gebhart/patrepeval huggingface dataset:
Validation of JAK2 and New Clinical Criteria for the Diagnosis of Polycythemia Vera (PV). (2005)

Abstract Although the pervasive presence of JAK2 in patients (pts) with PV has been noted in at least 7 published studies, its frequency has ranged from 66 to 97%. Although part of the reason for this wide range is false negative results due to the low sensitivity of sequence analysis, varying criteria used for the clinical diagnosis of PV are also likely to be an important factor. In more than 300 studies, the criteria of the Polycythemia Vera Study Group has been used, although many authors, including ourselves, have commented on their inadequacy. Alternative classifications have been the subject of debate mostly centered about using the rbc-Cr51 mass. Our criteria included the use of CR51 labeled red cells to establish first, an increase in red blood cell volume and second, I125 to establish an increase in plasma volume. Exception was made for men with a HCT ≥60%, and women ≥56%. If hypervolemic, the major causes of secondary polycythemia were excluded: congenital polycythemias and those secondary to impaired oxygenation, or benign or malignant tumors. This implied a serum erythropoietin level of ≤5u/ml. The aforementioned and 3 of the following 5 were required: splenomegaly, WBC, ≥12,000/ul, platelet count ≥600,000/ul, abnormal marrow histology. We used them to clinically diagnose 61 patients subsequently undergoing therapeutic trials whose blood was analyzed for the JAK2 V617F mutation by allele specific PCR from 679 patients with myeloproliferative diseases, including normal controls. Of 61 patients, with the phenotypic characteristics of p. vera, 59 (97%) were positive for the JAK2 mutation. The 2 remaining patients, although phenotypically characteristic of PV, were negative on repeat examinations. One pt was newly diagnosed and untreated and the other had a 6 year remission after rIFNα followed by a 1 year remission on imatinib. We conclude that determination of JAK2 is consistent with PV in virtually all cases clinically diagnosed appropriately. Our data, to be presented, indicate that the combination of increased red cell mass, demonstration of JAK2 and increased platelet count establish the diagnosis of PV in virtually all cases.
Gathering requirements for a personal health management system (2011)

Applications are being designed to make health information available to the healthcare consumer. However, little is known about the support people need in using health information. We conducted semi-structured interviews to find out how people use health information to manage the chronic illness type-2 diabetes. We found that diabetics want to be motivated to treat the disease seriously and that the patient's social network takes on additional work that is unrelated to their existing social role to support the patient's health-related activities. Based on our findings, we propose a set of formative requirements to be included in the design of a personal health management system.
Synthesis of a Ligand Based upon a New Entry into the 3-Hydroxy-<i>N</i>-alkyl-2(1<i>H</i>)-pyridinone Ring System and Thermodynamic Evaluation of Its Gadolinium Complex (2000)

The synthesis of a new, more water soluble derivative of TREN-Me-3,2-HOPO (tris[(3-hydroxy-1-methyl-2-oxo-1,2- didehydropyridine-4-carboxamido)ethyl]amine) is presented. The synthesis starts with the condensation reaction of (N-methoxyethylamino)acetonitrile hydrochloride and oxalyl chloride to give 3,5-dichloro-N-(methoxyethyl)-2(1H)-pyrazinone. The 3-position is readily substituted with a benzyloxy group, and the pyrazinone is converted to ethyl 3-(benzyloxy)-N-(methoxyethyl)-2(1H)-pyridinone-4-carboxylate by a Diels-Alder cycloaddition with ethyl propiolate. Basic deprotection of the ester followed by activation, coupling to tren, and acidic deprotection of the benzyl groups gives the ligand TREN-MOE-3,2-HOPO (tris[(3-hydroxy-1-(methoxyethyl)- 2-oxo-1,2-didehydropyridine-4-carboxamido)ethyl]amine). The gadolinium complex of TREN-MOE-3,2-HOPO was prepared by metathesis, starting from gadolinium chloride. The solubility of the new metal complex is significantly enhanced. The four protonation constants (determined by potentiometry) for TREN-MOE-3,2-HOPO (log Ka1 = 8.08, log Ka2 = 6.85, log Ka3 = 5.81, log Ka4 = 4.98) are virtually identical to those reported for the parent ligand. The stability constants for the gadolinium complex of TREN-MOE-3,2-HOPO determined by potentiometry (log beta 110 = 19.69(2), log beta 111 = 22.80(2)) and by spectrophotometry (log beta 110 = 19.80(1), log beta 111 = 22.88(1), log beta 112 = 25.88(1)) differ slightly from those for the parent ligand; this follows from a change in the complexation model in which a new diprotonated species, [Gd(TREN-MOE-3,2-HOPO)(H)2]2+, was included. The presence of this extra species was demonstrated by factor analysis, comparison of spectral data, and nonlinear least-squares refinement. Significant formation of this species is observed between pH 3 and pH 1.5.
Efficient permutation instructions for fast software cryptography (2001)

Performing permutations in software can facilitate more widespread use of secure information processing and faster multimedia processing, but current instruction set architectures, even when augmented with subword-parallel multimedia instructions, do not provide efficient, bit-level software permutations. Four new instructions each offer a solution. They are: PPERM (a new, lower-cost version of PPERM3R that selects bits for one byte of the result); GRP (a permutation instruction that separates bits into left and right parts); CROSS (a permutation instruction using Benes interconnection network theory); and OMFLIP (a permutation instruction using enhanced Omega-Flip interconnection network theory).
Electrically produced artificial ventilation. (1988)

The induction of inspiration by delivering a burst of short-duration stimuli to body-surface electrodes is over a century old. The authors have used the term electroventilation to describe the technique. Inspiration can be produced with stimuli applied to electrodes placed bilaterally at the base of the neck, over the phrenic nerve motor points. Transchest electrodes placed anterior to the axillae can be used to stimulate the long thoracic and phrenic nerves. Paraxiphoid electrodes can be used to stimulate the phrenic nerves as they enter the diaphragm. With any of these electrode placements, inspired volumes in excess of spontaneous tidal volumes can be achieved in man, baboon, and dog. Of major importance is the need to use short-duration (less than 10-microseconds) pulses in the train of stimuli that produces contraction of the inspiratory muscles. The duration of inspiration is determined by the duration of the train, which is typically 0.5-1 s. The use of short-duration pulses minimizes the risk of producing cardiac arrhythmias and results in very little sensation at the skin.
Trackable and Targeted Phage as Positron Emission Tomography (PET) Agent for Cancer Imaging (2011)

In this report, we constructed a PET trackable nanoplatform based on phage particle and demonstrated the imaging capability of these targeted agents. We also demonstrated that the choice of chelator could have significant impact on imaging results of nano-agents. The method established in this research may be applicable to other receptor/ligand systems for theranostic agent construction, which could have an immediate and profound impact on the field of imaging/therapy and lay the foundation for the construction of next generation cancer specific theranostic agents.
Structural and Kinetic Analysis of Catalysis by a Thiamin Diphosphate-Dependent Enzyme, Benzoylformate Decarboxylase (2003)

Benzoylformate decarboxylase is a member of the family of enzymes that are dependent on the cofactor thiamin diphosphate. A structure of this enzyme binding (R)-mandelate, a competitive inhibitor, suggests that at least two hydrogen bonds are formed between the substrate, benzoylformate, and active site side chains. The first is between the carboxylate group of benzoylformate and the hydroxyl group of S26, and the second is between carbonyl group of the substrate and an imidazole nitrogen of H70. Steady-state kinetic studies indicate that the catalytic parameters are strongly affected in three active site mutants, S26A, H70A, and H281A. The K(m) of S26A was increased most dramatically, 25-fold more than that of the wild-type enzyme, while the K(i) of (R)-mandelate was increased 100-fold, suggesting that the serine hydroxyl is important for substrate binding. The k(cat) of H70A is reduced more than 3 orders of magnitude, strongly implicating this residue in catalysis, and H281 showed significant, but smaller magnitude, effects on both K(m) and k(cat). Stopped-flow experiments using an alternative substrate, p-nitrobenzoylformate, lead to kinetic resolution of the fate of key thiamin diphosphate-bound intermediates. Together, the experimental results suggest the following roles for residues in the active site. The residue H70 is important for the protonation of the 2-alpha-mandelyl-ThDP intermediate, thereby assisting in decarboxylation, and for the deprotonation of the 2-alpha-hydroxybenzyl-ThDP intermediate, aiding product release. H281 is involved in protonation of the enamine. Surprisingly, S26 appears to be involved not only in substrate binding but also in other steps of the reaction.
Study of early hematopoietic precursors in human cord blood. (1992)

Human cord blood is a source of transplantable stem cells. These stem cells express the antigen CD34, are resistant to treatment with 4-hydroperoxycyclophosphamide (CD34+/4-HCres), and do not give rise to colonies when plated in clonogenic assays. We studied the number of CD34+ cells present in cord blood and developed a two-step assay for early precursors (pre-colony-forming units, pre-CFU) capable of giving rise to committed progenitors. In this assay CD34+/4-HCres cord blood cells were cultured in suspension with different growth factors. After 7 days in suspension the remaining cells were plated in clonogenic assays, for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and mixed lineage colony-forming units (CFU-MIX), in the presence of pure factors or a combination of recombinant human (rh) interleukin 3 (IL-3) and medium conditioned by the PU34 primate cell line. Pre-CFU for all precursors were identified. These pre-CFU developed into committed progenitors in response to rhIL-3. The combinations of rhIL-3 plus rh interleukin 1 (IL-1) or rhIL-3 plus rh interleukin 6 (IL-6) did not enhance recovery of progenitors. The developing CFU-GM were responsive to rh granulocyte-macrophage colony-stimulating factor (GM-CSF) and rh granulocyte colony-stimulating factor (G-CSF) but much less so to rhIL-3. BFU-E and CFU-MIX developed in suspension but could only be detected when cells were replated in the presence of a combination of rhIL-3 and PU34 but not rhIL-3 alone. This assay may be useful in evaluating the number of early hematopoietic precursors present in cord blood samples and in defining growth factor combinations that could enhance hematopoietic recovery after cord blood stem cell transplants.
Perfluorocarbon temperature measurements using <sup>19</sup>F NMR (1992)

Measuring the T1 of the fluorine resonances of perfluorocarbons (PFC) is a unique method for monitoring oxygen tension in vivo. However, because T1 is also temperature sensitive, error in the pO2 determination due to animal-to-animal temperature variation may arise. Pathophysiologic conditions, such as ischemia, where temperature is not known a priori may also introduce error. Thus, measuring the PFC temperature is clearly desirable in order to correct for tissue temperature variations during the pO2 determination. Because the fluorine chemical shift of various fluorinated compounds has a significant temperature dependence, we evaluated the effect of temperature on the chemical shift of the fluorine resonances of perfluorotributylamine (FTBA). A linear relationship was found between chemical shift and temperature in vitro. In addition, the relative FTBA chemical shifts were essentially independent of pO2. Chemical shift temperature measurements in vivo, obtained from a 10 microL FTBA bubble in the preretinal vitreous space of the rabbit eye, were in good agreement (+/- 0.5 degrees C) with thermocouple measurements from the same location. Good agreement between the NMR determined temperature and core body temperature was also found. The implication of such temperature measurements for the ultimate accuracy of the pO2 determination based on PFC T1 measurements is discussed. To the best of our knowledge, this report describes the first absolute temperature measurement in vivo by NMR.
Pathogenesis of adrenocortical cancer (2010)

Adrenocortical cancer is a rare tumor with poor prognosis. Whereas most cases occur in a sporadic setting, there are very rare hereditary forms that are important for the understanding of tumor pathogenesis. The hereditary syndromes associated with adrenocortical cancer are: Li-Fraumeni's syndrome, Beckwith-Wiedemann's syndrome and familial adenomatous polyposis, whereas multiple endocrine neoplasia type 1, Carney's complex and McCune-Albright's syndrome mostly predispose to benign adrenocortical tumors. Overexpression of insulin like growth factor 2, activation of Wnt/beta-catenin and cAMP-protein kinase A signaling, as well as mutations of p53 and MEN1 genes are regarded as major pathogenetic mechanisms. Options for medical treatment of adrenocortical cancer are rather limited. Recently published molecular-bioinformatical studies have revealed several previously unknown pathogenetic pathways that may even represent potential drug targets. In this study, the pathogenesis of hereditary tumor syndromes, the alterations in sporadic tumors and the most recent molecular-bioinformatical observations are discussed.
Demonstration of a hybrid time/wavelength division multiplexed interferometric fibre sensor array (1991)

A 14-element interferometric sensor array based on a hybrid time/wavelength division addressing scheme is reported. The system uses two time-division addressed sub-arrays operating at 790 nm and 835 nm which are addressed via common input/output fibres using WDM couplers. Preliminary results obtained show crosstalk levels &lt; −50 dB electrical.
The Requirements of Concurrence of Actus Reus and Mens Rea in Homicide (2000)

The problem of non-concurrence in criminal law, with a brief discussion on the Shaiful Edham bin Adam case, is presented. The proposals of the Court of Appeal is assessed, and possible solutions are analysed. The moral congruence approach is suggested to be doctrinally more satisfactory.
Fast algorithm for list mode back-projection of Compton scatter camera data (1998)

A fast algorithm is presented for back-projection of Compton camera projection data in a list mode fashion, in which the number of operations per photon per image slice scales at less than the dimension N of the reconstructed image. The method focuses on the mesh of grid lines which delineate the pixels in the image, rather than on the pixels themselves, and involves computation of the intersection of back-projected Compton cones with just the outermost edges in the image and those grid lines near these image boundary intersection points, for each plane (or slice) of the image. Depending on the orientation of the back projected cone and the image space grid lines, between 4 and N+4 determinations (by quadratic solution) of cone/mesh intersections are required per image slice per photon. Thus the total number of floating point operations per image slice scales as 4 to N+4 times the number of detected photons. Three dimensional back-projections can be obtained simply by stepping through the sequence of planes in the image space parallel to the Compton aperture. Back-projected images are presented, using data generated by Monte Carlo simulations of a practical detector configuration and various source distributions.
Human semen and fertility regulation in men (1976)

Human semen and fertility regulation in men , Human semen and fertility regulation in men , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
A tissue sealant based on reactive multifunctional polyethylene glycol (2001)

A rapidly gelling synthetic tissue sealant was developed from tetra-succinimidyl and tetra-thiol-derivatized polyethylene glycol (PEG). The two reagents were dissolved in aqueous buffers at 20% (w/v) solids and sprayed on the tissue site, with the use of a sprayer/mixer device. Good adhesion to collagen membranes, PTFE grafts, and carotid artery was observed in vitro. In a burst test on collagen membranes with a 2-mm orifice defect, the gel sustained fluid pressures of 125 +/- 36 mm Hg (n = 18), fivefold greater than capillary blood pressure and one-half that observed in hypertension. On 0.4-mm-diameter puncture defects in PTFE grafts, pressures of 390-490 mm Hg were sustained, and on 0.6-0.9-mm puncture defects in carotid arteries, pressures of 490 to 840 mm Hg were sustained. In vitro data corresponded to results in vivo, where bleeding in rabbit arteries was stopped immediately in five out of six trials. A significant reduction in time to hemostasis and blood loss, compared to controls, was observed. Carotid artery and subcutaneous implant data in rabbits showed that the formula was compatible with biological tissue. Rapid gelling and effective sealing were dependent on the presence of active succinimidyl ester and thiol groups on PEG. HPLC and chemical substitution methods were useful in predicting whether batches of derivatized PEG would perform satisfactorily.
Cephalosporins having a heterocyclic catechol in the C3 side chain. I. Enhancement of efficacy against gram-negative bacteria. (1993)

Two groups of cephalosporins substituted with a variety of heterocyclic catechols in the C3 side chain were synthesized. One is a group of 3-(heterocyclic catechol-substituted methyl)cephalosporins and another is 3-[(E)-3-heterocyclic catechol-substituted 1-propen-1-yl]cephalosporins. Cephalosporins in the latter group showed higher in vivo efficacies than those in the former group having the same heterocyclic catechol, especially against Pseudomonas aeruginosa A9843A, although there was no significant difference between their in vitro activity. Among the latter group, the 5,6-dihydroxybenzimidazole derivative (6e) and the 2,6-dihydro-7-hydroxy-6-oxo- isoquinoline derivative (6b) showed much higher activity than ceftazidime (CAZ) and imipenem (IPM) against P. aeruginosa A9843A both in in vitro and in vivo studies.
Adeno-associated viruses undergo substantial evolution in primates during natural infections (2003)

Adeno-associated viruses (AAVs) are single-stranded DNA viruses that are endemic in human populations without known clinical sequelae and are being evaluated as vectors for human gene therapy. To better understand the biology of this virus, we examined a number of nonhuman primate species for the presence of previously uncharacterized AAVs and characterized their structure and distribution. AAV genomes were widely disseminated throughout multiple tissues of a variety of nonhuman primate species. Surprising diversity of sequence, primarily localized to hypervariable regions of the capsid protein, was detected. This diversity of sequence is caused, in part, by homologous recombination of co-infecting parental viruses that modify the serologic reactivity and tropism of the virus. This is an example of rapid molecular evolution of a DNA virus in a way that was formerly thought to be restricted to RNA viruses.
Corticotropin-Releasing Hormone Receptor Type 1 (<i>CRHR1</i>) Genetic Variation and Stress Interact to Influence Reward Learning (2011)

Stress is a general risk factor for psychopathology, but the mechanisms underlying this relationship remain largely unknown. Animal studies and limited human research suggest that stress can induce anhedonic behavior. Moreover, emerging data indicate that genetic variation within the corticotropin-releasing hormone type 1 receptor gene (CRHR1) at rs12938031 may promote psychopathology, particularly in the context of stress. Using an intermediate phenotypic neurogenetics approach, we assessed how stress and CRHR1 genetic variation (rs12938031) influence reward learning, an important component of anhedonia. Psychiatrically healthy female participants (n = 75) completed a probabilistic reward learning task during stress and no-stress conditions while 128-channel event-related potentials were recorded. Fifty-six participants were also genotyped across CRHR1. Response bias, an individual's ability to modulate behavior as a function of reward, was the primary behavioral variable of interest. The feedback-related positivity (FRP) in response to reward feedback was used as a neural index of reward learning. Relative to the no-stress condition, acute stress was associated with blunted response bias as well as a smaller and delayed FRP (indicative of disrupted reward learning) and reduced anterior cingulate and orbitofrontal cortex activation to reward. Critically, rs12938031 interacted with stress to influence reward learning: both behaviorally and neurally, A homozygotes showed stress-induced reward learning abnormalities. These findings indicate that acute, uncontrollable stressors reduce participants' ability to modulate behavior as a function of reward, and that such effects are modulated by CRHR1 genotype. Homozygosity for the A allele at rs12938031 may increase risk for psychopathology via stress-induced reward learning deficits.
<i>Ab initio</i> effective core potentials for molecular calculations. Potentials for the transition metal atoms Sc to Hg (1985)

Ab initio effective core potentials (ECP’s) have been generated to replace the Coulomb, exchange, and core-orthogonality effects of the chemically inert core electron in the transition metal atoms Sc to Hg. For the second and third transition series relative ECP’s have been generated which also incorporate the mass–velocity and Darwin relativistic effects into the potential. The ab initio ECP’s should facilitate valence electron calculations on molecules containing transition-metal atoms with accuracies approaching all-electron calculations at a fraction of the computational cost. Analytic fits to the potentials are presented for use in multicenter integral evaluation. Gaussian orbital valence basis sets are developed for the (3d,4s,4p), (4d,5s,5p), and (5d,6s,6p) orbitals of the first, second, and third transition series atoms, respectively. All-electron and valence-electron atomic excitation energies are also compared for the low-lying states of Sc–Hg, and the valence-electron calculations are found to reproduce the all-electron excitation energies (typically within a few tenths of an eV).