Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel recessive cone-rod dystrophy caused by POC1B mutation.

IMPORTANCE A new form of cone-rod dystrophy (CORD) is described and the gene responsible for the disease is identified. OBJECTIVE To clinically evaluate 4 patients and 5 control relatives, perform disease gene mapping, and identify the gene defect responsible for CORD. DESIGN, SETTING, AND PARTICIPANTS Prospective observational case series of 13 members of a consanguineous family and 113 unrelated control individuals. INTERVENTIONS Clinical investigations included eye examination with color fundus and autofluorescent imaging, spectral-domain optical coherence tomography, and electrophysiologic measurements. Linkage mapping was performed using single-nucleotide polymorphism genotype data. Candidate genes were analyzed for mutations via Sanger sequencing. MAIN OUTCOMES AND MEASURES Clinical diagnosis of CORD, disease gene mapping, and mutation identification. RESULTS The onset of CORD occurred in early childhood. The clinical phenotype was typical CORD with photophobia, decreased central vision, and dyschromatopsia. In all patients, a disrupted inner segment/outer segment line and the external limiting membrane were noted as a single blurry line at the central fovea, and the cone outer segment tip line was absent. In the midperipheral retina, the rod inner segment/outer segment line was disrupted and blurry, and the rod outer segment tip line was absent. Cone response was nonrecordable in all patients, whereas rod response was nonrecordable in the eldest patient and subnormal in the others. The Arden Index was abnormal in the youngest patient and flat in the others. The disease gene mapped to a less than 2-megabase recessive locus at 12q21.33 with a logarithm of odds score of 3.92. At the locus, we identified a homozygous missense POC1B p.R106P mutation that was predicted as damaging by online tools. CONCLUSIONS AND RELEVANCE POC1B is a novel gene for a new disease typical of CORD except that patients did not report night blindness. The clinical course was slowly progressive. Screening for POC1B mutation could benefit families afflicted with CORD.
Growth medium-independent genetic competence mutants of Bacillus subtilis

The development of competence in Bacillus subtilis is normally dependent on the growth medium. Expression of late competence genes occurs in glucose-minimal salts-based media but not in complex media. Expression is also inhibited when glutamine is added to competence medium and when glycerol is substituted for glucose. Mutations have been identified in two regulatory loci, mecA and mecB, which render competence development independent of these variables. Although in mec mutants the expression of late competence genes, as well as of competence itself, occurred in all media tested, this expression was still growth stage regulated. Thus at least some forms of medium-dependent and growth stage-specific regulation are genetically separable. One of the mecB mutations (mecB31) conferred oligosporogenicity. The mecB mutations were tightly linked by transformation to rif, lpm, and std markers and were located between rif-2103 and cysA14. The mecA42 mutant was linked by transduction to argC4.
Miniaturized branch-line coupler with coupling-dependent dual-frequency operation

A miniaturized branch-line coupler that is able to operate at two arbitrary frequencies is presented in this paper. The dual-band frequency ratio depends on the coupling coefficient in the proposed transmission line element. It will be shown later that the dual-band separation decreases as the coupling strength increases. By replacing the traditional quarter-wavelength lines with the proposed artificial transmission lines of a prescribed coupling coefficient, a size-reduced branch-line coupler can be implemented at dual frequencies of interest. An example of the 0.9- and 1.8-GHz branch-line coupler, which corresponds to a band ratio of 2, is experimentally developed and characterized. The presented coupler occupies only 44% footprint of the conventional coupler operating at the lower frequency of the dual-band operation. Excellent agreement between the simulated and measured results is obtained.
ANTIBODIES TO ALEUTIAN MINK DISEASE PARVOVIRUS IN FREE-RANGING EUROPEAN MINK (MUSTELA LUTREOLA) AND OTHER SMALL CARNIVORES FROM SOUTHWESTERN FRANCE

Owing to the rapid decline of the European mink (Mustela lutreola) in France, a national conservation action plan has been initiated, in which scientific research to improve understanding of the causes of the decline is one of the primary objectives. In order to investigate the possible role of Aleutian disease parvovirus (ADV) in decline of the species, a serologic survey was conducted from March 1996 to March 2002 in 420 free-ranging individuals of six species of small carnivores distributed in eight départements of southwestern France. Antibodies to ADV were detected in 17 of 75 American mink (Mustela vison), 12 of 99 European mink, 16 of 145 polecats (Mustela putorius), four of 17 stone martens (Martes foina), one of 16 pine martens (Martes martes), and three of 68 common genets (Genetta genetta). Seroprevalence was significantly higher in American mink than in other species. Seropositive individuals with gamma globulin levels >20% were observed in four European mink, four American mink, two stone martens, and one pine marten. Geographic distribution of positive animals indicates the virus has spread to all areas where European mink are found. Furthermore, a trend of increasing prevalence seems to appear in Mustela sp. sympatric with American mink. Although further investigations are necessary to evaluate the role of ADV in decline of European mink, evidence of the virus in the wild at the levels found in our study has implications for conservation of this species.
Fine-structure mapping of the three mouse alpha-fetoprotein gene enhancers

Multiple cellular enhancers have been identified previously in the 5'-flanking region of the mouse alpha-fetoprotein gene by transient expression assay. In this report the enhancers have been localized to three regions 200 to 300 base pairs in length at 2.5, 5.0, and 6.5 kilobases of DNA upstream of the transcriptional start site. Nucleotide sequence analysis of the three enhancers revealed areas of homology among them, the most significant of which were two regions of 10 and 18 nucleotides in length. Two of the enhancers were analyzed in detail and shown to be composed of multiple nonidentical domains, none of which was sufficient for full enhancer activity; rather, they acted in an additive fashion in generating the full activity of the enhancer. The tissue-specific activity of the enhancer at -2.5 kilobases was assessed by comparing the activities of subdomains in liver- and non-liver-derived cell lines and was found to be the result of both positive elements within the enhancer and at least one negative element to its 5' end. In contrast, the tissue specificity of the enhancer at -5.0 kilobases was maintained when the minimal essential region was tested alone. The nucleotide sequence similarities, as well as the differences among the enhancers, may explain their differing biological activities both in tissue culture and in vivo.
Lumped parameter model with inner state variables for modeling hot deformability of steels

F. Vode, J. Burja, F. Tehovnik, B. Arh, Institute of Metals and Technology, Ljubljana, Slovenia A novel method for description of stress-strain relationship for hot deformability of steels is presented. Laplacian transformation of stress-strain data obtained on cylindrical hot compression tests offer simple description of dynamical input/output relationship between strain (input) and stress (output). In this paper, strain/stress relationship is described using transfer function of the third order. Parameters of transfer function are determined by numerical optimization for temperatures 1 000, 1 100 and 1 200 °C and logarithmic strain rates 10, 5 and 1 s-1. Obtained relative model error is around 1 % for logarithmic deformations in the range 0,1 < < 0,8.
Mitochondrial toxicity in hearts of CD‐1 mice following perinatal exposure to AZT, 3TC, or AZT/3TC in combination

Antiretroviral therapies based on nucleoside reverse transcriptase inhibitors (NRTIs), like zidovudine (3′‐azido‐3′‐deoxythymidine; AZT) and lamivudine ((‐)2′,3′‐dideoxy‐3′‐thiacytidine; 3TC), markedly reduce mother‐to‐child transmission of the human immunodeficiency virus (HIV). However, AZT induces damage in nuclear DNA of mice exposed in utero and postnatally, and mitochondrial DNA (mtDNA) damage has been observed in both human and mouse neonates following perinatal exposure to AZT and AZT/3TC in combination. To provide animal data modeling the NRTI‐induced heart damage reported in human infants, we treated pregnant CD‐1 mice throughout gestation and treated their pups by direct gavage from postnatal day (PND) 4 through PND 28 with daily doses of 150 mg/kg body weight (bw)/day AZT, 75 mg/kg bw/day 3TC, 125/62.5 mg/kg bw/day AZT/3TC, or the vehicle control. Half the pups were euthanized on PND 28; the remainder received no further dosing, and were euthanized at week 10. Heart tissue was collected, total DNA was extracted, and mtDNA copy number relative to nuclear DNA copy number, mtDNA damage, and mtDNA mutation assays were performed using PCR‐based methods. Analyses revealed increases in mtDNA lesions in 4‐week‐old males and females treated with AZT or 3TC, but not in 10‐week‐old mice, suggesting that the damage resolved after treatment ceased. Interestingly, 10‐week‐old females treated with AZT/3TC had significant increases in mtDNA damage. Point mutations were elevated in 10‐week‐old females treated with AZT or AZT/3TC, but not 3TC; no increases in mutations were seen in either gender at 4 weeks of age. Our data suggest that AZT/3TC combination treatment produces greater mtDNA damage than either agent individually, and that female mice are more sensitive than males to AZT/3TC‐induced mtDNA damage. Environ. Mol. Mutagen. , 2006. Published 2006 Wiley‐Liss, Inc.
Therapeutic options for HIV-associated lymphomas

Importance of the field: The clinical features and natural history of HIV-associated lymphomas differ greatly from those observed in the general population. The failure to improve outcomes with treatment intensification indicates the need for the introduction of new therapeutic options. Areas covered in this review: This review summarizes reports from 1995 to the present which focus on the treatment strategies and their prognostic relevance in the setting of HIV-associated lymphomas. What the reader will gain: The identification of prognostic factors in rare tumors such as HIV-associated lymphomas is going to require the establishment of multi-institutional and cooperative group-supported tissue banks. The rarity of primary effusion lymphomas and plasmablastic lymphomas of the oral cavity type makes large prospective studies difficult and challenges the feasibility of defining therapy specific for a given subpopulation of patients. Take home message: HIV-associated lymphomas still represent a relevant field of clinical research. Standard methodologies for therapy in this patient population have yet to be established. However, rituximab plus chemotherapy should be offered to the majority of patients with HIV infection and diffuse large B-cell lymphomas; and the feasibility of intensive aggressive chemotherapy regimens has been successfully tested in HIV-associated Burkitt's lymphomas.
Carbonate platform growth and cyclicity at a terminal Proterozoic passive margin, Infra Krol Formation and Krol Group, Lesser Himalaya, India

Abstract The Infra Krol Formation and overlying Krol Group constitute a thick (< 2 km), carbonate‐rich succession of terminal Proterozoic age that crops out in a series of doubly plunging synclines in the Lesser Himalaya of northern India. The rocks include 18 carbonate and siliciclastic facies, which are grouped into eight facies associations: (1) deep subtidal; (2) shallow subtidal; (3) sand shoal; (4) peritidal carbonate complex; (5) lagoonal; (6) peritidal siliciclastic–carbonate; (7) incised valley fill; and (8) karstic fill. The stromatolite‐rich, peritidal complex appears to have occupied a location seaward of a broad lagoon, an arrangement reminiscent of many Phanerozoic and Proterozoic platforms. Growth of this complex was accretionary to progradational, in response to changes in siliciclastic influx from the south‐eastern side of the lagoon. Metre‐scale cycles tend to be laterally discontinuous, and are interpreted as mainly autogenic. Variations in the number of both sets of cycles and component metre‐scale cycles across the platform may result from differential subsidence of the interpreted passive margin. Apparently non‐cyclic intervals with shallow‐water features may indicate facies migration that was limited compared with the dimensions of facies belts. Correlation of these facies associations in a sequence stratigraphic framework suggests that the Infra Krol Formation and Krol Group represent a north‐ to north‐west‐facing platform with a morphology that evolved from a siliciclastic ramp, to carbonate ramp, to peritidal rimmed shelf and, finally, to open shelf. This interpretation differs significantly from the published scheme of a basin centred on the Lesser Himalaya, with virtually the entire Infra Krol–Krol succession representing sedimentation in a persistent tidal‐flat environment. This study provides a detailed Neoproterozoic depositional history of northern India from rift basin to passive margin, and predicts that genetically related Neoproterozoic deposits, if they are present in the High Himalaya, are composed mainly of slope/basinal facies characterized by fine‐grained siliciclastic and detrital carbonate rocks, lithologically different from those of the Lesser Himalaya.
microRNAs Downregulation in Cancer is Associated with Guanine Enrichment in the Terminal Loop Sequences of their Precursors.

BACKGROUND microRNAs (miRNAs) are small noncoding segments of RNA that negatively regulate gene expression at the post-transcriptional level and fine-tune gene functions. A global repression in miRNA expression is a phenomenon observed in different types of cancer. In this study we aimed to reveal a possible association of miRNAs downregulation in cancer, with the guanine (G) content in the terminal loop (TL) sequences of their precursors. METHODS Lists of most significantly downregulated miRNAs in different tumor types, obtained from previously published microarray experiments, were selected for bioinformatics analysis. The complete precursor, TL, and mature miRNA sequences, were analyzed for evaluation of nucleotide composition and motif enrichment. RESULTS Herein, we show an association of miRNAs downregulation in cancer, with G enrichment in the TL sequences of their precursors. High G (and GG) content was mostly found in repressed miRNAs of breast, lung and ovary cancers, predominantly in poorly differentiated tumors. The mature sequences of repressed miRNAs had significantly low G content and were enriched with an ACA motif. CONCLUSION This study suggests a new link between G enrichment of precursor miRNAs TLs and carcinogenesis, and the possible association of specific sequence motifs with the regulation of their expression.
Convergence Analysis and Tuning of a Sliding-Mode Ripple-Correlation MPPT

The development of fast maximum power point tracking (MPPT) algorithms for photovoltaic (PV) systems with high bandwidth and predictable response to irradiation transients is attractive for mobile applications and installations under fast changing weather conditions. This paper proposes the convergence analysis of a sliding-mode version of the MPPT based on ripple correlation control (RCC). The contribution of this paper is a dynamic model, useful to derive a set of design guidelines to tune the sliding-mode RCC-MPPT and achieve a desired dynamic performance under irradiation transients. The research is based on sliding control theory and it includes both the chattering phenomena analysis, and a discussion on the effects of reactive parasitic elements in the PV module. The proposed analysis and design have been validated by MATLAB simulations first, and then with experimental tests on a 35-W panel with a boost converter charging a 24-V battery. The results support the effectiveness of the proposed modeling procedure and design guidelines, showing good agreement between the model prediction and the experimental transient response.
Drug-induced liver damage -- a three-year study of patients from one gastroenterological department.

BACKGROUND The aim of our study was to analyze drug-induced liver disease over a 3-year period in one gastroenterological department. MATERIAL/METHODS International consensus standard definitions and criteria for assessing causality of adverse drug reactions were applied to all patients with abnormal hepatic test results. RESULTS Drugs were implicated in hepatic injury in 14 patients (8 females) in whom causal relationship between drug and liver disease was definite or highly probable. The drugs responsible were amoxicillin with clavulanic acid (3 cases), fluvastatin and pravastatin (3 cases), antituberculous drugs (2 cases), estrogens, roxithromycin, asacol, satolol, enalapril and thiamazol. A total of 78.6% (11 cases) were classified as hepatocellular or mixed hepatitis, while cholestatic injury was found in 21.4% (3 cases). There were no lethal or severe (prothrombin < 50%) hepatic drug reactions. In 13 patients the course of liver disease after withdrawal of the offensive drug was either acute or protracted, while in one patient there was chronic cholestasis (>3 years) resulting from injury to interlobular bile ducts by amoxicllin with clavulanic acid. CONCLUSIONS A thorough history of drug intake should be taken in all patients presenting with abnormal hepatic test results. Amoxicillin & clavulanic acid, cholesterol-lowering and antituberculin drugs were the most frequent hepatotoxic factors in our patients. In a majority of cases the liver injury was not severe, and resolved after prompt withdrawal of the responsible drug.
Protective Role for H-NS Protein in IS1 Transposition

ABSTRACT The transposase (InsAB′) of the insertion element IS1 can create breaks in DNA that lead to induction of the SOS response. We have used the SOS response to InsAB′ to screen for host mutations that affect InsAB′ function and thus point to host functions that contribute to the IS1 transposition mechanism. Mutations in the hns gene, which codes for a DNA binding protein with wide-ranging effects on gene expression, abolish the InsAB′-induced SOS response. They also reduce transposition, whether by simple insertion or cointegrate formation, at least 100-fold compared with the frequency seen in hns+ cells. Examination of protein profiles revealed that in an hns-null mutant, InsAB′ is undetectable under conditions where it constitutes the most abundant protein in hns+ cells. Likewise, brief labeling of the hns cells with [35S]methionine revealed very small amounts of InsAB′, and this was undetectable after a short chase. Transcription from the promoters used to express insAB′ was essentially unaltered in hns cells, as was the level of insAB′ mRNA. A mutation in lon, but not in ftsH or clpP, restored InsAB′ synthesis in the hns strain, and a mutation in ssrA partially restored it, implying that the absence of H-NS leads to a problem in completing translation of insAB′ mRNA and/or degradation of nascent InsAB′ protein.
Repeatability of corneal thickness measurements made by a scanning slit topography system

Two sets of corneal thickness (CT) measurements at five corneal locations were made with Orbscan on 33 normal young adults. No significant intravisit and intervisit differences at any of the corneal locations were found (Repeated measures anova, F < 0.49, p > 0.49). The 95% limits of agreement (95% LA) for between‐measurement differences for the central cornea was about ±19 μm (or 3%), indicating good repeatability; for the inferior, temporal and nasal corneal locations, the 95% LA were close to ±30 μm (≈4–5%); and for the superior corneal location, they were about ±35 μm (or 5.5%). The estimated number of repeated measurements that should be taken for accurate CT measurements (at any of the five corneal locations and excluding outliers of >3 S.D.) of 2% (standard error) is ≤2, and of 3% is 1. This study shows that only central CT measurements with the Orbscan are repeatable. The role of the Orbscan pachometry is therefore limited and is recommended for central CT measurements only.
Identification, Isolation and Characterization of IGF Binding Proteins as a Secretable Proteins of Human Endometrial Stromal Cell Culture

IGF-1, a high potent mitogenic factor with a dual function is believed to participate with female steroids and other growth factors to prepare endometrium receptivity for successful embryo implantation and further development. Stromal cells forms the functional receptive layer of endometrium structure. Analysis of the conditioned/defined medium of pure cultured human endometrial stromal cells have revealed that stromal cells in a monolayer culture secrete and produce three different types of proteins in a varying amounts. These proteins exhibit a high specificity as well as a high binding affinity for the radiolabeled IGF-1 peptide. The molecular weights of these proteins have been determined by SDS-Page electrophoresis after cross-linking with the radiolegand IGF-1 and then detected with autoradiography. By comparison to the migration of high molecular weights protein markers, these proteins have been identified to correspond to the IGFBP-1 (31 KDa), IGFBP-2 (36 KDa) and IGFBP-3 (45 KDa). The secretion of these binding proteins (IGFBP-1, -2, -3) by endometrial stromal cells may support the view of their biological importance in controlling the delivery and bioavailability of the high mitogen IGF-1 peptide to their nominative type-1 IGF-receptor on cell surface, thereby modulating its action. It seems likely that these IGFBPs may play a key role in switching on/off IGF-1 peptide action , thereby avoiding the uncontrolled proliferation effect of the IGF-1 that favor endometrium cancer development.
A Si-chip-based system for highly parallel electroporation of cells

A single-cell electroporation system is presented capable for efficient, highly parallel, and noninvasive transfection of biological cells as required in cloning experiments. The 2D geometry of Si-chips with cells cultivated on their surface enables good controllability and accessibility of the experiment using standard microscopic monitoring methods. On the basis of a modified silicon-on-insulator (SOI) technology chips are processed with 192 electroporation sites. The assembled chips are operated in a setup which allows application of a large variety of electrical protocols. First results from cell culture experiments prove feasibility.