Miracle-dz/UniFAR-FTUs huggingface dataset:
Raf-1 N-terminal sequences necessary for Ras-Raf interaction and signal transduction

Raf-1 is a serine/threonine protein kinase that transduces signals from cell surface receptors to the nucleus. Interaction of Ras with a regulatory domain in the N-terminal half of Raf-1 is postulated to regulate Raf-1 protein kinase and signaling activities. To better understand molecular interactions of Ras with Raf-1 and regulation of the Raf-1 kinase, a panel of Raf-1 N-terminal mutants expressed in the baculovirus-insect cell system was used for mapping the precise region necessary for Ras interaction in the context of full-length, functional Raf-1 kinase. An 80-amino-acid sequence in Raf-1 between positions 53 and 132 was found to confer the ability to bind Ras protein in vitro and in infected insect cells. Deletion of residues 53 to 132 abolished Raf-1 kinase activation by Ras in insect cells, indicating that activation of the Raf-1 kinase by Ras requires the capacity to physically interact with Ras. By contrast, deletion of this Ras-binding site did not diminish activation of Raf-1 kinase by Src, implying that Src and Ras can activate Raf-1 through independent mechanisms. Significantly, Raf-1 mutants lacking the entire zinc finger motif or containing substitutions of two critical cysteine residues in the zinc finger retained the ability to bind Ras and to be activated by this interaction. Consistent with results obtained in the baculovirus-insect cell system, deletion of residues 53 to 132 but not mutations in the zinc finger motif abrogated the ability of kinase-inactive, dominant negative Raf-1 to block Ras-mediated signaling in Xenopus oocytes. Together, these results provide evidence that the direct physical interaction of Ras with Raf-1 amino acids 53 to 132 is required for activation of the Raf-1 kinase and signaling activities by Ras but not by Src. Furthermore, the adjacent zinc finger motif in Raf-1 is not essential either for interaction with Ras or for activation of the Raf-1 kinase.
Effects of NPY-2 Receptor Antagonists, Semaglutide, PYY3-36, and Empagliflozin on Early MASLD in Diet-Induced Obese Rats

(1) Background: Modulators of the Neuropeptide Y (NPY) system are involved in energy metabolism, but the effect of NPY receptor antagonists on metabolic-dysfunction-associated steatotic liver disease (MASLD), a common obesity-related comorbidity, are largely unknown. In this study, we report on the effects of antagonists of the NPY-2 receptor (Y2R) in comparison with empagliflozin and semaglutide, substances that are known to be beneficial in MASLD. (2) Methods: Diet-induced obese (DIO) male Wistar rats were randomized into the following treatment groups: empagliflozin, semaglutide ± PYY3-36, the Y2R antagonists JNJ 31020028 and a food-restricted group, as well as a control group. After a treatment period of 8 weeks, livers were weighed and histologically evaluated. QrtPCR was performed to investigate liver inflammation and de novo lipogenesis (in liver and adipose tissue). Serum samples were analysed for metabolic parameters. (3) Results: Semaglutide + PYY3-36 led to significant weight loss, reduced liver steatosis (p = 0.05), and decreased inflammation, insulin resistance, and leptin levels. JNJ-31020028 prevented steatosis (p = 0.03) without significant weight loss. Hepatic downregulation of de novo lipogenesis-regulating genes (SREBP1 and MLXIPL) was observed in JNJ-31020028-treated rats (p ≤ 0.0001). Food restriction also resulted in significantly reduced weight, steatosis, and hepatic de novo lipogenesis. (4) Conclusions: Body weight reduction (e.g., by food restriction or drugs like semaglutide ± PYY3-36) is effective in improving liver steatosis in DIO rats. Remarkably, the body-weight-neutral Y2R antagonists may be effective in preventing liver steatosis through a reduction in de novo lipogenesis, making this drug class a candidate for the treatment of (early) MASLD.
Experimental infection with Rickettsia mooseri and antibody response of adult and newborn laboratory rats.

Quantitative studies of selected features of peripherally induced Rickettsia mooseri (= R. typhi) infection in Rattus norvegicus-derived white laboratory rats revealed a unique association between microbe and amplifying vertebrate host which appears to be especially conducive to maintenance of the enzootic cycle. Both adult and newborn (1-3 days old) rats were highly susceptible to percutaneous infection (ID50 = approximately 1 organism), but neither showed signs of disease or died even when inoculated with 10(4)-10(5) plaque-forming units. Gain in body weight of infected newborn rats was indistinguishable from that of uninfected newborn rats over the first 3 weeks of life. The course of the systemic infection, as measured by the rise and fall of R. mooseri titers in blood, brain and kidney and the serum antibody response, was almost identical in adult and newborn rats. Thus, despite their immaturity in certain immunological processes, newborn rats controlled postnatal R. mooseri infection about as well as did adult rats. The rickettsemic period of about 10 days corresponds to the period of infectivity of inoculated rats for fleas. Rickettsiae were not isolated from blood, brain or kidneys by methods employed for more than 4-5 weeks after infection. Serum antirickettsial antibodies persisted for at least 60 weeks postinfection, i.e., longer than the usual life span of rats in nature and, hence, are a valid measure of the cumulative experience of rat populations with R. mooseri infection.
Tertiary Stratigraphic Correlation in the Indo-Pacific Region and Australia

A correlation of the Tertiary stratal sequences throughout the area from India to the islands of the Western Pacific and to Australia is attempted. As far as it concerns the Miocene, reference is made to Drooger's work on the stratigraphic distribution of Miogypsinidae and of pelagic Foraminifera. Apparent discrepancies reported from Formosa and Saipan are examined and the factual data are found to be compatible with Drooger's dating of the entry of Orbulina . Abundant information from south. eastern Australia on foraminiferal biostratigraphy is reviewed. Upper Eocene to Miocene foraminiferal zones can be regionally recognised, among them the important Globigerinoides bispherica zone. While its placing in the Helvetian in accordance with Drooger's findings in Europe is compatible with n! '! w observations and is tentatively accepted, a Burdigalian age cannot be ruled out on present evidence. The occurrence of Paleocene, Eocene and Miocene distinctive markers leads to the first fairly detailed correlation of Australian and Indo-Pacific Tertiary strata.
On enhancing the debug architecture of a system-on-chip (SoC) to detect software attacks

The prevalent use of systems-on-chip (SoCs) makes them prime targets for software attacks. Proposed security countermeasures monitor software execution in real-time, but are impractical, and require impractical changes to the internal logic of intellectual property (IP) cores. We leverage the software observability provided by the readily available SoC debug architecture to detect attacks without modifying IP cores. We add hardware components to configure the debug architecture for security monitoring, to store a golden software execution model, and to notify a trusted kernel process when an attack is detected. Our evaluations show that the additions do not impact runtime software execution, and incur 9% area and power overheads on a low-cost processor core.
Dynein from Dictyostelium: primary structure comparisons between a cytoplasmic motor enzyme and flagellar dynein

We report here the cloning and sequencing of a cytoplasmic dynein heavy chain gene from the cellular slime mold Dictyostelium discoideum. Using a combination of approaches, we have isolated 14,318 bp of DNA sequence which contains an open-reading frame of 4,725 amino acids. The deduced molecular weight of the polypeptide predicted by this reading frame is 538,482 D. Overall, the polypeptide sequence is 51% similar and 28% identical to the recently published sequences of the beta-dynein heavy chain from sea urchin flagella (Gibbons, I. R., B. H. Gibbons, G. Mocz, and D. J. Asai. 1991. Nature (Lond.). 352: 640-643; Ogawa, K. 1991. Nature (Lond.). 352:643-645). It contains four GXXXXGKT/S motifs that form part of a consensus sequence for ATP-binding domains; these motifs are clustered near the middle of the polypeptide. The distribution of the regions sharing sequence similarity between the Dictyostelium and sea urchin heavy chain polypeptides suggests that the amino termini of dyneins may contain domains that specify axonemal or cytoplasmic functions.
Development of a surrogate matrix for cerebral spinal fluid for liquid chromatography/mass spectrometry based analytical methods.

RATIONALE In recent years, several liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods have been reported for the quantitative determination of drugs and metabolites in cerebral spinal fluid (CSF). Artificial CSF (aCSF) is often used as a surrogate for preparing calibration curves and quality control samples in these methods. However, aCSF does not accurately represent the composition of real CSF because it is missing all of the proteins and lipids, which may alter the electrospray ionization (ESI) response when performing LC/MS/MS analyses. In the current study we compared the mass spectral response of several compounds with a range of physiochemical properties in aCSF (essentially a mixture of salts and buffers), diluted plasma (ranging from 1:5 to 1:200) and real CSF to find the best surrogate for CSF in LC/MS/MS methods. METHODS A number of analytes from polar to non-polar, high protein binding to low protein binding, employing different sample preparation methods, were prepared in diluted plasma, actual CSF or aCSF and tested using LC/MS/MS. The analytes included cotinine and its metabolites, quetiapine, norquetiapine, chlorpromazine, efavirenz and lamivudine. The similarity of MS responses from these compounds in aCSF and diluted plasma to CSF was assessed by comparing the slopes of the calibration curves generated from using linear regression modeling. RESULTS For all compounds, the lowest percent difference in response ratio (0 to 17%) was observed from 1:200 diluted plasma. Our results indicated that, irrespective of the inherent physiochemical properties of the analytes or the method of sample preparation, 1:200 diluted plasma performed as the best surrogate for CSF in LC/MS/MS methods. CONCLUSIONS The percent difference in response ratio has been established to demonstrate how different compounds behave between CSF, aCSF and dilute plasma. Although among the compounds tested some of them showed a very similar MS response in actual and aCSF, there were analytes that demonstrated significant differences in ESI-MS signal when sprayed from these two matrices. However, even in such cases, 1:200 diluted plasma generated results with no significant difference from CSF. Therefore, we recommend that in order to develop robust and dependable bioanalytical LC/MS methods from CSF samples, it is more appropriate to prepare calibration curves and quality control samples in diluted plasma instead of aCSF. Copyright © 2016 John Wiley & Sons, Ltd.
The number of eigenstates: counting function and heat kernel

The main aim of this paper is twofold: (1) revealing a relation between the counting function N(lambda) (the number of the eigenstates with eigenvalue smaller than a given number) and the heat kernel K(t), which is still an open problem in mathematics, and (2) introducing an approach for the calculation of N(lambda), for there is no effective method for calculating N(lambda) beyond leading order. We suggest a new expression of N(lambda) which is more suitable for practical calculations. A renormalization procedure is constructed for removing the divergences which appear when obtaining N(lambda) from a nonuniformly convergent expansion of K(t). We calculate N(lambda) for D-dimensional boxes, three-dimensional balls, and two-dimensional multiply-connected irregular regions. By the Gauss-Bonnet theorem, we generalize the simply-connected heat kernel to the multiply-connected case; this result proves Kac's conjecture on the two-dimensional multiply-connected heat kernel. The approaches for calculating eigenvalue spectra and state densities from N(lambda) are introduced.
A Case Study of Sockpuppet Detection in Wikipedia

This paper presents preliminary results of using authorship attribution methods for the detection of sockpuppeteering in Wikipedia. Sockpuppets are fake accounts created by malicious users to bypass Wikipedia’s regulations. Our dataset is composed of the comments made by the editors on the talk pages. To overcome the limitations of the short lengths of these comments, we use an voting scheme to combine predictions made on individual user entries. We show that this approach is promising and that it can be a viable alternative to the current human process that Wikipedia uses to resolve suspected sockpuppet cases.
Rigidin E, a New Pyrrolopyrimidine Alkaloid from a Papua New Guinea Tunicate Eudistoma Species

A new pyrrolopyrimidine alkaloid, rigidin E (1) and the known metabolites rigidin (2) and 1-methylherbipoline (3) have been isolated from a Papua New Guinea tunicate Eudistoma sp. A combination of spectroscopic data were used to determine the structures of these metabolites.
Splitting Technique Initialization in Local PCA

The local Principal Component Analysis (PCA) reduces linearly redundant components that may present in higher dimensional space. It deploys an initial guess technique which can be utilized when the distribution of a given multivariate data is known to the user. The problem in initialization arises when the distribution is not known. This study explores a technique that can be easily integrated in the local PCA design and is efficient even when the given statistical distribution is unknown. The initialization using this proposed splitting technique not only splits and reproduces the mean vector but also the orientation of components in the subspace domain. This would ensure that all clusters are used in the design. The proposed integration with the reconstruction distance local PCA design enables easier data processing and more accurate representation of multivariate data. A comparative approach is undertaken to demonstrate the greater effectiveness of the proposed approach in terms of percentage error.
NUTRIENT DISTRIBUTIONS IN AN ESTUARY OF THE ARGENTINE COAST

ABSTRACT We performed a discrete sampling that was programmed to research the axial distribution of dissolved nutrients in surface waters of the Negro river estuary in Argentina. The total dissolved nitrogen (TDN) was composed mainly of NO3and NH4+; but NO2was not detected. Total dissolved phosphorus (TDP) was in PO4-3 and organic species. We obtained spatial and seasonal comparisons from data collected during 2013 and 2016. Both nutrients showed, by analysis of variance (ANOVA), significant differences among the seasons of the year (TDN p<0.0001 and TDP p<0.001). In the internal estuary, the lowest winter levels were 19.4 μM TDN/L, showing that there is a significant difference with autumn levels of 245.6 μM TDN/L by LSD Fischer test (p=0.05); however, the TDN levels in spring were lower than winter at the beginning of the external estuary, and these differences were not significant and could possibly be an indicator of atmospheric removal or re-sedimentation processes in the area. Average TDP values moved in the range between 1.82 μM/L in autumn at the highest, to the lowest values in winter of 0.93 μM/L. The Pearson correlation of N-NO3 and P-PO4 in mg/L to the environmental properties showed a negative correlation with salinity, with a range of 0 to 8% pH, and positive correlations with dissolved oxygen. These eutrophication conditions, as with other rivers of the world, could be generating biodiversity imbalances.
Multiple source domain adaptation: A sharper bound using weighted Rademacher complexity

Traditional supervised learning algorithms assume that the training data and the test data are drawn from the same probability distribution. Considering the assumption is not hold in modern applications of machine learning, domain adaptation problems are proposed when the data distribution in test domain is different from that in training domain. This paper studies the problem of domain adaptation with multiple sources, which has also received considerable attention in many areas. In this paper, we introduce a novelty complexity (weighted Rademacher complexity) to restrict the complexity of a hypothesis class in multiple source domain adaptation. We explore its self bounding properties and give new generalization bounds for multiple source domain adaptation. The results clearly show the benefits with respect to previous bounds for multiple source domain adaptation. We perform extensive experiments over well-known Amazon reviews benchmark data sets and the results demonstrate the well performance of our bound for the multiple source domain adaptation.
Heart and neural tube defects in transgenic mice overexpressing the Cx43 gap junction gene.

Transgenic mice were generated containing a cytomegaloviral promoter driven construct (CMV43) expressing the gap junction polylpeptide connexin 43. RNA and protein analysis confirmed that the transgene was being expressed. In situ hybridization analysis of embryo sections revealed that transgene expression was targeted to the dorsal neural tube and in subpopulations of neural crest cells. This expression pattern was identical to that seen in transgenic mice harboring other constructs driven by the cytomegaloviral promoter (Kothary, R., Barton, S. C., Franz, T., Norris, M. L., Hettle, S. and Surani, M. A. H. (1991) Mech. Develop. 35, 25-31; Koedood, M. , Fitchel, A. , Meier, P. and Mitchell, P. (1995) J. Virol. 69, 2194-2207), and corresponded to a subset of the endogenous Cx43 expression domains. Significantly, dye injection studies showed that transgene expression resulted in an increase in gap junctional communication. Though viable and fertile, these transgenic mice exhibited reduced postnatal viability. Examination of embryos at various stages of development revealed developmental perturbations consisting of cranial neural tube defects (NTD) and heart malformations. Interestingly, breeding of the CMV43 transgene into the Cx43 knockout mice extended postnatal viability of mice homozygote for the Cx43 knockout allele, indicating that the CMV43 trangsene may partially complement the Cx43 deletion. Both the Cx43 knockout and the CMV43 transgenic mice exhibit heart defects associated with malformations in the conotruncus, a region of the heart in which neural crest derivatives are known to have important roles during development. Together with our results indicating neural-crest-specific expression of the transgene in our CMV-based constructs, these observations strongly suggest a role for Cx43-mediated gap junctional communication in neural crest development. Furthermore, these observations indicate that the precise level of Cx43 function may be of critical importance in downstream events involving these migratory cell populations. As such, the CMV43 mouse may represent a powerful new model system for examining the role of extracardiac cell populations in cardiac morphogenesis and other developmental processes.
Hepatocyte Growth Factor and Clinical Diabetes in Postmenopausal Women

OBJECTIVE To investigate the association between circulating levels of hepatocyte growth factor (HGF), a mesenchymal-derived pleiotrophic factor that is elevated in obesity, and the prevalence of type 2 diabetes. RESEARCH DESIGN AND METHODS A cross-sectional analysis among 892 postmenopausal women within the Women's Health Initiative Observational Study (WHI-OS). RESULTS HGF levels positively correlated with BMI and homeostasis model assessment for insulin resistance. In the multivariable analysis comparing the highest tertile with the lowest tertile of HGF, the odds ratio for prevalent diabetes was 2.47 (95% CI [1.12–5.47], P for trend = 0.014) after accounting for age, race, BMI, and other risk factors for diabetes. CONCLUSIONS HGF levels are associated with the presence of type 2 diabetes in postmenopausal women. Future studies should consider the prospective evaluation of the association of HGF with the development of type 2 diabetes.
The effects of prior warning and lifting-induced fatigue on trunk muscle and postural responses to sudden loading during manual handling

This study investigated the effects of warning and lifting-induced fatigue on trunk muscle activity and postural responses to sudden loading. Thirty-one male subjects were subjected to sudden loading of a hand-held box with and without prior warning, before and after either lifting-induced fatigue or light callisthenic exercises. Results showed that warning did not alter the level of trunk muscle activity prior to sudden loading. Following warning, there was a reduction in all muscle and joint onset latencies and the magnitude of hip and knee flexion. Although fatigue did not influence muscle and joint initiation, it did negate the effects that warning had on reducing joint displacement. These findings indicate that warning prior to sudden loading may enhance postural responses, reduce ranges of joint motion and increase stability. However, the benefits of prior warning for reducing ranges of joint motion may not be present when a person is fatigued. Sudden unexpected loading and fatigue arising from manual handling practices in the workplace have been identified as contributing factors to the risk of low back injury. Findings from this study provide information that is important for the design of interventions intended to reduce the incidence of manual handling-related back injuries.
Redundancy in spatial databases

Spatial objects other than points and boxes can be stored in spatial indexes, but the techniques usually require the use of approximations that can be arbitrarily bad. This leads to poor performance and highly inaccurate responses to spatial queries. The situation can be improved by storing some objects in the index redundantly. Most spatial indexes permit no flexibility in adjusting the amount of redundancy. Spatial indexes based on z-order permit this flexibility. Accuracy of the query response increases with redundancy, (there is a “diminishing return” effect). Search time, as measured by disk accesses first decreases and then increases with redundancy. There is, therefore, an optimal amount of redundancy (for a given data set). The optimal use of redundancy for z-order is explored through analysis of the z-order search algorithm and through experiments.
Decoupled multimodel predictive control based on multi-observer for discrete-time uncertain nonlinear systems

This paper deals with a decoupled multimodel predictive control for discrete-time uncertain nonlinear systems. The control scheme is based on a multi-observer for the state estimation of uncertain nonlinear systems described by decoupled multimodel. A partial controller and observer is synthesized for each local model. In order to ensure the closed-loop performances, a supervisor is proposed to select the appropriate controller. Simulation example is carried out to exhibit the effectiveness of the proposed control strategy.