Miracle-dz/UniFAR-FTUs huggingface dataset:
Uncovering Functional Contributions of PMAT (Slc29a4) to Monoamine Clearance Using Pharmacobehavioral Tools

Plasma membrane monoamine transporter (PMAT, Slc29a4) transports monoamine neurotransmitters, including dopamine and serotonin, faster than more studied monoamine transporters, e.g., dopamine transporter (DAT), or serotonin transporter (SERT), but with ~400–600-fold less affinity. A considerable challenge in understanding PMAT’s monoamine clearance contributions is that no current drugs selectively inhibit PMAT. To advance knowledge about PMAT’s monoamine uptake role, and to circumvent this present challenge, we investigated how drugs that selectively block DAT/SERT influence behavioral readouts in PMAT wildtype, heterozygote, and knockout mice of both sexes. Drugs typically used as antidepressants (escitalopram, bupropion) were administered acutely for readouts in tail suspension and locomotor tests. Drugs with psychostimulant properties (cocaine, D-amphetamine) were administered repeatedly to assess initial locomotor responses plus psychostimulant-induced locomotor sensitization. Though we hypothesized that PMAT-deficient mice would exhibit augmented responses to antidepressant and psychostimulant drugs due to constitutively attenuated monoamine uptake, we instead observed sex-selective responses to antidepressant drugs in opposing directions, and subtle sex-specific reductions in psychostimulant-induced locomotor sensitization. These results suggest that PMAT functions differently across sexes, and support hypotheses that PMAT’s monoamine clearance contribution emerges when frontline transporters (e.g., DAT, SERT) are absent, saturated, and/or blocked. Thus, known human polymorphisms that reduce PMAT function could be worth investigating as contributors to varied antidepressant and psychostimulant responses.
Strategies to improve the vaccine distribution and community awareness of taking COVID-19 vaccine in rural areas in Indonesia

COVID-19 has spread worldwide, and several governments, including Indonesia, are actively vaccinating. However, numerous factors may contribute to decreased vaccination administration, including hesitation, a lack of information, and demographic considerations. Therefore, this review provides insights on maximizing vaccine distribution and raising community awareness about COVID-19 vaccination in rural regions with difficulty in transportation access, a lack of health care workers, and limited vaccine storage facilities. It was discovered that numerous potential methods, such as the Internet of Things (IoT), bio-tracking and bio-detect, P-median, and Vehicle Routing Problem (VRP), can monitor vaccination delivery in rural parts of Indonesia. The correct vaccine distribution system can monitor situations during distribution by combining IoT technology with bio-tracking and bio-detect in airborne transportation. Besides enhancing vaccine distribution technologies, healthcare professionals play a critical role in maintaining vaccine quality and improving community awareness of diseases. In particular, as a healthcare professional, a pharmacist has an essential role in ensuring the quality of the vaccine until it is administered to the patient and improving patients’ awareness of COVID-19 and the vaccinations. Pharmacists can collaborate with other healthcare professionals to educate the community to identify important information related to wrong perceptions about COVID-19 and vaccinations.
Biodynamics of supine humans and interaction with transport systems during vibration and shocks

This work investigates the effect of the contact surfaces on the biomechanical response of supine humans during whole-body vibration and shocks. Twelve participants were exposed to three-dimensional random vibration and shocks and were tested with two types of contact surfaces: (i) litter only, and (ii) litter with spinal board. The two configurations were tested with and without body straps to secure the supine human. The addition of the spinal board reduced the involuntary motion of the supine humans in most directions. There were significant reductions in the relative vertical accelerations at the neck and torso areas, especially during shocks (p < 0.01). The inclusion of body straps with the spinal board was more effective in reducing the relative motion in most directions when shocks were presented. This study shows that the ergonomic design of the human transport system and the underlying contacting surfaces should be studied during dynamic transport environments.
Fiber Model Considering the Local Instability Effect and Its Application to the Seismic Analysis of Eccentrically Compressed Steel Piers

To propose a seismic response calculation model for eccentrically compressed steel piers that can consider the local instability effect and horizontal bidirectional earthquake actions, in-plane and out-of-plane pseudo-static numerical simulation and bidirectional seismic response analysis are performed to study the applicability of the improved fiber model. The comparison results with the refined hybrid-element model show that the improved fiber model can accurately simulate the hysteretic performance of eccentrically compressed steel piers in the in-plane or out-of-plane directions and can be used to calculate the structural seismic requirements under the bidirectional action of rarely met earthquakes.
A reexamination of factor momentum: How strong is it?

Recent studies show that most financial market anomalies exhibit a momentum effect. Based on two datasets, (i) an original 22-factor sample and (ii) a more comprehensive 187-factor sample, we find that factor momentum effect is weak at the individual factor level. In both samples, only about 22%– 27% of the factors exhibit strong return continuation and dominate the factor momentum portfolio while the remaining factors do not. The factor momentum strategies do not outperform the corresponding long-only strategies in either sample. The choice of factors affects the ability of factor momentum to explain individual stock momentum
The importance of intermediate-dose Valacyclovir in primary CMV prophylaxis after Allogeneic-stem cell transplantation, and the advantages of step-wise pre-emptive treatment in CMV reactivation

Objective: Cytomegalovirus (CMV) reactivation and disease are still one of the most important causes of morbidity and mortality after allogeneic stem cell transplantation (ASCT). Letermovir prophylaxis has been clearly shown to be effective and well-tolerated. Drug interactions and cost are limitations. Alternative regimens such as Valacyclovir 3g-6g a day are of interest. In our study, we investigated the clinical results of intermediate dose (3 gr/d) valacyclovir after ASCT in primary CMV prophylaxis. Material and Methods: The data of 70 patients who underwent ASCT between 2019-2020 were retrospectively analyzed. Valacyclovir was given at a dose of 3 g/day to all patients for primary CMV prophylaxis after ASCT. If CMV reactivation developed during Valacyclovir prophylaxis, therapeutic oral Valganciclovir or parenteral Ganciclovir was gradually switched according to CMV DNA copy numbers. Results: The mean age of the patients included in the study was 45.5 years. The D+/R+ seropositivity was 97.2%. CMV reactivation developed in 37/70 (52.8%) patients within the first 100 days after transplantation. While CMV negativity could be achieved with oral VValganciclovir in 17 of the reactive patients (45.9%), hospitalization was required for parenteral ganciclovir use in 20 (28.1%) of them. The median PFS of patients with and without CMV reactivation was 10 months and 18 months, with a one-year PFS were 49.9% and 80.9%, respectively. One-year overall survival rates of patients with and without CMV reactivation were 52.9% and 92.9% respectively. Conclusion: It has become more important to prevent infections that may develop after ASCT with prophylaxis rather than treating. Post-transplant intermediate-dose Valacyclovir as primary prophylaxis has been shown to reduce CMV reactivation/disease rates at desired levels and reduce hospitalizations.
Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon’s role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid β burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid β burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid β secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid β homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid β secretion, defining a new way to target AD and other similar diseases therapeutically.
Continue or cease? A method to identify credit constraints under policy intervention and an implication for policy efficiency

ABSTRACT In this study, we consider the problem whereby policy intervention in the financial market might hide the existence of credit constraints. We develop a theoretical model of the representative borrower utilizing credit from private banks and a governmental financial institution. Using the exogenous change in the transaction technology for borrowing from the governmental institution, we can identify the existence of credit constraints even if the policy remains in the market. Additionally, our model shows that the inefficiency of policy intervention is larger when we consider the borrower’s choice of optimal effort.
Comparative Analysis and Ancestral Sequence Reconstruction of Bacterial Sortase Family Proteins Generates Functional Ancestral Mutants with Different Sequence Specificities

Gram-positive bacteria are some of the earliest known life forms, diverging from gram-negative bacteria 2 billion years ago. These organisms utilize sortase enzymes to attach proteins to their peptidoglycan cell wall, a structural feature that distinguishes the two types of bacteria. The transpeptidase activity of sortases make them an important tool in protein engineering applications, e.g., in sortase-mediated ligations or sortagging. However, due to relatively low catalytic efficiency, there are ongoing efforts to create better sortase variants for these uses. Here, we use bioinformatics tools, principal component analysis and ancestral sequence reconstruction, in combination with protein biochemistry, to analyze natural sequence variation in these enzymes. Principal component analysis on the sortase superfamily distinguishes previously described classes and identifies regions of relatively high sequence variation in structurally-conserved loops within each sortase family, including those near the active site. Using ancestral sequence reconstruction, we determined sequences of ancestral Staphylococcus and Streptococcus Class A sortase proteins. Enzyme assays revealed that the ancestral Streptococcus enzyme is relatively active and shares similar sequence variation with other Class A Streptococcus sortases. Taken together, we highlight how natural sequence variation can be utilized to investigate this important protein family, arguing that these and similar techniques may be used to discover or design sortases with increased catalytic efficiency and/or selectivity for sortase-mediated ligation experiments.
A Comparative Study of Cell Culture Conditions during Conversion from Primed to Naive Human Pluripotent Stem Cells

The successful reprogramming of human somatic cells into induced pluripotent stem cells (hiPSCs) represented a turning point in the stem cell research field, owing to their ability to differentiate into any cell type with fewer ethical issues than human embryonic stem cells (hESCs). In mice, PSCs are thought to exist in a naive state, the cell culture equivalent of the immature pre-implantation embryo, whereas in humans, PSCs are in a primed state, which is a more committed pluripotent state than a naive state. Recent studies have focused on capturing a similar cell stage in human cells. Given their earlier developmental stage and therefore lack of cell-of-origin epigenetic memory, these cells would be better candidates for further re-differentiation, use in disease modeling, regenerative medicine and drug discovery. In this study, we used primed hiPSCs and hESCs to evaluate the successful establishment and maintenance of a naive cell stage using three different naive-conversion media, both in the feeder and feeder-free cells conditions. In addition, we compared the directed differentiation capacity of primed and naive cells into the three germ layers and characterized these different cell stages with commonly used pluripotent and lineage-specific markers. Our results show that, in general, naive culture NHSM medium (in both feeder and feeder-free systems) confers greater hiPSCs and hESCs viability and the highest naive pluripotency markers expression. This medium also allows better cell differentiation cells toward endoderm and mesoderm.
Inter-Varietal Variation in Phenolic Profile, Sugar Contents, Antioxidant, Anti-Proliferative and Antibacterial Activities of Selected Brassica Species

The main objective of this research work was to evaluate the variation in nutritional profile, antioxidant, anti-proliferative and antibacterial activities of selected species of Brassica. Five locally grown Brassica species (cauliflower, broccoli, red cabbage, white cabbage and Chinese cabbage) were collected from Ayub Agriculture Research Institute (AARI), Faisalabad, Pakistan. Polyphenolic rich extracts of these Brassicaceae species were prepared by Soxhlet extraction technique using ethanol. Phenolic acids, flavonoids and sugar contents of the investigated species were determined and quantified by RP-HPLC. Antioxidant activity was carried out by measurement of total phenolic contents (TPC), total flavonoid contents (TFC), reducing potential and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. Anti-proliferative activity of all the extracts was determined by MTT assay on lung cancer cell line A549. Antibacterial activity was tested against the two bacterial strains, i.e., Bacillus cereus (B. cereus) and Escherichia coli (E. coli). HPLC analysis revealed the presence of gallic acid, p-coumaric acid, chlorogenic acid and benzoic acid as the major phenolic acids, whereas catechine was the major flavonoid in most of the extracts. The TPC ranged from 9.7 to 32.8 mg/g of dry plant material, measured GAE and TFC ranged from 7.7 to 23.7 mg/g of dry plant material, measured as CE. Higher TPC and TFC were found in red cabbage extract followed by cauliflower, broccoli, white cabbage and Chinese cabbage. Red cabbage extract also showed higher DPPH radical scavenging activity (IC50 = 2.3 µg/mL) followed by cauliflower, broccoli, white cabbage and Chinese cabbage. Maltodextrose was the major sugar followed by fructose in all species of Brassica. Promising anti-proliferative and antibacterial activities were also recorded by the selected Brassica extracts.
Optimization of the preparation process of electrostatic-solution blow spinning nanofiber yarn using response surface methodology

There are several methods of preparing nanofiber yarns, but little work has been reported using a combination of electrospinning and solution blowing methods (i.e., electrostatic-solution blow spinning) to prepare nanofiber yarns. In this study, a response surface method (RSM) based on Box–Behnken design was used to investigate the relationship between the yarn parameters and yarn diameter, and the process was optimized. The yarn diameter was simulated by electrostatic voltage, air pressure, winding speed and funnel velocity. The correlation coefficients before and after adjustment were 0.97 and 0.95, respectively, through variance analysis, which verified the accuracy of the yarn diameter model. The results showed that the influence of each experimental factor on the yarn diameter was in descending order of winding speed, electrostatic voltage, airflow and funnel velocity, and there were interactions among the factors. The BDD response model was used to obtain the best experimental conditions, which provided a good theoretical reference for the preparation of polyacrylonitrile nanofibers. In addition, the effects of voltage and air pressure on the diameter of the nanofiber and yarn and the effects of the twist coefficient on the shape and mechanical properties of the yarn were studied. The results showed that with the increase of voltage and air pressure, the diameter of the nanofiber decreased, and the yarn diameter decreased first and then increased. When the twist factor was 100, the twist angle of the yarn was 49.91°, the breaking strength was 12.92 MPa and the elongation at break was 81.34%.
Osteoarthritis-Induced Metabolic Alterations of Human Hip Chondrocytes

Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were stimulated with IL-1β, TNF, forskolin and opioid peptides. Mediators released from chondrocytes were measured, and mitochondrial functions and glycolysis were determined (Seahorse Analyzer). Unstimulated OA chondrocytes exhibited significantly higher release of IL-6, PGE2 and MMP1 and lower production of glycosaminoglycan than non-OA chondrocytes. Oxygen consumption rates (OCR) and mitochondrial ATP production were comparable in unstimulated non-OA and OA chondrocytes, although the non-mitochondrial OCR was higher in OA chondrocytes. Compared to OA chondrocytes, non-OA chondrocytes showed stronger responses to IL-1β/TNF stimulation, consisting of a larger decrease in mitochondrial ATP production and larger increases in non-mitochondrial OCR and NO production. Enhancement of cAMP by forskolin prevented IL-1β-induced mitochondrial dysfunction in OA chondrocytes but not in non-OA chondrocytes. Endogenous opioids, present in OA joints, influenced neither cytokine-induced mitochondrial dysfunction nor NO upregulation. Glycolysis was not different in non-OA and OA chondrocytes, independent of stimulation. OA induces persistent metabolic alterations, but the results suggest upregulation of cellular mechanisms protecting mitochondrial function in OA.
Exoplanet atmosphere retrievals in 3D using phase curve data with ARCiS: Application to WASP-43b

Aims. To create a retrieval framework which encapsulates the 3D nature of exoplanet atmospheres, and to apply it to observed emission phase curve and transmission spectra of hot Jupiter exoplanet WASP-43b. Methods. We present our 3D framework, which is freely available as a stand-alone module from GitHub. We use the atmospheric modelling and Bayesian retrieval package ARCiS (ARtful modelling Code for exoplanet Science) to perform 8 3D retrievals on simultaneous transmission (HST/WFC3) and phase-dependent emission (HST/WFC3, Spitzer/IRAC) observations of WASP-43b as a case study. We assess how input assumptions affect our retrieval outcomes. In particular we look at constraining equilibrium chemistry vs a free molecular retrieval, the case of no clouds vs parametrised clouds, and using Spitzer phase data that have been reduced from two different literature sources. For the free chemistry retrievals, we retrieve abundances of H2O, CH4, CO, CO2, AlO, and NH3 as a function of phase, with many more species considered for the equilibrium chemistry retrievals. Results. We find consistent super-solar C/O (0.6-0.9) and super-solar metallicities (1.7-2.9 dex) for all retrieval setups that assume equilibrium chemistry. Atmospheric heat distribution, hotspot shift (15.6 vs 4.5 for different Spitzer datasets), and temperature structure are influenced by the Spitzer emission phase data. Comparisons are made with other studies of WASP-43b, including available GCM simulations. Conclusions. The parametrised 3D setup we have developed provides a valuable tool to analyse extensive observational datasets such as spectroscopic phase curves. Near-future observations with missions such as the James Webb Space Telescope (JWST) and Ariel will greatly improve our understanding of the atmospheres of exoplanets such as WASP-43b.
Simple Compressive Strength Results of Sodium-Hydroxide- and Sodium-Silicate-Activated Copper Flotation Tailing Geopolymers

Geopolymers are created by mixing a source of aluminosilicates, which can be natural or by-products of other industries, with an alkaline solution, which dissolves the aluminates and silicates present in this source, where after a polymerization process, an N-A-S-H gel is formed, which is responsible for providing the properties that characterize geopolymers. Among the variety of existing geopolymers, those based on by-products from other industries stand out since they were demonstrated to be a less-polluting alternative for concrete production than ordinary Portland cement (OPC). Due to the above, it is essential to study copper flotation tailings as raw material to generate geopolymers. The excessive amounts of existing tailing deposits also produce different risks for the nearby communities. Therefore, using this industrial waste as a construction material would provide several environmental and economic benefits. This article reports on the experimental work carried out in the laboratory of the Sustainable Mining Research Center CIMS of the Engineering Consulting Company JRI, where the effect of the alkaline activator type on the compressive strength of geopolymers based on copper flotation tailings was analyzed. For this purpose, two geopolymeric mixtures were made with different kinds of alkaline activators; one activated using 100% NaOH and the other activated with 100% sodium silicate (SS). From the results, it was found that the geopolymers activated with 100% SS obtained the highest compressive strength, reaching 36.46 MPa with 7 days of curing at 90 °C, followed by the geopolymers activated with 100% NaOH, where a compressive strength of 22.98 MPa was obtained under the same curing conditions. On the other hand, it was found that both geopolymers created were not leachable according to the TCLP test performed, and thus, these geopolymers were classified as non-toxic materials. In addition, it was found that both geopolymers presented a high infiltration value, making them practically impermeable.