gebhart/patrepeval huggingface dataset:
Mechanisms of improving regional and global ventricular function by preload alterations during acute ischemia in the canine left ventricle. (1985)

We examined the influence of left ventricular end-diastolic pressure (LVEDP) on the mechanical interaction between ischemic and nonischemic areas during acute myocardial ischemia. Circumferentially oriented ultrasonic segment gauges were implanted in the midwall of the anterior apex and posterior apex of the left ventricle in seven anesthetized dogs. Stroke volume was measured with a flow probe around the ascending aorta in five of these animals. We varied LVEDP with vena caval occlusion and dextran infusions to three matched levels (7, 12, and 19 mm Hg) before and 30 min after complete occlusion of the mid left anterior descending coronary artery. With acute ischemia, the anterior apex or ischemic zone demonstrated marked segmental lengthening during isovolumetric systole (end-diastole to aortic valve opening) and akinesis during the ejection phase (aortic valve opening to closure). In the posterior apex or nonischemic area, isovolumetric shortening increased and ejection phase shortening decreased during acute ischemia when compared with those under control conditions at the same LVEDP. Thus, a portion of the shortening generated by the nonischemic area was expended in stretching the ischemic zone during isovolumetric systole, thereby reducing the amount of ejection phase shortening. As LVEDP was increased, there was a parallel decrease in both the amount of isovolumetric lengthening in the ischemic zone and the isovolumetric shortening in the nonischemic area. As a result, acute ischemia produced less of a reduction in ejection phase shortening in the nonischemic area and in stroke volume at high as compared with low LVEDP. We conclude that the ischemic zone imposes a mechanical disadvantage on the nonischemic area, the magnitude of which is directly proportional to the amount of isovolumetric lengthening or bulge in the ischemic zone. An increase in LVEDP during acute ischemia improves regional and global ventricular function by both the Frank-Starling mechanism in the nonischemic (but not the ischemic) area and by reducing the mechanical disadvantage that the ischemic zone imposes on the nonischemic area.
Participation of Maternal and Fetal CRH in Early Phases of Human Implantation: The Role of Antalarmin (2004)

The hypothalamic neuropeptide corticotropin-releasing hormone (CRH) is produced by several tissues of the female reproductive system. It is also secreted at inflammatory sites and possesses potent pro-inflammatory properties influencing both innate and acquired immune processes. Uterine CRH participates in local immune early pregnancy phenomena, such as decidualization of endometrial strom a and protection of the fetus from maternal immune system. This is maintained through induction of the expression of apoptotic FasL on invasive extravillous trophoblast and maternal decidual cells at the fetal-maternal interface. Furthermore, CRH increases apoptosis of activated T lymphocytes through FasL induction participating in the process of implantation and early pregnancy. Female rats treated with the non-peptidic CRH receptor 1 (CRHR1) specific antagonist antalarmin, in the first 6 days of gestation, have undergone a decrease of endometrial implantation sites and live embryos and markedly diminished endometrial FasL expression.
Five Sources of a Dorsal Root Potential: Their Interactions and Origins in the Superficial Dorsal Horn (1997)

The dorsal root potential (DRP) was measured on the lumbar dorsal roots of urethan anesthetized rats and evoked by stimulation of five separate inputs. In some experiments, the dorsal cord potential was recorded simultaneously. Stimulation of the L3 dorsal root produced a DRP on the L2 dorsal root containing the six components observed in the cat including the prolonged negative wave (DRP V of Lloyd 1952). A single shock to the myelinated fibers in the sural nerve produced a DRP on the L6 dorsal root after the arrival in the cord of the afferent volley. The shape of this DRP was similar to that produced by dorsal root stimulation. Repetitive stimulation of the myelinated fibers in the gastrocnemius nerve also produced a prolonged negative DRP on the L6 dorsal root. When a single stimulus (<5 microA; 200 micros) was applied through a microelectrode to the superficial Lissauer Tract (LT) at the border of the L2 and L3 spinal segments, a characteristic prolonged negative DRP (LT-DRP) began on the L2 dorsal root after some 15 ms. Stimulation of the LT evoked DRPs bilaterally. Recordings on nearby dorsal roots showed this DRP to be unaccompanied by stimulation of afferent fibers in those roots. The LT-DRP was unaffected by neonatal capsaicin treatment that destroyed most unmyelinated fibers. Measurements of myelinated fiber terminal excitability to microstimulation showed that the LT-DRP was accompanied by primary afferent depolarization. Repetitive stimulation through a microelectrode in sensorimotor cortex provoked a prolonged and delayed negative DRP (recorded L2-L4). Stimulation in the cortical arm area and recording on cervical dorsal roots showed that the DRP was evoked more from motor areas than sensory areas of cortex. Interactions were observed between the LT-DRP and that evoked from the sural or gastrocnemius nerves or motor cortex. The LT-DRP was inhibited by preceding stimulation of the other three sources but LT stimulation did not inhibit DRPs evoked from sural or gastrocnemius nerves on the L6 dorsal root or from motor cortex on the L3 root. However, LT stimulation did inhibit the DRP evoked by a subsequent Lissaeur tract stimulus. Recordings were made from superficial dorsal horn neurons. Convergence of input from LT sural, and gastrocnemius nerves and cortex was observed. Spike-triggered averaging was used to examine the relationship between the ongoing discharge of superficial dorsal horn neurons and the spontaneous DRP. The discharge of 81% of LT responsive cells was correlated with the DRP.
Molecular Pathways: Targeting Resistance in the Androgen Receptor for Therapeutic Benefit (2013)

Androgen receptor signaling is critical in the development and progression of prostate cancer, leading to intensive efforts to elucidate all potential points of inflection for therapeutic intervention. These efforts have revealed new mechanisms of resistance and raise the possibility that known mechanisms may become even more relevant in the context of effective androgen receptor suppression. These mechanisms include tumoral appropriation of alternative androgen sources, alterations in androgen receptor expression, androgen receptor mutations, truncated androgen receptor variants, alterations and cross-talk in recruitment of cofactors to androgen receptor binding sites in the genome, and androgen receptor-driven oncogenic gene fusions. New agents such as enzalutamide, EPI-001, androgen receptor-specific peptidomimetics, novel HSP90 inhibitors, and PARP inhibitors, as well as new approaches to cotargeting the androgen receptor pathway, point to the potential for more complete and durable control of androgen receptor-mediated growth.
Evolutionarily Conserved and Nonconserved Cellular Localizations and Functions of Human SIRT Proteins (2005)

Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to Sir2 (SIRT1 through SIRT7) for cellular localization, expression profiles, protein deacetylation activity, and effects on human cell lifespan. We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations: SIRT6 and SIRT7 are associated with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular p53 is a major in vivo substrate of SIRT1 deacetylase, but not the other six SIRT proteins; 4) SIRT1, but not the other two nuclear SIRT proteins, shows an in vitro deacetylase activity on histone H4 and p53 peptides; and 5) overexpression of any one of the seven SIRT proteins does not extend cellular replicative lifespan in normal human fibroblasts or prostate epithelial cells. This study supports the notion that multiple human SIRT proteins have evolutionarily conserved and nonconserved functions at different cellular locations and reveals that the lifespan of normal human cells, in contrast to that of lower eukaryotes, cannot be manipulated by increased expression of a single SIRT protein.
Peroxisomal ABC transporters (2006)

Peroxisomes perform a range of different functions, dependent upon organism, tissue type, developmental stage or environmental conditions, many of which are connected with lipid metabolism. This review summarises recent research on ATP binding cassette (ABC) transporters of the peroxisomal membrane (ABC subfamily D) and their roles in plants, fungi and animals. Analysis of mutants has revealed that peroxisomal ABC transporters play key roles in specific metabolic and developmental functions in different organisms. A common function is import of substrates for beta-oxidation but much remains to be determined concerning transport substrates and mechanisms which appear to differ significantly between phyla.
Evaluation of Biochemical Changes During In Vivo Erythrocyte Senescence in the Dog (1999)

One hypothesis to explain the age-dependent clearance of red blood cells (RBCs) from circulation proposes that denatured/oxidized hemoglobin (hemichromes) arising late during an RBC’s life span induces clustering of the integral membrane protein, band 3. In turn, band 3 clustering generates an epitope on the senescent cell surface leading to autologous IgG binding and consequent phagocytosis. Because dog RBCs have survival characteristics that closely resemble those of human RBCs (ie, low random RBC loss, ≈115-day life span), we decided to test several aspects of the above hypothesis in the canine model, where in vivo aged cells of defined age could be evaluated for biochemical changes. For this purpose, dog RBCs were biotinylated in vivo and retrieved for biochemical analysis at various later dates using avidin-coated magnetic beads. Consistent with the above hypothesis, senescent dog RBCs were found to contain measurably elevated membrane-bound (denatured) globin and a sevenfold enhancement of surface-associated autologous IgG. Interestingly, dog RBCs that were allowed to senesce for 115 days in vivo also suffered from compromised intracellular reducing power, containing only 30% of the reduced glutathione found in unfractionated cells. Although the small quantity of cells of age ≥110 days did not allow direct quantitation of band 3 clustering, it was nevertheless possible to exploit single-cell microdeformation methods to evaluate the fraction of band 3 molecules that had lost their normal skeletal linkages and were free to cluster in response to hemichrome binding. Importantly, band 3 in RBCs ≥112 days old was found to be 25% less restrained by skeletal interactions than band 3 in control cells, indicating that the normal linkages between band 3 and the membrane skeleton had been substantially disrupted. Interestingly, the protein 4.1a/protein 4.1b ratio, commonly assumed to reflect RBC age, was found to be maximal in RBCs isolated only 58 days after labeling, implying that while this marker is useful for identifying very young populations of RBCs, it is not a very sensitive marker for canine senescent RBCs. Taken together, these data argue that several of the readily testable elements of the above hypothesis implicating band 3 in human RBC senescence can be validated in an appropriate canine model.
A method for global protein expression and antibody screening on high- density filters of an arrayed cDNA library (1998)

We have developed a technique to establish catalogues of protein products of arrayed cDNA clones identified by DNA hybridisation or sequencing. A human fetal brain cDNA library was directionally cloned in a bacterial vector that allows IPTG-inducible expression of His6-tagged fusion proteins. Using robot technology, the library was arrayed in microtitre plates and gridded onto high-density in situ filters. A monoclonal antibody recognising the N-terminal RGSH6sequence of expressed proteins (RGS.His antibody, Qiagen) detected 20% of the library as putative expression clones. Two example genes, GAPDH and HSP90alpha, were identified on high-density filters using DNA probes and antibodies against their proteins.
Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes (2016)

Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is a reflection of levels of the endocannabinoids, anandamide (arachidonylethanolamide), and 2-arachidonoylglycerol, their production, metabolism, and the relative abundance and state of cannabinoid receptors. Its theory is that in certain conditions, whether congenital or acquired, endocannabinoid tone becomes deficient and productive of pathophysiological syndromes. When first proposed in 2001 and subsequently, this theory was based on genetic overlap and comorbidity, patterns of symptomatology that could be mediated by the endocannabinoid system (ECS), and the fact that exogenous cannabinoid treatment frequently provided symptomatic benefit. However, objective proof and formal clinical trial data were lacking. Currently, however, statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder. Additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS.
Characteristics of Polyester Arterial Grafts Coated with Albumin: The Role and Importance of the Cross-Linking Chemicals (1988)

Preclotting is mandatory prior to implanting a knitted polyester arterial graft, unless the structure is made impermeable to blood by coating with a bioerodible material. Before achieving wide-spread clinical acceptance, the technique of impregnating with cross-linked albumin must be optimized in order to develop a graft that is immediately implantable, easy to handle and suture and has improved healing characteristics. The choice of the chemical to cross-link the albumin is of paramount importance. In this study two alternative candidates have been evaluated by using a series of tests to measure the physical properties, the morphology and the cytocompatibility of albumin-coated grafts. A carbodiimide cross-linking agent appears more promising than glutaraldehyde, since it is equally effective in producing a blood impermeable prosthesis, yet presents improved biocompatibility and provokes a less intense inflammatory response from the host.
Prescription Opioids. II. Metabolism and Excretion Patterns of Hydrocodone in Urine Following Controlled Single-Dose Administration (2013)

Hydrocodone (HC) is a highly misused prescription drugs in the USA. Interpretation of urine tests for HC is complicated by its metabolism to two metabolites, hydromorphone (HM) and dihydrocodeine (DHC), which are also available commercially and are misused. Currently, there is interest in including HC and HM in the federal workplace drug-testing programs. This study characterized the disposition of HC in human urine. Twelve healthy, drug-free, adults were administered a single, oral 20 mg immediate-release dose of HC in a controlled clinical setting. Urine specimens were collected at timed intervals for up to 52 h and analyzed by LC-MS-MS (limit of quantitation = 50 ng/mL) with and without enzymatic hydrolysis. All specimens were also analyzed for creatinine and specific gravity (SG). HC and norhydrocodone (NHC) appeared within 2 h followed by HM and DHC. Peak concentrations of HC and metabolites occurred at 3-9 h. Peak hydrolyzed concentrations were in the order: NHC > HC > HM > DHC. Only HM was excreted extensively as a conjugated metabolite. At a cutoff concentration of 50 ng/mL, detection times were ∼28 h for HC, 40 h for NHC, 26 h for HM and 16 h for DHC. Some specimens did not contain HC, but most contained NHC, thereby facilitating interpretation that HC was the administered drug. Creatinine and SG measures were highly correlated. Creatinine corrections of HC urinary data had variable effects of lowering or raising concentrations. These data suggest that drug-testing requirements for HC should include a hydrolysis step and a test for HM.
Contractility‐Dependent Modulation of Cell Proliferation and Adhesion by Microscale Topographical Cues (2008)

Engineering of cellular assembly on biomaterial scaffolds by utilizing microscale topographical cues has emerged as a powerful strategy in cardiovascular tissue engineering and regenerative medicine. However, the mechanisms through which these cues are processed to yield changes in canonical cell behaviors remain unclear. Previously, we showed that when mixtures of cardiomyocytes and fibroblasts were cultured on polydimethylsiloxane surfaces studded with microscale pillars (micropegs), fibroblast proliferation was dramatically suppressed, which suggests that the micropegs could be exploited to minimize fibrosis and scar formation. Here, we demonstrate that this effect relies on altered adhesive and micromechanical interactions between individual cells and micropegs. First, we show that the proliferation of a cell physically attached to a micropeg is significantly lower than that of a cell cultured on a featureless region of the substrate. Micropeg adhesion is accompanied by a marked elongation in cell and nuclear shape. When fibroblast contractility is pharmacologically attenuated through low-dose inhibition of either Rho-associated kinase or myosin light chain kinase, the potency with which micropeg adhesion suppresses cell proliferation is significantly reduced. Together, our results support a model in which cell fate decisions may be directly manipulated within tissue engineering scaffolds by the inclusion of microtopographical structures that alter cellular mechanics.
Chk1 Inhibitors for Novel Cancer Treatment (2006)

Chemo- and radiotherapies that target DNA are the mainstay of cancer treatment. In response to DNA damage, cells are arrested in multiple checkpoints in the cell cycle to allow the damaged DNA to be repaired before progressing into mitosis. Normal cells are arrested in the G1 phase mediated by the p53 tumor suppressor, and p53-deficient cancer cells are arrested in the S or G2 phase. Checkpoint kinase 1 (Chk 1) is a serine / threonine protein kinase and a key mediator in the DNA damage-induced checkpoint network. When the G2 or S checkpoint is abrogated by the inhibition of Chk1, p53-deficient cancer cells undergo mitotic catastrophe and eventually apoptosis, whereas normal cells are still arrested in the G1 phase. Thus, Chk1 inhibitors can preferentially potentiate the efficacy of DNA damaging agents in cancer cells, and Chk1 is an attractive therapeutic target for cancer treatment, especially since approximately 50% of all human cancers are p53-deficient. This review discusses the rationale of Chk1 as an anticancer target, the structural basis for designing Chk1 inhibitors, and recently disclosed Chk1 inhibitors.
The Effect of Al0.7Ga0.3As Etch Stop Removal on the Preparation of Wafer‐Bonded Compliant Substrates (1999)

Preparation of GaAs‐based compliant substrates that utilize wafer bonding generally relies on integrated etch stop layers to provide the precise control required to stop selectively on GaAs layers less than 100 Å thick. We demonstrate that removing an etch stop layer with HF or leaves the underlying GaAs layers with rms roughness of 10–20 Å and peak‐to‐peak roughness of 65–150 Å. Following the selective etch, the morphology of the underlying GaAs layer is improved with a wet chemical digital etch comprised of alternate soaks in and , which results in a GaAs surface with rms roughness of ∼2 Å and peak‐to‐peak roughness of ∼20 Å. Lattice‐matched junctions deposited on thin‐bonded GaAs substrates and test substrates that are prepared for growth using the digital etch have electrical characteristics comparable to those deposited on a bulk epi‐ready GaAs substrates. However, similar lattice‐mismatched junctions deposited on the thin‐bonded GaAs substrates and test substrates have dark currents that are more than an order of magnitude higher than those deposited on bulk epi‐ready GaAs substrates. These results suggest that despite the smoothing of the digital etch, the material that remains on the surface of the thin GaAs layer is responsible for the degradation observed in the lattice‐mismatched devices deposited on the thin‐bonded GaAs substrates. © 1999 The Electrochemical Society. All rights reserved. ©2001 American Geophysical Union
Primary Amyloidoma of the Brain Parenchyma (2005)

Amyloidoma can occur within the brain parenchyma. Periventricular amyloidomas developed in a man aged 69 years as gadolinium-enhancing lesions on magnetic resonance imaging. The lesions were composed of amyloid AL lambda with congophilia resistant to potassium permanganate. There was no evidence of systemic amyloidosis or an underlying inflammatory or neoplastic disorder.
Large magnetoresistance in bccCo∕MgO∕CoandFeCo∕MgO∕FeCotunnel junctions (2004)

By use of first-principles electronic structure calculations, we predict that the magnetoresistance of the bcc $\mathrm{Co}(100)∕\mathrm{Mg}\mathrm{O}(100)∕\mathrm{bcc}\mathrm{Co}(100)$ and $\mathrm{Fe}\mathrm{Co}(100)∕\mathrm{Mg}\mathrm{O}(100)∕\mathrm{Fe}\mathrm{Co}(100)$ tunneling junctions can be several times larger than the very large magnetoresistance predicted for the $\mathrm{Fe}(100)∕\mathrm{Mg}\mathrm{O}(100)∕\mathrm{Fe}(100)$ system. The origin of this large magnetoresistance can be understood by considering the electrons at the Fermi energy traveling perpendicular to the interfaces. For the minority spins there is no state with ${\ensuremath{\Delta}}_{1}$ symmetry whereas for the majority spins there is only a ${\ensuremath{\Delta}}_{1}$ state. The ${\ensuremath{\Delta}}_{1}$ state decays much more slowly than the other states within the MgO barrier. In the absence of scattering which breaks the conservation of momentum parallel to the interfaces, the electrons traveling perpendicular to the interfaces undergo total reflection if the moments of the electrodes are antiparallel. These arguments apply equally well to systems with other well ordered tunnel barriers and for which the most slowly decaying complex energy band in the barrier has ${\ensuremath{\Delta}}_{1}$ symmetry. Examples include systems with (100) layers constructed from Fe, bcc Co, or bcc FeCo electrodes and Ge, GaAs, or ZnSe barriers.