Miracle-dz/UniFAR-FTUs huggingface dataset:
Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives.

We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2beta autoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2betaA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.
A pseudaffective reflex and its spinal path

IF in the cat under deep chloroform narcosis the cerebral hemispheres and thalamencephalon be carefully ablated, and the body temperature maintained, on relaxing the depth of chloroformisation a number of motor reactions can be observed against the background of 'decerebrate rigidity. ' Among these reactions are some mimetic movements simulating expression of certain affective states. These 'pseud-affective' reflexes we have endeavoured to utilise for elucidation of the spinal path conducting those impulses that, were the brain intact, would, we may presume, evoke 'pain. ' The search for such a path is as regards channels from skin a search for a path as specific as those of the special senses. The truncation of the brain at the mesencephalon annihilates the neural mechanism to which the affective psychosis is adjunct. But it leaves fairly intact the reflex motor machinery whose concurrent action is habitually taken as outward expression of an inward feeling. When the expression occurs it may be assumed that had the brain been present the feeling would have occurred. A spinal translesion which prevents occurrence of the expression in response to a stimulus that previously excited the expression has therefore been regarded by us in the following experimrrents to be such as would, were the brain present, induce analgesia in regard to that stimulus. Apart from that assumption it is clear that such a lesion can be used for determining the path of a nociceptive, reaction. That a reflex action should exhibit purpose is no longer considered evidence that any psychical process attaches to it, let alone any dictate of 'choice' or ' will. ' By the Darwinian hypothesis, of no less value in physiology than in morphology, every reflex must be purposive. But the assignnient of a particular purpose to a particular reflex is often difficult and
Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges

Schizophrenia (SZ) is a heritable brain disease originating from a complex interaction of genetic and environmental factors. The genes underpinning the neurobiology of SZ are largely unknown but recent data suggest strong evidence for genetic variations, such as single nucleotide polymorphisms, making the brain vulnerable to the risk of SZ. Structural and functional brain mapping of these genetic variations are essential for the development of agents and tools for better diagnosis, treatment and prevention of SZ. Addressing this, neuroimaging methods in combination with genetic analysis have been increasingly used for almost 20 years. So-called imaging genetics, the opportunities of this approach along with its limitations for SZ research will be outlined in this invited paper. While the problems such as reproducibility, genetic effect size, specificity and sensitivity exist, opportunities such as multivariate analysis, development of multisite consortia for large-scale data collection, emergence of non-candidate gene (hypothesis-free) approach of neuroimaging genetics are likely to contribute to a rapid progress for gene discovery besides to gene validation studies that are related to SZ.
Beam Test Measurements With 3D-DDTC Silicon Strip Detectors on n-Type Substrate

For the planned luminosity upgrade of the CERN LHC to the sLHC new radiation hard technologies for the tracking detectors are investigated. Corresponding to the luminosity increase, the radiation dose will be approximately a factor of ten higher than for the detectors currently installed in the LHC experiments. One option for radiation tolerant detectors are 3D silicon detectors with columnar electrodes penetrating into the silicon bulk. This article reports results of beam test measurements performed with 3D-DDTC (Double-Sided, Double Type Column) silicon strip detectors, where the columns do not pass through the detector completely. The devices were produced by IMB-CNM (Barcelona, Spain) and by FBK-irst (Trento, Italy). Important properties like space-resolved charge collection and efficiency are investigated.
Exclusive destruction of mitotic spindles in human cancer cells

We identified target proteins modified by phenanthrenes that cause exclusive eradication of human cancer cells. The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. Their activity prevented the binding of NuMA to α-tubulin and kinesins in human cancer cells, and caused aberrant spindles. The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. Concomitantly, PJ34 induced tumor growth arrest of human malignant tumors developed in athymic nude mice, indicating the relevance of its activity for cancer therapy.
Antidiarrheal Activity of Wood Creosote: Inhibition of Muscle Contraction and Enterotoxin-Induced Fluid Secretion in Rabbit Small Intestine

Wood creosote has long been used as an antidiarrheal agent, but its mechanism of action is not well understood. To elucidate the mechanism of its antidiarrheal activity, we have addressed questions whether it inhibits fluid secretion induced by Escherichia coli heat-stable enterotoxin (STa) in rabbit jejunum in vivo, and whether it inhibits muscle contraction of isolated rabbit ileum ex vivo. Wood creosote (10–100 mg/l) instilled in a ligated loop of jejunum inhibited STa-induced fluid secretion (p < 0.05). It also inhibited the spontaneous phasic, acetylcholine-induced tonic and Ba2+-induced tonic contractions of longitudinal and circular muscles of ileum dose-dependently with IC50 values of 130–530 mg/l. These data provide further evidence that the antidiarrheal activity of wood creosote is attributable to its antisecretory and antimotility effects.
Incubation period of Creutzfeldt–Jakob disease in human growth hormone recipients in France

Objective: To estimate the statistical distribution of the incubation period of Creutzfeldt–Jakob disease (CJD) in human growth hormone (hGH) recipients in France. Background: Published papers suggest that the median incubation period of hGH-related CJD is approximately 15 years, but there are as yet no statistical data that support this assertion. Methods: Of the 1,361 hGH recipients who were included in this study, 55 had developed CJD at the time of the study. Individual data on hGH treatment history were available. Different mathematical models were used to estimate the statistical distribution of the incubation period. One main feature of the models was to take into account the occurrence of future CJD cases. Results: Models showed that the mean incubation period was 9 to 10 years, and the 95th percentile of the distribution was 15 to 16 years. Data and models indicated that the incubation period was significantly shorter in homozygotes at codon 129 of the prion protein gene than in heterozygotes. Conclusions: The short mean incubation period of CJD in French hGH recipients may be due to high infectivity in hormone lots. Estimates of the 95th percentile indicate that the number of hGH-related CJD cases may continue to increase in the coming years.
Formative Assessment Design for PDA Integrated Ecology Observation

Ubiquitous computing and mobile technologies provide a new perspective for designing innovative outdoor learning experiences. The purpose of this study is to propose a formative assessment design for integrating PDAs into ecology observations. Three learning activities were conducted in this study. An action research approach was applied to continually revise the worksheet designs. Twenty-seven 5 th and 6 th graders’ observation skills using PDAs, and their extended inquiry performance using e-diaries were assessed. An e-library, and online scoring and feedback systems were developed accordingly. The results suggest that the embedded formative assessment designs were effective for guiding and supporting the students’ learning progress. The activity worksheets successfully helped the students focus their outdoor learning attention on the target tasks. The e-library provided reliable resources to clarify their observed descriptions, while the automatic scoring and feedback systems were especially helpful in sustaining the students’ persistent effort. Most students demonstrated substantial improvements in their observation skills, and extended their inquiry abilities. The well designed online formative assessment embedded in the activity worksheet is very promising for PDA integrated learning.
Plasma Catecholamine Levels in Preterm Infants

ABSTRACT. Catecholamine levels were measured in cord arterial blood from preterm infants. Relatively lower catecholamine levels were found in the preterm infants than in term infants, although no significant correlation was found between noradrenaline and adrenaline levels and either gestational age or birthweight. Significantly higher catecholamine levels were found after labour. Preterm females had significantly higher catecholamine levels than boys after asphyxia and tended also to have higher catecholamine levels without asphyxia, although not significant. Catecholamine levels were also significantly elevated in those infants with a low Apgar score (<7 at 5 min) and those who were acidotic (cord arterial pH <7.25). A good correlation was found between a low Apgar score and the presence of acidosis.
Effects of peroxisome proliferators and 12‐O‐tetradecanoyl phorbol‐13‐acetate on intercellular communication and connexin43 in two hamster fibroblast systems

Effects of 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA) and the hepatic peroxisome proliferators (HPPs) clofibrate, methyl clofenapate (MCP), di(2‐ethylhexyl)phthalate (DEHP) and mono(2‐ethylhexyl)phthalate (MEHP) were studied in 2 gap junctional intercellular communication (GJIC) systems, metabolic cooperation in V79 cells and microinjection/dye transfer in Syrian hamster embryo (SHE) cells and V79 cells. TPA inhibited GJIC in both systems but was considerably more potent in V79 cells. SHE cells showed a rapid and transient inhibition of GJIC after exposure to HPPs, with maximal inhibition occurring at 5–15 min. The transient inhibition could be caused by metabolization of the compounds. Clofibrate and MEHP produced strong inhibition of metabolic cooperation in V79 cells at high concentrations, while the effect of MCP and DEHP was lower. However, DEHP, MEHP and clofibrate strongly inhibited dye transfer in V79 cells after a 30 min exposure. Clofibrate also showed a dose‐ and time‐dependent effect on dye transfer in V79 cells. The phosphorylation status of the gap junction protein connexin43 (Cx43) changed minimally in SHE cells after exposure to TPA or HPPs. Cx43 from V79 cells was strongly affected by TPA, but not by HPPs. Immunofluorescence of Cx43 disappeared in both cell types when they were exposed to TPA and MEHP, but not to the other HPPs. Thus, there is no direct correlation between the inhibition of GJIC and changes in the phosphorylation status of Cx43 or the appearance of Cx43 in immunofluorescence experiments. The discrepancies may partly be explained by binding of accessory proteins to Cx43. We point out sequences that may be involved in such binding. Int. J. Cancer 73:240–248, 1997. © 1997 Wiley‐Liss, Inc.
A 13.56MHz fully integrated 1X/2X active rectifier with compensated bias current for inductively powered devices

Wireless power transfer has a broad range of applications ranging from mobile phone chargers to biomedical implants. For cochlear implants [1] and retinal prostheses [2], having a miniaturized form factor and being battery-less are highly desirable. Such devices require real-time power transfer in the range of 10 to 100mW [3], and as human tissue specific absorption rate (SAR) increases with frequency, inductively-coupled power links that operate at 13.56MHz or lower in ISM bands are commonly used, as shown in Fig. 4.2. 1. However, lower transmission frequency means larger matching and filtering capacitors that are bulky. In addition, the received AC input amplitude VAC,Peak would fluctuate due to changes in distance and orientation between the coupling coils. Hence, comparator- controlled power switches (active diodes) are used to replace diodes so that the rectifier could work at a lower VAC,Peak and still achieve a high voltage conversion ratio (VCR) and power conversion efficiency (PCE) [4]. In this research, we present the first fully integrated 1X/2X active rectifier in the 30mW range with all capacitors fabricated on-chip, also shown in Fig. 4.2. 1. This is made possible by a switching arrangement that avoids connecting the output capacitors in series in the 2X mode. Reverse current is reduced for VAC,Peak that ranges from 1.25 to 4V by a bias current that is quasi-inversely proportional to the output DC voltage, as explained later; and efficiency is carefully measured by the insertion of a sensing resistor plus an additional capacitor to reduce distortion.
Pasture availability and genotype effects in rabbits: 2. Development of gastro-intestinal tract and immune function of the vermiphorm appendix.

The aim of this trial was to investigate the effect of pasture availability on gastro-intestinal tract and lymphoid follicle development from the vermiphorm appendix (VA) of weaned rabbits of the Leprino of Viterbo and New Zealand White (NZW) breeds. Weaned Leprino of Viterbo and NZW weaned rabbits, (30 days old; 40 animals/breed) were divided into two groups, placed into bicellular cages (17 rabbits/m) or wired pens (10 rabbits/m) and provided with an external grass pasture (1 rabbit/20 m). Rabbits were slaughtered at 90 days of age and body weights were recorded. The gastro-intestinal tracts were excised and weighed. Length, diameter and weight of VA were recorded as well as the number and area of the lymphoid follicles. Differences in pasture availability and locomotive activity were associated with different slaughter weights. Rabbits reared with pasture available exhibited a higher gastro-intestinal tract weight (P<0.05), in particular NZW rabbits which showed the greatest pasture intake. As expected, the highest weight of full gastro-intestinal tract (P<0.05) was observed in the two breeds with pasture availability. A slight increase in the number of lymphoid follicles in the VA from animals reared with pasture could explain a better health condition, even taking into account that this structure represents only a part of the total lymphoid tissue associated with the gut.
Anatomical hubs from spectral clustering of structural connectomes

The analysis of the structural brain networks have recently gathered extensive interest due to its crucial role in unveiling the fundamental principles of the brain. The uniformity of structural networks inferred from diffusion tensor imaging across different individuals is however, unknown. This paper presents a method to infer group-wise consistent structural clusters from the connectome Laplacian graph. The spectral clustering of the cortical networks from diffusion tensor imaging was applied on 146 healthy subjects using 3 random groups, and on groups based on gender and age, to determine the optimal number of clusters. The results show six consistent sub-networks of structural connections that was validated using known cluster validity indices, showing highly reproducible clusters for random groups and groups based on gender; while, cluster differences were observed between younger and older groups in areas related to memory.
Antispasmodic effect of Ocimum selloi essential oil on the guinea-pig ileum

Ocimum selloi is an herbal species popularly used in Brazil as antispasmodic. Herein, we report the antispasmodic effect of O. selloi essential oil (OS) in segments of guinea-pig ileum. OS did not reduce the tonus of the ileum. In contrast, OS reduced the contraction induced by carbachol (100 μM), BaCl2 (0.03 M) and low- and high-K+ concentrations (25 and 60 mM, respectively). OS shifted the concentration–response curve for calcium to the right in a parallel manner. GC/MS analysis showed that OS consists mostly of methyl chavicol (97.57%). These results suggest that OS antispasmodic effect is mediated through calcium channel blockade. In addition, OS effect and mode of action could be accounted for methyl chavicol.
Impact of hyperglycaemia and cholesterol levels on the outcome of hepatitis C virus (HCV) treatment in HIV/HCV‐coinfected patients

High serum total cholesterol and low‐density lipoprotein (LDL) levels have been demonstrated to increase the probability of a sustained viral response (SVR) in chronic hepatitis C. Conversely, insulin resistance reduces SVR rates. We investigated the influence of baseline glucose and lipid values on the outcome of hepatitis C virus (HCV) treatment in HIV‐1 infected subjects.
Experimental and Numerical Study of Electrical Crosstalk in Photonic-Integrated Circuits

This paper presents measurement results on electrical crosstalk between interconnect lines and electro-optical phaseshifters in photonic-integrated circuits. The results indicate that overall crosstalk originates from radiative and substrate coupling between lines and from shared ground connections. The latter is the main noise source in the structures measured in this paper and keeps crosstalk above -25 dB for interconnects and above -20 dB for phase-shifters independent of coupling distance. Measurements on the effect of electrical crosstalk on optical modulation show that -20 dB of coupling degrades modulation performance significantly, leading to at least 2-dB power penalty. A simulation approach is presented that reproduces the experimental results and gives insight into crosstalk mechanisms.
Selection for Visual Failure Detection

The visual difference between outcomes in many robotics tasks is often subtle, such as the tip of a screw being near a hole versus in the hole. Furthermore, these small differences are often only observable from certain viewpoints or may even require information from multiple viewpoints to fully verify. We introduce and compare three approaches to selecting viewpoints for verifying successful execution of tasks: (1) a random forest-based method that discovers highly informative fine-grained visual features, (2) SVM models trained on features extracted from pre-trained convolutional neural networks, and (3) an active, hybrid approach that uses the above methods for two-stage multi-viewpoint classification. These approaches are experimentally validated on an IKEA furniture assembly task and a quadrotor surveillance domain.
Review: Enhancers in Autoimmune Arthritis: Implications and Therapeutic Potential

Genome-wide association studies (GWAS) have identified hundreds of single-nucleotide polymorphisms (SNPs) associated with autoimmune diseases, including autoimmune arthritis. So far, it has proven difficult to translate these findings into disease understanding and novel therapeutic approaches as the majority of these SNPs are not located in protein-coding regions. Recently, various studies found that a large number of autoimmune disease–associated SNPs affect DNA regulatory units, suggesting that altered epigenetic control of transcription is an important process in disease pathogenesis (1,2). Technical developments have allowed for detailed analysis of the epigenetic profile of diseaseassociated cells, creating new opportunities to study gene regulation in the context of disease. In this review, we will discuss these advances in the field of epigenetics, focusing on (super)enhancers associated with autoimmune arthritis. Furthermore, we will describe how enhancer profiling of disease-specific cells can contribute to better understanding of disease pathogenesis. Additionally, we will outline strategies that can target enhancer activity and discuss their potential use as therapeutic approaches in the treatment of autoimmune arthritis.
Fusion to Listeriolysin O and Delivery by Listeria monocytogenes Enhances the Immunogenicity of HER-2/neu and Reveals Subdominant Epitopes in the FVB/N Mouse1

Five overlapping fragments of rat HER-2/neu have been expressed in recombinant Listeria monocytogenes. Each fragment of HER-2/neu is secreted as a fusion protein with a truncated, nonhemolytic form of listeriolysin O (LLO). Lm-LLO-EC1, Lm-LLO-EC2, and Lm-LLO-EC3 overlap the extracellular domain of HER-2/neu, whereas Lm-LLO-IC1 and Lm-LLO-IC2 span the intracellular domain. All five strains controlled the growth of established NT-2 tumors, a rat HER-2/neu-expressing tumor line derived from a spontaneously arising mammary tumor in a FVB/N HER-2/neu-transgenic mouse. The antitumor effect of each of these vaccine constructs was abrogated by the in vivo depletion of CD8+ T cells, although only one known epitope has been defined previously and is present in Lm-LLO-EC2. Anti-HER-2/neu CTL responses were generated by each of the rLm vaccine constructs. With the use of a panel of 3T3 cell lines expressing overlapping fragments of HER-2/neu, regions of HER-2/neu with potential CD8+ T cell epitopes have been defined. DNA vaccines expressing either a fragment or full-length HER-2/neu were constructed in LLO-fused and non-LLO-fused forms. CTL analysis of the DNA vaccines revealed a broadening in the regions of HER-2/neu recognizable as targets when the target Ag is fused to LLO. These studies show the efficacy of L. monocytogenes-based HER-2/neu vaccines in a murine model of breast cancer and also that the immunogenicity of self-Ags can be increased by fusion to LLO and delivery by L. monocytogenes revealing subdominant epitopes.
Stock, Recruitment and Reference Points : Assessment and Management of Atlantic Salmon

Cet ouvrage rassemble les connaissances disponibles sur l'ecologie du saumon atlantique et les methodes modernes d'evaluation des stocks pour une tâche specifique : l'etablissement de points de reference. Les approches bayesiennes qui prennent en compte l'incertitude sont mises en avant tout au long du livre. Les methodes d'analyse stock-recrutement, le transport de points de reference, l'analyse de risque et l'utilisation d'indicateurs d'abondance sont presentes sous une forme facilement comprehensible et applicable par des chercheurs, des enseignants, des professionnels ou des etudiants.