gebhart/patrepeval huggingface dataset:
The ThiL enzyme is a valid antibacterial target essential for both thiamine biosynthesis and salvage pathways in Pseudomonas aeruginosa (2020)

Thiamine pyrophosphate (TPP) is an essential cofactor for various pivotal cellular processes in all living organisms, including bacteria. Thiamine biosynthesis occurs in bacteria but not in humans; therefore, the enzymes in this pathway are attractive targets for antibiotic development. Among these enzymes, thiamine monophosphate kinase (ThiL) catalyzes the final step of this pathway, phosphorylating thiamine monophosphate to produce TPP. Here, we extensively investigated ThiL in <i>Pseudomonas aeruginosa</i>, a major pathogen responsible for hospital-acquired infections. We demonstrate that <i>thiL</i> deletion abolishes not only thiamine biosynthesis but also thiamine salvage capability and results in growth defects of the Δ<i>thiL</i> strain even in the presence of thiamine derivatives, except for TPP. Most importantly, the pathogenesis of the Δ<i>thiL</i> strain was markedly attenuated, compared with that of WT cells, with lower inflammatory cytokine induction and 10<sup>3</sup>-10<sup>4</sup>-fold decreased bacterial loads in an <i>in vivo</i> infection model in which the intracellular TPP level was in the submicromolar range. To validate <i>P. aeruginosa</i> ThiL (PaThiL) as a drug target, we further characterized its biochemical properties, determining a <i>V</i><sub>max</sub> of 4.0 ± 0.2 nmol·min<sup>-1</sup> and <i>K<sub>m</sub></i> values of 111 ± 8 and 8.0 ± 3.5 μm for ATP and thiamine monophosphate, respectively. An <i>in vitro</i> small-molecule screening assay identified PaThiL inhibitors including WAY213613, a noncompetitive inhibitor with a <i>K<sub>i</sub></i> value of 13.4 ± 2.3 μm and potential antibacterial activity against <i>P. aeruginosa</i> These comprehensive biological and biochemical results indicate that PaThiL represents a potential drug target for the development of an augmented repertoire of antibiotics against <i>P. aeruginosa</i>.
An Efficient Synthesis of 2-(Methylaminomethyl)-4,5-Dialkyl-1H-Imidazoles (1998)

A mild and convenient synthesis of 2-(methylaminomethyl)-4,5-dialkyl-1H-imidazoles is described. The procedure was used in the preparation of 2-(methylaminomethyl)-4,5,6,7-tetrahydro-1H-benzimidazole 1 and 2-(methylaminomethyl)-4,5-dimethyl-1H-imidazole 2.
CYP19A1 gene polymorphism and polycystic ovarian syndrome (2014)

Objective The CYP19 gene product enzyme aromatase mediates the conversion of the androgen testosterone to estradiol.The aim of this study is to investigate whether the CYP19A1 gene single nucleotide polymorphism( SNP) is associated with the susceptibility to polycystic ovary syndrome( PCOS) and serum hormone levels.Methods We conducted a case-controlled study,which included 373 PCOS patients and 313 healthy controls.We genotyped SNP rs2899470 in the subjects using the polymerase chain reactionrestriction fragment length polymorphism( PCR-RFLP) method and analyzed the frequencies of genotypes and alleles as well as the association of different genotypes with age,menarchal age,body mass index( BMI),and serum levels of hormones.Results The genotypic distributions of rs2899470 GG,TG,and TT in the PCOS women were 44.5%,49.6%,and 5.9%,respectively,significantly different from 39.3%,48.6%,and 12.1% in the healthy controls( P = 0.013).The frequency of the G allele was 69.3% in the former,remarkably higher than 63.6% in the latter( P = 0.025).The rs2899470 genotypic frequencies were associated with the serum E2 /T levels in the PCOS patients.Conclusion SNP rs2899470 in the CYP19A1 gene is associated with the susceptibility to PCOS,and so is the genotype of rs2899470 with serum E2 /T levels,which may be attributed mainly to the reduced activity of aromatase.
Cholesterol Alone is Sufficient to Specifically Trigger Perfringolysin O Oligomerization and Prepore Formation (2006)

Perfringolysin O (PFO) is a pore‐forming toxin secreted by Clostridium perfringens. Upon encountering a cholesterol‐containing membrane, the toxin oligomerizes and spontaneously inserts into the bilayer to form a large pore (diameter ~300 Å). The C‐terminus of PFO (domain 4) mediates its initial binding to the membrane, and this binding triggers the structural rearrangements required to initiate the oligomerization of PFO monomers. Although significant progress has been made in characterizing PFO structural changes during pore formation, the mechanism by which cholesterol effects PFO binding to the membrane and pore formation remains unknown. Using multiple independent fluorescence techniques, we have found that PFO binds to cholesterol dispersed in aqueous solution in the same manner as to cholesterol‐containing liposomal membranes. The topography of domain 4 when bound to cholesterol aggregates is indistinguishable to that observed with membrane bilayers. Moreover, the binding of domain 4 to cholesterol aggregates triggers the same conformational change in a distant domain that occurs when PFO interacts with liposomes. These results reveal that cholesterol alone is sufficient to trigger the conformational changes required for oligomerization and pore formation, thereby indicating that direct PFO‐cholesterol interactions are involved in and required for effecting each stage of the PFO cytolytic mechanism. Supported by NIH (USA) AI 37657 and by the R. A. Welch Foundation.
Study of optical pumping of alkali atomic beam in strong magnetic fields (1992)

Using rate equation formalism, we got an analytic expression describing the optical pumping of an alkali atomic beam in strong magnetic fields. By comparing with the traditional description in single velocity approximation, the influence of velocity distribution in a practical alkali atomic beam on the pumping effect was quantitatively discussed. It turned out that the rate equation treatment in single velocity approximation might result in an error within twenty percent. Laser optical pumping of 7Li atomic beam in a strong magnetic field (0.15 T) was experimentally studied, and the results are in agreement with the theory in which the velocity distribution is taken into account.
Three-dimensional imaging of porcine joints down to the subcellular level (2022)

Joint tissues consist of trabecular and cortical bone as well as calcified and hyaline cartilage, which presents a challenge for hard X-ray-based visualization on the sub-cellular level due to the wide range of local X-ray absorption values. The density of the calcified tissues requires rather high photon energy, which often leads to insufficient contrast within the cartilage and impedes the visualization of individual biological cells. Decalcification of the tissues reduces the total and local X-ray absorption values and allows for selecting a lower photon energy. Further contrast enhancement can be achieved by ethanol fixation and paraffin tissue embedding. In this study, we (i) searched for an appropriate visualization method to investigate lesions generated by a laser osteotome and (ii) visualized a decalcified porcine joint after ethanol fixation and subsequent paraffin embedding using laboratory- and synchrotron radiation-based microtomography. The experiments at the ANATOMIX beamline of Synchrotron SOLEIL were performed in off-axis scan mode with a pixel size of 1.3 µm. Individual cells in all layers of the joint could be made visible and the effect of ethanol fixation and paraffin embedding demonstrated.
Intermolecular Cross-Coupling of Simple Arenes via C−H Activation by Tuning Concentrations of Arenes and TFA (2006)

Formation of unsymmetrical biaryls from simple arenes has been achieved successfully in a catalytic system of Pd(OAc)2/CF3CO2H(TFA)/K2S2O8 just by tuning the concentrations of arenes and TFA under mild conditions. A proposed mechanism containing two-step aromatic C−H activation on this novel intermolecular cross-coupling of arenes is also suggested and partly supported by experiments.
An Adaptive De-blocking Method based on Measuring Flatness of Macroblock (2006)

Block artifact is a serious problem which generally emerges in video or image compression system based on block. In H.264, strength, a value which indicates the degree of block artifact, is obtained by the prediction mode, reference frames and motion vectors. However, in some cases, the de-blocking method in H.264 is not so satisfactory because of the ignorance of image behavior. According to the research of HVS (human visual system), the blockiness in flat region is much more easily observed than that in complicated region. Thus, it is needed to evaluate the flatness of a particular region so as to measure the strength of blockiness. In this paper, a de-blocking method which is based on the flatness of two adjacent blocks is proposed. In the experiment, it is proved that this flatness-based de-blocking method has more superior performance than the traditional one in H.264
The efficacy of a topically applied combination of cyphenothrin and pyriproxyfen against the southern African yellow dog tick, Haemaphysalis elliptica, and the cat flea, Ctenocephalides felis, on dogs (2010)

The objective of this study was to determine the therapeutic and residual efficacy of a topically applied combination of cyphenothrin (40%) and pyriproxyfen (2%) against the tick Haemaphysalis elliptica and the flea Ctenocephalides felis on dogs. Twelve dogs were infested with 50 ticks 2 days before they were treated and with approximately 100 fleas 6 days before treatment and again 2 days before treatment and with 50 ticks and approximately 100 fleas at weekly intervals thereafter. They were ranked according to their flea counts and sex 5 days before treatment and randomly allocated to an untreated control group of 6 dogs and a treated group of 6 dogs. Ticks and fleas were collected from the dogs 48 h after treatment and 48 h after each infestation and live and dead ticks and live fleas were counted. The counts of ticks and fleas were transformed to geometric means, and efficacy was calculated by comparing these means. The product had a therapeutic efficacy of 83.1% against H. elliptica and 97.5% against C. felis 2 days after treatment. The residual period of protection during which efficacy was > or = 90% was 5 weeks for both H. elliptica and C. felis.
Deficiency in mitochondrial anionic phospholipid synthesis impairs cell wall biogenesis (2005)

Cardiolipin (CL) is the signature lipid of the mitochondrial membrane and plays a key role in mitochondrial physiology and cell viability. The importance of CL is underscored by the finding that the severe genetic disorder Barth syndrome results from defective CL composition and acylation. Disruption of PGS1, which encodes the enzyme that catalyses the committed step of CL synthesis, results in loss of the mitochondrial anionic phospholipids phosphatidylglycerol and CL. The pgs1Delta mutant exhibits severe growth defects at 37 degrees C. To understand the essential functions of mitochondrial anionic lipids at elevated temperatures, we isolated suppressors of pgs1Delta that grew at 37 degrees C. The present review summarizes our analysis of suppression of pgs1Delta growth defects by a mutant that has a loss-of-function mutation in KRE5, a gene involved in cell wall biogenesis.
Synthesis of Poly (alkylene oxide) Adducts of Carbazole and Their Physical Properties (1986)

A synthesis and properties of the polyalkylene oxide adducts of carbazole as nonionic surfactants have been studied.The adducts have the following properties;1) Extremely low foaming, 2) Excellent electro-conductivity, 3) High resistant toward thermal decompostion.The oxide adducts should find application not only as water-soluble surfactants but also as oil-soluble and useful additives for the modification of resin properties.
Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5) (2016)

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
Knee Injury Patterns Among Men and Women in Collegiate Basketball and Soccer (1995)

Women's participation in intercollegiate athletics has increased dramatically in recent years. Greater participation has increased awareness of health and medical issues specific to the female athlete. Some reports have noted a higher susceptibility to knee injury, specifically injuries to the anterior cruciate ligament, in female athletes as compared with their male counterparts. We performed a 5-year evaluation of anterior cruciate ligament injuries in collegiate men's and women's soccer and basketball programs using the National College Athletic Association Injury Surveillance System. Results showed significantly higher anterior cruciate ligament injury rates in both female sports compared with the male sports. Noncontact mechanisms were the primary cause of anterior cruciate ligament injury in both female sports. Possible causative factors for this increase in anterior cruciate ligament injuries among women may be extrinsic (body movement, muscular strength, shoe-surface interface, and skill level) or intrinsic (joint laxity, limb alignment, notch dimensions, and ligament size).
Current and emerging treatment options in the management of Friedreich ataxia (2010)

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia. Oxidative damage within the mitochondria seems to have a key role in the disease phenotype. Therefore, FRDA treatment options have been mostly directed at antioxidant protection against mitochondrial damage. Available evidence seems to suggest that patients with FRDA should be treated with idebenone, because it is well tolerated and may reduce cardiac hypertrophy and, at higher doses, also improve neurological function, but large controlled clinical trials are still needed. Alternatively, gene-based strategies for the treatment of FRDA may involve the development of small-molecules increasing frataxin gene transcription. Animal and human studies are strongly needed to assess whether any of the potential new treatment strategies, such as iron-chelating therapies or treatment with erythropoietin or histone deacetylase inhibitors and other gene-based strategies, may translate into an effective therapy for this devastating disorder. In this review, we try to provide an answer to some questions related to current and emerging treatment options in the management of FRDA.
The Economics of Recommender Systems: Evidence from a Field Experiment on MovieLens (2023)

We conduct a 6 month field experiment on a movie-recommendation platform to identify if and how recommendation systems affect consumption. We use within-consumer randomization at the good level and elicit beliefs about unconsumed goods to disentangle exposure from informational effects. We have three experimental groups: (a) control, (b) exposed, and (c) recommended + exposed goods where only goods in (c) are recommended and we elicit beliefs about goods in (b) and (c). Comparing across these treatment arms we find recommendations increase consumption beyond its role in exposing goods to consumers. We provide support for an informational mechanism: recommendations affect consumers' beliefs, which in turn explain consumption. Recommendations reduce uncertainty about goods consumers are most uncertain about and induce information acquisition. Finally, we find evidence for spatial correlation in beliefs.
EFFICACY OF COMBINATION SALVAGE CHEMOTHERAPY WITH METHOTREXATE, ACTINOMYCIN D AND ETOPOSIDE FOR ADVACED GERM CELL TUMOR PATIENTS WITH CHORIOCARCINOMA COMPONENT (2009)

You have accessJournal of Urology1 Apr 2009EFFICACY OF COMBINATION SALVAGE CHEMOTHERAPY WITH METHOTREXATE, ACTINOMYCIN D AND ETOPOSIDE FOR ADVACED GERM CELL TUMOR PATIENTS WITH CHORIOCARCINOMA COMPONENT Tomoaki Terakawa, Hideaki Miyake, Atsushi Takenaka, and Masato Fujisawa Tomoaki TerakawaTomoaki Terakawa More articles by this author , Hideaki MiyakeHideaki Miyake More articles by this author , Atsushi TakenakaAtsushi Takenaka More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(09)60570-XAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "EFFICACY OF COMBINATION SALVAGE CHEMOTHERAPY WITH METHOTREXATE, ACTINOMYCIN D AND ETOPOSIDE FOR ADVACED GERM CELL TUMOR PATIENTS WITH CHORIOCARCINOMA COMPONENT." The Journal of Urology, 181(4S), pp. 198–199 © 2009 by American Urological AssociationFiguresReferencesRelatedDetails Volume 181Issue 4SApril 2009Page: 198-199 Advertisement Copyright & Permissions© 2009 by American Urological AssociationMetricsAuthor Information Tomoaki Terakawa More articles by this author Hideaki Miyake More articles by this author Atsushi Takenaka More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement PDF downloadLoading ...
Movement of cholesterol between vesicles prepared with different phospholipids or sizes. (1985)

The rates of exchange of [4-14C]cholesterol between lipid vesicles prepared with different phospholipids and with different sizes have been measured. The first-order rate constants were higher using vesicles prepared from phosphatidylcholines with highly branched or polyunsaturated fatty acyl chains than with saturated diacyl or di-O-alkyl chains. The rate measurements indicate that the affinity of cholesterol for phospholipid does not vary significantly on change of the type of linkage (ether or ester) in phosphatidylcholine (PC) or of the positions of the fatty acyl chains in 1,2-diacyl-PC bearing one saturated and one unsaturated chain; furthermore, egg phosphatidylglycerol and egg phosphatidylethanolamine appear to have comparable affinities for cholesterol. However, the molecular packing in the bilayer and nearest-neighbor interactions involving cholesterol appear tightened more by N-palmitoylsphingomyelin than by dipalmitoyl-PC; on incorporation of 44 mol % of these phospholipids (which have the same fatty acyl chain composition) into either small or large unilamellar vesicles prepared with egg phosphatidylglycerol, the exchange rates were strikingly slower when the donor species contained sphingomyelin compared with PC. The rate of cholesterol exchange was 100% faster with small unilamellar vesicles than with large unilamellar vesicles as donors, suggesting that the looser packing in the highly curved small vesicles facilitates cholesterol desorption. The cholesterol exchange rate did not vary with the size of the acceptor vesicles, which indicates that desorption is the rate-limiting step in the exchange process in the presence of excess acceptors.
Multiple Conformers in Active Site of Human Dihydrofolate Reductase F31R/Q35E Double Mutant Suggest Structural Basis for Methotrexate Resistance (2009)

Methotrexate is a slow, tight-binding, competitive inhibitor of human dihydrofolate reductase (hDHFR), an enzyme that provides key metabolites for nucleotide biosynthesis. In an effort to better characterize ligand binding in drug resistance, we have previously engineered hDHFR variant F31R/Q35E. This variant displays a >650-fold decrease in methotrexate affinity, while maintaining catalytic activity comparable to the native enzyme. To elucidate the molecular basis of decreased methotrexate affinity in the doubly substituted variant, we determined kinetic and inhibitory parameters for the simple variants F31R and Q35E. This demonstrated that the important decrease of methotrexate affinity in variant F31R/Q35E is a result of synergistic effects of the combined substitutions. To better understand the structural cause of this synergy, we obtained the crystal structure of hDHFR variant F31R/Q35E complexed with methotrexate at 1.7-A resolution. The mutated residue Arg-31 was observed in multiple conformers. In addition, seven native active-site residues were observed in more than one conformation, which is not characteristic of the wild-type enzyme. This suggests that increased residue disorder underlies the observed methotrexate resistance. We observe a considerable loss of van der Waals and polar contacts with the p-aminobenzoic acid and glutamate moieties. The multiple conformers of Arg-31 further suggest that the amino acid substitutions may decrease the isomerization step required for tight binding of methotrexate. Molecular docking with folate corroborates this hypothesis.
Can we measure terrestrial photosynthesis from space directly, using spectral reflectance and fluorescence? (2007)

Abstract Attempts to estimate photosynthetic rate or gross primary productivity from remotely sensed absorbed solar radiation depend on knowledge of the light use efficiency (LUE). Early models assumed LUE to be constant, but now most researchers try to adjust it for variations in temperature and moisture stress. However, more exact methods are now required. Hyperspectral remote sensing offers the possibility of sensing the changes in the xanthophyll cycle, which is closely coupled to photosynthesis. Several studies have shown that an index (the photochemical reflectance index) based on the reflectance at 531 nm is strongly correlated with the LUE over hours, days and months. A second hyperspectral approach relies on the remote detection of fluorescence, which is a directly related to the efficiency of photosynthesis. We discuss the state of the art of the two approaches. Both have been demonstrated to be effective, but we specify seven conditions required before the methods can become operational.
Contrast‐enhanced MR angiography of the run‐off vasculature: Intraindividual comparison of gadobenate dimeglumine with gadopentetate dimeglumine (2003)

Greater vascular enhancement of the run-off vasculature is obtained after Gd-BOPTA, particularly in the smaller more distal vessels. Enhancement differences are not merely dose dependent, but may be due to different vascular enhancement characteristics of the agents.
Identification of 1-Arylmethyl-3- (2-aminoethyl)-5-aryluracil as Novel Gonadotropin-Releasing Hormone Receptor Antagonists (2003)

Based on SAR from bicyclic GnRH antagonists such as 6-aminomethyl-7-arylpyrrolo[1,2-a]pyrimid-4-ones (1) and 2-aryl-3-aminomethylimidazolo[1,2-a]pyrimid-5-ones (2a,b), a series of novel uracil compounds (4) were derived as the GnRH antagonists. Their syntheses and initial SAR are discussed herein. This is the first time that monocycle-based GnRH receptor antagonists are reported.