gebhart/patrepeval huggingface dataset:
Alcoholic, Nonalcoholic, and Toxicant-Associated Steatohepatitis: Mechanistic Similarities and Differences (2015)

Hepatic steatosis and steatohepatitis are common histologic findings that can be caused by multiple etiologies. The three most frequent causes for steatosis/steatohepatitis are alcohol (alcoholic steatohepatitis, ASH), obesity/metabolic syndrome (nonalcoholic steatohepatitis, NASH), and environmental toxicants (toxicant-associated steatohepatitis, TASH). Hepatic steatosis is an early occurrence in all three forms of liver disease, and they often share common pathways to disease progression/severity. Disease progression is a result of both direct effects on the liver as well as indirect alterations in other organs/tissues such as intestine, adipose tissue, and the immune system. Although the three liver diseases (ASH, NASH, and TASH) share many common pathogenic mechanisms, they also exhibit distinct differences. Both shared and divergent mechanisms can be potential therapeutic targets. This review provides an overview of selected important mechanistic similarities and differences in ASH, NASH, and TASH.
The safety of intravitreal hyaluronidase. A clinical and histologic study. (1990)

The authors previously developed a new model of preretinal neovascularization in the rabbit eye using hyaluronidase for enzymatic vitreolysis. The purpose of this study was to evaluate the safety of intravitreal injections of hyaluronidase. Concentrations of 1, 15, 30, 50, and 150 IU of hyaluronidase in 0.1 ml of 0.9% saline were injected intravitreally and aspirated repetitively until the vitreous was partially liquified. The animals were examined with indirect ophthalmoscopy, fundus photography, and fluorescein angiography before injection and on days 1 and 7 after injection. Light and electron microscopic retinal sections were prepared from enucleated eyes at days 1 and 7. All concentrations of hyaluronidase were effective in producing partial vitreolysis. Eyes treated with 1 IU showed no abnormalities on days 1 or 7. Eyes treated with 15 IU showed no retinal abnormalities on day 1, but on day 7 histologic abnormalities were present in two of four eyes. At higher concentrations, clinical and histologic changes were seen in proportion to the concentration and included focal whitening, edema, vitreous haze, vascular abnormalities, and retinal necrosis at the highest doses. Histologic evaluation of the retina revealed marked destruction in all layers at the higher concentrations. The authors conclude that 1 IU of intravitreal hyaluronidase is sufficient for partial vitreolysis and nontoxic to the rabbit retina.
Molecular Basis of Herbicide Resistance in Plants in Amaranthus hybridus (1983)

Resistance of different species of weeds to s-triazines, a commonly used class of herbicides, has been shown to involve a change in the binding affinity of the herbicide to a chloroplast polypeptide of 32,000 daltons. A single amino acid difference in this 32,000-dalton protein appears to be responsible for resistance to the herbicide in Amaranthus hybridus.
The Effect of Plasma Induced Separation (2003)

This paper describes the results of experimental work for surface electrical discharge influence on separation processes in high-speed flow. It could be related to the fields of Weakly Ionized Plasma and Flow Control. Different aerodynamic situations are explored: plane wall, profiled plate, and backstep. In the first case the effect of plasma-induced separation is demonstrated. Energetic threshold is measured. In the second case a stabilization of the separation line was found as well as screening effect. In configuration with backstep the flow transformation to separation-less mode has been obtained.
Efficient pitch filter encoding for variable rate speech processing (1999)

Analysis-by-synthesis techniques are used in a wide variety of speech coding standards and applications for rates below 16 kbps. The presence of a long-term predictor, commonly known as the adaptive codebook, is critical to coder performance at the lower rates. Unfortunately, the encoding rate and computational requirements for high-quality encoding of pitch filter parameters can be excessive. Several popular approaches explore the trade-off between predictor order, allocated bit rate, and computational requirements for long-term predictor optimization. We investigate the relative performance of several long-term predictor structures and present a new approach to vector quantization of the pitch filter coefficients having a subjective quality equivalent to other schemes, but at a lower coding rate and requiring significantly less closed-loop computation. The performance is evaluated in a variable-rate CELP coder at an average rate of 2 kbps and in Federal Standard 1016 CELP.
Functional immunomics: Microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes (2004)

One's present repertoire of antibodies encodes the history of one's past immunological experience. Can the present autoantibody repertoire be consulted to predict resistance or susceptibility to the future development of an autoimmune disease? Here, we developed an antigen microarray chip and used bioinformatic analysis to study a model of type 1 diabetes developing in nonobese diabetic male mice in which the disease was accelerated and synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We obtained sera from 19 individual mice, treated the mice to induce cyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9 mice became severely diabetic, whereas 10 mice permanently resisted diabetes. We again obtained serum from each mouse after CAD induction. We then analyzed, by using rank-order and superparamagnetic clustering, the patterns of antibodies in individual mice to 266 different antigens spotted on the chip. A selected panel of 27 different antigens (10% of the array) revealed a pattern of IgG antibody reactivity in the pre-CAD sera that discriminated between the mice resistant or susceptible to CAD with 100% sensitivity and 82% specificity (P = 0.017). Surprisingly, the set of IgG antibodies that was informative before CAD induction did not separate the resistant and susceptible groups after the onset of CAD; new antigens became critical for post-CAD repertoire discrimination. Thus, at least for a model disease, present antibody repertoires can predict future disease, predictive and diagnostic repertoires can differ, and decisive information about immune system behavior can be mined by bioinformatic technology. Repertoires matter.
Roles as metabolic regulators of the non-nutrients, capsaicin and capsiate, supplemented to diets. (2003)

Capsaicin is a pungent principle of hot red pepper and a non-nutrient. Capsaicin supplementation to high fat diet prevents fat deposit in the adipose tissue through secretion of adrenaline from the adrenal gland via activation of adrenal sympathetic nerve in rats. The chemical structure of a capsaicin analog found in non-pungent red pepper which was selected and fixed from a pungent variety was recently determined by our group to be a novel compound, capsiate. The gastrointestinal absorption and the metabolism of capsiate after oral administration in rats was studied. Capsiate rapidly disappeared from upper region of the gastrointestinal tract. It was cleaved to vanillyl alcohol and vanillic acid. The cleaved products were excreted in the urine as a conjugated complex such as glucuronide. The effect of capsiate on adrenaline secretion from the adrenal medulla of anesthetized rats was investigated. Capsiate evoked rapid and transient adrenaline secretion as dose-dependent manner. Capsazepine, a specific inhibitor of vanilloid (capsaicin) receptor subtype 1 (VR1), blocked capsiate-induced adrenaline secretion to show the participation of VR1 for this response. These results support that non-nutrients such as capsaicin and capsiate are well absorbed into blood and play important roles in regulating energy and lipid metabolism.(Communicated by Tadashi INAGAMI, M. J. A., Sept. 12, 2003)
Spectral sensitivity of mollies: comparing surface‐ and cave‐dwelling Atlantic mollies,Poecilia mexicana (2006)

The visual pigments of cones and rods in three species of mollies, Poecilia mexicana , Poecilia latipinna and their asexual hybrid Poecilia formosa , were examined using microspectrophotometry. In P. mexicana , populations from extreme photic habitats were used: one population originated from a clear water habitat, one from a milky water habitat and another from a completely dark cave. Ultraviolet‐sensitive cones were found in all species. Differences in the λ max values of the visual pigments were small between species and among the three P. mexicana populations, but dark‐reared cave fishes showed appreciably higher variance. The hybrid species P. formosa showed a highly variable long wavelength cone absorbance, ranging from 528·9 to 598·5 nm, suggesting multiple opsin expression or chromophore mixing.
A POSSIBLE MECHANISM FOR THE BACTERICIDAL EFFECT OF VISIBLE LIGHT (2011)

Visible light at high intensity was found to kill bacteria while low-power light in the visible and near infrared region enhances bacterial proliferation. The present review summarizes evidence demonstrating that the mechanism of visible light- bacteria interaction involves reactive oxygen species (ROS) generation. The ROS are photo induced by bacterial endogenous photosensitizers. Phototoxic effects were found to involve induction of high amounts of reactive oxygen species (ROS) by the bacteria while low amounts of ROS may promote their proliferation. Intense blue light, preferably at 415nm, is better than red light for bacteria killing.
Robust online appearance models for visual tracking (2005)

We propose a framework for learning robust, adaptive appearance models to be used for motion-based tracking of natural objects. The approach involves a mixture of stable image structure, learned over long time courses, along with 2-frame motion information and an outlier process. An online EM-algorithm is used to adapt the appearance model parameters over time. An implementation of this approach is developed for an appearance model based on the filter responses from a steerable pyramid. This model is used in a motion-based tracking algorithm to provide robustness in the face of image outliers, such as those caused by occlusions. It also provides the ability to adapt to natural changes in appearance, such as those due to facial expressions or variations in 3D pose. We show experimental results on a variety of natural image sequences of people moving within cluttered environments.
Glycosaminoglycan Therapy Prevents TGF-β1 Overexpression and Pathologic Changes in Renal Tissue of Long-Term Diabetic Rats (2000)

Chronic induction of the prosclerotic cytokine transforming growth factor beta (TGF-beta) has been implicated in the pathogenesis of diabetic nephropathy. In a rat model of diabetes mellitus-induced glomerulosclerosis, daily administration of a modified heparin (mH) glycosaminoglycan (GAG) preparation with low anticoagulant activity prevented glomerular and tubular matrix accumulation, as well as overexpression of TGF-beta1 mRNA and albuminuria, without obvious side effects. To elucidate the molecular mechanisms of GAG/mH inhibitory actions on TGF-beta1, studies using cultured mesangial cells were also performed. In these cells, high glucose-induced, dose-dependent increases in TGF-beta1 mRNA and bioactive TGF-beta protein expression were inhibited by GAG/mH treatment, whereas basal TGF-beta1 expression was not affected. Both the heparin-derived GAG and dermatan sulfate were effective, indicating that the heparin chemical structure is not necessary for inhibitory activity. Coincubation of GAG with active TGF-beta1 demonstrated no inhibitory effect on TGF-beta1 bioactivity, excluding a neutralizing effect of GAG on TGF-beta1 a the protein level. Furthermore, it was demonstrated that GAG inhibited phorbol myristate acetate-induced translocation of protein kinase C-alpha (PKC-alpha) and -beta1 and activation of PKC-alpha, as well as high glucose-induced activation of PKC-alpha. These results suggest that GAG inhibit TGF-beta1 overexpression at the transcriptional level, possibly via inhibition of high glucose-activated PKC. The findings indicate the potential of GAG therapy for the prevention of diabetic glomerulosclerosis by the inhibition of chronic disease-induced TGF-beta1 mRNA overexpression.
Gradient characterization using a Fourier‐transform technique (1998)

This paper describes a technique for characterizing the gradient subsystem of a magnetic resonance (MR) system. The technique uses a Fourier-transform analysis to directly measure the k-space trajectory produced by an arbitrary gradient waveform. In addition, the method can be easily extended to multiple dimensions and can be adapted to measuring residual gradient effects such as eddy currents. Several examples of gradient waveform and eddy-current measurements are presented. Also, it is demonstrated how the eddy-current measurements can be parameterized with an impulse-response formalism for later use in system tuning. When compared to a peak-fitting analysis, this technique provides a more direct extraction of the k-space measurements, which reduces the possibility of analysis error. This approach also has several advantages as compared to the conventional eddy-current measurement technique, including the ability to measure very short time constant effects.
On deriving unknown vulnerabilities from zero-day polymorphic and metamorphic worm exploits (2005)

Vulnerabilities that allow worms to hijack the control flow of each host that they spread to are typically discovered months before the worm outbreak, but are also typically discovered by third party researchers. A determined attacker could discover vulnerabilities as easily and create zero-day worms for vulnerabilities unknown to network defenses. It is important for an analysis tool to be able to generalize from a new exploit observed and derive protection for the vulnerability.Many researchers have observed that certain predicates of the exploit vector must be present for the exploit to work and that therefore these predicates place a limit on the amount of polymorphism and metamorphism available to the attacker. We formalize this idea and subject it to quantitative analysis with a symbolic execution tool called DACODA. Using DACODA we provide an empirical analysis of 14 exploits (seven of them actual worms or attacks from the Internet, caught by Minos with no prior knowledge of the vulnerabilities and no false positives observed over a period of six months) for four operating systems.Evaluation of our results in the light of these two models leads us to conclude that 1) single contiguous byte string signatures are not effective for content filtering, and token-based byte string signatures composed of smaller substrings are only semantically rich enough to be effective for content filtering if the vulnerability lies in a part of a protocol that is not commonly used, and that 2) practical exploit analysis must account for multiple processes, multithreading, and kernel processing of network data necessitating a focus on primitives instead of vulnerabilities.
Targeted nanoparticles for detecting and treating cancer (2006)

Abstract Enabled by their size and supramolecular structures, nanoparticles (that is, particles of approximately 10 to 100 nanometers) promise to be particularly capable agents in the detection, diagnosis, and treatment of cancer. When loaded with chemotherapeutic agents, nanoparticle delivery to cancerous tissues relative to healthy tissues may be favorably biased by size and through the attachment of targeting ligands to the surface of the particle. Nanoparticles may be made from a variety of materials, and in addition to chemotherapeutic payloads, nanoparticles can incorporate non‐bioactive elements useful as diagnostic and device agents. For example, the inclusion of iron oxide colloids enables nanoparticle use as magnetic resonance imaging (MRI) contrast agents, and also, through the application of an alternating magnetic field (AMF), enables the particle to generate enough heat to be used for hyperthermic therapeutic applications. In this report, we also introduce novel Magnetic Nanoparticle Hydro‐Gel (MagNaGel TM ) materials comprised of chemotherapeutic agents, iron oxide colloids, and targeting ligands. MagNaGel particles were fabricated in the 20‐ to 40‐nm size range with very narrow size dispersion. These particles demonstrate high (&gt;10 wt %) chemotherapeutic loading, tumor‐associated biomolecular binding, good magnetic susceptibility, and attractive toxicity and circulation profiles in mouse models. Looking forward, the convergence of drug and device on the nano‐scale promises treatment modalities that cannot be practiced through traditionally distinct drug and device combinations. MagNaGel nanoparticles are drug‐device hybrids that, when used in conjunction with diagnostic MRI and inductive heating, may play a key role in new and powerful cancer treatment regimens. Drug Dev. Res. 67:70–93, 2006. © 2006 Wiley‐Liss, Inc.
Brown Recluse Spider Envenomation of the Eyelid (1995)

Summary The authors developed a rabbit model of the brown recluse (BR) spider envenomation of the human eyelid. The spider bite causes cutaneous necrosis and systemic toxicity in human eyelids, possibly leading to disseminated intravascular coagulation, hemolysis, and death. The treatment has been controversial. The animal model evaluated the effects of single- and combined-agent therapy in four phases: venom dose response, time course, therapeutic effectiveness (steroid vs. dapsone vs. antivenom), and optimal therapy (steroid and dapsone; steroid and antivenom; and dapsone and anti-venom combination groups). The combination dapsone and antivenom treatment group was the optimal animal regimen, although not completely effective in eliminating microscopic necrosis. The authors also report dramatic clinical improvement in human inflammatory response with dapsone therapy and recommend immediate dapsone therapy combined with specific BR venom, if available, in humans.
Apoptotic cell death upon contact of CD4+ T lymphocytes with HIV glycoprotein-expressing cells is mediated by caspases but bypasses CD95 (Fas/Apo-1) and TNF receptor 1 (1997)

Loss of CD4+ T helper lymphocytes is central to the development of immunodeficiency after infection with HIV. In this study, we demonstrate that contact of primary uninfected CD4+ T lymphocytes with HIV-infected or HIV envelope glycoprotein-expressing cells results in apoptotic cell death of both uninfected and infected cells. Apoptosis was blocked by inhibitors of caspases/IL-1beta-converting enzyme-like proteases. This finding provides conclusive evidence that cytotoxicity upon contact of HIV-infected and uninfected primary cells is an active process and represents another example for the role of caspases in the induction of apoptosis. Prevention of apoptosis by inhibition of caspases did not block the formation of syncytia, indicating that apoptosis occurs either in a subpopulation of cells or in syncytia. Cell death was not mediated by the CD95 (Fas/Apo-1) or TNF receptor 1 molecules, which indicates a different pathway of apoptosis induction. The data indicate that initiation of apoptosis significantly shortens the life span of uninfected CD4+ T cells upon contact with HIV-infected cells and may represent a factor that contributes to the destruction of CD4+ T lymphocytes in vitro. Elucidation of the mechanism that initiates apoptosis in this situation will add to our understanding of both HIV pathogenesis and apoptotic signaling.
Quantitative analysis of image factors in a cultural heritage tourist destination (2012)

The tourism consumer's purchase decision process is, to a great extent, conditioned by the image the tourist has of the different destinations that make up his or her choice set. In a highly competitive international tourist market, those responsible for destinations' promotion and development policies seek differentiation strategies so that they may position the destinations in the most suitable market segments for their product in order to improve their attractiveness to visitors and increase or consolidate the economic benefits that tourism activity generates in their territory. To this end, the main objective we set ourselves in this paper is the empirical analysis of the factors that determine the image formation of Tarragona city as a cultural heritage destination. Without a doubt, UNESCO's declaration of Tarragona's artistic and monumental legacies as World Heritage site in the year 2000 meant important international recognition of the quality of the cultural and patrimonial elements offered by the city to the visitors who choose it as a tourist destination. It also represents a strategic opportunity to boost the city's promotion of tourism and its consolidation as a unique destination given its cultural and patrimonial characteristics. Our work is based on the use of structured and unstructured techniques to identify the factors that determine Tarragona's tourist destination image and that have a decisive influence on visitors' process of choice of destination. In addition to being able to ascertain Tarragona's global tourist image, we consider that the heterogeneity of its visitors requires a more detailed study that enables us to segment visitor typology. We consider that the information provided by these results may prove of great interest to those responsible for local tourism policy, both when designing products and when promoting the destination.
FoxO Transcription Factors Promote Autophagy in Cardiomyocytes (2009)

In the heart, autophagy is required for normal cardiac function and also has been implicated in cardiovascular disease. FoxO transcription factors promote autophagy in skeletal muscle and have additional roles in regulation of cell size, proliferation, and metabolism. Here we investigate the role of FoxO transcription factors in regulating autophagy and cell size in cardiomyocytes. In cultured rat neonatal cardiomyocytes, glucose deprivation leads to decreased cell size and induction of autophagy pathway genes LC3, Gabarapl1, and Atg12. Likewise, overexpression of either FoxO1 or FoxO3 reduces cardiomyocyte cell size and induces expression of autophagy pathway genes. Moreover, inhibition of FoxO activity by dominant negative FoxO1 (Delta256) blocks cardiomyocyte cell size reduction upon starvation, suggesting the necessity of FoxO function in cardiomyocyte cell size regulation. Under starvation conditions, endogenous FoxO1 and FoxO3 are localized to the nucleus and bind to promoter sequences of Gabarapl1 and Atg12. In vivo studies show that cellular stress, such as starvation or ischemia/reperfusion in mice, results in induction of autophagy in the heart with concomitant dephosphorylation of FoxO, consistent with increased activity of nuclear FoxO transcription factors. Together these results provide evidence for an important role for FoxO1 and FoxO3 in regulating autophagy and cell size in cardiomyocytes.
Stable Antibody-Producing Murine Hybridomas (1983)

A method is described for obtaining antibody-producing hybridomas that are preferentially retained in cultures of fused mouse spleen and myeloma cells. Hybridomas are produced by fusing mouse myeloma cells that are deficient in adenosine phosphoribosyltransferase (APRT) with mouse spleen cells containing Robertsonian 8.12 translocation chromosomes. The cell fusion mixtures are exposed to a culture medium that can be utilized only by APRT-positive cells, which results in the elimination of both unfused APRT-deficient myeloma cells and non-antibody-producing APRT-deficient hybridomas that arise by segregation of the 8.12 translocation chromosomes containing the APRT genes and the active heavy chain immunoglobulin gene.