gebhart/patrepeval huggingface dataset:
Reactive Oxygen Species Production in the Mitochondrial Matrix: Implications for the Mechanism of Mitochondrial Mutation Accumulation (2005)

The vicious cycle theory postulates that typical mitochondrial DNA (mtDNA) mutations cause their host mitochondria to generate more superoxide and other reactive oxygen species (ROS) than do normal mitochondria, thereby promoting the occurrence of additional mtDNA mutations at an ever-accelerating rate. However, nearly all the loss-of-function mtDNA mutations seen in vivo are large deletions, which (as the original statement of the theory indeed noted, though this has been widely overlooked) should not trigger a vicious cycle because they will prevent the assembly of the potentially superoxide-generating enzyme complexes. Consistent with this is the observation that each cell exhibiting loss of mtDNA-encoded function in vivo contains copies of a single, evidently clonally expanded, mutant mtDNA species, whereas the vicious cycle theory predicts a spectrum of mutant forms in each cell. Two recent papers, however, unveil a way in which mtDNA mutations could indeed promote ROS production of their host mitochondria. MtDNA mutations probably shift the intramitochondrial NAD(+)/NADH redox couple towards NADH, and this is now shown in vitro to cause ROS production by alpha-ketoglutarate dehydrogenase, an essential enzyme of the TCA cycle. This does not revive the vicious cycle theory, but it has complex implications for the two most plausible more recent theories, known as "survival of the slowest" and "crippled mitochondria." It may also prove to explain other recent observations in mitochondrially mutant cells in vivo.
Exceeding 5000-Fold Concentration of Dilute Analytes in Micellar Electrokinetic Chromatography (1998)

When a neutral analyte zone is injected into a charged pseudostationary phase, the length of the zone is predicted to be narrowed by 1/(1 + k), where k is the retention factor. The conditions for zone narrowing to occur assume negligible electroosmotic flow, a relatively constant electric field along the capillary column, and no pseudostationary phase in the injected analyte mixture. The theoretically expected concentration enhancement was demonstrated experimentally. Consequently, the detection sensitivity of analytes in micellar electrokinetic chromatography (MEKC) can be improved significantly. For example, 9 to 18 parts per billion of an environmentally important racemic herbicide spiked in lake water was separated by MEKC and detected by ultraviolet absorption.
Regulation of cellular function by connexin hemichannels. (2011)

Gap junctions and hemichannels are formed by a family of proteins called connexins. Till date up to twenty one different connexins have been characterized and their expression was observed to be spatio-temporally regulated. Gap junctions and hemichannels are involved in transfer of a variety of less than 1 kDa small molecules such as, ions, small metabolites, cAMP, ATP, IP3, prostaglandins, etc. Post-translational modifications of connexins and their interaction with other proteins are reported to be the key regulators of channel functions. Studies during the past decade or so, suggest the physiological important of connexin hemichannels mediating the communication between the cell and its environment. Molecules conveyed through the hemichannels elicit a variety of signaling pathways and influence cellular functions such as, cell cycle, tissue homeostasis, migration, mechanotransduction, oxidative stress. The purpose of the current review is to compile the reported studies so far and provide a general overview in our understanding how the molecular transfer through hemichannels regulates cellular signaling and functions.
A New Class of Chiral Conjugated Polymers with a Propeller-Like Structure (1997)

A new class of chiral conjugated materials, “propeller” polymers, have been designed and synthesized. By using the transition metal catalyzed cross-coupling reactions including the coupling of terminal alkynes with aryl halides and the Suzuki reaction, chiral binaphthyl monomers are reacted with o-phenylene and m-phenylene halides to construct the “propeller” polymers. Due to the chirality of the binaphthyl units and the rigidity of the conjugated system, the dipole units in these novel materials are expected to form a novel propeller-like three-dimensional configuration. Molecular weights of these polymers are analyzed by gel permeation chromatography and laser light scattering. The structures of these polymers are studied by using NMR, UV, IR, CD, and fluorescence spectroscopic methods. The repeat units of these materials are synthesized which provide further evidence for the structure of the polymers. The thermal properties of these polymers are studied by using thermal gravimetric analysis as well as differential scanning calorimetry.
Histology of familial thyroid tumours linked to a gene mapping to chromosome 19p13.2 (1999)

This paper describes the pathology of thyroid tumours showing an autosomal mode of inheritance linked to a gene that maps to chromosome 19p13.2. All the affected members from the family (seven males and two females; mean age 23 years) were clinically euthyroid and presented with nodular goitre; tumour recurrence after thyroidectomy was observed in four. In four of the five patients studied, the tumours were multifocal, bilateral well demarcated or encapsulated and composed of follicles, papillae, trabeculae/solid areas (often resembling hyalinizing trabecular adenoma of the thyroid) or an admixture, formed by cells with pale to intense cytoplasmic eosinophilia. A diagnosis of multiple adenomatous goitre was made in the thyroidectomy specimen from two patients, while the other two patients showed, in addition to multiple adenomas, a co-existent oxyphil papillary carcinoma. The fifth patient had an oxyphil cell carcinoma. All tumours were of follicular cell origin as shown by immunocytochemistry. Less than a third of the benign tumours and all three carcinomas showed a variable number of neoplastic cells diffusely immunostained for mitochondria. Histological findings of a 'multiple adenomatous goitre', non-endemic 'multinodular goitre' or multiple neoplasms of follicular cell origin with the morphology of those described here, particularly in young patients, should alert the pathologist and physician to the possibility of an inherited trait, with its implications for family screening. The tumours are usually benign and well demarcated but because of multicentricity and consequently increased risk of recurrence and/or progression to carcinoma, total thyroidectomy should be advocated.
Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles. (1997)

Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.
Improving Movie Gross Prediction through News Analysis (2009)

Traditional movie gross predictions are based on numerical and categorical movie data from The Internet Movie Database (IMDB). In this paper, we use the quantitative news data generated by Lydia, our system for large-scale news analysis, to help people to predict movie grosses. By analyzing two different models (regression and k-nearest neighbor models), we find models using only news data can achieve similar performance to those using IMDB data. Moreover, we can achieve better performance by using the combination of IMDB data and news data. Further, the improvement is statistically significant.
4D-CT reconstruction with unified spatial-temporal patch-based regularization (2015)

In this paper, we consider a limited data reconstruction problem for temporarily evolving computed tomography (CT), where some regions are static during the whole scan and some are dynamic (intensely or slowly changing). When motion occurs during a tomographic experiment one would like to minimize the number of projections used and reconstruct the image iteratively. To ensure stability of the iterative method spatial and temporal constraints are highly desirable. Here, we present a novel spatial-temporal regularization approach where all time frames are reconstructed collectively as a unified function of space and time. Our method has two main differences from the state-of-the-art spatial-temporal regularization methods. Firstly, all available temporal information is used to improve the spatial resolution of each time frame. Secondly, our method does not treat spatial and temporal penalty terms separately but rather unifies them in one regularization term. Additionally we optimize the temporal smoothing part of the method by considering the non-local patches which are most likely to belong to one intensity class. This modification significantly improves the signal-to-noise ratio of the reconstructed images and reduces computational time. The proposed approach is used in combination with golden ratio sampling of the projection data which allows one to find a better trade-off between temporal and spatial resolution scenarios.
Prevention of covered conductor burndown on distribution circuits (1980)

When an overhead conductor in a multigrounded neutral distribution system breaks and falls to the ground without simultaneously contacting the multigrounded neutral conductor, there is a significant probability of it coming to rest on a high-impedance surface, such as concrete or asphalt. The motivation to prevent burndown of overhead distribution conductors is discussed. 5 refs.
Factors affecting consumers’ “Webad” visits (1998)

Attracting consumers to a marketer Web site is critical to the effectiveness of a Web presence, and longer visits are a possible measure of success of these Web sites. Since marketers are interested in consumers’ longer visits at their Web sites, it becomes important to examine the factors that influence visits. The present study uses an empirical approach to determine the factors that affect individual exposure to material at Web sites created with a commercial intent.
The author replies (1986)

Diseases of the Colon & Rectum: April 1986 - Volume 29 - Issue 4 - p 289 doi: 10.1007/BF02553046
Hybridase activity of human ribonuclease-1 revealed by a real-time fluorometric assay (2006)

Human ribonuclease-1 (hRNase-1) is an extracellular enzyme found in exocrine pancreas, blood, milk, saliva, urine and seminal plasma, which has been implicated in digestion of dietary RNA and in antiviral host defense. The enzyme is characterized by a high catalytic activity toward both single-stranded and double-stranded RNA. In this study, we explored the possibility that hRNase-1 may also be provided with a ribonuclease H activity, i.e. be able to digest the RNA component of RNA:DNA hybrids. For this purpose, we developed an accurate and sensitive real-time RNase H assay based on a fluorogenic substrate made of a 12 nt 5'-fluorescein-labeled RNA hybridized to a complementary 3'-quencher-modified DNA. Under physiological-like conditions, hRNase-1 was found to cleave the RNA:DNA hybrid very efficiently, as expressed by a kcat/K(m) of 330 000 M(-1) s(-1), a value that is over 180-fold higher than that obtained with the homologous bovine RNase A and only 8-fold lower than that measured with Escherichia coli RNase H. The kinetic characterization of hRNase-1 showed that its hybridase activity is maximal at neutral pH, increases with lowering ionic strength and is fully inhibited by the cytosolic RNase inhibitor. Overall, the reported data widen our knowledge of the enzymatic properties of hRNase-1 and provide new elements for the comprehension of its biological function.
Evidence for involvement of the insula in the psychotropic effects of THC in humans: a double-blind, randomized pharmacological MRI study (2011)

The main reason for recreational use of cannabis is the 'high', the primary psychotropic effect of Δ9-tetrahydrocannabinol (THC). This psychoactive compound of cannabis induces a range of subjective, physical and mental reactions. The effect on heart rate is pronounced and complicates bloodflow-based neuroimaging of psychotropic effects of THC. In this study we investigated the effects of THC on baseline brain perfusion and activity in association with the induction of 'feeling high'. Twenty-three subjects participated in a pharmacological MRI study, where we applied arterial spin labelling (ASL) to measure perfusion, and resting-state functional MRI to assess blood oxygen level-dependent signal fluctuation as a measure of baseline brain activity. Feeling high was assessed with a visual analogue scale and was compared to the imaging measures. THC increased perfusion in the anterior cingulate cortex, superior frontal cortex, and insula, and reduced perfusion in the post-central and occipital gyrus. Baseline brain activity was altered, indicated by increased amplitude of fluctuations in resting-state functional MRI signal after THC administration in the insula, substantia nigra and cerebellum. Perfusion changes in frontal cortex were negatively correlated with ratings of feeling high, suggesting an interaction between cognitive control and subjective effects of THC. In conclusion, an acute THC challenge altered baseline brain perfusion and activity, especially in frontal brain areas involved in cognitive and emotional processes, and the insula, associated with interoceptive awareness. These changes may represent the THC-induced neurophysiological correlates of feeling high. The alterations in baseline brain perfusion and activity also have relevance for studies on task-related effects of THC on brain function.
"just let the cane hit it" (2014)

Sighted people often have the best of intentions when they want to help a blind person navigate, but their well meaning is also often coupled with a lack of knowledge and understanding about how a person navigates without vision. As a result what sighted people think is the right feedback is too often the wrong feedback to give to a person with a visual impairment. Understanding how to provide feedback to blind navigators is crucial to the design of assistive technologies for navigation. In our research investigating the design of a personal pedestrian navigation device, we observed firsthand the ways that sighted people seemingly misunderstand how many blind people navigate when using a white cane mobility aid. Throughout our qualitative end user studies that included focus groups and observations (including couple-based observations with a close companion) we gathered data that explicitly shows how the language and understanding of sighted vs. blind pedestrians differs greatly and even how it can be dangerous when people interfere in the wrong way. From our findings we discuss why it is difficult for a blind person to navigate like a sighted person to ensure designers are aware of the difficulties and designing with new training in mind, not simply designing from their own point of view. We also want to encourage advocacy and empathy amongst the sighted community towards this activity of walking around independently.
Towards model-based gesture recognition (2002)

We propose a new technique for gesture recognition that involves both physical and control models of gesture performance, and describe preliminary experiments done to validate the approach. The technique incorporates underlying dynamics and control models are used to augment a set of Kalman-filter-based recognizer modules so that each filters the input data under the a priori assumption that one of the gestures is being performed. The recognized gesture is the filter output that most closely matches the output of an unaugmented Kalman filter. In our preliminary experiments, we treated gestures made with simple motions of the right arm, done while tracking only hand position. We modeled the path that the hand traverses while performing a gesture as a point-mass moving through air. The control model for each specific gesture was simply an experimentally determined sequence of applied forces plus a proportional control based on spatial position. Our experiments showed that even using such a simple set of models we were able to obtain results reasonably comparable with a carefully hand-constructed feature-based discriminator on a limited set of spatially-distinct planar gestures.
Allelic losses at chromosome 8p21-23 are early and frequent events in the pathogenesis of lung cancer. (1999)

Allelic losses on the short arm of chromosome 8 (8p) have been reported as frequent events in several cancers, including lung. However, no comprehensive mapping analysis of chromosome 8p in lung cancer tumors has been performed, and no data are available about the stage at which these abnormalities occur during the multistage development of lung cancer. Using 26 microsatellite markers, we mapped the chromosome 8 regions frequently deleted in lung cancer in 13 small cell carcinoma and 17 non-small cell lung carcinoma cell lines and in 68 microdissected archival primary lung tumors (22 small cell lung carcinomas, 25 squamous cell carcinomas, and 21 adenocarcinomas). We also studied the role of 8p deletions in lung cancer pathogenesis by examining 95 microdissected normal epithelium and preneoplastic samples from 11 surgically resected squamous cell lung carcinomas and from 58 bronchoscopy biopsy samples obtained from 31 current and former smokers. High frequencies of deletions at 8p21-23 regions were detected in lung cancer cell lines and in primary lung tumors. Deletions commenced early during the multistage development of lung cancer at the hyperplasia/metaplasia stage in cancer patients and in smokers without cancer. Allelic deletions persisted for up to 48 years after smoking cessation. There was a progressive increase of the overall 8p21-23 loss of heterozygosity frequency and in the size of the deleted region with increasing severity of histopathological preneoplastic changes. In epithelial samples from resected squamous cell lung carcinomas, we compared the presence of loss of heterozygosity at 8p21-23 with deletions at chromosomes 3p and 9p. Of interest, the pattern of deletions was not random, and 8p21-23 allelic losses always followed 3p deletions and usually followed 9p deletions. We conclude that 8p21-23 deletions are frequent and early events in the pathogenesis of lung carcinomas.
Intravenous delivery of GS-441524 is efficacious in the African green monkey model of SARS-CoV-2 infection (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, has infected over 260 million people over the past 2 years. Remdesivir (RDV, VEKLURY®) is currently the only antiviral therapy fully approved by the FDA for the treatment of COVID-19. The parent nucleoside of RDV, GS-441524, exhibits antiviral activity against numerous respiratory viruses including SARS-CoV-2, although at reduced in vitro potency compared to RDV in most assays. Here we find in both human alveolar and bronchial primary cells, GS-441524 is metabolized to the pharmacologically active GS-441524 triphosphate (TP) less efficiently than RDV, which correlates with a lower in vitro SARS-CoV-2 antiviral activity. In vivo, African green monkeys (AGM) orally dosed with GS-441524 yielded low plasma levels due to limited oral bioavailability of <10%. When GS-441524 was delivered via intravenous (IV) administration, although plasma concentrations of GS-441524 were significantly higher, lung TP levels were lower than observed from IV RDV. To determine the required systemic exposure of GS-441524 associated with in vivo antiviral efficacy, SARS-CoV-2 infected AGMs were treated with a once-daily IV dose of either 7.5 or 20 mg/kg GS-441524 or IV RDV for 5 days and compared to vehicle control. Despite the reduced lung TP formation compared to IV dosing of RDV, daily treatment with IV GS-441524 resulted in dose-dependent efficacy, with the 20 mg/kg GS-441524 treatment resulting in significant reductions of SARS-CoV-2 replication in the lower respiratory tract of infected animals. These findings demonstrate the in vivo SARS-CoV-2 antiviral efficacy of GS-441524 and support evaluation of its orally bioavailable prodrugs as potential therapies for COVID-19.
The Conserved Chimeric Transcript UPGRADE2 Is Associated with Unreduced Pollen Formation and Is Exclusively Found in Apomictic Boechera Species (2013)

In apomictic Boechera spp., meiotic diplospory leads to the circumvention of meiosis and the suppression of recombination to produce unreduced male and female gametes (i.e. apomeiosis). Here, we have established an early flower developmental staging system and have performed microarray-based comparative gene expression analyses of the pollen mother cell stage in seven diploid sexual and seven diploid apomictic genotypes to identify candidate factors for unreduced pollen formation. We identified a transcript unique to apomictic Boechera spp. called UPGRADE2 (BspUPG2), which is highly up-regulated in their pollen mother cells. BspUPG2 is highly conserved among apomictic Boechera spp. genotypes but has no homolog in sexual Boechera spp. or in any other taxa. BspUPG2 undergoes posttranscriptional processing but lacks a prominent open reading frame. Together with the potential of stably forming microRNA-like secondary structures, we hypothesize that BspUPG2 functions as a long regulatory noncoding messenger RNA-like RNA. BspUPG2 has apparently arisen through a three-step process initiated by ancestral gene duplication of the original BspUPG1 locus, followed by sequential insertions of segmentally duplicated gene fragments, with final exonization of its sequence structure. Its genesis reflects the hybridization history that characterizes the genus Boechera.