Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing uncertainties from physical parameters and modelling choices in an atmospheric large eddy simulation model

In this study, we investigate uncertainties in a large eddy simulation of the atmosphere, employing modern uncertainty quantification methods that have hardly been used yet in this context. When analysing the uncertainty of model results, one can distinguish between uncertainty related to physical parameters whose values are not exactly known, and uncertainty related to modelling choices such as the selection of numerical discretization methods, of the spatial domain size and resolution, and the use of different model formulations. While the former kind is commonly studied e.g. with forward uncertainty propagation, we explore the use of such techniques to also assess the latter kind. From a climate modelling perspective, uncertainties in the convective response and cloud formation are of particular interest, since these affect the cloud-climate feedback, one of the dominant sources of uncertainty in current climate models. Therefore we analyse the DALES model in the RICO case, a well-studied convection benchmark. We use the VECMA toolkit for uncertainty propagation, assessing uncertainties stemming from physical parameters as well as from modelling choices. We find substantial uncertainties due to small random initial state perturbations, and that the choice of advection scheme is the most influential of the modelling choices we assessed. This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantification in silico’.
Loss or Gain? Unpacking Nonprofit Autonomy-Interdependence Paradox in Collaborations

Nonprofit organizations interested in collaborating with other entities find it difficult to strike a balance between keeping their autonomy and reaping the benefits from collaborating with other organizations. Although interorganizational collaborations come with various benefits, such as reducing competition over limited resources, participating in collaborative relationships can also damage the autonomy of individual nonprofits. Using an original survey of 275 nonprofits, we examine how various dimensions of collaborative relationships affect an individual nonprofit’s autonomy. Our findings suggest that having highly specified administrative arrangements and stronger trust as well as reciprocity among partner organizations serve as critical factors to secure the autonomy of individual organizations. We also find that nonprofit organizations engaged in mostly informal relationships and in partnerships across sectors feel less threatened about maintaining their autonomy. Our post hoc analysis further suggests that organizational autonomy is a significant antecedent for seeking more collaborations. To this end, we discuss how nonprofits can keep their organizational autonomy without giving up collaborating with other entities by strategically managing several aspects of the collaborative relationships.
“I Assumed He Didn’t Exist”: The Birth Father as the Invisible Member of the Adoption Kinship Network

Historically, paternity has been constructed on the basis of uncertainty. Men and fathers have been underrepresented in studies of reproductive processes and parenting. In adoption, the figure of the birth father has been invisibilized and stereotyped. As part of a qualitative study of origins, identity, and adoption, carried out in Chile, the narratives about their birth father of adults, who had been adopted and sought their origins, were analyzed. The results show that (a) most interviewees had not thought to seek their birth father because they assumed he “did not exist”; (b) information about him is mediated by the birth mother, who acts as a gatekeeper; and (c) when the figure is present, it is usually depersonalized as genetic material or personalized negatively. The birth father omission in the adoption process poses challenges for both past and contemporary adoptions, in which birth fathers are ever more visible and heterogeneous.
Anxieties and Coping among Filipino New Fathers with Postnatal Depression

Existing evidence suggests that postnatal depression is common in fathers of newborns among low- and middle-income countries because parents from this region experience socioeconomic difficulties. Common socioeconomic difficulties include educational attainment, employment status, and monthly income. Through the number of available participants, this study screened 50 new fathers coming from barangays of Cabanatuan City, Province of Nueva Ecija, Philippines. This study made use of the Becks Depression Inventory to carefully select new fathers without depression before childbirth. Remaining participants were administered Edinburgh Postnatal Depression Scale (EPDS) and Gotland Male Depression Scale (GMDS) 24–72 hours after the childbirth. From this, the researcher was left with seven new fathers who were invited for an in-depth interview. Using the role strain theory and depressive symptoms from the EPDS and GMDS, the researcher drafted a general idea of where to begin the interview. Structured questions were followed to meet the theoretical sensitivity and domains of the tools used (EPDS and GMDS). Qualitative analysis revealed FEAR among new fathers with Postnatal Depression coming from difficulties in financial responsibility, emotional responses, adaptability and role transition.
EFFECT OF OPERATING PARAMETERS ON THE SEPARATION OF SUGARS BY NANOFILTRATION

ABSTRACT Due to the complexity of fermentation mixtures, separation of solutes and secondary substrates has a special importance. Membrane processes such as nanofiltration may offer good alternatives for the separation of fermentation products or recovery of substrates. For an efficient separation, the membrane type and operating parameters such as feed flow rate, operating pressure, and feed should be optimized. In this study the separation and recovery of sugars were targeted. It was found that with an increase of the feed flow rate, permeate flux increased since the effect of concentration polarization was minimized. As a result, experiments were carried out at the highest possible flow rate. The effect of pressure was studied at five pressures (10–50 bar). It was found that there is a linear relationship between the pressure and permeate flux up to 30 bars. Beyond 30 bars the effect of pressure became less significant. Thus, 30 bars was chosen as the operating pressure. To investigate the effect of co.
Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria

The tumor microenvironment is characterized by anomalous vascularization, hypoxia, and acidity at the core of solid tumors that culminates in concentrated necrosis and immune system dysregulation among other effects. While this environment presents several challenges for the development of oncotherapeutics that deliver their activity via the enhanced permeability and retention (EPR) effect of the leaky blood vessels around a tumor, oncolytic bacteria, or a class of bacteria with a noted capacity to lyse solid tumors, are attracted to the very environment found at the center of solid tumors that confounds other therapeutics. It is this capacity that allows for a potent, active penetration from the tumor margins into the core, and subsequent colonization to facilitate lysis and immune reactivation. Clostridium novyi in particular has recently shown great promise in preclinical and clinical trials when administered directly to the tumor. These studies indicate that C. novyi is uniquely poised to effectively accomplish the long sought after “holy grail” of oncotherapeutics: selective tumor localization via intravenous delivery. This study reports the development of efficient methods that facilitate experimental work and therapeutic translation of C. novyi including the ability to work with this obligate micro-anaerobe on the benchtop. Additionally, this study seeks to utilize this newfound experimental flexibility to address several gaps in the current knowledge regarding the efficacy of CRIPSR/Cas9-mediated gene insertion in this species to further develop this oncolytic bacteria and the genetic customization of bacteria in general.
Identification and Regulation of Tomato Serine/Arginine-Rich Proteins Under High Temperatures

Alternative splicing is an important mechanism for the regulation of gene expression in eukaryotes during development, cell differentiation or stress response. Alterations in the splicing profiles of genes under high temperatures that cause heat stress (HS) can impact the maintenance of cellular homeostasis and thermotolerance. Consequently, information on factors involved in HS-sensitive alternative splicing is required to formulate the principles of HS response. Serine/arginine-rich (SR) proteins have a central role in alternative splicing. We aimed for the identification and characterization of SR-coding genes in tomato (Solanum lycopersicum), a plant extensively used in HS studies. We identified 17 canonical SR and two SR-like genes. Several SR-coding genes show differential expression and altered splicing profiles in different organs as well as in response to HS. The transcriptional induction of five SR and one SR-like genes is partially dependent on the master regulator of HS response, HS transcription factor HsfA1a. Cis-elements in the promoters of these SR genes were predicted, which can be putatively recognized by HS-induced transcription factors. Further, transiently expressed SRs show reduced or steady-state protein levels in response to HS. Thus, the levels of SRs under HS are regulated by changes in transcription, alternative splicing and protein stability. We propose that the accumulation or reduction of SRs under HS can impact temperature-sensitive alternative splicing.
MACC1 Is Associated With Epithelial–Mesenchymal Transition and Can Predict Poor Prognosis in Nasopharyngeal Carcinoma

Background Given the reported correlation between the oncogene metastasis-associated in colon cancer 1 (MACC1) and nasopharyngeal carcinoma (NPC), as well as between MACC1 and epithelial–mesenchymal transition (EMT), we speculated that EMT is a likely causative link between MACC1 expression and poor NPC prognosis. Thus, we aim to clarify the relationship between MACC1 and EMT in NPC prognosis. Material and Methods We performed immunohistochemical examination of tissue sections from 128 NPC patients that were divided into six groups corresponding to high and low protein expression of MACC1 and two EMT-related proteins, vimentin and E-cadherin, and Kaplan–Meier (KM) survival analyses were performed. Results KM survival analysis showed that upregulation of MACC1 and vimentin and downregulation of E-cadherin were significantly associated with reduced survival in NPC. Short hairpin RNA (shRNA) interference and immunoblotting in the NPC cell line HNE-1 led to increased E-cadherin but decreased vimentin levels. MACC1 overexpression was significantly correlated with poor 5-year overall survival, metastasis-free survival, and disease-free survival (P<0.05) but not with poor relapse-free survival (P>0.05). Univariate analyses revealed that MACC1, E-cadherin, and vimentin levels along with T and N tumor classifications and cancer staging are significant prognostic factors of NPC (P<0.05). Conclusion Our findings showed the association between MACC1 and EMT in NPC malignancy and support the role of MACC1 as a prognostic biomarker and molecular target for NPC treatment.
Weighted Gene Co-expression Network Analysis Reveals Different Immunity but Shared Renal Pathology Between IgA Nephropathy and Lupus Nephritis

Both IgA nephropathy (IgAN) and lupus nephritis (LN) are immunity-related diseases with a complex, polygenic, and pleiotropic genetic architecture. However, the mechanism by which the genetic variants impart immunity or renal dysfunction remains to be clarified. In this study, using gene expression datasets as a quantitative readout of peripheral blood mononuclear cell (PBMC)- and kidney-based molecular phenotypes, we analyzed the similarities and differences in the patterns of gene expression perturbations associated with the systematic and kidney immunity in IgAN and LN. Original gene expression datasets for PBMC, glomerulus, and tubule from IgAN and systemic lupus erythematosus (SLE) patients as well as corresponding controls were obtained from the Gene Expression Omnibus (GEO) database. The similarities and differences in the expression patterns were detected according to gene differential expression. Weighted gene co-expression network analysis (WGCNA) was used to cluster and screen the co-expressed gene modules. The disease correlations were then identified by cell-specific and functional enrichment analyses. By combining these results with the genotype data, we identified the differentially expressed genes causatively associated with the disease. There was a significant positive correlation with the kidney expression profile, but no significant correlation with PBMC. Three co-expression gene modules were screened by WGCNA and enrichment analysis. Among them, blue module was enriched for glomerulus and podocyte (P < 0.05) and positively correlated with both diseases (P < 0.05), mainly via immune regulatory pathways. Pink module and purple module were enriched for tubular epithelium and correlated with both diseases (P < 0.05) through predominant cell death and extracellular vesicle pathways, respectively. In genome-wide association study (GWAS) enrichment analysis, blue module was identified as the high-risk gene module that distinguishes LN from SLE and contains PSMB8 and PSMB9, the susceptibility genes for IgAN. In conclusion, IgAN and LN showed different systematic immunity but similarly abnormal immunity in kidney. Immunological pathways may be involved in the glomerulopathy and cell death together with the extracellular vesicle pathway, which may be involved in the tubular injury in both diseases. Blue module may cover the causal susceptibility gene for IgAN and LN.
Autofocusing Algorithm for Pixel-Super-Resolved Lensfree On-Chip Microscopy

In recent years, lensfree on-chip microscopy has developed into a promising and powerful computational optical microscopy technique that allows for wide-field, high-throughput microscopic imaging without using any lenses. However, due to the limited pixel size of the state-of-the-art image sensors, lens-free on-chip microscopy generally suffers from low imaging resolution, which is far from enough to meet the current demand for high-resolution microscopy. Many pixel super-resolution techniques have been developed to solve or at least partially solve this problem by acquiring a series of low-resolution holograms with multiple lateral sub-pixel shifting or axial distances. However, the prerequisite of these pixel super-resolution techniques is that the propagation distance of each low-resolution hologram can be obtained precisely, which faces two major challenges. On the one hand, the captured hologram is inherent pixelated and of low resolution, making it difficult to determine the focal plane by evaluating the image sharpness accurately. On the other hand, the twin-image is superimposed on the backpropagated raw hologram, further exacerbating the difficulties in accurate focal plane determination. In this study, we proposed a high-precision autofocusing algorithm for multi-height pixel-super-resolved lensfree on-chip microscopy. Our approach consists of two major steps: individual preliminary estimation and global precise estimation. First, an improved critical function that combines differential critical function and frequency domain critical function is proposed to obtain the preliminary focus distances of different holograms. Then, the precise focus distances can be determined by further evaluating the global offset of the averaged, low-noise reconstruction from all backpropagated holograms with preliminary focus distances. Simulations and experimental results verified the validity and effectiveness of the proposed algorithm.
Antiviral Essential Oil Components Against SARS-CoV-2 in Pre-procedural Mouth Rinses for Dental Settings During COVID-19: A Computational Study

COVID-19 mainly spreads through cough or sneeze droplets produced by an infected person. The viral particles are mostly present in the oral cavity. The risk of contracting COVID-19 is high in the dental profession due to the nature of procedures involved that produce aerosols. Along with other measures to limit the risk of infection, pre-procedural mouth rinses are beneficial in reducing the viral particles in the oral cavity. In this study, the antiviral efficacy of essential oil components has been determined specifically against SARS-CoV-2 by molecular docking and conceptual DFT approach. Based on the binding affinities of the components against the receptor binding domain of the S1 glycoprotein, cuminal, carvacrol, myrtanol, and pinocarveol were found to be highly active. The molecular descriptor values obtained through conceptual DFT also indicated the above-mentioned components to be active based on the correlation between the structure and the activity of the compounds. Therefore, pre-procedural mouth rinses with these components included may be specifically suitable for dental procedures during the COVID-19 period.
Recent trends in postoperative mortality after liver resection- A systemic review and metanalysis of studies published in last 5 years and metaregression of various factors affecting 90 days mortality.

Aim: The aim of this systemic review and meta-analysis was to analyse 90 days mortality after liver resection, and also study various factors associated with mortality via univariate and multivariate metaregression. Methods: PubMed, Cochrane library, Embase, google scholar, web of science with keywords like liver resection, mortalit, hepatectomy. Weighted percentage 90 days mortalities were analysed. univariate metaregression was done by DerSimonian-Liard methods. Major hepatectomy, open surgery, cirrhotic livers, blood loss, hepatectomy for hepatocellular carcinoma, hepatectomy for colorectal liver metastasis were taken as moderators in metaregression analysis. We decided to enter all co-variants in multivariate model to look for mixed effects. Heterogeneity was assessed using the Higgins I2 test, with values of 25%, 50% and 75% indicating low, moderate and high degrees of heterogeneity. Cohort studies were assessed for bias using the Newcastle-Ottawa Scale to assess for the risk of bias. Publication bias was assessed using funnel plot. Funnel plot asymmetry was evaluated by Egger test. Results: Total 29931 patients data who underwent liver resections for various etiologies were pooled from 41 studied included1257 patients died within 90 days post operatively. Weighted 90 days mortality was 3.6% (95% C.I 2.8% -4.4%). However, heterogeneity of the analysis was high with I2 94.625%. (p<0.001). We analysed various covariates like major hepatectomy, Age of the patient, blood loss, open surgery, liver resections done for hepatocellular carcinoma or colorectal liver metastasis and cirrhotic liver to check for their association with heterogeneity in the analysis and hence 90 days mortality. On univariate metaregression analysis major hepatectomy (p<0.001), Open hepatectomy (p<0.001), blood loss (p=0.002) was associated with heterogeneity in the analysis and 90 days mortality. On multivariate metaregression Major hepatectomy(p=0.003) and Open surgery (p=0.012) was independently associated with higher 90 days mortality, and liver resection for colorectal liver metastasis was independently associated with lesser 90 days mortality (z= -4.11,p<0.01). Residual heterogeneity after all factor multivariate metaregression model was none (I2=0,Tau2=0, H2=1) and nonsignificant (p=0.49). Conclusion: Major hepatectomy, open hepatectomy, and cirrhotic background is associated with higher mortality rates and colorectal liver metastasis is associated with lower peri operative mortality rates.
MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway

Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in the development of sepsis. In this study, we investigated the regulatory pathway of miR-let-7b/TLR4/NF-κB in neutrophils. We also explored the downstream cytokines released by neutrophils following miR-let-7b treatment and its therapeutic effects in cecal ligation and puncture (CLP)-induced septic mice. Six-to-eight-week-old male C57BL/6 mice underwent CLP following treatment with miR-let-7b agomir. Survival (n=10), changes in liver and lungs histopathology (n=4), circulating neutrophil counts (n=4), the liver-body weight ratio (n=4–7), and the lung wet-to-dry ratio (n=5–6) were recorded. We found that overexpression of miR-let-7b could significantly down-regulate the expression of human-derived neutrophilic TLR4 at a post-transcriptional level, a decreased level of proinflammatory factors including interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and an upregulation of anti-inflammatory factor IL-10 in vitro. After miR-let-7b agomir treatment in vivo, neutrophil recruitment was inhibited and thus the injuries of liver and lungs in CLP-induced septic mice were alleviated (p=0.01 and p=0.04, respectively), less weight loss was reduced, and survival in septic mice was also significantly improved (p=0.013). Our study suggested that miR-let-7b could be a potential target of sepsis.
Lactic Acid Fermentation Is Required for NLRP3 Inflammasome Activation

Activation of the Nod-like receptor 3 (NLRP3) inflammasome is important for activation of innate immune responses, but improper and excessive activation can cause inflammatory disease. We previously showed that glycolysis, a metabolic pathway that converts glucose into pyruvate, is essential for NLRP3 inflammasome activation in macrophages. Here, we investigated the role of metabolic pathways downstream glycolysis – lactic acid fermentation and pyruvate oxidation—in activation of the NLRP3 inflammasome. Using pharmacological or genetic approaches, we show that decreasing lactic acid fermentation by inhibiting lactate dehydrogenase reduced caspase-1 activation and IL-1β maturation in response to various NLRP3 inflammasome agonists such as nigericin, ATP, monosodium urate (MSU) crystals, or alum, indicating that lactic acid fermentation is required for NLRP3 inflammasome activation. Inhibition of lactate dehydrogenase with GSK2837808A reduced lactate production and activity of the NLRP3 inflammasome regulator, phosphorylated protein kinase R (PKR), but did not reduce the common trigger of NLRP3 inflammasome, potassium efflux, or reactive oxygen species (ROS) production. By contrast, decreasing the activity of pyruvate oxidation by depletion of either mitochondrial pyruvate carrier 2 (MPC2) or pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) enhanced NLRP3 inflammasome activation, suggesting that inhibition of mitochondrial pyruvate transport enhanced lactic acid fermentation. Moreover, treatment with GSK2837808A reduced MSU-mediated peritonitis in mice, a disease model used for studying the consequences of NLRP3 inflammasome activation. Our results suggest that lactic acid fermentation is important for NLRP3 inflammasome activation, while pyruvate oxidation is not. Thus, reprograming pyruvate metabolism in mitochondria and in the cytoplasm should be considered as a novel strategy for the treatment of NLRP3 inflammasome-associated diseases.