gebhart/patrepeval huggingface dataset:
Active Centers of α‐Chymotrypsin and of Streptomyces griseus Proteases 1 and 3 (1980)

A number of peptides of the general formula Ac-Pro-Ala-X-Phe-NH2, where X = Gly, Ala, Leu, Phe or Pro, have been synthesized for the study of S2-P2 enzyme-substrate interactions in three serine proteases: alpha-chymotrypsin and Streptomyces griseus proteases 1 and 3. All three enzymes interacted favorably with those peptides with hydrophobic, non-aromatic, P2 amino acid residues, leucine being optimal. The increase in kcat/Km on going from the P2 glycine to the P2 leucine peptide was 30-fold in alpha-chymotrypsin and greater than 150-fold and 350-fold in the Streptomyces enzymes, being due to both increased affinities and higher acylation rates. Hydrophobic S2-P2 interactions, particularly in S. griseus proteases 1 and 3, appear to be the most important enzyme-substrate interactions apart from S1-P1. The kinetic data is discussed in relation to the tertiary structures of the active centers of the enzymes.
Rate of Temperature Increase in Human Muscle During 1 MHz and 3 MHz Continuous Ultrasound (1995)

To achieve the thermal effects of ultrasound, the tissue temperature must be raised from 1 to > or = 4 degrees C, depending on the desired outcome of the treatment. In the past 25 years, there have been no in vivo studies that have measured rate of change in temperature during 1-MHz ultrasound treatments, and none have ever been performed with the 3-MHz frequency. Thus, we are left to pure speculation regarding how long to administer an ultrasound treatment. We performed this study to plot the rate of temperature increase during ultrasound treatments delivered at various intensities and frequencies. We inserted two 23-gauge thermistors into each subjects' medial triceps surae at the following depths: 1 MHz at depths of 2.5 and 5.0 cm (12 subjects) and 3 MHz at depths of .8 and 1.6 cm (12 subjects). Each subject received a total of four 10-minute treatments, one each at .5, 1.0, 1.5, and 2.0 W/cm2, and temperature was measured every 30 seconds. No significant difference was found in the rate of heating at the two depths (p = .987) within the same frequency and dose levels. The 3-MHz frequency heated significantly faster than the 1-MHz frequency at all doses tested (p < .001). On average, the rate of temperature increased per minute at the two depths of the 1-MHz frequency was: .04 degrees C at .5 W/cm2; .16 degrees C at 1.0 W/cm2; .33 degrees C at 1.5 W/cm2; and .38 degrees C at 2.0 W/cm2. The rate of temperature increase per minute at the two depths of the 3-MHz frequency was: .3 degrees C at .5 W/cm2; .58 degrees C at 1.0 W/cm2; .89 degrees C at 1.5 W/cm2; and 1.4 degrees C at 2.0 W/cm2. The results of this research should enable clinicians to choose the correct frequency, intensity, and treatment time when using thermal ultrasound.
L‐asparaginase treatment in acute lymphoblastic leukemia (2010)

Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available: the native asparaginase derived from Escherichia coli (E. coli asparaginase), a pegylated form of this enzyme (PEG-asparaginase), and a product isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, debate on the optimal formulation and dosage of these agents continues. This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL.
Triacylglycerol synthesis in cultured rat hepatocytes (1989)

The limiting role of diacylglycerol acyltransferase with respect to triacylglycerol synthesis in cultured rat hepatocytes was evaluated by following the inhibition of the overall synthetic flux by 2-bromooctanoate acting as an inhibitor of the diacylglycerol acyltransferase step. The flux-control coefficient of diacylglycerol acyltransferase in intact cultured hepatocytes amounted to 0.76 in the presence of saturating glycerol and either palmitate or oleate as the fatty acyl substrates. The flux-control coefficient of diacylglycerol acyltransferase in lysolecithin-permeabilized cultured hepatocytes amounted to 0.80 and 0.99 in the presence of saturating glycerol 3-phosphate and either palmitate or oleate as the fatty acyl substrate, respectively. Hence, triacylglycerol synthesis in liver cells under the experimental conditions employed is rate-limited by the diacylglycerol acyltransferase.
Treatment of acute bleeds with recombinant activated factor VII during immune tolerance therapy. (1998)

In our clinic, five patients with haemophilia A and one patient with haemophilia B and inhibitors have been treated with immune tolerance induction (ITI) since 1995. Bleeding symptoms during this period have been treated with recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). Four of the six patients did not need rFVIIa during ITI other than for port-a-cath insertions, but two have been treated intensively because of repeated bleeding problems. The first of these developed inhibitors at the age of 2 years after 11 days of exposure to factor VIII (FVIII). He was treated for 40 bleeding episodes before ITI started, and during ITI he was treated another 24 times, including eight treatments for joint bleeds. Treatment was effective for the different types of bleeding episode. However, in spite of repeated treatment for these joint bleeds, he developed two target joints with synovitis (right knee and left elbow). The synovitis only showed signs of regression when inhibitor levels were reduced due to the ITI regimen. The second patient, now 5 years old, has severe haemophilia B. He developed inhibitors and anaphylaxia having received prophylactic treatment from the age of 1 year. He has now received ITI with 120 units/kg body weight per day of FIX for 68 weeks. In the event of trauma and bleeding he is treated promptly with rFVIIa by his parents at home. Treatment is started with 160-180 microg/kg body weight and, if needed, another dose of 90 microg/kg is given after 3 h. During 1996, 35 bleeds or traumas were treated. The total amount of rFVIIa administered to this child was 211.2 mg. All but one joint bleed and all muscle bleeds needed more than one injection. The need for another injection is judged by the parents and the child from clinical signs, such as pain and swelling. Neither of these two boys have shown any signs of thrombosis or disseminated intravascular coagulation. In summary, rFVIIa is a well tolerated and effective therapy for acute bleeding episodes during ITI. Dosing and intervals can be the same as for patients not on ITI therapy. Early intervention at home can minimize the risk of synovitis.
Graphene as a Massless Electrode for Ultrahigh-Frequency Piezoelectric Nanoelectromechanical Systems (2015)

Designing "ideal electrodes" that simultaneously guarantee low mechanical damping and electrical loss as well as high electromechanical coupling in ultralow-volume piezoelectric nanomechanical structures can be considered to be a key challenge in the NEMS field. We show that mechanically transferred graphene, floating at van der Waals proximity, closely mimics "ideal electrodes" for ultrahigh frequency (0.2 GHz < f0 < 2.6 GHz) piezoelectric nanoelectromechanical resonators with negligible mechanical mass and interfacial strain and perfect radio frequency electric field confinement. These unique attributes enable graphene-electrode-based piezoelectric nanoelectromechanical resonators to operate at their theoretically "unloaded" frequency-limits with significantly improved electromechanical performance compared to metal-electrode counterparts, despite their reduced volumes. This represents a spectacular trend inversion in the scaling of piezoelectric electromechanical resonators, opening up new possibilities for the implementation of nanoelectromechanical systems with unprecedented performance.
DNA Content and DNA-Based Centromeric Index of the 24 Human Chromosomes (1973)

The chromosomes of two human males were identified by fluorescent banding, restained, and measured by scanning microscopy and computer analysis. The two variables, DNA content and DNA-based centromeric index, provided almost complete discrimination of chromosome types. Some chromosomes showed significant differences in DNA content between the men, and for one man two pairs of chromosomes showed significant differences between homologs.
Differentiation of Human Circulating Fibrocytes as Mediated by Transforming Growth Factor-β and Peroxisome Proliferator-activated Receptor γ (2007)

Fibrocytes are a distinct population of fibroblast-like progenitor cells in peripheral blood that have recently been shown to possess plasticity to differentiate along mesenchymal lineages, including commitment to myofibroblast and adipocyte cells. Here, we demonstrated that transforming growth factor (TGF) beta1 drives fibrocyte-to-myofibroblast differentiation through activating Smad2/3 and SAPK/JNK MAPK pathways, which in turn stimulates alpha-smooth muscle actin expression. We determined that SAPK/JNK signaling acts in a positive feedback loop to modulate Smad2/3 nuclear availability and Smad2/3-dependent transcription. Conversely, fibrocyte-to-adipocyte differentiation is driven by the peroxisome proliferator-activated receptor (PPAR) gamma agonist troglitazone, which is associated with cytoplasmic lipid accumulation and induction of aP2. Treatment with troglitazone also disrupted TGF beta 1-activated SAPK/JNK signaling, leading to decreased Smad2/3 transactivation activity and alpha-smooth muscle actin expression. Interestingly, TGF beta 1 was demonstrated to have reciprocal inhibition on fibrocyte differentiation to adipocytes. By activating SAPK/JNK signaling, which is normally suppressed during adipogenesis, PPARgamma-dependent transactivation activity and induction of aP2 expression were disrupted. Taken together, within the context of the local microenvironmental niche, the delicate balance of PPARgamma and TGF beta 1 activation drives the selection of an adipocyte or myofibroblast differentiation pathway through SAPK/JNK signaling.
Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions (2006)

Acetylation of histone H4 on lysine 16 (H4-K16Ac) is a prevalent and reversible posttranslational chromatin modification in eukaryotes. To characterize the structural and functional role of this mark, we used a native chemical ligation strategy to generate histone H4 that was homogeneously acetylated at K16. The incorporation of this modified histone into nucleosomal arrays inhibits the formation of compact 30-nanometer-like fibers and impedes the ability of chromatin to form cross-fiber interactions. H4-K16Ac also inhibits the ability of the adenosine triphosphate-utilizing chromatin assembly and remodeling enzyme ACF to mobilize a mononucleosome, indicating that this single histone modification modulates both higher order chromatin structure and functional interactions between a nonhistone protein and the chromatin fiber.
Mechanism of Alanine Hyperproduction by Arthrobacter oxydans HAP-1: Metabolic Shift to Fermentation under Nongrowth Aerobic Conditions (1999)

ABSTRACT Arthrobacter oxydans HAP-1 hyperproduces dl -alanine in a non-growth-associated manner. We found that decreased activities of pyruvate dehydrogenase and of the enzyme catalyzing NADH oxidation in the stationary phase are paralleled by a shift of pyruvate metabolism to alanine synthesis by l -alanine dehydrogenase. We propose that this enzyme functions as an electron sink even under aerobic conditions.
CRISPR-Cas Systems in Bacteria and Archaea: Versatile Small RNAs for Adaptive Defense and Regulation (2011)

Bacteria and archaea have evolved defense and regulatory mechanisms to cope with various environmental stressors, including virus attack. This arsenal has been expanded by the recent discovery of the versatile CRISPR-Cas system, which has two novel features. First, the host can specifically incorporate short sequences from invading genetic elements (virus or plasmid) into a region of its genome that is distinguished by clustered regularly interspaced short palindromic repeats (CRISPRs). Second, when these sequences are transcribed and precisely processed into small RNAs, they guide a multifunctional protein complex (Cas proteins) to recognize and cleave incoming foreign genetic material. This adaptive immunity system, which uses a library of small noncoding RNAs as a potent weapon against fast-evolving viruses, is also used as a regulatory system by the host. Exciting breakthroughs in understanding the mechanisms of the CRISPR-Cas system and its potential for biotechnological applications and understanding evolutionary dynamics are discussed.
Lessons from ECLIPSE: a review of COPD biomarkers (2013)

The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational controlled multicentre international study aimed at defining clinically relevant subtypes of chronic obstructive pulmonary disease (COPD) and identifying novel biomarkers and genetic factors. So far, the ECLIPSE study has produced more than 50 original publications and 75 communications to international meetings, many of which have significantly influenced our understanding of COPD. However, because there is not one paper reporting the biomarker results of the ECLIPSE study that may serve as a reference for practising clinicians, researchers and healthcare providers from academia, industry and government agencies interested in COPD, we decided to write a review summarising the main biomarker findings in ECLIPSE.
A WD-FYVE protein binds to the kinases Akt and PKCζ/λ (2006)

WD (tryptophan-aspartic acid dipeptide)-repeat proteins play a central role in signal transduction cascades by co-ordinating the interaction of key signalling molecules. We identified a novel propeller-FYVE [domain identified in Fab1p, YOTB, Vac1p and EEA1 (early endosome antigen 1)] protein, ProF, which is expressed in various cell lines and tissues and consists of seven WD-repeats and a FYVE domain. WD-repeat proteins offer a platform for protein-protein interactions by folding into a seven-bladed propeller-like structure, while the FYVE domain binds to phosphatidylinositol 3-phosphate present mainly on intracellular membranes. The ProF protein partially co-localizes with EEA1 on vesicular structures and binds to the protein kinases Akt and PKCzeta/lambda (protein kinase Czeta/lambda) via its WD-repeat propeller. ProF interacts more strongly with the kinases after hormonal stimulation. Endogenously expressed ProF and the two kinases interact in brain and in the preadipocyte cell line 3T3-L1, suggesting a role in secretory vesicular processes. In summary, we describe a new binding partner for kinases, located on vesicular structures in specialized cells, which may play a role for the spatial organization of signalling cascades.
Crystal structure of GGA2 VHS domain and its implication in plasticity in the ligand binding pocket (2003)

Golgi-localized, gamma-ear-containing, ARF binding (GGA) proteins regulate intracellular vesicle transport by recognizing sorting signals on the cargo surface in the initial step of the budding process. The VHS (VPS27, Hrs, and STAM) domain of GGA binds with the signal peptides. Here, a crystal structure of the VHS domain of GGA2 is reported at 2.2 A resolution, which permits a direct comparison with that of homologous proteins, GGA1 and GGA3. Significant structural difference is present in the loop between helices 6 and 7, which forms part of the ligand binding pocket. Intrinsic fluorescence spectroscopic study indicates that this loop undergoes a conformational change upon ligand binding. Thus, the current structure suggests that a conformational change induced by ligand binding occurs in this part of the ligand pocket.
PKC1, a protein kinase C homologue of Saccharomyces cerevisiae, participates in microtubule function through the yeast EB1 homologue, BIM1 (2001)

These results suggest that Pkc1p plays a role which is relevant to microtubule functions and that this role is mediated by a hitherto unknown PKC signalling pathway and by Bim1p
Particle-mediated DNA vaccination of mice, monkeys and men: looking beyond the dogma. (2002)

Data generated in the early phases of experimentation in a new field of scientific exploration sometimes results in hasty conclusions about the generality of the data. To some degree, this has happened at least twice in the relatively new area of DNA immunization. Early data seemed to indicate firstly that particle-mediated epidermal DNA immunization induced predominantly Th2-type cellular immune responses, and secondly that DNA immunization was not very successful in humans. This review highlights the current body of data showing that particle-mediated DNA immunization is highly effective in the induction Th1-type responses and is an efficient method for inducing immune responses in humans.
Unilateral Transplantation of Human Fetal Mesencephalic Tissue into the Caudate Nucleus of Patients with Parkinson's Disease (1992)

Although the case patients continued to be disabled by their disease, unilateral intracaudate grafts of fetal tissue containing dopamine diminished the symptoms and signs of parkinsonism during 18 months of evaluation.
ChemInform Abstract: Catalytic Asymmetric Homo‐Aldol Reaction of Pyruvate — A Chiral Lewis Acid Catalyst that Mimics Aldolase Enzymes. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Superamphiphobic surfaces (2014)

Superamphiphobicity is an effect where surface roughness and surface chemistry combine to generate surfaces which are both superhydrophobic and superoleophobic, i.e., contact angles (θCA) greater than 150° along with low contact angle hysteresis (CAH) not only towards probing water but also for low-surface-tension 'oils'. In this review, we summarize the research on superamphiphobic surfaces, including the characterization of superamphiphobicity, different techniques towards the fabrication of surface roughness and surface modification with low-surface-energy materials as well as their functional applications.
Expression of NCAM isoforms during skeletal myogenesis in the mouse embryo (1992)

We have examined the developmental patterns of neural cell adhesion molecule (NCAM) gene expression in embryonic mouse skeletal muscle cells by in situ hybridization. Moreover, by utilising exon-specific cRNA probes, we have examined tissue specific splicing of the NCAM gene. We show that there is a distinct sequence of NCAM isoform expression during skeletal muscle development. Since NCAMs are also expressed in other cell types, particularly neurons, NCAM mRNAs have been colocalised with acetylcholine receptor alpha (AChR alpha) gene transcripts to identify muscle-specific expression. NCAM is first detected in somites as they first form, prior to their differentiation into muscle and nonmuscle compartments. Myotomes, the first skeletal muscle masses to form in the embryo, express mRNAs for the transmembrane 180 and 140 kDa isoforms of NCAM. Both of these transcripts are also detected in the neural tube, and their spatial pattern of expression changes with development. Transcripts containing the muscle-specific domain (MSD) of the NCAM gene are not detected prior to 11 days postcoitum (p.c.), at a time when rostral somites already contain well-developed myotomes. As the level of MSD mRNAs increases at 12 days p.c., the 140 and 180 kDa transcript levels decrease in skeletal muscle masses. The level of all NCAM isoform transcripts declines between 13 and 15 days p.c. in muscle. However, the 180 and 140 kDa NCAM isoforms are expressed at a high level in neural tissue and in other locations in the developing embryo such as in smooth muscle, around vibrissae follicles, and in the perichondrial zone of digits.
Mechanism of solid state pressure welding (1975)

welded area was in agreement with measured fracture strength.It was concluded that the strength attained after a given deformation is determined by the fractional welded area at that deformation.
Profiles of Cytokines (TNFα and IL-6) and Acute Phase Proteins (CRP and α1AG) related to the Disease Course in Patients with Systemic Lupus Erythematosus (1993)

Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) play a main role in inducing acute phase protein production by hepatocytes. This study describes the serum levels of TNF alpha and IL-6 in relation to serum levels of C-reactive protein (CRP) and alpha 1-acid glycoprotein (alpha 1AG) in three systemic lupus erythematosus (SLE) patients. Disease courses of these patients were divided in a total of 19 clinical periods, according to the clinical symptoms and interleukin profiles. Significantly elevated TNF alpha levels were found in all but three of the defined periods, without being associated with disease activity. In only four of the defined periods elevated TNF alpha were observed combined with elevated IL-6 and CRP levels. Two of these periods coincided with minor symptoms of SLE, one with an exacerbation and the other one with a systemic infection while SLE activity was low. All other periods showed varying combinations of elevated TNF alpha and/or IL-6 levels being followed or not by elevated CRP levels. Significantly raised alpha 1AG levels were measured in all clinical periods. In most of the observed periods a dissociation was found between TNF alpha and IL-6 and also between the different cytokine (TNF alpha and IL-6) levels and acute phase protein (CRP and alpha 1AG) levels. These data could not be explained by differences in disease course or influences of medication. We conclude that more factors other than TNF alpha and IL-6 must play a role in the regulatory pathway of the acute phase response in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochemical Genetics of the Bacterial Insect-Control AgentBacillus thuringiensis:Basic Principles and Prospects for Genetic Engineering (1984)

Biochimie et genetique des endotoxines delta de B-thuringiensis. Perspectives d'utilisation du genie genetique pour augmenter la production de la toxine
Inverse Polymerase Chain Reaction (2003)

Since the first report on cDNA cloning in 1972 (), this technology has been developed into a powerful and universal tool in the isolation, characterization, and analysis of both eukaryotic and prokaryotic genes. But the conventional methods of cDNA cloning require much effort to generate a library that is packaged in phage or plasmid and then survey a large number of recombinant phages or plasmids. There are three major limitations in those methods. First, substantial amount (at least 1 µg) of purified mRNA is needed as starting material to generate libraries of sufficient diversity (). Second, the intrinsic difficulty of multiple sequential enzymatic reactions required for cDNA cloning often leads to low yields and truncated clones (). Finally, screening of a library with hybridization technique is time consuming.