gebhart/patrepeval huggingface dataset:
USING THE FREE‐RESPONSE SCORING TOOL TO AUTOMATICALLY SCORE THE FORMULATING‐HYPOTHESES ITEM (1994)

ABSTRACT Large‐scale institutional testing, and testing in general, are in a period of rapid change. Among the more obvious dimensions is the growing use of constructed‐response items and of computer‐based testing. This study explores the potential for using a computer‐based scoring procedure for the formulating‐hypotheses item. This item type presents a situation and asks the examinee to generate explanations for it. Each explanation is judged right or wrong and the number of creditable explanations summed to produce an item score. Scores were generated for 30 examinees' responses to each of eight items by a semantic pattern‐matching program and independently by five human raters. On its initial scoring run, the program agreed highly with the raters' mean item scores for some questions and improved its concurrence substantially as modifications to the automatic scoring process were made. By the final run, correlations between the program and the raters on item scores ranged from .89 to .97, and mean human‐machine discrepancies ran from .6 to 1.1 on a 16‐point scale. At the individual‐hypothesis level, the proportion agreement ranged from .80 to .94, which, given the large disproportion of correct responses in the sample, was little better than chance. Also detected was a tendency on the part of the program to erroneously classify wrong responses as correct. We conclude that F‐H items might be more effectively scored by a semiautomatic system that combines machine processing with a small number of human judges, and we present a preliminary configuration for such a process.
Hantaviruses: A Global Disease Problem (1997)

Hantaviruses are carried by numerous rodent species throughout the world. In 1993, a previously unknown group of hantaviruses emerged in the United States as the cause of an acute respiratory disease now termed hantavirus pulmonary syndrome (HPS). Before than, hantaviruses were known as the etiologic agents of hemorrhagic fever with renal syndrome, a disease that occurs almost entirely in the Eastern Hemisphere. Since the discovery of the HPS-causing hantaviruses, intense investigation of the ecology and epidemiology of hantaviruses has led to the discovery of many other novel hantaviruses. Their ubiquity and potential for causing severe human illness make these viruses an important public health concern; we reviewed the distribution, ecology, disease potential, and genetic spectrum.
Simultaneous Quantification of Prostate-specific Antigen and Human Glandular Kallikrein 2 mRNA in Blood Samples from Patients with Prostate Cancer and Benign Disease (2002)

The presence of PC cells in the blood circulation is an early event in PC progression, and quantitative assays for PSA and hK2 mRNA discriminate benign from PC cases. Further studies are needed to determine the diagnostic accuracy and prognostic value of the assays.
The Structural Basis of Ribosome Activity in Peptide Bond Synthesis (2000)

Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli) playing the same general base role as histidine-57 in chymotrypsin. The unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.
EFNS guidelines on the treatment of cluster headache and other trigeminal‐autonomic cephalalgias (2006)

Cluster headache and the other trigeminal-autonomic cephalalgias [paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome] are rare but very disabling conditions with a major impact on the patient's quality of life. The objective of this study was to give evidence-based recommendations for the treatment of these headache disorders based on a literature search and consensus amongst a panel of experts. All available medical reference systems were screened for any kind of studies on cluster headache, paroxysmal hemicrania and SUNCT syndrome. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies resulting in level A, B or C recommendations and good practice points. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7 l/min over 15 min and 6 mg subcutaneous sumatriptan are drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability). Although no class I or II trials are available, steroids are clearly effective in cluster headache. Therefore, the use of at least 100 mg methylprednisone (or equivalent corticosteroid) given orally or at up to 500 mg i.v. per day over 5 days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as alternative treatments. Surgical procedures, although in part promising, require further scientific evaluation. For paroxysmal hemicranias, indomethacin at a daily dose of up to 225 mg is the drug of choice. For treatment of SUNCT syndrome, large series suggest that lamotrigine is the most effective preventive agent, with topiramate and gabapentin also being useful. Intravenous lidocaine may also be helpful as an acute therapy when patients are extremely distressed and disabled by frequent attacks.
AMP-Activated Protein Kinase: Possible Target for Treatment of Type 2 Diabetes (2000)

A considerable amount of data have accumulated showing that contraction of muscle has an acute insulin-like effect, triggering the uptake of glucose. Chronic muscle contraction, as seen in endurance training has effects on insulin sensitivity, enhancing the effect of insulin on glucose uptake. Endurance training results in an increase in levels of GLUT4 in the muscle. This increase in GLUT4 is thought to be responsible in part for the enhancement of insulin sensitivity. Recent experiments have demonstrated that acute and chronic effects of muscle contraction on glucose uptake and the increase in GLUT4 may be due to activation of a protein kinase, AMP-activated protein kinase (AMPK). This kinase is activated by the increase in 5'-AMP and the decline in creatine phosphate that occur during muscle contraction. Phosphorylated AMPK then presumably phosphorylates undefined target proteins, which in turn increase glucose uptake and transcription of the GLUT4 gene. Experiments have demonstrated that this kinase, normally activated during exercise, can be activated artificially in muscle by injecting non-exercising rats with 5-aminoimidazole-4-carboxamide-riboside (AICAR), an adenosine analog. AICAR is taken up into muscle and phosphorylated to form an analog of 5'-AMP. Acute (stimulation of glucose uptake into muscle) and chronic (increase in GLUT4) effects of exercise can be reproduced by injection of this drug. These observations open the door to the possibility of treatment of patients with type 2 diabetes with AMPK activators.
Functional reconstitution of a purified proline permease from Candida albicans: interaction with the antifungal cispentacin (1997)

We have purified proline permease to homogeneity from Candida albicans using an L-proline-linked agarose matrix as an affinity column. The eluted protein produced two bands of 64 and 67 kDa by SDS-PAGE, whereas it produced a single band of 67 kDa by native PAGE and Western blotting. The apparent Km for L-proline binding to the purified protein was 153 microM. The purified permease was reconstituted into proteoliposomes and its functionality was tested by imposing a valinomycin-induced membrane potential. The main features of L-proline transport in reconstituted systems, viz. specificity and sensitivity to N-ethylmaleimide, were very similar to those of intact cells, The antifungal cispentacin, which enters C. albicans cells via an inducible proline permease, competitively inhibited the L-proline binding and translocation in reconstituted proteoliposomes. However, the uptake of L-proline in proteoliposomes reconstituted with the purified protein displayed monophasic kinetics with an apparent Km of 40 microM.
Energy and Exergy Analyses of Thin-Layer Drying of Pineapple Slices (2017)

Energy and exergy analyses of thin-layer drying of pineapple slices (Ananas comosus L.) were conducted in a laboratory tunnel dryer. Drying experiments were carried out at three temperatures (100, 115 and 130 °C) and an air velocity of 1.45 m/s. The effects of drying variables on energy utilisation, energy utilisation ratio, exergy loss and exergy efficiency were studied. The enthalpy difference of the gas increased as the inlet gas temperature increase. It is observed that at the 75 minutes of the drying process the outlet gas enthalpy achieves a maximum value that is very close to the inlet value and remains constant until the end of the drying process. This behaviour is due to the reduction of the total enthalpy within the system, or in other words, the reduction of the effective heat transfer from the hot gas flow to the vegetable being dried. Further, the outlet entropy exhibits a significant increase that is not only due to the temperature variation, but also to the increase of water vapour phase contained in the hot gas flow. The maximum value of the exergy efficiency curve corresponds to the maximum value observed within the drying rate curves. This maximum value represents the stage when the available energy is efficiently used in the removal of the moisture within the solid. As the drying rate decreases, the available energy is started to be less employed. The exergetic efficiency was directly dependent on the evaporation flux and since the convective drying is less efficient that other types of dryer, it is likely that the exergetic efficiency has relatively low values.
Behavior of varroa mites in worker brood cells of Africanized honey bees (2009)

The ectoparasitic mite Varroa destructor is currently the most important pest of the honey bee, Apis mellifera. Because mite reproduction occurs within the sealed cell, the direct observation of varroa activity inside the cell is difficult. A video observation method using transparent polystyrol cells containing infested brood was used to analyze the behavior of varroa mites in worker brood of Africanized honey bees. We recorded how mites feed on the larva and pupa, construct a fecal accumulation site and how the bee larva carried out some longitudinal movements around the cell. The feeding activity of the foundress mite varies during the course of the cycle. On the prepupa mites were found to feed often (0.3 +/- 0.2 bouts h(-1)) for a period of 8.7 +/- 8.4 min h(-1) and there was no preference for a specific segment as feeding site. On the opposite, during the pupal stage mites fed less often (0.1 +/- 0.1 bouts h(-1)) for a period of 6.2 +/- 4.0 min h(-1) and almost always at a particular site (92.4%). On pupa, 83.7% of the feeding was on the 2nd abdominal segment (n = 92), and only few perforations were found on the thorax. Varroa shows a preference for defecation in the posterior part of the cell (cell apex), close to the bee's anal zone. We found a high correlation between the position of the feeding site on the pupa and the position of the fecal accumulation on the cell wall. Most infested cells have only one fecal accumulation site and it was the favorite resting site for the mite, where it spent 24.3 +/- 3.9 min h(-1). Longitudinal displacements were observed in 28.0% (n = 25) of the analyzed bee larvae. Turning movements around the cell, from the bottom to the top, were carried out by these larvae, mainly during the second day (47.7 +/- 22.5 min h(-1)), just before pupation, with a total time of 874.9 +/- 262.2 min day(-1) (n = 7 individuals). These results in worker brood of Africanized bees demonstrate adaptations of varroa mites to parasitizing the developing bee inside the capped brood cells.
Potential bile acid metabolites. XV. Synthesis of 4.BETA.-hydroxylated bile acids; unique bile acids in human fetal bile. (1989)

The 4 beta-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, and cholic acids were synthesized from their respective parent compounds. The principal reactions employed were 1) beta-face cis-dihydroxylation of delta 3 intermediates with osmium tetroxide-N-methylmorpholine N-oxide, 2) selective cathylation of vicinal 3 beta,4 beta-diols followed by oxidation of the resulting 4 beta-monocathylates, or direct selective oxidation at C-3 of 3 beta,4 beta-diols with pyridinium chlorochromate, and 3) stereoselective reduction of the 3-oxo compounds with tert-butylamine-borane complex. The results of analysis of the prepared 4 beta-hydroxylated bile acids with a diequatorial trans-glycol structure and their 3 beta-epimers by proton and carbon-13 nuclear magnetic resonance spectroscopies are briefly discussed along with the mass spectrometric properties.
Human cells compromised for p53 function exhibit defective global and transcription-coupled nucleotide excision repair, whereas cells compromised for pRb function are defective only in global repair (1999)

After exposure to DNA-damaging agents, the p53 tumor suppressor protects against neoplastic transformation by inducing growth arrest and apoptosis. A series of investigations has also demonstrated that, in UV-exposed cells, p53 regulates the removal of DNA photoproducts from the genome overall (global nucleotide excision repair), but does not participate in an overlapping pathway that removes damage specifically from the transcribed strand of active genes (transcription-coupled nucleotide excision repair). Here, the highly sensitive ligation-mediated PCR was employed to quantify, at nucleotide resolution, the repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in genetically p53-deficient Li-Fraumeni skin fibroblasts, as well as in human lung fibroblasts expressing the human papillomavirus (HPV) E6 oncoprotein that functionally inactivates p53. Lung fibroblasts expressing the HPV E7 gene product, which similarly inactivates the retinoblastoma tumor-suppressor protein (pRb), were also investigated. pRb acts downstream of p53 to mediate G(1) arrest, but has no demonstrated role in DNA repair. Relative to normal cells, HPV E6-expressing lung fibroblasts and Li-Fraumeni skin fibroblasts each manifested defective CPD repair along both the transcribed and nontranscribed strands of the p53 and/or c-jun loci. HPV E7-expressing lung fibroblasts also exhibited reduced CPD removal, but only along the nontranscribed strand. Our results provide striking evidence that transcription-coupled repair, in addition to global repair, are p53-dependent in UV-exposed human fibroblasts. Moreover, the observed DNA-repair defect in HPV E7-expressing cells reveals a function for this oncoprotein in HPV-mediated carcinogenesis, and may suggest a role for pRb in global nucleotide excision repair.
A New Class of Dimeric α-Interferons (IFN-α) Made by the Dock and Lock (DNL) Method for Improved Cancer Therapy. (2007)

Abstract Background: IFN-α2 is indicated for the therapy of hairy cell leukemia, chronic myelogenous leukemia, follicular lymphoma, and malignant melanoma. As is the case for most cytokines, the pharmacokinetic (PK) properties of IFN-α2 are critical for dosing and efficacy. In vivo, the protein is quickly degraded, diffuses widely throughout the body, and has a rapid rate of renal clearance. Pegylation of IFN-α2 significantly increases the serum half-life and reduces renal clearance, thus enhancing its efficacy. However, established pegylation of IFN-α2 results in a mixture of positional isomers and reduced in vitro activity, as known for PEGASYS (Roche) and PEG-INTRON (Schering-Plough). Methods: To improve the PK properties and the potency, the DNL method (Rossi et al. Proc. Natl. Acad. Sci. USA, 2006,103:6841) was used to generate novel agents having two copies of IFN-α2b conjugated to polyethylene glycol (PEG). Results: A fusion protein (DDD2-IFN-α2b) composed of IFN-α2b with a dimerization-and-docking domain (DDD2) and a six-His tag was expressed both in myeloma cells and in E. coli. Two PEG-based modules, each composed of a fluorescent molecule, an anchor domain (AD) and either a 20-kDa PEG (IMP362) or a 30-kDa PEG (IMP413), were synthesized. Combining DDD2-IFN-α2b and IMP362 or IMP413 under redox conditions resulted in the desirable DNL conjugates consisting of two copies of IFN-α2b and one PEG linked site-specifically via the DDD and AD interaction. The cytotoxic activity of DDD2-IFN-α2b on Daudi lymphoma cells was similar to that of commercially available recombinant IFN-α2 (rhIFN-α2). The purity and identity of the two DNL conjugates (α2b-413 and α2b-362) were demonstrated by SDS-PAGE, immunoblotting, and fluorescence imaging. Both also showed potent cytotoxic activity on Daudi cells in vitro and superior PK properties to PEG-INTRON. For example, the mean blood residence times for α2b-362 (10.3 h) and α2b-413 (21.7 h) were significantly longer than those of rhIFN-α2 (0.7 h) and PEG-INTRON (5.1 h). Initial studies in mice bearing Daudi xenografts showed a significant therapeutic advantage over PEG-INTRON for both α2b-362 and α2b-413. Animals given 14,000 IU of PEG-INTRON had a median survival (MS) of 32 days compared to 21 days for saline control, whereas those receiving α2b-362 at 14,000 IU, 7,000 IU and 3,500 IU resulted in MS of 45, 41 and 32 days, respectively. More remarkably, α2b-413 was the most effective, achieving MS of 46, &gt;53, and &gt;53 days with 3,500 IU, 7,000 IU and 14,000 IU, respectively, all statistically significant improvements (P&lt; 0.0028) compared to PEG-INTRON given at each equivalent activity. Conclusions: The DNL method provides a novel pegylation strategy for generating a dimeric IFN-α2b that is linked site-specifically to a single PEG at the predetermined location. Since the resulting conjugates exhibit improved PK and efficacy in a Burkitt lymphoma model, they may represent a new class of interferons for use in cancer and infectious disease therapy.
Single-copy transduction and expression of human gamma-globin in K562 erythroleukemia cells using recombinant adeno-associated virus vectors: the effect of mutations in NF-E2 and GATA-1 binding motifs within the hypersensitivity site 2 enhancer [published erratum appears in Blood 1995 Feb 1;85(3):862] (1993)

The use of recombinant adeno-associated virus (rAAV) vectors provides a new strategy to investigate the role of specific regulatory elements and trans-acting factors in globin gene expression. We linked hypersensitivity site 2 (HS2) from the locus control region (LCR) to a A gamma-globin gene (A gamma*) mutationally marked to allow its transcript to be distinguished from endogenous gamma-globin mRNA. The vector also contains the phosphotransferase gene that confers resistance to neomycin (NeoR). HS2 region mutations within the NF-E2 motifs prevented NF-E2 binding while preserving AP-1 binding. Another set in the GATA-1 motif prevented binding of the factor. Several NeoR K562 clones containing a single unrearranged RAAV genome with the A gamma* gene linked to the native HS2 core fragment (WT), mutant NF-E2 HS2 (mut-NFE2), mutant GATA-1 HS2 (mut-GATA1), or no HS [(-)HS] were identified. In uninduced K562 cells, mut-NFE2 clones expressed A gamma* mRNA at the same level as the WT clones, compared with a lack of A gamma* signal in the (-)HS2 clones. However, hemin induction of mut-NFE2 clones did not result in an increase in the A gamma* signal above the level seen in uninduced cells. Mut-GATA1 clones expressed the A gamma* mRNA at the same level as WT clones in both uninduced and induced cells. Thus, GATA-1 binding to this site does not appear to be required for the enhancing function of HS2 in this context. This single-copy rAAV transduction model is useful for evaluating the effects of specific mutations in regulatory elements on the transcription of linked genes.
The addition of bryostatin 1 to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy improves response in a CHOP-resistant human diffuse large cell lymphoma xenograft model. (2000)

The incidence of non-Hodgkin's lymphoma has been increasing at a rate of 4% per year since 1950; more than 62,000 cases will be diagnosed in the United States in 2000. Diffuse large cell lymphoma (DLCL) is the prototype of curable non-Hodgkin's lymphoma. Empirically designed chemotherapy regimens did not increase the cure rate of 30-40% achieved by the original four-drug regimen introduced in the 1970s [cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)]. We studied the antitumor effects of the CHOP regimen alone or in combination with a unique protein kinase C activator, bryostatin 1, on a xenograft model for resistant DLCL in mice with severe combined immune deficiency (WSU-DLCL2-SCID). In this model, the efficacy of bryostatin 1 given at 75 microg/kg, i.p., alone for 1 or 2 days [B(1x) and B(2x)]was compared with the efficacy of CHOP alone, bryostatin 1 + CHOP (B+CHOP) given concurrently, bryostatin 1 for 1 day followed by CHOP on day 2 [B(1x)-CHOP], and bryostatin 1 for 2 days followed by CHOP on day 3 [B(2x)-CHOP]. CHOP doses were as follows: (a) cyclophosphamide, 40 mg/kg, i.v.; (b) doxorubicin, 3.3 mg/kg, i.v.; (c) vincristine, 0.5 mg/kg, i.v.; and (d) prednisone, 0.2 mg/kg, every day for 5 days, p.o. Tumor growth inhibition (T/C), tumor growth delay (T-C), and log10 kill for B(1x), B(2x), CHOP, B+CHOP, B(1x)-CHOP and B(2x)-CHOP were 49%, 39%, 25.8%, 15.1%, 14.6%, and 12%; 6, 7, 16, 25, 12, and 15 days; and 0.6, 0.5, 2.2, 3.6, 1.7, and 2.0, respectively. To begin elucidating the mechanism whereby bryostatin 1 potentiated the effects of CHOP in the mouse model; we studied the effect of bryostatin 1 on Bax, Bcl-2, and poly(ADP-ribose) polymerase proteins in vitro and in vivo. Bax protein increased in a time-dependent manner without any measurable change in Bcl-2 expression. However, significant cleavage of the preapoptotic marker poly(ADP-ribose) polymerase was not recorded, and the percentage of apoptotic cells detected by flow cytometry increased only slightly (approximately 8%) after 96 h of bryostatin 1 exposure. The in vitro and in vivo results emphasize the superiority of combining bryostatin 1 with the CHOP regimen against the WSU-DLCL2 model. One possible mechanism may be the modulatory effects of bryostatin 1 on the Bax:Bcl-2 family of apoptosis-regulatory proteins. The use of this combination should be further explored clinically in the treatment of lymphoma.