gebhart/patrepeval huggingface dataset:
Serological diagnosis of hantavirus infections by an enzyme-linked immunosorbent assay based on detection of immunoglobulin G and M responses to recombinant nucleocapsid proteins of five viral serotypes (1997)

Worldwide, hantaviruses cause more than 100,000 human infections annually. Rapid and accurate methods are important both in monitoring acute infections and for epidemiological studies. We and others have shown that the amino termini of hantavirus nucleocapsid proteins (Ns) are sensitive tools for the detection of specific antibodies in hantavirus disease. Accordingly, we expressed truncated Ns (amino acids 1 to 117) in Escherichia coli from the five hantaviruses known to be pathogenic to man; Hantaan (HTN), Seoul (SEO), Dobrava (DOB), Sin Nombre (SN), and Puumala (PUU) viruses. In order to obtain pure antigens for use in an enzyme-linked immunosorbent assay (ELISA), the recombinant proteins were purified by polyhistidine-metal chelate affinity chromatography. Polyclonal animal antisera and a panel of serum specimens from hantavirus-infected individuals from Scandinavia, Slovenia, Russia, Korea, China, and the United States were used to evaluate the usefulness of the method. With both human and animal sera, it was possible to designate the antibody response into two groups: those with HTN, SEO, and DOB virus reactivity on the one hand and those with SN and PUU virus reactivity on the other. In sera from Scandinavia, European Russia, and the United States, the antibody response was directed mainly to the PUU and SN virus group. The sera from Asia reacted almost exclusively with the HTN, SEO, and DOB types of viruses. This was true for both the immunoglobulin M (IgM) and IgG antibody responses, indicating that this type of discrimination can be done during the acute phase of hantavirus infections. Both the HTN, SEO, and DOB virus and the PUU and SN virus types of antibody response patterns were found in patients from the Balkan region (Solvenia).
INTRAVESICAL RESINIFERATOXIN VERSUS BOTULINUM-A TOXIN INJECTIONS FOR NEUROGENIC DETRUSOR OVERACTIVITY: A PROSPECTIVE RANDOMIZED STUDY (2004)

In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients. Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin.
Investigational treatments for Type 2 diabetes mellitus: exenatide and liraglutide (2006)

Although a number of compounds are currently used to treat Type 2 diabetes mellitus, achieving a sustained glycaemic control over time is often not possible using oral antidiabetics. Endogenous incretins exhibit beneficial effects that could be useful for Type 2 diabetes mellitus treatment, such as stimulating insulin secretion during hyperglycaemia, improving β-cell mass and function, reducing glucagon secretion, delaying gastric emptying, reducing postprandial hyperglycaemia and diminishing body weight; however, their short half-life makes them unsuitable for treatment. Incretin mimetics such as liraglutide and exenatide were developed to overcome this limitation. This review discusses the effects of these compounds and their potential as a new class of antidiabetic agents.
Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer. (1996)

IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.
Physiological and Pathophysiological Implications of Upper Airway Reflexes in Humans. (2000)

The upper airway is a vital part of the respiratory tract. Although the upper airway serves several functions, protection of the airway and preservation of airway patency are the most essential functions subserved by upper airway reflexes. Various types of nerve endings have been identified in and under the epithelium of the upper airway, and afferent nerve endings are the natural starting of all reflex activity. The upper airway reflexes consist of many different types of reflex responses such as sneezing, apnea, swallowing, laryngeal closure, coughing, expiration reflex, and negative pressure reflex. Although the activation of upper airway reflexes does not necessarily occur at one particular site of the respiratory tract, individual reflex response is usually considered to be highly specific for the particular respiratory site which has been affected. The upper airway reflexes are modified by many factors such as sleep, anesthesia, and background chemical ventilatory drive. Both depression and exaggeration of upper airway reflexes cause clinical problems. Depression of upper airway reflexes enhances the chance of pulmonary aspiration and compromises the maintenance of the airway, whereas exaggeration of airway reflexes such as laryngospasm and prolonged paroxysm of cough can be harmful and dangerous. In this review, various aspects of upper airway reflexes are discussed focusing on the functions of upper airway reflexes in humans and some pathophysiological problems related to clinical medicine.
Proprotein-processing endoproteases PC6 and furin both activate hemagglutinin of virulent avian influenza viruses (1994)

Among the proprotein-processing subtilisin-related endoproteases, furin has been a leading candidate for the enzyme that activates the hemagglutinin (HA) of virulent avian influenza viruses. In the present study, we examined the cleavage activity of two other recently isolated ubiquitous subtilisin-related proteases, PACE4 and PC6, using wild-type HA of A/turkey/Ireland/1378/83 (H5N8) and a series of its mutant HAs. Vaccinia virus-expressed wild-type HA was not cleaved in human colon adenocarcinoma LoVo cells, which lack active furin. This processing defect was corrected by the expression of furin and PC6 but not of PACE4 and a control wild-type vaccinia virus. PC6 showed a sequence specificity similar to that with the endogenous proteases in cultured cells. When LoVo cells were infected with a virulent avian virus, A/turkey/Ontario/7732/66 (H5N9), only noninfectious virions were produced because of the lack of HA cleavage. However, when the cells were coinfected with vaccinia virus that expressed either furin or PC6, the avian virus underwent multiple cycles of replication, indicating that both furin and PC6 specifically cleave the virulent virus HA at the authentic site. These data suggest that PC6, as well as furin, can activate virulent avian influenza viruses in vivo, implying the presence of multiple HA cleavage enzymes in animals.
Biological screening of Brazilian medicinal plants (2000)

In this study, we screened sixty medicinal plant species from the Brazilian savanna ("cerrado") that could contain useful compounds for the control of tropical diseases. The plant selection was based on existing ethnobotanic information and interviews with local healers. Plant extracts were screened for: (a) molluscicidal activity against Biomphalaria glabrata, (b) toxicity to brine shrimp (Artemia salina L.), (c) antifungal activity in the bioautographic assay with Cladosporium sphaerospermum and (d) antibacterial activity in the agar diffusion assay against Staphylococcus aureus, Escherichia coli, Bacillus cereus and Pseudomonas aeruginosa. Forty-two species afforded extracts that showed some degree of activity in one or more of these bioassays.
SNS/PN3 and SNS2/NaN sodium channel‐like immunoreactivity in human adult and neonate injured sensory nerves (2000)

Two tetrodotoxin-resistant voltage-gated sodium channels, SNS/PN3 and SNS2/NaN, have been described recently in small-diameter sensory neurones of the rat, and play a key role in neuropathic pain. Using region-specific antibodies raised against different peptide sequences of their alpha subunits, we show by Western blot evidence for the presence of these channels in human nerves and sensory ganglia. The expected fully mature 260 kDa component of SNS/PN3 was noted in all injured nerve tissues obtained from adults; however, for SNS2/NaN, smaller bands were found, most likely arising from protein degradation. There was increased intensity of the SNS/PN3 260 kDa band in nerves proximal to the site of injury, whereas it was decreased distally, suggesting accumulation at sites of injury; all adult patients had a positive Tinel's sign at the site of nerve injury, indicating mechanical hypersensitivity. Injured nerves from human neonates showed similar results for both channels, but neonate neuromas lacked the SNS2/NaN 180 kDa molecular form, which was strongly present in adult neuromas. The distribution of SNS/PN3 and SNS2/NaN sodium channels in injured human nerves indicates that they represent targets for novel analgesics, and could account for some differences in the development of neuropathic pain in infants.
Identification and characterization of subpopulations in undifferentiated ES cell culture (2008)

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass (ICM) and the epiblast, and have been suggested to be a homogeneous population with characteristics intermediate between them. These cells express Oct3/4 and Rex1 genes, which have been used as markers to indicate the undifferentiated state of ES cells. Whereas Oct3/4 is expressed in totipotent and pluripotent cells in the mouse life cycle, Rex1 expression is restricted to the ICM, and is downregulated in pluripotent cell populations in the later stages, i.e. the epiblast and primitive ectoderm (PrE). To address whether ES cells comprise a homogeneous population equivalent to a certain developmental stage of pluripotent cells or a heterogeneous population composed of cells corresponding to various stages of differentiation, we established knock-in ES cell lines in which genes for fluorescent proteins were inserted into the Rex1 and Oct3/4 gene loci to visualize the expression of these genes. We found that undifferentiated ES cells included at least two different populations, Rex1(+)/Oct3/4(+) cells and Rex1(-)/Oct3/4(+) cells. The Rex1(-)/Oct3/4(+) and Rex1(+)/Oct3/4(+) populations could convert into each other in the presence of LIF. In accordance with our assumption that Rex1(+)/Oct3/4(+) cells and Rex1(-)/Oct3/4(+) cells have characteristics similar to those of ICM and early-PrE cells, Rex1(+)/Oct3/4(+) cells predominantly differentiated into primitive ectoderm and contributed to chimera formation, whereas Rex1(-)/Oct3/4(+) cells differentiated into cells of the somatic lineage more efficiently than non-fractionated ES cells in vitro and showed poor ability to contribute to chimera formation. These results confirmed that undifferentiated ES cell culture contains subpopulations corresponding to ICM, epiblast and PrE.
Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. (1994)

Vitamin C supplementation is effective in reducing sorbitol accumulation in the erythrocytes of diabetics. Given its tissue distribution and low toxicity, we suggest a superiority for vitamin C over pharmaceutic ARIs.
Origins of netropsin binding affinity and specificity: correlations of thermodynamic and structural data. (1987)

We report complete thermodynamic profiles for netropsin binding to an oligomeric and to several polymeric DNA host duplexes. These data allow us to reach the following conclusions: netropsin binding by deep penetration into the minor groove is overwhelmingly enthalpy driven and exhibits a very high binding affinity (K approximately 10(9) at 25 degrees C); deep penetration into the minor groove is required to form those drug-DNA interactions responsible for the enthalpy-driven high binding affinity of netropsin; I-C base pairs form binding sites for netropsin that thermodynamically are equivalent to those formed by A-T base pairs; the positive binding entropies reflect entropic contributions from molecular events other than just water spine disruption; the thermodynamic binding data primarily reflect local netropsin-DNA interactions rather than long-range binding-induced conformational changes at regions distant from the binding site; the enhanced binding affinity associated with deep penetration of netropsin into the minor groove does not result from more favorable electrostatic interactions; the binding of netropsin to the central AATT core of the decamer duplex [d(GCGAATTCGC)]2 is thermodynamically modeled best by netropsin binding to the poly[d(AT)].poly[d(AT)] duplex rather than the poly(dA).poly(dT) duplex. We propose correlations between our thermodynamic data and specific molecular interactions defined by NMR and x-ray structural studies on similar and identical drug-DNA complexes.
Drosophila drop-dead mutations accelerate the time course of age-related markers (1997)

Mutations of the drop-dead gene in Drosophila melanogaster lead to striking early death of the adult animal. At different times, after emergence from the pupa, individual flies begin to stagger and, shortly thereafter, die. Anatomical examination reveals gross neuropathological lesions in the brain. The life span of flies mutant for the drop-dead gene is four to five times shorter than for normal adults. That raises the question whether loss of the normal gene product might set into motion a series of events typical of the normal aging process. We used molecular markers, the expression patterns of which, in normal flies, change with age in a manner that correlates with life span. In the drop-dead mutant, there is an acceleration in the temporal pattern of expression of these age-related markers.
VIRAL SERINE PROTEINASE INHIBITOR (SERP-1) EFFECTIVELY DECREASES THE INCIDENCE OF GRAFT VASCULOPATHY IN HETEROTOPIC HEART ALLOGRAFTS1 (2001)

Treatment of allograft recipients with SERP-1 in combination with CsA early after transplantation significantly decreases the incidence of GVD when compared to grafts treated with only CsA. These results demonstrate the clinical potential for this novel serine protease inhibitor to prevent GVD in solid organ transplantation.
Instruction set definition and instruction selection for ASIPs (1994)

Application Specific Instruction set Processors (ASIPs) are field or mask programmable processors of which the architecture and instruction set are optimised to a specific application domain. ASIPs offer a high degree of flexibility and are therefore increasingly being used in competitive markets like telecommunications. However, adequate CAD techniques for the design and programming of ASIPs are missing hitherto. An interactive approach for the definition of optimised microinstruction sets of ASIPs is presented. A second issue is a method for instruction selection when generating code for a predefined ASIP. A combined instruction set and data-path model is generated, onto which the application is mapped. >
Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours (2005)

BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor (VEGFR) inhibitor that targets tumour cell proliferation and tumour angiogenesis. This Phase I study was undertaken to determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and tumour response profile of oral BAY 43-9006 in patients with advanced, refractory solid tumours. BAY 43-9006 was administered daily for repeated cycles of 21 days on/7 days off. A total of 44 patients were enrolled at doses from 50 to 800 mg b.i.d. Pharmacokinetic profiles of BAY 43-9006 in plasma were determined during the first treatment cycle. The most frequently reported adverse events over multiple cycles were gastrointestinal (75%), dermatologic (71%), constitutional (68%), pain (64%), or hepatic (61%) related. A MTD of 400 mg b.i.d. BAY 43-9006 was defined. BAY 43-9006 was absorbed rapidly; steady-state conditions were reached within 7 days. BAY 43-9006 exposure increased nonproportionally with increasing dose. In all, 32 patients were evaluated for tumour response: 15 patients showed tumour progression, 16 patients experienced stable disease (>6 months in eight patients), and one patient with renal cell carcinoma achieved a partial response. BAY 43-9006 given for 21 days with 7 days off treatment was safe, well tolerated, and showed antitumour activity.
Nanomolar concentrations of Bowman-Birk soybean protease inhibitor suppress x-ray-induced transformation in vitro. (1985)

Experiments reported here indicate a crude soybean extract, if defatted with acetone, effectively blocks cell transformation in vitro. An active component of this crude extract is the Bowman-Birk trypsin and chymotrypsin inhibitor. The chymotrypsin-inhibitory region of the Bowman-Birk inhibitor is responsible for suppressing in vitro transformation. Another low molecular weight soybean trypsin inhibitor does not significantly suppress transformation. The Bowman-Birk inhibitor (i) has an irreversible effect on the transformation process, (ii) can suppress radiation-induced transformation even when added to cultures many days after the carcinogen exposure, and (iii) is effective in its ability to suppress transformation when present in the medium at a concentration as low as 0.125 nM.
Co-transfer of plasmids in association with conjugative transfer of mupirocin or mupirocin and penicillin resistance in methicillin-resistant Staphylococcus aureus (2000)

Two distinct strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients in a dermatology ward were also resistant to mupirocin. The mupirocin resistance plasmids from both strains were indistinguishable by EcoRI and HindIII restriction digest analysis, except for the presence of genes apparently mediating penicillinase production in some transconjugants. Conjugative transfer of the plasmid mediating mupirocin resistance from one of these strains to a recipient S. aureus was accompanied in some cases by co-transfer of plasmids mediating resistance to tetracycline or erythromycin; in some instances a plasmid which possessed no apparent resistance markers was also transferred. The second strain demonstrated conjugative transfer of penicillin and mupirocin resistance as well as transfer of a plasmid mediating gentamicin resistance, but transfer of erythromycin resistance was not apparently plasmid-mediated.
Ultralight Multiwalled Carbon Nanotube Aerogel (2010)

Ultralight multiwalled carbon nanotube (MWCNT) aerogel is fabricated from a wet gel of well-dispersed pristine MWCNTs. On the basis of a theoretical prediction that increasing interaction potential between CNTs lowers their critical concentration to form an infinite percolation network, poly(3-(trimethoxysilyl) propyl methacrylate) (PTMSPMA) is used to disperse and functionalize MWCNTs where the subsequent hydrolysis and condensation of PTMSPMA introduces strong and permanent chemical bonding between MWCNTs. The interaction is both experimentally and theoretically proven to facilitate the formation of a MWCNT percolation network, which leads to the gelation of MWCNT dispersion at ultralow MWCNT concentration. After removing the liquid component from the MWCNT wet gel, the lightest ever free-standing MWCNT aerogel monolith with a density of 4 mg/cm(3) is obtained. The MWCNT aerogel has an ordered macroporous honeycomb structure with straight and parallel voids in 50-150 μm separated by less than 100 nm thick walls. The entangled MWCNTs generate mesoporous structures on the honeycomb walls, creating aerogels with a surface area of 580 m(2)/g which is much higher than that of pristine MWCNTs (241 m(2)/g). Despite the ultralow density, the MWCNT aerogels have an excellent compression recoverable property as demonstrated by the compression test. The aerogels have an electrical conductivity of 3.2 × 10(-2) S·cm(-1) that can be further increased to 0.67 S·cm(-1) by a high-current pulse method without degrading their structures. The excellent compression recoverable property, hierarchically porous structure with large surface area, and high conductivity grant the MWCNT aerogels exceptional pressure and chemical vapor sensing capabilities.
Damage produced by ion mplantation in silicon (1970)

Abstract Silicon specimens were irradiated with Ne+, B+, P+ and Sb+ ions. The energy was 80kV, and the doses in the range 1013 to 1016 ions/cm2. The resulting structural damage was investigated by both scanning and transmission electron microscopy. The SEM electron channelling pattern method was used to determine the variation of gross damage with ion type, dose, depth below the surface, and annealing treatment. The TEM method was used to study the detailed nature of the defects formed by the annealing. These included dislocations, rod-like structures, micro-twins, semi-polycrystalline material, misoriented zones, etc. The results are briefly compared with known electrical properties of implanted silicon, and some correlations noted.
Analysis of the Yield of Phase II Combination Therapy Trials in Medical Oncology (2010)

The contributory value of combination chemotherapy phase II trials done by 2001-2002 standards is low despite the participation of more than 16,000 subjects. Future phase II studies of combination regimens require better methods to screen for treatments most likely to improve standards of care.
Prevalence of prostate cancer (PC) clinical states (CS) in the United States: Estimates using a dynamic progression model. (2011)

4637 Background: Understanding the prognosis at all stages in the PC disease continuum is essential to improve treatment and reduce morbidity and mortality. We provide a dynamic progression model to estimate prevalence of distinct PC CSs. This model enables estimation of annual prevalence of each CS, annual flows between CSs and provides a framework to evaluate impact of novel therapies. Methods: This PC dynamic progression model uses U.S. estimates of PC incidence from SEER and progression from one CS to another and mortality for each CS from published clinical trials. The simulation begins in 1990, introducing incident patient (pt) cohorts allocated across initial CSs (Table). Each year additional incident PC cohorts are layered into the model. Results: The model provides estimates of point prevalence for each PC CS. Results indicate that after 19 years of simulation, 95.5% (N=2,179,270) of prevalent PC patients have localized or locally advanced PC (L1-L3) and 4.5% (N=102,464) have metastatic PC (M1-M4). Conclusions: This dynamic PC progression model allows quantification of individual disease CSs by accounting explicitly for pt movement through the disease continuum. The model incorporates clinical data on available therapies for each CS and can be adapted easily to account for changing benefits from future therapies. Clinical state Definition 2009 prevalence Active disease* Annual progression hazard (%) Annual mortality hazard (%) Active surveillance Localized: no treatment 160,670 NA L1 Localized: definitive local therapy (tx) 1,195,060 83,380 5.2 3.8 L2 Rising PSA noncastrate, nonmetastatic: hormone tx 747,370 142,840 5.3 7.2 L3 Nonmetastatic castrate-resistant PC (CRPC): rising PSA postsurgery/radiation/hormone tx 76,170 48,450 36.6 14.5 M1 Metastatic noncastrate: newly diagnosed metastatic PC 35,880 17,493 16.9 19.5 M2 Asymptomatic metastatic CRPC (mCRPC): 1st line chemo 4,579 3,712 30.4 35.6 M3 Symptomatic mCRPC: 1st line chemo 30,839 26,928 46.3 29.4 M4 Symptomatic mCRPC: failed 1st line chemo, 2nd line chemo 31,166 27,406 NA 49.9 Total prevalence 2,281,734 350,209 * Excludes pts in remission and/or not on tx.