Miracle-dz/UniFAR-FTUs huggingface dataset:
Hilar somatostatin interneuron loss reduces dentate gyrus inhibition in a mouse model of temporal lobe epilepsy

In patients with temporal lobe epilepsy, seizures usually start in the hippocampus, and dentate granule cells are hyperexcitable. Somatostatin interneurons are a major subpopulation of inhibitory neurons in the dentate gyrus, and many are lost in patients and animal models. However, surviving somatostatin interneurons sprout axon collaterals and form new synapses, so the net effect on granule cell inhibition remains unclear.
Procollagen trafficking, processing and fibrillogenesis

Collagen fibrils in the extracellular matrix allow connective tissues such as tendon, skin and bone to withstand tensile forces. The fibrils are indeterminate in length, insoluble and form elaborate three-dimensional arrays that extend over numerous cell lengths. Studies of the molecular basis of collagen fibrillogenesis have provided insight into the trafficking of procollagen (the precursor of collagen) through the cellular secretory pathway, the conversion of procollagen to collagen by the procollagen metalloproteinases, and the directional deposition of fibrils involving the plasma membrane and late secretory pathway. Fibril-associated molecules are targeted to the surface of collagen fibrils, and these molecules play an important role in regulating the diameter and interactions between the fibrils.
PACAP-induced migraine: a possible CNS effect?

Sir, The two peptides pituitary adenyl cyclase-activating polypeptide-38 (PACAP) and vasoactive intestinal polypeptide (VIP), given intravenously in humans, both dilate extracerebral cranial arteries, but only PACAP38 (Schytz et al. , 2009)—not vasoactive intestinal polypeptide (Rahmannn et al. , 2008)—induces migraine-like attacks in patients with migraine. Possible mechanisms for the difference in migraine induction were investigated in a recent crossover study in which 16 of 24 patients with migraine developed migraine after intravenous PACAP infusion, and vasoactive intestinal polypeptide infusion induced migraine in 4 of 24 patients (Amin et al. , 2014). Magnetic resonance angiography showed dilatation of the superficial temporal artery and the extracranial part of the middle meningeal artery after both polypeptides whereas there was no effect on the middle cerebral artery with neither polypeptide (Amin et al. , 2014). The vasodilatation of the superficial temporal artery and middle meningeal artery was the same for both polypeptides after 20 min but only persisted after 2 h for PACAP38. The migraine-like attacks were treated effectively with subcutaneous sumatriptan ( n = 6) and this was associated with a constriction of superficial temporal artery and middle meningeal artery but …
Global longitudinal strain is associated with heart failure outcomes in hypertrophic cardiomyopathy

Objective We hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures. Methods Retrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006–2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF. Results Mean age was 50.0±15.0 years; 322 (68%) were men. At a median of 4.3 years (IQR 0.1–7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine–Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end-systolic volume. Moreover, GLS was particularly associated with the secondary end-point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III–IV, LV end-systolic volume, E/E′, and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035). Conclusions In patients with HCM, reduced GLS is an independent factor associated with poor cardiac outcomes, and particularly HF outcomes.
A System of Adaptive Keyword Search in XML

Existing LCA-based approaches for XML keyword search have several fundamental flaws, among which, the most important one is that the search results are eternally determined nonadjustable. In this paper, we present a system of adaptive keyword search in XML, called AdaptiveXKS. It employs a novel and flexible result model and a corresponding scoring function, within which, four critical metrics are weighted and the associated parameters can also be modified. Through the interface the system administrator or the users can adjust some parameters according to their search intentions. One of three searching algorithms could also be chosen freely in order to catch specific querying requirements, which reveals the adaptiveness as the biggest merit of this system. Extensive experiments show that AdaptiveXKS outperforms existing keyword search systems in both precision and recall.
Search Engines as a Security Threat

Because they implement vulnerable security policies, search engines are excellent tools for helping hackers to attack machines anonymously, search for easy targets or gather confidential data. Securing all channels against hackers trying to penetrate a vulnerable system isn't possible, but there is no reason for search engines to be wide-open channels that continue to help hackers find and penetrate weak systems. Because it is so easy to use a search engine to cloak an attack, search-engine-based hacker abuse has become a real threat that poses serious risks. However, not all blame should fall on those who operate the search engines. Search engines aren't responsible for the huge numbers of poorly configured and insecure machines all over the Internet even if the search engines do aid in identifying them, but the search engines must take some blame if they continue to provide easy ways to locate weak and penetrable machines.
Reduced Defense of Central Blood Volume During Acute Lower Body Negative Pressure–Induced Hypovolemic Circulatory Stress in Aging Women

ABSTRACT Elderly humans are more vulnerable to trauma and hemorrhage than young and elderly men and respond with decreased defense of central blood volume during acute experimental hypovolemia induced by lower body negative pressure (LBNP). However, these defense mechanisms have not been evaluated in elderly women. The aim of this study was to determine the effectiveness of compensatory responses to defend central blood volume during experimental hypovolemia in elderly and young women. Cardiovascular responses in 34 women, 12 elderly (66 ± 1 years) and 22 young women (23 ± 0.4 years), were studied during experimental hypovolemia induced by LBNP of 11 to 44 mmHg. Air plethysmography was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as net capillary fluid transfer from tissue to blood in the arm. Lower body negative pressure seemed to create comparable hypovolemia measured as total calf volume increase in elderly and young women. Heart rate increased less in elderly women (LBNP of 44 mmHg: 20 ± 2 vs. 37 ± 4%; P < 0.01) but with similar (%) increase in forearm vascular resistance. Mobilization of capacitance blood from the peripheral circulation was both slower and decreased by ∼60% in elderly women (P < 0.001), and net capillary fluid absorption from surrounding tissues was reduced by ∼40% (P < 0.01, LBNP of 44 mmHg). Elderly women responded with less increase in heart rate but with equal forearm vascular resistance (%) response during LBNP. Furthermore, the compensatory capacitance response was both slower and substantially decreased, and net capillary fluid absorption considerably reduced, collectively indicating less efficiency to defend central blood volume in elderly than in young women.
Disparity in the DNA translocase domains of SWI/SNF and ISW2

An ATP-dependent DNA translocase domain consisting of seven conserved motifs is a general feature of all ATP-dependent chromatin remodelers. While motifs on the ATPase domains of the yeast SWI/SNF and ISWI families of remodelers are highly conserved, the ATPase domains of these complexes appear not to be functionally interchangeable. We found one reason that may account for this is the ATPase domains interact differently with nucleosomes even though both associate with nucleosomal DNA 17–18 bp from the dyad axis. The cleft formed between the two lobes of the ISW2 ATPase domain is bound to nucleosomal DNA and Isw2 associates with the side of nucleosomal DNA away from the histone octamer. The ATPase domain of SWI/SNF binds to the same region of nucleosomal DNA, but is bound outside of the cleft region. The catalytic subunit of SWI/SNF also appears to intercalate between the DNA gyre and histone octamer. The altered interactions of SWI/SNF with DNA are specific to nucleosomes and do not occur with free DNA. These differences are likely mediated through interactions with the histone surface. The placement of SWI/SNF between the octamer and DNA could make it easier to disrupt histone–DNA interactions.
Vaccinia-like cytoplasmic replication of the giant Mimivirus

Poxviruses are considered to be unique among all DNA viruses, because their infection cycle is carried out exclusively in the host cytoplasm. Such an infection strategy is of interest, because it necessitates generation of elaborate factories in which viral replication and assembly are promoted. By using diverse imaging techniques, we show that the infection cycle of the largest virus currently identified, the Acanthamoeba polyphaga Mimivirus, similarly occurs exclusively in the host cytoplasm. We further show that newly synthesized mRNAs accumulate at discrete cytoplasmic sites that are distinct from the sites where viral replication occurs, and this is observed in vaccinia infection. By revealing substantial physiologic similarity between poxviruses and Mimivirus and thus, implying that an entirely cytoplasmic viral replication might be more common than generally considered, these findings underscore the ability of DNA viruses to generate large and elaborate replication factories.
Peripheral vascular response to inspiratory breath hold in paediatric homozygous sickle cell disease

• What is the central question of this study? Autonomic nervous dysfunction is implicated in complications of sickle cell anaemia (SCA). In healthy adults, a deep inspiratory breath hold (IBH) elicits rapid transient SNS‐ mediated vasoconstriction detectable using Laser Doppler Flux (LDF) assessment of the finger‐tip cutaneous micovasculature. • What is the main finding and its importance? We demonstrate significantly increased resting peripheral blood flow and sympathetic activity in African children with SCA compared to sibling controls and increased sympathetic stimulation in response to vasoprovocation with DIG. This study is the first to observe an inverse association between resting peripheral blood flow and haemoglobin oxygen saturation (SpO2). These phenomena may be an adaptive response to the hypoxic exposure in SCA.
Non-intrusive monitoring and service adaptation for WS-BPEL

Web service processes currently lack monitoring and dynamic (runtime) adaptation mechanisms. In highly dynamic processes, services frequently need to be exchanged due to a variety of reasons. In this paper we present VieDAME, a system which allows monitoring of BPEL processes according to Quality of Service (QoS) attributes and replacement of existing partner services based on various (pluggable) replacement strategies. The chosen replacement services can be syntactically or semantically equivalent to the BPEL interface. Services can be automatically replaced during runtime without any downtime of the overall system. We implemented our solution with an aspect-oriented approach by intercepting SOAP messages and allow services to be exchanged during runtime with little performance penalty costs, as shown in our experiments, thereby making our approach suitable for high-availability BPEL environments.
Functional Hybrid Modeling from an Object-Oriented Perspective

The modeling and simulation of physical systems is of key importance in many areas of science and engineering, and thus can benefit from high-quality software tools. In previous research we have demonstrated how functional programming can form the basis of an expressive language for causal hybrid modeling and simulation. There is a growing realization, however, that a move toward non-causal modeling is necessary for coping with the ever increasing size and complexity of modeling problems. Our goal is to combine the strengths of functional programming and non-causal modeling to create a powerful, strongly typed fully declarative modeling language that provides modeling and simulation capabilities beyond the current state of the art: in particular, support for highly structurally dynamic systems. Additionally, we think our approach could serve as a semantical framework for studying modeling and simulation languages supporting structural dynamism, and maybe even as a core language in systems where the surface syntax is more conventional. Although our work is still in its very early stages, we believe that this paper clearly articulates the need for improved modeling languages and shows how functional programming techniques can play a pivotal role in meeting this need.
A network flow solution to some nonlinear 0-1 programming problems, with applications to graph theory

A network flow technique is used to solve the unconstrained nonlinear 0-1 programming problem, which is maximizing the ratio of two polynomials, assuming that all the nonlinear coefficients in the numerator are non-negative and all the nonlinear coefficients in the denominator are nonpositive. Two examples are an investment selection problem to maximize the rate of return, and a decomposition approach to a scheduling problem studied by Sidney and Lawler. The proposed algorithm requires the solution of a sequence of minimum-cut problems in a related network, and can be extended to some more general problems of the same type. This approach is also applied to find the density of a graph (the maximum ratio, among its subgraphs, of the number of edges to the number of nodes) and its arboricity, for which polynomial algorithms are described. It is also useful in providing a bounding scheme for the maximum-clique and vertex packing problems.
Agents with an Attitude

We describe a virtual marketplace where buying and selling agents that learn from experience enter the market with an ’attitude’ (a mental state) formulated as a complex function of prior experience(s), market conditions, product information as well as personal characteristics such as importance of time vs. importance of price and the commitment level to the purchase/sale of the product. Agents learn by using prior experiences to adjust their attitude. While buying and selling agents are assumed to have opposing interests, and are thus engaged in a competitive negotiation, we will show here that the mental state model can also be extended to other types of situations where agents are deliberating in a cooperative environment.
Efficient message transport interface between agent framework and event service

Multi-agent techniques have been continuously evolving as ubiquitous and pervasive computing emerges as a key post-internet paradigm. In the ubiquitous environment, the applications need to exchange the requests asynchronously using an event-based model. While interoperability between the agent platform and event service platform is important for the applications, it has not received much attention yet. In this paper, we propose the Message Transport Interface (MTI), which allows communication between the JADE platform and CORBA-based platform supporting event service. We also develop a new information bus adapter for augmenting the omniEvent service, which is used for autonomic administration of the channels. The developed system has been implemented in both C++ and Java for Linux and Windows platform, including the pocket PC adapter for mobile computing. Experimental results reveal that the proposed schemes allow much smaller process time than the existing omniEvent service. They are parts of a ubiquitous computing middleware called Component-based Autonomic Layered Middleware (CALM), which is currently under development.
Kernel Recursive Least Squares for the CMAC Neural Network

—The Cerebellar Model Articulation Controller (CMAC) neural network is an associative memory that is biologically inspired by the cerebellum, which is found in the brains of animals. The standard CMAC uses the least mean squares algorithm to train the weights. Recently, the recursive least squares algorithm was proposed as a superior algorithm for training the CMAC online as it can converge in one epoch, and does not require tuning of a learning rate. However, the RLS algorithms computational speed is dependant on the number of weights required by the CMAC which is often large and thus can be very computationally inefficient. Recently also, the use of kernel methods in the CMAC was proposed to reduce memory usage and improve modeling capabilities. In this paper the Kernel Recursive Least Squares (KRLS) algorithm is applied to the CMAC. Due to the kernel method, the computational complexity of the CMAC becomes dependant on the number of unique training data, which can be significantly less than the weights required by non-kernel CMACs. Additionally, online sparsification techniques are applied to further improve computational speed.
Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation

TO THE EDITOR: In their recent article on the cost-effectiveness of dabigatran versus warfarin, Freeman and colleagues (1) did not account for some of the highest costs associated with warfarin administration. Each time that prothrombin time is measured, the logistics involved cost money. Patients must travel to the laboratory to have blood drawn, or family members must take them. If patients are homebound, the cost of visiting nurses is high. The authors also did not account for the costs of prothrombin time measurement for physicians, patients, and caregivers. For example, when one of my patients undergoes measurement of prothrombin time, a nurse in my office obtains the result and communicates it to me. I respond to the result, and this response must then be transmitted to the patient or, often, the patient’s caretaker or visiting nurse. Elaborate games of “phone tag” ensue. All of this costs money. The potential for error and delayed communication is huge. If the health care system would take into account the entire cost of warfarin administration, one would hope that insurers would cover newer drugs, such as dabigatran.
G protein‐coupled receptor 30 contributes to improved remyelination after cuprizone‐induced demyelination

Estrogen exerts neuroprotective and promyelinating actions. The therapeutic effect has been shown in animal models of multiple sclerosis, in which the myelin sheath is specifically destroyed in the central nervous system. However, it remains unproven whether estrogen is directly involved in remyelination via the myelin producing cells, oligodendrocytes, or which estrogen receptors are involved. In this study, we found that the membrane‐associated estrogen receptor, the G protein‐coupled receptor 30 (GPR30), also known as GPER, was expressed in oligodendrocytes in rat spinal cord and corpus callosum. Moreover, GPR30 was expressed throughout oligodendrocyte differentiation and promyelinating stages in primary oligodendrocyte cultures derived from rat spinal cords and brains. To evaluate the role of signaling via GPR30 in promyelination, a specific agonist for GPR30, G1, was administered to a rat model of demyelination induced by cuprizone treatment. Histological examination of the corpus callosum with oligodendrocyte differentiation stage‐specific markers showed that G1 enhanced oligodendrocyte maturation in corpus callosum of cuprizone‐treated animals. It also enhanced oligodendrocyte ensheathment of dorsal root ganglion (DRG) neurons in co‐culture and myelination in cuprizone‐treated animals. This study is the first evidence that GPR30 signaling promotes remyelination by oligodendrocytes after demyelination. GPR30 ligands may provide a novel therapy for the treatment of multiple sclerosis. © 2012 Wiley Periodicals, Inc.
The online evaluation of speech synthesis using eye movements

This paper describes an eye tracking experiment to study the processing of diphone synthesis, unit selection synthesis, and human speech taking segmental and suprasegmental speech quality into account. The results showed that both factors influenced the processing of human and synthetic speech, and confirmed that eye tracking is a promising albeit time consuming research method to evaluate synthetic speech.
SURVEY AND SUMMARY: Roles of 5-substituents of tRNA wobble uridines in the recognition of purine-ending codons

Many tRNA molecules that recognize the purine-ending codons but not the pyrimidine-ending codons have a modified uridine at the wobble position, in which a methylene carbon is attached directly to position 5 of the uracil ring. Although several models have been proposed concerning the mechanism by which the 5-substituents regulate codon-reading properties of the tRNAs, none could explain recent results of the experiments utilizing well-characterized modification-deficient strains of Escherichia coli. Here, we first summarize previous studies on the codon-reading properties of tRNA molecules with a U derivative at the wobble position. Then, we propose a hypothetical mechanism of the reading of the G-ending codons by such tRNA molecules that could explain the experimental results. The hypothesis supposes unconventional base pairs between a protonated form of the modified uridines and the G at the third position of the codon stabilized by two direct hydrogen bonds between the bases. The hypothesis also addresses differences between the prokaryotic and eukaryotic decoding systems.
Analysis of ThiC Variants in the Context of the Metabolic Network of Salmonella enterica

ABSTRACT In bacteria, the 4-amino-hydroxymethyl-2-methylpyrimidine (HMP) moiety of thiamine is synthesized from 5-aminoimidazole ribotide (AIR), a branch point metabolite of purine and thiamine biosynthesis. ThiC is a member of the radical S-adenosylmethionine (AdoMet) superfamily and catalyzes the complex chemical rearrangement of AIR to HMP-P. As reconstituted in vitro, the ThiC reaction requires AdoMet, AIR, and reductant. This study analyzed variants of ThiC in vivo and in vitro to probe the metabolic network surrounding AIR in Salmonella enterica. Several variants of ThiC that required metabolic perturbations to function in vivo were biochemically characterized in vitro. Results presented herein indicate that the subtleties of the metabolic network have not been captured in the current reconstitution of the ThiC reaction.