Miracle-dz/UniFAR-FTUs huggingface dataset:
Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior

Proper response to stress and social stimuli depends on orchestrated development of hypothalamic neuronal circuits. Here we address the effects of the developmental transcription factor orthopedia (Otp) on hypothalamic development and function. We show that developmental mutations in the zebrafish paralogous gene otpa but not otpb affect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus, otpa and otpb differentially regulate neuropeptide switching in a newly identified subset of OXT neurons that co-express the corticotropin-releasing hormone (CRH). Single-cell analysis revealed that these neurons project mostly to the hindbrain and spinal cord. Ablation of this neuronal subset specifically reduced adult social preference without affecting stress behavior, thereby uncoupling the contribution of a specific OXT cluster to social behavior from the general otpa−/− deficits. Our findings reveal a new role for Otp in controlling developmental neuropeptide balance in a discrete OXT circuit whose disrupted development affects social behavior. DOI: http://dx.doi. org/10.7554/eLife.22170. 001
A novel fuzzy self tuning technique of single neuron PID controller for brushless DC motor

In this paper, a combination ANN/Fuzzy techniques are used to design a Novel Fuzzy Single Neuron PID (NFSNPID) controller to achieve high performance brushless DC motor. The design steps include two parts. The first part uses the genetic algorithm (GA) to obtain the optimum parameters of Single Neuron PID (SNPID) controller, while the former deals with the design of fuzzy logic control to update the weights of SNPID control online. To demonstrate the designed controller effectiveness, a comparative study is made with between the NFSNPID, Conventional Fuzzy Single Neuron PID CFSNPID and SNPID. All controllers were used to drive, separately, the brushless DC motor against the sudden change of load and operating speed. The performed simulations show better results that motivate for further investigations.
Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance

Although peptides are safe and useful as therapeutics, they are often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy for increasing the efficacy of peptide therapies. Natriuretic peptide receptor B (NPR-B) and its naturally occurring ligand, C-type natriuretic peptide (CNP), are potent stimulators of endochondral bone growth, and activating the CNP/NPR-B system is expected to be a powerful strategy for treating impaired skeletal growth. CNP is cleared by natriuretic peptide clearance receptor (NPR-C); therefore, we investigated the effect of reducing the rate of CNP clearance on skeletal growth by limiting the interaction between CNP and NPR-C. Specifically, we generated transgenic mice with increased circulating levels of osteocrin (OSTN) protein, a natural NPR-C ligand without natriuretic activity, and observed a dose-dependent skeletal overgrowth phenotype in these animals. Skeletal overgrowth in OSTN-transgenic mice was diminished in either CNP- or NPR-C–depleted backgrounds, confirming that CNP and NPR-C are indispensable for the bone growth–stimulating effect of OSTN. Interestingly, double-transgenic mice of CNP and OSTN had even higher levels of circulating CNP and additional increases in bone length, as compared with mice with elevated CNP alone. Together, these results support OSTN administration as an adjuvant agent for CNP therapy and provide a potential therapeutic approach for diseases with impaired skeletal growth.
L2-Nonexpansive Neural Networks

This paper proposes a class of well-conditioned neural networks in which a unit amount of change in the inputs causes at most a unit amount of change in the outputs or any of the internal layers. We develop the known methodology of controlling Lipschitz constants to realize its full potential in maximizing robustness, with a new regularization scheme for linear layers, new ways to adapt nonlinearities and a new loss function. With MNIST and CIFAR-10 classifiers, we demonstrate a number of advantages. Without needing any adversarial training, the proposed classifiers exceed the state of the art in robustness against white-box L2-bounded adversarial attacks. They generalize better than ordinary networks from noisy data with partially random labels. Their outputs are quantitatively meaningful and indicate levels of confidence and generalization, among other desirable properties.
Sex, Scavengers, and Chaperones: Transcriptome Secrets of Divergent Symbiodinium Thermal Tolerances

Corals rely on photosynthesis by their endosymbiotic dinoﬂagellates ( Symbiodinium spp.) to form the basis of tropical coral reefs. High sea surface temperatures driven by climate change can trigger the loss of Symbiodinium from corals (coral bleaching), leading to declines in coral health. Different putative species (genetically distinct types) as well as conspeciﬁc populations of Symbiodinium can confer differing levels of thermal tolerance to their coral host, but the genes that govern dinoﬂagellate thermal tolerance are unknown. Here we show physiological and transcriptional responses to heat stress by a thermo-sensitive (physiologically susceptible at 32 (cid:2) C) type C1 Symbiodinium population and a thermo-tolerant (physiologically healthy at 32 (cid:2) C) type C1 Symbiodinium population. After nine days at 32 (cid:2) C, neither population exhibited physiological stress, but both displayed up-regulation of meiosis genes by (cid:3) 4-fold and enrichment of meiosis functional gene groups, which promote adaptation. After 13 days at 32 (cid:2) C, the thermo-sensitive population suffered a signiﬁcant decrease in photosynthetic efﬁciency and increase in reactive oxygen species (ROS) leakage from its cells, whereas the thermo-tolerant population showed no signs of physiological stress. Correspondingly, only the thermo-tolerant population demonstrated up-regulation of a range of ROS scavenging and molecular chaperone genes by (cid:3) 4-fold and enrichment of ROS scavenging and protein-folding functional gene groups. The physiological and transcriptional responses of the Symbiodinium populations to heat stress directly correlate with the bleaching susceptibilities of corals that harbored these same Symbiodinium populations. Thus, our study provides novel, foundational insights into the molecular basis of dinoﬂagellate thermal tolerance and coral bleaching.
Sarcopenia is associated with incident albuminuria in patients with type 2 diabetes: A retrospective observational study

Sarcopenia, defined as age‐related loss of skeletal muscle mass and function, increases the risk of albuminuria. However, it has still unknown whether sarcopenia could increase the risk for the progression of albuminuria. A total 238 patients with type 2 diabetes (mean age 64 ± 12 years; 39.2% women) were studied in the present retrospective observational study. The prevalence of sarcopenia was 17.6%. During the median follow‐up period of 2.6 years, albuminuria was measured 5.8 ± 1.8 times, and progression of albuminuria was observed in 14.9% of patients with normoalbuminuria, as was 11.5% in those with microalbuminuria. Sarcopenia was significantly associated with both progression (hazard ratio 2.61, 95% confidence interval 1.08–6.31, P = 0.034) and regression (hazard ratio 0.23, 95% confidence interval 0.05–0.98, P = 0.048) of albuminuria by multivariate Cox regression analysis. The present data suggest that sarcopenia is an important determinant of both progression and regression of albuminuria in patients with type 2 diabetes.
Resistance to Multiple Temperate and Tropical Stem and Sheath Diseases of Rice

Reaction to sheath blight, stem rot, and aggregated sheath spot were tested in 641 tropical japonica and indica rice lines. Disease resistance was mapped independently from flowering time and plant height. Quantitative trait loci of major effect for resistance to the three diseases were found. A multiple disease resistance quantitative trait locus was found on chromosome 9 across tropical japonica and indica populations.
Metallurgical quality evaluation of the wind turbine main shaft 42CrMo4 steel: microscopic and Mössbauer studies

Abstract In this paper, the results of the complex examination of the 42CrMo4 steel samples are presented. The samples were taken from the metallurgical forging prepared for the production of the wind turbine main shaft. The samples underwent Mössbauer spectroscopic analysis, as well as the measurement of its mechanical characteristics such as hardness and strength are analysed. Conversion electron Mössbauer spectrometry confirmed phase purity and isotropy of the investigated 42CrMo4 steel. The method provided accurate results, proving Mössbauer spectrometry to be an effective tool for the wind turbine main shaft analysis.
UBASH3B-mediated silencing of the mitotic checkpoint: Therapeutic perspectives in cancer

ABSTRACT Defects in mitosis can lead to aneuploidy, which is a common feature of human cancers. Spindle Assembly Checkpoint (SAC) controls fidelity of chromosome segregation in mitosis to prevent aneuploidy. The ubiquitin receptor protein Ubiquitin Associated and SH3 Domain Containing B (UBASH3B) was recently found to control SAC silencing and faithful chromosome segregation by relocalizing Aurora B kinase to the mitotic microtubules. Accordingly, loss and gain of function of UBASH3B have strong effects on mitotic progression. Downregulation of UBASH3B prevents SAC satisfaction leading to inhibition of chromosome segregation, mitotic arrest, and cell death. In contrast, increased cellular levels of UBASH3B trigger premature and uncontrolled chromosome segregation. Interestingly, elevated levels of UBASH3B were found in aggressive tumors. Therefore, we raised the question whether the oncogenic potential of UBASH3B is linked to its role in chromosome segregation. Here we show that in cancer cells expressing high levels of UBASH3B and SAC proteins, downregulation of UBASH3B, can further potentiate SAC response inducing mitotic arrest and cell death. Moreover, data mining approaches identified a correlation between mRNA levels of UBASH3B and SAC components in a set of primary patient tumors including kidney and liver carcinomas. Thus, inhibition of UBASH3B may offer an attractive therapeutic perspective for cancers.
Clinically Meaningful Comparisons Over Time: An Approach to Measuring Patient Similarity based on Subsequence Alignment

Longitudinal patient data has the potential to improve clinical risk stratification models for disease. However, chronic diseases that progress slowly over time are often heterogeneous in their clinical presentation. Patients may progress through disease stages at varying rates. This leads to pathophysiological misalignment over time, making it difficult to consistently compare patients in a clinically meaningful way. Furthermore, patients present clinically for the first time at different stages of disease. This eliminates the possibility of simply aligning patients based on their initial presentation. Finally, patient data may be sampled at different rates due to differences in schedules or missed visits. To address these challenges, we propose a robust measure of patient similarity based on subsequence alignment. Compared to global alignment techniques that do not account for pathophysiological misalignment, focusing on the most relevant subsequences allows for an accurate measure of similarity between patients. We demonstrate the utility of our approach in settings where longitudinal data, while useful, are limited and lack a clear temporal alignment for comparison. Applied to the task of stratifying patients for risk of progression to probable Alzheimer's Disease, our approach outperforms models that use only snapshot data (AUROC of 0.839 vs. 0.812) and models that use global alignment techniques (AUROC of 0.822). Our results support the hypothesis that patients' trajectories are useful for quantifying inter-patient similarities and that using subsequence matching and can help account for heterogeneity and misalignment in longitudinal data.
Genome-wide association study reveals genetic loci and candidate genes for average daily gain in Duroc pigs

Objective Average daily gain (ADG) is an important target trait of pig breeding programs. We aimed to identify single nucleotide polymorphisms (SNPs) and genomic regions that are associated with ADG in the Duroc pig population. Methods We performed a genome-wide association study involving 390 Duroc boars and by using the PorcineSNP60K Beadchip and two linear models. Results After quality control, we detected 3,5971 SNPs, which included seven SNPs that are significantly associated with the ADG of pigs. We identified six quantitative trait loci (QTL) regions for ADG. These QTLs included four previously reported QTLs on Sus scrofa chromosome (SSC) 1, SSC5, SSC9, and SSC13, as well as two novel QTLs on SSC6 and SSC16. In addition, we selected six candidate genes (general transcription factor 3C polypeptide 5, high mobility group AT-hook 2, nicotinamide phosphoribosyltransferase, oligodendrocyte transcription factor 1, pleckstrin homology and RhoGEF domain containing G4B, and ENSSSCG00000031548) associated with ADG on the basis of their physiological roles and positional information. These candidate genes are involved in skeletal muscle cell differentiation, diet-induced obesity, and nervous system development. Conclusion This study contributes to the identification of the casual mutation that underlies QTLs associated with ADG and to future pig breeding programs based on marker-assisted selection. Further studies are needed to elucidate the role of the identified candidate genes in the physiological processes involved in ADG regulation.
Acute Renal Failure in Intensive Care Burn Patients (ARF in Burn Patients)

The purpose of this study was to establish the incidence and mortality of burn patients with acute renal failure (ARF) at the Helsinki Burn Centre and to analyze the associated factors. The files of 238 intensive care (ICU) patients of a total of 1380 burn patients admitted to our institution between November 1988 and December 2001 were studied retrospectively. Of all admitted burn patients, 17.2% needed ICU. According to our criteria (S-Cr >120 &mgr;mol/l = 1.4 mg/dl), 39.1% of the ICU patients suffered from ARF and one in three of these required renal replacement therapy. The proportion of all admitted burn patients requiring renal replacement therapy was 2.3%. The mortality of ICU patients with ARF was 44.1% whereas that of patients without ARF was only 6.9%. Renal function recovered in all survivors. The nonsurvivors had a larger burned total body surface area, were older, and had more inhalation injuries and a higher abbreviated burn severity index score. The prognosis for patients with early ARF was worse than that for patients with late ARF. Rhabdomyolysis caused by flame injury was associated with high mortality. In this study we observed that ARF is associated with higher mortality even in minor burns when compared with patients without ARF. Flame burn with rhabdomyolysis and subsequent ARF predicts very poor survival. If a patient with severe ARF survives, the renal failure recovers over time.
Cerebral vasomotor reactivity in reversible cerebral vasoconstriction syndrome

Background Altered cerebrovascular tone is implicated in reversible cerebral vasoconstriction syndrome (RCVS). We evaluated vasomotor reactivity using bedside transcranial Doppler in RCVS patients. Methods In this retrospective case-control study, middle cerebral artery (MCA) blood flow velocities were compared at rest and in response to breath-hold in RCVS (n = 8), Migraineurs (n = 10), and non-headache Controls (n = 10). Hyperventilation response was measured in RCVS. Results In RCVS, Breath Holding Index (BHI) was severely reduced in seven of eight patients and 14/16 MCAs; seven of 16 MCAs showed exhausted (BHI < 0.1) or inverted (BHI < 0) vasomotor reactivity. Mean BHI in RCVS (0.23 ± 0.5) was significantly lower than Migraine (1.52 ± 0.57) and Controls (1.51 ± 0.32), p < 0.001. Triphasic velocity responses were seen in all groups. The maximum Vmean decline during the middle negative phase was −15.5 ± 9.2% in RCVS, −15.4 ± 7% in Migraine, and −10.3 ± 5% in Controls (p = 0.04). In the late positive phase, average Vmean increase was 6.2 ± 14% in RCVS, which was significantly lower (p < 0.001) than Migraine (30.5 ± 11%) and Controls (30.2 ± 6%). With hyperventilation, RCVS patients showed 23% decrease in Vmean. Conclusion Cerebral arterial tone is abnormal in RCVS, with proximal vasoconstriction and abnormally reduced capacity for vasodilation. Further studies are needed to determine the utility of BHI to diagnose RCVS before angiographic reversibility is established, and to estimate prognosis.
Characteristics of Metacordyceps yongmunensis, a New Species from Korea

Metacordyceps yongmunensis is a newly reported species from Korea, which is very similar to Cordyceps species in morphological characters. It grows on large lepidopteran pupa, and numerous white stromata grow on a single host. Mycelial growth characteristics of M. yongmunensis isolates were studied in different media and at different temperatures. Also, different carbon sources, nitrogen sources, and mineral salts were tested for mycelial growth of M. yongmunensis. Schizophyllum (mushroom) genetics complete medium plus yeast extract, Schizophyllum (mushroom) genetics minimal medium, and Martin’s peptone dextrose agar produced longer colony diameters and more compact mycelial density than other media. The optimum temperature for mycelial growth was 25°C. Carbon sources such as sucrose, soluble starch, dextrose, glucose, dextrin, maltose, and fructose showed better mycelial growth, whereas peptone, yeast extract and tryptone resulted in the best mycelial growth of all of the nitrogen sources tested. All of the mineral salts tested showed similar growth as the control, except K2HPO4 which showed longer colony diameter and more compact mycelial density. The compact colonies were white and cottony with a greenish margin. The results showed that M. yongmunensis is an easy fungus to growas it grew from 30 to more than 50 mm in 2 wk.
Genome-wide DNA methylation sequencing reveals miR-663a is a novel epimutation candidate in CIMP-high endometrial cancer

Aberrant DNA methylation is widely observed in many cancers. Concurrent DNA methylation of multiple genes occurs in endometrial cancer and is referred to as the CpG island methylator phenotype (CIMP). However, the features and causes of CIMP-positive endometrial cancer are not well understood. To investigate DNA methylation features characteristic to CIMP-positive endometrial cancer, we first classified samples from 25 patients with endometrial cancer based on the methylation status of three genes, i.e. MLH1, CDH1 (E-cadherin) and APC: CIMP-high (CIMP-H, 2/25, 8.0%), CIMP-low (CIMP-L, 7/25, 28.0%) and CIMP-negative (CIMP(-), 16/25, 64.0%). We then selected two samples each from CIMP-H and CIMP(-) classes, and analyzed DNA methylation status of both normal (peripheral blood cells: PBCs) and cancer tissues by genome-wide, targeted bisulfite sequencing. Genomes of the CIMP-H cancer tissues were significantly hypermethylated compared to those of the CIMP(-). Surprisingly, in normal tissues of the CIMP-H patients, promoter region of the miR-663a locus is hypermethylated relative to CIMP(-) samples. Consistent with this finding, miR-663a expression was lower in the CIMP-H PBCs than in the CIMP(-) PBCs. The same region of the miR663a locus is found to be highly methylated in cancer tissues of both CIMP-H and CIMP(-) cases. This is the first report showing that aberrant DNA methylation of the miR-663a promoter can occur in normal tissue of the cancer patients, suggesting a possible link between this epigenetic abnormality and endometrial cancer. This raises the possibility that the hypermethylation of the miR-663a promoter represents an epimutation associated with the CIMP-H endometrial cancers. Based on these findings, relationship of the aberrant DNA methylation and CIMP-H phenotype is discussed.
Quantification of Phenolic Compounds and In Vitro Radical Scavenging Abilities with Leaf Extracts from Two Varieties of Psidium guajava L.

Guava leaf (Psidium guajava L.) extracts are used in both traditional medicine and the pharmaceutical industry. The antioxidant compounds in P. guajava leaves can have positive effects including anti-inflammatory, anti-hyperglycemic, hepatoprotective, analgesic, anti-cancer effects, as well as protecting against cardiovascular diseases. In the present study, phenolic compounds and in vitro antioxidant capacity were measured in extracts obtained with polar and non-polar solvents from leaves of two varieties of guava, Calvillo Siglo XXI and Hidrozac. The quantity of total phenolics and total flavonoids were expressed as equivalents of gallic acid and quercetin, respectively. Hydroxyl radical, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and Oxygen Radical Absorbance Capacity using fluorescein (ORAC-FL) in vitro tests were used to assess the radical scavenging abilities of the extracts. The total phenolics were higher in the aqueous fraction of the variety Calvillo Siglo XXI, while in the Hidrozac variety total phenolics were higher in the acetone and chloroform fractions. Total flavonoids were higher in all fractions in the variety Calvillo Siglo XXI. Total phenolics showed a highly positive correlation for ORAC-FL, and a moderately positive correlation with hydroxyl radicals. Finally, total flavonoids showed a slightly positive correlation for ORAC-FL and hydroxyl radicals. Both varieties of guava leaf extract showed excellent antioxidant properties.