Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated Approach of In Vivo and In Vitro Evaluation of the Involvement of Hepatic Uptake Organic Anion Transporters in the Drug Disposition in Rats Using Rifampicin as an Inhibitor

Cumulative studies describe the importance of drug transporters as one of the key determinants of pharmacokinetics that necessi-tate investigation and assessment of the involvement of drug transporters in drug discovery and development. The present study investigated an integrated in vivo and in vitro approach to determine the involvement of organic anion transporting polypeptides (Oatps) in the disposition of drugs in rats using rifampicin as an inhibitor. When bromosulfophthalein (BSP) and HMG-CoA reductase inhibitors (statins), which were used as model substrates for Oatps, were administered intravenously (3 and 1 mg/kg, re-spectively) to rats pretreated with rifampicin orally (30 mg/kg), the total plasma clearance of BSP and statins was attenuated compared with that in control rats, suggesting the involvement of Oatps in the disposition of these drugs in vivo. On the other hand, the pharmacokinetics of midazolam, used as a model substrate of cytochrome P450 3a (Cyp3a), was unchanged between control rats and rifampicin-pretreated rats. The involvement of Oatps in the disposition of statins observed in vivo was further clarified by employing an in vitro hepatic uptake study and media-loss assay in the presence or absence of 100 m M rifampicin. Hepatic intrinsic clearance was reduced in the presence of rifampicin in both the media-loss assay and hepatocyte uptake study. The present study suggests in vivo investigations in rats using rifampicin together with in vitro investigations with a media-loss assay and/or uptake assay using rat hepatocytes can help determine whether a clinical drug-drug interaction study is necessary in drug development.
Turbulence in stratified shear flows: implications for interpreting shear-induced mixing in the ocean

Abstract Direct numerical simulations of the time evolution of homogeneous stably stratified turbulent sheer flows have been performed for several Richardson numbers Ri and Reynolds numbers Rλ. The results show excellent agreement with length scale models developed from laboratory experiments to characterize oceanic turbulence. When the Richardson number Ri is less than the stationary value Ris, the turbulence intensity grows at all scales; the growth rate is a function of Ri. The size of the vertical density inversions also increases. When Ri ≥ Ri, the largest turbulent eddies become vertically constrained by buoyancy when the Ellison (turbulence) scale LEand the Ozmidov (buoyancy) scale LO are equal. At this point the mixing is most efficient and the flux Richardson number or mixing efficiency is Rf ≈ 0.20 for the stationary Richardson number Ris = 0.21. The vertical mass flux becomes countergradient when ϵ ≈ 19vN2, and vertical density overturns are suppressed in few than half of a Brunt-Vaisala period.
Impact of ship emissions on marine boundary layer NOx and SO2 Distributions over the Pacific Basin

The impact of ship emissions on marine boundary layer (MBL) NOx and SO2 levels over the Pacific Ocean has been explored by comparing predictions (with and without ships) from a global chemical transport model (GCTM) against compiled airborne observations of MBL NOx and SO2. For latitudes >15°N, which define that part of the Pacific having the heaviest shipping, this analysis revealed significant model over prediction for NOx and a modest under prediction for SO2 when ship emissions were considered. Possible reasons for the difference in NOx and SO2 were explored using a full‐chemistry box model. These results revealed that for an actual plume setting the NOx lifetime could be greatly shortened by chemical processes promoted by ship plume emissions themselves. Similar chemical behavior was not found for SO2.
Orbital forcing, climatic interactions, and glaciation cycles

We consider forced oscillations of a nonlinear climatic oscillator. The oscillator includes radiation balance, oceanic thermal inertia, a highly simplified hydrological cycle, the mass balance and plastic flow of ice sheets, the elasticity of the earth's crust, and the viscosity of its upper mantle, as well as their various interactions. This system exhibits self-sustained periodic oscillations with amplitude of a few degrees Celsius in the absence of any periodic forcing. The oscillator's free period, depending on model parameters, lies roughly between 5000 yr and 15000 yr (5–15 ka). The model is subjected to forcing at the astronomical periodicities of precession, 19 and 23 ka, obliquity, 41 ka, and eccentricity, 100 ka and 400 ka. The forcing is assumed to act on the climatic system by variations in mean annual insolation, in the case of eccentricity, as well as by its effect on the ice-mass balance through the nonlinear precipitation-temperature feedback. The effects investigated only cause small changes in ice mass V and global temperature T when self-sustained oscillations are absent. In their presence, nonlinearly resonant response to the forcings leads to large changes in T and V; this response obtains at the frequency of the forcing, due to the mechanism of entrainment. The nonlinear character of the response also leads to combination tones. These are linear combinations of the forcing frequencies with integer coefficients, among which the largest occur near 100 and 10 ka. Sharp peaks in spectral density at the forcing frequencies and at their combination tones are superimposed on a continuous background. The spectral power in the background decreases with increasing frequency, like random red noise. This deterministic aperiodic behavior limits the predictability of glaciation cycles.
Stroke Incidence According to Cardiorespiratory Fitness: A Cohort Study of 483,379 Hypertensive Patients

Objectives: We assessed stroke incidence in hypertensive patients according to cardiorespiratory fitness (CRF) and changes in CRF. Methods: A prospective cohort study of 483,379 US Veterans. Participants completed a maximal standardized Exercise Treadmill test (ETT) performed within the Veterans Affairs medical centers across the United States between 1999 and 2020. None exhibited evidence of unstable cardiovascular disease during the ETT. Participants were stratified into 5 age-and-gender specific CRF categories based on the peak metabolic equivalents (METs) achieved. A subgroup of participants with two ETT evaluations (n=110,576) were also assigned to 4 categories based on MET changes from the initial ETT to the final ETT. Multivariable Cox models, adjusted for age, and co-morbidities were used to estimate HRs and 95% CIs for stroke risk. Results: The mean age {+/-} standard deviation (SD) was 59.4{+/-}9.0 years. During the median follow-up time of 10.6 years (5,182,179 person-years), there were 15,925 stroke events with an average annual rate of 3.1 events per 1,000 person-years. In a final adjusted model, relatively poor CRF was the strongest predictor of stroke risk than any other comorbidity (HR: 2.24; 95% CI: 2.10-2.40; P< 0.001). For each 1-MET higher exercise capacity, the risk was 10% lower (0.90, 95% CI 0.90-0.91, p<0.001). Compared to the Least-fit, stroke risk was 23% lower for Low-fit individuals (HR 0.77; 95% CI, 0.73-0.80; p<0.001); and declined progressively to 55% for those in the highest CRF category (HR 0.45; 95% CI 0.42-0.48; p<0.001). We also assessed stroke incidence according to change in CRF. Compared to fit individuals during both evaluations, the risk was 27% higher for those who became unfit (HR 1.27, 95% CI 1.15-1.41, p<0.001), and not significantly different for unfit who became fit (HR 1.10, 95% CI 0.97-1.25, p=0.13). Conclusions: Poor CRF was the strongest predictor of stroke incidence in hypertensive patients, regardless of age race, or gender. The association was independent, inverse, and graded for all stroke types. Changes in CRF over time reflected inverse changes in stroke risk, suggesting that risk of stroke can be modulated by improved CRF.
The Antibacterial and Antifungal Activity of Chlorhexidine Diacetate Incorporated into Acrylic Resins Used in Provisional Restorations

Objective The surface of provisional restorations applied before conventional or implant- supported fixed restorations may cause bacterial or fungal biofilm formation. The aim of this study was to evaluate the antimicrobial activity of acrylic resins used in provisional restorations modified with chlorhexidine diacetate. Methods 120 cylindrical, auto-polymerized resin samples modified with chlorhexidine diacetate were prepared at concentrations of 0 (control), 1, 3, 5 wt %. The antimicrobial activity was examined against Streptococcus mutans, Enterococcus faecalis, and Candida albicans using Crystal Violet quantification, MTT assay, and Scanning Electron Microscopy. Data were analyzed by ANOVA and paired sample t-tests (α=0.05). Results The addition of chlorhexidine diacetate influenced the growth rate and metabolic activity of microorganisms. The antimicrobial effect against C. albicans and S. mutans statistically increased with the percentage of chlorhexidine diacetate. E. faecalis bacteria were less affected by chlorhexidine diacetate compared to other pathogens. Conclusion It has been shown that the effectiveness of CHDA in inhibiting the proliferation of microorganisms correlated positively with increasing concentration levels. More research is needed to confirm the impact of different chlorhexidine concentrations on the mechanical properties, clinical efficacy, and antimicrobial properties of CDHA.
Judged Distance to Virtual Objects in the near Visual Field

Errors in judged depth of nearby virtual objects presented via see-through, helmet mounted displays are examined as a function of monocular, biocular and stereoscopic viewing conditions, accommodative demand and subjects’ age. These errors are argued to be related to changes in binocular vergence. Suggestions for improved control of the judged distance to virtual objects and the cause of the judgment errors are briefly discussed.
SUSTAINING LOCAL WATERSHED INITIATIVES: LESSONS FROM LANDCARE AND WATERSHED COUNCILS 1

ABSTRACT: In the last decade, watershed groups (WG) established through government initiatives have become an important part of the natural resource management landscape in developed economies. In this paper, the authors reflect upon their research and experience with Landcare in Victoria, and to a lesser extent with Watershed Councils in Oregon, to identify the principles that appear fundamental to sustaining effective WG. In the first instance, these groups must be established at a local scale using social as well as biophysical boundaries. It is also critical that WG are embedded within a supportive institutional framework that identifies realistic roles for private landowners, local organizations such as WG, and regional planning bodies. Without broad stakeholder representation, the perceived benefits of participation are quickly forfeited. It is simply unrealistic to expect an effective network of WG to be sustained without substantial investment by government to provide for program management, group coordination, and cost sharing for on‐ground work. There must also be the commitment and skills within a program to establish processes that build trust and competency amongst citizens and agencies. These principles should also provide a foundation for the critical evaluation of WG programs.
SpikingJelly: An open-source machine learning infrastructure platform for spike-based intelligence

Spiking neural networks (SNNs) aim to realize brain-inspired intelligence on neuromorphic chips with high energy efficiency by introducing neural dynamics and spike properties. As the emerging spiking deep learning paradigm attracts increasing interest, traditional programming frameworks cannot meet the demands of the automatic differentiation, parallel computation acceleration, and high integration of processing neuromorphic datasets and deployment. In this work, we present the SpikingJelly framework to address the aforementioned dilemma. We contribute a full-stack toolkit for preprocessing neuromorphic datasets, building deep SNNs, optimizing their parameters, and deploying SNNs on neuromorphic chips. Compared to existing methods, the training of deep SNNs can be accelerated 11×, and the superior extensibility and flexibility of SpikingJelly enable users to accelerate custom models at low costs through multilevel inheritance and semiautomatic code generation. SpikingJelly paves the way for synthesizing truly energy-efficient SNN-based machine intelligence systems, which will enrich the ecology of neuromorphic computing.
Timing of initiation of anti-retroviral therapy predicts post-treatment control of SIV replication

One approach to ‘functional cure’ of HIV infection is to induce durable control of HIV replication after the interruption of antiretroviral therapy (ART). However, the major factors that determine the viral ‘setpoint’ level after treatment interruption are not well understood. Here we combine data on ART interruption following SIV infection for 124 total animals from 10 independent studies across 3 institutional cohorts to understand the dynamics and predictors of post-treatment viral control. We find that the timing of treatment initiation is an important determinant of both the peak and early setpoint viral levels after treatment interruption. During the first 3 weeks of infection, every day of delay in treatment initiation is associated with a 0.22 log10 copies/ml decrease in post-rebound peak and setpoint viral levels. However, delay in initiation of ART beyond 3 weeks of infection is associated with higher post-rebound setpoint viral levels. For animals treated beyond 3 weeks post-infection, viral load at ART initiation was the primary predictor of post-rebound setpoint viral levels. Potential alternative predictors of post-rebound setpoint viral loads including cell-associated DNA or RNA, time from treatment interruption to rebound, and pre-interruption CD8+ T cell responses were also examined in the studies where these data were available. This analysis suggests that optimal timing of treatment initiation may be an important determinant of post-treatment control of HIV.
Global Initiative for Childhood Cancer Control: Increasing access, improving quality, saving lives

cancer cases and 10 million deaths(1). In particular, regarding the childhood cancer, nearly 280,000 children and adolescents aged from 0 to 19 years old develop the disease each year in the world(2) and, of them, 9 out of 10 live in lowand middle-income countries, where treatments are generally not available or present high costs(2). In Latin America and the Caribbean, it is estimated that at least 29,000 individuals aged less than 19 years old will develop cancer each year. In high-income countries, more than 80% of the children and adolescents with cancer are cured; however, this rate is approximately 20% in lowand middle-income countries(3). The preventable deaths due to cancer in this population group from lowand middle-income countries are related to underdiagnosis, late or incorrect diagnosis, health care access difficulties, advanced-stage disease at the time of diagnosis, and lack of access to treatments and supportive care in reference centers or to health professionals with specialized knowledge and training. They can also be due to treatment abandonment as a result of the families’ difficulties bearing the direct health care costs, to deaths due to drug toxicities and to higher recurrence rates. Underlying reasons for this disparity have been linked to health system indicators such as annual per capita national expenditure in health, number of physicians and nurses per 1,000 inhabitants and
The rotary bottom boundary layer

We derive a simple analytical model of the boundary layer induced by rotary tidal currents flowing over a horizontal bottom in the absence of strong vertical stratification, formulating explicit estimates of the shear velocity, dissipation, and friction factors relating inviscid velocity to bottom shear stress. Accordingly, these friction factors may be calibrated by an observed velocity profile through the rotary bottom boundary layer, thereby reducing the empiricism of existing depth averaged models of tidal hydraulics. We illustrate the procedure by analyzing measured M2 rotary current profiles on the outer Europeann shelf with good model accuracy; the local dissipation-based friction factor compares favorably with a global value based upon a calibrated numerical model of the northwest European shelf as well.
Post-Transplant Cyclophosphamide for the Prevention of Graft-vs.-Host Disease in Allogeneic Hematopoietic Cell Transplantation: A Guide to Management for the Advanced Practitioner

Cyclophosphamide remains a critical component to haploidentical transplant conditioning regimens. Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical bone marrow transplant setting. The relative ease of administration compared with ex vivo manipulations and efficacy in reducing GVHD has led to increasing PTCy use in transplant centers around the world. The role of PTCy has expanded to haploidentical transplantation with myeloablative conditioning regimens and peripheral blood progenitor cells as the donor source. Moreover, encouraging results in GVHD management have been shown with the use of PTCy alone or in combination with other immunosuppressives in the human leukocyte antigen–matched donor setting. The toxicity profile of cyclophosphamide varies extensively depending on dose, duration, overall drug exposure, and, potentially, pharmacogenetics. This review highlights the pharmacology, pharmacokinetics, and toxic effects of cyclophosphamide and offers practical guidance for clinical application in the post-transplant setting. We summarize data on the management of high-dose cyclophosphamide toxicities and provide insights into the pharmacogenetic implications on drug efficacy and safety data.
Large Byzantine water storage cisterns

At least 36 cisterns, excavated reservoirs, were constructed in Istanbul during Byzantine times. The largest known covered cistern is the Basilica cistern which was probably completed in the early 6th century. Figure 1 shows a plan view of the 140 × 70 m structure, which now lies partly under a road in a busy area of Istanbul. It was originally supplied by aqueduct from springs in Marmara, west of the city. Figure2 gives a general view of the interior, where the roof is supported by 336 columns. Figure 3 shows the base of one of the column which appears to be made from a scrap sculpture of the Medusa's head. There are constant inflows of water at various points in the roof of the cistern, as can be seen from the pool of water, splashes and drips. At the time the photograph was taken in March 1988, it had not rained for at least 15 days, hence the inflow could not have been direct recharge. The water was clear and odour-free and was certainly not sewage. The probable source was leaking water mains which, without the cistern, would percolate to the water table. Thus Figure 3 provides some evidence that leaking mains recharge groundwater as argued in recent articles (Lerner 1986, 1988a, b). My thanks to Professor Okay Eroskay of Istanbul University for help with the photography.
An update on current and novel molecular diagnostics for the diagnosis of invasive fungal infections

ABSTRACT Background Invasive fungal infections cause millions of infections annually, but diagnosis remains challenging. There is an increased need for low-cost, easy to use, highly sensitive and specific molecular assays that can differentiate between colonized and pathogenic organisms from different clinical specimens. Areas covered We reviewed the literature evaluating the current state of molecular diagnostics for invasive fungal infections, focusing on current and novel molecular tests such as polymerase chain reaction (PCR), digital PCR, high-resolution melt (HRM), and metagenomics/next generation sequencing (mNGS). Expert opinion PCR is highly sensitive and specific, although performance can be impacted by prior/concurrent antifungal use. PCR assays can identify mutations associated with antifungal resistance, non-Aspergillus mold infections, and infections from endemic fungi. HRM is a rapid and highly sensitive diagnostic modality that can identify a wide range of fungal pathogens, including down to the species level, but multiplex assays are limited and HRM is currently unavailable in most healthcare settings, although universal HRM is working to overcome this limitation. mNGS offers a promising approach for rapid and hypothesis-free diagnosis of a wide range of fungal pathogens, although some drawbacks include limited access, variable performance across platforms, the expertise and costs associated with this method, and long turnaround times in real-world settings.
GEOLOGY OF THE CHLORIDE QUADRANGLE, ARIZONA

The Chloride quadrangle includes the southern two-thirds of the Cerbat Mountains, a range composed mostly of presumably Precambrian crystalline rocks. The oldest rocks are quartzite, mica schist, hornblende-diopside schist, and amphibolite. Younger and larger in amount are granite and granite gneiss. Gabbroic and dioritic gneiss, pegmatite, aplite, diabase, and mylonite also occur as part of the basement complex. The earliest rocks were strongly folded, but igneous intrusion and granitization have obliterated most of the folds. The rock types and the history of the basement complex compare closely with the Archean in the Grand Canyon. The area contains no Paleozoic rocks and probably no Mesozoic rocks. Intrusions of granite porphyry associated with mineralization are believed to be Tertiary. Dikes of granite porphyry, pegmatite, aplite, and lamprophyre are associated with these intrusions. Small areas of andesitic and rhyolitic extrusive rocks of Tertiary (? ) age occur along the flanks of the range. Quaternary basalt caps these rocks in some places. Several periods of faulting and erosion are visible in the volcanic rocks. The latest faulting has produced the present mountains. The greatest displacement has been on the west side, and the Cerbat Range is an eastward-tilted fault block, modified in part into a horst. This mountain building seems to have occurred in late Tertiary and Quaternary time. Recent fault-block movement is suggested by the presence of canyon terraces and by the dissection of the pediment at the west base of the range.