Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug Interaction Potential of Soy Extract and Panax Ginseng

To determine if soy extract or Panax ginseng increases the urinary excretion of the 6‐β‐hydroxycortisol/cortisol ratio as a marker of cytochrome P450 (CYP) 3A enzyme induction, subjects received a soy extract containing 50 mg isoflavones twice daily (n = 20) or Panax ginseng 100 mg standardized to 4% ginsenosides twice daily (n = 20) for 14 days. Neither Panax ginseng nor soy extract significantly altered the urinary 6‐β‐OH‐cortisol/cortisol ratio, suggesting that unlike St. John's wort, they are not CYP3A inducers. Studies in vitro using human liver microsomes were performed to determine the effect of soy extract on probe substrates of CYP and UDP glucuronosyltransferase (UGT). Unhydrolyzed soy extract produced very little inhibition of CYP1A2, CYP2A6, and CYP2D6 and a trend of activation of CYP3A4. Hydrolyzed soy extract showed inhibition of all of the CYPs tested, particularly CYP2C9 and CYP3A4. UGT2B15 was the only UGT significantly inhibited. Even though both soy extract and ginseng have been shown to activate CYP3A4 in vitro, there is a lack of an in vitro correlation with the in vivo effects.
Transformation analysis of three linkage groups in Staphylococcus aureus

While studying a set of multiply marked mutants of Staphylococcus aureus strain 8325 by transformation, several instances of apparent genetic linkage were encountered. After showing that these linked transformations were readily inactivated by shearing of the deoxyribonucleic acid (DNA) but were resistant to dilution of the DNA, and showing that mixtures of DNA failed to form double transformants, it was concluded that the linkages were legitimate rather than the result of congression. Three linkage groups were defined: thy-101-lys-115-trp-103-thr-106, pyr-141-hisGb15-nov-pur-102, and pur-110-ilv-129. The positions of the previously studied trp and his operons corresponded to the trp-103 and hisGb15 loci. The ilv-129 position adjacent to pur-110 probably corresponds to the ilv-leu gene cluster. The distance over which linkage was detected was greater by transformation than by generalized transduction.
CO Metabolism in the Acetogen Acetobacterium woodii

ABSTRACT The Wood-Ljungdahl pathway allows acetogenic bacteria to grow on a number of one-carbon substrates, such as carbon dioxide, formate, methyl groups, or even carbon monoxide. Since carbon monoxide alone or in combination with hydrogen and carbon dioxide (synthesis gas) is an increasingly important feedstock for third-generation biotechnology, we studied CO metabolism in the model acetogen Acetobacterium woodii. When cells grew on H2-CO2, addition of 5 to 15% CO led to higher final optical densities, indicating the utilization of CO as a cosubstrate. However, the growth rate was decreased by the presence of small amounts of CO, which correlated with an inhibition of H2 consumption. Experiments with resting cells revealed that the degree of inhibition of H2 consumption was a function of the CO concentration. Since the hydrogen-dependent CO2 reductase (HDCR) of A. woodii is known to be very sensitive to CO, we speculated that cells may be more tolerant toward CO when growing on formate, the product of the HDCR reaction. Indeed, addition of up to 25% CO did not influence growth rates on formate, while the final optical densities and the production of acetate increased. Higher concentrations (75 and 100%) led to a slight inhibition of growth and to decreasing rates of formate and CO consumption. Experiments with resting cells revealed that the HDCR is a site of CO inhibition. In contrast, A. woodii was not able to grow on CO as a sole carbon and energy source, and growth on fructose-CO or methanol-CO was not observed.
Aminoglycoside-associated acute kidney injury in elderly patients with and without shock.

OBJECTIVES Multiresistant Gram-negative pathogens pose major healthcare concerns with a limited therapeutic armamentarium. Aminoglycosides (AG) are under-utilized due to nephrotoxicity. We aimed to evaluate AG-associated acute kidney injury (AG-AKI) in elderly inpatients, with and without shock. METHODS We examined the incidence and predictors of AG-AKI by KDIGO criteria and extended renal dysfunction (ERD) in patients aged >60 years. ERD represented a composite of hospital mortality or absence of renal recovery over 6 months following AG-AKI. RESULTS Two hundred and seventy-eight patients (aged 74 ± 8 years) were studied; 43% and 19% received >7 and >10 days of AG therapy, respectively, and 70% gentamicin (versus amikacin). Thirteen per cent had shock and 17% developed AG-AKI. Comparing all patients with shock versus no shock, AG-AKI developed in 33% versus 14%, respectively (P = 0.005); correspondingly among 47 patients with AG-AKI, more with shock had stage 2/3 AKI (92% versus 43%) and dialysis (50% versus 9%) (P < 0.01), but more had other strong AKI confounders than AG therapy alone (83% versus 40%, P = 0.02). Multivariate analyses identified mechanical ventilation, frusemide administration and AG therapy >10 days as predictors of AG-AKI (P < 0.05), whereas shock, pneumonia and frusemide administration predicted more severe stage 2/3 AG-AKI (P < 0.05). Hospital mortality was 30% versus 7% with AG-AKI versus none (P < 0.001). Twenty-three of 211 (11%) patients with extended analysis had ERD, with 47% experiencing renal recovery following AG-AKI. Mechanical ventilation and contrast administration during index hospitalization predicted ERD (P < 0.05). CONCLUSIONS AG-AKI is common in the elderly, with a significant risk of ERD, but the cause and severity are greatly influenced by critical illness and shock, more so than AG therapy alone.
BILIPSCHITZ EMBEDDINGS OF METRIC SPACES INTO EUCLIDEAN SPACES

When does a metric space admit a bilipschitz embedding into some finite-dimensional Euclidean space? There does not seem to be a simple answer to this question. Results of Assouad [A1], [A2], [A3] do provide a simple answer if one permits some small ("snowflake") deformations of the metric, but unfortunately these deformations immediately disrupt some basic aspects of geometry and analysis, like rectifiability, differentiability, and curves of finite length. Here we discuss a (somewhat technical) criterion which permits more modest deformations, based on small powers of an $A_1$ weight. For many purposes this type of deformation is quite innocuous, as in standard results in harmonic analysis about $A_p$ weights [J], [Ga], [St2]. In particular, it cooperates well with "uniform rectifiability" [DS2], [DS4].
Structural modelling and molecular dynamics of a multi-stress responsive WRKY TF-DNA complex towards elucidating its role in stress signalling mechanisms in chickpea

Chickpea is a premier food legume crop with high nutritional quality and attains prime importance in the current era of 795 million people being undernourished worldwide. Chickpea production encounters setbacks due to various stresses and understanding the role of key transcription factors (TFs) involved in multiple stresses becomes inevitable. We have recently identified a multi-stress responsive WRKY TF in chickpea. The present study was conducted to predict the structure of WRKY TF to identify the DNA-interacting residues and decipher DNA-protein interactions. Comparative modelling approach produced 3D model of the WRKY TF with good stereochemistry, local/global quality and further revealed W19, R20, K21, and Y22 motifs within a vicinity of 5 Å to the DNA amongst R18, G23, Q24, K25, Y36, Y37, R38 and K47 and these positions were equivalent to the 2LEX WRKY domain of Arabidopsis. Molecular simulations analysis of reference protein -PDB ID 2LEX, along with Car-WRKY TF modelled structure with the DNA coordinates derived from PDB ID 2LEX and docked using HADDOCK were executed. Root Mean Square (RMS) Deviation and RMS Fluctuation values yielded consistently stable trajectories over 50 ns simulation. Strengthening the obtained results, neither radius of gyration, distance and total energy showed any signs of DNA-WRKY complex falling apart nor any significant dissociation event over 50 ns run. Therefore, the study provides first insights into the structural properties of multi-stress responsive WRKY TF-DNA complex in chickpea, enabling genome wide identification of TF binding sites and thereby deciphers their gene regulatory networks.
A Pilot Study to Examine the Feasibility and Effects of a Home-Based Aerobic Program on Reducing Fatigue in Children With Acute Lymphoblastic Leukemia

Background: Fatigue is one of the most frequent symptoms experienced by children with cancer during treatment. Effective management of fatigue is essential for improving children's quality of life. Objective: The aim of this study was to examine the feasibility of a home-based aerobic exercise intervention to reduce fatigue in children with acute lymphoblastic leukemia (ALL). Methods: A 6-week home-based aerobic exercise intervention was implemented for children who were in the intervention group, whereas patients in the control group received routine care. Multivariate analysis was used to examine the effects of the aerobic exercise intervention on the children's self-reported levels of fatigue at posttest and 1-month follow-up. Two types of analysis were used: intent-to-treat analysis and per-protocol analysis. Results: This study was conducted with 22 children with ALL: 12 in the intervention group and 10 in the control group who were matched by age and sex. For per-protocol analysis, the finding indicated that children who received the exercise intervention reported significantly lower "general fatigue" subscale than those in the control group at the 1-month follow-up measurement. For intent-to-treat analysis, the findings indicated that there were no intervention and time effect for any of the 3 fatigue subscales at either posttest or 1-month follow-up. Conclusion: The finding indicated that the exercise program is feasible and warrants being tested in a clinical trial with a much larger sample of children for ALL. Implications for Practice: It suggests that a home-based exercise program may reduce fatigue for ALL children who are undergoing maintenance chemotherapy.
Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with prrsv

This study was designed to evaluate the efficacy of an inactivated vaccine based on a European-type strain of porcine reproductive and respiratory syndrome virus (prrsv) against the reproductive form of the syndrome in breeding gilts, and any congenital disease in their piglets. Five gilts were vaccinated twice, following the manufacturer's instructions, before they were inseminated. Nine additional gilts remained unvaccinated and served as positive (five gilts) and negative (four gilts) controls. A European wild-type strain genetically divergent from the vaccine strain was used to challenge the five vaccinated and five unvaccinated positive control gilts at 90 days' gestation. The vaccination of the five seronegative gilts did not produce any clinical signs or adverse reactions. However, the vaccine failed to prevent the clinical signs associated with prrsv infection, viraemia after the challenge and transplacental infection of their piglets. The reproductive performance of the vaccinated gilts was similar to that of the unvaccinated positive controls, and there were no statistically significant differences in most of the parameters tested. However, the preweaning mortality of the piglets born to the vaccinated gilts was significantly lower than that of the piglets born to the positive control gilts.
Improving susceptibility mapping using a threshold‐based K‐space/image domain iterative reconstruction approach

To improve susceptibility quantification, a threshold‐based k‐space/image domain iterative approach that uses geometric information from the susceptibility map itself as a constraint to overcome the ill‐posed nature of the inverse filter is introduced. Simulations were used to study the accuracy of the method and its robustness in the presence of noise. In vivo data were processed and analyzed using this method. Both simulations and in vivo results show that most streaking artifacts inside the susceptibility map caused by the ill‐defined inverse filter were suppressed by the iterative approach. In simulated data, the bias toward lower mean susceptibility values inside vessels has been shown to decrease from around 10% to 2% when choosing an appropriate threshold value for the proposed iterative method. Typically, three iterations are sufficient for this approach to converge and this process takes less than 30 s to process a 512 × 512 × 256 dataset. This iterative method improves quantification of susceptibility inside vessels and reduces streaking artifacts throughout the brain for data collected from a single‐orientation acquisition. This approach has been applied to vessels alone as well as to vessels and other structures with lower susceptibility to generate whole brain susceptibility maps with significantly reduced streaking artifacts. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Postnatal development of the hamster cochlea. II. Growth and differentiation of stereocilia bundles

The postnatal development of stereocilia was studied in the Syrian golden hamster. The purpose was to describe tae morphological changes underlying the differentiation of stereocilia bundles and to define the time course of their growth in different regions of the cochlea. Differentiation of the hair bundle occurred by progressive changes in stereocilia number, dimensions, and spatial relationships. The overall transformation of the bundle is interpreted as a four‐stage process involving the initial production of stereocilia (stage I), differentiation into tall and short populations (stage II), formation of distinct ranks (stage III), and resorption of excess stereocilia (stage IV). The orientation and arrangement of stereocilia during stage II began to occur before the tectorial membrane grew over the hair cell field.
A Theoretical Perspective of Coinductive Logic Programming

In this paper we study the semantics of Coinductive Logic Programming and clarify its intrinsic computational limits, which prevent, in particular, the definition of a complete, computable, operational semantics. We propose a new operational semantics that allows a simple correctness result and the definition of a simple meta-interpreter. We compare, and prove the equivalence, with the operational semantics defined and used in other papers on this topic.
Kinetics of the Accumulation of Jasmonic Acid and Its Derivatives in Systemic Leaves of Tobacco (Nicotiana tabacum cv. Xanthi nc) and Translocation of Deuterium-Labeled Jasmonic Acid from the Wounding Site to the Systemic Site

In plants, the mobile signal needed for wound-induced systemic acquired resistance (WSR) has been elusive. The signal compound involved in WSR is supposed to be JA or its derivatives. On the basis of kinetic study of the accumulation of JA or its derivatives, it was discovered that JA, JA-Ile, tuberonic acid (TA, 12-OH epi-JA), and tuberonic acid glucoside (TAG) accumulated in systemic tissues in response to mechanical wounding stress in the tobacco plant (Nicotiana tabacum). Attempts to recover deuterium-labeled JA in systemic leaves after feeding the wounded leaves with deuterium-labeled JA were successfully done. It was also found that the translocated deuterium-labeled JA was metabolized to TA in systemic leaves under feeding of deuterium-labeled JA to the wounding leaves.
UvA-DARE ( Digital Academic Repository ) Reconstruction of a collaborative mathematical learning process

The study focused on the interaction between two secondary school students while they were working on computerized mathematical investigation tasks related to probability theory. The aim was to establish how such interaction helped the students to learn from one another, and how it may have hindered their learning process. The assumption was that interaction is beneficial for students if they can perform certain key activities, namely showing, explaining, justifying, and reconstructing their work. Both students attained mathematical level raising. However, the student who explained frequently and criticized himself attained more mathematical level raising than the student who did not explain her work frequently or criticize herself.
Reliability of self-affine measurements.

Reliability and accuracy of the determination of self-affine exponents are studied and quantified from the analysis of synthetic self-affine profiles and surfaces. The self-affine exponent is measured using different methods either relying on the determination of a ``fractal dimension'' (i.e., box counting and divider methods) or directly analyzing the self-affine exponent. The second group of methods includes the variable bandwidth, the first return and the multireturn probability distribution, and the power spectrum. The accuracy of all these methods is assessed in terms of the difference between an ``input'' self-affine exponent used for the synthetic construction and the ``output'' exponent measured by those different methods. The statistical results of this study provide a quantitative estimate of the dependence of the accuracy with the system size and the value of the self-affine exponent. Artifacts in the measurement of self-affine profiles or surfaces, misorientation, signal amplification, and local geometric filtering, which lead to biased estimates of the self-affine exponent, are also discussed.
Regulating ATP turnover rates over broad dynamic work ranges in skeletal muscles.

It has long been appreciated that rates of ATP utilization and production need to be extremely closely balanced. To put it in molecular rather than molar terms, in human muscle engaged in a 15-min work protocol, approximately 3.3 x 10(20) ATP/g are used and resynthesized at approximately 100 times the resting cycling rates before fatigue, during which time only a 20-25% decrease in the ATP pool is sustained. Analysis of how such remarkable regulatory precision is achieved suggests that in resting muscle myosin behaves as a latent catalyst whose full catalytic potential 1) is realized with the arrival of an activator signal (Ca2+) and 2) is tempered with reaction products; such proactive control, initiated at ATP utilization, sets the required flux through ATP-producing pathways. For any given enzyme step in ATP-producing pathways, reaction velocity (v) becomes the independent parameter, with substrate concentration ([S], the dependent parameter) being adjusted accordingly. Because the dynamic range for muscles (change from resting to maximum ATP turnover rates) can exceed 100-fold, in many studies of working muscle the percent change in ATP turnover rate exceeds (sometimes by very large margins) the percent change in [S]. These observations are not easily explained by current metabolic regulation models but are consistent with pathway enzymes behaving as latent catalysts in resting muscle. In this view, the unmasking of such latent catalytic potential is the main explanation for how large changes in v can be achieved with modest (sometimes immeasurable) changes in [S]. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of Intrathecal Non-NMDA EAA Receptor Antagonist LY293558 in Rats: A New Class of Drugs for Spinal Anesthesia

Background Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non–N-methyl-d-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Methods Rats were tested before and 15–240 min after intrathecal injection of 5 nmol (in 10 &mgr;l) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 &mgr;l bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Results Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Conclusion Drugs like LY293558 that block &agr;-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.
MtLAX 2 , a Functional Homologue of the Arabidopsis Auxin In fl ux Transporter AUX 1 , Is Required for Nodule Organogenesis 1 [ CC-BY ]

Department of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, United Kingdom (S.R., F.R., J.L., C.-W.L., J.S., D.C., C.B., G.O., J.D.M.); Plant Biology Division, Samuel Roberts Noble Foundation, 2510 Sam Noble Parkway, Ardmore, Oklahoma 73401 (S.R., X.C., J.W.); Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, United Kingdom (S.W., J.A.D.); Plant and Crop Science Division, School of Biosciences, University of Nottingham, Nr Loughborough LE12 5RD, United Kingdom (M.J.B., R.S.); and Babraham Institute, Babraham Hall, Babraham CB22 3AT, United Kingdom (S.W.)
Pharmacodynamic and Pharmacokinetic Characterization of the Aldosterone Synthase Inhibitor FAD286 in Two Rodent Models of Hyperaldosteronism: Comparison with the 11β-Hydroxylase Inhibitor Metyrapone

Aldosterone synthase (CYP11B2) inhibitors (ASIs) represent an attractive therapeutic approach for mitigating the untoward effects of aldosterone. We characterized the pharmacokinetic/pharmacodynamic relationships of a prototypical ASI, (+)-(5R)-4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl]benzonitrile hydrochloride (CGS020286A, FAD286, FAD) and compared these profiles to those of the 11β-hydroxylase inhibitor metyrapone (MET) in two rodent models of secondary hyperaldosteronism and corticosteronism. In chronically cannulated Sprague-Dawley rats, angiotensin II (ANG II) (300 ng/kg bolus + 100 ng/kg/min infusion) or adrenocorticotropin (100 ng/kg + 30 ng/kg/min) acutely elevated plasma aldosterone concentration (PAC) from ∼0.26 nM to a sustained level of ∼2.5 nM for 9 h. Adrenocorticotropin but not ANG II elicited a sustained increase in plasma corticosterone concentration (PCC) from ∼300 to ∼1340 nM. After 1 h of Ang II or adrenocorticotropin infusion, FAD (0.01–100 mg/kg p.o.) or MET (0.1–300 mg/kg p.o.) dose- and drug plasma concentration-dependently reduced the elevated PACs over the ensuing 8 h. FAD was ∼12 times more dose-potent than MET in reducing PAC but of similar or slightly greater potency on a plasma drug concentration basis. Both agents also decreased PCC in the adrenocorticotropin model at relatively higher doses and with similar dose potencies, whereas FAD was 6-fold weaker based on drug exposures. FAD was ∼50-fold selective for reducing PAC versus PCC, whereas MET was only ∼3-fold selective. We conclude that FAD is a potent, orally active, and relatively selective ASI in two rat models of hyperaldosteronism. MET is an order of magnitude less selective than FAD but is, nevertheless, more potent as an ASI than as an 11β-hydroxylase inhibitor.