Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioprinting and Preliminary Testing of Highly Reproducible Novel Bioink for Potential Skin Regeneration

Three-dimensional (3D) bioprinting is considered as a novel approach in biofabricating cell-laden constructs that could potentially be used to promote skin regeneration following injury. In this study, a novel crosslinked chitosan (CH)–genipin (GE) bioink laden with keratinocyte and human dermal fibroblast cells was developed and printed successfully using an extruder-based bioprinter. By altering the composition and degree of CH–GE crosslinking, bioink printability was further assessed and compared with a commercial bioink. Rheological analysis showed that the viscosity of the optimised bioink was in a suitable range that facilitated reproducible and reliable printing by applying low pressures ranging from 20–40 kPa. The application of low printing pressures proved vital for viability of cells loaded within the bioinks. Further characterisation using MTT assay showed that cells were still viable within the printed construct at 93% despite the crosslinking, processing and after subjecting to physiological conditions for seven days. The morphological study of the printed cells showed that they were mobile within the bioink. Furthermore, the multi-layered 3D printed constructs demonstrated excellent self-supportive structures in a consistent manner.
Statistical Perspectives of Stochastic Optimization

In this technical note, we leverage theory from stochastic approximations to characterize the asymptotic variance of a general class of stochastic optimization procedures. We show that one approach to tuning parameters of such procedures is to minimize the asymptotic variance, and we illustrate such tuning in simulations. Using this result, we also obtain new statistical insights on popular methods employing mini-batches, adaptive gradients, and variance reduction.
Genetically Encoded Tools for Research of Cell Signaling and Metabolism under Brain Hypoxia

Hypoxia is characterized by low oxygen content in the tissues. The central nervous system (CNS) is highly vulnerable to a lack of oxygen. Prolonged hypoxia leads to the death of brain cells, which underlies the development of many pathological conditions. Despite the relevance of the topic, different approaches used to study the molecular mechanisms of hypoxia have many limitations. One promising lead is the use of various genetically encoded tools that allow for the observation of intracellular parameters in living systems. In the first part of this review, we provide the classification of oxygen/hypoxia reporters as well as describe other genetically encoded reporters for various metabolic and redox parameters that could be implemented in hypoxia studies. In the second part, we discuss the advantages and disadvantages of the primary hypoxia model systems and highlight inspiring examples of research in which these experimental settings were combined with genetically encoded reporters.
The Tone from Above: The Effect of Communicating a Supportive Regulatory Strategy on Reporting Quality

In collaboration with the Authority for the Financial Markets in the Netherlands, we manipulate the content of official letters that instruct financial intermediaries to submit a mandatory self‐assessment. As part of the Registered Report Process, we submitted our hypotheses, experimental procedure, and planned statistical analyses before data collection. We predicted that a request indicating a supportive regulatory attitude has a positive effect on reporting quality on average. We also predicted this effect to be stronger for small firms and for firms with a long‐term orientation, and to become negative for firms with a short‐term orientation. Planned analyses show that a supportive letter reduced reporting quality unless firms had a long‐term orientation, supporting the moderating influence of time horizon, but providing no support for the expected average effect or for moderation by firm size.
Sedentary Behavior and the Use of Wearable Technology: An Editorial

Globally, we continue to face a mounting issue of obesity combined with inactivity; sedentary behaviour is independently associated with poor health outcomes including disease and mortality. As such, exploring ways to try to reduce sedentary behaviour and decrease the risk of diseases is an important area of consideration. The role of wearable technology, such as fitness trackers, to encourage and subsequently increase physical activity is relatively well documented. These devices have been successful at encouraging populations to increase daily activity levels. While time being sedentary is often correlated with physical activity participation, this is not always the case. Therefore, it may be just as important to consider the activity an individual is not doing when evaluating health and well-being. This Editorial will summarize the importance of distinguishing between physical activity and sedentary behaviour. It will also discuss how wearable technology, in the form of fitness trackers, may be used to encourage someone to break up sedentary bouts more often. Finally, we will consider important future research directions.
Analytical Modelling and Optimization of a Piezoelectric Cantilever Energy Harvester with In-Span Attachment

In this paper, the location of masses and of a piezoelectric patch for energy harvesting reported onto a vibrating cantilever beam is studied and optimized. To this aim, a genetic algorithm is adapted and utilized to optimize the voltage amplitude generated by the piezoelectric patches by choosing attachment mass, attachment mass moment of inertia, attachment location, piezoelectric patch location and force location on the beam as parameters. While an analytical approach is proposed to evaluate the voltage amplitude, a multi-layer perceptron neural network is trained by the derived characteristic matrix to obtain an approximate function for natural frequencies based on the attachment parameters. The trained network is then used in the core of genetic algorithm to find the best optimization variables for any excitation frequency. Numerical simulation by COMSOL Multiphysics finite element software validates the calculated voltage by analytical approach. The optimization method successfully matches the natural frequency of the beam with the excitation frequency which therefore maximizes the output energy. On the other hand, the superiority of the optimized design over the conventional configuration in harvesting the energy at high frequency excitation is also approved.
Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays

Inherited retinal dystrophies and optic neuropathies cause chronic disabling loss of visual function. The development of recombinant adeno-associated viral vectors (rAAV) gene therapies in all disease fields have been promising, but the translation to the clinic has been slow. The safety and efficacy profiles of rAAV are linked to the dose of applied vectors. DNA changes in the rAAV gene cassette affect potency, the expression pattern (cell-specificity), and the production yield. Here, we present a library of rAAV vectors and elements that provide a workflow to design novel vectors. We first performed a meta-analysis on recombinant rAAV elements in clinical trials (2007–2020) for ocular gene therapies. We analyzed 33 unique rAAV gene cassettes used in 57 ocular clinical trials. The rAAV gene therapy vectors used six unique capsid variants, 16 different promoters, and six unique polyadenylation sequences. Further, we compiled a list of promoters, enhancers, and other sequences used in current rAAV gene cassettes in preclinical studies. Then, we give an update on pro-viral plasmid backbones used to produce the gene therapy vectors, inverted terminal repeats, production yield, and rAAV safety considerations. Finally, we assess rAAV transgene and bioactivity assays applied to cells or organoids in vitro, explants ex vivo, and clinical studies.
The Analysis of the Urban Sprawl Measurement System of the Yangtze River Economic Belt, Based on Deep Learning and Neural Network Algorithm

In the context of rapid urbanization, the spread of cities in the Yangtze River Economic Belt is intensifying, which has an impact on the green and sustainable development of these cities. It is necessary to establish an accurate urban sprawl measurement system. First, the regulation theory of urban sprawl is explained. According to the actual development situation of cities in the Yangtze River Economic Belt, smart growth theory is selected as the basic regulation method of urban sprawl. Second, the back propagation neural network (BPNN) algorithm under deep supervised learning is applied to construct a smart evaluation model of land use growth. Finally, based on the actual development of cities in the Yangtze River Economic Belt, the quantitative growth measurement method is selected to construct a measurement system of urban sprawl in the Yangtze River Economic Belt, and the empirical analysis is carried out. The training results show that the proposed BPNN smart growth evaluation model, based on deep supervised learning, has good evaluation accuracy, and the error is within the preset range. The analysis of the quantitative growth-based measurement system in the increase of urban construction land shows that the increase in urban construction land area of the Yangtze River Economic Belt from 2014 to 2019 was 78.67 km2. Meanwhile, the increases in urban construction land area in different years are different. The empirical results show that the population composition of the Yangtze River Economic Belt and the urban construction area between 2005 and 2019 show a trend of increasing annually; at the same time, urban sprawl development shows a staged characteristic. It is of great significance to apply deep learning fusion neural network algorithm in the construction of the urban sprawl measurement system, which provides a quantitative basis for the in-depth analysis and discussion of urban sprawl.
Characterization of concurrent target suppression by JNJ-61178104, a bispecific antibody against human tumor necrosis factor and interleukin-17A

ABSTRACT Tumor necrosis factor (TNF) and interleukin (IL)-17A are pleiotropic cytokines implicated in the pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). JNJ-61178104 is a novel human anti-TNF and anti-IL-17A monovalent, bispecific antibody that binds to both human TNF and human IL-17A with high affinities and blocks the binding of TNF and IL-17A to their receptors in vitro. JNJ-61178104 also potently neutralizes TNF and IL-17A-mediated downstream effects in multiple cell-based assays. In vivo, treatment with JNJ-61178104 resulted in dose-dependent inhibition of cellular influx in a human IL-17A/TNF-induced murine lung neutrophilia model and the inhibitory effects of JNJ-61178104 were more potent than the treatment with bivalent parental anti-TNF or anti-IL-17A antibodies. JNJ-61178104 was shown to engage its targets, TNF and IL-17A, in systemic circulation measured as drug/target complex formation in normal cynomolgus monkeys (cyno). Surprisingly, quantitative target engagement assessment suggested lower apparent in vivo target-binding affinities for JNJ-61178104 compared to its bivalent parental antibodies, despite their similar in vitro target-binding affinities. The target engagement profiles of JNJ-61178104 in humans were in general agreement with the predicted profiles based on cyno data, suggesting similar differences in the apparent in vivo target-binding affinities. These findings show that in vivo target engagement of monovalent bispecific antibody does not necessarily recapitulate that of the molar-equivalent dose of its bivalent parental antibody. Our results also offer valuable insights into the understanding of the pharmacokinetics/pharmacodynamics and target engagement of other bispecific biologics against dimeric and/or trimeric soluble targets in vivo.
Absence of HTATIP2 Expression in A549 Lung Adenocarcinoma Cells Promotes Tumor Plasticity in Response to Hypoxic Stress

HIV-1 Tat Interactive Protein 2 (HTATIP2) is a tumor suppressor, of which reduced or absent expression is associated with increased susceptibility to tumorigenesis and enhanced tumor invasion and metastasis. However, whether the absent expression of HTATIP2 is a tumor-promoting factor that acts through improving tumor adaptation to hypoxia is unclear. Here, we established a stable HTATIP2-knockdown A549 human lung adenocarcinoma cell line (A549shHTATIP2) using lentiviral-delivered HTATIP2-targeting short hairpin RNA (shRNA), employed a double subcutaneous xenograft model and incorporated photoacoustic imaging and metabolomics approaches to elucidate the impact of the absent HTATIP2 expression on tumor response to hypoxic stress. Results from the in vivo study showed that A549shHTATIP2 tumors exhibited accelerated growth but decreased intratumoral oxygenation and angiogenesis and reduced sensitivity to sorafenib treatment as compared with their parental counterparts. Moreover, results of the immunoblot and real-time PCR analyses revealed that the HIF2α protein and mRNA levels in vehicle-treated A549shHTATIP2 tumors were significantly increased (p < 0.01 compared with the parental control tumors). Despite the strong HIF2α-c-Myc protein interaction indicated by our co-immunoprecipitation data, the increase in the c-Myc protein and mRNA levels was not significant in the A549shHTATIP2 tumors. Nonetheless, MCL-1 and β-catenin protein levels in A549shHTATIP2 tumors were significantly increased (p < 0.05 compared with the parental control tumors), suggesting an enhanced β-catenin/c-Myc/MCL-1 pathway in the absence of HTATIP2 expression. The finding of significantly decreased E-cadherin (p < 0.01 compared with vehicle-treated A549shHTATIP2 tumors) and increased vimentin (p < 0.05 compared with sorafenib-treated A549 tumors) protein levels in A549shHTATIP2 tumors implicates that the absence of HTATIP2 expression increases the susceptibility of A549 tumors to sorafenib-activated epithelial-mesenchymal transition (EMT) process. Comparison of the metabolomic profiles between A549 and A549shHTATIP2 tumors demonstrated that the absence of HTATIP2 expression resulted in increased tumor metabolic plasticity that enabled tumor cells to exploit alternative metabolic pathways for survival and proliferation rather than relying on glutamine and fatty acids as a carbon source to replenish TCA cycle intermediates. Our data suggest a mechanism by which the absent HTATIP2 expression modulates tumor adaptation to hypoxia and promotes an aggressive tumor phenotype by enhancing the HIF2α-regulated β-catenin/c-Myc/MCL-1 signaling, increasing the susceptibility of tumors to sorafenib treatment-activated EMT process, and improving tumor metabolic plasticity.
WHOLE ROCK GEOCHEMISTRY AND TECTONIC SETTING OF JURASSIC AGED LISAR GRANITE, TALESH MOUNTAINS, NORTH IRAN

Kuzey Iran’daki Gec Jura yasli Lisar graniti, Ust Kretase kumlu kirectaslari ile bindirme ve dogrultu atimli faylar araciligiyla tektonik iliskili olup, Elburz kusaginin batidaki devami olan Talis Dagi’nda Paleosen yasli polijenik konglomeralar tarafindan ortulmektedir. Granite ait kayac numuneleri pembe renkli ve iri kristalli olup; K-feldispat, kuvars, plajiyoklaz, biyotit ve amfi bol icermektedir. Kayaclar icerisindeki bosluklari dolduran cok sayidaki silikaca zengin aplitik damarlarin isaret ettigi sekilde, Lisar granitinin genislemeli bir ortamda yerlesmis olmasi muhtemeldir. Granit ornekleri orta duzeyde altere olup; feldispatlar serizite, kil mineralleri ve biyotitler ise kismen klorite donusmustur. Lisar graniti yuksek potasyumlu bir magmadan turemis olup, A tipi karakter sunmakta ve A2 alt grubundandir. Granite ait kayac ornekleri belirgin negatif Eu anomalisi ve hafi f nadir toprak elementleri (NTE) iceriginden agir nadir toprak elementleri (NTE) icerigine dogru bir azalma ile karakterize edilir. Graniti olusturan eriyikler, manto malzemesinden gelen olasi katkilar ile birlikte, alt kitasal kabugun kismi ergimesinden kaynaklanmistir. Lisar graniti, Paleotetis Okyanusunun kapanmasi ve devaminda gelen carpismalari takip eden, Kuzey Iran’daki Kimmeriyen carpisma sonrasi magmatizmasini temsil etmektedir.
A Software Framework for Heterogeneous Wireless Sensor Network Towards Environmental Monitoring

A wireless sensor network (WSN) is typically composed of spatially distributed miniature sensors that help collect large amounts of real-time environmental data from buildings. These environmental data (e.g., temperature, humidity, CO2 concentration) can assist a series of heating, ventilation, and air conditioning (HVAC) equipment to increase the building energy efficiency. From a system design perspective, heterogeneous wireless sensor networks need to address two challenges. First, sensor data acquisition, conversion, fusion, and packaging involve a series of software processing. Since each type of environmental sensor typically has unique processing requirements, it is difficult to develop an efficient software framework to combine the processing of multiple heterogeneous sensors. Second, during normal operation of a heterogeneous wireless sensor network, if users insert or remove some environmental sensors, the entire WSN system should operate normally. In this work, in order to solve the above two system design challenges, we have developed a low-power, low-cost, small form-factor WSN development platform, and its software framework can perform efficient data acquisition, conversion, fusion, and packaging for multiple heterogeneous sensors. Our proposed software framework enables easy and rapid WSN system deployment without affecting the overall functionality of each node. The proposed design differs from existing WSN platforms in that it emphasizes advanced high-level usability and reduces time to market without sacrificing low-level features. The proposed WSN system has been implemented and tested in an office building for indoor fire hazard detection. The experimental results show that our software framework can successfully complete data acquisition, conversion, fusion, and packaging tasks for three heterogeneous environmental sensors. In addition, we have verified that our software framework supports robust system operation when inserting or removing sensors from an existing heterogeneous WSN system.
TERDIURNAL TIDES IN THE MLT REGION OVER CACHOEIRA PAULISTA ( 22 . 7 ◦ S ; 45 ◦ W )

Five years of winds measurements obtained by a SkiYmet meteor radar at Cachoeira Paulista (22.7◦S, 45.0◦W) are used to investigate the terdiurnal tide. This type of tide is frequently observed in the meteor region but the mechanisms responsible for its production are not yet completely explained. Among the possible causes are solar direct forcing and nonlinear interactions between the diurnal and semidiurnal tides. Nonlinear interaction between diurnal and semidiurnal tides can generate two secondary waves: a diurnal tide and a terdiurnal tide. The origin and seasonal distribution of the terdiurnal tide may indicate the presence of a secondary diurnal tide as a cause of variability in the primary diurnal tide. In this work we analyze the winds data in search of evidence for these mechanisms.
Computed tomography-based diagnosis of occult fragility hip fractures offer shorter waiting times with no inadvertent missed diagnosis

Purpose: Surgical delay due to the wait for advanced cross-sectional imaging in occult fragility hip fracture management is not well studied. Our study aims to investigate computed tomography (CT) as an alternative to the gold standard magnetic resonance imaging (MRI) in occult hip fracture workup to decrease surgical delay. Methods: We conducted a retrospective review of all CTs and MRIs performed between 2015 and 2017 for patients with clinically suspected fragility hip fractures and negative plain radiographs to investigate surgical delay resulting from the wait for advanced imaging and representations due to missed fractures. Results: A total of 243 scans (42 CTs and 201 MRIs) were performed for occult hip fracture workup over the study timeframe, of which 49 patients (20%) had occult hip fractures [CT: 6 (14%), MRI: 43 (21%), p = 0.296)]. There were no readmissions for fracture in the 12 months following a negative scan. The CT group had shorter waiting times (CT: 29 ± 24 h, MRI: 44 ± 32 h, p = 0.004) without significantly reducing surgical delay (CT: 82 ± 36 h, MRI: 128 ± 58 h, p = 0.196). The MRI group had a higher number of patients with a cancer history (p = 0.036), reflective of the practice for workup of possible metastases as a secondary intention. Conclusion: Advanced cross-sectional imaging wait times in occult hip fracture workup contribute significantly to surgical delay. Modern CT techniques are not inferior to MRI in detecting occult fractures and may be a suitable alternative in the absence of a cancer history if MRI cannot be obtained in a timely fashion or is contraindicated. Clinicians should utilize the more readily available imaging modality to reduce surgical delay.
Prior exposure of agriculture cephalosporin ceftiofur impaired conjugation of blaCTX‐M‐65 gene‐bearing plasmid in Salmonella Saintpaul

Although a link between agricultural cephalosporin use and resistance in Salmonella has been demonstrated with the drug ceftiofur, the underlying mechanism of the correlation is unclear. This study investigated the impact of ceftiofur exposure in S. Saintpaul on ceftriaxone resistance, the gene expression and the conjugative transfer of the blaCTX‐M‐65 gene.
Geometric background charge: dislocations on capillary bridges

Recent experiments have shown that colloidal crystals confined to weakly curved capillary bridges introduce groups of dislocations organized into ‘pleats’ as means to relieve the stress caused by the Gaussian curvature of the surface. We consider the onset of this curvature-screening mechanism, by examining the energetics of isolated dislocations and interstitials on capillary bridges with free boundaries. The boundary provides an essential contribution to the problem, akin to a background charge that “neutralizes” the unbalanced integrated curvature of the surface. This makes it favorable for topologically neutral dislocations and groups of dislocations – rather than topologically charged disclinations and scars – to relieve the stress caused by the unbalanced Gaussian curvature of the surface. This effect applies to any crystal on a surface with non-vanishing integrated Gaussian curvature and stress-free boundary conditions. We corroborate the analytic results by numerically computing the energetics of a defective lattice of springs confined to surfaces with weak positive and negative curvatures.