Miracle-dz/UniFAR-FTUs huggingface dataset:
Isochrony in the olivocerebellar system underlies complex spike synchrony

In a recent issue of The Journal of PhysiologyBaker & Edgley (2006) published results which they interpreted as showing a non-uniform olivocerebellar conduction time in the rat. Baker and Edgley used the climbing fibre reflex to measure conduction time to different points along a folial wall. This reflex is initiated by electrical stimulation of the cerebellar white matter, which triggers antidromic spikes in olivocerebellar axons that invade the inferior olive (IO). Current generated by these spikes spreads to neighbouring IO neurones via the gap junctions that electrically couple IO neurones (Llinas et al. 1974). This spreading excitation can trigger orthodromic spikes that return to the cerebellar cortex and trigger Purkinje cell complex spikes (CSs). Baker and Edgley found that climbing fibre reflex latency varied with recording electrode depth, and inferred from this that conduction time between the IO and cerebellar cortex varies systematically with cortical location. This study conflicts with results by us and others that indicate a near uniform olivocerebellar conduction time in rats and turtles (Sugihara et al. 1993; Lang & Rosenbluth, 2003; Ariel, 2005). Below we discuss several troubling issues with this new study, but first we would like to make the point that spontaneous CS synchrony patterns almost necessitate a uniform olivocerebellar conduction time.
Role of CD8 regulatory T‐cells in multiple sclerosis

We were positively intrigued by the article of Correale and Villa about CD8 regulatory T-cells (Treg) in multiple sclerosis (MS) patients. Several interesting issues were elucidated in this study. First, no numerical differences in CD25þFoxP3þ CD8þ T-cells were found in this small study with 10 MS patients and 10 healthy controls (HC). This is in line with another recent study and also with our findings in a larger cohort of 32 stable MS patients and 37 HC (our unpublished work). Second, no functional differences could be found in the suppressive capacity of CD8þCD25þFoxP3þ T-cells derived from peripheral blood of MS patients compared to HC. It is of note that in the CD4þ Treg subset, the CD25þFoxP3þ cells consist of at least 2 distinct populations: cells coexpressing the IL-7R (CD127) vs IL-7R–negative cells. Importantly, FoxP3 acts as a suppressor of the promoter of the IL-7R gene. It has hence been suggested that functionally active FoxP3 suppresses IL-7R expression and that IL-7R expression is therefore a proxy of the suppressive capacity of Tregs. Accordingly, IL-7R–negative regulatory T-cells are considered to be the most effectively suppressive Tregs. Within our CD25þFoxP3þ CD8 T-cells, we found a significantly decreased percentage of IL-7R CD25þFoxP3þ CD8 T-cells in MS patients compared to HC (Fig). In parallel, a significantly increased frequency of IL-7Rþ regulatory CD8 T-cells in MS patients was detected. As expected, in view of the suppressor action of FoxP3 on the IL-7R promoter, the level of FoxP3 expression was significantly higher in IL-7R CD25þFoxP3þ T-cells compared to IL-7RþCD25þFoxP3þ T-cells (data not shown). In conclusion, the balance between CD8 regulatory T-cells with a potentially high suppressive capacity and those with a potentially low suppressive capacity based on IL-7R expression is disturbed in MS patients. Therefore, we suggest to stratify CD8 Treg according to IL-7R expression and it would be of interest to assess if differential IL-7R expression on the T-cell clones used by Correale and Villa is related with their suppressor function.
Dynamic regulation of FoxP3 expression controls the balance between CD4+ T cell activation and cell death

The forkhead‐family transcription factor FoxP3 is important for the development and function of CD4+CD25+ regulatory T cells. While the overall phenotypic effects of FoxP3 expression are evident, the mechanism by which FoxP3 regulates T cell activation is not well understood. CD4+ T cells from mice that express a FoxP3 Tg are refractory to TCR‐mediated stimulation, failing to proliferate or produce cytokines, but possess suppressive activity towards normal T cells. In this report we show that these T cells express elevated levels of mRNA for pro‐apoptotic genes and undergo rapid apoptosis following stimulation. These T cells also display slower cell cycle transit following activation, suggesting that FoxP3 is capable of regulating the ability of T cells to respond to TCR‐mediated activation. Lastly, we show that contrary to expected results, under Th1 or Th2 driving conditions, CD4+ T cells from FoxP3 Tg mice differentiate into effector cells. Concomitant with differentiation is a loss of FoxP3 mRNA and protein. These data demonstrate that FoxP3 levels regulate T cell function, and that FoxP3 itself is dynamically regulated during effector T cell differentiation.
NDP gene mutations in 14 French families with Norrie disease

Norrie disease is a rare X‐inked recessive condition characterized by congenital blindness and occasionally deafness and mental retardation in males. This disease has been ascribed to mutations in the NDP gene on chromosome Xp11.1. Previous investigations of the NDP gene have identified largely sixty disease‐causing sequence variants. Here, we report on ten different NDP gene allelic variants in fourteen of a series of 21 families fulfilling inclusion criteria. Two alterations were intragenic deletions and eight were nucleotide substitutions or splicing variants, six of them being hitherto unreported, namely c.112C>T (p.Arg38Cys), c.129C>G (p.His43Gln), c.133G>A (p.Val45Met), c.268C>T (p.Arg90Cys), c.382T>C (p.Cys128Arg), c.23479‐1G>C (unknown). No NDP gene sequence variant was found in seven of the 21 families. This observation raises the issue of misdiagnosis, phenocopies, or existence of other X‐linked or autosomal genes, the mutations of which would mimic the Norrie disease phenotype. © 2003 Wiley‐Liss, Inc.
The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma

Here, we propose a new model for understanding the Warburg effect in tumor metabolism. Our hypothesis is that epithelial cancer cells induce the Warburg effect (aerobic glycolysis) in neighboring stromal fibroblasts. These cancer-associated fibroblasts, then undergo myo-fibroblastic differentiation, and secrete lactate and pyruvate (energy metabolites resulting from aerobic glycolysis). Epithelial cancer cells could then take up these energy-rich metabolites and use them in the mitochondrial TCA cycle, thereby promoting efficient energy production (ATP generation via oxidative phosphorylation), resulting in a higher proliferative capacity. In this alternative model of tumorigenesis, the epithelial cancer cells instruct the normal stroma to transform into a wound-healing stroma, providing the necessary energy-rich micro-environment for facilitating tumor growth and angiogenesis. In essence, the fibroblastic tumor stroma would directly feed the epithelial cancer cells, in a type of host-parasite relationship. We have termed this new idea the "Reverse Warburg Effect. " In this scenario, the epithelial tumor cells "corrupt" the normal stroma, turning it into a factory for the production of energy-rich metabolites. This alternative model is still consistent with Warburg's original observation that tumors show a metabolic shift towards aerobic glycolysis. In support of this idea, unbiased proteomic analysis and transcriptional profiling of a new model of cancer-associated fibroblasts (caveolin-1 (Cav-1) deficient stromal cells), shows the up-regulation of both i) myo-fibroblast markers and ii) glycolytic enzymes, under normoxic conditions. We validated the expression of these proteins in the fibroblastic stroma of human breast cancer tissues that lack stromal Cav-1. Importantly, a loss of stromal Cav-1 in human breast cancers is associated with tumor recurrence, metastasis, and poor clinical outcome. Thus, an absence of stromal Cav-1 may be a biomarker for the "Reverse Warburg Effect", explaining its powerful predictive value.
Event-history analysis for left-truncated data.

"This paper aims at providing a practical guidance for coping with social science event-history data that are left-truncated, especially when the length of exposure prior to observation is known. Only the case of single events is treated, although much of the discussion should be applicable to the case of repeated events, in which only the first spell is likely to be left-truncated. Marital dissolution data from the Panel Study of Income Dynamics (PSID) are used as an example. "
SERS characterization based on silver nanoparticle dimer in microfluidic laminar flow for molecule trace detection

This paper focuses on metal nanoparticles “dimer” with a molecular bridge for highly sensitive trace detection by Surface Enhanced Raman Spectroscopy (SERS). We clarified Raman intensity was determined from a concentration of particle dimers in mixing of a nanoparticle and a molecule solutions by characterization of SERS with the experimental and the analytical studies. This is because the particle dimer gives us higher enhancement factor of SERS intensity than the conventionally-used larger cluster of nanoparticles. Furthermore we proposed a multilayered mixing of nanoparticles and molecule solutions to achieve a higher concentration of the particle dimer in an entire laser spot of a portable Raman spectroscope.
Isolation of a trypsin‐like serine protease gene family from the sheep blowfly Lucilia cuprina

Various protease inhibitors active against both trypsin‐ and chymotrypsin‐like serine proteases were used to characterize gut proteases from Lucilia cuprina by in vitro feeding assays. Significant larval growth retardation was observed on feeding first‐instar larvae with trypsin inhibitors, particularly soybean trypsin inhibitor. Feeding of chymostatin, a specific chymotrypsin inhibitor, resulted in no significant growth retardation. This information suggests that trypsin‐like serine proteases are probably the major gut digestive enzymes. A DNA fragment obtained by PCR which coded for part of a putative trypsin gene from L. cuprina was used to isolate a four‐member multigene family of trypsins. The full nucleotide sequence of one of the genes and partial sequence from the other three genes were determined. Transcription of at least one of the genes has been confirmed. All four of the genes appear to have arisen by two separate gene duplication events.
Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine

The period of cell genesis of rod and cone photoreceptor cells has been determined in the retinas of C57BL/6J mice. Embryonic mice were exposed to a single dose of 3H‐thymidine at embryonic day (E) 10‐18 by injecting pregnant mice intraperitoneally. Animals at postnatal ages were injected subcutaneously once between postnatal day (P) 0‐10. The eyes were removed at one to three months of age. After fixation, they were embedded in glyol methacrylate, sectioned at 1.5 μm and prepared for autoradiographic analysis. All of the cone cells are generated over a relatively short time interval during the fetal period. In the posterior retina, the peak of cone cell genesis occurs at E13‐E14, and no cones are generated after E16. The rods, by contrast, are generated later and over a longer time period. They first begin to be generated in the posterior retina on E13, but the peak of cell genesis in not reached until the day of birth, and some rods are generated as late as P5. For both rods and cones the peaks of cell genesis in the peripheral retina occur two to three days later than in the posterior retina. The findings demonstrate that rods and cones are developmentally distinct cell types in the mouse retina.
Complete mitochondrial genome of Acipenser schrenckii (Acipenseriformes, Acipenseridae)

Abstract The complete nucleotide sequence of Acipenser schrenckii mtDNA is 16,592 bp long (Accession No. KC820796). The total mitochondrial genome is consisted of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The gene organization and arrangement is identical to typical vertebrates.
Laser Technology in Orthopedics: Preliminary Study on Low Power Laser Therapy to Improve the Bone-Biomaterial Interface

Low Power Laser (LPL) seems to enhance the healing of bone defects and fractures. The effect of LPL In other orthopedic areas such as osteointegration of implanted prosthetic bone devices is still unclear. In the present study, 12 rabbits were used to evaluate whether Ga-AI-As (780 nm) LPL stimulation has positive effects on osteointegration. Hydroxyapatite (HA) cylindrical nails were drilled into both distal femurs of rabbits. From postoperative day 1 and for 5 consecutive days, the left femura of all rabbits were given LPL treatment (Laser Group-LG) with the following parameters: 300 Joule/cm2 1 Watt, 300 Hertz, pulsating emission, 10 minutes. The right femura were sham-treated (Control Group-CG). At 4 and 8 weeks after implantation, histologic and histomorphometric investigations evaluated bone-biomaterial-contact. Histomorphometry showed a higher degree of osteointegration at the HA-bone interface in the LG Group at 4 (p<0.0005) and 8 weeks (p<0.001). These preliminary positive results seem to support the hypothesis that LPL treatment can be considered a good tool to enhance the bone-implant interface in orthopedic surgery.
Psychological interventions for multiple sclerosis.

BACKGROUND The unpredictable, variable nature of Multiple Sclerosis (MS), and the possibility of increasing disability, means that a diagnosis can have substantial psychological consequences. OBJECTIVES To assess the effectiveness of psychological interventions for people with MS. SEARCH STRATEGY We searched 19 databases up to December 2004; Cochrane MS Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsychINFO, CINAHL and 14 others. We searched reference lists of articles, wrote to corresponding authors of the 13 papers identified by June 2004, and searched for trials in progress using 3 research registers. SELECTION CRITERIA Randomised controlled trials of interventions described as wholly or mostly based on psychological theory and practice, in people with MS. Primary outcome measures were disease specific and general quality of life, psychiatric symptoms, psychological functioning, disability, and cognitive outcomes. Secondary outcome measures were number of relapses, pain, fatigue, health care utilisation, changes in medication, and adherence to other therapies. DATA COLLECTION AND ANALYSIS Pertinent studies were identified from abstracts by one author. Full papers were independently compared to selection criteria by four authors. Key details were extracted from relevant papers using a standard format, and studies scored on three dimensions of quality. The review is organised into four mini-reviews (MR) dependent on the intervention's target population; people with cognitive impairments (MR1), people with moderate to severe disability (MR2), people with MS (no other criteria) (MR3), and people with depression (MR4). MAIN RESULTS Overall 16 studies were identified and included. MR1: three trials (n=145). Some evidence of effectiveness of cognitive rehabilitation on cognitive outcomes, although this was difficult to interpret because of the large number of outcome measures used. MR2: three trials (n=80). One small trial suggesting psychotherapy may help with depression. MR3: seven studies (n=688). Some evidence that cognitive behavioural therapy may help people adjust to, and cope with, having MS (three trials). The other trials were diverse in nature and some difficult to interpret because of multiple outcome measures. MR4: three trials (n=93). Two small studies of cognitive behavioural therapy showed significant improvements in depression. AUTHORS' CONCLUSIONS The diversity of psychological interventions identified indicates the many ways in which they can potentially help people with MS. No definite conclusions can be made from this review. However there is reasonable evidence that cognitive behavioural approaches are beneficial in the treatment of depression, and in helping people adjust to, and cope with, having MS.
Strategies for Real-Time Spatial Analysis Using Massively Parallel SIMD Cpmputers: An Application to Urban Traffic Flow Analysis

Abstract The current research focuses upon the development of a methodology for undertaking real-time spatial analysis in a supercomputing environment, specifically using massively parallel SIMD computers. Several approaches that can be used to explore the parallelization characteristics of spatial problems are introduced. Within the focus of a methodology directed toward spatial data parallelism, strategies based on both location-based data decomposition and object-based data decomposition are proposed and a programming logic for spatial operations at local, neighborhood and global levels is also recommended. An empirical study of real-time traffic flow analysis shows the utility of the suggested approach for a complex, spatial analysis situation. The empirical example demonstrates that the proposed methodology, especially when combined with appropriate programming strategies, is preferable in situations where critical, real-time, spatial analysis computations are required. The implementation of this exa.
Effect of Norepinephrine on Ketogenesis, Fatty Acid Oxidation, and Esterification in Isolated Rat Hepatocytes

Recent studies in man demonstrated a marked ketogenic effect of increased plasma norepinephrine concentrations as observed in diabetic ketoacidosis. Since this effect may have been due either to increased substrate supply for ketogenesis (lipolysis) or to direct hepatic activation of ketogenesis, the latter mechanism was examined in isolated rat hepatocytes. Incubation of hepatocytes with norepinephrine (10−7 to 10−4 M) resulted in a dose-dependent increase in conversion of the long-chain fatty acid [1−14C]palmitate into ketone bodies and CO2. Norepinephrine decreased [1-14C]palmitate conversion into triglycerides without affecting fatty acid uptake. Norepinephrine enhanced ketogenesis from [1-14C]palmitate in a physiologic range of fatty acid concentrations (0.5–2.5 mM), but failed to affect fatty acid esterification to phospholipids or mono- and diglycerides. In contrast to long-chain fatty acids, oxidation of the medium-chain fatty acid [1-14C]octanoate to ketone bodies was not enhanced by norepinephrine, whereas CO2 production increased. The effect of norepinephrine on [1-14C]fatty acid oxidation was blocked by the a, receptor blocker prazosine. The results demonstrate that norepinephrine diverts long-chain fatty acids into the pathways of oxidation and ketogenesis away from esterification, suggesting enhanced carnitine-dependent mitochondrial fatty acid uptake. The studies using octanoate indicated that norepinephrine also enhanced fatty acid oxidation by increasing the flux of acetyl-CoA through the Krebs cycle. The data suggest that stress-associated sympathetic activation and norepinephrine discharge, as observed in diabetic ketoacidosis, result in direct activation of ketogenesis in the liver.
A stable smoothly wavelength-tunable picosecond pulse generator

Smooth wavelength tuning over 10 nm has been realized in a dispersion-tuned harmonically mode-locked fiber ring laser. Supermode noise is suppressed by 13 dB by adding a semiconductor optical amplifier (SOA) into the cavity and the suppression improves as the SOA gain increases. 5.3-ps pulses are obtained at a repetition rate of 10 GHz. A simple numerical model demonstrates the effects of the intracavity dispersion and the SOA on the pulse characteristics.
Gene organization of a novel defensin of Ixodes ricinus: first annotation of an intron/exon structure in a hard tick defensin gene and first evidence of the occurrence of two isoforms of one member of the arthropod defensin family

Antimicrobial peptides (defensins) are effectors of the immune system. Herein, we describe a novel Ixodes ricinus defensin gene(s), analyse its structure and compare it with other known antimicrobial peptides from different tick species. For the first time, an intron/exon structure is discovered in a hard‐tick defensin gene. The intron/exon genomic organization of the gene is similar to the organization in Ornithodoros moubata, but not to that of the intronless defensins of Dermacentor variabilis and Ixodes scapularis. The analysis of the deduced amino acid sequences of different recombinants from the I. ricinus cDNA library reveals the presence of two defensin isoforms with three amino acid substitutions. Whether or not these substitutions affect the biological properties of the peptides is currently unknown. The expression of the defensin gene is strongly induced in the tick midgut after infection with Borrelia burgdorferi.
The Placebo Response its putative role as a functional salutogenic mechanism of the central nervous system

328 ABSTRACT The concept of placebo has evolved over time. Generally believed to be the basis of the premodern pharmacopoeia, the placebo has been adopted in practice as a harmless but unscientific approach towards alleviating symptoms. Currently, many medical scientists view placebos pejoratively as confounding elements in the analysis of randomized control trials.This article examines the changing attitudes towards placebos and the persistent controversies that surround their administration.The possible role of the placebo response as a functional salutogenic brain mechanism is considered, and elements of Edelman’s neurobiological model of self and attractor theory are combined to explain how a unitary response by the central nervous system might yield diverse placebo effects. It is concluded that placebo responses are rooted in the complexity of mind/body interactions and that their underlying physiological mechanisms may be elucidated via methods that directly examine brain activity as the basis of subjective experience.
Association Between Contact Lens Discomfort and Pre-lens Tear Film Kinetics

Purpose The relationship between contact lens wettability and comfort has been extensively evaluated; however, a direct correlation between the characteristics of the pre-lens tear film and the symptoms associated with contact lens discomfort has yet to be established. In addition, there is relatively limited knowledge relating to the entire tear film kinetics during the inter-blink period in contact lens wearers. The purpose of this analysis was to identify the characteristics of the pre-lens tear film kinetics that may be associated with the symptoms of contact lens discomfort. Methods The study population comprised 202 soft (hydrogel and silicone hydrogel) contact lens wearers attending pre-screening visits at the OTG-i research clinic. All participants completed the Ocular Surface Disease Index (OSDI) questionnaire and the tear film was quantified via post hoc, masked analysis of high definition digital Tearscope videos recorded at the visit. The tear film kinetics of the least symptomatic wearers (OSDI lowest quintile scores, n = 45) were compared to the tear film kinetics of the most symptomatic wearers (OSDI highest quintile scores, n = 43). The hypothesis tested was that the tear film kinetics of asymptomatic wearers were better than tear film kinetics of symptomatic wearers. Results The distribution of lens types worn was as follows: Daily Disposable 46.5%, 1-Month Replacement 39.6%, and 2-Week Replacement 13.6%. 48.2% of lenses were silicone hydrogel and 51.8% hydrogel. Symptomatic wearers had a shorter break-up time (4.7 s vs. 6.0 s; p = 0.003), lesser surface coverage by the tear film during the interblink period (95.1% vs. 98.5%; p < 0.001) and greater surface exposure at the time of the blink (9.4% vs. 3.9%; p = 0.001). Conclusions The current study demonstrated that the tear film kinetics of asymptomatic and symptomatic contact lens wearers were different, the findings supporting the hypothesis of poorer tear film kinetics for symptomatic than asymptomatic wearers in a general contact lens wearing population.