Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased hepatitis C virus (HCV)‐specific CD4+CD25 + regulatory T lymphocytes and reduced HCV‐specific CD4+ T cell response in HCV‐infected patients with normal versus abnormal alanine aminotransferase levels

CD4+CD25+ T regulatory cells may play a role in the different clinical presentations of chronic hepatitis C virus (HCV) infection by suppressing CD4+ T cell responses. Peripheral CD4+CD25+ T cells from chronic HCV carriers with normal and abnormal alanine aminotransferase (ALT) were analysed for specificity and effect on HCV‐specific CD4+ T cell reactivity by flow cytometry for intracellular cytokine production and proliferation assay. HCV‐specific CD4+CD25+high T cells consistently produced transforming growth factor (TGF)‐β but only limited amounts of interleukin (IL)‐10 and no IL‐2 and interferon (IFN)‐γ. The HCV‐specific TGF‐β response by CD4+CD25+high T cells was significantly greater in patients with normal ALT compared to patients with elevated ALT. In addition, a significant inverse correlation was found between the HCV‐specific TGF‐β response by CD4+CD25+high T cells and liver inflammation. In peripheral blood mononuclear cells (PBMC), both HCV antigen‐induced IFN‐γ production and proliferation of CD4+ T cells were greater in patients with elevated ALT compared with patients with normal ALT. Depletion of CD4+CD25+ cells from PBMC resulted in an increase of both IFN‐γ production and proliferation of HCV‐specific CD4+ T cells that was significantly greater in patients with normal ALT levels compared with patients with elevated ALT. In addition, CD4+CD25+ T cells from patients with normal ALT levels proved to be significantly more potent to suppress CD4+ T cell reactivity with respect to those from patients with elevated ALT. In conclusion, these data support the hypothesis that CD4+CD25+ cells may play a role in controlling chronic inflammatory response and hepatic damage in chronic HCV carriers.
Differentiation‐induced alterations in cyclic AMP signaling in the Cath.a differentiated (CAD) neuronal cell line

Regulation of intracellular cyclic AMP is critical to the modulation of many cellular activities, including cellular differentiation. Moreover, morphological differentiation has been linked to subsequent alterations in the cAMP signaling pathway in various cellular models. The current study was designed to explore the mechanism for the previously reported enhancement of adenylate cyclase activity in Cath.a differentiated cells following differentiation. Differentiation of Cath.a differentiated cells stably expressing the D2L dopamine receptor markedly potentiated both forskolin‐ and A2‐adenosine receptor‐stimulated cAMP accumulation. This enhancement was accompanied by a twofold increase in adenylate cyclase 6 (AC6) expression and a dramatic loss in the expression of AC9. The ability of Ca2+ to inhibit drug‐stimulated cAMP accumulation was enhanced following differentiation, as was D2L dopamine receptor‐mediated inhibition of Gαs‐stimulated cAMP accumulation. Differentiation altered basal and drug‐stimulated phosphorylation of the cAMP‐response element‐binding protein, which was independent of changes in protein kinase A expression. The current data suggest that differentiation of the neuronal cell model, Cath.a differentiated cells induces significant alterations in the expression and function of both the proximal and distal portions of the cAMP signaling pathway and may impact cellular operations dependent upon this pathway.
Generalization of Orthogonal Frequency Division Multiplexing With Index Modulation

Recently, orthogonal frequency division multiplexing (OFDM) with index modulation (OFDM-IM) was proposed. By selecting a fixed number of subcarriers as active subcarriers to carry constellation symbols, the indices of these active subcarriers may carry additional bits of information. In this paper, we propose two generalization schemes of OFDM-IM, named OFDM with generalized index modulation 1 (OFDM-GIM1) and OFDM-GIM2, respectively. In OFDM-GIM1, the number of active subcarriers in an OFDM subblock is no longer fixed. Dependent on the input binary string, different numbers of active subcarriers are assigned to carry constellation symbols. In OFDM-GIM2, independent index modulation is performed on the in-phase and quadrature component per subcarrier. Through such ways, a higher spectral efficiency than that of OFDM-IM may be achieved. Since both generalization schemes proposed suffer from BER performance loss in low SNR region, an interleaving technique is proposed to tackle this problem. Finally, noting that the two generalization schemes are compatible with each other, the combination of these two schemes, named OFDM-GIM3, has also been investigated. Computer simulation results clearly show our proposed scheme's superiority in both spectral efficiency and BER performance compared to existing works.
Lidocaine abolishes the myocardial protective effect of sevoflurane post‐conditioning

Background: Post‐ischemic administration of volatile anesthetics activates ischemia–reperfusion injury salvage process and decreases myocardial damage. However, the mechanisms underlying anesthetic post‐conditioning and effects of lidocaine on it remain unclear. Here we report the cardioprotection of sevoflurane‐induced post‐conditioning and the effects of lidocaine on it.
Autosomal dominant retinitis pigmentosa (adRP; RP6): cosegregation of RP6 and the peripherin-RDS locus in a late-onset family of Irish origin.

We recently reported the localization of a gene for late-onset autosomal dominant retinitis pigmentosa (adRP; RP6), on the short arm of chromosome 6, by linkage analysis in a large family of Irish origin. It is notable that the gene encoding peripherin-RDS, a photoreceptor-specific protein, recently has been physically mapped on 6p. In our own analysis, an intrageneic marker derived from this gene cosegregated with the adRP disease locus with zero recombination (lod score 5.46 at q = .00). Using the CEPH reference panel, we now report the mapping of the peripherin-RDS gene relative to other 6p markers in the CEPH data base. Incorporation of these data into a multipoint analysis produced a lod score for adRP of 8.21, maximizing at the peripherin-RDS locus. This study provides strong evidence suggesting a role for peripherin-RDS in the etiology of one form of adRP.
Effect of smoking on atopic predisposition and sensitisation to allergens.

BACKGROUND Previous studies elsewhere have shown higher serum immunoglobulin E (IgE) levels in smokers and an association between smoking and sensitisation to allergens. Such information is not available for Indian population. Hence, the present study was carried out to evaluate the effect of smoking on atopic predisposition and sensitisation to aeroallergens. METHODS A total of 70 subjects were included in the present study comprising of 25 smokers, 22 reformed smokers and 23 non-smokers. Absolute eosinophil count (AEC), serum total IgE levels and skin prick test (SPT) against common aeroallergens were performed in all the subjects along with breath carbon monoxide (CO) levels and pulmonary function tests. RESULTS Smokers showed significantly higher serum total IgE levels (328.80 +/- 161.82 IU/mL) as compared to reformed smokers 177.27 +/- 86.47 IU/mL) and non-smokers (29.56 +/- 9.75 IU/mL). A number of subjects among smokers and reformed smokers elicited positive SPT reactions to various allergen extracts. Non-smokers did not show any significant positive skin reaction. The AECs were slightly higher in smokers (350 +/- 1145.61/mm3) as compared to reformed smokers (305 +/- 146.33/ mm3). Breath CO was considerably higher (greater than three times) in smokers than reformed smokers. However, reformed smokers showed greater airways obstruction than smokers. The former also had higher Brinkman index (646.81 +/- 392.32) as compared to the latter (448.36 +/- 279.86). CONCLUSIONS Smokers had significantly higher IgE serum levels than reformed smokers and non-smokers. Smoking seems to induce an atopic orientation and allergen sensitisation in individuals.
Transport Distraction Osteogenesis Using Nitinol Spring: An Exploration in Canine Mandible

Some experiments in rabbits have presented the potential feasibility of using shape memory alloy spring for continuous distraction osteogenesis. To confirm the effectiveness of such method, we established canine models for the exploratory experiments of transport distraction osteogenesis using nitinol springs. Simple devices, including an internal 60-mm long sinusoid-shaped nitinol springs were used in the study. All dogs needed only one operation. In theoperation, osteotomy was performed to create a 40-mm unilateral segmental mandibular body defect and a tooth-bearing transport bone disc. After reconstructive fixation of the remnant mandible, the spring was constricted and anchored across the distraction gap to activate transport distraction immediately. At the second experimental stage, an ePTFE sheet was further fixed to protect the defect and distraction gap before closing the incision. Control dogs underwent the same operation except for anchoring of the spring to examine the spontaneous bone regeneration. Automatic bone transportation, as a gradual slowdown process, was observed under the effect of the spring. The transport disc could get to the opposite side of the defect, or stopped halfway when ePTFE sheet intervened. Mandibular reconstruction was achieved in all these dogs and better in dogs with sheet protection. No integrated bone mass was found in the defect of control dogs. The study further proves that continuous distraction osteogenesis using nitinol springs is a practical technique, although the devices need more improvement for better control of the process of distraction and the quality of regenerated bone.
Involvement of NF-kappaB p50/p65 heterodimer in activation of the human pro-interleukin-1beta gene at two subregions of the upstream enhancer element.

A region between-3134 and -2729 bp upstream from the transcription site of the human pro-interleukin 1beta (proIL-1beta) gene was identified as an LPS-responsive enhancer element. In this study, the influence of the sequences located between -3134 and -2987 on the transcriptional activity of the proIL-1beta gene in LPS-stimulated Raw 264.7 cells was examined in detail. The results obtained by transient transfection of fos -CAT constructs that contained serial 5'-deletion mutations showed that the region between -3134 and -3059 appears to be required for the induction of transcription by LPS. Gel shift assay studies with synthetic oligonucleotides corresponding to partial sequences of the latter region and nuclear extracts from stimulated cells revealed specific protein binding sites between -3110 and -3090 and between -3079 and -3059. These specific bindings were time and LPS dose dependent. The results of supershift analysis using specific antibodies against transcription factors suggested that both binding complexes contained the NF-kappaB components p50 and p65, and did not contain other NF-kappaB proteins (p52, c-Rel, Rel B), AP-1 proteins (c-Fos, C-Jun), CREB or C/EBPbeta (NF-IL6). Mutation of either of the putative NF-kappaB-binding sites in the enhancer element decreased the LPS-stimulated transcriptional activity. These data indicated that two NF-kappaB-binding sites, which are located between -3134 and -3059, are critical for the activation of proIL-1beta gene transcription.
Decoding the similarities and differences among mycobacterial species

Mycobacteriaceae comprises pathogenic species such as Mycobacterium tuberculosis, M. leprae and M. abscessus, as well as non-pathogenic species, for example, M. smegmatis and M. thermoresistibile. Genome comparison and annotation studies provide insights into genome evolutionary relatedness, identify unique and pathogenicity-related genes in each species, and explore new targets that could be used for developing new diagnostics and therapeutics. Here, we present a comparative analysis of ten-mycobacterial genomes with the objective of identifying similarities and differences between pathogenic and non-pathogenic species. We identified 1080 core orthologous clusters that were enriched in proteins involved in amino acid and purine/pyrimidine biosynthetic pathways, DNA-related processes (replication, transcription, recombination and repair), RNA-methylation and modification, and cell-wall polysaccharide biosynthetic pathways. For their pathogenicity and survival in the host cell, pathogenic species have gained specific sets of genes involved in repair and protection of their genomic DNA. M. leprae is of special interest owing to its smallest genome (1600 genes and ~1300 psuedogenes), yet poor genome annotation. More than 75% of the pseudogenes were found to have a functional ortholog in the other mycobacterial genomes and belong to protein families such as transferases, oxidoreductases and hydrolases.
Dietary isoflavones act on bone marrow osteoprogenitor cells and stimulate ovary development before influencing bone mass in pre‐pubertal piglets

Food containing soybeans provide isoflavone phytoestrogens that can preserve bone mass in postmenopausal women, and prevent bone loss in ovariectomized rats. But their effects on bone remain unclear, particularly on bone formation during growth. Two groups of eight pre‐pubertal piglets were fed a basal or an isoflavone‐enriched (S800) diet for 6 weeks. The S800 diet contained 800 mg SoyLife™/kg, providing 2.8 mg isoflavones/kg body weight/day. Several bones were collected and tested for bone strength and density. Bone marrow was collected from humeri together with blood samples and genital tracts. The plasma concentrations of isoflavones were increased in the pigs fed S800, but growth rate, body weight, plasma bone markers, bone mineral density, and strength were all unaffected. In contrast, cultured stromal cells from S800 pigs had more alkaline phosphatase‐rich cells and mineralized nodules, secreted more osteocalcin, osteoprotegerin and RANK‐L, synthesized more osteoprotegerin, and RANK‐L. Cultured mononucleated nonadherent bone marrow cells from S800 pigs developed fewer tartrate‐resistant acid phosphatase mononucleated cells (osteoclast progenitors) when cultured with 1,25(OH)2D3, and resorbed a smaller area of dentine slices. Freshly isolated bone marrow osteoclast progenitors from S800 pigs had more caspase‐3 cleavage activity, and synthesized less RANK. Both osteoclast and osteoblast progenitors had ERα and ERβ, whose syntheses were stimulated by the S800 diet. The S800 piglets had heavier ovaries with more follicles, but their uterus weight was unaffected. We conclude that dietary isoflavones have no detectable effect on the bone mass of growing female piglets, but act on bone marrow osteoprogenitors via ERs—mainly ERβ, and stimulate ovary development. J. Cell. Physiol. 212: 51–59, 2007. © 2007 Wiley‐Liss, Inc.
Erythroid cell-specific mRNA stability elements in the alpha 2-globin 3' nontranslated region

Very little is known about the mechanisms mediating longevities of mRNAs. As a means of identifying potential cis- and trans-acting elements which stabilize an individual mRNA, naturally occurring mutations that decreased stability of the normally long-lived globin mRNA were analyzed. Our previous studies demonstrated that a subset of mutations which allowed the translating ribosome to read through into the alpha 2-globin 3' nontranslated region (NTR) targeted the mutant mRNAs for accelerated turnover in erythroid cells but not in several nonerythroid cell lines (I. M. Weiss and S. A. Liebhaber, Mol. Cell. Biol. 14:8123-8132, 1994). These results suggested that translational readthrough interfered with some feature of the alpha 2-globin 3' NTR required for message stability in erythroid cells. To define the cis-acting sequences which comprise this erythroid cell-specific stability determinant, scanning mutagenesis was performed on the alpha 2-globin 3' NTR, and the stability of each mutant mRNA was examined during transient expression. Three cytidine-rich regions which are required for longevity of the alpha 2-globin mRNA were identified. However, in contrast to the readthrough mutations, base substitutions in these elements destabilize the message through a translation-independent mechanism. To account for these results, we propose that the cis-acting elements form a complex or determinant in the normal alpha 2-globin mRNA which protects the message from degradation in erythroid cells. Disruption of this determinant, by translational readthrough or because mutations in an element prevent or inhibit its formation, targets the message for accelerated turnover in these cells.
Age-Related Changes in Vascular Endothelial Growth Factor Dependency and Angiopoietin-1–Induced Plasticity of Adult Blood Vessels

Abstract— Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are essential for vascular development, but this dependency has been assumed not to persist into adult life. In this study, we report that after 10 days of systemic treatment of 4-, 8-, and 16-week-old mice with VEGF-Trap, an inhibitor of VEGF, the number of capillaries in the tracheal mucosa was reduced by 39%, 28%, and 14%, respectively. The magnitude of the reduction decreased with age (r2 = 0.6, P <0.001), but was still significant at 16 weeks. A corresponding age-related decrease in vascular endothelial growth factor receptor-2 (VEGFR-2) immunoreactivity suggests that diminished VEGFR-2 expression may contribute to resistance to VEGF signaling inhibition. VEGF-Trap further reduced VEGFR-2 expression in tracheal capillaries. By comparison, systemic treatment with adenovirus encoding Ang1 led to a significant enlargement of tracheal venules with little age effect (64%, 56%, and 49% increase in diameter at 10 days). When Ang1 was given in combination with VEGF-Trap, tracheal vessels presented the typical response to each factor, showing that the Ang1 effect was not VEGF-mediated, yet Ang1 seems to have a protective effect, as judged by prevention of VEGF-Trap–induced reduction in tracheal capillaries in the oldest group. Together, these findings indicate that VEGF and Ang1 participate in blood vessel survival and plasticity in adult life.
Modified C-reactive protein might be a target autoantigen of TINU syndrome.

BACKGROUND AND OBJECTIVES The cross-reactive antigen(s) of tubulointerstitial nephritis and uveitis (TINU) syndrome from renal tubulointerstitia and ocular tissue remain unidentified. The authors' recent study demonstrated that the presence of serum IgG autoantibodies against modified C-reactive protein (mCRP) was closely associated with the intensity of tubulointerstitial lesions in lupus nephritis. The study presented here investigates the possible role of IgG autoantibodies against mCRP in patients with TINU syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS mCRP autoantibodies were screened by ELISA with purified human C-reactive protein in 9 patients with TINU syndrome, 11 with drug-associated acute interstitial nephritis, 20 with IgA nephropathy, 19 with minimal change disease, 20 with ANCA-associated vasculitis, 6 with Sjogren's syndrome, and 12 with amyloidosis. mCRP expression was analyzed by immunohistochemistry in renal biopsy specimens from the 9 patients with TINU syndrome and 40 from disease controls. Frozen normal human kidney and iris were used to demonstrate co-localization of human IgG and mCRP from patients with TINU syndrome with laser scanning confocal microscopy. RESULTS The mCRP autoantibodies were detected in all nine patients with TINU syndrome, significantly higher than that of those with disease controls (P < 0.05). The renal histologic score of mCRP in TINU syndrome was significantly higher than that in disease controls (P < 0.05). The staining of mCRP and human IgG were co-localized in renal and ocular tissues. CONCLUSIONS It is concluded that mCRP might be a target autoantigen in TINU syndrome.
A stable and low power on-chip system clock circuit for sensor nodes and low Power Timers

In this paper we present a 2μW temperature compensated on-chip digitally controlled oscillator and a 70nW uncompensated, ultra low power oscillator. The temperature compensated oscillator has a temperature stability of 8ppm/C while uncompensated oscillator has a stability of 4%/C. The uncompensated oscillator is calibrated using stable oscillator often to achieve high effective temperature stability. This combination gives us a stability of 8ppm/C @ 250nW if temperature changes by 1C every second. A calibration scheme for the oscillator is also presented.
Transcriptional Profiling Identifies Two Members of the ATP-binding Cassette Transporter Superfamily Required for Sterol Uptake in Yeast*

In contrast to lipoprotein-mediated sterol uptake, free sterol influx by eukaryotic cells is poorly understood. To identify components of non-lipoprotein-mediated sterol uptake, we utilized strains of Saccharomyces cerevisiae that accumulate exogenous sterol due to a neomorphic mutation in the transcription factor, UPC2. Two congenic upc2-1strains, differing quantitatively in aerobic sterol uptake due to a modifying mutation in the HAP1 transcription factor, were compared using DNA microarrays. We identified 9 genes as responsive toUPC2 that were also induced under anaerobiosis, when sterol uptake is essential. Deletion mutants in these genes were assessed for sterol influx in the upc2-1 background. UPC2itself was up-regulated under these conditions and was required for aerobic sterol influx. Deletion of the ATP-binding cassette transporters YOR011w (AUS1) orPDR11, or a putative cell wall protein encoded byDAN1, significantly reduced sterol influx. Sodium azide and vanadate inhibited sterol uptake, consistent with the participation of ATP-binding cassette transporters. We hypothesized that the physiological role of Aus1p and Pdr11p is to mediate sterol uptake when sterol biosynthesis is compromised. Accordingly, expression ofAUS1 or PDR11 was required for anaerobic growth and sterol uptake. We proposed similar molecules may be important components of sterol uptake in all eukaryotes.
On the consistent treatment of the quasi-hydrostatic layers in hot star atmospheres

CONTEXT: Spectroscopic analysis remains the most common method to derive masses of massive stars, the most fundamental stellar parameter. While binary orbits and stellar pulsations can provide much sharper constraints on the stellar mass, these methods are only rarely applicable to massive stars. Unfortunately, spectroscopic masses of massive stars heavily depend on the detailed physics of model atmospheres. AIMS: We demonstrate the impact of a consistent treatment of the radiative pressure on inferred gravities and spectroscopic masses of massive stars. Specifically, we investigate the contribution of line and continuum transitions to the photospheric radiative pressure. We further explore the effect of model parameters, e.g., abundances, on the deduced spectroscopic mass. Lastly, we compare our results with the plane-parallel TLUSTY code, commonly used for the analysis of massive stars with photospheric spectra. METHODS: We calculate a small set of O-star models with the Potsdam Wolf-Rayet (PoWR) code using different approaches for the quasi-hydrostatic part. These models allow us to quantify the effect of accounting for the radiative pressure consistently. We further use PoWR models to show how the Doppler widths of line profiles and abundances of elements such as iron affect the radiative pressure, and, as a consequence, the derived spectroscopic masses. RESULTS: Our study implies that errors on the order of a factor of two in the inferred spectroscopic mass are to be expected when neglecting the contribution of line and continuum transitions to the radiative acceleration in the photosphere. Usage of implausible microturbulent velocities, or the neglect of important opacity sources such as Fe, may result in errors of approximately 50% in the spectroscopic mass. A comparison with TLUSTY model atmospheres reveals a very good agreement with PoWR at the limit of low mass-loss rates.