gebhart/patrepeval huggingface dataset:
Identification of a GH110 Subfamily of α1,3-Galactosidases (2008)

In search of alpha-galactosidases with improved kinetic properties for removal of the immunodominant alpha1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of alpha-galactosidases (CAZy GH110) with highly restricted substrate specificity and neutral pH optimum (Liu, Q. P., Sulzenbacher, G., Yuan, H., Bennett, E. P., Pietz, G., Saunders, K., Spence, J., Nudelman, E., Levery, S. B., White, T., Neveu, J. M., Lane, W. S., Bourne, Y., Olsson, M. L., Henrissat, B., and Clausen, H. (2007) Nat. Biotechnol. 25, 454-464). One member of this family from Bacteroides fragilis had exquisite substrate specificity for the branched blood group B structure Galalpha1-3(Fucalpha1-2)Gal, whereas linear oligosaccharides terminated by alpha1,3-linked galactose such as the immunodominant xenotransplantation epitope Galalpha1-3Galbeta1-4GlcNAc did not serve as substrates. Here we demonstrate the existence of two distinct subfamilies of GH110 in B. fragilis and thetaiotaomicron strains. Members of one subfamily have exclusive specificity for the branched blood group B structures, whereas members of a newly identified subfamily represent linkage specific alpha1,3-galactosidases that act equally well on both branched blood group B and linear alpha1,3Gal structures. We determined by one-dimensional (1)H NMR spectroscopy that GH110 enzymes function with an inverting mechanism, which is in striking contrast to all other known alpha-galactosidases that use a retaining mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant alpha3Gal xenotransplantation epitope.
The Clinical Use of Disulfiram (Antabuse®): A Review (1988)

Disulfiram is a potent alcohol-sensitizing drug, the effectiveness of which remains unproven in the treatment of alcoholism after 40 years of use. Its clinical utility is more closely associated with nonspecific, nonpharmacological factors (such as social class, patient compliance, patient personality characteristics, and treatment structure) than with its aversive biochemistry. Disulfiram is not effective as a sole alternative to a structured treatment program. Disulfiram retains a place in standard alcoholism treatment programs because clinicians have found this agent useful for selected alcoholic patients. Clinical studies and clinical lore describe these patients as older, relapse-prone, socially stable, cognitively intact, not depressed, compulsive, capable of following rules, and tolerant of dependence. Another distinctly responsive (but evasive) group is court-probated patients. These characteristics also describe patients who are well-known to have good outcomes without disulfiram, thus they do not help clinicians to select suitable patients for this medication. Consequently, this article proposes the following selection criteria: (1) patients who can tolerate a treatment relationship; (2) patients who are relapse-prone (but in treatment); (3) patients who have failed with less structured approaches; (4) patients in early abstinence who are in crisis or under severe stress; (5) patients in established recovery for whom individual or group psychotherapy is a relapse risk; and (6) patients who specifically request it. With or without disulfiram, a treatment program needs to be highly structured and predictable in order to be useful to newly recovering patients. Recovery is a process with discernible phases of development, and the provision of structure is the core of early treatment, where behavior change is more important than insight. A well-structured program will have phases through which a patient may progress. Generally speaking, disulfiram is most useful early to establish sobriety and to allow time for other support structures, such as AA, therapist-patient relationships, and new personal relationships, to take hold. Disulfiram is best given to patients with prior treatment failures, early in treatment, briefly during crises in established sobriety, or to support unusual stresses, such as psychotherapy. Prescriptions should be short-term and not allow automatic refills. It should be necessary to attend a treatment program in order to obtain them. Supervision and monitoring dramatically increase compliance.(ABSTRACT TRUNCATED AT 400 WORDS)
Toxicity of Alkyl 2-Cyanoacrylates (1966)

A FAMILY of adhesives, the alkyl 2-cyanoacrylates, have been receiving increasing attention from surgeons in the hope of improving various surgical procedures. Whether used to replace or to supplement suture techniques, the use of such adhesives necessarily involves the introduction of a foreign body into the operative site. Consequently it seemed worthwhile to investigate the effects of these materials upon bacterial growth. Methyl 2-cyanoacrylate has been available for a considerable period of time and it has long been known to be self-sterilizing.<sup>1</sup>When a drop of this material was added to agar plates, it inhibited the growth of bacteria within a concentric zone.<sup>2</sup>Cultures of the methyl monomer failed to develop bacterial growth. However, spores have been shown to be capable of surviving, though not of developing, within this material. As a result of the interest evolved by the introduction of the methyl monomer, higher homologues of lesser
Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. I. Identification of the protein and delineation of its target nucleotide sequence (1993)

The current paper reports the identification of a protein in rat liver nuclei that binds to the sterol regulatory element (SRE-1) in the promoter of the gene for the low density lipoprotein receptor. The 10-base pair SRE-1 is embedded within a 16-base pair sequence designated Repeat 2 located immediately upstream of a related sequence designated Repeat 3. To confirm that DNA recognition by the SRE-1 binding protein (SREBP) correlates with sterol-regulated transcription, we synthesized an artificial promoter that contains two copies of wild-type or mutant Repeat 2 + 3 sequences immediately upstream of a TATA box from adenovirus. The synthetic promoters were inserted upstream of a reporter gene and tested for transcriptional activity in the absence and presence of sterols after transient transfection into monkey CV-1 cells. The reporter gene with two copies of the wild-type Repeat 2 + 3 sequence was transcribed actively in sterol-deprived cells and was repressed by more than 80% when sterols were present. Binding of SREBP to the SRE-1 sequence, assessed by gel mobility shift assays, correlated precisely on a nucleotide-by-nucleotide basis with the transcriptional activity of each of 16 synthetic promoters with point mutations in Repeat 2. The SREBP bound to the nine mutant promoters that were positive for sterol-regulated transcription, and it did not bind to any of the nine point mutants that abolished transcription. We conclude that SREBP is a DNA binding protein that mediates sterol-regulated transcription of the low density lipoprotein receptor gene.
Association of Polymorphism (Val66Met) of Brain-Derived Neurotrophic Factor with Suicide Attempts in Depressed Patients (2008)

These preliminary data suggest that BDNF may play a role in the suicidal behaviour of depressed patients.
Efficacy of Tilmicosin in the Control of Experimental Mycoplasma Gallisepticum Infection in Chickens (1997)

This study was conducted to evaluate the efficacy of 5-day, "in water" tilmicosin medication for the prevention of experimental Mycoplasma gallisepticum (MG) disease in 10-day-old specific-pathogen-free (SPF) chickens. Birds were inoculated intratracheally and into the sinus with the MG R-P10 strain. A limited dose titration of the antibiotic over the expected effective range was included, using six groups of 60 birds each: UI: uninfected untreated group; IUT: infected untreated group; IT1 to IT4: four infected treated groups, which were administered 50, 100, 200, or 300 mg/liter of tilmicosin. The birds were given tilmicosin from 8 to 13 days of age and were inoculated at 10 days of age. The birds were observed for 11 days postchallenge before terminal postmortem examination was completed including, assessment of lesions and sampling for mycoplasma culture and serology. Body-weight gains of the different groups were compared. The results showed that tilmicosin medication at dose levels of 50-300 mg/liter significantly decreased growth losses and respiratory signs due to MG infection (P < 0.05). Significant reduction in air sac and peritonitis lesions were obtained by treatment with 100, 200 or 300 mg/liter for 5 days (P < 0.05). A significant reduction in the proportion of MG-culture-positive birds was obtained at a dose level of 50 mg/liter (P < 0.05). Increasing the dose resulted in a further decrease in the number of MG shedding chickens to the extent that with the two highest doses of tilmicosin, no bird was serologically positive on day 21, compared to 46/58 positively infected untreated birds (day 21).
Extending CO 2 cryogenic aerosol cleaning for advanced optical and EUV mask cleaning (2011)

Cryogenic CO<sub>2</sub> aerosol cleaning being a dry, chemically-inert and residue-free process is used in the production of optical lithography masks. It is an attractive cleaning option for the mask industry to achieve the requirement for removal of all printable soft defects and repair debris down to the 50nm printability specification. In the technique, CO<sub>2</sub> clusters are formed by sudden expansion of liquid from high to almost atmospheric pressure through an optimally designed nozzle orifice. They are then directed on to the soft defects or debris for momentum transfer and subsequent damage free removal from the mask substrate. Unlike aggressive acid based wet cleaning, there is no degradation of the mask after processing with CO<sub>2</sub>, i.e., no critical dimension (CD) change, no transmission/phase losses, or chemical residue that leads to haze formation. Therefore no restriction on number of cleaning cycles is required to be imposed, unlike other cleaning methods. CO<sub>2</sub> aerosol cleaning has been implemented for several years as full mask final clean in production environments at several state of the art mask shops. Over the last two years our group reported successful removal of all soft defects without damage to the fragile SRAF features, zero adders (from the cleaning and handling mechanisms) down to a 50nm printability specification. In addition, CO<sub>2</sub> aerosol cleaning is being utilized to remove debris from Post-RAVE repair of hard defects in order to achieve the goal of no printable defects. It is expected that CO<sub>2</sub> aerosol cleaning can be extended to extreme ultraviolet (EUV) masks. In this paper, we report advances being made in nozzle design qualification for optimum snow properties (size, velocity and flux) using Phase Doppler Anemometry (PDA) technique. In addition the two new areas of focus for CO<sub>2</sub> aerosol cleaning i.e. pellicle glue residue removal on optical masks, and ruthenium (Ru) film on EUV masks are presented. Usually, the residue left over after the pellicle has been removed from returned masks (after long term usage/exposure in the wafer fab), requires a very aggressive SPM wet clean, that drastically reduces the available budget for mask properties (CD, phase/transmission). We show that CO<sub>2</sub>aerosol cleaning can be utilized to remove the bulk of the glue residue effectively, while preserving the mask properties. This application required a differently designed nozzle to impart the required removal force for the sticky glue residue. A new nozzle was developed and qualified that resulted in PRE in the range of 92-98%. Results also include data on a patterned mask that was exposed in a lithography stepper in a wafer production environment. On EUV mask, our group has experimentally demonstrated that 50 CO<sub>2</sub> cleaning cycles of Ru film on the EUV Front-side resulted in no appreciable reflectivity change, implying that no degradation of the Ru film occurs.
Phytosterols Promote Liver Injury and Kupffer Cell Activation in Parenteral Nutrition–Associated Liver Disease (2013)

Parenteral nutrition-associated liver disease (PNALD) is a serious complication of PN in infants who do not tolerate enteral feedings, especially those with acquired or congenital intestinal diseases. Yet, the mechanisms underlying PNALD are poorly understood. It has been suggested that a component of soy oil (SO) lipid emulsions in PN solutions, such as plant sterols (phytosterols), may be responsible for PNALD, and that use of fish oil (FO)-based lipid emulsions may be protective. We used a mouse model of PNALD combining PN infusion with intestinal injury to demonstrate that SO-based PN solution causes liver damage and hepatic macrophage activation and that PN solutions that are FO-based or devoid of all lipids prevent these processes. We have furthermore demonstrated that a factor in the SO lipid emulsions, stigmasterol, promotes cholestasis, liver injury, and liver macrophage activation in this model and that this effect may be mediated through suppression of canalicular bile transporter expression (Abcb11/BSEP, Abcc2/MRP2) via antagonism of the nuclear receptors Fxr and Lxr, and failure of up-regulation of the hepatic sterol exporters (Abcg5/g8/ABCG5/8). This study provides experimental evidence that plant sterols in lipid emulsions are a major factor responsible for PNALD and that the absence or reduction of plant sterols is one of the mechanisms for hepatic protection in infants receiving FO-based PN or lipid minimization PN treatment. Modification of lipid constituents in PN solutions is thus a promising strategy to reduce incidence and severity of PNALD.
MELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts. (1992)

The pathogenetic mechanism of the mitochondrial tRNA(LeuUUR) gene mutation responsible for the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome was investigated in transformants obtained by transfer of mitochondria from three genetically unrelated MELAS patients into human mitochondrial DNA (mtDNA)-less (rho 0) cells. Marked defects in mitochondrial protein synthesis and respiratory activity were observed in transformants containing virtually pure mutant mtDNA, as compared to the parent of the rho 0 cells (the 143B cell line) or to transformants containing exclusively wild-type mtDNA, derived from one of the patients or a maternally related asymptomatic individual. A striking protective effect against the mutation was exerted in the transformants by levels of residual wild-type mtDNA above 6%. The MELAS mutation occurs within the mtDNA binding site for a protein factor (mTERF) that promotes termination of transcription at the 16S rRNA/tRNA(LeuUUR) gene boundary. A marked decrease in affinity of purified mTERF for the mutant target sequence was observed in in vitro assays. By contrast, RNA transfer hybridization experiments failed to show any significant change in the steady-state amounts of the two rRNA species, encoded upstream of the termination site, and of the mRNAs encoded downstream, in the transformants carrying the MELAS mutation.
Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin (1994)

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX), on urinary bladder carcinogenesis induced by N-butyl-N(4-hydroxybutyl)nitrosamine (OH-BBN) was investigated in male ICR mice. Mice were given 250 p.p.m. OH-BBN in drinking water for 20 weeks and after a 1 week interval with tap water, water containing AX or CX at a concentration of 50 p.p.m. was administered during subsequent 20 weeks. Other groups of mice were treated with AX or CX alone or untreated. At the end of the study (week 41), the incidences of preneoplastic lesions and neoplasms in the bladder of mice treated with OH-BBN and AX or CX were smaller than those of mice given OH-BBN. In particular, AX administration after OH-BBN exposure significantly reduced the incidence of bladder cancer (transitional cell carcinoma) (P < 0.003). However, the inhibition of the frequencies of such lesions in mice treated with OH-BBN and CX was not significant. Treatment with AX or CX also decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), a new index of cell proliferation, in the transitional epithelium exposed to OH-BBN. Preneoplasms and neoplasms induced by OH-BBN, and the antiproliferative potential, was greater for AX than CX. These results indicate that AX is a possible chemopreventive agent for bladder carcinogenesis and such an effect of AX may be partly due to suppression of cell proliferation.
&#945;-Synuclein- and MPTP-Generated Rodent Models of Parkinsons Disease and the Study of Extracellular Striatal Dopamine Dynamics: A Microdialysis Approach (2010)

The classical animal models of Parkinson's disease (PD) rely on the use of neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine and, more recently, the agricultural chemicals paraquat and rotenone, to deplete dopamine (DA). These neurotoxins elicit motor deficits in different animal species although MPTP fails to induce a significant dopaminergic neurodegeneration in rats. In the attempt to better reproduce the key features of PD, in particular the progressive nature of neurodegeneration, alternative PD models have been developed, based on the genetic and neuropathological links between -synuclein ( -syn) and PD. In vivo microdialysis was used to investigate extracellular striatal DA dynamics in MPTP- and -syn-generated rodent models of PD. Acute and sub-acute MPTP intoxication of mice both induce prolonged release of striatal DA. Such DA release may be considered the first step in MPTP-induced striatal DA depletion and nigral neuron death, mainly through reactive oxygen species generation. Although MPTP induces DA reduction, neurochemical and motor recovery starts immediately after the end of treatment, suggesting that compensatory mechanisms are activated. Thus, the MPTP mouse model of PD may be unsuitable for closely reproducing the features of the human disease and predicting potential long-term therapeutic effects, in terms of both striatal extracellular DA and behavioral outcome. In contrast, the -syn-generated rat model of PD does not suffer from a massive release of striatal DA during induction of the nigral lesion, but rather is characterized by a prolonged reduction in baseline DA and nicotine-induced increases in dialysate DA levels. These results are suggestive of a stable nigrostriatal lesion with a lack of dopaminergic neurochemical recovery. The -syn rat model thus reproduces the initial stage and slow development of PD, with a time-dependent impairment in motor function. This article will describe the above experimental PD models and demonstrate the utility of microdialysis for their characterization.
CLINICAL MANIFESTATIONS OF GRAFT-VERSUS-HOST DISEASE IN HUMAN RECIPIENTS OF MARROW FROM HL-A-MATCHED SIBLING DONOR,S (1974)

Sixty-one evaluable patients, 19 with advanced aplastic anemia and 42 with end stage hematological malignancies, were conditioned for marrow grafting with total body irradiation or cyclophosphamide, or a combination of both. Marrow graft donors were siblings matched at the HL-A region and nonreactive in mixed leukocyte culture. All patients received methotrexate postgrafting to modify anticipated graft-versus-host disease (GVHD). Forty-three of the 61 patients developed clinically recognizable GVHD. In seven GVHD was limited to the skin. In the remaining patients, skin involvement was more severe and was followed by gastrointestinal involvement manifested by anorexia, nausea, diarrhea, abdominal pain, and malabsorption and/or liver involvement manifested by hepatomegaly, rises in serum glutamic oxaloacetic acid transaminase, and bilirubin. The severity of GVHD showed no correlation with the underlying disease, the conditioning regimen, or the day of onset after grafting. Fourteen of 25 patients without GVHD or with only skin involvement are alive. By contrast, only 5 of 36 with severe GVHD are alive. Twenty-six of the 36 patients with severe GVHD succumbed to infection, whereas only 4 of 25 without GVHD or with only skin involvement did so. The results show that despite histocompatibility matching and methotrexate therapy, GVHD remains a serious and often fatal complication of marrow transplantation.
Validation study toward measuring the mechanical properties of blood clots using resonant acoustic spectroscopy with optical vibrometry (2012)

Clot elastic modulus (CEM) has recently been shown to correlate with various hemostatic and thrombotic disorders and may be an important diagnostic parameter in cardiovascular diseases. Current methods of CEM measurement lack repeatability and require large sample volume. We present a novel method named resonant acoustic spectroscopy with optical vibrometry (RASOV) that has the potential to assess CEM with higher accuracy and speed, and lower sample volume. To validate RASOV, we measured the acoustic spectrum of agarose gel with varied concentrations in open-faced rectangular wells. Results showed a linear relationship between the natural resonant frequency and agarose content within a concentration range of 4 to 12 mg/mL. Furthermore, we observed that the resonant frequencies decrease with increasing transducer mass. As a highly accurate, resonance-based method, RASOV has great potential for biomechanical properties measurement, especially for human blood.
Nuclear Hormone Receptors and Gene Expression (2001)

The nuclear hormone receptor superfamily includes receptors for thyroid and steroid hormones, retinoids and vitamin D, as well as different "orphan" receptors of unknown ligand. Ligands for some of these receptors have been recently identified, showing that products of lipid metabolism such as fatty acids, prostaglandins, or cholesterol derivatives can regulate gene expression by binding to nuclear receptors. Nuclear receptors act as ligand-inducible transcription factors by directly interacting as monomers, homodimers, or heterodimers with the retinoid X receptor with DNA response elements of target genes, as well as by "cross-talking" to other signaling pathways. The effects of nuclear receptors on transcription are mediated through recruitment of coregulators. A subset of receptors binds corepressor factors and actively represses target gene expression in the absence of ligand. Corepressors are found within multicomponent complexes that contain histone deacetylase activity. Deacetylation leads to chromatin compactation and transcriptional repression. Upon ligand binding, the receptors undergo a conformational change that allows the recruitment of multiple coactivator complexes. Some of these proteins are chromatin remodeling factors or possess histone acetylase activity, whereas others may interact directly with the basic transcriptional machinery. Recruitment of coactivator complexes to the target promoter causes chromatin decompactation and transcriptional activation. The characterization of corepressor and coactivator complexes, in concert with the identification of the specific interaction motifs in the receptors, has demonstrated the existence of a general molecular mechanism by which different receptors elicit their transcriptional responses in target genes.