gebhart/patrepeval huggingface dataset:
Two E2 binding sites alone are sufficient to function as the minimal origin of replication of human papillomavirus type 18 DNA (1995)

Replication of papillomaviruses requires an origin of replication and two virus-encoded proteins, E1 and E2. Using a transient replication assay for human papillomavirus type 18 (HPV-18) DNA, we have found that two adjacent sequences present within the origin of replication can independently support replication. The first, a 77-bp region, contains one E2 binding site (E2BS) and a 16-bp inverted repeat element that probably corresponds to the E1 binding site (E1BS). The other, an 81-bp region, includes two E2BS but lacks the putative E1BS. A synthetic 33-bp oligonucleotide containing two high-affinity E2BS was also found to function as an origin of replication. Replication of all these plasmids was absolutely dependent on the presence of the HPV-18 E1 and E2 proteins. The HPV-1a E1 and E2 proteins were also found to support replication of a plasmid containing the complete HPV-18 origin but failed to replicate a plasmid containing two E2BS alone. Our results suggest that the E2 protein can target E1 to the origin through the formation of an E1-E2 complex which is likely to be involved the initiation of replication.
Effect of eicosapentaenoic acid, protein and amino acids on protein synthesis and degradation in skeletal muscle of cachectic mice (2004)

Atrophy of skeletal muscle reduces both the quality and quantity of life of patients with cancer cachexia. Loss of muscle mass is thought to arise from a reduction in protein synthesis combined with an enhanced rate of protein degradation, and few treatments are available to counteract this process. Eicosapentaenoic acid (EPA) has been shown to attenuate the enhanced protein degradation, but to have no effect on protein synthesis. This study examines the effect of EPA combined with a protein and amino-acid supplementation on protein synthesis and degradation in gastrocnemius muscle of mice bearing the cachexia-inducing MAC16 tumour. Muscles from cachectic mice showed an 80% reduction in protein synthesis and about a 50-fold increase in protein degradation compared with muscles from nontumour-bearing mice of the same age and weight. Treatment with EPA (1 g kg(-1)) daily reduced protein degradation by 88%, but had no effect on protein synthesis. Combination of EPA with casein (5.35 g kg(-1)) also had no effect on protein synthesis, but when combined with the amino acids leucine, arginine and methionine there was almost a doubling of protein synthesis. The addition of carbohydrate (10.7 g kg(-1)) to stimulate insulin release had no additional effect. The combination involving the amino acids produced almost a doubling of the ratio of protein synthesis to protein degradation in gastrocnemius muscle over that of EPA alone. No treatment had a significant effect on tumour growth rate, but the inclusion of amino acids had a more significant effect on weight loss induced by the MAC16 tumour than that of EPA alone. The results suggest that combination therapy of cancer cachexia involving both inhibition of the enhanced protein degradation and stimulation of the reduced protein synthesis may be more effective than either treatment alone.
Biological Functions and Biogenesis of Secreted Bacterial Outer Membrane Vesicles (2010)

Gram-negative bacteria produce outer membrane vesicles (OMVs) that contain biologically active proteins and perform diverse biological processes. Unlike other secretion mechanisms, OMVs enable bacteria to secrete insoluble molecules in addition to and in complex with soluble material. OMVs allow enzymes to reach distant targets in a concentrated, protected, and targeted form. OMVs also play roles in bacterial survival: Their production is a bacterial stress response and important for nutrient acquisition, biofilm development, and pathogenesis. Key characteristics of OMV biogenesis include outward bulging of areas lacking membrane-peptidoglycan bonds, the capacity to upregulate vesicle production without also losing outer membrane integrity, enrichment or exclusion of certain proteins and lipids, and membrane fission without direct energy from ATP/GTP hydrolysis. Comparisons of similar budding mechanisms from diverse biological domains have provided new insight into evaluating mechanisms for outer membrane vesiculation.
Effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection (2000)

Acute hepadnavirus infections either resolve or progress to chronicity. Factors that influence chronicity as an outcome of hepatitis B virus (HBV) infection in humans can be studied experimentally in the woodchuck model. Accordingly, several woodchuck hepatitis virus (WHV) inocula were characterized. Representative inocula had high titers of infectious virus (approximately 10(7.7)-10(9.5) woodchuck 50% infectious doses per milliliter [WID(50%)/mL] by subcutaneous inoculation), with 1 WID(50%) ranging between 21 and 357 physical virion particles. WHV7P1 (standard high dose, 5 x 10(6) WID(50%)) produced a 72% chronicity rate (i.e., percent chronic of total infected) in neonatal woodchucks (1-3 days old). Comparable doses of WHV8P1 resulted in a lower chronicity rate in neonates (34% chronic) indicating that it represented a strain different from WHV7P1. Neonatal woodchucks were more susceptible to chronic infection by high doses of WHV7P1 (range, 65%-75% chronic) compared with 8-week-old weanlings (33% chronic) and adult woodchucks (0% chronic; i.e., all resolved). High doses of cloned wild-type viruses also induced high rates of chronicity in neonates (70%-80% chronic). Chronicity rates in neonates were decreased for low doses of WHV7P1 (500 WID(50%), 9% chronic) and for high doses of a precore WHeAg-minus mutant WHV8 clone (17% chronic). Thus, both age and viral determinants can influence chronicity as an outcome of experimental WHV infection. Standardized inocula will enable the study of mechanisms that initiate and maintain chronic hepadnavirus infection and also provide a means for developing WHV carriers for therapeutic studies.
The Structure of Avian Type XII Collagen (1989)

The monoclonal antibody 75d7, specific for type XII collagen (Sugrue, S.P., Gordon, M.K., Seyer, J., Dublet, B., van der Rest, M., and Olsen, B. R. (1989) J. Cell Biol., in press), was used to characterize the intact form of type XII collagen from chick embryo leg tendons. On an immunoblot of a 6% polyacrylamide gel of tendon extracts, one sharp band is recognized by the antibody at Mr = 220,000, while two fuzzy and poorly resolved bands are seen at Mr = 270,000 and Mr = 290,000. By immunoprecipitation of radiolabeled tendon culture media and electrophoresis of the precipitated material, bands with the same mobilities are observed, indicating that type XII collagen is not proteolytically processed in the extracellular space. Type XII collagen was extracted from tendons with 1 M NaCl in a Tris-HCl buffer and partially purified by concanavalin A-Sepharose and gel permeation chromatographies, using dot immunoblots to monitor the purification. Fractions highly enriched in bacterial collagenase-sensitive proteins with the same electrophoretic properties as type XII collagen were obtained. These fractions did not stain with Alcian blue and neither they nor the immunostained type XII collagen were affected by chondroitinase ABC digestion, indicating that type XII collagen is not a proteoglycan. A disulfide-bonded trimeric CNBr peptide was isolated by affinity chromatography on an antibody column and further purified by gel electrophoresis. Its NH2-terminal amino acid sequence was shown to be unique, demonstrating that type XII collagen is a homotrimer [alpha 1 (XII)]3. After bacterial collagenase digestion, both the immunopurified radiolabeled preparation and the purified tendon extract fraction showed by gel electrophoresis the presence of a large disulfide-bonded, 3 x 190-kDa, collagenase-resistant domain. Rotary shadowing and electron microscopy of the purified type XII fraction demonstrated that the molecule has the structure of a cross consisting of a 75 nm collagenase-sensitive tail, a central globule, and three 60 nm arms each ending in a small globule. After heat denaturation and renaturation, only a very large globule can be seen, attached to the triple helical tail. These results show that type XII collagen has a unique structure and is different from the other matrix constituents described so far.
Wide-field-of-view solar occultation gas filter correlation radiometer for stratospheric methane measurements from a sounding rocket (2003)

A wide field of view Gas Filter Correlation Radiometer (GFCR) has been developed to make solar occultation measurements of the vertical methane distribution in the stratosphere from a sounding rocket platform. The GFCR has demonstrated a 50° solar acceptance angle that allows for a GFCR measurement during every rotation of the payload without active orientation control. The flat surface of a plano-convex ZnSe lens was etched to diffuse the projected image of the sun. By diffusing the incident solar radiation through a wide angle, sufficient radiation could be directed to the collimating GFCR optics even when the optical axis points as far as ± 25° away from the Sun. The system can be configured to measure other gaseous species with spectral bands in the 2 - 6 &#956;m region by simply changing the bandpass filter and the correlation gas. In a laboratory calibration, the optical density of methane in a test cell was varied from 10^-4 to 10<sup>-2</sup> atm·m as the GFCR correlation cell optical density was held at 2.5×10<sup>-3</sup> atm-m. The process showed that measurements with a signal to noise ratio > 30:1 can be expected when the system operates in altitudes from 25 to 40 km. The GFCR performed with a correlation of 99.7% to the prediction of a theoretical model created with the HITRAN database. Sensitivity to gas distributions at other altitudes can be optimized by changing the gas pressure in the correlation cell. The payload featuring the GFCR is scheduled to be launched on an Enhanced Orion sub-orbital sounding rocket from NASA Wallops Flight Facility in April 2003. Future applications include validation and truthing for space-born remote sensing systems.
Ex-vivo testing of crystalline lens substitutes: a pilot study (2000)

ABSTRACT The paper reviews two techniques being developed for ex-vivo testing of crystalline lens substitutes. The techniques may beused to test polymers developed for the Restore Accommodation (RA) project. Harvested rabbit and human lenses were usedin preliminary tests to determine the feasibility of topographical analysis of the crystalline lens and ex-vivo cell culturing ofthe lens capsule. Lens capsules were cultured to test formation of posterior capsule opacification (PCO) in the presence ofRA polymers. Feasibility of analyzing lens shape with the PARTM Sys Corneal Topography System was determined usingwhole lenses. Preliminary results indicate that topography and cell culturing of lens capsules may be used to evaluate RApolymers. 1. INTRODUCTION The Restore Accommodation (RA) project is a multinational effort to restore accommodation in presbyopes. The concept isto replace senile lens material with polymers that share the same mechanical properties as young human lens material.'5 Theprevention of posterior capsule opacification (PCO) 6,7
A Comparison in a Lung Model of Low- and High-flow Regulators for Transtracheal Jet Ventilation (1992)

There is widespread agreement that transtracheal jet ventilation (TTJV) using a percutaneously inserted intravenous (iv) catheter through the cricothyroid membrane is a simple, quick, relatively safe, and extremely effective treatment for the situation in which neither ventilation nor intubation can be achieved. No study has reported whether a low-flow pressure-reducing regulator (LFR) can provide enough driving pressure and flow under a variety of clinical circumstances for adequate TTJV. We determined, using a high-flow regulator (HFR) as our control, the tidal volume (VT) (measured by integrating a pneumotachograph signal) that a LFR could deliver via a Carden jet injector through 14- and 20-G iv catheters initially at an inspiratory:expiratory ratio (I:E) = 1:1 (unit of time = 1 s) in a mechanical model that had varying lung compliance (Cset, 10-100 ml/cmH2O) and airway diameters (proximal trachea 15.0, 4.5, or 3.0 mm ID and distal mainstem bronchi 9.0 or 4.5 mm ID). The lowest Cset (10 ml/cmH2O) and smallest airway diameter (tracheal diameter = 3.0 mm, bronchial diameter = 9.0 mm) resulted in the lowest VT (220 and 320 ml for the 20- and 14-G iv catheters, respectively, with the LFR), and the highest Cset (100 ml/cmH2O) and largest airway diameter (tracheal diameter = 15 mm, bronchial diameter = 9.0 mm) resulted in the highest VT (780 and 1040 ml for the 20- and 14-G iv catheters, respectively, with the LFR). The VT produced during TTJV was greatly dependent on air entrainment (measured by a second pneumotachograph), with the contribution to total VT ranging from 15 to 74%; the amount of air entrainment was independently confirmed by excellent agreement between measured and calculated alveolar oxygen concentrations. Decreasing Cset (with the largest airway diameter) and decreasing airway diameter (at Cset = 50 ml/cmH2O) over the full range studied resulted in approximately a 45-80% decrease in VT for all iv catheter/regulator combinations. Increasing Cset and narrowing airway diameter over the full range studied resulted in a progressive increase in end-expiratory volume (EEV) for all iv catheter/regulator combinations. The I:E ratio was also varied from 1:3 to 3:1 (unit of time = 1 s) using the 14-G catheter at Cset = 50 ml/cmH2O with both regulators at the extremes of the proximal tracheal diameters (15.0 and 3.0 mm ID), and we found that jet ventilation through a proximal tracheal diameter of 3.0 mm with the HFR at I:E ratios = 1:1 and 3:1, EEV exceeded the capacity of the mechanical lung (4,000 ml).(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of carbodiimide crosslinking conditions on the physical properties of laminated intestinal submucosa (2001)

Functional tissue engineering of load-bearing repair tissues requires the design and production of biomaterials that provide a remodelable scaffold for host infiltration and tissue regeneration while maintaining the repair function throughout the remodeling process. Layered constructs have been fabricated from chemically and mechanically cleaned porcine intestinal collagen using ethyl-3(3-dimethylamino) propyl carbodiimide (EDC) and an acetone solvent. By varying the concentration of the crosslinker from 1 to 10 mM and the solvent from 0 to 90% acetone, the strength, stiffness, maximum strain, thermal stability, lamination strength, and suture retention strength can be adjusted. These parameters have either functional importance or the potential to modify the remodeling kinetics, or they have both. This study investigates the interdependence of these parameters, the specific effects that variations in concentration can achieve, and how the two crosslinking variables interact. The results demonstrate that there is substantial latitude in the design of these constructs by these straightforward crosslinking modifications. These data provide the basis for studying the in vivo response to crosslinking conditions that will supply the requisite strength while still allowing host cell infiltration and remodeling.
Supportive treatment in weight-losing cancer patients due to the additive adverse effects of radiation treatment and/or chemotherapy. (2000)

The reversal of anorexia and weight loss especially in patients with advanced cancer suffering from radiation treatment (RT) -related complications and debilitated furtherly during RT would be a welcome relief. The purpose of this study is to evaluate the feasibility of supportive treatment with megestrol acetate (MA) in our weight-losing cancer patients increasingly experiencing anorexia, smell, taste, and weight loss due to the additive adverse effects of RT +/- chemotherapy and how MA changes the additive role of the severity of RT reactions on such patients. From June 1997 to October 1998, 100 eligible patients were enrolled on a randomized, placebo-controlled clinical trial. Of the 100 patients, 46 received MA during RT and 4 after the end of the RT, and 50 received placebo for 3 months. Subjective parameters were assessed by a brief questionnaire form based on scoring from 1 to 5, according to the degree of the loss or change for each parameter of malnutrition, appetite, taste and smell developed by us. At the end of the study a statistically significant weight gain was achieved in the patient group receiving MA compared to the placebo group (+3 to +5 kg versus -3.7 to -5.9 kg, p=0.000). Significant improvements were seen in performance status (p=0.000), appetite (p=0.000), malnutrition (p=0.000), loss of taste (p=0.000) and smell qualities (p=0.02) in the MA group compared to the placebo group. In the MA group there was no statistically significant difference related to the weight changes according to the grade of either the acute or late RT effects (p=0.65 and 0.07, respectively). Whereas, in the placebo group a statistically significant additive effect of the acute and late RT effects was detected on weight loss (p=0.008 and 0.007, respectively). We observed no side-effects of MA in a 3-month time follow-up. The use of MA 480 mg/day during RT was effective in reversing anorexia and weight loss in spite of the acute RT effects, and helped most patients to well tolerate specific tumor therapy. Further evaluation of its mechanisms of action on RT-related adverse effects, tumor response relationships, and effect on patient survival are researched.
Gold and silver nanoparticles: A class of chromophores with colors tunable in the range from 400 to 750 nm (2003)

This paper presents several solution-phase methods for the large-scale synthesis of metal nanoparticles with controllable compositions (e.g., spherical nanoparticles of gold/silver alloys), morphologies (e.g., nanospheres, triangular nanoplates, circular nanodisks, and nanocubes of silver), and structures (e.g., solid vs. hollow colloids). Spectral measurements indicated that the positions of surface plasmon resonance (SPR) bands for these nanoparticles could be tuned by varying all these parameters. The number of SPR peaks was found to increase as the symmetry of the nanoparticles decreased. In addition to their use as chromophores with strong extinction coefficients, these nanoparticles could serve as a platform to probe binding events of chemical and biochemical species on their surfaces. Gold nanoshells with hollow interiors were, in particular, shown to exhibit a much higher sensitivity to environmental changes than gold solid colloids with roughly the same size.
Polyaniline, a novel conducting polymer. Morphology and chemistry of its oxidation and reduction in aqueous electrolytes (1986)

The emeraldine salt form of polyaniline, conducting in the metallic regime, can be synthesized electrochemically as a film exhibiting a well defined fibrillar morphology closely resembling that of polyacetylene. Cyclic voltammograms of chemically synthesized and electrochemically synthesized polyaniline are essentially identical. Probable chemical changes which occur and the compounds which are formed when chemically synthesized poly-aniline is electrochemically oxidized and reduced between –0.2 and 1.0 V vs. SCE in aqueous HCl solutions at pH values ranging from –2.12 (6.0 mol dm–3) to 4.0 have been deduced from cyclic voltametric studies. These are shown to be consistent with previous chemical and conductivity studies of emeraldine base and emeraldine salt forms of polyaniline. It is proposed that the emeraldine salt form of polyaniline has a symmetrical conjugated structure having extensive charge delocalization resulting from a new type of doping of an organic polymer–salt formation rather than oxidation which occurs in the p-doping of all other conducting polymer systems.
Separation of transcriptional activation and silencing functions of the RAP1-encoded repressor/activator protein 1: isolation of viable mutants affecting both silencing and telomere length. (1991)

The repressor/activator protein 1 (RAP1) binds to the upstream activating sites of many genes, the silencer elements flanking the unexpressed mating-type loci HMR and HML, and the poly(C1-3A) sequences at telomeres, suggesting that RAP1 might have three distinct regulatory functions. To determine the in vivo role of RAP1 in repression of the HMR silent locus, we developed a screen to isolate rap1 mutants specifically defective in silencing. Fifteen independent mutants defining four different rap1 alleles were isolated. These alleles are defective to different extents in repression of an HMR locus containing a mutated, but fully functional, silencer. All four alleles are missense mutations in only three codons within a small C-terminal region of the gene. These silencing-defective mutants have no apparent growth defects, indicating that expression of the large number of essential genes that have promoters containing RAP1-binding sites is normal. A transcriptional silencing function of RAP1 can therefore be genetically separated from its presumably essential activation functions. Surprisingly, three of the silencing-defective rap1 alleles have significantly longer telomeres, suggesting that the function of RAP1 in both transcriptional silencing and telomere-length regulation may be related. In addition, we have demonstrated that increased gene dosage of either SIR1 or SIR4, two other factors required for silencing, suppresses the silencing defect of the rap1 mutants. The properties of SIR4 dosage suppression suggest that SIR4 protein may interact directly with RAP1 at silencers.
Gradient Estimation Using Stochastic Computation Graphs (2015)

In a variety of problems originating in supervised, unsupervised, and reinforcement learning, the loss function is defined by an expectation over a collection of random variables, which might be part of a probabilistic model or the external world. Estimating the gradient of this loss function, using samples, lies at the core of gradient-based learning algorithms for these problems. We introduce the formalism of stochastic computation graphs---directed acyclic graphs that include both deterministic functions and conditional probability distributions---and describe how to easily and automatically derive an unbiased estimator of the loss function's gradient. The resulting algorithm for computing the gradient estimator is a simple modification of the standard backpropagation algorithm. The generic scheme we propose unifies estimators derived in variety of prior work, along with variance-reduction techniques therein. It could assist researchers in developing intricate models involving a combination of stochastic and deterministic operations, enabling, for example, attention, memory, and control actions.
Inhibition of Hepatitis B Virus DNA Polymerase by Thymidine Triphosphate Analogues in vitro (1991)

A series of thymidine triphosphate analogues was tested for effect inhibitory on DNA polymerase activity in isolated hepatitis B virus (HBV) particles. The most efficient compounds were 2′,3′-dideoxy-3′-fluoro-5-vinyluridine triphosphate [50% inhibititory dose (ID 50 ) = 0.25 μm], 2′,3′-dideoxy-3′-fluoro-5-bromovinyluridine triphosphate (ID 50 = 0.80 μm), 2′,3′-dideoxy-3′-fluoro-4-thiothymidine triphosphate (ID 50 = 0.80 μm) and 2′,3′-dideoxy-3′-fluoro-5-bromouridine triphosphate (ID 50 = 1.00 μm). The inhibitors only moderately influenced the cellular DNA polymerase α (ID 50 ranging from 10 μm to 140 μm) but had a noteworthy effect on DNA polymerase β (ID 50 ranging from 0.8 μm to 7.0 μm), which could be associated with toxicity and mutagenicity in human cells. Kinetic analysis revealed a competitive type of inhibition for the most efficient compound, fluoro-5-vinyluridine triphosphate. The inhibition constant ( K i ) was estimated to be 0.25 μm compared with a Michaelis constant ( K m ) value of about 0.4 μm for the substrate.