Miracle-dz/UniFAR-FTUs huggingface dataset:
The Lipid-binding Domain of Wild Type and Mutant α-Synuclein

α-Synuclein (αS) is linked to Parkinson disease through its deposition in an amyloid fibril form within Lewy Body deposits, and by the existence of three αS point mutations that lead to early onset autosomal dominant Parkinsonism. The normal function of αS is thought to be linked to the ability of the protein to bind to the surface of synaptic vesicles. Upon binding to vesicles, αS undergoes a structural reorganization from a dynamic and disordered ensemble to a conformation consisting of a long extended helix. In the presence of small spheroidal detergent micelles, however, this extended helix conformation can convert into a broken helix state, in which a region near the middle of the helix unwinds to form a linker between the two resulting separated helices. Membrane-bound conformations of αS likely mediate the function of the protein, but may also play a role in the aggregation and toxicity of the protein. Here we have undertaken a study of the effects of the three known PD-linked mutations on the detergent- and membrane-bound conformations of αS, as well as factors that govern the transition of the protein between the extended helix and broken helix states. Using pulsed dipolar ESR measurements of distances up to 8.7 nm, we show that all three PD-linked αS mutants retain the ability to transition from the broken helix to the extended helix conformation. In addition, we find that the ratio of protein to detergent, rather than just the absolute detergent concentration, determines whether the protein adopts the broken or extended helix conformation.
Maximizing power saving with state transition overhead for multiple mobile subscriber stations in WiMAX

In the IEEE 802.16e/m standard, three power saving classes (PSCs) are defined to save the energy of a mobile sub-scriber station (MSS). However, how to set the parameters of PSCs to maximize the power saving and guarantee the quality of service is not specified in the standard. Thus, many algorithms were proposed to set the PSCs in IEEE 802.16 networks. However, most of the proposed algorithms consider only the power saving for a single MSS. In the algorithms designed for multiple MSSs, the sleep state, which is set for activation of state transition overhead power, is not considered. The PSC setting for real-time connections in multiple MSSs with consideration of the state transition overhead is studied. The problem is non-deterministic polynomial time hard (NP-hard), and a suboptimal algorithm for the problem is proposed. Simulation results demonstrate that the energy saving of the proposed algorithm is higher than that of state-of-the-art algorithms and approaches the optimum limit.
Pulsatile Hormonal Signaling to Extracellular Signal-regulated Kinase

Background: Cellular decoding of stimulus dynamics is poorly understood. Results: GnRH pulses activate ERK, and response kinetics determine sensitivity to different pulse features. Conclusion: The system is sensitive to pulse frequency but robust to width; this distinction develops through the cascade and is dictated by response kinetics. Significance: We describe mathematical and biochemical “design features” for pulsatile hormonal signaling. Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses that stimulate synthesis and secretion of pituitary gonadotropin hormones and thereby mediate control of reproduction. It acts via G-protein-coupled receptors to stimulate effectors, including ERK. Information could be encoded in GnRH pulse frequency, width, amplitude, or other features of pulse shape, but the relative importance of these features is unknown. Here we examine this using automated fluorescence microscopy and mathematical modeling, focusing on ERK signaling. The simplest scenario is one in which the system is linear, and response dynamics are relatively fast (compared with the signal dynamics). In this case integrated system output (ERK activation or ERK-driven transcription) will be roughly proportional to integrated input, but we find that this is not the case. Notably, we find that relatively slow response kinetics lead to ERK activity beyond the GnRH pulse, and this reduces sensitivity to pulse width. More generally, we show that the slowing of response kinetics through the signaling cascade creates a system that is robust to pulse width. We, therefore, show how various levels of response kinetics synergize to dictate system sensitivity to different features of pulsatile hormone input. We reveal the mathematical and biochemical basis of a dynamic GnRH signaling system that is robust to changes in pulse amplitude and width but is sensitive to changes in receptor occupancy and frequency, precisely the features that are tightly regulated and exploited to exert physiological control in vivo.
Glucocorticoids and fetal programming.

Glucocorticoids Glucocorticoid hormones (cortisol in humans and most mammals, corticosterone in rats, mice and most lower vertebrates) are produced by the adrenal glands, predominantly under the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Receptors for glucocorticoids are members of the nuclear hormone receptor superfamily and, when activated by their hormone ligands, regulate (positively or negatively) the transcription of target genes, either by directly binding to palindromic DNA sequences or indirectly via interactions with other transcription factors, such as AP1 and the cyclic AMP response element binding protein, CREB. Glucocorticoids play a series of key roles in physiology, maintaining fuel metabolism under basal conditions and underpinning many of the body’s adjustments to stressful stimulation. During prenatal and early postnatal mammalian development, glucocorticoid levels are generally low, although towards term they rise in many species and effectively signal the onset of late fetal tissue maturation in preparation for extrauterine existence. Key targets for such late effects include the lung (surfactant secretion), gut, liver and brain. Indeed, when premature labour threatens, synthetic glucocorticoids, such as dexamethasone, are exploited to accelerate maturation of the lung and gut; such therapy efficaciously reduces the incidence of postnatal respiratory distress syndromes. But are all effects of prenatal glucocorticoids uniformly beneficial? From the earliest therapeutic exploitation of glucocorticoids in pregnancy, it became apparent that they caused reductions in birthweight. This was observed in experimental animals, including non-human primates, and in humans [l-51. However, the potential significance of birthweight reduction for later pathophysiology has only recently begun to be appreciated.
Forschendes Lernen im Dortmunder Logistikstudium

Der Diskurs uber die Frage nach der Qualitat und den Entwicklungspotenzialen von Studium und Lehre bleibt nicht mehr nur beschrankt auf einen Zirkel von Hochschuldidaktiker/inne/n und an Hochschuldidaktik Interessierten, sondern erreicht in den Hochschulen mehr und mehr einzelne Fakultaten und Institute. Einen bedeutsamen Anschub erhalt dieser Qualitatsdiskurs nicht zuletzt aus den „Hohen hochschulpolitischer Spitzenorganisationen“ (Szczyrba & Wildt 2009) wie der Hochschulrektorenkonferenz, dem Wissenschaftsrat, der KMK sowie auch den Forderinitiativen von Stifterverband der Deutschen Wissenschaft, Mercator- und VW-Stiftung. Beide letztgenannten Stiftungen haben Anfang 2009 die Initiative „Bologna – Zukunft der Lehre“ gestartet, die mit dem Ziel verbunden ist, „gemeinsam die Lehre an deutschen Hochschulen zu starken und Verantwortung fur ihre Weiterentwicklung und praktische Verbesserung zu ubernehmen. Konkret geht es darum, die Studierbarkeit von Studiengangen zu erhohen, Abbrecherquoten zu senken, Betreuungsrelationen zu verbessern und die Mobilitat zwischen Hochschulen auszubauen“
La perception des systèmes vocaliques étrangers: une étude inter-langues

L'objectif de ce papier est de comprendre si la "densite" du systeme vocalique d'une langue, en d'autres termes, le nombre de voyelles dans la langue, joue un role dans la perception vocalique. Les resultats d'une experience d'identification dans trois langues (francais, anglais et espagnol) tendent a montrer que les sujets espagnols sont capables, sans hesitation, de categoriser des stimuli absents de leur espace de production. En revanche, les resultats des sujets anglais montrent une tres grande difficulte dans la tâche de categorisation. Les resultats des sujets francais sont intermediaires. Nous concluons qu'un nombre peu eleve de voyelles dans le systeme vocalique facilite la tâche de categorisation des sujets. De plus, le systeme anglais semble etre plus complexe en ce qui concerne le type d'indices necessaires pour identification des voyelles.
The evaluation of an enzyme immunoassay for the assessment of progesterone in canine plasma.

In the past the authors relied heavily on endoscopy, vaginal cytology, and behavior of the bitch to predict optimal breeding time. However, these methods are not without problems. The onset of estrus is not a good indication of ovulation (1), and with increasing numbers of bacteria the vaginal cytology may show only partial cornification (2). Behavioral differences between the young bitch and the older bitch make prediction of ovulation very difficult. However, the fact remains that, in spite of different methods used, the time of ovulation is the most important criterion for predicting the optimal breeding time. The peripheral plasma progesterone level reaches 3-8 ng/mL when ovulation occurs in the bitch (3). Therefore, it is of utmost importance to be able to monitor serial progesterone concentrations to accurately identify the time of ovulation and, therefore, to determine optimal breeding time. In the bitch, immature oocytes are ovulated and about two days are required before the ova are fertilizable (4). The measurement of progesterone in milk and plasma by means of an enzyme-linked immunosorbent assay (ELISA) has been described (5,6). The principle of this ELISA method is based upon competition between progesterone in a plasma/serum sample and progesterone linked to an enzyme molecule. The ELISA test kit evaluated in this study (Ovusure, Elanco Division of Eli Lilly Canada Inc., Scarborough, Ontario) operates on this same principle. The kit includes standard reference samples (0.5, 1.0, 5.0 and 10.0 ng/mL) and can be performed with either plasma or serum. We compared the test kit to our established radioimmunoassay (RIA) for progesterone (7). The ELISA is potentially fast, simple, and safe to use. Our main interest was to determine the correlation between the two assays and hence the validity of the ELISA. A total of 46 blood samples (numbered 1-46) were collected from bitches. Thirty plasma samples were assayed immediately for progesterone concentrations by the ELISA method. Then the plasma samples were frozen at 20°C for various periods of time. Subsequently, all 46 samples were assayed by ELISA and by radioimmunoassay. Results of representative cases are presented in Table 1. Values of progesterone greater than 10 ng/mL and less than 0.5 ng/mL are listed as >10 ng/mL and <0.5 ng/mL, respectively, since the ELISA kit only gives absolute values between
CagA EPIYA polymorphisms in Colombian Helicobacter pylori strains and their influence on disease-associated cellular responses.

AIM To investigate the influence of the CagA diversity in Helicobacter pylori (H. pylori) strains from Colombia on the host cell biology. METHODS Eighty-four H. pylori-cagA positive strains with different Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs patterns, isolated from patients with gastritis (n = 17), atrophic gastritis (n = 17), duodenal ulcer (n = 16), intestinal metaplasia (n = 16) and gastric cancer (n = 18), were included. To determine the integrity of the cag pathogenicity island (cagPAI) we evaluated the presence of cagA, cagT, cagE, and cag10 genes by polymerase chain reaction. AGS gastric epithelial cells were infected with each strain and assayed for translocation and tyrosine phosphorylation of CagA by western blot, secretion of interleukin-8 (IL-8) by enzyme-linked immuno sorbent assay after taking supernatants from cocultures and cell elongation induction. For cell elongation quantification, coculture photographs were taken and the proportion of "hummingbird" cells (> 15 μm) was determined. RESULTS Overall 72% (60/84) of the strains were found to harbor a functional cagPAI. Levels of phosphorylated CagA were significantly higher for isolates from duodenal ulcer than the ones in strains from gastritis, atrophic gastritis, intestinal metaplasia and gastric cancer (49.1% ± 23.1% vs 21.1% ± 19.5%, P < 0.02; 49.1% ± 23.1% vs 26.2% ± 14.8%, P < 0.045; 49.1% ± 23.1% vs 21.5% ± 19.5%, P < 0.043 and 49.1% ± 23.1% vs 29.5% ± 27.1%, P < 0.047 respectively). We observed variable IL-8 expression levels ranging from 0 to 810 pg/mL and from 8.8 to 1442 pg/mL at 6 h and 30 h post-infection, respectively. cagPAI-defective strains did not induce detectable levels of IL-8 at 6 h post-infection. At 30 h post-infection all strains induced IL-8 expression in AGS cells, although cagPAI-defective strains induced significantly lower levels of IL-8 than strains with a functional cagPAI (57.1 ± 56.6 pg/mL vs 513.6 ± 338.6 pg/mL, P < 0.0001). We did not observe differences in the extent of cell elongation induction between strains with a functional or a defective cagPAI in 6 h cocultures. At 24 h post infection strains with functional cagPAI showed high diversity in the extent of hummingbird phenotype induction ranging from 7% to 34%. cagPAI defective strains induced significantly lower levels of elongation than strains with functional cagPAI with one or more than one EPIYA-C motif (15.1% ± 5.2% vs 18.9% ± 4.7%, P < 0.03; and 15.1% ± 5.2% vs 20.0% ± 5.1%, P < 0.003 respectively). No differences were observed in cellular elongation induction or IL-8 expression among H. pylori strains bearing one and more than one EPIYA-C motifs, neither at 6 h nor at 24 h of coculture. There were no associations between the levels of induction of cell elongation or IL-8 expression and number of EPIYA motifs or pathology. CONCLUSION The present work describes a lack of association between H. pylori CagA protein EPIYA motifs variations from Colombian isolates and disease-associated cellular responses.
Mechanisms of early trauma-induced coagulopathy: The clot thickens or not?

Abstract Traumatic-induced coagulopathy (TIC) is a hemostatic disorder that is associated with significant bleeding, transfusion requirements, morbidity and mortality. A disorder similar or analogous to TIC was reported around 70 years ago in patients with shock, hemorrhage, burns, cardiac arrest or undergoing major surgery, and the condition was referred to as a “severe bleeding tendency,” “defibrination syndrome,” “consumptive disorder,” and later by surgeons treating US Vietnam combat casualties as a “diffuse oozing coagulopathy. ” In 1982, Moore’s group termed it the “bloody vicious cycle,” others “the lethal triad,” and in 2003 Brohi and colleagues introduced “acute traumatic coagulopathy” (ATC). Since that time, early TIC has been cloaked in many names and acronyms, including a “fibrinolytic form of disseminated intravascular coagulopathy (DIC). ” A global consensus on naming is urgently required to avoid confusion. In our view, TIC is a dynamic entity that evolves over time and no single hypothesis adequately explains the different manifestations of the coagulopathy. However, early TIC is not DIC because an increased thrombin-generating potential in vitro does not imply a clinically relevant thrombotic state in vivo as early TIC is characterized by excessive bleeding, not thrombosis. DIC with its diffuse anatomopathologic fibrin deposition appears to be a latter phase progression of TIC associated with unchecked inflammation and multiple organ dysfunction.
Selective Protection: A Cost-Efficient Backup Scheme for Link State Routing

In recent years, there are substantial demands to reduce packet loss in the Internet. Among the schemes proposed, finding backup paths in advance is considered to be an effective method to reduce the reaction time. Very commonly, a backup path is chosen to be a most disjoint path from the primary path, or in the network level, backup paths are computed for all links (e.g., IPRFF). The validity of this straightforward choice is based on 1) all the links may fail with equal probability; and 2) facing the high protection requirement today, having links not protected or sharing links between the primary and backup paths just simply look weird. Nevertheless, indications from many research studies have confirmed that the vulnerability of the links in the Internet is far from equality. In addition, we have seen that full protection schemes may introduce high costs. In this paper, we argue that such approaches may not be cost effective. We first analyze the failure characteristics based on real world traces from CERNET2, the China education and Research NETwork 2. We observe that the failure probabilities of the links is heavy-tail, i.e., a small set of links caused most of the failures. We thus propose a selective protection scheme. We carefully analyze the implementation details and the overhead for general backup path schemes of the Internet today. We formulate an optimization problem where the routing performance (in terms of network level availability) should be guaranteed and the backup cost should be minimized. This cost is special as it involves computation overhead. Consequently, we propose a novel Critical-Protection Algorithm which is fast itself. We evaluate our scheme systematically, using real world topologies and randomly generated topologies. We show significant gain even when the network availability requirement is 99.99\% as compared to that of the full protection scheme.
Learning from your mistakes: does it matter if you’re out in left foot, I mean field?

ABSTRACT Studies have shown that generating errors prior to studying information (pencil–? ) can improve target retention relative to passive (i.e., errorless) study, provided that cues and targets are semantically related (pencil–ink) and not unrelated (pencil-frog). In two experiments, we manipulated semantic proximity of errors to targets during trial-and-error to examine whether it would modulate this error generation benefit. In Experiment 1, participants were shown a cue (band–? ) and asked to generate a related word (e.g., drum). Critically, they were given a target that either matched the semantic meaning of their guess (guitar) or mismatched it (rubber). In Experiment 2, participants studied Spanish words where the English translation either matched their expectations (pariente–relative) or mismatched it (carpeta–folder). Both experiments show that errors benefit memory to the extent that they overlap semantically with targets. Results are discussed in terms of the retrieval benefits of activating related concepts during learning.
Sentential Context Modulates the Involvement of the Motor Cortex in Action Language Processing: An fMRI Study

Theories of embodied cognition propose that language comprehension is based on perceptual and motor processes. More specifically, it is hypothesized that neurons processing verbs describing bodily actions, and those that process the corresponding physical actions, fire simultaneously during action verb learning. Thus the concept and motor activation become strongly linked. According to this view, the language-induced activation of the neural substrates for action is automatic. By contrast, a weak view of embodied cognition proposes that activation of these motor regions is modulated by context. In recent studies it was found that action verbs in literal sentences activate the motor system, while mixed results were observed for action verbs in non-literal sentences. Thus, whether the recruitment of motor regions is automatic or context dependent remains a question. We investigated functional magnetic resonance imaging activation in response to non-literal and literal sentences including arm and leg related actions. The sentence structure was such that the action verb was the last word in the subordinate clause. Thus, the constraining context was presented well before the verb. Region of interest analyses showed that action verbs in literal context engage the motor regions to a greater extent than non-literal action verbs. There was no evidence for a semantic somatotopic organization of the motor cortex. Taken together, these results indicate that during comprehension, the degree to which motor regions are recruited is context dependent, supporting the weak view of embodied cognition.
Parsimony and Phylogenetic Inference Using DNA Sequences : Some Methodological Strategies

Sequence data of DNA are becoming increasingly important within systematic and evolutionary biology. With this expanding emphasis, many investigators have rising expectations that sequence variation offers an almost unlimited potential to resolve phylogenetic relationships and thereby provide us with a highly robust, if not definitive, description of the pattern of life's history (e. Various reasons have been given in support of this expectation. One of the most common is that because DNA is the physical information system recording aU inherited attributes of organismal history, direct comparison of its structure provides the most basic of all data for phylogenetic reconstruction. Inasmuch as all historical change is encoded in DNA, it is reasoned, it makes sense to examine that change directly. A second argument is one of large numbers: we can obtain far more character-state data from DNA sequences than we can, say, from traditional morphological comparisons, and therefore, statistically, as additional data are examined, true patterns of phylogenetic relationships will eventually emerge. Furthermore, it is often claimed that because morphology is so readily subject to convergence when compared to sequence data, obtaining more and more of the latter represents our best hope for resolving the phylogenetic pattern. Technological innovations are also fueling the rush to obtain sequence data. Comparative sequence data are much easier and less expensive to collect than they were even a year ago. Just as importantly, there has been a rapid growth in the amount of computer hardware and software that makes the analysis of comparative sequence data readily accessible to workers at all levels of expertise (Platnick, 1989; see also many of the papers 184-PARSIMONY AND PHYlOGENETIC INFERENCE 185 in Do? little, 1990). In particular, the availability of tree-building algorithms for microcomputers has been a contributing factor to the marked increase in the. numbers of papers that use DNA sequences to answer phylogenetic questions (see summary in Swofford and Olsen, 1990). At its simplest, therefore, it is relatively straightforward to collect comparative sequence data, analyze them with a given tree-building method, and publish the results. Yet, it is clear from the literature that phylogenetic inference using sequence data is anything but simple. There is, for example, substantial disagreement over the best method to resolve relationships from sequence data. And even if agreement could be reached on a general method, it still is not clear how that method might be applied in order to obtain a phy-logenetic hypothesis that …