gebhart/patrepeval huggingface dataset:
Exposure to placental ischemia impairs postpartum maternal renal and cardiac function in rats (2017)

Women with a history of preeclampsia (PE) have an increased risk to develop cardiovascular and renal diseases later in life, but the mechanisms underlying this effect are unknown. In rats, we assessed whether placental ischemia results in long-term effects on the maternal cardiovascular and renal systems using the reduced uterine perfusion pressure (RUPP) model for PE. Sprague-Dawley rats received either a Sham or RUPP operation at gestational <i>day 14</i> The rats were followed for 8 wk after delivery (Sham <i>n</i> = 12, RUPP <i>n</i> = 21) at which time mean arterial pressure (MAP; conscious), 24-h albuminuria, glomerular filtration rate (GFR; transcutaneous, FITC-sinistrin), and cardiac function (Vevo 770 system) were assessed. Subsequently, all rats were euthanized for mesenteric artery vasorelaxation and histology of heart and kidney. At 8 wk after delivery, there was no difference in MAP and albuminuria. However, RUPP rats showed a significantly reduced GFR [2.61 ± 0.53 vs. 3.37 ± 0.74 ml/min; <i>P</i> = 0.01]. Ultrasound showed comparable cardiac structure, but RUPP rats had a lower left ventricular ejection fraction (62 ± 7 vs. 69 ± 10%; <i>P</i> = 0.04). Heart and kidney histology was not different between Sham or RUPP rats. Furthermore, there were no differences in endothelial-dependent or -independent vasorelaxation. We show that exposure to placental ischemia in rats is accompanied by functional disturbances in maternal renal and cardiac function 8 wk after a preeclamptic pregnancy. However, these changes were not dependent on differences in blood pressure, small artery vasorelaxation, or cardiac and renal structure at this time point postpartum.
Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity. (1986)

The beta subunit of purified insulin receptor is phosphorylated on a serine residue by purified preparations of protein kinase C (ATP: protein phosphotransferase, EC 2.7.1.37). This phosphorylation is inhibited by antibodies to protein kinase C and stimulated by phospholipids, diacylglycerol, and Ca2+. The phosphorylation of the receptor by protein kinase C does not affect its insulin-binding activity but does inhibit by 65% the receptor's intrinsic tyrosine-specific protein kinase activity (ATP: protein-tyrosine O-phosphotransferase, EC 2.7.1.112). These results indicate that activators of protein kinase C, such as phorbol esters, desensitize cells to insulin by direct protein kinase C action on the insulin receptor.
DGAT: Novel Therapeutic Target for Obesity and Type 2 Diabetes Mellitus (2003)

Obesity is currently an exceptionally common problem in humans. The last several years have produced a significant number of breakthroughs in obesity related areas of investigation. Triglycerides are considered the main form of storage of excess calories in fat. A key enzyme in the synthesis of triglycerides is acylCoA: diacylglycerol acyltransferase (DGAT). Recent studies have shown that mice deficient in this enzyme are resistant to diet induced obesity and have increased insulin and leptin sensitivity. These effects suggest that inhibition of DGAT in vivo may be a novel therapeutic target not only for obesity but also for diabetes.
Phase Separation in Silica Sol–Gel System Containing Poly(ethylene oxide). I. Phase Relation and Gel Morphology (1994)

Abstract Phase separation and gelation behaviors have been studied for the acid-catalyzed, alkoxide-based silica systems containing poly(ethylene oxide) (PEO) with an average molecular weight of 100000. Gels with micrometer range interconnected porous morphology were obtained similarly to the systems containing other water-soluble polymers, in which the structure development by the spinodal decomposition and the gel forming process take place concurrently. In spite of the morphological similarity, the thermogravimetric analysis revealed that the reacting solution decomposed into phases one rich in PEO and the other rich in solvent. Macropore volume of gels depended mainly on the amount of solvent phase.
Axonal regulation of myelin protein mRNA levels in actively myelinating Schwann cells (1988)

Upon transection of a peripheral nerve, axons distal to the transection degenerate. As a consequence of this axonal degeneration, myelin-forming Schwann cells cease biosynthesis of new myelin membrane, contribute to phagocytosis of previously formed myelin, and markedly down-regulate expression of myelin-specific markers. Among the most prominent of these down-regulated markers are the major structural proteins of peripheral myelin, Po and myelin basic protein (MBP). We have used slot blot and in situ hybridization techniques to demonstrate that for actively myelinating Schwann cells, down-regulation of the Po and MBP genes occurs primarily at the level of mRNA expression. Together with other recent data, these findings strongly argue for axonal modulation of Po and MBP gene transcription during active myelination.
A comparison of photoplethysmography and ECG recording to analyse heart rate variability in healthy subjects (2009)

Measures of heart rate variability (HRV) are widely used to assess autonomic nervous system (ANS) function. The signal from which they are derived requires accurate determination of the interval between successive heartbeats; it can be recorded via electrocardiography (ECG), which is both non-invasive and widely available. However, methodological problems inherent in the recording and analysis of ECG traces have motivated a search for alternatives. Photoplethysmography (PPG) constitutes another means of determining the timing of cardiac cycles via continuous monitoring of changes in blood volume in a portion of the peripheral microvasculature. This technique measures pulse waveforms, which in some instances may prove a practical basis for HRV analysis. We investigated the feasibility of using earlobe PPG to analyse HRV by applying the same analytic process to PPG and ECG recordings made simultaneously. Comparison of 5-minute recordings demonstrated a very high degree of correlation in the temporal and frequency domains and in nonlinear dynamic analyses between HRV measures derived from PPG and ECG. Our results confirm that PPG provides accurate interpulse intervals from which HRV measures can be accurately derived in healthy subjects under ideal conditions, suggesting this technique may prove a practical alternative to ECG for HRV analysis. This finding is of particular relevance to the care of patients suffering from peripheral hyperkinesia or tremor, which make fingertip PPG recording impractical, and following clinical interventions known to introduce electrical artefacts into the electrocardiogram.
Identification of Components of Electron Transport Chains in the Extremely Thermoacidophilic Crenarchaeon Metallosphaera sedula through Iron and Sulfur Compound Oxidation Transcriptomes (2008)

The crenarchaeal order Sulfolobales collectively contain at least five major terminal oxidase complexes. Based on genome sequence information, all five complexes are found only in Metallosphaera sedula and Sulfolobus tokodaii, the two sequenced Sulfolobales capable of iron oxidization. While specific respiratory complexes in certain Sulfolobales have been characterized previously as proton pumps for maintaining intracellular pH and generating proton motive force, their contribution to sulfur and iron biooxidation has not been considered. For M. sedula growing in the presence of ferrous iron and reduced inorganic sulfur compounds (RISCs), global transcriptional analysis was used to track the response of specific genes associated with these complexes, as well as other known and putative respiratory electron transport chain elements. Open reading frames from all five terminal oxidase or bc(1)-like complexes were stimulated on one or more conditions tested. Components of the fox (Msed0467 to Msed0489) and soxNL-cbsABA (Msed0500 to Msed0505) terminal/quinol oxidase clusters were triggered by ferrous iron, while the soxABCDD' terminal oxidase cluster (Msed0285 to Msed0291) were induced by tetrathionate and S(0). Chemolithotrophic electron transport elements, including a putative tetrathionate hydrolase (Msed0804), a novel polysulfide/sulfur/dimethyl sulfoxide reductase-like complex (Msed0812 to Msed0818), and a novel heterodisulfide reductase-like complex (Msed1542 to Msed1550), were also stimulated by RISCs. Furthermore, several hypothetical proteins were found to have strong responses to ferrous iron or RISCs, suggesting additional candidates in iron or sulfur oxidation-related pathways. From this analysis, a comprehensive model for electron transport in M. sedula could be proposed as the basis for examining specific details of iron and sulfur oxidation in this bioleaching archaeon.
Latent Sequence Decompositions (2016)

We present the Latent Sequence Decompositions (LSD) framework. LSD decomposes sequences with variable lengthed output units as a function of both the input sequence and the output sequence. We present a training algorithm which samples valid extensions and an approximate decoding algorithm. We experiment with the Wall Street Journal speech recognition task. Our LSD model achieves 12.9% WER compared to a character baseline of 14.8% WER. When combined with a convolutional network on the encoder, we achieve 9.6% WER.
H Blood Types in Pigs as Predictors of Stress Susceptibility (1976)

At least two genotypes in the H system of blood groups in pigs are responsible for blood types associated with the porcine stress syndrome (PSS), and at least three genotypes are responsible for blood types associated with freedom from PSS. Two blood types, each of which apparently may result from more than one genotype, are associated with PSS in some pigs and not in others.
Effectively incorporating selected multimedia content into medical publications (2011)

Until fairly recently, medical publications have been handicapped by being restricted to non-electronic formats, effectively preventing the dissemination of complex audiovisual and three-dimensional data. However, authors and readers could significantly profit from advances in electronic publishing that permit the inclusion of multimedia content directly into an article. For the first time, the de facto gold standard for scientific publishing, the portable document format (PDF), is used here as a platform to embed a video and an audio sequence of patient data into a publication. Fully interactive three-dimensional models of a face and a schematic representation of a human brain are also part of this publication. We discuss the potential of this approach and its impact on the communication of scientific medical data, particularly with regard to electronic and open access publications. Finally, we emphasise how medical teaching can benefit from this new tool and comment on the future of medical publishing.
Impact of Capsid Conformation and Rep-Capsid Interactions on Adeno-Associated Virus Type 2 Genome Packaging (2005)

Single-stranded genomes of adeno-associated virus (AAV) are packaged into preformed capsids. It has been proposed that packaging is initiated by interaction of genome-bound Rep proteins to the capsid, thereby targeting the genome to the portal of encapsidation. Here we describe a panel of mutants with amino acid exchanges in the pores at the fivefold axes of symmetry on AAV2 capsids with reduced packaging and reduced Rep-capsid interaction. Mutation of two threonines at the rim of the fivefold pore nearly completely abolished Rep-capsid interaction and packaging. This suggests a Rep-binding site at the highly conserved amino acids at or close to the pores formed by the capsid protein pentamers. A different mutant (P. Wu, W. Xiao, T. Conlon, J. Hughes, M. Agbandje-McKenna, T. Ferkol, T. Flotte, and N. Muzyczka, J. Virol. 74:8635-8647, 2000) with an amino acid exchange at the interface of capsid protein pentamers led to a complete block of DNA encapsidation. Analysis of the capsid conformation of this mutant revealed that the pores at the fivefold axes were occupied by VP1/VP2 N termini, thereby preventing DNA introduction into the capsid. Nevertheless, the corresponding capsids had more Rep proteins bound than wild-type AAV, showing that correct Rep interaction with the capsid depends on a defined capsid conformation. Both mutant types together support the conclusion that the pores at the fivefold symmetry axes are involved in genome packaging and that capsid conformation-dependent Rep-capsid interactions play an essential role in the packaging process.
Yaba Monkey Tumor Virus Encodes a Functional Inhibitor of Interleukin-18 (2007)

Interleukin-18 (IL-18) is a critical proinflammatory cytokine whose extracellular bioactivity is regulated by a cellular IL-18 binding protein (IL-18BP). Many poxviruses have acquired variants of this IL-18BP gene, some of which have been shown to act as viral virulence factors. Yaba monkey tumor virus (YMTV) encodes a related family member, 14L, which is similar to the orthopoxvirus IL-18BPs. YMTV 14L was expressed from a baculovirus system and tested for its ability to bind and inhibit IL-18. We found that YMTV 14L bound both human IL-18 (hIL-18) and murine IL-18 with high affinity, at 4.1 nM and 6.5 nM, respectively. YMTV 14L was able to fully sequester hIL-18 but could only partially inhibit the biological activity of hIL-18 as measured by gamma interferon secretion from KG-1 cells. Additionally, 17 hIL-18 point mutants were tested by surface plasmon resonance for their ability to bind to YMTV 14L. Two clusters of hIL-18 surface residues were found to be important for the hIL-18-YMTV 14L interaction, in contrast to results for the Variola virus IL-18BP, which has been shown to primarily interact with a single cluster of three amino acids. The altered binding specificity of YMTV 14L most likely represents an adaptation resulting in increased fitness of the virus and affirms the plasticity of poxviral inhibitor domains that target cytokines like IL-18.
Leukemic Stem Cells in Childhood High-Risk ALL/t(9;22) and t(4;11) Are Present in Primitive Lymphoid-Restricted CD34+CD19− Cells (2005)

Open questions in the pathogenesis of childhood acute lymphoblastic leukemia (ALL) are which hematopoietic cell is target of the malignant transformation and whether primitive stem cells contribute to the leukemic clone. Although good-prognosis ALL is thought to originate in a lymphoid progenitor, it is unclear if this applies to high-risk ALL. Therefore, immature CD34(+)CD19(-) bone marrow cells from 8 children with ALL/t(9;22) and 12 with ALL/t(4;11) were purified and analyzed by fluorescence in situ hybridization, reverse transcription-PCR (RT-PCR), and colony assays. Fifty-six percent (n = 8, SD 31%) and 68% (n = 12, SD 26%) of CD34(+)CD19(-) cells in ALL/t(9;22) and ALL/t(4;11), respectively, carried the translocation. In addition, 5 of 168 (3%) and 22 of 228 (10%) myeloerythroid colonies expressed BCR/ABL and MLL/AF4. RT-PCR results were confirmed by sequence analysis. Interestingly, in some patients with ALL/t(4;11), alternative splicing was seen in myeloid progenitors compared with the bulk leukemic population, suggesting that these myeloid colonies might be part of the leukemic cell clone. Fluorescence in situ hybridization analysis, however, shows that none of these myeloid colonies (0 of 41 RT-PCR-positive colonies) originated from a progenitor cell that carries the leukemia-specific translocation. Thus, leukemic, translocation-positive CD34(+)CD19(-) progenitor/stem cells that were copurified by cell sorting were able to survive in these colony assays for up to 28 days allowing amplification of the respective fusion transcripts by sensitive RT-PCR. In conclusion, we show that childhood high-risk ALL/t(9;22) and t(4;11) originate in a primitive CD34(+)CD19(-) progenitor/stem cell without a myeloerythroid developmental potential.
Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease (2009)

Adaptive immune processes have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that peripheral T cell abnormalities may be present in afflicted patients. We tested this hypothesis by characterizing circulating T cells in COPD patients and correlated these findings with disease severity, smoking status, and use of inhaled glucocorticosteroids (ICS). Compared with normal controls, a lesser proportion of peripheral CD4 T cells from COPD subjects produced IL-10, whereas the CD8 T cells from these patients were more often activated and more frequently produced both IFN-gamma and IL-4. COPD severity was significantly and inversely associated with the proportion of circulating CD4 T cells and directly correlated with CD4 production of IL-2, as well as frequency of CD8 T cell activation and CD8 IFN-gamma production. Adjustments for current smoking status and ICS use by linear regression showed independent, and generally inhibitory, effects of these clinical variables on the abnormal T cell functions of these patients. We conclude that circulating T cells from COPD patients are abnormally activated and elaborate proinflammatory mediators with admixed features of Th1 and Th2 responses. Furthermore, many of these effector processes are significantly correlated with disease severity. These findings further implicate adaptive immune processes in COPD progression and indicate that facile assays of peripheral lymphocytes may provide useful insights into disease mechanisms. Current smoking and ICS use had independent effects on T cell functions among the COPD subjects, illustrating the importance of controlling for clinical parameters as covariates in immunological studies of patients afflicted with this disease.
Universal Translators for Nucleic Acid Diagnosis (2009)

Defined broadly, molecular translators are constructs that can convert any designated molecular input into a unique output molecule. In particular, the development of universal nucleic acid translators would be of significant practical value in view of the expanding biomedical importance of gene diagnostics. Currently, diagnostic assays for nucleic acids must be individually developed and optimized for each new sequence because inputs for one assay are sequence-specific and are therefore incompatible with any other assay designed for the detection of a different nucleic acid. However, if a desired nucleic acid sequence could be translated in vitro into a predetermined nucleic acid output for which there is already a known diagnostic assay, then that single assay could be easily adapted to detect nearly any strand. Here we investigate PCR-independent isothermal molecular translation strategies that function without the need for post-translation purification and can be implemented with commercially available components. Translation yields up to 96% are obtained in 5 min at room temperature with minimal background reaction (<1%) and with discrimination of single nucleotide polymorphisms in the input sequence. Furthermore, we apply these translators to adapt a high-gain HIV diagnostic system for high-throughput detection of hepatitis C, avian influenza (H5N1), and smallpox without making changes to the underlying assay. Finally, we show the feasibility of translating small-molecule interactions into nucleic acid outputs by demonstrating the utility of a DNA aptamer for translating adenosine into a readily detectable output DNA sequence. Additionally, equilibrium expressions are described in order to facilitate rational engineering of aptameric translators for label-free detection of any molecule that an aptamer can recognize.
A Pilot Study of Interleukin-11 in Subjects with Chronic Hepatitis C and Advanced Liver Disease Nonresponsive to Antiviral Therapy (2004)

The findings from this pilot study suggest that rhIL-11 may be beneficial for patients with hepatic inflammation and advanced liver disease associated with chronic HCV infection. Larger clinical trials are warranted to further evaluate the long-term antiinflammatory and antifibrotic effects of rhIL-11.
Engineered Repressible Lethality for Controlling the Pink Bollworm, a Lepidopteran Pest of Cotton (2012)

The sterile insect technique (SIT) is an environmentally friendly method of pest control in which insects are mass-produced, irradiated and released to mate with wild counterparts. SIT has been used to control major pest insects including the pink bollworm (Pectinophora gossypiella Saunders), a global pest of cotton. Transgenic technology has the potential to overcome disadvantages associated with the SIT, such as the damaging effects of radiation on released insects. A method called RIDL (Release of Insects carrying a Dominant Lethal) is designed to circumvent the need to irradiate insects before release. Premature death of insects' progeny can be engineered to provide an equivalent to sterilisation. Moreover, this trait can be suppressed by the provision of a dietary antidote. In the pink bollworm, we generated transformed strains using different DNA constructs, which showed moderate-to-100% engineered mortality. In permissive conditions, this effect was largely suppressed. Survival data on cotton in field cages indicated that field conditions increase the lethal effect. One strain, called OX3402C, showed highly penetrant and highly repressible lethality, and was tested on host plants where its larvae caused minimal damage before death. These results highlight a potentially valuable insecticide-free tool against pink bollworm, and indicate its potential for development in other lepidopteran pests.
Cloning and Characterization of cDNA Encoding Potentially Functional Mouse Glandular Kallikrein (1997)

We cloned a cDNA (pPRC-1) which was comprised of 841 nucleotides from the cDNA library of a male ICR mouse submandibular gland (). The nucleotide sequences of pPRC-1 were identical to those of exons 2 and 3 of the mGK-21 gene, a potentially functional glandular kallikrein identified in a Balb/c mouse, except for one nucleotide residue. Although this substitution changes Ile (ATT) in pPRC-1 to Val (GTT) in mGK-21, this difference has been explained by strain polymorphism. From the amino acid sequences predicted from its cDNA, we speculated that mGK-21 gene products/pGK21 consist of 261 amino acids including the -terminal signal peptide (residues 1~17), the short propeptide (residues 17~24), and the active peptide (residues 25~261). Although we did not demonstrate the enzyme activity of pGK21, it was assumed that pGK 21 was involved in the maturation of certain bioactive polypeptide(s) in mouse SMG for the following reasons : (a) mGK-21 gene was apparently expressed in a male ICR mouse SMG: (b) the proposed active site , , and residues were completely conserved in pGK21 just like other glandular kallikreins; (c) the cloned cDNA was translated to a predicted 27 kDa polypeptide chain in vitro: (d) the 27 kDa polypeptide chain produced by CHO cells was produced to a putative active form by trypsin.