gebhart/patrepeval huggingface dataset:
Surface tension in situ in flooded alveolus unaltered by albumin (2014)

In the acute respiratory distress syndrome, plasma proteins in alveolar edema liquid are thought to inactivate lung surfactant and raise surface tension, T. However, plasma protein-surfactant interaction has been assessed only in vitro, during unphysiologically large surface area compression (%ΔA). Here, we investigate whether plasma proteins raise T in situ in the isolated rat lung under physiologic conditions. We flood alveoli with liquid that omits/includes plasma proteins. We ventilate the lung between transpulmonary pressures of 5 and 15 cmH2O to apply a near-maximal physiologic %ΔA, comparable to that of severe mechanical ventilation, or between 1 and 30 cmH2O, to apply a supraphysiologic %ΔA. We pause ventilation for 20 min and determine T at the meniscus that is present at the flooded alveolar mouth. We determine alveolar air pressure at the trachea, alveolar liquid phase pressure by servo-nulling pressure measurement, and meniscus radius by confocal microscopy, and we calculate T according to the Laplace relation. Over 60 ventilation cycles, application of maximal physiologic %ΔA to alveoli flooded with 4.6% albumin solution does not alter T; supraphysiologic %ΔA raise T, transiently, by 51 ± 4%. In separate experiments, we find that addition of exogenous surfactant to the alveolar liquid can, with two cycles of maximal physiologic %ΔA, reduce T by 29 ± 11% despite the presence of albumin. We interpret that supraphysiologic %ΔA likely collapses the interfacial surfactant monolayer, allowing albumin to raise T. With maximal physiologic %ΔA, the monolayer likely remains intact such that albumin, blocked from the interface, cannot interfere with native or exogenous surfactant activity.
The Anesthetic Effects of Etomidate: Species-Specific Interaction with α2-Adrenoceptors (2007)

The sedative effects of etomidate exhibit a species-specific interaction with alpha2-adrenoceptors. Although the decrease in potency of etomidate by atipamezole may be caused by an interaction with alpha2-adrenoceptors in X. laevis tadpoles, results in mice indicate that the hypnotic effect of etomidate does not require alpha2-adrenoceptors.
Disease Resistance and Abiotic Stress Tolerance in Rice Are Inversely Modulated by an Abscisic Acid–Inducible Mitogen-Activated Protein Kinase[W] (2003)

Mitogen-activated protein kinase (MAPK) cascades play an important role in mediating stress responses in eukaryotic organisms. However, little is known about the role of MAPKs in modulating the interaction of defense pathways activated by biotic and abiotic factors. In this study, we have isolated and functionally characterized a stress-responsive MAPK gene (OsMAPK5) from rice. OsMAPK5 is a single-copy gene but can generate at least two differentially spliced transcripts. The OsMAPK5 gene, its protein, and kinase activity were inducible by abscisic acid as well as various biotic (pathogen infection) and abiotic (wounding, drought, salt, and cold) stresses. To determine its biological function, we generated and analyzed transgenic rice plants with overexpression (using the 35S promoter of Cauliflower mosaic virus) or suppression (using double-stranded RNA interference [dsRNAi]) of OsMAPK5. Interestingly, suppression of OsMAPK5 expression and its kinase activity resulted in the constitutive expression of pathogenesis-related (PR) genes such as PR1 and PR10 in the dsRNAi transgenic plants and significantly enhanced resistance to fungal (Magnaporthe grisea) and bacterial (Burkholderia glumae) pathogens. However, these same dsRNAi lines had significant reductions in drought, salt, and cold tolerance. By contrast, overexpression lines exhibited increased OsMAPK5 kinase activity and increased tolerance to drought, salt, and cold stresses. These results strongly suggest that OsMAPK5 can positively regulate drought, salt, and cold tolerance and negatively modulate PR gene expression and broad-spectrum disease resistance.
2.8-A Structure of penicillin-sensitive D-alanyl carboxypeptidase-transpeptidase from Streptomyces R61 and complexes with beta-lactams. (1985)

The crystallographic structure of the penicillin-sensitive D-alanyl carboxypeptidase-transpeptidase from Streptomyces R61 has been solved to 2.8-A resolution. The 38,000-dalton serine peptidase has two regions of secondary structure, an alpha/beta cluster, and a region which contains five helical segments. The beta sheet is composed of five beta strands. The tertiary structure has no homology with the classic serine proteases or with the zinc carboxypeptidases. The binding at a common site of three types of beta-lactam (a penicillin, a cephalosporin, a monocyclic beta-lactam) and a desazacyclobutanone has been observed in Fourier difference maps. The binding site sequence is Val-Gly-Ser-Val-Thr-Lys. The beta-lactam ring lies near the enzyme's catalytic serine at position 37, and the C3 substituent of a cephalosporin falls near lysine 40.
Textbook of Clinical Chemistry. N. W. Tietz, Ed., W. B. Saunders Co., Philadelphia, PA 19105, September 1985, xxvi + 1919 pp, $59.95. ISBN 0-7216-8886-1 (1986)

Journal Article Textbook of Clinical Chemistry. N. W. Tietz, Ed., W. B. Saunders Co., Philadelphia, PA 19105, September 1985, xxvi + 1919 pp, $59.95. ISBN 0-7216-8886-1 Get access Seymour Bakerman Seymour Bakerman East Carolina Univ. School of Med. Greenville, NC 27834-4354 Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 32, Issue 4, 1 April 1986, Page 717, https://doi.org/10.1093/clinchem/32.4.717 Published: 01 April 1986
RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice (2012)

Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with RAGE-null versus wild-type bone marrow resulted in significantly improved axonal regeneration and restoration of function. Diabetic RAGE-null mice displayed higher numbers of invading macrophages in the nerve segments postcrush compared with wild-type animals, and these macrophages in diabetic RAGE-null mice displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow-derived macrophages with advanced glycation end products (AGEs), which accumulate in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE-dependent manner. Blockade of RAGE may be beneficial in the acute complications of diabetic neuropathy, at least in part, via upregulation of regeneration signals.
Hemoglobin Content of Single Erythrocytes from Fetuses with Parents Having Heterozygous β-Thalassemia (1985)

The hemoglobin content of single erythrocytes was determined by microspectrophotometry as total extinction (TE) at 415 nm in subjects with a wide spectrum of hemoglobin levels and erythrocyte indices. Precise measurements of the cellular area (A) and the ratio TE/A were also recorded. A significant correlation was found between TE and mean corpuscular hemoglobin (MCH), A and mean corpuscular volume, and TE/A and mean cell hemoglobin concentration (MCHC) for the cases studied. In addition, TE, A and TE/A were determined in fetal erythrocytes obtained by fetoscopy at the 20th week of gestation for prenatal diagnosis of beta-thalassemia. The mean red cell TE and TE/A of the group of fetuses diagnosed to have thalassemia major were significantly lower than those of the group of normal controls and with heterozygous beta-thalassemia. The significant differences of TE, A and TE/A between maternal and fetal blood allowed a safe distinction of the latter. The calculated MCH of the fetuses with thalassemia major was 12% less than that of the normal controls; the respective difference of the mean cell size was 5% and that of MCHC 3% lower than normal.
Ontogeny and the effects of in utero brain ischemia on interleukin‐1β and interleukin‐6 protein expression in ovine cerebral cortex and white matter (2012)

Interleukin (IL)-1β and IL-6 have been implicated in brain development, injury progression, and fetal/maternal immune interactions. We examined IL-1β and IL-6 protein expression in cerebral cortex (CC) and white matter (WM) from non-ischemic ovine fetuses at 87-90, 122-127, and 135-137 days of gestation, pregnant ewes at 87-90 and 135-137 days of gestation, and fetuses exposed to 48 or 72h of reperfusion after ischemia. Protein expression was determined by Western immunoblot. In non-ischemic CC, IL-1β was higher (P<0.05) in adult sheep and fetuses at 135-137 than 87-90 and 122-127 days, and IL-6 higher at 122-127 than 87-90 days, and in adults than fetuses at 87-90, 122-127, and 135-137 days of gestation. In non-ischemic fetal WM, IL-6 was higher at 135-137 than 87-90 days, but IL-1β did not differ. In CC, IL-1β was higher in ewes at 135-137 than 87-90 days and IL-6 at 135-137 days and in non-pregnant adults than ewes at 87-90 days of gestation. In WM, IL-1β was higher in ewes at 135-137 than 87-90 days of gestation, but IL-6 did not differ. Forty-eight and 72h after ischemia, CC IL-1β was higher than in non-ischemic fetuses. Seventy-two hours after ischemia, IL-1β and IL-6 were higher in WM than CC. In conclusion, IL-1β and IL-6 exhibit developmental regulation in fetal brain, change during gestation in brains of pregnant ewes, show regional differences in normal brains of fetuses and ewes, demonstrate differential responses after ischemia in CC and WM, and IL-1β but not IL-6 increases after ischemia in CC.
Integrated Approach to Rotary-Steerable Drilling Optimization Using Concurrent Real-time Measurement of Near-bit Borehole Caliper and Near-bit Vibration (2008)

Abstract A novel sensor system, integrated into a rotary steerable system (RSS), has led to a new level of drilling optimization by providing the concurrent real-time measurement of near-bit borehole caliper and near-bit vibration. This new sensor system gathers all the information 2 to 3 meters above the drill bit, whereas conventional MWD/LWD sensor measurements are made 20 to 40 meters away from the bit. Integration of these sensors with an RSS resulted in consistent measurements of borehole caliper and the three principal types of downhole vibration (torsional, lateral, and axial), which has helped facilitate comparative analysis of drill bit and BHA performance for different BHAs and wells. Additionally the real-time drilling data was available to a multi-disciplinary drilling optimization team consisting of engineers and researchers. Remote satellite communication and Internet technologies enabled the team to monitor the downhole drilling conditions around the clock and to provide critical feedback to rig site engineers for minimizing vibration-related failures and for improving drilling efficiencies. This paper will discuss the application of real-time near-bit caliper and vibration measurements while drilling with various hole-size RSS. One unique feature of this particular RSS is a shop-configurable point-the-bit or push-the-bit mode, depending upon the application. This paper also shows a comparison of borehole conditions and vibration between point-the-bit and push-the-bit modes using an identical RSS, having consistency in stiffness, weight, force applying capability and control system. Through the integrated sensor and team approach, the ability to detect borehole washout conditions and/or BHA instability due to vibration allows RSS operators to take timely remedial action before the occurrence of downhole RSS failure. As a result, the performance and survivability of the RSS has been remarkably improved.
A loose ligature-induced mononeuropathy produces hyperalgesias mediated by both the injured sciatic nerve and the adjacent saphenous nerve (1993)

An experimental mononeuropathy was produced in rats by unilateral loose ligation of the sciatic nerve, with a contralateral sham surgery. Repeated bilateral sensory testing was performed over time to investigate any threshold differences between the loose ligature side and the contralateral control side. A prolonged reduction in the mean withdrawal threshold to heat was observed on the loose ligature side over the medial dorsum of the hindpaw (MDH), and over the plantar surface of the hindpaw (PSH). Following loose ligature there was also a significant reduction in the von Frey fiber withdrawal thresholds over the lateral dorsum of the hindpaw (LDH) and the medial dorsum of the hindpaw (MDH). In a second experiment the saphenous nerves were transected bilaterally in rats who had an earlier unilateral loose sciatic ligation. The heat hyperalgesia that had been previously observed over the MDH was abolished, and no withdrawal response could be elicited with the largest von Frey fiber over the MDH, indicating that the MDH hyperalgesia induced by sciatic loose ligature was mediated by the saphenous nerve. This adjacent neuropathic hyperalgesia (ANH) resembles the saphenous mediated ANH observed over the MDH following sciatic transection, follows the same temporal course of onset, and may share a similar pathogenesis. The heat threshold over the PSH and the pressure threshold over the LDH were unaffected by the bilateral saphenous transection, demonstrating that following loose sciatic ligation both of these thresholds are mediated by the sciatic nerve.
Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice (1997)

The acute phase proteins alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antitrypsin (alpha 1-AT) were shown to inhibit, by a mechanism unidentified to date, the lethality induced by TNF both in normal mice and in mice sensitized with galactosamine. We found that both bovine alpha 1-AGP and human alpha 1-AT also inhibited specifically the induction of apoptosis of hepatocytes by TNF/ galactosamine in vivo. This inhibition is specific for TNF, since apoptosis induced by TNF and actinomycin D was also inhibited, while similar apoptosis of hepatocytes induced by anti-Fas remained unaffected. The observation that these acute phase proteins did not affect the induction by TNF of IL-6, nitric oxide, or serum amyloid P excludes a nonselective inhibition of the TNF-activated pathways. The protection conferred by alpha 1-AGP and alpha 1-AT is presumably indirect, since these proteins did not inhibit TNF/actinomycin D-induced apoptosis in the hepatoma cell lines HepG2 and BWTG3.
Stochastic Expression of the Interferon-β Gene (2012)

Virus infection of mammalian cells induces the production of high levels of type I interferons (IFNα and β), cytokines that orchestrate antiviral innate and adaptive immunity. Previous studies have shown that only a fraction of the infected cells produce IFN. However, the mechanisms responsible for this stochastic expression are poorly understood. Here we report an in depth analysis of IFN-expressing and non-expressing mouse cells infected with Sendai virus. Mouse embryonic fibroblasts in which an internal ribosome entry site/yellow fluorescent protein gene was inserted downstream from the endogenous IFNβ gene were used to distinguish between the two cell types, and they were isolated from each other using fluorescence-activated cell sorting methods. Analysis of the separated cells revealed that stochastic IFNβ expression is a consequence of cell-to-cell variability in the levels and/or activities of limiting components at every level of the virus induction process, ranging from viral replication and expression, to the sensing of viral RNA by host factors, to activation of the signaling pathway, to the levels of activated transcription factors. We propose that this highly complex stochastic IFNβ gene expression evolved to optimize both the level and distribution of type I IFNs in response to virus infection.
DNA sequencing using polymerase substrate-binding kinetics (2015)

Next-generation sequencing (NGS) has transformed genomic research by decreasing the cost of sequencing. However, whole-genome sequencing is still costly and complex for diagnostics purposes. In the clinical space, targeted sequencing has the advantage of allowing researchers to focus on specific genes of interest. Routine clinical use of targeted NGS mandates inexpensive instruments, fast turnaround time and an integrated and robust workflow. Here we demonstrate a version of the Sequencing by Synthesis (SBS) chemistry that potentially can become a preferred targeted sequencing method in the clinical space. This sequencing chemistry uses natural nucleotides and is based on real-time recording of the differential polymerase/DNA-binding kinetics in the presence of correct or mismatch nucleotides. This ensemble SBS chemistry has been implemented on an existing Illumina sequencing platform with integrated cluster amplification. We discuss the advantages of this sequencing chemistry for targeted sequencing as well as its limitations for other applications.
Expression of a Truncated, Kinase-Defective TGF-β Type II Receptor in Mouse Skeletal Tissue Promotes Terminal Chondrocyte Differentiation and Osteoarthritis (1997)

Members of the TGF-beta superfamily are important regulators of skeletal development. TGF-betas signal through heteromeric type I and type II receptor serine/threonine kinases. When over-expressed, a cytoplasmically truncated type II receptor can compete with the endogenous receptors for complex formation, thereby acting as a dominant-negative mutant (DNIIR). To determine the role of TGF-betas in the development and maintenance of the skeleton, we have generated transgenic mice (MT-DNIIR-4 and -27) that express the DNIIR in skeletal tissue. DNIIR mRNA expression was localized to the periosteum/perichondrium, syno-vium, and articular cartilage. Lower levels of DNIIR mRNA were detected in growth plate cartilage. Transgenic mice frequently showed bifurcation of the xiphoid process and sternum. They also developed progressive skeletal degeneration, resulting by 4 to 8 mo of age in kyphoscoliosis and stiff and torqued joints. The histology of affected joints strongly resembled human osteo-arthritis. The articular surface was replaced by bone or hypertrophic cartilage as judged by the expression of type X collagen, a marker of hypertrophic cartilage normally absent from articular cartilage. The synovium was hyperplastic, and cartilaginous metaplasia was observed in the joint space. We then tested the hypothesis that TGF-beta is required for normal differentiation of cartilage in vivo. By 4 and 8 wk of age, the level of type X collagen was increased in growth plate cartilage of transgenic mice relative to wild-type controls. Less proteoglycan staining was detected in the growth plate and articular cartilage matrix of transgenic mice. Mice that express DNIIR in skeletal tissue also demonstrated increased Indian hedgehog (IHH) expression. IHH is a secreted protein that is expressed in chondrocytes that are committed to becoming hypertrophic. It is thought to be involved in a feedback loop that signals through the periosteum/ perichondrium to inhibit cartilage differentiation. The data suggest that TGF-beta may be critical for multifaceted maintenance of synovial joints. Loss of responsiveness to TGF-beta promotes chondrocyte terminal differentiation and results in development of degenerative joint disease resembling osteoarthritis in humans.
Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice (2016)

Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways. The up-regulated Fgf21 levels in NAFLD were implied to be a protective response against the NAFLD-induced adverse effects, e.g. lipotoxicity, oxidative stress and endoplasmic reticulum stress. An in vivo PPARα challenge demonstrated the dysregulation of PPARα signalling in the presence of NAFLD, which resulted in a stochastically increasing hepatic expression of Fgf21. Notably, elevated plasma Fgf21 was associated with declining expression of Klb, Fgf21's crucial co-receptor, which suggests a resistance to Fgf21. Therefore, although liver fat accumulation is a benign stage of NAFLD, the elevated plasma Fgf21 likely indicated vulnerability to metabolic stressors that may contribute towards progression to end-stage NAFLD. In conclusion, plasma levels of Fgf21 reflect liver fat accumulation and dysregulation of metabolic pathways in the liver.
Hydrazines and Azides via the Metal-Catalyzed Hydrohydrazination and Hydroazidation of Olefins (2006)

The discovery, study, and implementation of the Co- and Mn-catalyzed hydrohydrazination and hydroazidation reactions of olefins are reported. These reactions are equivalent to direct hydroaminations of C-C double bonds with protected hydrazines or hydrazoic acid but are based on a different concept in which the H and the N atoms come from two different reagents, a silane and an oxidizing nitrogen source (azodicarboxylate or sulfonyl azide). The hydrohydrazination reaction using di-tert-butyl azodicarboxylate is characterized by its ease of use, large functional group tolerance, and broad scope, including mono-, di-, tri-, and tetrasubstituted olefins. Key to the development of the hydroazidation reaction was the use of sulfonyl azides as nitrogen sources and the activating effect of tert-butyl hydroperoxide. The reaction was found to be efficient for the functionalization of mono-, di-, and trisubstituted olefins, and only a few functional groups are not tolerated. The alkyl azides obtained are versatile intermediates and can be transformed to the free amines or triazoles without isolation of the azides. Preliminary mechanistic investigations suggest a rate-limiting hydrocobaltation of the alkene, followed by an amination reaction. Radical intermediates cannot be ruled out and may be involved.