gebhart/patrepeval huggingface dataset:
Longitudinal study of excretion of metabolites of polycyclic aromatic hydrocarbons in urine from two psoriatic patients. (1993)

Coal tar, which is widely used in the treatment of patients with atopic dermatitis, chronic eczema, and psoriasis, contains a large amount of polycyclic aromatic hydrocarbons (PAH). Some of the PAH compounds are known either to be carcinogenic or to potentiate the effects of other carcinogenic substances. In the present study, the excretion patterns of 1-hydroxypyrene (metabolite of pyrene) and alpha-naphthol (metabolite of naphthalene) in urine were studied in 2 patients, both treated once a day with coal tar pitch covering more than 50% of the skin. After 1 week of treatment, the concentration of both alpha-naphthol and 1-hydroxypyrene increased approximately 100 times. However, the concentration after 3 weeks of treatment was decreased to approximately the concentration measured before initiation of the treatment, even though the patients were coal tar-treated with unchanged intensity. The measured concentrations of alpha-naphthol and 1-hydroxypyrene in the urine of the 2 patients exceeded by order of magnitude the levels measured in the urine of occupationally exposed workers, and in view of the present study, epidemiological studies are needed to clarify to what extent coal tar treatment results in an increased risk of skin cancer, and e.g. bladder cancer.
Bicarbonate Enhances the Hydroxylation, Nitration, and Peroxidation Reactions Catalyzed by Copper, Zinc Superoxide Dismutase (2000)

The effect of bicarbonate anion (HCO(3)(-)) on the peroxidase activity of copper, zinc superoxide dismutase (SOD1) was investigated using three structurally different probes: 5, 5'-dimethyl-1-pyrroline N-oxide (DMPO), tyrosine, and 2, 2'-azino-bis-[3-ethylbenzothiazoline]-6-sulfonic acid (ABTS). Results indicate that HCO(3)(-) enhanced SOD/H(2)O(2)-dependent (i) hydroxylation of DMPO to DMPO-OH as measured by electron spin resonance, (ii) oxidation and nitration of tyrosine to dityrosine, nitrotyrosine, and nitrodityrosine as measured by high pressure liquid chromatography, and (iii) oxidation of ABTS to the ABTS cation radical as measured by UV-visible spectroscopy. Using oxygen-17-labeled water, it was determined that the oxygen atom present in the DMPO-OH adduct originated from H(2)O and not from H(2)O(2). This result proves that neither free hydroxyl radical nor enzyme-bound hydroxyl radical was involved in the hydroxylation of DMPO. We postulate that HCO(3)(-) enhances SOD1 peroxidase activity via formation of a putative carbonate radical anion. This new and different perspective on HCO(3)(-)-mediated oxidative reactions of SOD1 may help us understand the free radical mechanism of SOD1 and related mutants linked to amyotrophic lateral sclerosis.
Calcium sensing receptor: molecular cloning in rat and localization to nerve terminals. (1995)

We have molecularly cloned a calcium sensing receptor (CaSR) from a rat striatal cDNA library. Rat CaSR displays 92% overall homology to its bovine counterpart with seven putative transmembrane domains characteristic of the superfamily of guanine nucleotide-binding proteins and significant homology with the metabotropic glutamate receptors. Northern blot analysis reveals two transcripts in thyroid, kidney, lung, ileum, and pituitary. In brain highest regional expression of the RNA occurs in the hypothalamus and the corpus striatum. Immunohistochemistry reveals discrete punctate localizations throughout the brain that appear to be associated with nerve terminals. No staining is evident in cell bodies of neurons or glia. Cerebral arteries display an intense network of CaSR immunoreactive fibers associated with vessel innervation. CaSR on nerve terminal membranes may regulate neurotransmitter disposition in response to Ca2+ levels in the synaptic space.
HIV Type 1 Subtype C Drug Resistance among Pediatric and Adult South African Patients Failing Antiretroviral Therapy (2008)

The emergence of HIV drug resistance is a major obstacle to effective antiretroviral (ARV) treatments. This study examined the drug resistance profiles among South African patients virologically failing ARV therapies between 2000 and 2003, prior to the introduction of a national treatment program. Samples were obtained from 65 HIV-1 subtype C-infected patients (39 children and 26 adults) who had received at least two nucleoside reverse transcriptase inhibitors (NRTIs) and either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Resistance assays were performed using the HIV-1 ViroSeq Genotyping System and mutations were defined according to the Stanford Sequence Resistance Database. Ninety-one percent of patients harbored resistance mutations; the most frequent NRTI mutations were M184V/I (37%), D67N (32%), T215Y/F (25%), K70R (21%), M41L (20%), K219Q/E (14%), and K65R (14%), reflecting the frequent use of lamuvidine and zidovudine. K103N (25%), V106M (20%), and G190A (17%) were found among patients failing nevirapine- or efavirenz-containing regimens. Of the patients who received PIs, the most common mutations were V82A/T (12%), M46I (11%), and L90M (8%). Mutations were similar among adults and children. These data indicate that HIV-1 drug resistance develops in South African subtype C-infected patients failing ARV therapy with mutations comparable to those found among patients infected with subtype B viruses.
pH-Dependent Modulation of Relaxivity and Luminescence in Macrocyclic Gadolinium and Europium Complexes Based on Reversible Intramolecular Sulfonamide Ligation (2001)

A series of macrocyclic Eu, Gd, and Tb complexes has been prepared in which the intramolecular ligation of a beta-arylsulfonamide nitrogen is rendered pH-dependent, giving rise to changes in the hydration state, q, at the lanthanide center. In complexes based on DO3A, variation of the p-substituent in the arylsulfonamide moiety determines the apparent protonation constant log K(MLH) with values of 5.7, 6.4, and 6.7 for the -CF(3), -Me, and -OMe substituents, respectively. Introduction of three beta-carboxyalkyl substituents, alpha to three ring nitrogens, inhibits displacement of the bound water by added protein and also suppresses intermolecular binding by endogenous anions (lactate, HCO(3)(-)). Measurements of the pH dependence of the form and intensity of the Eu complexes revealed that intramolecular carboxylate coordination occurred competitively. This was reduced either by enhancing the electron density at the sulfonamide nitrogen or by enlarging the chelate ring from 7--8. Amplification of the relaxivity changes in the pH range 8--5 occurred on protein binding, and over the pH range 7.4--6.8 a 48% change in relaxivity was defined for [Gd.3a] (298 K, 65.6 MHz) in 50% human serum solution.
Pathogenesis of Group A Streptococcal Infections (2000)

Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. A resurgence of invasive streptococcal diseases and rheumatic fever has appeared in outbreaks over the past 10 years, with a predominant M1 serotype as well as others identified with the outbreaks. emm (M protein) gene sequencing has changed serotyping, and new virulence genes and new virulence regulatory networks have been defined. The emm gene superfamily has expanded to include antiphagocytic molecules and immunoglobulin-binding proteins with common structural features. At least nine superantigens have been characterized, all of which may contribute to toxic streptococcal syndrome. An emerging theme is the dichotomy between skin and throat strains in their epidemiology and genetic makeup. Eleven adhesins have been reported, and surface plasmin-binding proteins have been defined. The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. Vaccine strategies have focused on recombinant M protein and C5a peptidase vaccines, and mucosal vaccine delivery systems are under investigation.
The AT&T interactive consumer video services platform (2002)

Interactive video services for consumers, delivered to residences via broadband networks and standard TV's, could be offered over the next several years. Such services include movie on demand, video telephony, interactive television, home shopping, computer games, etc. Economics dictate that a common infrastructure be deployed that can support all the services envisioned today, with future expandability. This paper presents a comprehensive large-scale end-to-end services platform architecture meeting these requirements and describes the field trials of this system scheduled to begin in 1994.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Substrate Specificity of Human Kallikrein 6 (2005)

Human kallikrein 6 (hK6) is abundantly expressed in the central nervous system and is implicated in demyelinating disease. This study provided biochemical data about the substrate specificity and activation of hK6 by glycosaminoglycans and by kosmotropic salts, which followed the Hofmeister series. The screening of fluorescence resonance energy transfer (FRET) peptide families derived from Abz-KLRSSKQ-EDDnp resulted in the finding that Abz-AFRFSQ-EDDnp (where Abz is ortho-aminobenzoic acid and EDDnp is N-[2,4-dinitrophenyl]ethylenediamine)) is the best synthetic substrate described so far for hK6 (kcat/Km 38,667 s(-1) mm(-1)). It is noteworthy that the AFRFS sequence was found as a motif in the amino-terminal domain of seven human ionotropic glutamate receptor subunits. We also examined the hK6 hydrolytic activity on FRET peptides derived from human myelin basic protein, precursor of the Abeta amyloid peptide, reactive center loop of alpha1-antichymotrypsin, plasminogen, and maturation and inactivation cleavage sites of hK6, which were described earlier as natural substrates for hK6. The best substrates were derived from myelin basic protein. The hK6 maturation cleavage site was poorly hydrolyzed, and no evidence was found to support a two-step self-activation process reported previously. Finally, we assayed FRET peptides derived from sequences that span the cleavage sites for activation of protease-activated receptors (PAR) 1-4, and only the substrate with the PAR 2 sequence was hydrolyzed. These results further supported the hypothesis that hK6 expressed in the central nervous system is involved in normal myelin turnover/demyelination processes, but it is unlikely to self-activate. This report also suggested the possible modulation of ionotropic glutamate receptors and activation of PAR 2 by hK6.
The Regulatory Role of Vα14 NKT Cells in Innate and Acquired Immune Response (2003)

A novel lymphocyte lineage, Valpha14 natural killer T (NKT) cells, is now well established as distinct from conventional alphabeta T cells. Valpha14 NKT cells express a single invariant Valpha14 antigen receptor that is essential for their development. Successful identification of a specific ligand, alpha-galactosylceramide(alpha-GalCer), and the establishment of gene-manipulated mice with selective loss of Valpha14 NKT cells helped elucidate the remarkable functional diversity of Valpha14 NKT cells in various immune responses such as host defense by mediating anti-nonself innate immune reaction, homeostatic regulation of anti-self responses, and antitumor immunity.
A Novel Approach to the Simultaneous Measurement of Phase and Amplitude Noises in Oscillator (1989)

This paper presents a signal processing technique called time-domain phase unwrapping applied to the measurement of phase noise in oscillators and which overcomes the dynamic range problem of using phase detectors. The technique can be applied also to the measurement of the amplitude noise of the oscillator. In this paper, the associated theories and the preliminary experimental results are included.
Bile Acids: An Underrecognized and Underappreciated Cause of Chronic Diarrhea (2012)

Bile acid malabsorption is a common cause of chronic watery diarrhea; however, its role appears to be poorly appreciated among clinicians. As such, bile acid diarrhea remains an underrecognized cause of chronic diarrhea, resulting in many patients incorrectly diagnosed and interfering and delaying proper treatment. In this review, we briefly discuss the synthesis, enterohepatic circulation, and function of bile acids. We then focus on the role of bile acids in bile acid malabsorption including the diagnostic and treatment options. By recognizing that bile acid malabsorption is a relatively common cause of chronic diarrhea, we hope that more physicians will more effectively evaluate and treat patients with this condition.
Nuclear Localization of NPR1 Is Required for Activation of PR Gene Expression (2000)

Systemic acquired resistance (SAR) is a broad-spectrum resistance in plants that involves the upregulation of a battery of pathogenesis-related (PR) genes. NPR1 is a key regulator in the signal transduction pathway that leads to SAR. Mutations in NPR1 result in a failure to induce PR genes in systemic tissues and a heightened susceptibility to pathogen infection, whereas overexpression of the NPR1 protein leads to increased induction of the PR genes and enhanced disease resistance. We analyzed the subcellular localization of NPR1 to gain insight into the mechanism by which this protein regulates SAR. An NPR1-green fluorescent protein fusion protein, which functions the same as the endogenous NPR1 protein, was shown to accumulate in the nucleus in response to activators of SAR. To control the nuclear transport of NPR1, we made a fusion of NPR1 with the glucocorticoid receptor hormone binding domain. Using this steroid-inducible system, we clearly demonstrate that nuclear localization of NPR1 is essential for its activity in inducing PR genes.
Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity (2004)

During B-cell development in the mouse, Bruton tyrosine kinase (Btk) and the adaptor protein SLP-65 (Src homology 2 [SH2] domain-containing leukocyte protein of 65 kDa) limit the expansion and promote the differentiation of pre-B cells. Btk is thought to mainly function by phosphorylating phospholipase Cgamma2, which is brought into close proximity of Btk by SLP-65. However, this model was recently challenged by the identification of a role for Btk as a tumor suppressor in the absence of SLP-65 and by the finding that Btk function is partially independent of its kinase activity. To investigate if enzymatic activity is critical for the tumor suppressor function of Btk, we crossed transgenic mice expressing the kinase-inactive K430R-Btk mutant onto a Btk/SLP-65 double-deficient background. We found that K430R-Btk expression rescued the severe developmental arrest at the pre-B-cell stage in Btk/SLP-65 double-deficient mice. Moreover, K430R-Btk could functionally replace wild-type Btk as a tumor suppressor in SLP-65- mice: at 6 months of age, the observed pre-B-cell lymphoma frequencies were approximately 15% for SLP-65- mice, 44% for Btk/SLP-65-deficient mice, and 14% for K430R-Btk transgenic mice on the Btk/SLP-65-deficient background. Therefore, we conclude that Btk exerts its tumor suppressor function in pre-B cells as an adaptor protein, independent of its catalytic activity.
Evaluation of a novel subtilisin inhibitor gene and mutant derivatives for the expression and secretion of mouse tumor necrosis factor alpha by Streptomyces lividans (1997)

In order to evaluate the expression and secretion signals of the highly secreted subtilisin inhibitor of Streptomyces venezuelae CBS762.70 (VSI) for the production of heterologous proteins by Streptomyces lividans, mouse tumor necrosis factor alpha (mTNF) was chosen as a model protein. The mTNF cDNA was fused to the vsi signal sequence. The analysis of secretion by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and biological activity measurements revealed an efficient translocation of mTNF. Up to 300 mg of secreted biologically active mTNF per liter could be obtained in shaken-flask cultures. By analyzing the effects of mutations in the N region of the VSI signal peptide on secretion, we found that decreasing the +3 charge of the wild-type protein to +2 resulted in a 3- to 10-fold increase in secretion.
Deletion of the Dystrophin Muscle-Promoter Region Associated with X-Linked Dilated Cardiomyopathy (1993)

Several forms of hereditary dilated cardiomyopathy have been identified; with the exception of those resulting from mutations of mitochondrial DNA,1,2 no pathological finding can be used to differentiate the conditions, so their distinction depends on the pattern of transmission. Autosomal recessive, autosomal dominant, and matrilinear forms have been reported; several families with X-linked dilated cardiomyopathy have also been described3–5. X-linked dilated cardiomyopathy is a progressive myocardial disease presenting as congestive heart failure in teenage boys without clinical signs of skeletal myopathy5. No information is available on the pathogenetic defect involved in this disorder, although cardiomyopathy is . . .
Lignoceroyl‐CoASH ligase: enzyme defect in fatty acid β‐oxidation system in X‐linked childhood adrenoleukodystrophy (1986)

We have previously reported that the peroxisomal beta-oxidation system for very long chain fatty acids is defective in X-linked childhood adrenoleukodystrophy [(1984) Proc. Natl. Acad. Sci. USA 81, 4203-4207]. In order to elucidate the specific enzyme defect, we examined the oxidation of [1-14C]lignoceric acid, [1-14C]lignoceroyl-CoA and (1-14C)-labelled alpha,beta-unsaturated lignoceroyl-CoA (substrates for the 1st, 2nd, and 3rd steps of the beta-oxidation cycle, respectively). These studies suggest that the pathognomonic accumulation of very long chain fatty acids in X-linked childhood ALD may be due to the defective activity of peroxisomal very long chain (lignoceroyl-CoA) acyl-CoA ligase.
Powder technology and pharmaceutical processes (1994)

Part 1 Background to pharmaceutical engineering: sampling, M. Deleuil physico-chemical transformations of powders, M. Soustelle structure and texture of solids, G. Thomas surface-activity of water, J. Yvon et al particle and powder dynamics, M. Deleuil et al motion, heat and mass transfers, C. Laguerie. Part 2 Powders and multiphase product processes: crystallization, R. David and D. Giron drying, G. Rios et al - drying operations, G. Rios, dewatering and impregnation soaking processes (DIS processes), A.L. Raoult-Wack, freeze-drying, R. Bentejac, fluid bed drying, R. Joulie storage, feeding, proportioning, D. Schulze, pneumatic conveying, P. Hilgraf mixing, J. Bridgwater granulation and coating, Z.D. Ormos, moist agglomeration of pharmaceutical powders (size enlargement of particulate material), the production of granules by moist agglomeration of powders in mixers/kneaders, H. Leuenberger extrusion/spheronisation, J.M. Newton assessment of powder compaction, E. Doelker, tabletting - an industrial view point, A. Lewis and G. Simpkin new processes - application of spherical crystallization to particulate design of pharmaceuticals for direct tabletting and coating, and new drug delivery systems, Y. Kawashima, microencapsulation processes for the manufacture of systems providing modified release of the active constituent, H. Porte and G. Couarraze dissolution and powder technology, W.A. Hanson tentative conclusions, M. Deleuil.
Iridium-catalyzed borylation of arenes and heteroarenes via C-H activation (2006)

Abstract Direct C-H borylation of aromatic compounds catalyzed by a transition-metal complex was studied as an economical protocol for the synthesis of aromatic boron derivatives. Iridium complexes generated from Ir(I) precursors and 2,2'-bipyridine ligands efficiently catalyzed the reactions of arenes and heteroarenes with bis(pinacolato)diboron or pinacolborane to produce a variety of aryl- and heteroarylboron compounds. The catalytic cycle involves the formation of a tris(boryl)iridium(III) species and its oxidative addition to an aromatic C-H bond.
Polymer Electrolytes for Lithium-Ion Batteries (1998)

The motivation for lithium battery development and a discussion of ion conducting polymers as separators begin this review, which includes a short history of polymer electrolyte research, a summary of the major parameters that determine lithium ion transport in polymer matrices, and consequences for solid polymer electrolyte development. Two major strategies for the application of ion conducting polymers as separators in lithium batteries are identified: One is the development of highly conductive materials via the crosslinking of mobile chains to form networks, which are then swollen by lithium salt solutions ("gel electrolytes"). The other is the construction of solid polymer electrolytes (SPEs) with supramolecular architectures, which intrinsically give rise to much enhanced mechanical strength. These materials as yet exhibit relatively common conductivity levels but may be applied as very thin films. Molecular composites based on poly(p-phenylene)- (PPP)-reinforced SPEs are a striking example of this direction. Neither strategy has as yet led to a "breakthrough" with respect to technical application, at least not for electrically powered vehicles. Before being used as separators, the gel electrolytes must be strengthened, while the molecularly reinforced solid polymer electrolytes must demonstrate improved conductivity.
Molecular Ecological Analysis of Fecal Bacterial Populations from Term Infants Fed Formula Supplemented with Selected Blends of Prebiotics (2008)

Supplementation of infant formulas with prebiotic ingredients continues the effort to mimic functional properties of human milk. In this double-blind, controlled, 28-day study, healthy term infants received control formula (control group; n = 25) or control formula supplemented with polydextrose (PDX) and galactooligosaccharide (GOS) (4 g/liter) (PG4 group; n = 27) or with PDX, GOS, and lactulose (LOS) (either 4 g/liter [PGL4 group; n = 27] or 8 g/liter [PGL8 group; n = 25]). A parallel breast-fed group (BF group) (n = 30) was included. Stool characteristics, formula tolerance, and adverse events were monitored. Fecal bacterial subpopulations were evaluated by culture-based selective enumeration (Enterobacteriaceae), quantitative real-time PCR (Clostridium clusters I, XI, and XIV, Lactobacillus, and Bifidobacterium), and fluorescence in situ hybridization (FISH) (Bifidobacterium). Fecal bacterial community profiles were examined by using 16S rRNA gene PCR-denaturing gradient gel electrophoresis. The daily stool consistency was significantly softer or looser in the BF group than in all of the groups that received formula. The formulas were well tolerated, and the incidences of adverse events did not differ among feeding groups. Few significant changes in bacterial subpopulations were observed at any time point. The bacterial communities were stable; individual profiles tended to cluster by subject rather than by group. Post hoc analysis, however, demonstrated that the bacterial community profiles for subjects in the BF, PG4, PGL4, and PGL8 groups that first received formula at a younger age were less stable than the profiles for subjects in the same groups that received formula at an older age, but there was no difference for the control group. These data indicate that formulas containing PDX, GOS, and LOS blends are more likely to influence gut microbes when administration is begun in early infancy and justify further investigation of the age-related effects of these blends on fecal microbiota.