Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular dynamics analysis of structural factors influencing back door pi release in myosin.

The back door has been proposed to be an exit pathway from the myosin active site for phosphate (P(i)) generated by adenosine 5'-triphosphate hydrolysis. We used molecular dynamics simulations to investigate the interaction of P(i) with the back door and the plausibility of P(i) release via this route. Molecular dynamics simulations were performed on the Dictyostelium motor domain with bound Mg.adenosine 5'-diphosphate (ADP) and P(i), modeled upon the Mg.ADP. BeF(x) and Mg.ADP. V(i) structures. Simulations revealed that the relaxation of ADP and free P(i) from their initial positions reduced the diameter of the back door via motions of switch 1 and switch 2 located in the upper and lower 50-kDa subdomains, respectively. In neither simulation could P(i) freely diffuse out the back door. Water molecules, however, could flux through the back door in the Mg.ADP. BeF(x)-based simulation but not in the Mg.ADP. V(i)-based simulation. In neither structure was water observed fluxing through the main (front door) entrance. These observations suggest that the ability of P(i) to leave via the back door is linked tightly to conformational changes between the upper and lower 50-kDa subdomains. The simulations offer structural explanations for (18)O-exchange with P(i) at the active site, and P(i) release being the rate-limiting step in the myosin adenosine 5'-triphosphatase.
Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury.

IMPORTANCE Calcium-channel blockers are metabolized by the cytochrome P450 3A4 (CYP3A4; EC 1.14.13.97) enzyme. Blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor of CYP3A4 and azithromycin is not, which makes comparisons between these 2 macrolide antibiotics useful in assessing clinically important drug interactions. OBJECTIVE To characterize the risk of acute adverse events following coprescription of clarithromycin compared with azithromycin in older adults taking a calcium-channel blocker. DESIGN, SETTING, AND PARTICIPANTS Population-based retrospective cohort study in Ontario, Canada, from 2003 through 2012 of older adults (mean age, 76 years) who were newly coprescribed clarithromycin (n = 96,226) or azithromycin (n = 94,083) while taking a calcium-channel blocker (amlodipine, felodipine, nifedipine, diltiazem, or verapamil). MAIN OUTCOMES AND MEASURES Hospitalization with acute kidney injury (primary outcome) and hospitalization with hypotension and all-cause mortality (secondary outcomes examined separately). Outcomes were assessed within 30 days of a new coprescription. RESULTS There were no differences in measured baseline characteristics between the clarithromycin and azithromycin groups. Amlodipine was the most commonly prescribed calcium-channel blocker (more than 50% of patients). Coprescribing clarithromycin vs azithromycin with a calcium-channel blocker was associated with a higher risk of hospitalization with acute kidney injury (420 patients of 96,226 taking clarithromycin [0.44%] vs 208 patients of 94,083 taking azithromycin [0.22%]; absolute risk increase, 0.22% [95% CI, 0.16%-0.27%]; odds ratio [OR], 1.98 [95% CI, 1.68-2.34]). In a subgroup analysis, the risk was highest with dihydropyridines, particularly nifedipine (OR, 5.33 [95% CI, 3.39-8.38]; absolute risk increase, 0.63% [95% CI, 0.49%-0.78%]). Coprescription with clarithromycin was also associated with a higher risk of hospitalization with hypotension (111 patients of 96,226 taking clarithromycin [0.12%] vs 68 patients of 94,083 taking azithromycin [0.07%]; absolute risk increase, 0.04% [95% CI, 0.02%-0.07%]; OR, 1.60 [95% CI, 1.18-2.16]) and all-cause mortality (984 patients of 96,226 taking clarithromycin [1.02%] vs 555 patients of 94,083 taking azithromycin [0.59%]; absolute risk increase, 0.43% [95% CI, 0.35%-0.51%]; OR, 1.74 [95% CI, 1.57-1.93]). CONCLUSIONS AND RELEVANCE Among older adults taking a calcium-channel blocker, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically significant greater 30-day risk of hospitalization with acute kidney injury. These findings support current safety warnings regarding concurrent use of CYP3A4 inhibitors and calcium-channel blockers.
Determining u-turn adjustment factor for signalized intersections in Doha, Qatar

This paper summarizes the work conducted to estimating a U-turn adjustment factor at selected signalized intersections in Doha, Qatar. Unfortunately, the Highway Capacity Manual (HCM) 2010 does not consider the effect of U-turn traffic on the capacity of signalized intersection; therefore, a few researchers attempted to develop U-turn adjustment factors to be added to the HCM analysis of signalized intersections when heavy U-turn traffic exists. To achieve this, the average headway was measured for U-tuning and left-turning vehicles at three different intersections in Doha. To estimate the U-turn adjustment factor, 198 queues with 2,327 U-turn vehicles and 1,564 left-turn vehicles were used to develop a regression model with the headway as the dependent variable and the U-turn percentage as the independent variable. The resulting quadratic model shows an increase in the average headway as the percentage of U-Turn traffic increases, with an R 2 of 0.591. This indicates that the presence of U-turning vehicles has a significant effect on increasing the average headway thus reducing the capacity of signalized intersection. The result shows the U-Turn adjustment factor ranges from 0.76 for 100% of U-turn traffic to 0.95 for 10% of U-turn traffic.
Biofeedback provides long term benefit for patients with intractable, slow and normal transit constipation

Background—Many patients with idiopathic constipation do not respond to conventional medical treatments. Recently biofeedback has been proposed as an alternative treatment but the long term results, and which patients benefit, are unknown. Treatment has usually been restricted to patients with normal colonic transit and impaired pelvic floor coordination on straining. Aims—To determine the efficacy and long term outcome of biofeedback treatment in idiopathic constipation. Methods—One hundred consecutive contactable patients who had completed a course of biofeedback more than 12 months previously were identified. Pretreatment details of bowel function and symptoms, whole gut transit time, and anorectal physiological testing, which had been previously prospectively collected, were collated. Follow up consisted of structured interview. Sixty five per cent had slow transit and 59% had paradoxical pelvic floor contraction on straining. Results—Median follow up was 23 months (range 12–44). On long term follow up 55% felt that biofeedback had helped and 57% felt their constipation was improved. There was a significant reduction in need to strain, abdominal pain, bloating, and oral laxative use. Spontaneous bowel frequency was significantly improved by treatment. Patients with slow and normal transit, males and females, and those with and without paradoxical contraction of the anal sphincter on straining, benefited equally from treatment. Anorectal testing did not predict outcome. Conclusion—This study suggests that biofeedback is an effective long term treatment for the majority of patients with idiopathic constipation unresponsive to traditional treatments. Pelvic floor abnormalities and transit time should not form selection criteria for treatment.
Understanding the Information Security Awareness Process in Real Estate Organizations Using the SECI Model

Information security awareness plays a key role in organizations using information systems for their business operations. Recent trends have indicated that not only critical infrastructure sectors but also organizations such as retail services are targeted by criminals as long as there is data of interest and the level of information security (and awareness) is relatively low. One such example concerns real estate organizations where they process their customers’ personal and sensitive information. In this study, we applied Nonaka’s Socialization, Externalization, Internalization, and Combination (SECI) model as the theoretical lens to understand how real estate business employees gain awareness and understanding of information security. Data collected from 105 real estate organizations is tested using the structural equation modelling approach. The results indicate Socialization, Internalization and Combination were found to support the development of information security awareness among employees while data analysis does not support Externalization.
Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer's disease‐linked APPswe/PS1ΔE9 mice

Experience in complex environments induces numerous forms of brain plasticity, improving structure and function. It has been long debated whether brain plasticity can be induced under neuropathological conditions, such as Alzheimer's disease (AD), to an extent that would reduce neuropathology, rescue brain structure, and restore its function. Here we show that experience in a complex environment rescues a significant impairment of hippocampal neurogenesis in transgenic mice harboring familial AD‐linked mutant APPswe/PS1ΔE9. Proliferation of hippocampal cells is enhanced significantly after enrichment, and these proliferating cells mature to become new neurons and glia. Enhanced neurogenesis was accompanied by a significant reduction in levels of hyperphosphorylated tau and oligomeric Aβ, the precursors of AD hallmarks, in the hippocampus and cortex of enriched mice. Interestingly, enhanced expression of the neuronal anterograde motor kinesin‐1 was observed, suggesting enhanced axonal transport in hippocampal and cortical neurons after enrichment. Examination of synaptic physiology revealed that environmental experience significantly enhanced hippocampal long‐term potentiation, without notable alterations in basal synaptic transmission. This study suggests that environmental modulation can rescue the impaired phenotype of the Alzheimer's brain and that induction of brain plasticity may represent therapeutic and preventive avenues in AD. —Y. ‐S. Hu, P. Xu, G. Pigino, S. T. Brady, J. Larson, O. Lazarov. Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer's disease‐linked APPswe/PS1ΔE9 mice. FASEB J. 24, 1667–1681 (2010). www.fasebj. org
Behavior of Low-Voltage Surge Protective Devices Under High-Current Derivative Impulses

It has been observed by scientists that maximum rate of change of current with respect to time of subsequent return strokes could be as high as 150 kA/mus. This fact is not reflected in the present day testing of surge protecting devices (SPDs). Usually, they are tested with 8/20 mus current impulses the time derivative of which are considerably less than the time derivatives of subsequent return stroke current pulses. When SPDs are subjected to current impulses with a high-current derivative, the voltage yields on their terminals will be highly influenced by the inductance of the lead connections. Therefore, a high di/dt impulse current can produce a voltage across the SPDs terminals that can exceed the threshold level of the protected equipment, causing partial or permanent damage in their insulation. In this study, the behavior of few selected surge protective components for fast current transients is analyzed and compared with standard 8/20 muS current impulses. The experiment was performed on disk type varistors and ceramic type gas discharge tubes (GDT). The result show that, the clamping voltages due to fast transients for tested component is considerably greater than the ones observed with standard 8/20 muS current impulses.
Expression of a Codon-Optimized dsdA Gene in Tobacco Plastids and Rice Nucleus Confers D-Serine Tolerance

D-serine is toxic to plants. D-serine ammonia lyase, which is encoded by the dsdA gene, can attenuate this toxicity with high specificity. In the present study, we explored the function of codon-optimized dsdA with tobacco plastids and rice nuclear transformation system. It was shown that dsdA gene was site-specifically integrated into the tobacco plastid genome and displayed a high level of expression. Genetic analysis of the progenies showed that dsdA gene is maternally inherited and confers sufficient D-serine resistance in tobacco. The effective screening concentrations of D-serine for seed germination, callus regeneration and foliar spray were 10, 30, and 75 mM, respectively. In addition, calluses from homozygous transgenic rice lines also showed significant tolerance to D-serine (up to 75 mM). Our study proves the feasibility of using dsdA gene as a selectable marker in both plastid and nuclear transformation systems.
Persistent Alterations in Dendrites, Spines, and Dynorphinergic Synapses in the Nucleus Accumbens Shell of Rats with Neuroleptic-Induced Dyskinesias

Chronic treatment of humans or experimental animals with classical neuroleptic drugs can lead to abnormal, tardive movements that persist long after the drugs are withdrawn. A role in these neuroleptic-induced dyskinesias may be played by a structural change in the shell of the nucleus accumbens where the opioid peptide dynorphin is upregulated in treated rats that show vacuous chewing movements (VCMs). The shell of the nucleus accumbens normally contains a dense plexus of dynorphinergic fibers especially in its caudomedial part. After 27 weeks of haloperidol administration and 18 weeks of withdrawal, the immunoreactive labeling of this plexus is intensified when compared with that after vehicle treatment. In addition, medium spiny neurons here show a significant increase in spine density, dendritic branching, and numbers of terminal segments. In the VCM-positive animals, the dendritic surface area is reduced, and dynorphin-positive terminals contact more spines and form more asymmetrical specializations than do those in animals without the syndrome (VCM-negative and vehicle-treated groups). Persistent, neuroleptic-induced oral dyskinesias could therefore be caused by incontrovertible alterations, involving terminal remodeling or sprouting, to the synaptic connectivity of the accumbal shell.
Barriers to access to care reported by women living with HIV across 27 countries

Increased access to successful antiretroviral therapy (ART) is necessary in order to achieve an AIDS-free generation. Importantly, slightly over half of the people living with HIV are women. Small studies have described many barriers to accessing treatment and care among women living with HIV. This cross-sectional, non-interventional, epidemiological study assessed the prevalence of barriers to accessing care for women living with HIV across 27 countries, divided into four global regions. HIV-positive women attending routine clinical visits were offered the opportunity to participate in the study. Data describing the study sites and demographic characteristics of the participating women were collected. Participating women filled out questionnaires including the Barriers to Care Scale (BACS) questionnaire, on which they reported the extent to which they found each of the 12 potential barriers to accessing health care problematic. A total of 1931 women living with HIV were included in the study: 760 from Western Europe and Canada (WEC), 532 from Central and Eastern Europe (CEE), 519 from Latin America (LA), and 120 from China. The mean age of participating women was 40.1 ± 11.4 years. A total of 88.2% were currently taking ART. A total of 81.8% obtained HIV treatment under a government health plan. The most prevalent barrier to care was community HIV/AIDS stigma. Community HIV/AIDS knowledge, lack of supportive/understanding work environments, lack of employment opportunities, and personal financial resources were also highly prevalent barriers to accessing care. These findings indicate that, more than 30 years after the start of the AIDS epidemic, stigma is still a major issue for women living with HIV. Continued efforts are needed to improve community education on HIV/AIDS in order to maximize access to health care among women living with HIV.
Hearing loss in patients with vestibulotoxic reactions to gentamicin therapy.

OBJECTIVES To determine whether patients with vestibulotoxic reactions to gentamicin have hearing thresholds worse than predicted by distributions of better-ear hearing thresholds in people of the same age and sex in the general population, and, if so, to measure the severity and audiometric pattern of that hearing loss. DESIGN Retrospective case series from previously published prospective and retrospective studies of vestibular function in patients receiving gentamicin. SETTING Tertiary neurotological practice. PATIENTS Convenience sample of 33 consecutive patients seen for objective evidence of vestibulotoxic reactions after systemic gentamicin therapy. Twenty-five of 33 patients underwent valid and complete audiometry. MAIN OUTCOME MEASURES Age- and sex-corrected better-ear pure tone thresholds, 0.5 to 6.0 kHz. The better-ear audiogram was defined in 2 ways: primarily, the audiogram of the ear with the better average threshold at 0.5, 1.0, and 2.0 kHz; secondarily, the composite audiogram taking the better threshold for each frequency. RESULTS Patients exhibiting vestibulotoxic reactions to gentamicin therapy had hearing thresholds that were similar to those seen in the general population at 0.5, 3.0, and 6.0 kHz. Median thresholds were 6 to 7 dB worse than expected at 1.0 and 2.0 kHz (95% confidence intervals, 2-13 dB and 3-12 dB, respectively). The largest median difference was 15 dB at 4.0 kHz (95% confidence interval, 3-23 dB), but this difference was not significant for the more conservative composite definition of the better ear. CONCLUSIONS Patients with vestibulotoxic reactions to gentamicin therapy have little additional hearing loss compared with the general population. Physicians should monitor both auditory and vestibular function when aminoglycosides, especially gentamicin, must be used.
Recent Advances in Non-invasive Brain Stimulation for Major Depressive Disorder

Non-invasive brain stimulation (NBS) is a promising treatment for major depressive disorder (MDD), which is an affective processing disorder involving abnormal emotional processing. Many studies have shown that repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) over the prefrontal cortex can play a regulatory role in affective processing. Although the clinical efficacy of NBS in MDD has been demonstrated clinically, the precise mechanism of action remains unclear. Therefore, this review article summarizes the current status of NBS methods, including rTMS and tDCS, in the treatment of MDD. The article explores possible correlations between depressive symptoms and affective processing, highlighting the relevant affective processing mechanisms. Our review provides a reference for the safety and efficacy of NBS methods in the clinical treatment of MDD.
Recording advances for neural prosthetics

An important challenge for neural prosthetics research is to record from populations of neurons over long periods of time, ideally for the lifetime of the patient. Two new advances toward this goal are described, the use of local field potentials (LFPs) and autonomously positioned recording electrodes. LFPs are the composite extracellular potential field from several hundreds of neurons around the electrode tip. LFP recordings can be maintained for longer periods of time than single cell recordings. We find that similar information can be decoded from LFP and spike recordings, with better performance for state decodes with LFPs and, depending on the area, equivalent or slightly less than equivalent performance for signaling the direction of planned movements. Movable electrodes in microdrives can be adjusted in the tissue to optimize recordings, but their movements must be automated to be a practical benefit to patients. We have developed automation algorithms and a meso-scale autonomous electrode testbed, and demonstrated that this system can autonomously isolate and maintain the recorded signal quality of single cells in the cortex of awake, behaving monkeys. These two advances show promise for developing very long term recording for neural prosthetic applications.
Assignment and Scheduling in Flexible Job-Shops by Hierarchical Optimization

In this paper, we propose a new hierarchical method for the flexible job-shop scheduling problem (FJSP). This approach is mainly adapted to a job-shop problem (JSP) with high flexibility and is based on the decomposition of the problem in an assignment subproblem and a sequencing subproblem. For the first subproblem, we propose two methods: the first one is based successively on a heuristic approach and a local search; the second one, however, is based on a branch-and-bound algorithm. The quality of the assignment is evaluated by a lower bound. For the second subproblem we apply a hybrid genetic algorithm to deal with the sequencing problem. Computational tests are finally presented.
Mark-Release-Recapture Reveals Extensive Movement of Bed Bugs (Cimex lectularius L.) within and between Apartments

Understanding movement and dispersal of the common bed bug (Cimex lectularius L.) under field conditions is important in the control of infestations and for managing the spread of bed bugs to new locations. We investigated bed bug movement within and between apartments using mark-release-recapture (m-r-r) technique combined with apartment-wide monitoring using pitfall-style interceptors. Bed bugs were collected, marked, and released in six apartments. The distribution of marked and unmarked bed bugs in these apartments and their 24 neighboring units were monitored over 32 days. Extensive movement of marked bed bugs within and between apartments occurred regardless of the number of bed bugs released or presence/absence of a host. Comparison of marked and unmarked bed bug distributions confirms that the extensive bed bug activity observed was not an artifact of the m-r-r technique used. Marked bed bugs were recovered in apartments neighboring five of six m-r-r apartments. Their dispersal rates at 14 or 15 d were 0.0–5.0%. The estimated number of bed bugs per apartment in the six m-r-r apartments was 2,433–14,291 at 4–7 d after release. Longevity of bed bugs in the absence of a host was recorded in a vacant apartment. Marked large nymphs (3rd– 5th instar), adult females, and adult males continued to be recovered up to 57, 113, and 134 d after host absence, respectively. Among the naturally existing unmarked bed bugs, unfed small nymphs (1st– 2nd instar) were recovered up to 134 d; large nymphs and adults were still found at 155 d when the study ended. Our findings provide important insight into the behavioral ecology of bed bugs in infested apartments and have significant implications in regards to eradication programs and managing the spread of bed bugs within multi-occupancy dwellings.