Ub-X bonds (Ub is ubiquitin and X an alcohol, an amine, or a protein) through a thioester intermediate that is produced by nucleophilic attack of the Cys residue of a Cys-SH/His-Im catalytic diad. We are studying the mechanism of UCH-L1, a UCH that is implicated in Parkinson's disease, and now wish to report our initial findings. (i) Pre-steady-state kinetic studies for UCH-L1-catalyzed hydrolysis of Ub-AMC (AMC, 7-amido-4-methylcoumarin) indicate that k(cat) is rate-limited by acyl-enzyme formation. Thus, K(m) = K(s), the dissociation constant for the Michaelis complex, and k(cat) = k(2), the rate constant for acyl-enzyme formation. (ii) For K(assoc) (=K(s)(-)(1)), DeltaC(p) = -0.8 kcal mol(-)(1) deg(-)(1) and is consistent with coupling between substrate association and a conformational change of the enzyme. For k(2), DeltaS(++) = 0 and suggests that in the E-S, substrate and active site residues are precisely aligned for reaction. (iii) Solvent isotope effects are (D)K(assoc) = 0.5 and (D)k(2) = 0.9, suggesting that the substrate binds to a form of free enzyme in which the active site Cys exists as the thiol. In the resultant Michaelis complex, the diad has tautomerized to ion pair Cys-S(-)/His-ImH(+). Subsequent attack of thiolate produces the acyl-enzyme species. In contrast, isotope effects for association of UCH-L1 with transition-state analogue ubiquitin aldehyde suggest that an alternative mechanistic pathway can sometimes be available to UCH-L1 involving general base-catalyzed attack of Cys-SH by His-Im.
Noncanonical Secondary Structure Stabilizes Mitochondrial tRNA Ser(UCN) by Reducing the Entropic Cost of Tertiary Folding (2015)

Mammalian mitochondrial tRNA(Ser(UCN)) (mt-tRNA(Ser)) and pyrrolysine tRNA (tRNA(Pyl)) fold to near-canonical three-dimensional structures despite having noncanonical secondary structures with shortened interhelical loops that disrupt the conserved tRNA tertiary interaction network. How these noncanonical tRNAs compensate for their loss of tertiary interactions remains unclear. Furthermore, in human mt-tRNA(Ser), lengthening the variable loop by the 7472insC mutation reduces mt-tRNA(Ser) concentration in vivo through poorly understood mechanisms and is strongly associated with diseases such as deafness and epilepsy. Using simulations of the TOPRNA coarse-grained model, we show that increased topological constraints encoded by the unique secondary structure of wild-type mt-tRNA(Ser) decrease the entropic cost of folding by ∼2.5 kcal/mol compared to canonical tRNA, offsetting its loss of tertiary interactions. Further simulations show that the pathogenic 7472insC mutation disrupts topological constraints and hence destabilizes the mutant mt-tRNA(Ser) by ∼0.6 kcal/mol relative to wild-type. UV melting experiments confirm that insertion mutations lower mt-tRNA(Ser) melting temperature by 6-9 °C and increase the folding free energy by 0.8-1.7 kcal/mol in a largely sequence- and salt-independent manner, in quantitative agreement with our simulation predictions. Our results show that topological constraints provide a quantitative framework for describing key aspects of RNA folding behavior and also provide the first evidence of a pathogenic mutation that is due to disruption of topological constraints.