Miracle-dz/UniFAR-FTUs huggingface dataset:
A sodium channel mutation causing epilepsy in man exhibits subtle defects in fast inactivation and activation in vitro

1 Generalized epilepsy with febrile seizures plus (GEFS+) is a benign epileptic syndrome of humans. It is characterized by febrile and afebrile generalized seizures that occur predominantly in childhood and respond well to standard antiepileptic therapy. A mutation in the β1‐subunit of the voltage‐gated sodium channel, linked to chromosome 19q13 (GEFS+ type 1) has been found in one family. For four other families, linkage was found to chromosome 2q21‐33 (GEFS+ type 2) where three genes encoding neuronal sodium channel α‐subunits are located (SCN1‐3A). Recently, the first two mutations were identified in SCN1A. 2 We introduced one of these mutations, which is highly conserved to SCN1A, into the cDNA of the gene SCN4A encoding the α‐subunit of the human skeletal muscle sodium channel (hSkm1). The mutation is located in the S4 voltage sensor of domain IV, predicting substitution of histidine for the fifth of eight arginines (R1460H in hSkm1). Functional studies were performed by expressing the α‐subunit alone in the mammalian tsA201 cell line using the whole‐cell patch clamp technique. 3 Compared to wild‐type (WT), mutant R1460H channels showed small defects in fast inactivation. The time course of inactivation was slightly (1.5‐fold) slowed and its voltage dependence reduced, and recovery from inactivation was accelerated 3‐fold. However, there was no increase in persistent sodium current as observed for SCN4A mutations causing myotonia or periodic paralysis. The activation time course of R1460H channels was slightly accelerated. Slow inactivation was slightly but significantly stabilized, confirming the importance of this region for slow inactivation. 4 The combination of activation and fast inactivation defects can explain the occurrence of epileptic seizures, but the effects were much more subtle than the inactivation defects described previously for mutations in SCN4A causing disease in skeletal muscle. Hence, with regard to pathological excitability, our results suggest a greater vulnerability of the central nervous system compared to muscle tissue.
How to sample the carbon isotopes of tropical ecosystems without leaving your armchair

Well-dated records of terrestrial environmental change in Southeast Asia spanning the past 50 kyr (kyr = 1,000 y) are few and far between. The problem is often one of preservation. Organic-based paleoenvironmental proxies in warm and wet tropical environments are often subject to severe microbial degradation processes rendering them unsuitable for radiocarbon (14C) dating. Notable exceptions to this problem include tropical speleothems, which can be dated using the 230Th method (1) and can provide information on the relative intensities of isotopically depleted Asian monsoonal rainfall back to ∼400 kyr ago (2). Speleothem records tell us little about the specific ecosystem responses to past rainfall and temperature changes, however. How can we tell how much rain is needed to maintain dense tropical rain forest as opposed to more open grasslands? Pollen and charcoal records go some way toward filling this knowledge gap in tropical settings (e.g., refs. 3–5), but they can be affected by biases in the representation of local plant species and are sometimes difficult to date accurately. In PNAS, a relatively innovative technique is explored in insular Southeast Asia that uses the vegetation-derived carbon isotope (δ13C) records preserved in cave guano deposits (6).
VISION, COGNITION AND DEVELOPMENTAL CHARACTERISTICS OF GIRLS AND WOMEN WITH RETT SYNDROME

Forty‐two females with Rett syndrome, aged 2.5 to 47 years, were assessed with the Teller Acuity Cards and a new version of the Fagan test for age 2 years and above, and their parents were interviewed about the children's communication skills. The visual function of the subjects indicated arrested development, and they scored significantly lower on the Fagan test than a normal comparison group. Their visual processing and memory deteriorated somewhat with age, while those of the comparison group showed a slight increase. Both age at onset of Rett syndrome symptomatology and speech measures were inversely correlated with visual processing and memory, indicating that age at recession may have differential consequences for different functions. Among the subjects, persistent looking was associated with low cognitive function. The results have implications for intervention, and demonstrate that the paradigm of preferential looking may be useful in cognitive assessment of females with Rett syndrome.
Using a structural equation model to assess the equivalence between assessment instruments: the dimension of sensation seeking as measured by Zuckerman's SSS-V and Arnett's AISS

The aim of this instrumental study is to analyze the degree of equivalence between the construct of sensation seeking as measured by Sensation Seeking Scale form V, SSS-V and Arnett Inventory of Sensation Seeking, AISS. A structural equation model is employed in order to analyze the equivalence. The study includes 322 participants aged between 18 and 77. First, the equivalence between the SSS-V and the AISS was analyzed using the total sample. Second, two different age groups were established (18- 30 years old age group, n = 183; and 40-77 years old age group, n = 84), assessing the degree of equivalence in both cases. Based on the total sample and the 40-77 years old age group the results suggest that both instruments are not measuring the same dimension. However, in the 18-30 years old age group the disattenuated correlation obtained by the structural equation model was estimated to be 1.00, which means that, the SSS-V and AISS measure essentially the same dimension for this age group. These results are discussed taking into account the theoretical proposal of Zuckerman and Arnett, and the content (items) of the SSS-V and AISS.
Capturing 0 day Exploits with PERFectly Placed Hardware Traps

Advanced software exploitation is a rapidly changing field of study. In recent years, clever ways to bypass existing exploit defenses have become mainstream. Reactive defensive solutions based on known exploitation techniques have been proven ineffective, and easily circumvented. In this paper, we discuss a new system for early detection and prevention of unknown exploits. Our system uses Performance Monitoring Unit hardware to enforce coarse-grained Control Flow Integrity (CFI). By using hardware features that exist in modern processor architectures, and real-time CFI policy enforcement, we hope to prove that our approach is effective, suitable for practical use, while staying resistant to bypass.
Automatic registration of multisensor images with affine deformation based on triangle area representation

Abstract. A new automatic feature-based registration algorithm of multisensor images with affine deformation is presented. Although the feature-based registration methods have an advantage in reducing computational load over the area-based ones, certain typical issues such as complex deformation and grayscale discrepancy existing in a multisensor image pair will make the design of a robust feature descriptor challenging. To deal with these issues, in contrast with most existing feature-based methods that describe feature points directly, we introduce an additional procedure of feature quadrilateral construction in the proposed algorithm. Then the descriptors for the constructed feature quadrilaterals are designed based on the affine-invariance property of triangle area representation. By doing these, the proposed algorithm’s robustness to both affine deformation and grayscale discrepancy can be guaranteed. Besides, since the calculation of feature descriptors only involves simple algebraic operations, the proposed method has low computational load. Experimental results using real multisensor image pairs are presented to show the merits of the proposed method.
Top-down and bottom-up deficits in conflict adaptation after frontal lobe damage

The ability to adaptively control our responses to conflicting information is crucial if we are to respond in a flexible manner to the environment. The “conflict monitoring model” proposes that the prefrontal cortex is responsible of reactive adjustments in cognitive control. We present neuropsychological data contrasting the performance of patients with prefrontal lesions with the one exhibited by patients with lesions outside the frontal lobe and nonlesioned participants, on the processes involved in the dynamic adaptation to conflicting stimulus information. Relative to both lesioned and nonlesioned control groups, prefrontal patients were impaired in adapting to conflict when all features of the conflicting stimuli and their associated responses changed on consecutive trials. However, the prefrontal patients also showed an unusually large conflict adaptation effect when the stimuli and/or response features repeated across trials. We conclude that prefrontal cortex is relevant both for genuine “top-down” conflict monitoring and for regulating the influence of “bottom-up” responses based on the integration of stimulus features across trials.
Microbialite genetic diversity and composition relate to environmental variables.

Microbialites have played an important role in the early history of life on Earth. Their fossilized forms represent the oldest evidence of life on our planet dating back to 3500 Ma. Extant microbialites have been suggested to be highly productive and diverse communities with an evident role in the cycling of major elements, and in contributing to carbonate precipitation. Although their ecological and evolutionary importance has been recognized, the study of their genetic diversity is yet scanty. The main goal of this study was to analyse microbial genetic diversity of microbialites living in different types of environments throughout Mexico, including desert ponds, coastal lagoons and a crater-lake. We followed a pyrosequencing approach of hypervariable regions of the 16S rRNA gene. Results showed that microbialite communities were very diverse (H' = 6-7) and showed geographic variation in composition, as well as an environmental effect related to pH and conductivity, which together explained 33% of the genetic variation. All microbialites had similar proportions of major bacterial and archaeal phyla.
Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue

Objectives: Visceral adipose tissue is a major site for expression of proinflammatory and procoagulant genes during acute systemic inflammation. In this study, we tested whether the loss of fat mass by dietary restriction would remove the major source of these factors resulting in improved tolerance to sepsis and endotoxemia. Design: Prospective, laboratory controlled experiments. Setting: Aging and critical care research laboratory in a university hospital. Subjects: Middle-aged (12-month old) male C57BL/6 mice. Interventions: Mice were subjected to 40% dietary restriction for 3 weeks followed by induction of abdominal sepsis or endotoxemia by intraperitoneal injection with cecal slurry or lipopolysaccharide, respectively. Measurements and Main Results: Compared with freely fed mice, dietary restricted mice exhibited dramatically improved survival (80% vs 0% after sepsis; p < 0.001 and 86% vs 12% after endotoxemia; p = 0.013) and significantly reduced visceral fat-derived messenger RNA expression of interleukin-6, thrombospondin-1, plasminogen activator inhibitor-1, and tissue factor, which positively correlated with fat mass. Plasma levels of interleukin-6 were significantly reduced by dietary restriction and correlated with adipose interleukin-6 messenger RNA levels and fat mass (p < 0.001; R 2 = 0.64 and 0.89). In vitro culture of visceral fat explants from naive dietary restricted mice showed significantly reduced interleukin-6 secretion compared with that from freely fed mice in response to lipopolysaccharide. Analysis of major adipose immune cell populations by flow cytometry demonstrated that macrophages were the only cell population reduced by dietary restriction and that CD11c+/CD206+ (M2-type) and CD11c–/CD206– (double negative) macrophages, in addition to T cells, are the major immune cell populations that produce interleukin-6 in middle-aged mice during systemic inflammation. Conclusions: Short-term dietary restriction drastically improved the survival outcome of middle-aged mice during both polymicrobial sepsis and sterile endotoxemia. Improved survival was accompanied by a significantly attenuated inflammatory response in adipose tissue, which is likely due to alterations of both fat mass quantity and qualitative changes, including a reduction in macrophage populations.
Canaan Bound: The African-American Great Migration Novel

Drawing on a wide range of major literary voices, including Richard Wright, Ralph Ellison, and Toni Morrison, as well as lesser-known writers such as William Attaway (Blood on the Forge) and Dorothy West (The Living Is Easy), Rodgers conducts a kind of literary archaeology of the Great Migration. He mines the writers' biographical connections to migration and teases apart the ways in which individual novels relate to one another, to the historical situation of black America, and to African-American literature as a whole. In reading migration novels in relation to African-American literary texts such as slave narratives, folk tales, and urban fiction, Rodgers affirms the southern folk roots of African-American culture and argues for a need to stem the erosion of southern memory.
University of Groningen Immunotherapy based on influenza virosomes and recombinant Semliki Forest virus

Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination against infectious diseases in general aims at the induction of humoral immune responses to prevent infection. This humoral immune response is mediated by antibodyproducing B cells. On the other hand, therapeutic immunisation against virally-infected cells and tumour cells requires the induction of cytotoxic T lymphocytes (CTL) that can specifically recognise and lyse infected cells or transformed tumour cells. The induction of Major Histocompatibility Complex (MHC) class I restricted CTL activity is optimally achieved by synthesis of antigens within APCs, for example after immunisation with live attenuated virus. However, immunisation with live vaccines bears the risk of causing disease. Therefore, alternative vaccine delivery systems are sought that enable introduction of nonreplicating antigen into the MHC class I presentation pathway. Furthermore, for the induction of effective humoral and cellular responses, MHC class II restricted activation of T helper cells is required. Among other delivery systems, as described in this theme issue of Advanced Drug Delivery Reviews, virosomes seem ideally suited for delivery of antigens into both MHC pathways. In this review we will focus on the use of virosomes as carrier vehicles for the intracellular delivery of protein antigens and DNA, and the induction of a cellular immune response (CTL response) against encapsulated protein antigens and proteins expressed by virosome-associated plasmids.
Characterization of Functional Hepatitis C Virus Envelope Glycoproteins

ABSTRACT Hepatitis C virus (HCV) encodes two envelope glycoproteins, E1 and E2, that assemble as a noncovalent heterodimer which is mainly retained in the endoplasmic reticulum. Because assembly into particles and secretion from the cell lead to structural changes in viral envelope proteins, characterization of the proteins associated with the virion is necessary in order to better understand how they mature to be functional in virus entry. There is currently no efficient and reliable cell culture system to amplify HCV, and the envelope glycoproteins associated with the virion have therefore not been characterized yet. Recently, infectious pseudotype particles that are assembled by displaying unmodified HCV envelope glycoproteins on retroviral core particles have been successfully generated. Because HCV pseudotype particles contain fully functional envelope glycoproteins, these envelope proteins, or at least a fraction of them, should be in a mature conformation similar to that on the native HCV particles. In this study, we used conformation-dependent monoclonal antibodies to characterize the envelope glycoproteins associated with HCV pseudotype particles. We showed that the functional unit is a noncovalent E1E2 heterodimer containing complex or hybrid type glycans. We did not observe any evidence of maturation by a cellular endoprotease during the transport of these envelope glycoproteins through the secretory pathway. These envelope glycoproteins were recognized by a panel of conformation-dependent monoclonal antibodies as well as by CD81, a molecule involved in HCV entry. The functional envelope glycoproteins associated with HCV pseudotype particles were also shown to be sensitive to low-pH treatment. Such conformational changes are likely necessary to initiate fusion.
Rate-dependent measures of repolarization predict inducibility of ventricular arrhythmias.

OBJECTIVE The aim of this study was to compare the rate-dependent measures of repolarization in patients with and without inducible ventricular arrhythmias, and so to assess the potential arrhythmogenic role of rate-dependent heterogeneities in cardiac repolarization. METHODS Two groups of patients were studied during invasive electrophysiological procedures for standard clinical indications. A normal group (n = 17) with supraventricular tachycardia, structurally normal hearts and no inducible ventricular arrhythmias (PES-) and an inducible group (n = 13) with inducible ventricular arrhythmias (PES+). In each patient, we delivered a series of S1-S2 pacing sequences with a baseline S2 of 500 ms, which was progressively reduced. At the same time, a 12-lead electrocardiogram (ECG) was recorded. T-waves were extracted from each ECG recording, and 12 different T-wave measures were obtained from each patient across a range of coupling intervals. These included conventional measures, and those obtained from principal component analysis (PCA) of repolarization waveforms. RESULTS At baseline S2, there was no significant difference between the PES- and PES+ using conventional T-wave measures. There were significant differences at baseline S2 between groups using PCA-derived measures. These differences showed rate dependence and were larger at shorter coupling intervals. Two dynamic ECG measurements identified subjects who were inducible during PES; maximum relative T-wave residuum >0.10 (odds ratio: 38.5, 95% CI: 4.7-318.5; P < 0.001) and maximum T-wave shape index <0.007 (odds ratio: 180.0, 95% CI: 10.2-3167.0; P < 0.001). CONCLUSION T-wave shape index is rate dependent and discriminates between PES- and PES+ patients. We propose that patients with inducible arrhythmias have rate-dependent heterogeneity of repolarization which could be a useful tool for risk stratification.
Customizing dependability attributes for mobile service platforms

Mobile service platforms are used to facilitate access to enterprise services such as email, product inventory, or design drawing databases by a wide range of mobile devices using a variety of access protocols. This paper presents a quality of service (QoS) architecture that allows flexible combinations of dependability attributes such as reliability, timeliness, and security to be enforced on a per service request basis. In addition to components that implement the underlying dependability techniques, the architecture includes policy components that evaluate a request's requirements and dynamically determine an appropriate execution strategy. The architecture has been integrated into an experimental version of iMobile, a mobile service platform being developed at AT&T. This paper describes the design and implementation of the architecture, and gives initial experimental results for the iMobile prototype.
Sustained-release bupropion in the treatment of SSRI nonresponder pathologic gamblers: pilot study and review of the literature

Background: Pathologic gambling (PG) is a prevalent and disabling impulse-control disorder. Recent studies have consistently demonstrated that PG patients respond well to treatment with selective serotonin reuptake inhibiters (SSRIs), mood stabilizers and opioid antagonists. These findings have supported the observation that PG is strongly associated with mood disorders, obsessive–compulsive spectrum disorders, panic disorder and addictive disorders. The aim of the study was to show the effectiveness of bupropion sustained release in PG. Methods: A total of 16 male PGs who had failed two previous trials of SSRI pharmacotherapy were enrolled in the study and were treated with bupropion sustained release for 12 weeks. A comprehensive psychiatric diagnostic evaluation was performed on all patients at baseline, and patients were screened for symptoms of gambling, depression and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale and the Clinica.
A research about a MIMO system identification algorithm based on ANN using slide mode variable structure

Applying sliding mode variable structure control to train neural networks is proposed in this paper, which can not only increases learning rate but also improves the stability of neural-network. Furthermore, this method helps to promote the generalization capacity of neural-network. In order to improve the generalization ability, two sliding mode objective functions are designed based on previous researches for a new neural-network learning algorithm. Simulation analysis shows that the proposed algorithm increases the generalization ability and robustness of neural-network, meanwhile, enhances the identification accuracy.
Quality of life in children and adolescents undergoing spinal deformity surgery.

BACKGROUND Quality of life measurements evaluate surgical results from patients' reported outcomes. OBJECTIVE To assess the impact of spinal deformity treatment using the Scoliosis Research Society-22 questionnaire. METHODS SRS-22 data was collected in 545 consecutive patients (425 females-120 males) pre-operatively, 6-, 12- and 24-months post-operatively. Variables included type and age of surgery (mean: 15.14 ± 2.07 years), gender, diagnosis and year of surgery. Age at surgery was divided in: 10-12, 13-15, and 15-19 years. RESULTS Mean pre-operative SRS-22 scores for the whole group were: function 3.77 ± 0.75; pain 3.7 ± 0.97; self-image 3.14 ± 0.66; mental health 3.86 ± 0.77; total 3.62 ± 0.66. Mean 2-year post-operative scores were: function 4.39 ± 0.42; pain 4.59 ± 0.56; self-image 4.39 ± 0.51; mental health 4.43 ± 0.56; satisfaction 4.81 ± 0.40; total 4.52 ± 0.37 (p< 0.0001). Males performed better at 2-years post-surgery (4.62 ± 0.25) compared to females (4.49 ± 0.39), (p= 0.004). Patients with spondylolisthesis performed worse pre-operatively (2.93 ± 0.26) compared to other diagnoses (p< 0.0001). This did not impact 2-year post-operative outcomes. There were no significant changes regarding age or year of surgery, type of operation or between the 3 age groups. CONCLUSIONS All individual domains and total SRS-22 scores improved significantly with incremental change during post-operative follow-up. Patient satisfaction was very high for all individual diagnosis. 2-year post-operative outcomes compared favorably to reported SRS-22 scores in healthy adolescents.