gebhart/patrepeval huggingface dataset:
INCB018424, an Oral, Selective JAK2 Inhibitor, Shows Significant Clinical Activity in a Phase I/II Study in Patients with Primary Myelofibrosis (PMF) and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF). (2007)

Abstract Background: A mutation in the Janus tyrosine kinase 2 gene (JAK2 V617F) has been recognized in Philadelphia chromosome-negative myeloproliferative disorders, including PV (∼95% of patients), ET (∼50%) and PMF (∼50%). INCB018424 is a potent and orally bioavailable selective JAK2 inhibitor with &gt;80-fold selectivity against a broad panel of kinases, including JAK3. INCB018424 potently inhibits JAK2 V617F mediated signaling and malignant cell survival in vitro and in vivo in mice. Preclinical safety studies with INCB018424 demonstrated an excellent safety profile with no off-target toxicities. Methods: A phase I/II trial of INCB018424 given orally BID is being conducted in patients with PMF and Post-PV/ET MF. Both JAK2 V617F and JAK2 wild type patients are eligible. PK and PD data are being collected. Responses are being evaluated using the International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT) (Tefferi et al., Blood, 108, 1497–1503, 2006). Results: The initial dose of 25 mg PO BID resulted in a rapid and marked reduction in splenomegaly. All 3 patients in the first cohort of patients achieved a reduction in spleen size that is consistent with a clinical improvement response provided it is sustained for 8 weeks; spleen sizes of 25, 22, and 7 cm below the left costal margin have decreased to 8, 10, and 0 cm in the first month of therapy. At two months follow-up, the patient with a baseline spleen size of 22 cm is now down to 2 cm. All 3 patients also noted significant symptomatic improvement. The second cohort of 3 patients started therapy at an increased dose (50 mg PO BID) and at one week follow-up, the initial two patients (one JAK2 wild type, one JAK2 V617F) had decreases in spleen size from 22 cm to 17 cm and from 22 cm to 16 cm, respectively. No dose-limiting toxicities or other significant adverse events occurred in any patients to date. PK/PD analyses demonstrated that administration of INCB018424 resulted in plasma drug concentrations sufficient to markedly inhibit JAK2, as shown by suppression of phosphorylated STAT3 (a substrate of JAK2) in whole blood cells in all 3 patients in the first cohort. The 3 patients in the first cohort were all JAK2 V617F mutation positive: percentages of JAK2 V617F positive whole blood cells before therapy were 79%, 49% and 91%, and after one month of therapy, they were 59%, 48% and 78%, respectively. Conclusions: Initial results show marked reduction in splenomegaly and symptomatic improvement, without significant toxicity. The percentage of blood cells with JAK2 V617F mutation appears to be decreasing in patients on therapy. Updated results on current and future patients will be presented at the meeting.
Ten distinct circular ssDNA components, four of which encode putative replication-associated proteins, are associated with the faba bean necrotic yellows virus genome. (1998)

Four further circular ssDNA components (C7-C10), about 1 kb in size and structurally similar to the previously described components (C1-C6) found associated with a Syrian (Sy) isolate of faba bean necrotic yellows virus (FBNYV), have been identified. Similar to C1 and C2, two of the new components (C7 and C9) encode putative replication-associated (Rep) proteins of 33.2 and 32.7 kDa, respectively, the former of which is 90% identical to the C10 Rep protein of milk vetch dwarf virus (MDV). C8 encodes a putative protein (17.4 kDa) whose function is unknown, but which is highly conserved between FBNYV and the other nanoviruses MDV, subterranean clover stunt virus and banana bunchy top virus. The putative protein (19.7 kDa) encoded by C10 contains an LXCXE motif, which is also present in the homologues of its relatives, suggesting that they may all interact with plant retinoblastoma-like proteins. Sequence information for seven components of an Egyptian (Eg) FBNYV isolate indicated that six of them share > 96% identity with FBNYV-Sy. However, the C1 Rep protein of FBNYV-Eg was only 63.5% identical to that of FBNYV-Sy, but was 88.3 % identical to the MDV-C2 Rep protein. We conclude that the FBNYV genome consists of seven to ten components, six of which encode non-Rep proteins. All ten components of the FBNYV genome, except the Rep components C2 and C9, had closely related counterparts in the MDV genome. In spite of this similarity, FBNYV and MDV appear to be distinct virus species.
Thermodynamic studies of base pairing involving 2,6-diaminopurine (1988)

The thermal stabilities of oligodeoxyribonucleotide duplexes containing 2,6-diaminopurine (D) matched with each of the four normal DNA bases were determined by optical melting techniques. Comparison of optical melting curves yielded relative stabilities for the D-containing standard base pairs in an otherwise identical base-pair sequence. The D:T pair was found to be more stable than the A:T pair in dC3DG3:dC3TG3, as stable as the A:T in dCT3DT3G:dCA3TA3G, and less stable than the A:T in dCA3DA3G:dCT7G. The order of stabilities for X:Y in the DNA duplex dCA3XA3G:dCT3YT3G is: (A:T) greater than (T:D) congruent to (D:T) greater than or equal to (T:A) greater than (C:D) congruent to (D:A) congruent to (D:G) greater than or equal to (D:C) congruent to (G:D) congruent to (D:D) greater than or equal to (A:D). Implications of these results for design of DNA oligonucleotide probes are discussed.
Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from Northern Peru (2001)

A 3-day course of nitazoxanide suspension is as efficacious as a standard 5-day course of metronidazole suspension in treating giardiasis in children.
Regulation of phosphorylation of tau by cyclin‐dependent kinase 5 and glycogen synthase kinase‐3 at substrate level (2006)

Microtubule associated protein tau, which is expressed in six alternatively spliced molecular isoforms in human brain, is abnormally hyperphosphorylated in Alzheimer disease and related tauopathies. Here, we show (i) that GSK-3alpha and neither GSK-3beta nor cdk5 can phosphorylate tau at Ser262 and phosphorylation at Ser235 by cdk5 primes phosphorylation at Thr231 by GSK-3alpha/beta; (ii) that tau isoforms with two N-terminal inserts (tau4L, tau3L) are phosphorylated by cdk5 plus GSK-3 at Thr231 markedly more than isoforms lacking these inserts (tau4, tau3); and (iii) that Thr231 is phosphorylated approximately 50% more in free tau than in microtubule-bound tau, and the phosphorylation at this site results in the dissociation of tau from microtubules. These findings suggest that the phosphorylation of tau at Thr231 and Ser262 by cdk5 plus GSK-3, which inhibits its normal biological activity, is regulated both by its amino terminal inserts and its physical state.
Molecular Characterization of Human 4Ig-B7-H3, a Member of the B7 Family with Four Ig-Like Domains (2004)

In an effort to characterize molecules with immunoregulatory potential, we raised mAbs to human dendritic cells. We selected an Ab that recognizes a molecule that is induced on monocytes differentiated in vitro toward dendritic cells. Retroviral expression cloning identified this molecule as B7-H3, a member of the B7 family described recently. In contrast to an earlier report, in which B7-H3 was described as a molecule consisting of two Ig-like domains, our cDNA encoded a type I membrane protein with four Ig-like domains, and the molecule identified by us was therefore named 4Ig-B7-H3. mRNA analysis as well as Western blotting experiments performed by us did not reveal evidence for a small B7-H3. B7-H3 is not expressed on peripheral blood lymphocytes, monocytes, or granulocytes. Upon in vitro stimulation, the expression of B7-H3 is induced on T cells, B cells, and NK cells. A number of different approaches were used to investigate the function of human B7-H3. In contrast to an earlier report, our data do not support a costimulatory role of B7-H3 in anti-CD3-mediated activation of the TCR-complex resulting in T cell proliferation and IFN-gamma production.
Colloidal Metal−Insulator−Metal Ensemble Chemiresistor Sensor (1998)

A colloidal metal−insulator−metal ensemble chemiresistor sensor based on a monolayer stabilized metal nanocluster transducer film is described. In the example presented, the thin transducer film is composed of 2-nm gold clusters encapsulated by octanethiol monolayers and is deposited on an interdigital microelectrode. Responses to organic vapor exposures are large (resistance changes up to 2-fold or more), fast (90% response in less than 1 s), reversible, and selective. Chemiresistor sorption isotherms for toluene, tetrachloroethylene, 1-propanol, and water vapors are nonlinear and illustrate the high sensitivity and selectivity (ppm detection for toluene and tetrachloroethylene; negligible response for 1-propanol and water).
Fibrinolysis with Des-Kringle Derivatives of Plasmin and Its Modulation by Plasma Protease Inhibitors (1998)

Quantitative characterization of the interaction of des-kringle1-5-plasmin (microplasmin) with fibrin(ogen) and plasma protease inhibitors may serve as a tool for further evaluation of the role of kringle domains in the regulation of fibrinolysis. Comparison of fibrin(ogen) degradation products yielded by plasmin, miniplasmin (des-kringle1-4-plasmin), microplasmin, and trypsin on SDS gel electrophoresis indicates that the differences in the enzyme structure result in different rates of product formation, whereas the products of the four proteases are very similar in molecular weight. Kinetic parameters show that plasmin is the most efficient enzyme in fibrinogen degradation, and the kcat/KM ratio decreases in parallel with the loss of the kringle domains. The catalytic sites of the four proteases have similar affinities for fibrin (KM values between 0.12 and 0.21 microM). Trypsin has the highest catalytic constant for fibrin digestion (kcat = 0.47 s-1), and among plasmins with different kringle structures, the loss of kringle5 results in a markedly lower catalytic rate constant (kcat = 0.0076 s-1 for microplasmin vs 0.048 s-1 for miniplasmin and 0.064 s-1 for plasmin). In addition, microplasmin is inactivated by plasmin inhibitor (k" = 3.9 x 10(5) M-1 s-1) and antithrombin (k" = 1.4 x 10(3) M-1 s-1) and the rate of inactivation decreases in the presence of fibrin(ogen). Heparin (250 nM) accelerates the inactivation of microplasmin by antithrombin (k" = 10.5 x 10(3) M-1 s-1 ), whereas that by plasmin inhibitor is not affected (k" = 4.2 x 10(5) M-1 s-1).
Botulinum toxin A blocks glutamate exocytosis from guinea-pig cerebral cortical synaptosomes (1987)

The exocytotic release of L-glutamate from guinea-pig cerebral cortical synaptosomes can be extensively inhibited by preincubation with botulinum neurotoxin type A at 37 degrees C for 1-2 h. The toxin has no effect on synaptosomal respiratory control, respiratory capacity, ATP synthesis, plasma-membrane 86Rb+ permeability or plasma-membrane potential, does not inhibit the entry of 45Ca2+ into the synaptosome upon depolarization and does not alter the ability of intrasynaptosomal mitochondria to sequester Ca2+. The blockade of Ca2+-dependent glutamate release may be totally reversed by the Ca2+/2 H+-exchange ionophore ionomycin, but not by increasing extracellular Ca2+ concentration. It is suggested (a) that exocytosis is triggered by the penetration of Ca2+ into an intracellular hydrophobic milieu; (b) that this stage is blocked by the toxin and (c) that ionomycin is able to bypass this block and deliver Ca2+ to the exocytotic apparatus.
The structure of cellular solids (1997)

The structure of cells has fascinated natural philosophers for at least 300 years. Hooke examined their shape, Kelvin analysed their packing, and Darwin speculated on their origin and function. The subject is important to us here because the properties of cellular solids depend directly on the shape and structure of the cells. Our aim is to characterize their size, shape and topology: that is, the connectivity of the cell walls and of the pore space, and the geometric classes into which these fall.
Chapter 17: Random Processes* (2007)

To model noise in measurement and filtering processes requires concepts more general than that of a random variable. This is because we need to discuss the results of passing a noisy signal through a linear filter. As was the case in chapter 9, it is easier to present this material in terms of functions of a single variable, though the theory is easily adapted to functions of several variables. After giving the basic definitions, we consider some important examples of random processes and analyze the effect of a linear shift invariant filter on random inputs. The chapter concludes with an analysis of noise in the continuum model for filtered back-projection. Our discussion of random processes is very brief, aimed squarely at the goal of analyzing the effects of noise in the filtered back-projection algorithm. 17.1 Random Processes in Measurements To motivate this discussion, we think of the familiar example of a radio signal. A radio station broadcasts a signal sb(t) as an electromagnetic wave. A receiver detects a signal sr(t), which we model as a sum Here F is a filtering operation that describes the propagation of the broadcast signal. For the purposes of this discussion we model F as attenuation; that is, F(sb) = λsb for a 0 < λ < 1. The other term is noise. In part, the noise records “random” aspects of the life history of the broadcast signal that are not modeled by F. Beyond that it is an aggregation of other signals that happen to be present at the carrier frequency of the broadcast signal. The existence of the second part is easily verified by tuning an (old) radio to a frequency for which there is no local station. Practically speaking, it is not possible to give a formula for the noise. Because we cannot give an exact description of the noise, we instead describe it in terms of its statistical properties. We begin with the assumption that the noise is a bounded function of t. What can be done to specify the noise further? Recall the ensemble average definition of the probability of an event as the average of the results of many “identical experiments.” In the radio example, imagine having many different radios, labeled by a set . For each α ∊ we let sr,a(t) be the signal received by radio α at time t. The collection of radios is the sample space. The value of sr,a at a time t is a function on the sample space—in other words, a random variable. From the form given previously we see that
Counteracting the Nogo Receptor Enhances Optic Nerve Regeneration If Retinal Ganglion Cells Are in an Active Growth State (2004)

Mature retinal ganglion cells (RGCs), like other CNS neurons, cannot regrow injured axons into a myelin-rich environment. If stimulated by macrophage-derived factors, however, RGCs can regenerate their axons for considerable distances through the distal optic nerve. Using this "sensitized background," we investigated the effects of either increasing the expression or suppressing the activity of the Nogo receptor (NgR). NgR mediates the growth-inhibiting effects of three myelin proteins, Nogo, OMgp (oligodendrocyte-myelin glycoprotein), and MAG (myelin-associated glycoprotein). Transfecting growth-sensitized RGCs with adeno-associated viruses expressing a dominant-negative form of NgR (NgR(DN)) increased axon regeneration several-fold; however, when the growth program of RGCs was not activated, NgR(DN) expression had no beneficial effects. Overexpression of wild-type NgR blocked almost all regeneration from growth-sensitized RGCs and caused axons proximal to the lesion site to retract. We conclude that gene therapy is an effective approach to enhancing axon regeneration in the CNS and that inactivation of NgR functioning greatly enhances axon regeneration provided the intrinsic growth program of neurons is activated.
Microwave-Assisted Chemical Functionalization of Hydrogen-Terminated Porous Silicon Surfaces (2003)

This paper describes the chemical functionalization of hydrogen-terminated porous silicon surfaces with simple and functional 1-alkenes under microwave irradiation to give organic monolayers covalently attached to the surface through Si−C bonds. Using microwaves as a source of energy led to a remarkable increase in the rate of the hydrosilylation reaction and a higher surface coverage. This technique yields highly stable organic monolayers and allows the introduction of different functional groups on the surface (acid and ester) required for immobilization of more complex structures on the surface.
Clinical Information Technology Capabilities in Four U.S. Hospitals (2006)

This assessment tool demonstrates initial evidence of validity and reliability.
Genes and genomes: Sequencing 5‐methylcytosine residues in genomic DNA (1994)

To analyse the biological role of 5-methylation of cytosine residues in DNA requires precise and efficient methods for detecting individual 5-methylcytosines (5-MeCs) in genomic DNA. The methods developed over the past decade rely on either differential enzymatic or chemical cleavage of DNA, or more recently on differential sensitivity to chemical conversion of one base to another. The most commonly used methods for studying the methylation profile of DNA, including the bisulphite base-conversion method, are reviewed.
Laser lift-off of GaN thin film and its application to the flexible light emitting diodes (2012)

The high performance GaN light emitting diode (LED) from sapphire wafer has been transferred on a plastic substrate with 308nm XeCl laser lift-off (LLO) for next generation flexible lighting applications. SU-8 passivation with thermal release tape (TRT) adhesive enables structure coverage and adhesion so that it can be an excellent candidate for a carrier substrate for non-wetting transfer process using laser liftoff technology. The dimensions of the laser beam are also investigated in two types (3μm x 5cm and 1.2mm x 1.2mm) to reduce stress when decomposition of GaN occurs. With careful optimization of carrier substrate and laser beam conditions, we can fabricate flexible GaN LED on polyimide substrates which shows similar electrical properties to the GaN LED on bulk sapphire substrate.
Estimating the Prevalence of Binge Eating Disorder in a Community Sample From the United States (2016)

DSM-5 BED criteria resulted in higher BED prevalence estimates than with DSM-IV-TR criteria. Most BED respondents did not report being formally diagnosed, indicating an unmet need in BED recognition and diagnosis.
Temperature dependence of the threshold electric field in a hot electron VCSEL (Invited Paper) (2005)

The operation of the Hot Electron Light Emitting and Lasing in Semiconductor Heterostructure -- Vertical Cavity Surface Emitting Laser (HELLISH-VCSEL) devices is based on hot carrier transport parallel to the layers of Ga<sub>1-x</sub>Al<sub>x</sub>As p-n junction. It is therefore a field - effect device and the light emission from the device is independent of the polarity of the applied voltage. In this study, we present the temperature dependence of the operational characteristics of the device. Experimental studies comprising of the measurements of the I-V characteristics, electroluminescence, reflectivity, and temperature dependent light-applied electric field (L-F) characteristics are conducted to find the optimum operating temperature of the device.
<title>Three-dimensional inspection of integrated circuits: a depth from focus approach</title> (1992)

Optical inspection of integrated circuit images is an application of image understanding which is becoming an important field in the microelectronics industry. When the inspection is performed by optical microscopy, a small depth of field of an optical system causes problems dealing with focusing when structures with large depth variations are imaged. We propose a method which takes advantage of this effect to make a depth map of the circuit surface. The method is based on the analysis of defocusing on a series of images obtained by continuously varying the distance between the circuit surface and the center of the optical system. Morphological algorithms working in three-dimensional spaces are used to ensure the coherence of the results.
SQL and management of external data (2001)

In late 2000, work was completed on yet another part of the SQL standard [1], to which we introduced our readers in an earlier edition of this column [2].Although SQL database systems manage an enormous amount of data, it certainly has no monopoly on that task. Tremendous amounts of data remain in ordinary operating system files, in network and hierarchical databases, and in other repositories. The need to query and manipulate that data alongside SQL data continues to grow. Database system vendors have developed many approaches to providing such integrated access.In this (partly guested) article, SQL's new part, Management of External Data (SQL/MED), is explored to give readers a better notion of just how applications can use standard SQL to concurrently access their SQL data and their non-SQL data.
Immunodeficiency with hyper-IgM (HIM). (1992)

Immunodeficiency with hyper-IgM (HIM) is a rare disorder characterized by recurrent infections associated with low IgG and IgA, and normal to increased IgM serum levels. Both primary and secondary forms of HIM syndrome have been reported. Among primary HIM syndrome, evidence for genetic heterogeneity is provided by the occurrence of the disease as X-linked, autosomal recessive, or autosomal dominant trait. The most common clinical manifestations include upper and lower respiratory tract infections, otitis, diarrhoea, oral ulcers, lymphoid hyperplasia, and autoimmunity. Recurrent neutropaenia is a frequent finding. Immunological abnormalities consist of lack of IgG and IgA secretion, and failure to respond to vaccination. Lymph nodes show absence of germinal centres. Few patients with a concurrent T-cell defect, and clinical expression of combined immune deficiency, have been reported. The gene responsible for the X-linked HIM syndrome (HIGM1) has been tentatively assigned to Xq24-27. However, carrier detection and prenatal diagnosis are not yet possible. Pathogenetic hypotheses include failure of B-cell differentiation, and defective regulation of immunoglobulin isotype switching due to abnormal T-cell-mediated signals. Treatment is mainly based upon regular administration of intravenous immunoglobulins. Steroids may be useful in the treatment of neutropaenia and of severe autoimmune manifestations.