Miracle-dz/UniFAR-FTUs huggingface dataset:
The CD63 homologs, Tsp42Ee and Tsp42Eg, restrict endocytosis and promote neurotransmission through differential regulation of synaptic vesicle pools

The Tetraspanin (Tsp), CD63, is a transmembrane component of late endosomes and facilitates vesicular trafficking through endosomal pathways. Despite being widely expressed in the human brain and localized to late endosomes, CD63's role in regulating endo- and exocytic cycling at the synapse has not been investigated. Synaptic vesicle pools are highly dynamic and disruptions in the mobilization and replenishment of these vesicle pools have adverse neuronal effects. We find that the CD63 homologs, Tsp42Ee and Tsp42Eg, are expressed at the Drosophila neuromuscular junction to regulate synaptic vesicle pools through both shared and unique mechanisms. Tsp42Ee and Tsp42Eg negatively regulate endocytosis and positively regulate neurotransmitter release. Both tsp mutants show impaired locomotion, reduced miniature endplate junctional current frequencies, and increased endocytosis. Expression of human CD63 in Drosophila neurons leads to impaired endocytosis suggesting the role of Tsps in endocytosis is conserved. We further show that Tsps influence the synaptic cytoskeleton and membrane composition by regulating Futsch loop formation and synaptic levels of SCAR and PI(4,5)P2. Finally, Tsp42Ee and Tsp42Eg influence the synaptic localization of several vesicle-associated proteins including Synapsin, Synaptotagmin, and Cysteine String Protein. Together, our results present a novel function for Tsps in the regulation of vesicle pools and provide insight into the molecular mechanisms of Tsp-related synaptic dysfunction.
Protection challenges in seat positions with large rearward adjustment in frontal collisions: An approach using stochastic human body model simulations

Novel seat positions enabled by self-driving cars have been investigated in various studies in recent years. However, there is little research on the effect of increased rearward seat adjustments. To predict challenges associated with the possibility to move the seat further backwards in the car than currently possible as driver, appropriate methods have to be defined. A detailed human body model, a THUMS v4.1 in particular, tissue-based injury risk evaluation methods, a generic vehicle interior and a Latin hypercube design of experiments taking the variability of real-world crashes into account was established. In a first step, 200 simulations at current representative seat positions and a driving occupant posture were performed. The results were then compared to field data from an accident database to evaluate the accuracy of the method. The predictions exceeded the injury risks for the abdomen, head, and upper extremities, while underestimating the risk for thoracic and lower extremity injuries. A good match was observed for injuries of the neck and spine. In a second step, the 200 simulations were run again, but with the seat adjusted rearwards significantly. In this seat configuration, with the exception of the head and the upper extremities, increased injury risks were predicted for all body regions. The highest increases affected the lower extremities (+28%)—predominantly pelvic fractures—and the neck (+9%). In addition, (partial) submarining occurred in almost 50% of cases with the rearward adjusted seat—as opposed to none in the conventional seat position. The established method could be used in future studies to design safety measures addressing these identified potential safety risks.
ZnO/Zn(OH)2 nanoparticles and self-cleaning coatings for the photocatalytic degradation of organic pollutants

Zinc oxide (ZnO) nanostructures have emerged as efficient heterogeneous photocatalysts for the degradation of organic pollutants in aqueous solutions and industrial wastewaters. In this work, a simple and effective method is reported for the synthesis of zinc oxide/zinc hydroxide (ZnO/Zn(OH)2) hybrid nanoparticles using a mineral acid to enhance the photocatalytic activity of ZnO. Infrared spectroscopy reveals the presence of hydroxyl groups in ZnO/Zn(OH)2 nanoparticles. X-ray diffraction shows the formation of hexagonal wurtzite ZnO nanoparticles, which retain their wurtzite structure after acid treatment but additional diffractions for Zn(OH)2 are also recorded. The optical bandgap of resulting ZnO and ZnO/Zn(OH)2 nanoparticles is reduced to 3.05 and 3.08 eV, respectively. In the initial photocatalysis experiments, ZnO/Zn(OH)2 nanoparticles exhibit 3.5-times improved degradation and removal of sunset yellow dye, a model organic pollutant, from deionized water compared to pristine ZnO nanoparticles. Hence, for further studies, ZnO/Zn(OH)2 coatings are fabricated on glass slides with a uniform surface morphology as shown by the atomic force microscopy. The time-dependent UV-visible spectroscopy reveals the photocatalytic degradation of sunset yellow over the surface of ZnO/Zn(OH)2 coatings. The degradation reaction follows the pseudofirst-order mechanism with a rate constant of 2.9 × 10–2 min−1. The recyclability and stability experiments reveal the retention of appreciable photocatalytic activity of ZnO/Zn(OH)2 coatings (with >92% degradation efficiency after six successive cycles). The results are compared with recent examples from the pertinent literature. The surface hydroxyl groups on ZnO/Zn(OH)2 nanoparticles and bandgap lowering enhance the anchoring of dye molecules and electron transfer reactions.
Understanding the contribution of metabolism to Mycobacterium tuberculosis drug tolerance

Treatment of Mycobacterium tuberculosis (Mtb) infections is particularly arduous. One challenge to effectively treating tuberculosis is that drug efficacy in vivo often fails to match drug efficacy in vitro. This is due to multiple reasons, including inadequate drug concentrations reaching Mtb at the site of infection and physiological changes of Mtb in response to host derived stresses that render the bacteria more tolerant to antibiotics. To more effectively and efficiently treat tuberculosis, it is necessary to better understand the physiologic state of Mtb that promotes drug tolerance in the host. Towards this end, multiple studies have converged on bacterial central carbon metabolism as a critical contributor to Mtb drug tolerance. In this review, we present the evidence that changes in central carbon metabolism can promote drug tolerance, depending on the environment surrounding Mtb. We posit that these metabolic pathways could be potential drug targets to stymie the development of drug tolerance and enhance the efficacy of current antimicrobial therapy.
Using different training strategies for urban land-use classification based on convolutional neural networks

Urban land-use scene classification from high-resolution remote-sensing imagery at high quality and accuracy is of paramount interest for urban planning, government policy-making and urban change detection. In recent years, urban land-use classification has become an ongoing task in areas addressable primarily by remote sensing, and numerous deep learning algorithms have achieved high performance on this task. However, both dataset and methodology problems still exist in the current approaches. Previous studies have relied on limited data sources, resulting in saturated classification results, and they have difficulty achieving comprehensive classification results. The previous methods based on convolutional neural networks (CNNs) focused primarily on model architecture rather than on the hyperparameters. Therefore, to achieve more accurate classification results, in this study, we constructed a new large dataset for urban land-use scene classification. More than thirty thousand remote sensing scene images were collected to create a dataset with balanced class samples that includes both higher intra-class variations and smaller inter-class dissimilarities than do the previously available public datasets. Then, we analysed two possible strategies for exploiting the capabilities of three existing popular CNNs on our datasets: full training and fine tuning. For each strategy, three types of learning rate decay were applied: fixed, exponential and polynomial. The experimental results indicate that fine tuning tends to be the best-performing strategy, and using ResNet-V1-50 and polynomial learning rate decay achieves the best results for the urban land-use scene classification task.
Impact of a probiotic chewable tablet on stool habits and microbial profile in children with functional constipation: A randomized controlled clinical trial

Constipation is a common and typically multifactorial childhood complaint, and the clinical management of childhood functional constipation (FC) is challenging. A randomized, single-blind, placebo-controlled, multi-center clinical trial was conducted in 92 children (47 from Beijing, China and 45 from Shanghai, China) aged 4–12 with FC according to Rome III criteria. Children were assigned to receive a probiotic chewable tablet (5 × 109 CFU/day, n = 47), consisting of Lactobacillus acidophilus DDS-1® and Bifidobacterium animalis subsp. lactis UABla-12™ or placebo (n = 45), twice daily for 4 weeks, followed by a week follow-up period. Results suggested that the probiotic group showed a faster and more pronounced normalization of stool frequency over the intervention period (3.15 vs. 1.83) when compared to placebo group (2.51 vs. 1.87). Meanwhile, the percentage of subjects with hard defecation decreased from 43 to 14% in the probiotic group, while the percentage of subjects with normal defecation increased from 56 to 80% in the probiotic group, further confirming the normalization of stools habits. This randomized controlled trial demonstrated the potential of a probiotic chewable tablet containing L. acidophilus DDS-1® and B. Lactis UABla-12™ as a daily probiotic dosage form for children with FC.
Coffee and caffeine consumption and risk of renal cell carcinoma: A Mendelian randomization study

Background The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association. Materials and methods In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10–8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources. Results The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512–1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10–8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676–1.125, p = 0.292). Conclusion Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.
A rapid and standardized workflow for functional assessment of bacterial biosensors in fecal samples

Gut metabolites are pivotal mediators of host-microbiome interactions and provide an important window on human physiology and disease. However, current methods to monitor gut metabolites rely on heavy and expensive technologies such as liquid chromatography-mass spectrometry (LC-MS). In that context, robust, fast, field-deployable, and cost-effective strategies for monitoring fecal metabolites would support large-scale functional studies and routine monitoring of metabolites biomarkers associated with pathological conditions. Living cells are an attractive option to engineer biosensors due to their ability to detect and process many environmental signals and their self-replicating nature. Here we optimized a workflow for feces processing that supports metabolite detection using bacterial biosensors. We show that simple centrifugation and filtration steps remove host microbes and support reproducible preparation of a physiological-derived media retaining important characteristics of human feces, such as matrix effects and endogenous metabolites. We measure the performance of bacterial biosensors for benzoate, lactate, anhydrotetracycline, and bile acids, and find that they are highly sensitive to fecal matrices. However, encapsulating the bacteria in hydrogel helps reduce this inhibitory effect. Sensitivity to matrix effects is biosensor-dependent but also varies between individuals, highlighting the need for case-by-case optimization for biosensors’ operation in feces. Finally, by detecting endogenous bile acids, we demonstrate that bacterial biosensors could be used for future metabolite monitoring in feces. This work lays the foundation for the optimization and use of bacterial biosensors for fecal metabolites monitoring. In the future, our method could also allow rapid pre-prototyping of engineered bacteria designed to operate in the gut, with applications to in situ diagnostics and therapeutics.
Elemental stoichiometry and insect chill tolerance: Evolved and plastic changes in organismal Na+ and K+ content in Drosophila

Acclimation and evolutionary adaptation can produce phenotypic change that allows organisms to cope with challenges like those associated with climate change. Determining the relative contributions of acclimation and adaptation is of central importance to understanding animal responses to change. Rates of evolution have traditionally been considered slow relative to ecological processes that shape biodiversity. Many organisms nonetheless show patterns of spatial genetic variation suggestive of adaptation and some evidence is emerging that adaptation can act sufficiently fast to allow phenotypic tracking in response to environmental change (‘adaptive tracking’). In Drosophila, both plastic and evolved differences in chill tolerance are associated with ionoregulation. Here we combine acclimation, latitudinal field collections, and a replicated field experiment to assess the effects of acclimation and adaptation on chill coma recovery and elemental (Na and K) stoichiometry in both sexes of Drosophila melanogaster. Acclimation and spatial adaptation both shape chill coma recovery, with acclimation producing the greatest magnitude response. Leveraging knowledge on the physiological mechanisms that underlie variation in chill tolerance traits, we find that the relationship between K content and chill tolerance differs among flies acclimated vs. adapted to cold. Taken together, these data reinforce the importance of acclimation in responses to abiotic challenges and illustrate that the mechanisms of phenotypic change can differ between acclimation and basal tolerance adaptation.
Effects andActionMechanismofHuoxue Tongluo Formula on the Formation of Neutrophil Extracellular Traps

Excessive inltration and uncontrolled activation of neutrophil extracellular traps (NETs) are likely to destroy normal tissue architecture and cause uncontrolled inammation. e present research attempted to screen potential signaling pathways of Huoxue Tongluo Formula (HXTLF) aecting the formation of NETs using network pharmacology technique. Active chemical components of HXTLF and therapeutic targets related to vasculitis were screened, and a chemical components-targets network diagram of HXTLF was constructed by Cytoscape. Finally, the inhibitory eect and mechanism of HXTLF on the formation of NETs were explored in vitro using LPS-induced NETs. Immunouorescence and Western blot were conducted to determine the protein uorescence intensity and relative expression. e experimental results illustrated that HXTLF mediated the expression levels of H3Cit and myeloperoxidase (MPO) protein in neutrophils activated by LPS, inhibited NETs formation, and reduced the concentration of interleukin(IL-) 1β, a proinammatory factor in cells. Additionally, we activated and inhibited the AKT1 signaling pathway using the corresponding activator and inhibitor to explore the regulatory mechanism of HXTLF on AKT1 and other molecules in the treatment of vasculitis. e results demonstrated that HXTLF could inhibit the phosphorylation of AKT1, IKK, and NF-κB proteins, inhibit NETs formation, and reduce IL-1β concentration, indicating that AKT1 exerts a vital role in the treatment of vasculitis after HXTLF administration. e current study initially revealed the pharmacological mechanism of HXTLF for vasculitis management using network pharmacology techniques and tests in vitro, which is expected to provide important theoretical basis for elucidating the molecular mechanism of HXTLF and promoting its clinical application.
Randomization Systems and Technology

When we compare treatments we want to make sure that the two groups are as alike as possible so that the comparison is a fair one. We want to be confident that any di ﬀ er-encebetweenthegroupsisduetoour treatmentandnotto other factors thatdi ﬀ erentiatethetwo groups. For this reason we have to be careful about how we allocate patients into study groups, and this chapter will describe the various methods used to accomplish this.
Expiring neighborhood: Architecture as a tool for marketing ?home? in Istanbul/Turkey

Istanbul is one of the metropolitan areas connected to the globe in many ways. Since 1980, Turkey is open to the effects of the consumer culture. TV series, imported goods, brand names, commercials, working practices, etc. changed not only our everyday life, but our values as well. Competing? , ? show off? and ? money? are the basic motivation for the society instead of ? solidarity? , ? sensitivity? and ? respect? Architecture is in use of the economy policy as one of the tools supporting the social change towards a capital oriented mass. The criterion to buy a house is its exchange value instead of its use value as a ? home? A house is not considered as a ? home ? to enjoy our individual/family life any more. Masses are being manipulated to think the house as an asset for investment on sale. The program and the spatial organization of the houses depend on the rules of marketing, instead of beauty, strength, or use as it used to be in the history of architecture.Considering the percentage of housing in the context of the built environment, and the effect of the space on the human mind/body, it is easy to imagine this consumerist approach of housing will cause a big change on the urban dynamics. The neighborhoods in Istanbul are already under attack of the contractor companies. High-rise residences with some commercial facilities have been constructed and sold for high prices. In a short period, this pattern of production has become a conventional practice of the production of housing. This paper presents a fragment from the current everyday life in Istanbul drifting attention to the contradiction in-between the demands of the housing market and the embedded value of the societal relations at the neighborhoods. The target is showing the upcoming danger of losing the human values, values of architecture and the city as a living organism, and questioning the possibilities for a better future.
. 3 Towards Classification of Technical Sound Events with Deep Learning Models

: Sounds of machines and mechanical systems contain a lot of information about the observed object and its state. Experienced engineers and technical service staff can often identify or classify a certain technical object with state via its sound. An equivalent automated system with such capabilities is difficult to realise because of noisy unknown surroundings. In this paper, we show an approach to implement the mentioned characteristics with deep learning methods and enhance the power of a technical assistance system.
Reachability Analysis of Subconservative Discrete Chemical Reaction Networks

In this paper, we give a computational solution for the reachability problem of subconservative discrete chemical reaction networks (d-CRNs), namely whether there exists a valid state transition (reaction) sequence between a given initial and a target state. Using subconservativity, we characterize the reachable set of the d-CRN with well-deﬁned simplexes. Moreover, upper bounds are derived for the possible length of cycle-free state transition sequences. We show that the reachability and the related coverability problem in the case of subconservative d-CRNs can be decided in polynomial time by tracing them back to ﬁxed dimensional integer programming (IP) feasibility problems over a bounded integer lattice. The proposed computation model is also employed for determining feasible series of reactions be-tween given (sets of) states. We also show that if the rank of the stoichiometric matrix is less than or equal to 2, then the reachability problem is equivalent to the existence of a non-negative integer solution of the corresponding state equation.
Sacroperineal Reconstruction With Inferior Gluteal Artery Perforator Flaps After Resection of Locally Advanced Primary and Recurrent Anorectal Malignancy

Abstract Modern interdisciplinary concepts with involvement of various surgical specialties can considerably reduce perioperative morbidity after sacroperineal resection of locally advanced primary or recurrent anorectal malignancies. Resultant defects can represent a major challenge for reconstruction particularly with chemoradiotherapy. The aim is to assess the long-term outcomes of sacroperineal reconstruction using inferior gluteal artery perforator flaps. We performed a retrospective data analysis on 31 patients who were treated with inferior gluteal artery perforator flaps (n = 61) over the period 2009–2021. The demographic data, comorbidities, operative details, and outcomes with special focus on wound infection and dehiscence were recorded. The median age was 42 year (range, 25–82 years) with preponderance of males (n = 21). The follow-up period ranged from 6 to 80 months. Early minor complications included superficial wound dehiscence (3), which was managed conservatively, whereas the major (2) included deep wound collection and infection (1), which required surgical drainage, and perineal hernia, which required repair. All flaps survived completely. Inferior gluteal artery perforator flaps are safe, robust, and reliable with less donor side morbidity and positive impact on quality of life. It should be considered as a valuable tool in the reconstructive armamentarium of sacroperineal defects within a multidisciplinary setting.
Bose-Einstein Condensation on Holographic Screens

Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha, Iran, P. O. Box: 55134-441We consider a boson gas on holographic screens of the Rindler and Schwartzschild spacetimes. It is shownthat the gas on the stretched horizon isin a Bose-Einstein condensed statewith the Hawking temperature T