Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanistic Insight into the Chemiluminescent Decomposition of Cypridina Dioxetanone and the Chemiluminescent, Fluorescent Properties of the Light Emitter of Cypridina Bioluminescence

Cypridina bioluminescence has been increasingly used in bioimaging, bioanalysis and biomedicine, due to high quantum yield and high signal-to-noise ratio. However, there is still no consensus regarding different aspects of the chemiluminescent mechanism of this system, which impairs the development of new applications. Herein, we have used a theoretical DFT and TD-DFT approach to: (i) determine the identity of the dioxetanone species responsible for efficient chemiexcitation; (ii) identify the bioluminescent emitter and determine if light-emission occurs from the fluorescent or chemiluminescent state. Our results demonstrate that upon oxygenation of the imidazopyrazinone scaffold, a dioxetanone with a neutral amide group and a cationic guanidinopropyl group is formed. This species is efficiently chemiexcited (with no obvious charge transfer step) to the corresponding oxyluciferin with a neutral amide and cationic guanidinopropyl groups. After the "dark" chemiluminescent state, this oxyluciferin species is converted into a bright blue-emitting fluorescent state.
An Ultra-Low-Power High-Speed Cache Memory Comprising Hybrid TFET-FinFET SRAM Cells

–A hybrid static random access memory (SRAM) cell is presented where cross-coupled inverters are formed by tunnel field-effect transistors (TFETs) and the access transistors are made of high-performance fin field-effect transistors (FinFETs.) Read/write assist techniques are employed to achieve satisfactory stability characteristics even at ultra-low supply voltages of 60mV for the SRAM cell. A 128  128 SRAM array comprising hybrid TEFT/FinFET memory cells, address decoding, multiplexing and sensing was designed and simulated. The read delay (decoding + access delay + sensing) of the array was further improved by utilizing a dual - VDD approach whereby the peripheral circuitry was operated at 300mV supply voltage and the SRAM cells were supplied 100mV as their supply voltage. The result was a read delay latency as low as 1.12ns with satisfactory noise margins.
Spatial Pattern Analysis In Plant Ecology

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Causal distributed assert statements

Monitoring a program's execution is fundamental to the debugging, testing and maintenance phases of program development. This research addresses the issue of monitoring the execution of a distributed program. In particular, we are concerned with efficient techniques for evaluating global state predicates for distributed programs. The global state of a distributed program is not well-defined, making the monitoring task complex compared to that of a sequential programs. Processes of a distributed program execute concurrently, and the events of the program cannot be totally ordered. Each process has its own local memory, and the local memories are physically separate. Despite the difficulties of defining a distributed computation's states, monitoring a distributed program requires reasoning about constituent processes' execution as a single collective entity. We have extrapolated the semantics of the sequential program's assert statement into the distributed context. A distributed assert statement is a global predicate that is anchored at a control point of one processes, and that is evaluated when that process executes the assert. We have developed a runtime method for monitoring both stable and unstable properties that does not disrupt the computation of the distributed system. A distributed assert statement is evaluated with that statement's causal global state which incorporates the state of the system as a whole as it may have causal impact upon the assert statement. A runtime protocol has been implemented that constructs the causal global state and evaluates the assert statement. No additional synchronization or message passing is imposed on the distributed application although some message sizes are increased to propagate state information. The causal global state is immediately available providing real-time feedback.
On the classification of passenger cars in airborne SAR images using simulated training data and a convolutional neural network

SAR sensors play an important role in different fields of remote sensing. One of these is Automatic Target Recognition (ATR). In this paper, a new dataset for ATR is introduced, consisting of five classes of passenger cars imaged by SmartRadar of Hensoldt Sensors GmbH. The basic characteristics of the dataset and some details of the measurement campaign are provided. The second part of the paper deals with the creation of a sufficiently large database of training samples to train a Convolutional Neural Network (CNN) to classify these cars. Since training data are not as readily available as in the EO case, training data are simulated using the CohRaS SAR simulator of Fraunhofer IOSB, which is also briefly described. The basic setup of the CNN used for the classification task is outlined and some issues arising in the classification of the training data are discussed. The paper also contains some very preliminary classification results using the CNN and the simulated training data, and a discussion of these results.
Estimating the Prevalence of Fetal Alcohol Syndrome

Since the late 1970s, many studies have reported on the prevalence of fetal alcohol syndrome (FAS), alcohol-related birth defects (ARBD), and alcohol-related neurodevelopmental disorders (ARND). The three main types of research methods used in these studies are passive surveillance, clinic-based studies, and active case ascertainment. This article describes each of these methods, including their strengths and weaknesses, and summarizes the estimated prevalence of FAS produced by each of these approaches. The maternal risk factors associated with FAS and other alcohol-related anomalies include advanced maternal age, low socioeconomic status, frequent binge drinking, family and friends with drinking problems, and poor social and psychological indicators. Overall, the available literature points to a prevalence rate of FAS of 0.5 to 2 cases per 1,000 births in the United States during the 1980s and 1990s.
Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides

Conditions right for making nucleosides In the absence of biological catalysts and metabolism, can atmospheric and geochemical processes provide the substrates and conditions required for production of biological molecules? Becker et al. devised an abiotic synthetic scheme that allows for accumulation of both purine and pyrimidine nucleoside mono- and diphosphates (see the Perspective by Hud and Fialho). A key starting material for this chemistry, hydroxylamine and/or hydroxylamine disulfonate, can form under plausible early atmospheric conditions. Cycles between wet and dry conditions provide the environments necessary to complete formation of purine and pyrimidine bases essentially in one pot. Science, this issue p. 76; see also p. 32 Concurrent synthesis of complementary ribonucleotides from geochemical precursors can proceed via wet and dry cycles. Theories about the origin of life require chemical pathways that allow formation of life’s key building blocks under prebiotically plausible conditions. Complex molecules like RNA must have originated from small molecules whose reactivity was guided by physico-chemical processes. RNA is constructed from purine and pyrimidine nucleosides, both of which are required for accurate information transfer, and thus Darwinian evolution. Separate pathways to purines and pyrimidines have been reported, but their concurrent syntheses remain a challenge. We report the synthesis of the pyrimidine nucleosides from small molecules and ribose, driven solely by wet-dry cycles. In the presence of phosphate-containing minerals, 5′-mono- and diphosphates also form selectively in one-pot reactions. The pathway is compatible with purine synthesis, allowing the concurrent formation of all Watson-Crick bases.
The impact of routine childhood immunization with higher-valent pneumococcal conjugate vaccines on antimicrobial-resistant pneumococcal diseases and carriage: a systematic literature review

ABSTRACT Introduction: The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in childhood immunization programs reduced antimicrobial-resistant pneumococcal infections by vaccine serotypes. However, emerging antimicrobial-resistant non-vaccine serotypes, particularly serotype 19A, attenuated the overall effect. In 2010, higher-valent PCVs became available containing serotypes that are prone to become antimicrobial-resistant, like serotype 7F in PCV10 and PCV13, and serotype 19A in PCV13. Areas covered: This review evaluated literature published between June 1, 2008 and June 1, 2017 reporting on the effect of PCV10 or PCV13 implementation in routine infant immunization schedules on antimicrobial-resistant invasive pneumococcal disease (IPD), otitis media (OM), and nasopharyngeal carriage (NPC) in children and adults. Expert opinion: In countries with relatively high prior pneumococcal antimicrobial resistance (AMR), PCV13 childhood vaccination programs have reduced antimicrobial-resistant IPD, OM, and NPC in children and IPD in adults. The effectiveness of PCV13 against serotype 19A is likely an important contributing factor. Only few studies have documented the impact of PCV10 on AMR. Multiple factors may influence observed decreases in pneumococcal AMR including antimicrobial stewardship, case definition, time since PCV10/13 introduction, and pre-PCV10/13 AMR levels. This review emphasizes the importance of including impact on AMR when evaluating the full public health of pneumococcal vaccination programs.
First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of 89Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: 89Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most 89Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.
Placental growth factor negatively regulates retinal endothelial cell barrier function through suppression of glucose‐6‐phosphate dehydrogenase and antioxidant defense systems

We report that placental growth factor (PlGF) negatively affects the endothelial cell (EC) barrier function through a novel regulatory mechanism. The PlGF mAb promotes (but recombinant protein disrupts) EC barrier function, thus affecting the barrier‐forming protein levels, membrane distribution, and EC monolayer impedance by the electrical cell‐impedance sensing system, Western blot, and immunofluorescence staining. RNA sequencing‐based transcriptome analysis identified the up‐regulation of the pentose phosphate pathway (PPP) and the antioxidant defense protein by PlGF blockade. The PlGF and PlGF/VEGF dimers (but not VEGF‐A) down‐regulated the protein expression of glucose‐6‐phosphate dehydrogenase (G6PD) and peroxiredoxin (PRDX). G6PD inhibition and gene silencing (small interfering RNA) abolished the beneficial effects of PlGF inhibition on EC barrier function and PRDX3/6 protein expression. VEGF receptor (VEGFR)1 or VEGFR2 blockade prevented the inhibitory effect of PlGF on G6PD protein expression and EC barrier function. The PRDX6 played dual roles in EC barrier function through glutathione peroxidase and phospholipase A2 activity. In sum, PlGF negatively regulates EC barrier function through the activation of VEGFR1 and VEGFR2 and the suppression of the G6PD/PPP and the antioxidant pathways. —Huang, H. , Lennikov, A. , Saddala, M. S. , Gozal, D. , Grab, D. J., Khalyfa, A. , Fan, L. Placental growth factor negatively regulates endothelial cell barrier function through suppression of glucose‐6‐phosphate dehydrogenase and antioxidant defense systems. FASEB J. 33, 13695‐13709 (2019). www.fasebj. org
Data Validation System For A Relational Database

One of the most neglected areas in systems implementation is data validation. Most application systems fail to achieve its set goals because there is no adequate and efficient data validation system to filter out input data that is not correct. Improper input data is responsible for a large number of system failures; and such failures could have been avoided or reduced if proper input data had been fed into the system. In this paper we focused on enhancing and elaborating on existing data validation methods like limits checks, character checks, range checks, presence checks, consistency checks, format or picture checks and data type checks, to improve the performance of our application systems. We also develop a sample program that integrates these validation techniques. A report was finally generated based on validated customer records created for Fractal Construction Nigeria Limited. The system was developed using PHP, MYSQL and XAMPP web server. Keywords: Data validation, database, data base management system, database specification, relational model, normalization
Humeral Retroversion and Injury Risk After Proximal Humeral Epiphysiolysis (Little Leaguer’s Shoulder)

Background: The increased humeral retroversion on the dominant side of throwing athletes is thought to result from repetitive throwing motion. Little Leaguer’s shoulder—a rotational stress fracture of the proximal humeral epiphyseal plate—may influence the risk of humeral retroversion and injury of the shoulder or elbow joint. Purpose: To investigate the effect of Little Leaguer’s shoulder on humeral retroversion and the rates of shoulder and elbow injuries. Study Design: Cohort study; Level of evidence, 3. Methods: 10 high school baseball players (average age, 16.6 years; range, 16-18 years) who had experienced Little Leaguer’s shoulder during elementary or junior high school (average age, 12.6 years; range, 11-15 years) were enrolled in the study. As a control group, 22 high school baseball players (average age, 16.9 years; range, 16-18 years) who had never had any shoulder or elbow injury during elementary and junior high school were included. Humeral retroversion on ultrasonographic measurement, shoulder range of motion, and rates of shoulder and elbow injuries were evaluated. Results: Humeral retroversion was significantly greater on the dominant side than on the nondominant side in both players with Little Leaguer’s shoulder (dominant, 104°± 8°; nondominant, 84°± 12°; P < .001) and controls (dominant, 91°± 13°; nondominant, 81°± 10°; P < .001). In the dominant shoulder, humeral retroversion was greater in the Little Leaguer’s shoulder group than in the control group (P = .008). When the effects of humeral retroversion were excluded, maximal external rotation was significantly less in the dominant shoulder than in the nondominant shoulder in the Little Leaguer’s shoulder group (by 11°± 12°, P = .02), whereas no significant difference was found between dominant (110°± 11°) and nondominant (111°± 13°) shoulders in the control group (P = .64). The rates of shoulder and elbow pain were significantly higher in the Little Leaguer’s shoulder group (shoulder pain 80%, elbow pain 70%) than in the control group (shoulder pain 9%, P < .001; elbow pain 32%, P = .04). Conclusion: Humeral retroversion was increased in baseball players without any history of shoulder or elbow injury during elementary and junior high school and was further increased in players who had had Little Leaguer’s shoulder. Increased humeral retroversion after Little Leaguer’s shoulder may be a risk factor for future shoulder or elbow injury.
Dietary exposure to furan of the Austrian population

ABSTRACT In the period from 2007 to 2017 furan levels of foods were analysed by the Austrian Agency for Health and Food Safety. Based on these analytical data and the Austrian consumption data the dietary exposure of children and adults to furan was estimated by using a deterministic approach. For the adult population the mean and 95th percentile dietary exposures to furan were estimated at 0.31 µg/kg bodyweight per day and at 0.72 µg/kg bodyweight per day, respectively. The mean dietary exposure of children was estimated at 0.18 µg/kg bodyweight per day and is thus only about half as high as for Austrian adults. At the 95th percentile the dietary exposure of children was estimated at 0.49 µg/kg bodyweight per day. The main contributor to the total dietary exposure for adults is coffee followed by convenience products and for children the main contributors are grain products as well as convenience products, bread and snacks. Based on the BMDL10 of 0.064 mg/kg bodyweight per day for the development of cholangiofibrosis, the MOE-calculation revealed that the current levels of dietary exposure to furan are of concern for Austrian adult high consumers. The MOE-calculation, based on the BMDL10 of 1.31 mg/kg bodyweight per day for the development of hepatocellular adenomas, indicated a health concern for Austrian children and adults.
Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers

Antimicrobial drug concentrations in the gastrointestinal tract likely drive antimicrobial resistance in enteric bacteria. Our objective was to determine the concentration of ceftiofur and its metabolites in the gastrointestinal tract of steers treated with ceftiofur crystalline-free acid (CCFA) or ceftiofur hydrochloride (CHCL), determine the effect of these drugs on the minimum inhibitory concentration (MIC) of fecal Escherichia coli, and evaluate shifts in the microbiome. Steers were administered either a single dose (6.6 mg/kg) of CCFA or 2.2 mg/kg of CHCL every 24 hours for 3 days. Ceftiofur and its metabolites were measured in the plasma, interstitium, ileum and colon. The concentration and MIC of fecal E. coli and the fecal microbiota composition were assessed after treatment. The maximum concentration of ceftiofur was higher in all sampled locations of steers treated with CHCL. Measurable drug persisted longer in the intestine of CCFA-treated steers. There was a significant decrease in E. coli concentration (P = 0.002) within 24 hours that persisted for 2 weeks after CCFA treatment. In CHCL-treated steers, the mean MIC of ceftiofur in E. coli peaked at 48 hours (mean MIC = 20.45 ug/ml, 95% CI = 10.29–40.63 ug/ml), and in CCFA-treated steers, mean MIC peaked at 96 hours (mean MIC = 10.68 ug/ml, 95% CI = 5.47–20.85 ug/ml). Shifts in the microbiome of steers in both groups were due to reductions in Firmicutes and increases in Bacteroidetes. CCFA leads to prolonged, low intestinal drug concentrations, and is associated with decreased E. coli concentration, an increased MIC of ceftiofur in E. coli at specific time points, and shifts in the fecal microbiota. CHCL led to higher intestinal drug concentrations over a shorter duration. Effects on E. coli concentration and the microbiome were smaller in this group, but the increase in the MIC of ceftiofur in fecal E. coli was similar.
Individual periodic limb movements with arousal are temporally associated with nonsustained ventricular tachycardia: a case-crossover analysis.

STUDY OBJECTIVES Both periodic limb movements during sleep (PLMS) and arousals are associated with sympathetic nervous system activation and may be arrhythmogenic. We hypothesize a temporal relationship exists between individual PLMS, particularly with arousal, and nonsustained ventricular tachycardia (NSVT) events. METHODS A bidirectional time-stratified case-crossover design was used to assess temporal associations between PLMS and NSVT during sleep in 49 Osteoporotic Fractures in Men Sleep Study participants with NSVT in a community-based cohort (n = 2,911). Sleep time was divided into approximate 30-min segments. For each NSVT (n = 141), we selected a preceding 30-s hazard period and three randomly chosen 30-s control periods from sleep within the same segment and evaluated for PLMS, respiratory events, minimum saturation, and arousals. Odds ratios and 95% confidence intervals-OR (95% CI)-were determined by conditional logistic regression; covariates included EEG arousals, minimum saturation, and respiratory events in the same hazard/control period. RESULTS Participants with NSVT were 79.5 ± 6.2 years with a PLMS index of 32.1 (IQR: 10.1, 61.4) and apnea-hypopnea index of 17.1 (IQR: 9.4, 26.1). PLMS without arousal were not significantly associated with NSVT (OR = 0.80, 95% CI: 0.41-1.59). PLMS with arousal were associated with NSVT in unadjusted analyses (OR = 2.50, 95% CI: 1.11-5.65) and after adjustment (OR = 2.31, 95% CI: 1.02-5.25). Arousals associated with PLMS were associated with NSVT in unadjusted (OR = 2.84, 95% CI: 1.23-6.56) and adjusted analyses (OR = 2.61, 95% CI: 1.13-6.05). CONCLUSIONS PLMS with (but not without) arousals are temporally associated with a greater than twofold higher odds of subsequent NSVT episodes. PLMS-related arousals may be physiologically important ventricular arrhythmia triggers. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT00070681.