gebhart/patrepeval huggingface dataset:
Effects of Metformin on Collagen Glycation and Diastolic Dysfunction in Diabetic Myocardium (1998)

BACKGROUND: Collagen accumulation in the myocardial interstitium of diabetic animals is considered to promote diastolic stiffness through advanced glycosylation. Because in vitro data suggest that metformin can modify glycosylation, this study was undertaken in a canine diabetic model 4 months in duration. METHODS AND RESULTS: Untreated diabetics (group II) and diabetics treated with metformin alone (group III) or with insulin (group IV) were compared in the basal state and during volume infusion. Basal hemoglobin A(1c), heart rate, aortic pressure, and ejection fraction were comparable. Left ventricular end-diastolic pressure was significantly increased in the untreated diabetics of group II, associated with a reduced end-diastolic volume. By contrast these parameters in the metformin-treated diabetics of group III were comparable with those in the normals of group I. Similarly in group IV end-diastolic volume was higher than that in group II, but filling pressure, although lower, was not significantly so. Calculation of left ventricular chamber stiffness in the basal state indicated a higher level for group II compared with controls and the treatment groups. During the systemic infusion of dextran, the untreated diabetics of group II had the largest end-diastolic pressure increase and the smallest rise of end-diastolic volume of the treatment groups, consistent with a significantly greater chamber stiffness. Myocardial collagen concentration was increased in group II with an interstitial distribution on morphological exam. Levels of collagen-linked advanced glycosylation end products isolated from the left ventricular were significantly greater in group II than in group I. Treatment with metformin prevented the increment observed in the untreated diabetic but had no effect on the elevated collagen concentration. CONCLUSIONS: Untreated diabetics exhibited increased diastolic chamber stiffness associated with collagen-linked glycation in myocardium compared with control animals. Chronic metformin use prevented the abnormalities of function and composition.
Characterization of Heterologous Multigene Operons in Transgenic Chloroplasts. Transcription, Processing, and Translation (2005)

The first characterization of transcriptional, posttranscriptional, and translational processes of heterologous operons expressed via the tobacco (Nicotiana tabacum) chloroplast genome is reported here. Northern-blot analyses performed on chloroplast transgenic lines harboring seven different heterologous operons revealed that polycistronic mRNA was the predominant transcript produced. Despite the lack of processing of such polycistrons, large amounts of foreign protein accumulation was observed in these transgenic lines, indicating abundant translation of polycistrons. This is supported by polysome fractionation assays, which allowed detection of polycistronic RNA in lower fractions of the sucrose gradients. These results show that the chloroplast posttranscriptional machinery can indeed detect and translate multigenic sequences that are not of chloroplast origin. In contrast to native transcripts, processed and unprocessed heterologous polycistrons were stable, even in the absence of 3' untranslated regions (UTRs). Unlike native 5'UTRs, heterologous secondary structures or 5'UTRs showed efficient translational enhancement independent of cellular control. Abundant read-through transcripts were observed in the presence of chloroplast 3'UTRs but they were efficiently processed at introns present within the native operon. Heterologous genes regulated by the psbA (the photosystem II polypeptide D1) promoter, 5' and 3'UTRs have greater abundance of transcripts than the endogenous psbA gene because transgenes were integrated into the inverted repeat region. Addressing questions about polycistrons, and the sequences required for their processing and transcript stability, are essential in chloroplast metabolic engineering. Knowledge of such factors would enable engineering of foreign pathways independent of the chloroplast complex posttranscriptional regulatory machinery.
Traffic Accident Analysis Using Machine Learning Paradigms (2005)

Engineers and researchers in the automobile industry have tried to design and build safer automobiles, but traffic accidents are unavoidable. Patterns involved in dangerous crashes could be detected if we develop accurate prediction models capable of automatic classification of type of injury severity of various traffic accidents. These behavioral and roadway accident patterns can be useful to develop traffic safety control policies. We believe that to obtain the greatest possible accident reduction effects with limited budgetary resources, it is important that measures be based on scientific and objective surveys of the causes of accidents and severity of injuries. This paper summarizes the performance of four machine learning paradigms applied to modeling the severity of injury that occurred during traffic accidents. We considered neural networks trained using hybrid learning approaches, support vector machines, decision trees and a concurrent hybrid model involving decision trees and neural networks. Experiment results reveal that among the machine learning paradigms considered the hybrid decision tree-neural network approach outperformed the individual approaches. Povzetek: Stirje pristopi strojnega ucenja so uporabljeni za preiskovanje zakonitosti poskodb v prometnih nesrecah.
Does load-induced ventricular hypertrophy progress to systolic heart failure? (2005)

Ventricular hypertrophy develops in response to numerous forms of cardiac stress, including pressure or volume overload, loss of contractile mass from prior infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric proteins. Hypertrophic growth is believed to have a compensatory role that diminishes wall stress and oxygen consumption, but Framingham and other studies established ventricular hypertrophy as a marker for increased risk of developing chronic heart failure, suggesting that hypertrophy may have maladaptive features. However, the relative contribution of comorbid disease to hypertrophy-associated systolic failure is unknown. For instance, coronary artery disease is induced by many of the same risk factors that cause hypertrophy and can itself lead to systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy commonly progresses to systolic dysfunction without the contribution of intervening ischemia or infarction. In this review, we summarize findings from epidemiologic studies, preclinical experiments in animals, and clinical trials to lay out what is known-and not known-about this important question.
Transcriptomic Analysis Comparing Tumor-Associated Neutrophils with Granulocytic Myeloid-Derived Suppressor Cells and Normal Neutrophils (2012)

The role of myeloid cells in supporting cancer growth is well established. Most work has focused on myeloid-derived suppressor cells (MDSC) that accumulate in tumor-bearing animals, but tumor-associated neutrophils (TAN) are also known to be capable of augmenting tumor growth. However, little is known about their evolution, phenotype, and relationship to naïve neutrophils (NN) and to the granulocytic fraction of MDSC (G-MDSC).In the current study, a transcriptomics approach was used in mice to compare these cell types. Our data show that the three populations of neutrophils are significantly different in their mRNA profiles with NN and G-MDSC being more closely related to each other than to TAN. Structural genes and genes related to cell-cytotoxicity (i.e. respiratory burst) were significantly down-regulated in TAN. In contrast, many immune-related genes and pathways, including genes related to the antigen presenting complex (e.g. all six MHC-II complex genes), and cytokines (e.g. TNF-α, IL-1-α/β), were up-regulated in G-MDSC, and further up-regulated in TAN. Thirteen of the 25 chemokines tested were markedly up-regulated in TAN compared to NN, including striking up-regulation of chemoattractants for T/B-cells, neutrophils and macrophages.This study characterizes different populations of neutrophils related to cancer, pointing out the major differences between TAN and the other neutrophil populations.
Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice (2009)

Wnt signaling increases bone mass by stimulating osteoblast lineage commitment and expansion and forms the basis for novel anabolic therapeutic strategies being developed for osteoporosis. These strategies include derepression of Wnt signaling by targeting secreted Wnt pathway antagonists, such as sclerostin. However, such therapies are associated with safety concerns regarding an increased risk of osteosarcoma, the most common primary malignancy of bone. Here, we analyzed 5 human osteosarcoma cell lines in a high-throughput screen for epigenetically silenced tumor suppressor genes and identified Wnt inhibitory factor 1 (WIF1), which encodes an endogenous secreted Wnt pathway antagonist, as a candidate tumor suppressor gene. In vitro, WIF1 suppressed beta-catenin levels in human osteosarcoma cell lines, induced differentiation of human and mouse primary osteoblasts, and suppressed the growth of mouse and human osteosarcoma cell lines. Wif1 was highly expressed in the developing and mature mouse skeleton, and, although it was dispensable for normal development, targeted deletion of mouse Wif1 accelerated development of radiation-induced osteosarcomas in vivo. In primary human osteosarcomas, silencing of WIF1 by promoter hypermethylation was associated with loss of differentiation, increased beta-catenin levels, and increased proliferation. These data lead us to suggest that derepression of Wnt signaling by targeting secreted Wnt antagonists in osteoblasts may increase susceptibility to osteosarcoma.
An experimental time-compression system for satellite television transmission (1985)

We describe an experimental system for demonstrating time-compression multiplexing (TCM) of two NTSC color television signals in a satellite channel of 36 MHz. The system employs digital processing to derive line or field differentials from each picture. The television signals are then converted into interleaved lines (or fields) of unimpaired baseband video and companded line (or field) differentials. These signal components are finally time compressed and multiplexed into a combined signal for single-carrier FM transmission. With 4.5-m earth stations, the field-differential technique offers extremely good transmission quality suitable for TV distribution to cable head-ends (weighted signal-to-noise ratio, WSNR ≈ 51.5 dB), while the line-differential method provides a slightly lower WSNR ( ≈ 49 dB). We recommend the field-differential approach because of its superior overall picture quality. For larger receive stations (7m), higher picture quality (WSNR ≈ 56 dB) could be obtained. If 10-m earth stations are employed, the received video performance is practically indistinguishable from the corresponding one in the one-television-per-transponder case, and we infer that three pictures can indeed be sent with a graceful degradation as previously suggested. By choosing the parameters properly, the current TCM system can be optimized for a wide variety of applications with higher channel capacity.
The XQuery Formal Semantics: A Foundation for Implementation and Optimization (2002)

XQuery is a strongly typed, functional language, which supports the common processing, transformation, and querying tasks of a wide variety of XML applications. Following the tradition of other functional languages, XQuery includes a complete formal semantics. In this paper, we argue that basing an XQuery implementation on the XQuery Formal Semantics not only ensures correctness, but is a good foundation for optimization. We describe an architecture that we have implemented and that is based on the XQuery Formal Semantics and describe several logical and physical optimizations that can be easily integrated in the above architecture.
Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor. (1994)

The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicken T3R alpha (cT3R alpha) positioned between the DNA-binding domain of the yeast GAL4 protein and the potent 90-amino-acid transactivating domain of the herpes simplex virus VP16 protein (GAL4-T3R-VP16), we provide functional evidence that binding of ligand releases T3Rs and RARs from an inhibitory cellular factor. GAL4-T3R-VP16 does not bind T3 and does not activate transcription from a GAL4 reporter when expressed alone but is able to activate transcription when coexpressed with unliganded T3R or RAR. This activation is reversed by T3 or RA, suggesting that these receptors compete with GAL4-T3R-VP16 for a cellular inhibitor and that ligand reverses this effect by dissociating T3R or RAR from the inhibitor. A chimera containing the entire ligand-binding domain of cT3R alpha (amino acids 120 to 408) linked to VP16 [GAL4-T3R(408)-VP16] is activated by unliganded receptor as well as by T3. In contrast, GAL4-T3R containing the amino acid 120 to 408 ligand-binding region without the VP16 domain is activated only by T3. The highly conserved ninth heptad, which is involved in heterodimerization, appears to participate in the receptor-inhibitor interaction, suggesting that the inhibitor is a related member of the receptor gene family. In striking contrast to T3R and RAR, RXR activates GAL4-T3R-VP16 only with its ligand, 9-cis RA, but unliganded RXR does not appear to be the inhibitor suggested by these studies. Further evidence that an orphan receptor may be the inhibitor comes from our finding that COUP-TF inhibits activation of GAL4-T3R-VP16 by unliganded T3R and the activation of GAL4-T3R by T3. These and other results suggest that an inhibitory factor suppresses transactivation by the T3Rs and RARs while these receptors are bound to DNA and that ligands act, in part, by inactivating or promoting dissociation of a receptor-inhibitor complex.
Caveolin-1 Expression Is Required for the Development of Pulmonary Emphysema through Activation of the ATM-p53-p21 Pathway (2008)

Free radicals play a role in aging and age-related human diseases, including pulmonary emphysema. Cigarette smoke represents a source of oxidants and is considered an environmental hazard that causes pulmonary emphysema. Here, we show that caveolin-1 activates ataxia telangiectasia-mutated (ATM) after oxidative stress by sequestering the ATM inhibitor, the catalytic subunit of protein phosphatase 2A, into caveolar membranes. We demonstrate that cigarette smoke extracts promote stress-induced premature senescence in wild type but not caveolin-1 null lung fibroblasts and that caveolin-1 expression is required for activation of the ATM-p53-p21(Waf1)(/)(Cip1) pathway following stimulation with cigarette smoke extracts in vitro. In vivo studies show that caveolin-1 expression is necessary for cigarette smoking-induced senescence of lung fibroblasts and pulmonary emphysema. These findings bring new insights into the molecular mechanism underlying free radical activation of the ATM-p53 pathway and indicate that caveolin-1 is a novel therapeutic target for the treatment and/or prevention of pulmonary emphysema.
Three-Dimensional Super-Resolution Imaging by Stochastic Optical Reconstruction Microscopy (2008)

Recent advances in far-field fluorescence microscopy have led to substantial improvements in image resolution, achieving a near-molecular resolution of 20 to 30 nanometers in the two lateral dimensions. Three-dimensional (3D) nanoscale-resolution imaging, however, remains a challenge. We demonstrated 3D stochastic optical reconstruction microscopy (STORM) by using optical astigmatism to determine both axial and lateral positions of individual fluorophores with nanometer accuracy. Iterative, stochastic activation of photoswitchable probes enables high-precision 3D localization of each probe, and thus the construction of a 3D image, without scanning the sample. Using this approach, we achieved an image resolution of 20 to 30 nanometers in the lateral dimensions and 50 to 60 nanometers in the axial dimension. This development allowed us to resolve the 3D morphology of nanoscopic cellular structures.
In vitro effect of oestradiol on thymidine uptake in pulmonary vascular smooth muscle cell: role of the endothelium (1992)

1. The effect of different concentrations of oestradiol-17 beta (3-300 nM) on [3H]-thymidine uptake was studied in segments from canine pulmonary artery, and cultures of rat pulmonary vascular smooth muscle cells (VSMC). 2. Incubation with oestradiol-17 beta for 24 h, potentiated in a concentration-dependent manner [3H]-thymidine uptake in VSMC cultures. 3. Oestradiol-17 beta potentiated thymidine uptake by pulmonary arterial segments but only when the endothelium had been removed. Autoradiography showed dense incorporation of radioactive thymidine in the vascular smooth muscle cells of the media. 4. The non-steroidal oestrogen, stilboestrol (300 nM), also significantly potentiated [3H]-thymidine uptake, in both VSMC cultures and pulmonary artery segments. Testosterone was ineffective at a similar concentration. 5. Pre-incubation of the pulmonary VSMC with the anti-oestrogen tamoxifen (1 microM) antagonized the potentiating effect of oestradiol-17 beta on [3H]-thymidine incorporation. The effect of tamoxifen was less pronounced in pulmonary arterial segments. 6. These data suggest that oestrogen may promote proliferation of pulmonary VSMC. Endothelial injury or dysfunction may be an important factor in the expression of the oestrogenic effect. 7. We speculate that plasma oestrogen may be a contributing factor to the proliferative lesion observed in certain forms of pulmonary vascular injury in women.
PROPELLER MRI: Clinical testing of a novel technique for quantification and compensation of head motion (2001)

While head motion is considered a significant problem in magnetic resonance imaging (MRI), there is no data to quantify its extent, severity, or effect on image quality. PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) MRI offers a novel means of quantifying and compensating for head motion. We performed axial T2-weighted PROPELLER (motion corrected: P-CR; uncorrected: P-UNCR) and conventional MRI (CONV), with equal scan times, in five normal volunteers and 35 clinical subjects. Volunteers were examined lying still and performing two separate head movements (shake "no" and nod "yes") to assess detection and compensation of in-plane motion by PROPELLER MRI. Images were examined by three radiologists for motion artifact and for overall image quality. Head rotation and translation was detected in all subjects during each slice acquisition, with expected changes occurring with volunteer head motion. Motion artifact was less commonly seen on PROPELLER than CONV MR (chi(2) test P < 0.001). PROPELLER was preferred over CONV in all subjects (P < 0.05) and P-CR was judged superior to P-UNCR (P = 0.02). Intracranial pathology was equally or better demonstrated with PROPELLER. PROPELLER MRI offers a means of quantifying head motion, reducing motion artifact, and improving image quality.
Identification, Cloning, and Characterization of a Lactococcus lactis Branched-Chain α-Keto Acid Decarboxylase Involved in Flavor Formation (2005)

The biochemical pathway for formation of branched-chain aldehydes, which are important flavor compounds derived from proteins in fermented dairy products, consists of a protease, peptidases, a transaminase, and a branched-chain alpha-keto acid decarboxylase (KdcA). The activity of the latter enzyme has been found only in a limited number of Lactococcus lactis strains. By using a random mutagenesis approach, the gene encoding KdcA in L. lactis B1157 was identified. The gene for this enzyme is highly homologous to the gene annotated ipd, which encodes a putative indole pyruvate decarboxylase, in L. lactis IL1403. Strain IL1403 does not produce KdcA, which could be explained by a 270-nucleotide deletion at the 3' terminus of the ipd gene encoding a truncated nonfunctional decarboxylase. The kdcA gene was overexpressed in L. lactis for further characterization of the decarboxylase enzyme. Of all of the potential substrates tested, the highest activity was observed with branched-chain alpha-keto acids. Moreover, the enzyme activity was hardly affected by high salinity, and optimal activity was found at pH 6.3, indicating that the enzyme might be active under cheese ripening conditions.
Safe Visual Navigation via Deep Learning and Novelty Detection (2017)

Robots that use learned perceptual models in the real world must be able to safely handle cases where they are forced to make decisions in scenarios that are unlike any of their training examples. However, state-of-the-art deep learning methods are known to produce erratic or unsafe predictions when faced with novel inputs. Furthermore, recent ensemble, bootstrap and dropout methods for quantifying neural network uncertainty may not efficiently provide accurate uncertainty estimates when queried with inputs that are very different from their training data. Rather than unconditionally trusting the predictions of a neural network for unpredictable real-world data, we use an autoencoder to recognize when a query is novel, and revert to a safe prior behavior. With this capability, we can deploy an autonomous deep learning system in arbitrary environments, without concern for whether it has received the appropriate training. We demonstrate our method with a vision-guided robot that can leverage its deep neural network to navigate 50% faster than a safe baseline policy in familiar types of environments, while reverting to the prior behavior in novel environments so that it can safely collect additional training data and continually improve. A video illustrating our approach is available at:
ConToVi: Multi‐Party Conversation Exploration using Topic‐Space Views (2016)

Abstract We introduce a novel visual analytics approach to analyze speaker behavior patterns in multi‐party conversations. We propose Topic‐Space Views to track the movement of speakers across the thematic landscape of a conversation. Our tool is designed to assist political science scholars in exploring the dynamics of a conversation over time to generate and prove hypotheses about speaker interactions and behavior patterns. Moreover, we introduce a glyph‐based representation for each speaker turn based on linguistic and statistical cues to abstract relevant text features. We present animated views for exploring the general behavior and interactions of speakers over time and interactive steady visualizations for the detailed analysis of a selection of speakers. Using a visual sedimentation metaphor we enable the analysts to track subtle changes in the flow of a conversation over time while keeping an overview of all past speaker turns. We evaluate our approach on real‐world datasets and the results have been insightful to our domain experts.