Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics–small molecule drug interactions

ABSTRACT Introduction: Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.
1H NMR spectra of butane‐1,4‐diol and other 1,4‐diols: DFT calculation of shifts and coupling constants

The proton nuclear magnetic resonance (NMR) spectra of butane‐1,4‐diol, pentane‐1,4‐diol, (S,S)‐hexane‐2,5‐diol, 2,5‐dimethylhexane‐2,5‐diol and cyclohexane‐1,4‐diols (cis and trans) in benzene and some other solvents have been analysed. The conformer distribution and the NMR shifts of these diols in benzene have been computed on the basis of the density functional theory, the solvent being included by means of the integral‐equation‐formalism polarizable continuum model implemented in Gaussian 09. Relative Gibbs energies of all conformers are calculated at the Perdew, Burke and Ernzerhof (PBE)0/6‐311+G(d,p) level and NMR shifts by the gauge‐including atomic orbital method with the PBE0/6‐311+G(d,p) geometry and the cc‐pVTZ basis set. Vicinal three‐bond coupling constants for the acyclic diols are calculated from the relative conformer populations, the geometries and generalized Karplus equations developed by Altona's group; these correlate well with the experimental values. The solvent dependence of coupling constants for butane‐1,4‐diol is attributed to conformational change. Coupling constants for the rigid cyclohexane‐1,4‐diols do not change with solvent and are readily explained in terms of their geometries. The NMR shifts of hydrogen‐bonded protons in individual conformers of alkane‐1,n‐diols show a very rough correlation with the OH···OH distances. The computed overall NMR shifts for CH protons in 1,2‐diols, 1,3‐diols and 1,4‐diols are systematically high but correlate very well with the experimental values, with a gradient of 1.07 ± 0.01; those for OH protons correlate less well. Copyright © 2014 John Wiley & Sons, Ltd.
The mechanical waveform of the basilar membrane. I. Frequency modulations ("glides") in impulse responses and cross-correlation functions.

The purpose of this investigation is to present evidence from experimental as well as model results on temporal variations of the frequency of oscillation in the basilar membrane's impulse response. Stimuli were either clicks leading to a direct estimate of the impulse response, or bands of pseudo-random noise (one or two octaves wide) which lead to an indirect estimate of the impulse response via a cross-correlation procedure. The noise bands were centered at the best frequency of the BM location under observation. Responses were obtained from the basal turn of the guinea-pig cochlea, from a location with a best frequency (for the weakest stimuli) between 17.0 and 18.5 kHz. Data acquisition was done with a sample frequency of 208 kHz. Input-output cross-correlation functions were found to share with impulse responses the property that the initial oscillations have a noticeably lower frequency than the later ones. During the impulse response the frequency of oscillation increases gradually. This increase occurs and continues to beyond the time that the oscillations reach the largest amplitude. This frequency variation is called a "glide. " Using the "analytic signal" method the frequency of oscillation is found to increase continually throughout the duration of the main lobe of oscillation, even at the lowest tested stimulus intensities (about 20 dB SPL). At high stimulus intensity both the direct and indirect impulse response change their appearance drastically but the glide retains its basic form. In the case of the direct impulse response estimate the glide can be attributed to temporal variation of the degree of nonlinearity. For the indirect impulse response this is not true, because with a constant level noise stimulus there is no regular temporal variation of nonlinearity. In this case the glide should be interpreted as an intrinsic property of the cochlear system. From our and others' data the glide was found to exist over a topographic frequency range of best frequencies of at least from 1.76 to 18 kHz. Two examples of present-day models of the cochlea are discussed of which one is found to demonstrate the glide phenomenon in its response, and the other one does not.
Unravelling Airbnb Predicting Price for New Listing

This paper analyzes Airbnb listings in the city of San Francisco to better understand how different attributes such as bedrooms, location, house type amongst others can be used to accurately predict the price of a new listing that optimal in terms of the host's profitability yet affordable to their guests. This model is intended to be helpful to the internal pricing tools that Airbnb provides to its hosts. Furthermore, additional analysis is performed to ascertain the likelihood of a listings availability for potential guests to consider while making a booking. The analysis begins with exploring and examining the data to make necessary transformations that can be conducive for a better understanding of the problem at large while helping us make hypothesis. Moving further, machine learning models are built that are intuitive to use to validate the hypothesis on pricing and availability and run experiments in that context to arrive at a viable solution. The paper then concludes with a discussion on the business implications, associated risks and future scope.
Chemical characteristics of dimer interfaces in the legume lectin family

The Erythrina corallodendron lectin (EcorL) crystallizes in monoclinic and hexagonal crystal forms. Comparison of the newly determined hexagonal form (PDB code 1fyu) with the monoclinic form shows that the dimeric structure of EcorL reflects the inherent biological structure of the protein and is not an artifact of the crystal packing. To further understand the factors determining the dimerization modes of legume lectins, EcorL, concanavalin A (ConA), and Griffonia simplicifolia (GS4) were taken as representatives of the three unique dimers found in the family. Six virtual homodimers were generated. The hydropathy, amino acid composition, and solvation energy were calculated for all nine homodimers. Each of the three native dimers has a distinct chemical composition. EcorL has a dominant hydrophobic component, and ConA has a strong polar component, but in GS4 the three components contribute equally to the interface. This distribution pattern at the interface is unique to the native dimers and distinct from the partition observed in the virtual dimers. Amino acid composition of other members of the family that dimerize like EcorL or ConA maintain the same pattern of amino acids distribution observed in EcorL and ConA. However, lectins that dimerize like GS4 do not show a particularly distinct distribution. In all cases, the calculated solvation energy of the native dimer was lower than that of the virtual dimers, suggesting that the observed mode of dimerization is the most stable organization for the given sequence and tertiary structure. The dimerization type cannot be predicted by sequence analysis.
A sensitive assay for the quantification of reverse transcriptase activity based on the use of carrier‐bound template and non‐radioactive‐product detection, with special reference to human‐immunodeficiency‐virus isolation

A non‐radioactive 96‐well microtitre plate reverse transcriptase (RT) assay, based on the use of covalently bound riboadenosine homopolymer in the wells and 5‐bromodeoxyuridined 5′‐triphosphate (BrdUTP) as dNTP, is described. The whole assay is performed in a single well, including the quantitative detection of incorporated BrdU, which is performed immunologically using alkaline phosphatase‐conjugated anti‐BrdU antibody and colorometric reading. The system also allows the use of variable amounts of primer. The kinetics and characteristics of the assay using BrdUTP is similar to the use of [3H]dTTP. The sensitivity of the assay can be varied either by altering the duration of RT assay time and/or by prolonging the alkaline phosphatase reaction. Thus the assay can detect < 0.02 pg of recombinant human‐immunodeficiency‐virus (HIV) type I RT, < 0.005 m unit of avian‐myeloblastosis‐virus RT or < 0.02 m unit of recombinant Moloney‐murine‐leukaemia‐virus RT. The assay was found to be useful with various types of cell‐culture material, and a comparative study of 16 HIV‐infected lymphocyte cultures, using 10 microliters of supernatant medium for RT assay and 22.5 microliters for p24 antigen assay showed that the new RT assay was at least 25‐fold more sensitive than the p24 antigen assay. The results also show a good correlation between the RT activities found and the p24‐antigen level detected, with exception for HIV2 isolates, as they only became positive in the RT assay. The technical performance and the capacity of the test compared with other available RT kits is discussed, as well as its use for other applications.
Fatigue and quality of life of women with multiple sclerosis: a randomized controlled clinical trial.

AIM The aim of this study was to determine the effects of aquatic exercise on fatigue and the quality of life in women with multiple sclerosis (MS). METHODS This randomized controlled clinical trial was carried out in a multiple sclerosis clinic in Iran, where 37 outpatient women with MS were randomized into an exercise group (N.=18) and a control group (N.=19). In the exercise group, aquatic exercise was performed for 45 minutes, 3 times per week for 8 weeks. The control group did not receive any interventions (aquatic exercise) and were asked to maintain their normal treatments. The severity and perception of fatigue and quality of life (QoL) were measured using the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Multicultural Quality of Life Index (MQLIM) questionnaires. RESULTS The repeated measure ANOVA demonstrated significant effects of aquatic exercise on the changes in the scores of physical and psychosocial fatigue perception, QoL, and fatigue severity (P=0.001). However, its effect was not significant for cognitive fatigue perception (P>0.05). General linear models show that the percentages of variation, as explained by the aquatic exercises, were highest in the QoL and the physical and psychosocial fatigue perceptions. CONCLUSION Aquatic exercise can improve the QoL and decrease fatigue severity and fatigue perception, specifically in the physical and psychosocial domain for MS patients. However, it was not effective in improving cognitive fatigue perception.
Do Genetic Modifiers of High-Density Lipoprotein Cholesterol and Triglyceride Levels Also Modify Their Response to a Lifestyle Intervention in the Setting of Obesity and Type-2 Diabetes Mellitus?: The Action for Health in Diabetes (Look AHEAD) Study

Background—High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education. Methods and Results—We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention (P=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (P=0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (P=0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction (P=0.035). Apolipoprotein B (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction (P<0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (P=0.0009). Conclusions—This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.
The Meaning of Occupation, Occupational Need, and Occupational Therapy in a Military Context

Despite occupational therapists having strong historical ties to the Canadian military, there are currently no uniformed occupational therapists and only a few permanent occupational therapists employed by Canadian Forces. Occupational therapy is provided, in the main, through civilian occupational therapists. Occupational therapists have unique skills that can contribute to the existing Canadian Forces Physical Medicine and Rehabilitation Services Department. To establish the depth and scope of their work, this article explains the theoretical underpinnings of occupational therapy. Examples are provided of possible occupational therapy for populations of Canadian Forces members: (1) those with transient, intermittent injuries; (2) those returning from overseas missions with very serious injuries or severe injuries; and (3) those with permanent injuries who are transitioning from the Canadian Forces into the civilian workforce. Interventions for mental health issues are interwoven with those targeting physical issues. The article suggests that occupational therapists employed on a permanent basis by the Canadian Forces can contribute in a more comprehensive manner to the wider rehabilitation of Canadian Forces members. The article has applicability to occupational therapy military services in other countries.
Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

The assumption of a linear dose response used to describe the biological effects of high-LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high-energy charged (HZE) nuclei. Human fibroblast and lymphocyte cells were irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with oxygen (77 keV/μm), silicon (99 keV/μm) or Fe (175 keV/μm), Fe (195 keV/μm) or Fe (240 keV/μm) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Nonlinear regression models were used to evaluate possible linear and nonlinear dose-response models based on these data. Dose responses for simple exchanges for human fibroblasts irradiated under confluent culture conditions were best fit by nonlinear models motivated by a nontargeted effect (NTE). The best fits for dose response data for human lymphocytes irradiated in blood tubes were a linear response model for all particles. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low-particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high-LET radiation at the relevant range of low doses.
Relative Age of Proviral Porcine Endogenous Retrovirus Sequences in Sus scrofa Based on the Molecular Clock Hypothesis

ABSTRACT Porcine endogenous retroviruses (PERV) are discussed as putative infectious agents in xenotransplantation. PERV classes A, B, and C harbor different envelope proteins. Two different types of long terminal repeat (LTR) structures exist, of which both are present only in PERV-A. One type of LTR contains a distinct repeat structure in U3, while the other is repeatless, conferring a lower level of transcriptional activity. Since the different LTR structures are distributed unequally among the proviruses and, apparently, PERV is the only virus harboring two different LTR structures, we were interested in determining which LTR is the ancestor. Replication-competent viruses can still be found today, suggesting an evolutionary recent origin. Our studies revealed that the age of PERV is at most 7.6 × 106 years, whereas the repeatless LTR type evolved approximately 3.4 × 106 years ago, being the phylogenetically younger structure. The age determined for PERV correlates with the time of separation between pigs (Suidae, Sus scrofa) and their closest relatives, American-born peccaries (Tayassuidae, Pecari tajacu), 7.4 × 106 years ago.
Comparative analysis of selection schemes used in artificial bee colony algorithm

Artificial bee colony (ABC) algorithm, which has explicit strategies to balance intensification and diversification, is a simple and effective swarm intelligence algorithm for both continuous and combinatorial optimisation problems. Selection scheme, which is used by onlooker bees to select employed bees to follow, is an important factor for ABC algorithm to keep good balance between intensification and diversification. In this paper, a normalised fitness function for minimisation problem is first proposed for roulette wheel selection, so ABC can still have enough selection pressure in late stage. And then, aim to analyse the effect of different selection schemes, systematic experiments were carried for roulette wheel selection, rank selection, tournament selection, and disruptive selection on a set of test functions with different dimensions and different computation resources. Simulation results show that the suitability of a selection scheme depends not only on the features of test functions and but also on the computation resources used. No selection scheme can always outperform other selection schemes on all test functions.
Neurocognitive Improvement After Carotid Artery Stenting in Patients With Chronic Internal Carotid Artery Occlusion

Symptomatic internal carotid artery (ICA) occlusion with hemodynamic impairment remains a dismal disease when untreated. In this prospective, single-center, controlled study, we investigated the feasibility, safety, and long-term outcome of stenting by endovascular recanalization for patients with chronic ICA occlusion. Forty patients with symptomatic chronically occluded ICA were assigned to receive endovascular recanalization (group A, n = 18) or conservative management (group B, n = 22). The primary end point was 100% complete recanalization of the primary occlusion at 60 minutes, and secondary end points were improvement in neurologic function and cognitive function. Patients in the 2 groups were comparable in demographic and baseline characteristics. Successful recanalization was achieved in 88.9% (16 of 18) of patients with the restoration of Thrombolysis in Myocardial Ischemia/Thrombolysis in Cerebral Ischemia 2 or 3 flow. There was no procedural or new cerebral ischemic event. Improvement in brain perfusion was observed in 12 (12 of 18, 75%) patients on single-photon emission computed tomography. Improvement in neurologic function defined as a reduction of ≥4 points on the National Institutes of Health Stroke Scale (NIHSS) at 6 months was observed in group A (baseline, 6.83 ± 3.01 vs 6 months, 2.61 ± 1.20; P < .01) and group B (baseline, 6.05 ± 2.75 vs 6 months, 4.77 ± 1.69; P < .05). A significant difference in NIHSS scores was noted between group A and B at 1, 3, and 6 months (P < .05 or .001). Improvement in cognitive function defined as an increase of ≥8 on the Montreal Cognitive Assessment (MoCA) was observed in group A at 3 and 6 months (baseline, 14.67 ± 3.56 vs 3 months, 24.17 ± 3.55 and 6 months, 24.72 ± 2.85; P < .01). Significant improvement in MoCA was also observed in group B (P < .01). Furthermore, a significant difference in MoCA scores was noted between group A and B at 1, 3, and 6 months (P < .05 or .001). Endovascular recanalization is feasible and safe for patients with symptomatic chronic carotid artery occlusion. Successful carotid artery stenting can improve neurological function and global cognitive function than nonrevascularization.
Analyzing Work-integrated Learning assessment practices through the lens of autonomy principles

There is generally an increasing interest in the vocational aspects of higher education, including work integrated learning. Yet there is often an assumption that students will make connections between these two sites, but this is often not the case; connecting university knowledge and practices to those of working life thus remains a vexing problem. In this research article, we examine this connectivity with a focus on work-integrated learning (WIL) assessment as this may highlight what lecturers judge as important knowledge. The lens for examining assessment is that of the Legitimation Code Theory concept of Autonomy codes. Whereas we find that work and university practices and knowledge may be quite well connected, our theoretical lens reveals an unexpected outlying field that may be less well connected to disciplinary knowledge: that of writing and presentation practices judged as valuable by the lecturers. The paper suggests that the integration of the two fields, general writing and presentation and disciplinary knowledge and practices, may be improved for the purposes of strengthening student learning.