gebhart/patrepeval huggingface dataset:
The interaction of cholesterol absorption and cholesterol synthesis in man (1969)

The total miscible pool of cholesterol in the body is determined largely by the interaction of cholesterol absorption and synthesis. In the present study we have examined the net effects of this interplay in one normal and five hypercholesteremic subjects when various amounts of cholesterol were made available for absorption. Feeding large amounts of cholesterol to the normocholesteremic patient caused an expansion of body pools by as much as 20 g before the amount of cholesterol re-excreted as fecal neutral steroids each day came into balance with the cholesterol absorbed from the diet. There was no detectable decrease in total body synthesis of cholesterol nor any increase in conversion of cholesterol into bile acids. However, feedback control of cholesterol synthesis was demonstrable when large quantities of plant sterols were fed: in the hypercholesteremic patients thus studied, the absorption of both endogenous and exogenous cholesterol was then greatly reduced, and a compensatory increase in synthesis occurred. Thus, the plant sterol experiments, but not the cholesterol feeding experiment, demonstrated that feedback control by dietary cholesterol does occur in man. That feedback control by dietary cholesterol is relatively unimportant in man seems to be due to the fact that in the metabolic "steady state" the absorption mechanism is essentially saturated by the large amounts of endogenous cholesterol available for reabsorption. These findings demonstrate that there are important differences between man and various laboratory animals in regard to the interaction of absorption and synthesis as factors controlling the size of tissue pools of cholesterol.
The impact of prophylactic treatment on children with severe haemophilia (1996)

Twenty-seven children with severe haemophilia receiving regular prophylactic factor concentrate were evaluated to examine the overall effectiveness of prophylaxis in modern haemophilia care. The median age at the start of prophylaxis was 6.2 years (range 1.3-15.9 years) and the cumulative length of follow-up was 808 months (mean 30, rang 7-76 months). Nine patients required a central venous catheter for venous access (age range 1.3-5.2 years), eight boys could cannulate themselves and in 10 the parents performed regular venepuncture. The mean dose of concentrate given at the time of study was 31.8 U/kg three times weekly (range 12.5.6 U/kg) or 4900 U/kg/year (range 1900-8200). None developed an inhibitor on prophylaxis, though four had previously had an antibody. The median average annual number of bleeds in the 27 patients prior to prophylaxis was 14.7 (range 3.7-35.4). On prophylaxis this fell to 1.5 (range 0-12.5) (P<0.001) and in the group as a whole the frequency of bleeds diminished in successive years on prophylaxis. All 20 children with evidence of arthropathy improved on prophylaxis and eight had reversal of chronic damage such that their joints appeared normal at the time of study. There were reductions in the need for walking aids, in hospital admissions, and in numbers of school days lost for bleeding episodes. All families feel that prophylaxis has brought about an improvement in quality of life.
Antibiotic proteins of human polymorphonuclear leukocytes. (1989)

Nine polypeptide peaks with antibiotic activity were resolved from human polymorphonuclear leukocyte azurophil granule membranes. All but 1 of the 12 constituent polypeptides were identified by N-terminal sequence analysis. Near quantitative recovery of protein and activity permitted an assessment of the contribution of each species to the overall respiratory-burst-independent antimicrobial capacity of the cell. Three uncharacterized polypeptides were discovered, including two broad-spectrum antibiotics. One of these, a defensin that we have designated human neutrophil antimicrobial peptide 4, was more potent than previously described defensins but represented less than 1% of the total protein. The other, named azurocidin, was abundant and comparable to bactericidal permeability-increasing factor in its contribution to the killing of Escherichia coli.
Efficient DNA ligation in DNA–RNA hybrid helices by Chlorella virus DNA ligase (2013)

Single-stranded DNA molecules (ssDNA) annealed to an RNA splint are notoriously poor substrates for DNA ligases. Herein we report the unexpectedly efficient ligation of RNA-splinted DNA by Chlorella virus DNA ligase (PBCV-1 DNA ligase). PBCV-1 DNA ligase ligated ssDNA splinted by RNA with kcat ≈ 8 x 10(-3) s(-1) and K(M) < 1 nM at 25 °C under conditions where T4 DNA ligase produced only 5'-adenylylated DNA with a 20-fold lower kcat and a K(M) ≈ 300 nM. The rate of ligation increased with addition of Mn(2+), but was strongly inhibited by concentrations of NaCl >100 mM. Abortive adenylylation was suppressed at low ATP concentrations (<100 µM) and pH >8, leading to increased product yields. The ligation reaction was rapid for a broad range of substrate sequences, but was relatively slower for substrates with a 5'-phosphorylated dC or dG residue on the 3' side of the ligation junction. Nevertheless, PBCV-1 DNA ligase ligated all sequences tested with 10-fold less enzyme and 15-fold shorter incubation times than required when using T4 DNA ligase. Furthermore, this ligase was used in a ligation-based detection assay system to show increased sensitivity over T4 DNA ligase in the specific detection of a target mRNA.
The effects of different formula of medium on the lysine production of the ZL 9601 strain of Corynebacterium glutamicium (1998)

The effects of different formula of medium on the lysine production of ZL 9601 strain of Corynebacterium glutamicinum were studied with the method of orthogonal experiment design. The optical formula of medium mainly prepared with molasses were determined in shaking flask culture. The result showed that the high yield of lysine could be obtained with the medium formula: molasses 20%, hydrolyzed soybean meal 1.0%, corn steep liquor 0.6% under the proper ferment conditions (pH7.0, 30 degree C). The level of lysine production was 6.1% on the average.
Neuropsychological outcomes after epilepsy surgery: Systematic review and pooled estimates (2011)

In sum, epilepsy surgery is associated with specific cognitive changes, but may also improve cognition in some patients. The results provide base rate estimates of expected cognitive gains and losses associated with epilepsy surgery that may prove useful in clinical settings.
Nitric oxide in sepsis and endotoxaemia (1998)

Nitric oxide (NO) is one of many vasoactive substances released, from a variety of cells, under conditions of endotoxaemia and sepsis. Under physiological conditions it is produced by two constitutive calcium-dependent enzymes (nitric oxide synthase; NOS) in neurones (nNOS) and endothelial cells (eNOS) and has functions ranging from neurotransmission and vasodilatation to inhibition of platelet adhesion and aggregation. Following bacterial infection, especially with Gram-negative organisms, its formation from L-arginine is enhanced due to the cytokine-mediated induction of a NOS enzyme (iNOS) in cells (e.g. cardiac myocytes, vascular smooth muscle) that do not normally have the ability to synthesize NO. The result of this excessive NO production is enhanced bacterial lysis by activated macrophages, vasoplegia and myocardial depression. These cardiovascular effects can be alleviated by inhibitors of the L-arginine NO pathway, which results in elevated perfusion pressure, restored responsiveness to sympathetic nerve stimulation and to exogenous catecholamines, and to enhanced (endothelin-dependent) myocardial contractility. In patients in shock this approach also leads to detrimental effects (increased systemic vascular resistance, elevated pulmonary artery pressure, reduced cardiac output and oxygen delivery, increased platelet accumulation) and survival is not improved. Because some of these detrimental effects are due to inhibition of eNOS, attempts have been made to examine the effects of substances with a higher selectivity for the induced form of the enzyme. In experimental animals, one of these (L-canavanine) protects endothelial cells from damage, increases survival time and restores vascular responsiveness without increasing blood pressure or peripheral vascular resistance. However, whether even this approach will be of benefit to patients with sepsis remains in doubt since studies in iNOS knock-out mice do not support the concept that eliminating this particular source of NO improves ultimate survival.
The 1,2,3-triazole derivative KP-A021 suppresses osteoclast differentiation and function by inhibiting RANKL-mediated MEK-ERK signaling pathway (2015)

The triazole family of compounds has been implicated in modulating various biological processes such as inflammation, tumorigenesis, and infection. To our knowledge, this is the first study to demonstrate the effects of 1,2,3-triazole substituted biarylacrylonitrile compounds, including KP-A021, on the differentiation and function of osteoclasts. KP-A021 and its triazole derivatives, at a concentration that does not cause a cytotoxic response in bone marrow macrophages (BMMs), significantly inhibited osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) as assessed by tartrate-resistant acid phosphatase (TRAP) staining. KP-A021 also dramatically inhibited the expression of marker genes associated with osteoclast differentiation, such as TRAP, cathepsin K (Cat K), dendritic cell-specific transmembrane protein (DC-STAMP), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). Furthermore, KP-A021 inhibited actin ring formation in osteoclasts as well as resorption pit formation induced by osteoclasts. Analysis of the signaling pathway for KP-A021 indicated that this triazole compound inhibited the RANKL-induced activation of extracellular signal-regulated kinase (ERK) and its upstream signaling molecule, mitogen-activated protein kinase kinase1/2 (MEK1/2). Taken together, these results demonstrate that KP-A021 has an inhibitory effect on the differentiation and function of osteoclasts via modulation of the RANKL-induced activation of the MEK-ERK pathway.
Synthesis of Readily Modifiable Cyclodextrin Analogues via Cyclodimerization of an Alkynyl−Azido Trisaccharide (2004)

A convergent strategy for the synthesis of beta-cyclodextrin analogues is reported, utilizing preferential cyclodimerization of an azido-alkyne trisaccharide via Cu(I)-catalyzed [3 + 2] dipolar cycloaddition of the alkyne and azide functional groups. The resultant oligosaccharide macrocycle retains the binding propensity of cyclodextrins, as demonstrated by the similar ANS association constants measured for macrocycle 1 and beta-cyclodextrin. This new synthetic strategy opens up new avenues for modular preparation of functionally diverse cyclodextrin analogues that are otherwise inaccessible.
Enhanced Thermoelectric Properties of Boron-Substituted Single-Walled Carbon Nanotube Films (2018)

Atomic doping is the most fundamental approach to modulating the transport properties of carbon nanotubes. In this paper, we demonstrate the enhanced thermoelectric properties of boron-substituted single-walled carbon nanotube (B-SWCNT) films. The developed two-step synthesis of large quantities of B-SWCNTs readily enables the measurements of thermoelectricity of bulk B-SWCNT films. Complementary structural characterization implies the unique configuration of boron atoms at the doping sites of SWCNTs, successfully enabling carrier doping to SWCNTs. The developed boron substitution, in combination with chemical doping, is found to substantially improve the thermoelectric properties.
Induction of heme oxygenase‐1 expression by root canal sealers in human gingival fibroblasts is augmented by oxidative stress (2006)

Heme oxygenase-1 (HO-1) is known as a stress-inducible protein and functions as an antioxidant enzyme. It has been shown that HO-1 is induced rapidly by a variety of chemical and physical stimuli. However, little is known about the induction of cellular signaling events after cell exposure to root canal sealers. The aim of this study was to investigate the effects of zinc oxide-eugenol-based root canal sealer N2 and epoxy resin-based root canal sealer Topseal on the expression of HO-1 protein in cultured human gingival fibroblasts (HGFs). The results showed that both N2 and Topseal were cytotoxic to HGFs in a concentration-dependent manner (p < 0.05). The exposure of quiescent HGFs to N2 and Topseal resulted in the induction of HO-1 protein expression in a time-dependent manner (p < 0.05). Furthermore, to determine whether oxidative stress could modulate HO-1 expression in HGFs by root canal sealers, HGFs were pretreated with glutathione (GSH) synthesis precursor 2-oxothiazolidine-4-carboxylic acid (OTZ) and GSH synthesis inhibitor buthionine sulfoximine (BSO) for 24 h. The pretreatment with OTZ decreased the N2-induced HO-1 protein level by approximately 32% (p < 0.05). However, BSO enhanced the N2-induced HO-1 protein level by up to twofold (p < 0.05). Similar results were found by Topseal. The pretreatment with OTZ decreased the Topseal-induced HO-1 protein level by approximately 12% (p < 0.05). However, BSO enhanced the Topseal-induced HO-1 protein level by up to 1.7-fold (p < 0.05). Taken together, HO-1 expression might be one signal transduction pathway linked to the induction of stress-inducible protein by root canal sealers. In addition, the activation of HO-1 is augmented by oxidative stress. Factors that induce GSH synthesis may appear useful in preventing oxidative damage mediated by root canal sealers.
Small Molecule Inhibitors of the Class 1 Receptor Tyrosine Kinase Family (2002)

This review covers literature describing research progress in erbB family tyrosine kinase inhibition over the last year. Excellent recent reviews are available, thus we have focussed on current developments of leading small molecule drug candidates as well as their erbB family inhibition profile. The most advanced erbB family tyrosine kinase (TK) inhibitors are demonstrating promising anti-cancer activity in clinical trials and are discussed. Several inhibition strategies are emerging: EGFR TK selective, irreversible TK inhibition and dual EGFR/erbB2 TK inhibitors. While small structural differences are seen in the leading compounds, the variations in their inhibition profiles and compound properties suggest that biological systems judge structural diversity differently. The readers' attention is drawn to common issues of selectivity and potency generally encountered with kinase inhibitors.
Highly scalable video compression using a lifting-based 3D wavelet transform with deformable mesh motion compensation (2003)

This paper continues the development of a new framework for the construction of motion-compensated wavelet transforms for highly scalable video compression. The current authors recently proposed a motion adaptive wavelet transform based on motion-compensated lifting steps. This approach overcomes several limitations of existing methods. In particular, frame warping and block displacement methods cannot efficiently exploit complex motion without sacrificing invertibility. By contrast, the motion-compensated lifting transform remains invertible regardless of the motion model. The previous work was primarily in the context of a block motion model. However, block motion models inevitably yield discontinuous motion fields, which poorly represent complex motion in real video sequences. In this paper we consider the benefits of a continuous motion field, by incorporating a deformable mesh motion model into the existing framework. Experimental results show that this leads to improved compression performance. In addition, we show that the invertibility of continuous motion fields allows greater potential for compactly representing the motion information.
Trypanosome Capping Enzymes Display a Novel Two-Domain Structure (1998)

The ubiquitous m7G cap of eukaryotic mRNAs and of precursors to the spliceosomal small nuclear RNAs (snRNAs) is the result of an essential RNA modification acquired during transcript elongation. In trypanosomes, the m7G cap is restricted to the spliced leader (SL) RNA and the precursors of U2, U3, and U4 snRNAs. mRNA capping in these organisms occurs posttranscriptionally by trans splicing, which transfers the capped SL sequence to the 5' ends of all mRNAs. The SL cap is the most elaborate cap structure known in nature and has been shown to consist of an m7G residue followed by four methylated nucleotides. Using Crithidia fasciculata, we have characterized and purified the guanylyltransferase (capping enzyme), which transfers GMP from GTP to the diphosphate end of RNA. The corresponding gene codes for a protein of 697 amino acids, with the carboxy-terminal half of the C. fasciculata guanylyltransferase containing the six signature motifs previously identified in yeast capping enzymes. The amino-terminal half contains a domain that displays no resemblance to any other domain associated with capping enzymes. Intriguingly, this region harbors a consensus sequence for a phosphate-binding loop which is found in ATP- and GTP-binding proteins. This two-domain structure is also present in the Trypanosoma brucei capping enzyme, which shows 44% overall identity with the C. fasciculata capping enzyme. Thus, this structure appears to be common to all trypanosomatid protozoa and defines a novel class of capping enzymes.
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death (2001)

Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.
Myofascial Release Treatment of Specific Muscles of the Upper Extremity (Levels 3 and 4) (1996)

ABSTRACT Repetitive strain injuries, athletic injuries, post-traumatic biomechanical problems, peripheral nerve entrapment, and many other common syndromes respond well to soft-tissue treatment. This paper discusses myofascial release treatment (MRT). It is also a procedural guide for the examination and treatment of the most common, clinically significant muscles of the upper extremity. This is part one of four parts.
Expression of Interferon (IFN)-Stimulated Genes in Extrauterine Tissues during Early Pregnancy in Sheep Is the Consequence of Endocrine IFN-τ Release from the Uterine Vein (2007)

The ruminant conceptus synthesizes and secretes interferon (IFN)-tau, which presumably acts via an intrauterine paracrine mechanism to signal maternal recognition of pregnancy. The aims of this study were to determine whether IFN-stimulated genes (ISG) such as ISG15 and OAS-1 are differentially expressed in blood cells circulating in the uterus of ewes; whether extrauterine components of the reproductive tract such as the corpus luteum (CL) also express mRNA for these ISG, and whether antiviral activity is greater in uterine vein than in uterine artery during early pregnancy. The concentrations of mRNA for both ISG were significantly greater (P < 0.0001) in endometrium and jugular blood of 15-d pregnant ewes than in nonpregnant ewes. ISG15 and OAS-1 mRNA concentrations were also greater (P < 0.05) in CL from 15-d pregnant ewes than in nonpregnant ewes. Immunohistochemistry revealed intense staining for ISG15 in large luteal cells on d 15 of pregnancy. Blood cells from uterine artery and vein of 15-d pregnant ewes had similar ISG15 and OAS-1 mRNA concentrations, suggesting that these cells were not conditioned by IFN-tau within the uterus. By using an antiviral assay, uterine venous blood was found to contain 500- to 1000-fold higher concentrations of bioactive IFN-tau than in uterine arterial blood on d 15 of pregnancy. It is concluded that uterine vein releases IFN-tau, which induces ISG in extrauterine tissues such as the CL during the time of maternal recognition of pregnancy.
Two nearly identical terpene synthases catalyze the formation of nerolidol and linalool in snapdragon flowers (2008)

Terpenoids emitted from snapdragon flowers include three monoterpenes derived from geranyl diphosphate (GPP), myrcene, (E)-beta-ocimene and linalool, and a sesquiterpene, nerolidol, derived from farnesyl diphosphate (FPP). Using a functional genomics approach, we have isolated and biochemically characterized two nearly identical nerolidol/linalool synthases, AmNES/LIS-1 and AmNES/LIS-2, two enzymes responsible for the terpenoid profile of snapdragon scent remaining to be characterized. The AmNES/LIS-2 protein has an additional 30 amino acids in the N-terminus, and shares 95% amino acid sequence identity with AmNES/LIS-1, with only 23 amino acid substitutions distributed across the homologous regions of the proteins. Although these two terpene synthases have very similar catalytic properties, and synthesize linalool and nerolidol as specific products from GPP and FPP, respectively, they are compartmentally segregated. GFP localization studies and analysis of enzyme activities in purified leucoplasts, together with our previous feeding experiments, revealed that AmNES/LIS-1 is localized in cytosol, and is responsible for nerolidol biosynthesis, whereas AmNES/LIS-2 is located in plastids, and accounts for linalool formation. Our results show that subcellular localization of bifunctional enzymes, in addition to the availability of substrate, controls the type of product formed. By directing nearly identical bifunctional enzymes to more than one cellular compartment, plants extend the range of available substrates for enzyme utilization, thus increasing the diversity of the metabolites produced.