Miracle-dz/UniFAR-FTUs huggingface dataset:
Stream Temperature Modeling and Fiber Optic Temperature Sensing to Characterize Groundwater Discharge

The Ngongotaha Stream was used as a case study to assess the applicability of fiber optic distributed temperature sensing (FODTS) to identify the location of springs and quantify their discharge. Thirteen springs were identified, mostly located within a 115 m reach, five discharged from the right bank and eight from the left bank. To quantify groundwater discharge, a new approach was developed in which the one‐dimensional transient heat transport model was fitted to the FODTS measurements, where the main calibration parameters of interest were the unknown spring discharges. The spatial disposition of the groundwater discharge estimation problem was constrained by two sources of information; first, the stream gains ∼500 L/s as determined by streamflow gauging. Second, the temperature profiles of the left and right banks provide the spatial disposition of springs and their relative discharges. FODTS was used to measure stream temperature near the left and right banks, which created two temperature datasets. A weighted average of the two datasets was then calculated, where the weights reflected the degree of mixing between the right and left banks downstream of a spring. The new approach in this study marks a departure from previous studies, in which the general approach was to use the steady‐state thermal mixing model (Selker et al. 2006a; Westhoff et al. 2007; Briggs et al. 2012) to infer groundwater discharge, which is then used as an input into a transient model of the general form of equation to simulate stream temperature (Westhoff et al. 2007).
Verifying Data Integration Configurations for Semantical Correctness and Completeness

Data integration is the problem of combining data residing at different sources and providing the user with a unified view of these data. In medical informatics, such a unified view enables retrospective analyses based on more facts and prospective recruitment of more patients than any single data collection by itself. The technical part of data integration is based on rules interpreted by software. These rules define how to perform the translation of source database schemata into the target database schema. Translation rules are formulated by data managers who usually do not have the knowledge about meaning and acquisition methods of the data they handle. The professionals (data providers) collecting the source data who have the respective knowledge again usually have no sufficient technical background. Since data providers are neither able to formulate the transformation rules themselves nor able to validate them, the whole process is fault-prone. Additionally, in continuous development and maintenance of (meta-) data repositories, data structures underlie changes, which may lead to outdated transformation rules. We did not find any technical solution, which enables data providers to formulate transformation rules themselves or which provides an understandable reflection of given rules. Our approach is to enable data providers understand the rules regarding their own data by presenting rules and available context visually. Context information is fetched from a metadata repository. In this paper, we propose a software tool that builds on existing data integration infrastructures. The tool provides a visually supported validation routine for data integration rules. In a first step towards its evaluation, we implement the tool into the DZL data integration process and verify the correct presentation of transformation rules.
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens

WT P53-Induced Phosphatase 1 (WIP1) is a member of the magnesium-dependent serine/threonine protein phosphatase (PPM) family and is induced by P53 in response to DNA damage. In several human cancers, the WIP1 protein is overexpressed, which is generally associated with a worse prognosis. Although WIP1 is an attractive therapeutic target, no potent, selective, and bioactive small-molecule modulator with favorable pharmacokinetics has been reported. Phosphatase enzymes are among the most challenging targets for small molecules because of the difficulty of achieving both modulator selectivity and bioavailability. Another major obstacle has been the availability of robust and physiologically relevant phosphatase assays that are suitable for high-throughput screening. Here, we describe orthogonal biochemical WIP1 activity assays that utilize phosphopeptides from native WIP1 substrates. We optimized an MS assay to quantify the enzymatically dephosphorylated peptide reaction product in a 384-well format. Additionally, a red-shifted fluorescence assay was optimized in a 1,536-well format to enable real-time WIP1 activity measurements through the detection of the orthogonal reaction product, Pi. We validated these two optimized assays by quantitative high-throughput screening against the National Center for Advancing Translational Sciences (NCATS) Pharmaceutical Collection and used secondary assays to confirm and evaluate inhibitors identified in the primary screen. Five inhibitors were further tested with an orthogonal WIP1 activity assay and surface plasmon resonance binding studies. Our results validate the application of miniaturized physiologically relevant and orthogonal WIP1 activity assays to discover small-molecule modulators from high-throughput screens.
Recent Progress of Fiber Shaped Lighting Devices for Smart Display Applications—A Fibertronic Perspective

Advances in material science and nanotechnology have fostered the miniaturization of devices. Over the past two decades, the form‐factor of these devices has evolved from 3D rigid, volumetric devices through 2D film‐based flexible electronics, finally to 1D fiber electronics (fibertronics). In this regard, fibertronic strategies toward wearable applications (e.g., electronic textiles (e‐textiles)) have attracted considerable attention thanks to their capability to impart various functions into textiles with retaining textiles' intrinsic properties as well as imperceptible irritation by foreign matters. In recent years, extensive research has been carried out to develop various functional devices in the fiber form. Among various features, lighting and display features are the highly desirable functions in wearable electronics. This article discusses the recent progress of materials, architectural designs, and new fabrication technologies of fiber‐shaped lighting devices and the current challenges corresponding to each device's operating mechanism. Moreover, opportunities and applications that the revolutionary convergence between the state‐of‐the‐art fibertronic technology and age‐long textile industry will bring in the future are also discussed.
Customizable Ceramic Nanocomposites Using Carbon Nanotubes

A novel tweakable nanocomposite was prepared by spark plasma sintering followed by systematic oxidation of carbon nanotube (CNT) molecules to produce alumina/carbon nanotube nanocomposites with surface porosities. The mechanical properties (flexural strength and fracture toughness), surface area, and electrical conductivities were characterized and compared. The nanocomposites were extensively analyzed by field emission scanning electron microscopy (FE-SEM) for 2D qualitative surface morphological analysis. Adding CNTs in ceramic matrices and then systematically oxidizing them, without substantial reduction in densification, induces significant capability to achieve desirable/application oriented balance between mechanical, electrical, and catalytic properties of these ceramic nanocomposites. This novel strategy, upon further development, opens new level of opportunities for real-world/industrial applications of these relatively novel engineering materials.
The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.
The Application of Ribosome Engineering to Natural Product Discovery and Yield Improvement in Streptomyces

Microbial natural product drug discovery and development has entered a new era, driven by microbial genomics and synthetic biology. Genome sequencing has revealed the vast potential to produce valuable secondary metabolites in bacteria and fungi. However, many of the biosynthetic gene clusters are silent under standard fermentation conditions. By rational screening for mutations in bacterial ribosomal proteins or RNA polymerases, ribosome engineering is a versatile approach to obtain mutants with improved titers for microbial product formation or new natural products through activating silent biosynthetic gene clusters. In this review, we discuss the mechanism of ribosome engineering and its application to natural product discovery and yield improvement in Streptomyces. Our analysis suggests that ribosome engineering is a rapid and cost-effective approach and could be adapted to speed up the discovery and development of natural product drug leads in the post-genomic era.
Discrimination study between carcass yield and meat quality by gender in Korean native cattle (Hanwoo)

Objective The aim of this study was to identify a distribution pattern of meat quality grade (MQG) as a function of carcass yield index (CYI) and the gender of Hanwoo (bull, cow, and steer) to determine the optimum point between both yield and quality. We also attempted to identify how pre- and post-deboning variables affect the gender-specific beef quality of Hanwoo. Methods A total of 31 deboning variables, consisting of 7 pre-deboning and 24 post-deboning variables from bulls (n = 139), cows (n = 69), and steers (n = 153), were obtained from the National Institute of Animal Science (NIAS) in South Korea. The database was reconstructed to be suitable for a statistical significance test between the CYI and the MQG as well as classification of meat quality. Discriminant function analysis was used for classifying MQG using the deboning parameters of Hanwoo by gender. Results The means of CYI according to 1+, 1, 2, and 3 of MQG were 68.64±2.02, 68.85± 1.94, 68.62±5.88, and 70.99±3.32, respectively. High carcass yield correlated with low-quality grade, while high-quality meat most frequently was obtained from steers. The classification ability of pre-deboning parameters was higher than that of post-deboning parameters. Moisture and the shear force were the common significant parameters in all discriminant functions having a classification accuracy of 80.6%, 71%, and 56.9% for the bull, cow, and steer, respectively. Conclusion This study provides basic information for predicting the meat quality by gender using pre-deboning variables consistent with the actual grading index.
Boosting Water Oxidation through In Situ Electroconversion of Manganese Gallide: An Intermetallic Precursor Approach

Abstract For the first time, the manganese gallide (MnGa4) served as an intermetallic precursor, which upon in situ electroconversion in alkaline media produced high‐performance and long‐term‐stable MnOx‐based electrocatalysts for water oxidation. Unexpectedly, its electrocorrosion (with the concomitant loss of Ga) leads simultaneously to three crystalline types of MnOx minerals with distinct structures and induced defects: birnessite δ‐MnO2, feitknechtite β‐MnOOH, and hausmannite α‐Mn3O4. The abundance and intrinsic stabilization of MnIII/MnIV active sites in the three MnOx phases explains the superior efficiency and durability of the system for electrocatalytic water oxidation. After electrophoretic deposition of the MnGa4 precursor on conductive nickel foam (NF), a low overpotential of 291 mV, comparable to that of precious‐metal‐based catalysts, could be achieved at a current density of 10 mA cm−2 with a durability of more than five days.
RNase E Promotes Expression of Type III Secretion System Genes in Pseudomonas aeruginosa

The type III secretion system (T3SS) is a protein complex produced by many Gram-negative pathogens. It is capable of injecting effector proteins into host cells that can manipulate cell metabolism and have toxic effects. Understanding how the T3SS is regulated is important in understanding the pathogenesis of bacteria with such systems. Here, we show that RNase E, which is typically thought of as a global regulator of RNA stability, plays a role in regulating the T3SS in Pseudomonas aeruginosa. Depleting RNase E results in the loss of T3SS gene expression as well as a concomitant increase in biofilm formation. These observations are reminiscent of the phenotypes associated with the loss of activity of the posttranscriptional regulator RsmA. However, RNase E-mediated regulation of these systems does not involve changes in the abundance of RsmA and is independent of the known small regulatory RNAs that modulate RsmA activity. ABSTRACT Pseudomonas aeruginosa is an important opportunistic pathogen that employs a type III secretion system (T3SS) to inject effector proteins into host cells. Using a protein depletion system, we show that the endoribonuclease RNase E positively regulates expression of the T3SS genes. We also present evidence that RNase E antagonizes the expression of genes of the type VI secretion system and limits biofilm production in P. aeruginosa. Thus, RNase E, which is thought to be the principal endoribonuclease involved in the initiation of RNA degradation in P. aeruginosa, plays a key role in controlling the production of factors involved in both acute and chronic stages of infection. Although the posttranscriptional regulator RsmA is also known to positively regulate expression of the T3SS genes, we find that RNase E does not appreciably influence the abundance of RsmA in P. aeruginosa. Moreover, we show that RNase E still exerts its effects on T3SS gene expression in cells lacking all four of the key small regulatory RNAs that function by sequestering RsmA. IMPORTANCE The type III secretion system (T3SS) is a protein complex produced by many Gram-negative pathogens. It is capable of injecting effector proteins into host cells that can manipulate cell metabolism and have toxic effects. Understanding how the T3SS is regulated is important in understanding the pathogenesis of bacteria with such systems. Here, we show that RNase E, which is typically thought of as a global regulator of RNA stability, plays a role in regulating the T3SS in Pseudomonas aeruginosa. Depleting RNase E results in the loss of T3SS gene expression as well as a concomitant increase in biofilm formation. These observations are reminiscent of the phenotypes associated with the loss of activity of the posttranscriptional regulator RsmA. However, RNase E-mediated regulation of these systems does not involve changes in the abundance of RsmA and is independent of the known small regulatory RNAs that modulate RsmA activity.
The Spectrinome: The Interactome of a Scaffold Protein Creating Nuclear and Cytoplasmic Connectivity and Function

We provide a review of Spectrin isoform function in the cytoplasm, the nucleus, the cell surface, and in intracellular signaling. We then discuss the importance of Spectrin’s E2/E3 chimeric ubiquitin conjugating and ligating activity in maintaining cellular homeostasis. Finally we present spectrin isoform subunit specific human diseases. We have created the Spectrinome, from the Human Proteome, Human Reactome and Human Atlas data and demonstrated how it can be a useful tool in visualizing and understanding spectrins myriad of cellular functions. Impact statement Spectrin was for the first 12 years after its discovery thought to be found only in erythrocytes. In 1981, Goodman and colleagues 1 found that spectrin-like molecules were ubiquitously found in non-erythroid cells leading to a great multitude of publications over the next thirty eight years. The discovery of multiple spectrin isoforms found associated with every cellular compartment, and representing 2-3% of cellular protein, has brought us to today’s understanding that spectrin is a scaffolding protein, with its own E2/E3 chimeric ubiquitin conjugating ligating activity that is involved in virtually every cellular function. We cover the history, localized functions of spectrin isoforms, human diseases caused by mutations, and provide the spectrinome: a useful tool for understanding the myriad of functions for one of the most important proteins in all eukaryotic cells.
Co-delivery of free vancomycin and transcription factor decoy-nanostructured lipid carriers can enhance inhibition of methicillin resistant Staphylococcus aureus (MRSA)

Bacterial resistance to antibiotics is widely regarded as a major public health concern with last resort MRSA treatments like vancomycin now encountering resistant strains. TFDs (Transcription Factor Decoys) are oligonucleotide copies of the DNA-binding sites for transcription factors. They bind to and sequester the targeted transcription factor, thus inhibiting transcription of many genes. By developing TFDs with sequences aimed at inhibiting transcription factors controlling the expression of highly conserved bacterial cell wall proteins, TFDs present as a potential method for inhibiting microbial growth without encountering typical resistance mechanisms. However, the efficient protection and delivery of the TFDs inside the bacterial cells is a critical step for the success of this technology. Therefore, in our study, specific TFDs against S. aureus were complexed with two different types of nanocarriers: cationic nanostructured lipid carriers (cNLCs) and chitosan-based nanoparticles (CS-NCs). These TFD-carrier nanocomplexes were characterized for size, zeta potential and TFD complexation or loading efficiency in a variety of buffers. In vitro activity of the nanocomplexes was examined alone and in combination with vancomycin, first in methicillin susceptible strains of S. aureus with the lead candidate advancing to tests against MRSA cultures. Results found that both cNLCs and chitosan-based carriers were adept at complexing and protecting TFDs in a range of physiological and microbiological buffers up to 72 hours. From initial testing, chitosan-TFD particles demonstrated no visible improvements in effect when co-administered with vancomycin. However, co-delivery of cNLC-TFD with vancomycin reduced the MIC of vancomycin by over 50% in MSSA and resulted in significant decreases in viability compared with vancomycin alone in MRSA cultures. Furthermore, these TFD-loaded particles demonstrated very low levels of cytotoxicity and haemolysis in vitro. To our knowledge, this is the first attempt at a combined antibiotic/oligonucleotide-TFD approach to combatting MRSA and, as such, highlights a new avenue of MRSA treatment combining traditional small molecules drugs and bacterial gene inhibition.
Stroke Incidence and Case Fatality According to Rural or Urban Residence.

Background and Purpose- Recent findings suggest that in the United States, stroke incidence is higher in rural than in urban areas. Similar analyses in other high-income countries are scarce with conflicting results. In 2008, the Brest Stroke Registry was started in western France, an area that includes about 366 000 individuals living in various urban and rural settings. Methods- All new patients with stroke included in the Brest Stroke Registry from 2008 to 2013 were classified as residing in town centers, suburbs, isolated towns, or rural areas. Poisson regression was used to analyze stroke incidence and 30-day case fatality variations in the 4 different residence categories. Models with case fatality as outcome were adjusted for age, stroke type, and stroke severity. Results- In total, 3854 incident stroke cases (n=2039 women, 53%) were identified during the study period. Demographic and socio-economic characteristics and primary healthcare access indicators were significantly different among the 4 residence categories. Patterns of risk factors, stroke type, and severity were comparable among residence categories in both sexes. Age-standardized stroke rates varied from 2.90 per thousand (95% CI, 2.59-3.21) in suburbs to 3.35 (95% CI, 2.98-3.73) in rural areas for men, and from 2.14 (95% CI, 2.00-2.28) in town centers to 2.34 (95% CI, 2.12-2.57) in suburbs for women. Regression models suggested that among men, stroke incidence was significantly lower in suburbs than in town centers (incidence rate ratio =0.87; 95% CI, 0.77-0.99). Case fatality risk was comparable across urban categories but lower in rural patients (relative risk versus town centers: 0.76; 95% CI, 0.60-0.96). Conclusions- Stroke incidence was comparable, and the 30-day case fatality only slightly varied in the 4 residence categories despite widely different socio-demographic features covered by the Brest Stroke Registry.
Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion

The involvement of secretin (SCT) and its receptor (SCTR) in angiotensin II (ANGII)-mediated osmoregulation by forming SCTR/ angiotensin II type 1 receptor (AT1R) heteromer is well established. In this study, we demonstrated that SCTR/AT1R complex can mediate ANGII-induced aldosterone secretion/release through potentiating calcium mobilization. Through IHC and cAMP studies, we showed the presence of functional SCTR and AT1R in the primary zona glomerulosa (ZG) cells of C57BL/6N (C57), and functional AT1R and non-functional SCTR in SCTR knockout (SCTR-/-) mice. Calcium mobilization studies revealed the important role of SCTR on ANGII-mediated calcium mobilization in adrenal gland. The fluo4-AM loaded primary adrenal ZG cells from the C57 mice displayed a dose-dependent increase in intracellular calcium influx ([Ca2+]i) when exposed to ANGII but not from the SCTR-/- ZG cells. Synthetic SCTR transmembrane (TM) peptides STM-II/-IV were able to alter [Ca2+]i in C57 mice, but not the mice with mutated STM-II/-IV (STM-IIm/IVm) peptides. Through enzyme immunoassay (EIA), we measured the aldosterone release from primary ZG cells of both C57 and SCTR-/- mice by exposing them to ANGII (10nM). SCTR-/- ZG cells showed impaired ANGII-induced aldosterone secretion compared to the C57 mice. TM peptide, STM-II hindered the aldosterone secretion in ZG cells of C57 mice. These findings support the involvement of SCTR/AT1R heterodimer complex in aldosterone secretion/release through [Ca2+]i.