Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycine Antagonists Structurally Related to 4,5,6,7‐Tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol Inhibit Binding of [3H]Strychnine to Rat Brain Membranes

Abstract: [3H]Strychnine binding to rat pons + medulla membranes was used as a measure of glycine receptors or glycine receptor‐coupled chloride channels in vitro. A series of compounds structurally related to 4,5,6,7–tetrahydroisoxazolo[5,4–c]pyridin‐3–ol (THIP), which previously were shown to antagonize glycine responses in cat spinal cord, inhibited [3H]strychnine binding in micromolar concentrations. The most potent of these glycine antagonists, 5,6,7,8–tetrahydro‐4H‐isoxazolo[3,4–d]azepin‐3–ol (iso‐THAZ), was also the most potent inhibitor of [3H]strychnine binding, with a Ki of 1,400 nM. The Ki value for strychnine was 7.0 nM, whereas the Ki value for the mixed γ‐aminobutyric acid (GABA)/glycine antagonist 3α‐hydroxy‐16–imino‐5β‐17–aza‐androstan‐11–one (RU 5,135) was only 4.6 nM. Sodium chloride (1,000 mM) enhanced the affinity of strychnine, brucine, isostrychnine, and the nonselective GABA antagonist pitrazepin for [3H]strychnine binding sites, whereas the affinities of glycine, β‐alanine, and taurine were reduced. These sodium chloride shifts, however, were not predictive of antagonist or agonist properties, since the sodium chloride shift for the glycine antagonist iso‐THAZ and of the other THIP‐related antagonists were similar to those of the glycine‐like agonists. The various sodium chloride shifts show that different groups of ligands bind to glycine receptor sites in different ways.
Neurologic Adverse Effects during Concomitant Treatment with Ciprofloxacin, Nsaids, and Chloroquine: Possible Drug Interaction

OBJECTIVE: To report a case of neurologic adverse effects that developed during concomitant treatment with ciprofloxacin, nonsteroidal antiinflammatory drugs (NSAIDs), and chloroquine. Possible mechanisms for a drug interaction are discussed. CASE SUMMARY: A 68-year-old woman who was receiving chronic treatment with NSAIDs and chloroquine developed dizziness, anxiety, and tremors when ciprofloxacin 500 mg twice daily was begun for Salmonella osteitis. When she discontinued the antirheumatic treatment, there was a prompt relief of symptoms. After indomethacin was reintroduced, the patient developed signs and symptoms of peripheral neuropathy, which partially subsided when ciprofloxacin was discontinued. DISCUSSION: Enhanced neurologic adverse effects of ciprofloxacin when taken together with NSAIDs or chloroquine may result from reduced effects of gamma-aminobutyric acid. An alternative explanation could be that NSAIDs and chloroquine impair the elimination of ciprofloxacin, thereby contributing to toxic concentrations of the antibiotic. CONCLUSIONS: The possibility of interactions between ciprofloxacin and antirheumatic drugs should be considered.
Alcohol Consumption and Risk of Ischemic Heart Disease in Women

BACKGROUND Most studies suggest that alcohol use decreases the risk of coronary heart disease in men, however, this association has not been well established in women. METHOD This study investigates the relationship between alcohol use and ischemic heart disease (IHD) incidence among women aged 45 to 74 years in the Epidemiologic Follow-up Study of the First National Health and Nutrition Examination Survey. The cohort was free of heart disease at baseline. During the follow-up period (mean, 13 years), 884 IHD cases were identified through hospital records, reported hospital stays, or death certificates. RESULTS Women reporting any amount of alcohol use had about a 20% decrease in risk of IHD incidence compared with abstainers. Using a Cox regression model to adjust for known cardiovascular risk factors, this relative risk of IHD remained essentially unchanged. The greatest reduction in the risk of IHD (36% to 39%) was among women who consumed about half to two drinks per day compared with abstainers. CONCLUSIONS This study of a nationally representative sample with a mean follow-up of 13 years and a substantial number of IHD cases suggests that moderate alcohol use decreases the risk of IHD. However, the risk and benefits of moderate alcohol consumption need to be viewed within a broader perspective especially since the potentially harmful effects of alcohol have been well documented.
Detection and characterization of a phospholactoyl-enzyme adduct in the reaction catalyzed by UDP-N-acetylglucosamine enolpyruvoyl transferase, MurZ.

The MurZ enzyme catalyzes enolpyruvoyl transfer from phosphoenolpyruvate to the 3-OH of UDP-N-acetylglucosamine (UDP-GlcNAc) in Escherichia coli peptidoglycan biosynthesis. The kinetic mechanism of MurZ has been shown to involve the generation of a non-covalently bound tetrahedral phospholactoyl-UDP-GlcNAc intermediate [Marquardt, J.L. , et al. (1993) J. Am. Chem. Soc. 115, 10398-10399]. In the work described here, MurZ overproduced in E. coli copurified with 1 equiv of bound PEP. Enzyme free of bound PEP was prepared by incubation of purified MurZ with UDP-GlcNAc followed by removal of small molecules. Addition of either [14C]PEP or [32P]PEP to PEP-free enzyme led to stoichiometric labeling. The MurZ-PEP complex was stable to 6.7 M urea, and digestion of the [32P]PEP-labeled protein followed by SDS-PAGE generated a labeled peptide of molecular weight 5000. Solution NMR of MurZ incubated with [2-13C]PEP suggested a tetrahedral phospholactoyl enzyme adduct attached via C-2 to an enzyme nucleophile. The kon for generation of the phospholactoyl enzyme in the absence of UDP-GlcNAc was 0.24 microM-1 s-1, too slow to represent the binding order of the kinetically preferred pathway since the lower limit of the second-order binding constant for PEP (kcat/Km) is 15 microM-1 s-1. Rapid chemical quench analysis under single-turnover conditions using [32P]PEP in the presence of UDP-GlcNAc demonstrated that the covalent enzyme-phospholactoyl adduct appeared and decayed on a time scale consistent with catalysis. (ABSTRACT TRUNCATED AT 250 WORDS)
Hip pads reduce the overall risk of injuries in recreational snowboarders

Objective The purpose is to determine common injuries in recreational snowboarding as targets of preventive strategy and protective gear that reduces the overall risk of these injuries. Methods The subjects comprised 5561 injured recreational snowboarders. On the basis of patients’ self-reporting form, ‘the common snowboarding injuries’ (cut-off point >2.0% in prevalence) were decided, and all injured snowboarders were categorised into two groups: common injuries and the other injuries (control). Several factors such as age, gender, self-reported skill level, experienced seasons, experienced days, previous snowboarding school attendance and the use of protective gears (helmet, elbow pads, wrist guards, backbone guard, hip pads and knee pads) were recorded. Multiple logistic regression analysis was conducted to investigate which type of protective gear reduced the overall risk of the common injuries. Results The common snowboarding injuries consisted of eight types, in which distal radial fracture was the most common (17.7%), followed by head injury (9.4%) and clavicle fracture (6.5%). In univariate regression analysis, skill level, experienced seasons, experienced days and the use of hip pads and knee pads were manifested potential risk factors on the common injuries. In subsequent multivariate regression analysis, the use of hip pads was related with a lower overall risk of these common injuries (OR, 0.84; 95% CI, 0.75 to 0.95), specifically that of distal radial fracture and glenohumeral dislocation. Conclusions The use of hip pads is recommended for snowboarders as it reduces the overall risk of common snowboarding injuries.
Review of phase II trials of Taxol (paclitaxel) in patients with advanced ovarian cancer.

The efficacy and safety of paclitaxel in the treatment of advanced ovarian cancer has been assessed in several phase II trials. McGuire and associates at the Johns Hopkins Oncology Cancer reported results from a phase II trial in which paclitaxel-administered as a 24-hour intravenous (i.v.) infusion with premedication to avoid acute hypersensitivity reactions-yielded one complete response (CR) and 11 partial responses (PRs) (overall response rate, 30%) among 40 previously treated patients with ovarian cancer evaluable for response; 25 of the patients had been refractory to cisplatin therapy. Among 30 evaluable patients who took part in a study at the Albert Einstein Cancer Center, paclitaxel (180 to 250 mg/m2 as a 24-hour i.v. infusion every 21-28 days) produced an overall response rate of 20% (1 CR, 5 PRs). Four responding patients were resistant to previous cisplatin therapy. Median survival for responders was 27 months, and 6 months for nonresponders (P = 0.0001). The Gynecologic Oncology Group confirmed the activity of paclitaxel (175 mg/m2 as a continuous 24-hour i.v. infusion) in 41 evaluable cisplatin-resistant patients, among whom 15 (37%) responded (5 CR, 10 PR). A total of 8 of 27 (29%) patients with cisplatin-refractory disease responded (2/27 CR, 6/27 PR). Among 14 patients whose disease progressed more than 6 months following cisplatin therapy, 3 had CRs and 4 had PRs. Finally, the National Cancer Institute Treatment Referral Center protocol enrolled more than 2,000 patients; preliminary analysis of 1,000 patients included 663 evaluable for response with measurable disease. There are 27 CRs and 119 PRs; median time to progression for responding patients is 7 months. (ABSTRACT TRUNCATED AT 250 WORDS)
Increasing the reliability of structured P2P networks

Third generation P2P networks try to reduce the high signaling overhead observed in unstructured P2P networks by means of proactive routing. Therefore, a deterministically structured overlay network is established between the participating peers by making use of distributed hash tables (DHT). To ensure the correct execution of lookups it is crucial to keep up the network structure. The Chord protocol already proposes an efficient stabilize algorithm that works well in networks with low churn rates. However, as nodes join and leave the network more frequently, inconsistencies within the network structure appear, because the network is not capable of reacting fast enough to all changes in the topology. In this paper the authors proposed a modified stabilize algorithm that is based on available token techniques from ring networks. While decreasing the overhead in the network, a more stable overlay structure is established.
Systematic black-box analysis of collaborative web applications

Web applications, such as collaborative editors that allow multiple clients to concurrently interact on a shared resource, are difficult to implement correctly. Existing techniques for analyzing concurrent software do not scale to such complex systems or do not consider multiple interacting clients. This paper presents Simian, the first fully automated technique for systematically analyzing multi-client web applications. Naively exploring all possible interactions between a set of clients of such applications is practically infeasible. Simian obtains scalability for real-world applications by using a two-phase black-box approach. The application code remains unknown to the analysis and is first explored systematically using a single client to infer potential conflicts between client events triggered in a specific context. The second phase synthesizes multi-client interactions targeted at triggering misbehavior that may result from the potential conflicts, and reports an inconsistency if the clients do not converge to a consistent state. We evaluate the analysis on three widely used systems, Google Docs, Firepad, and ownCloud Documents, where it reports a variety of inconsistencies, such as incorrect formatting and misplaced text fragments. Moreover, we find that the two-phase approach runs 10x faster compared to exhaustive exploration, making systematic analysis practically applicable.
Feeding ecology of the black howler monkey (Alouatta pigra) in Northern Belize

We studied the feeding ecology of the black howler monkey (Alouatta pigra) from March 1994 to April 1995 in the Community Baboon Sanctuary in northern Belize, Central America. Activity and diet composition were recorded using continuous focal animal sampling. Diet composition was compared with the relative abundance of plant parts eaten by the howlers within the study site. The study animals spent an average of 24.4% of their time feeding, 61.9% resting, and approximately 9.8% traveling. In contrast to previously published reports on A. pigra, we found the diet composition to be similar to that of other Alouatta species (conforming to the folivore/frugivore profile), with 41% of feeding time spent eating fruit, 45% foliage, and 11% flowers. This contrast may indicate a wide degree of dietary flexibility that allows A. pigra to inhabit a variety of habitat types. We suggest that a high level of resource abundance throughout the year makes the Community Baboon Sanctuary excellent habitat for Alouatta pigra. Am. J. Primatol. 45:263–279, 1998. © 1998 Wiley‐Liss, Inc.
Application of design of experiments for formulation development and mechanistic evaluation of iontophoretic tacrine hydrochloride delivery

Abstract Objective: The objective of this investigation is to develop mathematical equation to understand the impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride. In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of the participating ions for the application of iontophoretic delivery was explored. Methods: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro-migration of tacrine ions with application of Kohlrausch’s law. Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer’s disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility. Conclusions: This investigation utilizes the design of experiment approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
Effects of Retrieval Practice on Consumer Memory for Brand Attributes

The effect of retrieval practice on memory for brand attributes was examined. Participants were presented with advertisements for fictional products so each contained a number of brand attributes relating to the nature of the product and its qualities. Following this, participants practiced recalling a subset of those attributes either 3 or 6 times. The act of retrieving some brand information inhibited the recall of other brand information that was not practiced, but only when repeated retrieval practice took place 6 times. This is the first demonstration of inhibitory effects in consumers' memory using the retrieval practice paradigm.
Nitrogen and water interactions in subsurface drip-irrigated cauliflower: I. Plant response.

Production of cauliflower (Brassica olearacea L. var. botrytis L.) in the southwestern U.S. is highly dependent on inputs of water and N fertilizer to achieve optimum yields and quality. Subsurface drip irrigation offers what is likely the ultimate in control of the plant root zone for crop production. However, the water and N-response characteristics of subsurface drip-irrigated cauliflower have not previously been reported. Three field experiments were conducted in southern Arizona in 1993-1996. The objectives were to determine: (i) an optimum range of soil water tension for subsurface drip-irrigated cauliflower, (ii) the effects and interactions of water and N fertilizer on crop yield and quality, and (iii) seasonal and daily N uptake for high-yielding cauliflower. The experiments were randomized complete block factorial with three irrigation regimes (low, medium, high), four N rates (60-600 kg N ha -1 ), and four replications. Irrigation was applied dally to maintain target soil water tensions and all N was applied by fertigation. With respect to marketable yield, curd weight, and curd diameter, the optimum soil water tension was approximately 10 to 12 kPa in this sandy loam soil during the 3 years. Marketable yields across all treatments ranged from 30 Mg ha -1 . Yields and quality were generally more responsive to N rate than to irrigation and showed significant irrigation by N rate interactions during 2 of the 3 years. At equivalent N rates, excessive irrigation generally resulted in lower yields and quality. Cauliflower accumulated up to 250 kg N ha -1 in the aboveground biomass and N-uptake fluxes were as high as 5 kg N ha -1 d -1 at the 12-leaf to folding growth stage.
Can "Collegiality" Be Measured?: Further Validation of a Faculty Assessment Model of Discretionary Behaviors.

The professoriate has been debating the value of adding collegiality as a fourth criterion in faculty evaluations. Collegiality is considered to be any extra-role behavior that represents individuals’ behavior that is discretionary, not recognized by the formal reward system and that, in the aggregate, promotes the effective functioning of the educational organization. The AAUP recommended against including collegial behaviors in faculty evaluations stating that the inclusion could hinder academic freedom by not allowing for dissent and that the construct of collegiality is amorphous which prevents the creation of an effective tool available to evaluate collegial behavior. Despite this opinion, faculty members continue to be denied tenure because they were cited as lacking civility. Efforts by researchers have been made to address the concern expressed by the AAUP about the amorphous nature of the construct by delineating the indicators associated with collegial behaviors. Initial efforts led to the creation of a list of collegial indicators validated by Research I and Research II professors who provided the basis for a subsequent assessment constructed based on the validated indicators. The current study has extended the validation of the indicators to a sample of Master’s university professors. Results suggested that there was agreement in representativeness of collegiality between university types. These results have further reduced the amorphous nature of the construct and allows for an expanded use of the assessment in faculty evaluations.
Highly Efficient and Specific Genome Editing in Silkworm Using Custom TALENs

Establishment of efficient genome editing tools is essential for fundamental research, genetic engineering, and gene therapy. Successful construction and application of transcription activator-like effector nucleases (TALENs) in several organisms herald an exciting new era for genome editing. We describe the production of two active TALENs and their successful application in the targeted mutagenesis of silkworm, Bombyx mori, whose genetic manipulation methods are parallel to those of Drosophila and other insects. We will also show that the simultaneous expression of two pairs of TALENs generates heritable large chromosomal deletion. Our results demonstrate that (i) TALENs can be used in silkworm and (ii) heritable large chromosomal deletions can be induced by two pairs of TALENs in whole organisms. The generation and the high frequency of TALENs-induced targeted mutagenesis in silkworm will promote the genetic modification of silkworm and other insect species.
Intertemporal Forecasts of Defaulted Bond Recoveries and Portfolio Losses

Variation in the composition of the defaulted debt pool and credit conditions at the time of default generate time variation in the distribution of recoveries on defaulted debt, and the related distribution of losses on portfolios of credit sensitive debt. We quantify the importance of accounting for such time variation in out-of-sample comparisons of alternative approaches to forecasting recoveries or losses given default (LGD) on defaulted bonds. Using simulations of losses on defaultable bond portfolios, we show that conditional mixture models improve forecasts of expected credit losses through capturing time variation in the recovery/LGD distribution. However, the best forecasts of instrument or firm-level recovery/LGD do not necessarily provide the best forecasts of portfolio-level losses, as the latter depend on the association between errors in the default and recovery/LGD forecasts. Our systematic comparisons of cross-sectional and intertemporal forecasting performance are enabled by a fast maximum-likelihood approach to estimating conditional mixtures of distributions.
The adhesion between fibre posts and composite resin cores: the evaluation of microtensile bond strength following various surface chemical treatments to posts.

AIM To evaluate the influence of various surface treatments to fibre posts on the microtensile bond strength with different composite resins. METHODOLOGY A total of 110 fibre posts were randomly divided into five groups, according to the surface pre-treatment performed. Group 1: immersion in 24% H(2)O(2) for 10 min and silanization for 60 s; group 2: immersion in 10% H(2)O(2) for 20 min and silanization for 60 s; group 3: immersion in 4% hydrofluoric acid gel for 60 s and silanization for 60 s; group 4: silanization of the post surface for 60 s and application of the bonding agent G-Bond; group 5: silanization of the post surface for 60 s (control group). After treatment, two posts were randomly selected from each group to evaluate the morphological aspect of the post surface with scanning electron microscopy. The remaining posts in each group were divided into five subgroups of five posts each, which differed in the type of composite resin used for the core build-up. Post-core strength were calculated and the differences among experimental groups were analysed with two-way anova and the Tukey test (alpha = 0.05). RESULTS The post-core strengths achieved in groups 1 and 2 were significantly higher (P < 0.05), than those of groups 3, 4 and 5. The post-core strength in the control group was significantly lower (P < 0.05) than all other groups. CONCLUSIONS Hydrogen peroxide and hydrofluoric acid both modified the surface morphology of fibre posts and with silane, significantly enhanced the interfacial strength between them and core materials.
An autonomous N‐terminal transactivation domain in Fos protein plays a crucial role in transformation.

To date, three functional domains have been defined in c‐Fos and v‐Fos proteins and have been shown to play a role in transactivation: the leucine zipper mediating hetero‐dimerization, the basic DNA contact site, and a C‐terminally located transactivation domain (C‐TA) harbouring the HOB1 and HOB2 motifs. While the bZip region, consisting of the leucine zipper and the DNA contact site, is indispensable for transformation, the C‐TA domain is not required and is actually altered by internal deletions in the FBR‐MuSV. We now show that the N‐terminal regions of c‐Fos and v‐Fos contain a second transactivation domain (N‐TA). A functionally crucial motif within the N‐TA domain, termed NTM, was pinpointed to a approximately 25 amino acid stretch around positions 60‐84 which is highly conserved in FosB. Analysis of LexA fusion proteins showed that the N‐TA domains of both c‐Fos and FosB function in an autonomous fashion in both fibroblasts and yeast. Most importantly, deletion of the NTM motif impairs the transforming properties of v‐Fos. Apart from the bZip region, the N‐TA domain is the only functional domain required for transformation by v‐Fos, at least when its expression is driven by the strong FBR‐MuSV‐LTR promoter.