Miracle-dz/UniFAR-FTUs huggingface dataset:
The distinct manifestation of young-onset amyotrophic lateral sclerosis in China

Abstract Objective Young-onset amyotrophic lateral sclerosis (ALS) refers to ALS patients with initial symptoms earlier than 45 years, representing a novel disease pattern. We aim to summarize the clinical and genetic features of 102 young-onset ALS patients in China. Methods: Clinical information and blood samples were collected from all registered patients, and we performed next generation sequencing techniques in an ALS customized panel to detect ALS-related genes. Results: A total of 95 sporadic ALS and seven familial ALS were involved in this study. Young-onset ALS showed male prevalence and had more spinal onset. With 44 patients carrying one or more variants, mutations in SPG11, ALS2, and SETX were the most frequent, followed by FUS variants. Other prevalent genes like SOD1, TARDBP, and C9ORF72 were relatively rare in young-onset patients. Conclusions: Our study highlighted distinct clinical manifestation and genetic background in young-onset ALS patients in China. These features should be verified in further investigations in other populations.
Genetic association of the AKT1 gene with schizophrenia in a British population

Objectives A number of studies have reported a genetic association of the AKT1 gene with schizophrenia, although some have failed to replicate the AKT1 association. This study was undertaken to further explore the AKT1 association with more single nucleotide polymorphisms in a British sample. Methods A total of 221 families, consisting of 148 fathers, 204 mothers and 222 offspring affected with schizophrenia, were recruited for genetic analysis. Analysis for allelic and haplotypic associations was performed with the UNPHASED program, using likelihood-based association analysis for nuclear families with missing parental genotype data. Results Allelic association was detected at rs1130214 (χ2=6.28, P=0.012) and at rs11847866 (χ2=4.64, P=0.031), although the remaining single nucleotide polymorphisms did not show allelic association with schizophrenia. The global P value of overall associations was 0.059 after 10000 permutations. Assessment using the Haploview program revealed rs1130214, rs2494746 and rs11847866 in the same linkage disequilibrium block and haplotype analysis showed disease association for the rs1130214-rs2494746-rs11847866 haplotypes (χ2=10.18, d.f.=4, P=0.037), of which the T-G-A haplotype was excessively transmitted (χ2=6.93, uncorrected P=0.008) and this haplotypic association survived Bonferroni correction (P=0.04). Conclusion The present results provide further evidence to support the AKT1 association with schizophrenia.
Prodrug bioactivation and oncolysis of diffuse liver metastases by a herpes simplex virus 1 mutant that expresses the CYP2B1 transgene

Herpes simplex virus 1 (HSV‐1) infection of cancer cells results in viral replication with cell destruction and liberation of progeny virion that infect adjacent tumor cells. rRp450 is a novel replication‐conditional HSV‐1 mutant that expresses both the endogenous herpes viral thymidine kinase gene and the rat p450 CYP2B1 transgene; p450 bioactivates such cancer prodrugs as cyclophosphamide.
Assessing the direct effects of deep brain stimulation using embedded axon models

To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.
UDP‐N‐Acetylglucosamine 4′‐Epimerase from the Intestinal Protozoan Giardia Intestinalis Lacks UDP‐Glucose 4′‐Epimerase Activity 1

ABSTRACT. The protozoan parasite Giardia intestinalis has a simple life cycle consisting of an intestinal trophozoite stage and an environmentally resistant cyst stage. The cyst is formed when a trophozoite encases itself within an external filamentous covering, the cyst wall, which is crucial to the cyst's survival outside of the host. The filaments in the cyst wall consist mainly of a β (1–3) polymer of N‐acetylgalactosamine. Its precursor, UDP‐N‐acetylgalactosamine, is synthesized from fructose 6‐phosphate by a pathway of five inducible enzymes. The fifth, UDP‐N‐acetylglucosamine 4′‐epimerase, epimerizes UDP‐N‐acetylglucosamine to UDP‐N‐acetylgalactosamine reversibly. The epimerase of G. intestinalis lacks UDP‐glucose/UDP‐galactose 4′‐epimerase activity and shows characteristic amino acyl residues to allow binding of only the larger UDP‐N‐acetylhexosamines. While the Giardia epimerase catalyzes the reversible epimerization of UDP‐N‐acetylglucosamine to UDP‐N‐acetylgalactosamine, the reverse reaction apparently is favored. The enzyme has a higher Vmax and a smaller Km in this direction. Therefore, an excess of UDP‐N‐acetylglucosamine is required to drive the reaction towards the synthesis of UDP‐N‐acetylgalactosamine, when it is needed for cyst wall formation. This forms the ultimate regulatory step in cyst wall biosynthesis.
End-of-life care in nursing home settings: Do race or age matter?

ABSTRACT Objective: One-quarter of all U.S. chronic-disease deaths occur in nursing homes, yet few studies examine palliative care quality in these settings. This study tests whether racial and/or age-based differences in end-of-life care exist in these institutional settings. Methods: We abstracted residents' charts (N = 1133) in 12 nursing homes. Researchers collected data on indicators of palliative care in two domains of care—advance care planning and pain management—and on residents' demographic and health status variables. Analyses tested for differences by race and age. Results: White residents were more likely than minorities to have DNR orders (69.5% vs. 37.3%), living wills (39% vs. 5%), and health care proxies (36.2% vs. 11.8%; p < .001 for each). Advance directives were highly and positively correlated with age. In-depth advance care planning discussions between residents, families, and health care providers were rare for all residents, irrespective of demographic characteristics. Nursing staff considered older residents to have milder and less frequent pain than younger residents. We found no disparities in pain management based on race. Significance of results: To the extent that advance care planning improves care at the end of life, racial minorities in nursing homes are disadvantaged compared to their white fellow residents. Focusing on in-depth discussions of values and goals of care can improve palliative care for all residents and may help to ameliorate racial disparities in end-of-life care. Staff should consider residents of all ages as appropriate recipients of advance care planning efforts and should be cognizant of the fact that individuals of all ages can experience pain. Nursing homes may do a better job than other health care institutions in eliminating racial disparities in pain management.
Characterization of Mutants Deficient in the l,d-Carboxypeptidase (DacB) and WalRK (VicRK) Regulon, Involved in Peptidoglycan Maturation of Streptococcus pneumoniae Serotype 2 Strain D39

ABSTRACT Peptidoglycan (PG) hydrolases play critical roles in the remodeling of bacterial cell walls during division. PG hydrolases have been studied extensively in several bacillus species, such as Escherichia coli and Bacillus subtilis, but remain relatively uncharacterized in ovococcus species, such as Streptococcus pneumoniae (pneumococcus). In this work, we identified genes that encode proteins with putative PG hydrolytic domains in the genome of S. pneumoniae strain D39. Knockout mutations in these genes were constructed, and the resulting mutants were characterized in comparison with the parent strain for growth, cell morphology, PG peptide incorporation, and in some cases, PG peptide composition. In addition, we characterized deletion mutations in nonessential genes of unknown function in the WalRKSpn two-component system regulon, which also contains the essential pcsB cell division gene. Several mutants did not show overt phenotypes, which is perhaps indicative of redundancy. In contrast, two new mutants showed distinct defects in PG biosynthesis. One mutation was in a gene designated dacB (spd_0549), which we showed encodes an l,d-carboxypeptidase involved in PG maturation. Notably, dacB mutants, similar to dacA (d,d-carboxypeptidase) mutants, exhibited defects in cell shape and septation, consistent with the idea that the availability of PG peptide precursors is important for proper PG biosynthesis. Epistasis analysis indicated that DacA functions before DacB in d-Ala removal, and immunofluorescence microscopy showed that DacA and DacB are located over the entire surface of pneumococcal cells. The other mutation was in WalRKSpn regulon gene spd_0703, which encodes a putative membrane protein that may function as a type of conserved streptococcal shape, elongation, division, and sporulation (SEDS) protein.
Defining C Preprocessor Macro Libraries with Functional Programs

The preprocessor of the C language provides a standard way to generate code at compile time. However, writing and understanding these macros is difficult. Lack of typing, statelessness and uncommon syntax are the main reasons of this difficulty. Haskell is a high-level purely functional language with expressive type system, algebraic data types and many useful language extensions. These suggest that Haskell code can be written and maintained easier than preprocessor macros. Functional languages have certain similarities to macro languages. By using these similarities this paper describes a transformation that translates lambda expressions into preprocessor macros. Existing compilers for functional languages generate lambda expressions from the source code as an intermediate representation. As a result it is possible to write Haskell code that will be translated into preprocessor macros that manipulate source code. This may result in faster development and maintenance of complex macro metaprograms.
Involvement of cysteine 306 and alanine 63 in the thermostability and oligomeric organization of glucose isomerase from Streptomyces sp. SK

The implication of the original alanine 63 (Ala63) and the unique cysteine 306 (Cys306) residues in the thermostability of the Streptomyces sp. SK glucose isomerase (SKGI) were investigated by site-directed mutagenesis and homology modelling. The Cys306 to Ala mutation within SKGI dramatically affected its thermal stability by decreasing the half-life from 80 to 15 min at 90°C while the Ala63 to Ser replacement shifted this half-life to 65 min. The electrophoretic analysis proves that the residue Cys306 participates in oligomerization of the SKGI. Its stabilizing role is materialized by hydrogen bonds established with arginines at positions 284 and 259, as deduced from the constructed three-dimensional model. We have also shown that the presence of an Ala63 instead of Ser63 seems to be more suitable for enzyme thermostability by maintaining hydrophobic pocket that contributes to the protection of the enzyme active site.
Color Doppler Blood Flow Indices of the Superior Mesenteric Artery as an Early Predictor of Necrotizing Enterocolitis in Preterm Neonates

Background: Necrotizing enterocolitis is the most common sever gastrointestinal emergency that affects premature newborns. It is often has a rapid onset with few signs that can be used to predict its occurrence. Its rapid onset and progression to morbidity and mortality initiates the researchers for seeking early diagnostic tools helping in detection infants at risk for development of the disease, for whom early preventive measures could be targeted. Previous studies have shown that high resistance patterns of mesenteric arterial Doppler flow velocimetry are associated with a significantly reduced tolerance to enteral feeding. Moreover, groups of infants deemed to be at increased risk of necrotizing enterocolitis tended to have high resistance patterns of flow in the superior mesenteric artery. AIM: To evaluate the Doppler blood flow indices of the superior mesenteric artery (SMA) in pre-term neonates at risk for developing necrotizing enterocolitis (NEC). Materials and Methods: This prospective study included 52 preterm neonates, whose gestational age was less than 34 weeks. All of the neonates were subjected to clinical assessments, laboratory investigations and color Doppler flow evaluation of the SMA (including PSV, EDV, RI and PI) on the first day of life. Necrotizing enterocolitis was diagnosed and classified based on Bell's staging criteria with Walsh and Kliegman's modifications. Clinical management and diagnosis of NEC were performed blind to the Doppler results. Statistical analysis was performed using the Mann-Whitney U test, and P-values less than or equal to 0.05 were statistically significant. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold values of PSV, EDV, RI and PI, using MedCalc software, version 12.7. 8.0. Results: The study included 52 preterm neonates, whose gestational age was less than 34 weeks. Twelve neonates (23%) developed NEC and were designated as group I, and the remaining 40 neonates (77%) were designated as group II. The median birth weights in groups I and II were 1000 and 1870 g, respectively, with a statistically significant difference of P < 0.05. Doppler indices of the SMA, peak systolic velocity (88.9 ±17 and 53 ±8.5 cm/s), end diastolic velocity (18.75±11.3 and 14.9±5.6 cm/s), resistive index (0.78±0.09 and 0.67±0.1) and pulsatility index (1.53±0.73 and 0.67 ± 0.15) were higher in group I than in group II, with statistically significant differences. Conclusion: Preterm infants with high resistance patterns of blood flow velocity in the SMA on the first day of life were at increased risk for developing necrotizing enterocolitis
Analysis of IL28B alleles with virologic response patterns and plasma cytokine levels in HIV/HCV-coinfected patients

Objectives:To estimate the impact of interleukin 28B (IL28B) polymorphisms (rs12980275, rs8099917, rs7248668, and rs11881222) and their haplotypes on hepatitis C virus (HCV) treatment (peg-interferon-&agr; and ribavirin) success in 324 HIV/HCV-coinfected patients. We also explore the behavior of plasma cytokine levels. Design:Retrospective follow-up study. Methods:Virologic response to HCV treatment was measured by plasma HCV viral load at different endpoints: rapid virologic response (RVR), early virologic response (EVR), end-of-treatment virologic response (ETVR) and sustained virologic response (SVR). IL28B polymorphisms were genotyped using GoldenGate assay. Finally, 13 cytokines were measured at baseline in 57 plasma samples using a multiplex immunoassay kit. Results:IL28B polymorphisms were strongly associated to virologic responses (RVR, EVR, ETVR, and SVR), although only for HCV genotypes 1 and 4 (P < 0.05). Strong linkage disequilibrium was detected for rs12980275/rs11881222 (r2 = 0.94) and rs8099917/rs7248668 (r2 = 0.99). IL28B haplotypes showed association but no improvement on treatment outcome prediction. Thus, the genotyping of only one single-nucleotide polymorphism was enough for predicting treatment response in GT1/4 patients with favorable rs12980275 (AA) genotype, while for subjects harboring unfavorable genotypes, the inclusion of rs8099917 was useful (SVR increased from 31 to 45%). Moreover, patients with rs12980275 (AA) that achieved SVR showed reduced plasma levels of Th1 (IFN-&ggr;), Th2 (IL-6 and IL-9), and proinflammatory (TNF-&agr;) cytokines. Conclusion:The presence of IL28B polymorphisms was significantly associated with HCV clearance during and after HCV therapy. The evaluated cytokine profile was much more favorable in patients with rs12980275 (AA) who achieved SVR.
Function and length scale integration in innovative products - technical solutions and new organisational models

This paper presents the issues typically occurring when integrating, into a single product, functions that can only be realised by employing different length scale features (macro, meso, micro and down to nano). The discussion is supported by the responses of a survey performed on 88 European research and development projects conducted by members of the multi-material micro manufacture (4M) community in Europe. Two main issues are highlighted as critical for a successful multi-scale integration. The first one relates to the concurrent design of materials properties and manufacturing processes. The second focuses on the need for new production approaches and organisational models applied by companies.
Mode'lisation, E'valuation et Ge'ne'ration de Techniques d'Interaction

La recherche en Interaction Homme-Machine a produit de nombreuses techniques d'interaction pour ameliorer l'utilisabilite des applications graphiques alors que les produits industriels n'en tirent que tres rarement profit. Ce constat est du a un manque d'outils pour faire des choix informes et mettre en oeuvre ces choix. Cette these propose trois outils utilisables en synergie pour favoriser l'adoption de techniques d'interaction avancees, depuis l'imagination d'une technique jusqu'a son implementation. Le premier outil, Complexity of Interaction Sequences (CIS), est un modele pour decrire une technique d'interaction et predire son efficacite dans un contexte d'utilisation donne. Le niveau d'abstraction eleve de CIS en fait un outil utilisable en amont de la conception et de l'evaluation afin de pouvoir envisager plusieurs techniques et apprecier leur efficacite a moindre cout. Le second outil, Touchstone, est une plateforme pour aider a la conception d'experimentations controlees. Son aspect exploratoire et son architecture modulaire permettent la reutilisation et facilitent la realisation d'experimentations controlees. Touchstone est non seulement destinee aux evaluateurs, mais egalement aux concepteurs grâce a sa fonction d'entrepot de resultats empiriques. Enfin, SwingStates est une boite a outils qui introduit un modele de dessin et des structures de controle adaptees a la programmation de techniques d'interaction avancees. SwingStates est une extension de Java Swing, une boite a outils largement utilisee pour le developpement d'interfaces graphiques, et offre ainsi de nouvelles possibilites au developpeur tout en restant dans leur cadre de travail habituel.
A High Quality Reflectance Model in Medical Image Visualization

The medical image visualization can help the doctor easy to diagnose, and the better quality can help doctor much more. The reflectance model is the key factor to make the quality better. Be enslaved to the computing power of CPU and GPU, some complicated reflectance models have not been used in medical visualization, the simple reflectance model-Phong model been used prevalently. With the growing computing power of GPU, this paper gives an improved reflectance model based on the Cook-Torrance reflectance model, which can render good quality in medical image visualization, and the velocity is 4 to 6 fps, that meet the real time rendering requirement. This reflectance model is a practical model for medical image visualization.
Hybrid brain-computer interface with motor imagery and error-related brain activity

Objective. Brain-computer interface (BCI) systems read and interpret brain activity directly from the brain. They can provide a means of communication or locomotion for patients suffering from neurodegenerative diseases or stroke. However, non-stationarity of brain activity limits the reliable transfer of the algorithms that were trained during a calibration session to real-time BCI control. One source of non-stationarity is the user’s brain response to the BCI output (feedback), for instance, whether the BCI feedback is perceived as an error by the user or not. By taking such sources of non-stationarity into account, the reliability of the BCI can be improved. Approach. In this work, we demonstrate a real-time implementation of a hybrid motor imagery BCI combining the information from the motor imagery signal and the error-related brain activity simultaneously so as to gain benefit from both sources. Main results. We show significantly improved performance in real-time BCI control across 12 participants, compared to a conventional motor imagery BCI. The significant improvement is in terms of classification accuracy, target hit rate, subjective perception of control and information-transfer rate. Moreover, our offline analyses of the recorded EEG data show that the error-related brain activity provides a more reliable source of information than the motor imagery signal. Significance. This work shows, for the first time, that the error-related brain activity classifier compared to the motor imagery classifier is more consistent when trained on calibration data and tested during online control. This likely explains why the proposed hybrid BCI allows for a more reliable means of communication or rehabilitation for patients in need.
Electrical performance evaluation of plasticized polyolefin formulation developed for manufacturing surge arresters housings

The performance and reliability of the electric power systems can be enhanced with the development of new polymer formulations, offering new concepts in equipment housing design and application. This paper reports the electrical and physicochemical properties of plasticized formulations based on HDPE, developed specifically for surge arresters housings. Plasticized HDPE surge arrester housings, 15 kV, were manufactured at ISO-9001 by one-shot injection molding technique. HDPE housed surge arresters were submitted to performance tests according to IEC 60.099-4 and exposed to artificial electrical aging tests and then physicochemically and electrically characterized. The physicochemical characterization comprised analysis by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), wide-angle X-ray diffraction (WAXRD), scanning electron microscopy (SEM), atomic force microscopy (AFM) and contact angle measurements. The FTIR results confirm the microstructural modifications of the aged HDPE due to oxidation phenomena, probably involving the formation of alcohol or carboxylic groups at surface level of surge arresters housings. The DSC technique shows no significant variation of the HDPE amorphous and crystalline content as a function of the electrical aging conditions. The TGA kinetics analysis shows significant changes in the activation energy for thermal degradation of the electrical aged and unaged HDPE surge arresters housings. The results obtained have demonstrated that the plasticized HDPE formulation has good stability at high electrical field and appears to be suitable for use in manufacturing surge arresters housings.