Miracle-dz/UniFAR-FTUs huggingface dataset:
Control and integration of cell signaling pathways during C. Elegans vulval development

Vulval development in the Caenorhabditis elegans hermaphrodite represents a simple, genetically tractable system for studying how cell signaling events control cell fata decisions. Current models suggest that proper specification of vulval cell fates relies on the integration of multiple signaling systems, including one that involves a receptor tyrosine kinase (RTK)→Ras→mitogen activated protein kinase (MAPK) cascade and one that involves a LIN‐12/Notch family receptor. In this review, we first discuss how genetic strategies are being used to identify and analyze components that control vulval cell fate decisions. We then describe the different signaling systems that have been elucidated and how they relate to one another. Finally, we highlight several recently characterized genes that encode positive regulators, negative regulators or potential targets of the RTK→Ras→MAPK cascade involved in vulval induction.
The genetics of sporadic ruptured and unruptured intracranial aneurysms: a genetic meta-analysis of 8 genes and 13 polymorphisms in approximately 20,000 individuals.

OBJECT Intracranial aneurysms (IAs) are thought to have a multifactorial origin. The authors undertook a comprehensive meta-analysis on all genes investigated using a case-control model in ruptured (subarachnoid hemorrhage) and unruptured aneurysms. METHODS Electronic databases were searched until and including July 2008 for any candidate gene studied in IA or subarachnoid hemorrhage using a case-control model. The ORs and 95% CIs were determined for each gene-disease association using fixed and random effect models. RESULTS Thirty studies of 8 genes and 13 polymorphisms were analyzed among 19,961 individuals (6622 cases and 13,339 controls). Two genes and 3 polymorphisms were associated with IA. The eNOS gene T786C polymorphism (OR 1.24, 95% CI 1.0-1.54; p = 0.05) and IL-6 gene G572C polymorphism (OR 7.08, 95% CI 2.85-17.57; p < 0.0001) both showed a significant association with ruptured/unruptured IA. The IL-6/G174C polymorphism exerted a significant protective effect against IA (OR 0.49, 95% CI 0.25-0.95; p = 0.04). The other candidate genes investigated (ACE, endoglin, APOE, elastin, MMP-3, and SERPINA3) showed no significant associations. CONCLUSIONS There is a likely genetic basis to sporadic IAs. However, the evidence base is small when compared against other complex disorders.
Characterization of the P Protein-Binding Domain on the 10-Kilodalton Protein of Borna Disease Virus

ABSTRACT The Borna disease virus (BDV) is the prototype member of the Bornaviridae, and it replicates in the cell nucleus. The BDV p24P and p40N proteins carry nuclear localization signals (NLS) and are found in the nuclei of infected cells. The BDV p10 protein does not have an NLS, but it binds with P and/or N and is translocated to the nucleus. Hence, p10 may play a role in the replication of BDV in the cell nucleus. Here, we show that the P-binding domain is located in the N terminus of p10 and that S3 and L16 are important for the interaction.
Best practice in reengineering: a successful example of the Porsche research and development center

Successful reengineering requires a systematic procedure for the useful implementation of methods and tools as well as a consideration of critical success factors. As an example of the reengineering of prototype part procurement in Porsche AG’s development centre, a specially developed 3x3 reengineering procedure is represented which not only implements methods and tools but also the reengineering project structure and experiences gained from it. The main aim of re‐engineering was to reduce the running time of the part procurement from 30 days to just one. This means a simultaneous reduction of the prototype construction time to about 20 hours. From results it can be established that after 20 weeks the success of the reengineering stabilised and the targeted running time of one day became apparent. The accompanying project evaluation crystallised various success factors. In particular the establishment of a competent and motivated team leader, as well as on‐line process controlling supported by IT implementation, have proved to be a successfully decisive measure and tool respectively.
Role of membrane transporters in the safety profile of drugs

It has increasingly been recognized that few molecules move across the cell membrane without the assistance of transporter proteins. Large superfamilies of transporter proteins have been identified in every living cell, including microorganisms and mitochondria. This report reviews the role of transporters in physiology and pharmacology, and identifies where this may have an impact on drug efficacy and toxicity. This new understanding will require a fresh appreciation of pharmacokinetics and drug effects, as the current paradigms are based largely on the assumption that drug molecules have a reasonable unrestricted permeability across membranes. Rather than just focusing on clearance changes and central compartment pharmacokinetics, it will become increasingly necessary to examine the peripheral tissue distribution of drugs to more accurately predict drug efficacy and toxicity.
Static analysis of Biological Regulatory Networks dynamics using abstract interpretation

The analysis of the dynamics of Biological Regulatory Networks (BRNs) requires innovative methods to cope with the state-space explosion. This paper settles an original approach for deciding reachability properties based on Process Hitting, which is a framework suitable for modelling dynamical complex systems. In particular, Process Hitting has been shown to be of interest in providing compact models of the dynamics of BRNs with discrete values. Process Hitting splits a finite number of processes into so-called sorts and describes the way each process is able to act upon (that is, to ‘hit’) another one (or itself) in order to ‘bounce’ it as another process of the same sort with further actions. By using complementary abstract interpretations of the succession of actions in Process Hitting, we build a very efficient static analysis to over- and under-approximate reachability properties, which avoids the need to build the underlying states graph. The analysis is proved to have a low theoretical complexity, in particular when the number of processes per sorts is limited, while a very large number of sorts can be managed. This makes such an approach very promising for the scalable analysis of abstract complex systems. We illustrate this through the analysis of a large BRN of 94 components. Our method replies quasi-instantaneously to reachability questions, while standard model-checking techniques regularly fail because of the combinatoric explosion of behaviours.
Mycotic keratitis: profile of Fusarium species and their mycotoxins

In this study, Fusarium species isolated from 29 patients with mycotic keratitis were identified and tested for their ability to produce mycotoxins. Members of the F. solani species complex (Fs complex) were the predominant species isolated, followed by F. verticillioides, F. dimerum, members of the F. oxysporum species complex Fo complex), F. incarnatum, F. chlamydosporum and F. lateritium. Of these, 76% of the Fusarium isolates produced fusaric acid, moniliformin or fumonisin B1. Many of the fusaria isolated are common aetiological agents of mycotic keratitis infections. However, F. incarnatum, F. chlamydosporum and F. lateritium have previously not been found in this infection. These findings indicate that a greater variety of fusarial species are becoming associated with mycotic keratitis infections. This paper further demonstrates the mycotoxin‐producing ability of these clinical isolates and assesses cellular cytotoxicity.
Effects of Neonatal Testicular Suppression with a GnRH Antagonist on Social Behavior in Group-Living Juvenile Rhesus Monkeys

Twenty-four male and eight female 1-year-old rhesus monkeys (Macaca mulatta) were observed for social interaction with other yearlings and with their mothers. The males comprised three groups which differed in the level of neonatal androgen exposure. One group received the GnRH antagonist Antide during their first four neonatal months (Antide n = 8), which suppressed pituitary LH secretion resulting in peak neonatal T levels < 0.7 nmol/liter. A second group received Antide treatment combined with a long-lasting testosterone replacement (Ant/And n = 8), which resulted in peak neonatal T levels of 29.1 +/- 3.8 nmol/liter. The third group (Vehicle n = 8) received the Antide and androgen vehicles and had intermediate peak T levels of 5.2 +/- 1.0 nmol/liter. Behavior of males was compared to that of unmanipulated control females living in the same social group (Control Female n = 8) when androgen levels were uniformly low (< 0.7 nmol/liter) in all male groups. Subjects received 12 weekly 30-min focal observations by an observer blind to the neonatal treatments. Marked sex differences were found in several categories of sociosexual behavior. All three groups of males engaged in significantly more sexual and play behavior than females, with the exception of quiet solitary play, which females exhibited significantly more frequently In addition, females exhibited significantly more interest in infants than did any male group. There were no differences between groups in agonistic behavior or time spent in contact with other individuals, but females spent significantly more time than any male group in proximity to other animals. Both females and Antide males initiated proximity and followed animals significantly more frequently than Ant/And males, but not Vehicle males. Proximity durations with mothers initiated and terminated by yearlings were longer for females than for any male group and for Antide males than for Ant/and males. Antide males were groomed significantly longer than any other group. These results demonstrate effects of neonatal testosterone exposure on social behavior in yearling rhesus. Suppression of neonatal T did not affect sexually dimorphic patterns of play and sexual behavior, but altered the character of interactions with their mothers. Whether this reflects a delay in the development of maternal independence or a fundamental alteration in patterns of social interaction remains to be resolved.
Relationships Between Plasma Levels and Psychological Effects of Benzodiazepines

In the past, pharmacokinetics of benzodiazepines have been extensively described. However, knowledge about relationships between their plasma levels and pharmacodynamic effects are scanty. Therefore, we investigated under several experimental conditions the disposition and the psychological response of the short acting midazolam (single dose 0,075 mg/kg i.v. and 15 mg po) and of the moderate long acting oxazepam (30 mg/die for 5 days). Psychological and psychomotoric effects were evaluated by analogue scales (sedation index), d-2 letter cancellation test, reaction time, critical flicker fusion frequency and adjective mood list. In general, good correlations were found between those tests and plasma levels, especially for midazolam. Analogue scales and reaction-time proved to be most useful in our "effect-kinetic" approach.
MIPS64 simulator on a mobile environment

There are several MIPS simulators which are already available for the students to use. However, majority of the existing works are developed in the year 2005 or older, all of which are PC-based while most of the people are now using mobile or tablet-based technologies. A mobile application called Mobile-based MIPS Simulator (MMIPSS) is a simulator for MIPS64 Architecture that is capable of simulating MIPS64 assembly codes. It also supports pipeline map of the assembly code and all types of MIPS64 static pipeline methods that are essential in understanding computer architecture and are not complete in majority of existing simulators.
HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro.

OBJECTIVES We investigated the in vitro phenotypic susceptibility of HIV-2 isolates from integrase inhibitor (INI)-naive patients to INIs and its relation to HIV-2 integrase gene polymorphism. METHODS We determined the phenotypic susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values were compared with those for HIV-1 reference strains. HIV-2 integrase gene polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the French HIV-2 cohort. RESULTS Median raltegravir and elvitegravir IC(50) values for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38% of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the HHCC and RKK motifs were fully conserved, at the same genomic positions as described in HIV-1. In subtype B isolates, the total length of the integrase gene varied, owing to the presence of stop codons at positions 288, 294, 297 and 302. Fourteen of the positions associated with substitutions conferring INI resistance in HIV-1 were polymorphic in HIV-2. CONCLUSIONS Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.
Analogue transformation acoustics: Generalizing transformation techniques to non-form-invariant equations

Using the idea of analogue spacetimes, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. We illustrate the use of the method by designing acoustic versions of a dynamic compressor and a spacetime cloak. The proposed method can be generalized to transform other kinds of physical fields beyond the constraint of form-invariance, finding potential applications in other branches such as quantum fluids and graphene electronics.
Three-Dimensional Finite Element Analysis of Lower Molar Tooth Restored with Fully Milled and Layered Zirconia Crowns

Comparing the principle stresses distributions for both fully milled zirconia (FMZ) crown made of yattria-stabilized zirconia (Y-TZP) and layered crowns made Y-TZP core and feldspathic porcelain veneer using finite element analysis, was shot in this study. A three dimensional finite element model was constructed under ANSYS environment. The natural prepared tooth or titanium (Ti) abutment/implant complex were modeled in 3D on commercial general purpose CAD/CAM software. Crown geometry was acquired by using 3D contact scanner, which goes through successive graphical modification before assembled in a 3D finite element model. Crown made from single material (FMZ) is stiffer than layered one. The crown outer layer (Porcelain) receives more energy and stresses (of order 3.8%) than if it was made from Zirconia. While the crown core (inner part) will receive less stresses (about 38%) and energy if it was coated by Porcelain.
Urban–rural mental health differences in Great Britain: findings from the National Morbidity Survey

Background. Studies of urban–rural differences in prevalence of non-psychotic mental disorder have not given consistent findings. Such differences have received relatively little study in Great Britain. Methods. Data from 9777 subjects in the Household Survey of the National Morbidity Survey of Great Britain were analysed for differences between urban, semi-rural and rural areas. Psychiatric morbidity was assessed by scores on the Revised Clinical Interview Schedule (CIS-R), together with alcohol dependence, drug dependence, receipt of treatment from general practitioners. Associations with other characteristics were examined by logistic regression. Results. Urban subjects had higher rates than rural of CIS-R morbidity, alcohol dependence and drug dependence, with semi-rural subjects intermediate. Urban subjects also tended to be members of more deprived social groups, with more adverse living circumstances and greater life stress, factors themselves associated with disorder. Urban–rural differences in alcohol and drug dependence were no longer significant after adjustment for these factors by logistic regression, and differences on CIS-R morbidity were considerably reduced. There were no differences in treatment. Conclusions. There are considerable British urban–rural differences in mental health, which may largely be attributable to more adverse urban social environments.
The role of adhesion molecules and T cells in ischemic renal injury

Purpose of reviewThe pathophysiology of ischemic acute renal failure is complex, incompletely understood and there are no specific therapies. Descriptive observations in human acute renal failure, as well as mechanistic studies in animals, have demonstrated an important pathophysiological role for leukocytes and leukocyte adhesion molecules. The purpose of this review is to summarize and interpret the recent advances on the role of T cells and leukocyte adhesion molecules in ischemic acute renal failure. Recent findingsEmerging data suggest that the T cell is involved in modulating the outcome of ischemic acute renal failure, as well as ischemic injury to other organs. These new data build on the established role of inflammation in acute renal failure, and identify novel therapeutic targets. In addition, identification of the role of the T cell in the immediate injury response extends current immunological models of T cell function. Studies on leukocyte adhesion in acute renal failure have now identified the selectins and their ligands as important components of the inflammatory response to ischemic injury. SummaryThe identification of T cells and new adhesion molecule pathways as modulators of ischemic acute renal failure offers novel and feasible therapeutic opportunities for both native and transplant acute renal failure. Rigorous clinical trials are required to translate these basic findings to the bedside. In addition, mechanistic studies are needed to elucidate the molecular mechanisms by which these pathways modulate kidney injury. The identification of T cell engagement in ischemic renal injury can also help explain long-standing observations linking alloantigen-independent and alloantigen-dependent renal damage.
Sinusoidal surface-mounted pm machine drive using a minimal resolution position encoder

This paper presents a high resolution position estimation system for sinusoidal surface PM machines based on a vector-tracking observer and a 90deg resolution encoder. It is shown here that this is the minimum amount of resolution needed for sinusoidal PM drives. The key implementation issues of this system are presented, and stability analysis is performed, leading to the definition of local stability limits, within which the actual position is tracked with bounded estimation error. The effect that non-uniform sector widths have on position estimation is also explored and a straightforward compensation method is proposed. Both simulation and experimental testing illustrate the performance and limitations of the proposed observer topology and of the drive when this observer is used for state feedback.
Marked for Destruction: MANNOSIDASE4 and 5 Process N-Linked Glycans into ER-Associated Degradation Tags

Elaborate chaperone systems in the endoplasmic reticulum (ER) fold nascent polypeptides and refold misfolded proteins, but if those systems fail or get overwhelmed, the resulting aberrant proteins can be harmful and even toxic to the cell. ER quality control is therefore a critical area of cell
Technological Unemployment: A New View

This paper extends the now familiar Shapiro-Stiglitz (1984) model of labor market behavior to reconsider the controversial proposition that some forms of innovation have persistent displacement effects. In particular, it finds that when distinctions between random production failures and reduced effort level are difficult to draw, the adoption f new methods of production that compel more effort, break down more often and/or allow for closer supervision will sometimes induce technological joblessness. The possible magnitude of such dislocation, its welfare effects and the possibilities for invention are then discussed in detail.
On the toxicokinetics and the metabolism of deoxynivalenol (don) in the pig

Eleven castrated male pigs weighing 88.1 ± 3.9 kg on average were adapted to a diet containing DON (4.2 mg DON/kg) over a period of 7 days. Feed was given restrictively with 1.1 kg per meal (two meals per day). On the day of measurement, all pigs were slaughtered at different time intervals following the morning meal containing DON (1, 2, 3, 4, 5, 6, 8, 15, 18 and 24 h after feeding), with the exception of one pig which was slaughtered unfed. DON and de-epoxy-DON were analysed in serum and digesta from consecutive segments of the digestive tract (stomach, small intestine divided into three parts of a similar length, caecum, colon, rectum). DON was rapidly and nearly completely absorbed while passing through the stomach and the proximal small intestine. Maximum serum concentration appeared 4.1 h after the DON-containing meal and half of the systemically absorbed DON was eliminated after 5.8 h. De-epoxy-DON appeared in increasing proportions from the distal small intestine and reached approximately 80% of the sum of DON plus de-epoxy-DON in faeces collected from the rectum. It was concluded that de-epoxydation of DON, which primarily occurs in the hindgut, probably does not contribute much to a detoxification in the pig.
The Effect of Prey Density on Predators: Conspicuousness and Attack Success Are Sensitive to Spatial Scale

In contrast to the numerous studies that have examined the response of predators to prey group size, little is known about how prey density affects prey detection and the accuracy of attacks. We demonstrate that increasing the density of Daphnia magna swarms increases conspicuousness to a natural predator, the three‐spined stickleback. Denser areas of groups were more conspicuous, as the fish attacked prey in denser parts of the group than would be expected if they attacked the nearest prey upon entering the feeding chamber. The spatial error of attacks also increased with the density around the target; hence, different stages of predation (searching for vs. successfully attacking prey) seem to select for opposing responses to prey density. However, whereas the effect of density on target selection only occurred using a global measure of density (average interindividual distance), the effect on attack error was only significant using a local measure of density (Voronoi polygon area). We believe this effect of spatial scale reflects the reduction in the number of prey in the visual field of the predator as an attack progresses, providing a perceptual basis for the importance of spatial scale in density‐dependent processes.
Control Oriented Modeling of Combustion Phasing for an HCCI Engine

A promising method for reducing emissions and fuel consumption of internal combustion engines is the Homogeneous charge compression ignition (HCCI) engine. Control of ignition timing must be realized before the potential benefits of HCCI combustion can be implemented in production engines. A model suitable for real time implementation is developed and this model is able to predict ignition timing with an average error of less than 2 crank angle degrees. A modified knock- integral model (MKIM), with correlations for gas exchange process and fuel heat release, is used to predict HCCI combustion timing (CA50, crank angle where 50% of the fuel mass is burnt). The MKIM model is parameterized using a thermokinetic simulation model. Experimental data from a single cylinder engine at several HCCI operation conditions and three fuel blends is used to validate the model.