gebhart/patrepeval huggingface dataset:
Suramin: prototype of a new generation of antitumor compounds. (1990)

Suramin is a polysulfonated compound originally developed nearly 75 years ago for use as a trypanocidal agent. Recent studies indicate that suramin can also disrupt mammalian cell function, notably by blocking growth factor--receptor interactions and by inhibiting the activity of enzymes that are critical for cell growth and proliferation. These observations, together with the finding that clinically achievable concentrations of the drug are toxic to many human tumor cell lines, have prompted clinical investigations of suramin's efficacy as an antitumor agent. This review considers the possible mechanisms that may underlie suramin's cytotoxic effects and discusses ongoing clinical trials in cancer patients.
Reliably estimating the noise in AVIRIS hyperspectral images (1996)

Abstract A new method is presented for computing the noise affecting each band of an AVIRIS hyperspectral image. Between-band (spectral) and within-band (spatial) correlations are used to decorrelate the image data via linear regression. Each band of the image is divided into small blocks, each of which is independently decorrelated. The decorrelation leaves noise-like residuals whose variance estimates the noise. A homogeneous set of these variances is selected and their values are combined to provide the best estimate of that band's noise. This method provides consistent noise estimates from images with very different land cover types. Its performance is validated by comparing its noise estimates with noise measures provided with two AVIRIS images. The method works well with inhomogeneous images (e.g., of a vegetated area such as Jasper Ridge) unlike a method described recently by Gao. The method is automatic and does not require the intervention of a human operator. Noise estimates are presented for 10 images recorded in the years 1989, 1990 and 1992. We show that the method can be used for both radiance and reflectance (atmospherically corrected) images.
The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation (2016)

The widespread use of antibiotics in the past 80 years has saved millions of human lives, facilitated technological progress and killed incalculable numbers of microbes, both pathogenic and commensal. Human-associated microbes perform an array of important functions, and we are now just beginning to understand the ways in which antibiotics have reshaped their ecology and the functional consequences of these changes. Mounting evidence shows that antibiotics influence the function of the immune system, our ability to resist infection, and our capacity for processing food. Therefore, it is now more important than ever to revisit how we use antibiotics. This review summarizes current research on the short-term and long-term consequences of antibiotic use on the human microbiome, from early life to adulthood, and its effect on diseases such as malnutrition, obesity, diabetes, and Clostridium difficile infection. Motivated by the consequences of inappropriate antibiotic use, we explore recent progress in the development of antivirulence approaches for resisting infection while minimizing resistance to therapy. We close the article by discussing probiotics and fecal microbiota transplants, which promise to restore the microbiota after damage of the microbiome. Together, the results of studies in this field emphasize the importance of developing a mechanistic understanding of gut ecology to enable the development of new therapeutic strategies and to rationally limit the use of antibiotic compounds.
Uptake kinetics of monoclonal antibodies by human malignant melanoma multicell spheroids. (1988)

Detailed uptake kinetics by multicell spheroids of three tumor associated monoclonal antibodies was investigated. The spheroids were established from a human melanoma cell line and the human colon adenocarcinoma cell line HT29 as in vitro models of poorly vascularized micrometastases in vivo. The selected antibodies 96.5, 140.240, and OST15 showed a wide range of reactivity against the melanoma cell but they all had negligible binding with the colon cancer cell. Uptake of the antibodies by small spheroids (about 300 micron diameter) was generally sigmoidal in shape with respect to incubation time, and amount of uptake followed the same trend of immunoreactivity of the antibodies with single cells. The correlation was weaker for spheroids with diameter greater than 500 micron presumably due to the increasing size of the necrotic core. By varying the concentration of the antibodies in the incubation medium from tracer dose (0.2 microgram/ml) to a higher dose (3 micrograms/ml), negligible changes in the amount of antibodies bound with their target spheroids were observed. Nonspecific binding between antibodies and spheroids, however, resulted in proportional increase in uptake.
Analysis of experimental biosensor/FIA lactose measurements (2003)

Whey is an abundant effluent in the production of cheese and casein. The biotechnological utilization of this economically important and nutritive source is limited mainly because of the presence of high percentages of lactose. This disaccharide has poor solubility, which can cause crystallization and insufficient sweetness in dairy food; additionally, part of the adult population suffers from associated lactose intolerance diseases. There are several methods to determine lactose such as spectrophotometry, polarimetry, infrared spectroscopy, titrimetry and chromatography. However these methods are tedious and time-consuming due to long sample preparation. These disadvantages stimulated the development of an enzymatic lactose biosensor. It employs two immobilized enzymes, beta-galactosidase and glucose oxidase and the quantitative analysis of lactose is based on determination of oxygen consumption in the enzymatic reaction. The influence of temperature on the biosensor signal was experimentally studied. It was observed that a nonlinear relationship exists between the electric response of the biosensor - provided by CAFCA (Computer Assisted Flow Control & Analysis - ANASYSCON, Hannover) - and lactose concentration. In this work, attempts were made to correlate these variables using a simple nonlinear model and multilayered neural networks, with the latter providing the best modeling of the experimental data.
A generic framework for building dialogue games for language learning: application in the flight domain (2011)

This paper presents a generic web-based dialogue game framework, "Mercurial", for language learning.The system capabilities are demonstrated within a flight domain application.The system randomly generates a flight-booking scenario according to the current difficulty level.The student accomplishes the scenario by interacting with the system through speech.The system gives real-time feedback on the dialogue progress and scores, and summarizes the whole dialogue at the end of each scenario.The system uses generic language understanding, language generation, dialogue management, and user simulation modules to conduct the dialogue and give contextual help.Preliminary experiments yielded positive feedback from the subjects.
Autonomous refresh of floating body cell (FBC) (2008)

Physics of autonomous refresh of FBC is presented. Current input to the floating body by impact ionization and output by charge pumping can balance to make FBC refresh by itself without sense amplifier operation. Thanks to this feature, multiple cells on a BL can be refreshed simultaneously, leading to a drastic reduction of BL charging current compared to the conventional refresh. 600 muA refresh current for 1 G-bit memory is achieved in 32 nm technology node with 4 ms retention time. If gate direct tunneling current is used as output, FBC can realize static RAM without periodical refresh when retaining data.
Pyruvic Acid Production by an F1-ATPase-defective Mutant ofEscherichia coliW1485lip2 (1994)

An F1-ATPase-defective mutant, TBLA-1, was constructed by the transduction of a defective gene for the alpha subunit of F1-ATPase, atpA401, into Escherichia coli W1485lip2, a lipoic acid-requiring pyruvic acid producer. The pyruvic acid production of the strain TBLA-1 was found to be improved markedly compared with that of strain W1485lip2. In cultures using a jar fermentor, the strain W1485lip2 consumed 50 g/liter of glucose and produced 25 g/liter of pyruvic acid after culture for 32h, while strain TBLA-1 consumed the same amount of glucose, and produced more than 30 g/liter of pyruvic acid in a 24-h culture. A revertant, No. 63-1, derived from the strain TBLA-1, had a normal level of F1-ATPase activity, and showed a similar pattern of pyruvic acid production to that of strain W1485lip2.
Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution (1997)

Virulence genes of pathogenic bacteria, which code for toxins, adhesins, invasins or other virulence factors, may be located on transmissible genetic elements such as transposons, plasmids or bacteriophages. In addition, such genes may be part of particular regions on the bacterial chromosomes, termed 'pathogenicity islands' (Pais). Pathogenicity islands are found in Gram-negative as well as in Gram-positive bacteria. They are present in the genome of pathogenic strains of a given species but absent or only rarely present in those of non-pathogenic variants of the same or related species. They comprise large DNA regions (up to 200 kb of DNA) and often carry more than one virulence gene, the G + C contents of which often differ from those of the remaining bacterial genome. In most cases, Pais are flanked by specific DNA sequences, such as direct repeats or insertion sequence (IS) elements. In addition, Pais of certain bacteria (e,g. uropathogenic Escherichia coli, Yersinia spp., Helicobacter pylori) have the tendency to delete with high frequencies or may undergo duplications and amplifications. Pais are often associated with tRNA loci, which may represent target sites for the chromosomal integration of these elements. Bacteriophage attachment sites and cryptic genes on Pais, which are homologous to phage integrase genes, plasmid origins of replication of IS elements, indicate that these particular genetic elements were previously able to spread among bacterial populations by horizontal gene transfer, a process known to contribute to microbial evolution.
Surveillance of Lyme borreliosis in Germany, 2002 and 2003 (2005)

Lyme borreliosis is a potentially serious infection common in Germany, but little data about its incidence, distribution, and clinical manifestations are available. Lyme borreliosis is not a notifiable disease in Germany, but six of Germany's 16 states - Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt and Thüringen, have enhanced notification systems, which do include Lyme borreliosis. The efforts made in these states to monitor confirmed cases through notification are therefore an important contribution to understanding the epidemiology of Lyme borreliosis in Germany. This report summarises the analysis of Lyme borreliosis cases submitted to the Robert Koch-Institut during 2002-2003. The average incidence of Lyme borreliosis of the six East German states was 17.8 cases per 100,000 population in 2002 and increased by 31% to 23.3 cases in 2003, respectively. Patient ages were bimodally distributed, with incidence peaks among children aged 5- 9 and elderly patients, aged 60- 64 in 2002, and 65- 69 in 2003. For both years, 55% of patients were female. Around 86% of notified cases occurred from May to October. Erythema migrans affected 2697 patients (89.3%) in 2002 and 3442 (86.7%) in 2003. For a vector-borne disease, like Lyme borreliosis, the risk of infection depends on the degree and duration of contact between humans and ticks harbouring Borrelia burgdorferi. As infectious ticks probably occur throughout Germany, it is likely that the situation in the remaining 10 German states is similar to that of the states in this study.
Growth of GaN by ECR-assisted MBE (1993)

High-quality GaN films have been grown on a variety of substrates by electron cyclotron resonance microwave plasma-assisted molecular beam epitaxy (ECR-MBE). The films were grown in two steps. First, a GaN-buffer was grown at low temperature and then the rest of the film was grown at higher temperatures. We found that this method of growth leads to a relatively small two-dimensional nucleation rate (∼20 nuclei/μm2 h) and high lateral growth rate (100 times faster than the vertical growth rate). This type of quasi-layer-by-layer growth results in a smooth surface morphology to within 100 Å. Growth on Si(1 0 0) leads to single-crystalline GaN films having the zinc-blende structure. Growth on Si(1 1 1) leads to GaN films having the wurtzitic structure with a large concentration of stacking faults. The crystallographic orientation and the surface morphology of GaN films on sapphire depends on the orientation of sapphire. To this date, the best films were grown on the basal plane of sapphire.
Design of a small peptide-based proteinase inhibitor by modeling the active-site region of barley chymotrypsin inhibitor 2 (1991)

A synthetic peptide-based proteinase inhibitor was constructed by modeling the regions responsible for inhibition in barley chymotrypsin inhibitor 2 (CI-2). The 18-residue peptide was designed by molecular modeling, based on the crystal structure of CI-2. The amino acid sequences that interact with the proteinase were preserved, as well as residues that maintain the structure of the inhibitory loop. A disulfide bridge was introduced to force the peptide to adopt a cyclic structure. Kinetic studies on binding of the cyclic peptide to subtilisin BPN', subtilisin Carlsberg, chymotrypsin, and pancreatic elastase show that the cyclic peptide retains both the inhibition properties, the kinetic mechanism, and the specificity of the original protein inhibitor. Formation of a cyclic structure was found to be essential, and activity was abolished by reduction of the disulfide. As with CI-2, tightest binding is found to subtilisin BPN', where the Ki value for the cyclic peptide was 28 x 10(-12) M, compared with 29 x 10(-12)M for CI-2 under identical conditions. This remarkable result shows that it is possible to use a short synthetic peptide to model the molecular recognition properties of the intact protein, in this case obtaining full functionality with just 18 residues instead of 83 for CI-2.
Avian colibacillosis: still many black holes (2015)

Avian pathogenic Escherichia coli (APEC) strains cause severe respiratory and systemic diseases, threatening food security and avian welfare worldwide. Intensification of poultry production and the quick expansion of free-range production systems will increase the incidence of colibacillosis through greater exposure of birds to pathogens and stress. Therapy is mainly based on antibiotherapy and current vaccines have poor efficacy. Serotyping remains the most frequently used diagnostic method, only allowing the identification of a limited number of APEC strains. Several studies have demonstrated that the most common virulence factors studied in APEC are all rarely present in the same isolate, showing that APEC strains constitute a heterogeneous group. Different isolates may harbor different associations of virulence factors, each one able to induce colibacillosis. Despite its economical relevance, pathogenesis of colibacillosis is poorly understood. Our knowledge on the host response to APEC is based on very descriptive studies, mostly restricted to bacteriological and histopathological analysis of infected organs such as lungs. Furthermore, only a small number of APEC isolates have been used in experimental studies. In the present review, we discuss current knowledge on APEC diversity and virulence, including host response to infection and the associated inflammatory response with a focus on pulmonary colibacillosis.
Estimating the sample complexity of a multi-class discriminant model (1999)

We study the generalization performance of a multiclass discriminant model. Several bounds on its sample complexity are derived from uniform convergence results based on different measures of capacity. This gives us an insight into the nature of the capacity measure which is best suited to study multiclass discriminant model.
[Analysis of c-kit gene mutations in gastrointestinal stromal tumors]. (2004)

The mutations in exon 11 of c-kit gene might partially represent one of the molecular mechanisms of GIST. It can be used as a marker for distinguishing benignancy and malignancy of GIST. The mutations did not involve the reading frame. Except for long frame deletion, most mutations also did not affect protein expression. Mutation of c-kit gene in GIST provides a new genotypic marker to distinguish GIST from authentic leiomyomas, leiomyosarcomas, schwannomas and etc.
The development of CNS-active LRRK2 inhibitors using property-directed optimisation (2013)

Mutations in PARK8/LRRK2 are the most common genetic cause of Parkinson's disease. Inhibition of LRRK2 kinase activity has neuroprotective benefits, and provides a means of addressing the underlying biochemical cause of Parkinson's disease for the first time. Initial attempts to develop LRRK2 inhibitors were largely unsuccessful and highlight shortcomings intrinsic to traditional, high throughput screening methods of lead discovery. Recently, amino-pyrimidine GNE-7915 was reported as a potent (IC50=9 nM) selective (1/187 kinases), brain-penetrant and non-toxic inhibitor of LRRK2. The use of in silico modelling, extensive in vitro assays and resource-efficient in vivo techniques to produce GNE-7915, reflects a trend towards the concerted optimisation of potency, selectivity and pharmacokinetic properties in early-stage drug development.
Effect of clenbuterol on growth, carcase and skeletal muscle characteristics in broiler chickens (1997)

1. Male and female broiler chickens (144 in total) were given diets supplemented with clenbuterol (CB) at 0 (control) and at 1 mg/kg between 28 and 49 d of age to study the effect of CB on growth, carcase and skeletal muscle. 2. CB improved growth in males by increasing daily weight gain and final live weight and by lowering food conversion ratio. In females it changed the carcase composition by reducing abdominal fat pad and by increasing the proportion of protein. Consequently, carcase protein gain was increased in both sexes (11% and 16%, respectively). 3. Skeletal muscle weights were enhanced by between 6% and 22%. Muscle fibre diameters were increased in extensor hallucis longus (EHL) but not in gastrocnemius (GAS) muscle. This increase was more pronounced in females. EHL total muscle fibre number remained unchanged. The proportion of fast-twitch glycolytic fibres was increased at the expense of fast-twitch oxidative fibres in males only. Nuclear/cytoplasm and DNA/protein ratios tended to be decreased by CB. 4. From the elevated EHL muscle RNA/DNA, unchanged protein/RNA and translation activity it is suggested that CB stimulated protein synthesis at the pretranslational level. Reduced protein degradation is deduced from decreased neutral calcium-dependent proteolytic activity. 5. It is concluded that broiler chickens respond to long-term CB treatment as has been shown in various mammals. However, the sex-specific response in growth, carcase composition and skeletal muscle cellularity is more clearly apparent in broiler chickens.
A double mirror W/C multilayer monochromator for radiation biology applications (1998)

A double-mirror multilayer monochromator was developed for the purpose of irradiating live cell cultures at the Synchrotron Radiation Center, University of Wisconsin-Madison. The monochromator is designed for the soft x-ray region with photon energies between 270 and 2400 eV. Multilayer mirrors with 55 bilayers of W/C and a bilayer spacing of d = 3.0 nm are sputter deposited on Si substrates. By proper masking of the sputtering sources, variation in the bilayer spacing over the area of the mirror is minimized. The uniformity of the bilayer spacing was measured to be delta d/d < 1%, over the 75 mm x 25 mm area of the mirrors. The reflectivity was measured as a function of energy to determine the integrated reflectivity and evaluate the contribution of the specular reflection and higher orders to the monochromatic beam. The use of suitable filters with a Si(Li) detector allows determination of the spectral output of the monochromator. The output power of the monochromator between 270 and 2400 eV is measured. The resolution of the monochromator is delta lambda/lambda = 0.04. Applications of the monochromator to radiation biology are discussed.
Minimally invasive access of the normal pericardium: Initial clinical experience with a novel device (1999)

The pericardial space is being investigated as a reservoir for local drug delivery to the heart and coronary arteries. Intrapericardial drug delivery is currently limited because the pericardial space is normally small and difficult to access by standard pericardiocentesis without invasive surgery or risk of cardiac injury. Clinical trials are being conducted to evaluate a novel, minimally invasive, pericardial access device (PerDUCER, Comedicus Inc., Columbia Heights, Minn.). As of October 26, 1998, 12 clinical trials have been completed on patients undergoing cardiac surgical procedures. In all patients, a stab incision was made 1" subxiphoid and a 17G angled cannula, with preloaded guidewire, was advanced into the mediastinal space. After cannula removal, a 19F sheath/dilator was inserted over the wire. In eight patients, a median sternotomy was performed and the position of the sheath over the anterior pericardium (PC) was visually verified. Four patients underwent a closed-chest, fluoroscopy-assisted procedure. In all patients, the PerDUCER was inserted into the chest, via the sheath, and positioned over the PC. The PC was captured by suction and a bleb was formed within a side-hole on the PerDUCER tip. A sheathed needle was advanced, puncturing the isolated bleb of PC. A guidewire was advanced through the needle into the pericardial space and the PerDUCER was removed. Guidewire insertion was successful in 10 patients (7 on first attempt, 3 on second) without adverse hemodynamic effects or arrhythmia. Other than the guidewire insertion site, there was no evidence of injury to the PC or the heart. These initial clinical trials suggest that the PerDUCER may provide safe, rapid and effective percutaneous insertion of a guidewire into the normal pericardial space.
Expression of desmin gene in skeletal and smooth muscle by in situ hybridization using a human desmin gene probe. (1990)

We have used a probe encoding for the human desmin gene to study the expression of the desmin gene in skeletal and smooth muscle by in situ hybridization. In human skeletal muscle, the results showed a strong and homogeneous level of desmin mRNA contrasting with the faintly immunostaining of the desmin protein. In smooth muscle cells of colon and uterus, in situ hybridization and immunofluorescence staining suggests that there are some cells which do not contain desmin. The optimal condition of desmin mRNA detection was in cryostat sections fixed with paraformaldehyde and in paraffin embedded tissue with the same fixative. The human desmin probe can be used as a marker of cell differentiation and a way to study the regulation of the expression of the desmin gene in pathological events.