gebhart/patrepeval huggingface dataset:
Tetrabenazine improves levodopa-induced peak-dose dyskinesias in patients with Parkinson�s disease (2013)

Since levodopa-induced peak dyskinesias (LIDs) may reflect, in part, a disproportionate phasic release of dopamine from synaptic vesicles, we examined the ability of the vesicular depletor tetrabenazine (TBZ) to reduce LIDs in 10 dyskinetic advanced Parkinson's disease (PD) patients. After basal evaluation, the patients received, through a slow titration, oral TBZ twice a day for six weeks (up to 50 mg daily) before being re-assessed after a challenge with levodopa. The primary outcome measure was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) dyskinesia score (items 32 to 34). TBZ was well tolerated. A clear treatment effect on LIDs emerged (up to 45%, p<0.05). In two patients a little worsening of motor performance necessitated an increase of the antiparkinsonian therapy, which did not worsen peak-dose LIDs. The patients experienced a clear benefit in terms of their quality of life. In this open-label pilot study, orally administered TBZ resulted in objective and subjective improvements in LIDs. Larger pharmacological studies are in progress.
Repeat polypeptide models of elastin as substrates for lysyl oxidase. (1980)

Synthetic repeat polypeptides analogous in sequence to the valine-rich regions of elastin have been tested as substrates for purified bovine aorta lysyl oxidase. These polypeptides, HCO(phi-Pro-Gly-Gly)n-Val-OMe, HCO(Val-Pro-Gly-phi-Gly)n-Val-OMe, and HCO-Val-(Ala-Pro-Gly-phi-Gly-Val)n-OMe, where phi = Val or Lys at approximately a 4:1 ratio and where n greater than or equal to 40, are models of the tetra-, penta-, or hexapeptide repeat sequences found in elastin. alpha-Aminoadipic delta-semialdehyde is generated in each of these upon incubation with lysyl oxidase at 37 degrees C, whereas the aldol and anhydrolysinonorleucine bifunctional cross-linkages were formed only in the incubation of enzyme with polypentapeptide. Incubation of the polypentapeptide at 55 degrees C, which enhances coacervation of the peptide, increases aldehyde formation and generates a much higher ratio of cross-linkages to aldehyde than occurred at 37 degrees C. These results demonstrate that lysyl oxidase can oxidize lysine in synthetic polypeptides and suggest important conformational aspects of lysyl oxidase substrates which may control substrate potential as well as the ability of peptidyl aldehyde, once formed by the enzyme, to condense to cross-linkage products.
Hadamard Matrices and Their Applications (1978)

An $n \times n$ matrix $H$ with all its entries $+1$ and $-1$ is Hadamard if $HH' = nI$. It is well known that $n$ must be 1, 2 or a multiple of 4 for such a matrix to exist, but is not known whether Hadamard matrices exist for every $n$ which is a multiple of 4. The smallest order for which a Hadamard matrix has not been constructed is (as of 1977) 268. Research in the area of Hadamard matrices and their applications has steadily and rapidly grown, especially during the last three decades. These matrices can be transformed to produce incomplete block designs, $t$-designs, Youden designs, orthogonal $F$-square designs, optimal saturated resolution III designs, optimal weighing designs, maximal sets of pairwise independent random variables with uniform measure, error correcting and detecting codes, Walsh functions, and other mathematical and statistical objects. In this paper we survey the existence of Hadamard matrices and many of their applications.
Modulation of human microglial cell superoxide production by cytokines (1995)

Reactive oxygen intermediates (e.g., superoxide [O2-]) generated by microglia may play a role in host defense and injury within the central nervous system. We investigated the effect of cytokines on human microglial cell O2- production on stimulation with phorbol myristate acetate. Priming of microglial cell cultures with interferon-gamma or tumor necrosis factor-alpha resulted in a dose- and time-dependent enhancement of O2- production. The priming effects of these cytokines were mediated through a protein kinase C signal transduction pathway. In contrast, astrocytes did not generate detectable O2- on phorbol myristate acetate stimulation. Treatment of microglia with transforming growth factor-beta, interleukin-4, or interleukin-10 suppressed in a dose-dependent manner the priming effects of tumor necrosis factor-alpha and interferon-gamma. The results of this study have implications for understanding the mechanisms by which cytokines and microglia contribute to processes of host defense and neurodegeneration via generation of reactive oxygen intermediates.
tert‐Butanol as an OH‐Scavenger in the Pulse Radiolysis of Oxygenated Aqueous Systems (1992)

Abstract The application of tert ‐butanol as an OH scavenger in aqueous, oxygenated solutions was studied by pulse radiolysis and computer simulation of the entire reaction mechanism. In such systems, the initially produced tert ‐butanol radical (· R tb ) reacts with O 2 with a rate constant of k = 1.4 · 10 9 M −1 s −1 . The UV absorption‐spectrum of the resulting tert ‐butanol peroxy‐radical, · OOR, tb , was determined. The rate constant for its dimerization, 2 · OOR tb R tb O 4 R tb , is k = 1.8 · 10 8 M −1 s −1 . The formation of HO 2 from the decay of R tb O 4 R tb has often been neglected in earlier studies. Our reinvestigation showed a yield of 5 ± 2%. In deoxygenated systems we confirmed the rate constant for · R tb dimerization to be k = 6 · 10 8 M −1 s −1 . The UV spectrum of · R tb was determined to be slightly different from literature data.
Elective cesarean delivery affects gut maturation and delays microbial colonization but does not increase necrotizing enterocolitis in preterm pigs (2007)

Although preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), the influences of cesarean section (CS) and vaginal delivery (VD) are unknown. Therefore, gut characteristics and NEC incidence and severity were evaluated in preterm pigs (92% gestation) delivered by CS or VD. An initial study showed that newborn CS pigs (n = 6) had decreased gastric acid secretion, absorption of intact proteins, activity of brush-border enzymes and pancreatic hydrolases, plasma cortisol, rectal temperature, and changes in blood chemistry, indicating impaired respiratory function, compared with VD littermates (n = 6). In a second experiment, preterm CS (n = 16) and VD (n = 16) pigs were given total parenteral nutrition (36 h) then fed porcine colostrum (VD-COL, n = 6; CS-COL, n = 6) or infant milk formula (VD-FORM, n = 10; CS-FORM, n = 10) for 2 days. Across delivery, FORM pigs showed significantly higher NEC incidence, tissue proinflammatory cytokines (IFN-gamma and IL-6), Clostridium colonization, and impaired intestinal function, compared with COL pigs. NEC incidence was equal for CS (6/16) and VD (6/16) pigs, CS pigs had decreased bacterial diversity and density, higher villus heights, and increased brush-border enzyme activities (lactase, aminopeptidases) compared with VD pigs. In particular, VD-FORM pigs showed reduced mucosal proportions, reduced lactase and aminopeptidases, and increased proinflammatory cytokine IL-6 compared with CS-FORM (P < 0.06). Despite the initial improvement of intestinal and metabolic functions following VD, gut function, and inflammation were similar, or more negatively affected in VD neonates than CS neonates. Both delivery modes exhibited positive and negative influences on the preterm gut, which may explain the similar NEC incidence.
Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells (2013)

The polyamines, putrescine, spermidine, and spermine, are essential polycations, intimately involved in the regulation of cellular proliferation. Although polyamines exert dynamic effects on the conformation of nucleic acids and macromolecular synthesis in vitro, their specific functions in vivo are poorly understood. We investigated the cellular function of polyamines by overexpression of a key catabolic enzyme, spermidine/spermine N(1)-acetyltransferase 1 (SAT1) in mammalian cells. Transient cotransfection of HeLa cells with GFP and SAT1 vectors suppressed GFP protein expression without lowering its mRNA level, an indication that the block in GFP expression was not at transcription, but at translation. Fluorescence single-cell imaging also revealed specific inhibition of endogenous protein synthesis in the SAT1 overexpressing cells, without any inhibition of synthesis of DNA or RNA. Overexpression of SAT1 using a SAT1 adenovirus led to rapid depletion of cellular spermidine and spermine, total inhibition of protein synthesis, and growth arrest within 24 h. The SAT1 effect is most likely due to depletion of spermidine and spermine, because stable polyamine analogs that are not substrates for SAT1 restored GFP and endogenous protein synthesis. Loss of polysomes with increased 80S monosomes in the polyamine-depleted cells suggests a direct role for polyamines in translation initiation. Our data provide strong evidence for a primary function of polyamines, spermidine and spermine, in translation in mammalian cells.
Fundamental properties of thin film resonators (2002)

The author presents an overview of the physical properties of thin film resonators, composite resonators using piezoelectric thin films, and filters employing coupled resonators. There are both similarities and substantial differences between thin-film resonators and conventional single-crystal resonators used at low frequencies. For most applications the thin-film resonator is fabricated with lateral dimensions in excess of 50 to 100 times the thickness and as such can be considered a one-dimensional device for the purposes of wave propagation and circuit modeling. Composite resonators consisting of piezoelectric films supported by membranes or bulk substrates form an important part of the thin-film resonator technology. An analysis of the general quasi-mode composite resonator is presented, and the results are summarized in electrical impedance equations cast in a matrix algebra format.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Phase I study of intravenous mycobacterial cell wall skeleton and trehalose dimycolate attached to oil droplets. (1984)

The toxic, clinical, and immunological effects of suspensions of mycobacterial cell wall skeleton (CWS) and trehalose dimycolate (TDM) attached to oil droplets and given intravenously in doses of 100-2,000 micrograms/m2 (CWS) every 1 or 2 weeks was investigated in this Phase I study. The major limiting side effects were fever and chills at a dose of 2 mg/m2 body surface area. There was no significant hematopoietic, renal, hepatic, or pulmonary toxicity. Evaluation of changes in the white cell count and lymphocyte and monocyte populations and function showed an increase in the white blood count, an increase in the number of T cells, and a decrease in blood monocytes. Measurements of lymphocyte blastogenesis, monocyte suppressor activity, and monocyte cytostasis showed no consistent changes. Intravenous therapy with oil/CWS/TDM was associated with complete regression of a bronchial squamous cell carcinoma in one of three patients receiving 2 mg/m2 weekly. Subsequent Phase II studies can be conducted at a weekly dose of 1-2 mg/m2.
Peptide Aldehydes and Nitriles as Transition State Analog Inhibitors of Cysteine Proteases (1995)

Enzymes efficiently catalyze reactions by stabilizing inherently unstable transition states. For cysteine proteases, part of the stabilization is provided by a region of the enzyme termed the oxyanion hole. Site-directed mutagenesis has been used to investigate further the role of the oxyanion hole of papain in the binding of putative transition state analog inhibitors of cysteine proteases. The dissociation constants Ki(obs) for inhibition of wild-type and mutant enzymes (Gln19Ala, Gln19Glu, and Gln19His) by the aldehyde Ac-Phe-Gly-CHO and the nitrile MeOCO-Phe-Gly-CN have been determined in the pH range 3.5-9.0. For the peptide nitrile inhibitor, mutation of Gln19 was found to cause important increases in Ki(obs), and thioimidate adducts with the papain mutants Gln19Ala and Gln19Glu are less stable by 1.4-2.4 kcal/mol. However, for the peptide aldehyde inhibitor, the mutations resulted in a small but significant increase in stability of the tetrahedral hemithioacetal adduct (0.4-1.2 kcal/mol). In that respect, the hemithioacetal formed between papain and a peptide aldehyde cannot be considered a good model of the transition state for cysteine protease-catalyzed reactions. The influence of the mutations on the pH dependency of inhibition also indicates that with respect to oxyanion hole interaction, the inhibition of papain by peptide nitriles is a process closer to that of substrate hydrolysis than is the inhibition by the corresponding peptide aldehydes. The nature of the intermediates and transition states in hydrolysis reactions catalyzed by cysteine proteases, as well as the use of enzyme-inhibitor adducts as their models, is discussed.
cAMP post-transcriptionally diminishes the abundance of adrenodoxin reductase mRNA. (1992)

Adrenodoxin reductase (AR; ferridoxin: NADP+ oxidoreductase, EC 1.18.1.2) is a flavoprotein that mediates electron transport from NADPH to all known mitochondrial forms of cytochrome P450. AR mRNA was found in all human adult and fetal tissues examined; however, it was vastly more abundant in tissues that synthesize steroid hormones. The ratio of the 18- form of mRNA lacking 18 alternately spliced bases to the 18+ form was approximately 100:1 and remained constant irrespective of the tissue or hormonal manipulation, indicating that the alternate splicing is a passive nonregulated event. AR protein was unchanged by forskolin treatment of human JEG-3 cytotrophoblast cells for 24 h, but the mRNA diminished. Phorbol 12-myristate 13-acetate and cycloheximide had no effect, even though these agents had the expected effects on P450scc and adrenodoxin mRNAs. cAMP decreased the abundance of AR mRNA expressed from both transfected plasmids and the endogenous gene, indicating the effect was post-transcriptional. AR gene transcription in JEG-3 cells and promoter-chloramphenicol acetyltransferase constructs transfected into JEG-3 cells were unresponsive to forskolin. Powerful basal transcription elements were identified between -46 and -214 bases from the principal transcriptional initiation site, a region containing six elements closely resembling the binding site for transcription factor SP1.
Association Between Energy Balance and Luteal Function in Lactating Dairy Cows (1988)

Our objective was to determine the relationship between energy balance and secretion of progesterone in lactating dairy cows. Eight primiparous and 24 multiparous lactating Holstein cows were studied from parturition to 100 d postpartum or conception. Cows calved normally and remained healthy throughout the study. All cows were fed ad libitum a total mixed diet formulated to satisfy requirements for maintenance and lactation. Intake of feed and production of milk per cow were measured twice daily. Body weight was determined weekly. Daily energy balance was determined by subtracting energy required for maintenance and lactation from intake of energy. Concentrations of progesterone were determined in milk sampled every 3rd d. For at least 4 successive d postpartum, 81% of cows were in negative energy balance. Variation in energy balance was explained largely by intake of energy. Duration of luteal phases was not associated with energy balance. Energy balance within 9 d postpartum was correlated positively with concentration of progesterone within second and third postpartum luteal phase. Postpartum interval to nadir and magnitude of nadir of energy balance interacted to reduce progesterone within second and third postpartum estrous cycles. Thus, in lactating cows, secretion of progesterone is reduced by spontaneous caloric deficit and is modulated by timing and magnitude of maximal caloric deficit. Spontaneous caloric deficit is a potential source of infertility in lactating dairy cows.
Tail Vein Assay of Cancer Metastasis (2001)

The most damaging change during cancer progression is the switch from a locally growing tumor to a metastatic killer. This switch involves numerous alterations that allow tumor cells to complete the complex series of events needed for metastasis. In considering steps required for successful metastasis, extravasation from blood vessels in target organs is regarded as a critical process. Circulating tumor cells arrested in the capillary beds of different organs must invade the endothelial cell lining of blood vessels and degrade its underlying basement membrane in order to escape into the extravascular tissue where they establish metastasis. This unit describes the most common assay applied to evaluate the metastatic potential of blood-borne tumor cells. The protocol is often called "experimental metastasis", distinct from "spontaneous metastasis", where the tumor cells are first allowed to form a primary tumor in the site of injection and then escape into lymphatic or blood circulation. Cultured tumor cells are injected into the tail vein and allowed to circulate. After 12 to 20 days the recipients are euthanized and the lungs are evaluated for the presence of metastatic tumors.
A Predictive Model for Time-to-Flowering in the Common Bean Based on QTL and Environmental Variables (2017)

The common bean is a tropical facultative short-day legume that is now grown in tropical and temperate zones. This observation underscores how domestication and modern breeding can change the adaptive phenology of a species. A key adaptive trait is the optimal timing of the transition from the vegetative to the reproductive stage. This trait is responsive to genetically controlled signal transduction pathways and local climatic cues. A comprehensive characterization of this trait can be started by assessing the quantitative contribution of the genetic and environmental factors, and their interactions. This study aimed to locate significant QTL (G) and environmental (E) factors controlling time-to-flower in the common bean, and to identify and measure G × E interactions. Phenotypic data were collected from a biparental [Andean × Mesoamerican] recombinant inbred population (F<sub>11:14</sub>, 188 genotypes) grown at five environmentally distinct sites. QTL analysis using a dense linkage map revealed 12 QTL, five of which showed significant interactions with the environment. Dissection of G × E interactions using a linear mixed-effect model revealed that temperature, solar radiation, and photoperiod play major roles in controlling common bean flowering time directly, and indirectly by modifying the effect of certain QTL. The model predicts flowering time across five sites with an adjusted <i>r</i>-square of 0.89 and root-mean square error of 2.52 d. The model provides the means to disentangle the environmental dependencies of complex traits, and presents an opportunity to identify <i>in silico</i> QTL allele combinations that could yield desired phenotypes under different climatic conditions.
Thickness-dependent mechanical properties of polydimethylsiloxane membranes (2009)

Polydimethylsiloxane (PDMS) has cross-linked network structures and its properties have been regarded as dimensionally independent. Here we demonstrate that both the mechanical strength and the Young's modulus of the PDMS membranes are thickness dependent and the transition from bulk behavior to dimension dependent is predicted to occur at a membrane thickness of about 200 mu m. The thickness-dependent phenomenon is attributed to shear stress during fabrication, which is proportional to the thickness-induced reorder of polymer chain coils to form stronger cross-linked networks.
Cell-Based Gene Transfer to the Pulmonary Vasculature: Endothelial Nitric Oxide Synthase Overexpression Inhibits Monocrotaline-Induced Pulmonary Hypertension (1999)

To circumvent the problems of in vivo transfection and avoid the use of viral vectors or proteins, we sought to establish whether smooth-muscle cells (SMCs) transfected ex vivo could be delivered via the systemic venous circulation into the pulmonary bed to achieve local transgene expression in the lung. Primary cultures of pulmonary artery SMCs from Fisher 344 rats were labeled with a fluorescent, membrane-impermeable dye chloromethyl trimethyl rhodamine or transfected with the beta-galactosidase (betaGal) reporter gene under the control of the cytomegalovirus (CMV) enhancer/promoter (pCMV-beta). Transfected or labeled SMCs (5 x 10(5) cells/animal) were delivered to syngeneic recipient rats by injection into the jugular vein; the animals were killed at intervals between 15 min and 2 wk; and the lungs, spleens, kidneys, and skeletal muscle were excised and examined. At 15 min after transplantation, injected cells were detected mainly in the lumen of small pulmonary arteries and arterioles, often in groups of three or more cells. After 24 h, labeled SMCs were found incorporated into the vascular wall of pulmonary arterioles, and transgene expression persisted in situ for 14 d with no evidence of immune response. Using simple geometric assumptions, it was calculated that approximately 57 +/- 5% of the labeled cells reintroduced into the venous circulation could be identified in the lungs after 15 min, 34 +/- 7% at 48 h, 16 +/- 3% at 1 wk, and 15 +/- 5% at 2 wk. Similar results were observed using cells transfected with the reporter gene betaGal. To determine whether this method of gene transfer could prove effective in inhibiting the development of pulmonary vascular disease, pulmonary artery SMCs were transfected with either the full-length coding sequence of endothelial nitric oxide synthase (NOS) under the control of the CMV enhancer/promoter or with the control vector (pcDNA3.1) and injected simultaneously with the pulmonary endothelial toxin monocrotaline. At 28 d after injection the right ventricular systolic pressure was significantly decreased from 50 +/- 4 mm Hg in animals injected with the null-transfected cells to 33 +/- 3 mm Hg in animals injected with the NOS-transfected cells (P < 0.01). These results suggest that a cell-based strategy of ex vivo transfection may provide an effective nonviral approach for the selective delivery of foreign transgenes to pulmonary microvessels in the treatment of pulmonary vascular disease.
A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis (2006)

Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.
Protective Role of the MER Tyrosine Kinase via Efferocytosis in Rheumatoid Arthritis Models (2018)

MER plays a protective role during joint inflammation and activating MER by its ligand PROS1 ameliorates disease. Treatment of mice with MER receptor agonistic antibodies is deleterious due to its counterproductive effect of blocking efferocytosis in the arthritic joint.