Miracle-dz/UniFAR-FTUs huggingface dataset:
A 40-year-old woman considering contraception.

This clinical conference presents the case of a 40-year-old married US woman who is seeking a highly effective contraceptive method since she does not want another pregnancy. Throughout most of her childbearing years the patient used a combination of vaginal diaphragm and condom. 18 months ago she began using oral contraceptives (OCs) for the first time. The OCs reduced the patients premenstrual emotional lability and the amount of menstrual flow but caused intermittent headaches. For this patient the benefits of OC use far outweighed the problem with headaches. Debated in this conference is the issue of whether women can safely use OCs up to menopause. It is noted that for most women in the later childbearing years the combined contraceptive and noncontraceptive benefits clearly exceed the health risks for all methods of contraception. Questions regarding the safety of OC use among older women have focused on the risks of cardiovascular disease venous thromboembolism breast cancer and cervical cancer. The general consensus of case discussants was that as long as the patient remains healthy and does not smoke she is at low risk for continuing to use OCs until menopause. Vasectomy is another feasible option if the couple decides a permanent method of contraception is acceptable.
Assessed value of high-sensitivity cardiac troponin T for cardiovascular disease among CKD patients

Abstract Objective To analyze the relationship between serum high-sensitivity cardiac troponin T (hs-cTnT) and cardiovascular disease (CVD) among non-dialysis chronic kidney disease (CKD) patients, and to further explore its value of evaluating and predicting CVD in this population. Methods Five hundred and fifty-seven non-dialysis CKD patients were involved in this cross-sectional study. The relationship between serum hs-cTnT and CVD was analyzed using comparison between groups and regression analysis, and its value on assessing cardiac structure and function was evaluated by ROC curves. Results Median level of hs-cTnT was 13 (7–29) ng/L, with 1.7% undetectable, 46.4% greater than 99th percentile of the general population. Multivariate analysis suggested that compared with the lowest quartile of hs-cTnT, the highest quartile was approximately six times as likely to develop into LVH (OR, 6.515; 95% CI, 3.478–12.206, p < 0.05) and 18 times as likely to progress to left ventricular diastolic dysfunction(OR, 18.741; 95% CI, 2.422–145.017, p < 0.05). And Ln cTnT level had a more modest association with LVEF (OR, −1.117; 95% CI, −5.839 to −0.594; p < 0.05). When evaluated as a screening test, the area under the curve of ROC curves for hs-cTnT was 0.718, 0.788 and 0.736, respectively (p < 0.05). With a specificity of 90% as a diagnostic criterion, the value of hs-cTnT to evaluate LVH, LVEF < 50%, left ventricular diastolic dysfunction increased across CKD stages, from CKD 1 stage to CKD 5 stage. Conclusions In CKD non-dialysis population, hs-cTnT and NT-proBNP were valuable for evaluating LVH, left ventricular systolic dysfunction and left ventricular diastolic dysfunction.
Production, purification, and preliminary characterization of a gonococcal growth inhibitor produced by a coagulase-negative staphylococcus isolated from the urogenital flora

Coagulase-negative staphylococcus no. 7, isolated from the urogenital flora, was grown on semisolid brain heart infusion medium. Supernatants were obtained by centrifuging frozen and thawed media which had supported the growth of the staphylococci at 37 degrees C. The kinetic of production revealed that the antigonococcal activity was detected at the end of the logarithmic phase of growth and that the maximum activity was obtained after 24 h of incubation. Production of inhibitory activity was detected in cultures grown between 35 and 39 degrees C and in a pH range of 6.9 to 9.4. The inhibitory substance was purified by methanol extraction, acetone fractionation, dialysis, and chromatography on Ultrogel AcA 54. The characterization of the inhibitor showed that it was a lipoprotein or a lipid-associated-protein and that the protein component could be separated from the lipids when chromatographed on Ultrogel AcA 54 in the presence of urea. The inhibitory activity was associated with the protein component which had a molecular weight of approximately 15,900. In polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and urea, the protein component was dissociated in a subunit estimated to be approximately 1,400 daltons.
The importance of the Thr 17 residue of phospholamban as a phosphorylation site under physiological and pathological conditions

The sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) is under the control of an SR protein named phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a, whereas phosphorylation of PLN at either the Ser16 site by PKA or the Thr17 site by CaMKII reverses this inhibition, thus increasing SERCA2a activity and the rate of Ca2+ uptake by the SR. This leads to an increase in the velocity of relaxation, SR Ca2+ load and myocardial contractility. In the intact heart, ßadrenoceptor stimulation results in phosphorylation of PLN at both Ser16 and Thr17 residues. Phosphorylation of the Thr17 residue requires both stimulation of the CaMKII signaling pathways and inhibition of PP1, the major phosphatase that dephosphorylates PLN. These two prerequisites appear to be fulfilled by ß-adrenoceptor stimulation, which as a result of PKA activation, triggers the activation of CaMKII by increasing intracellular Ca2+, and inhibits PP1. Several pathological situations such as ischemia-reperfusion injury or hypercapnic acidosis provide the required conditions for the phosphorylation of the Thr17 residue of PLN, independently of the increase in PKA activity, i.e., increased intracellular Ca2+ and acidosis-induced phosphatase inhibition. Our results indicated that PLN was phosphorylated at Thr17 at the onset of reflow and immediately after hypercapnia was established, and that this phosphorylation contributes to the mechanical recovery after both the ischemic and acidic insults. Studies on transgenic mice with Thr17 mutated to Ala (PLN-T17A) are consistent with these results. Thus, phosphorylation of the Thr17 residue of PLN probably participates in a protective mechanism that favors Ca2+ handling and limits intracellular Ca2+ overload in pathological situations. Correspondence A. Mattiazzi Centro de Investigaciones Cardiovasculares Facultad de Ciencias Médicas 60 y 120, (1900) La Plata Argentina Fax: +54-221-483-4833 E-mail: ramattia@atlas.med.unlp.edu. ar Presented at the XX Annual Meeting of the Federação de Sociedades de Biologia Experimental, Águas de Lindóia, SP, Brazil, August 24-27, 2004. Research supported by PICT #08592 (FONCYT), PIP #02256 and 02257 (CONICET) and Fogarty International Research Award Grant #1-R03-TW06294 (NIH). Received August 9, 2005 Accepted January 2, 2006
Introns and Splicing Elements of Five Diverse Fungi

ABSTRACT Genomic sequences and expressed sequence tag data for a diverse group of fungi (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Aspergillus nidulans, Neurospora crassa, and Cryptococcus neoformans) provided the opportunity to accurately characterize conserved intronic elements. An examination of large intron data sets revealed that fungal introns in general are short, that 98% or more of them belong to the canonical splice site (ss) class (5′GU…AG3′), and that they have polypyrimidine tracts predominantly in the region between the 5′ ss and the branch point. Information content is high in the 5′ ss, branch site, and 3′ ss regions of the introns but low in the exon regions adjacent to the introns in the fungi examined. The two yeasts have broader intron length ranges and correspondingly higher intron information content than the other fungi. Generally, as intron length increases in the fungi, so does intron information content. Homologs of U2AF spliceosomal proteins were found in all species except for S. cerevisiae, suggesting a nonconventional role for U2AF in the absence of canonical polypyrimidine tracts in the majority of introns. Our observations imply that splicing in fungi may be different from that in vertebrates and may require additional proteins that interact with polypyrimidine tracts upstream of the branch point. Theoretical protein homologs for Nam8p and TIA-1, two proteins that require U-rich regions upstream of the branch point to function, were found. There appear to be sufficient differences between S. cerevisiae and S. pombe introns and the introns of two filamentous members of the Ascomycota and one member of the Basidiomycota to warrant the development of new model organisms for studying the splicing mechanisms of fungi.
Evidence That HIV Budding in Primary Macrophages Occurs through the Exosome Release Pathway*

Lipid rafts are specialized regions of cell membranes enriched in cholesterol and sphingolipids that are involved in immune activation and signaling. Studies in T-cells indicate that these membrane domains serve as sites for release of human immunodeficiency virus (HIV). By budding through lipid rafts in T-cells, HIV selectively incorporates raft markers and excludes non-raft proteins. This process has been well studied in T-cells, but it is unknown whether lipid rafts serve as budding sites for HIV in macrophages. Recently, we proposed a new model of retroviral biogenesis called the Trojan exosome hypothesis (Gould, S. J., Booth, A., and Hildreth, J. E. K. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 10592-10597). This model proposes that retroviruses coopt the existing cellular machinery for exosomal release. Here, we performed the first test designed to differentiate between the lipid raft hypothesis of retroviral biogenesis and the Trojan exosome hypothesis. Using macrophages, we examined the relative abundance of several host proteins on the cell surface, in lipid rafts, and on both HIV particles and exosomes derived from these cells. Our results show significant differences in the abundance of host proteins on the cell surface and in HIV. Moreover, our data demonstrate discordance in the abundance of some proteins in lipid rafts and in HIV. Finally, our data reveal a strong concordance between the host cell protein profile of exosomes and that of HIV. These results strongly support the Trojan exosome hypothesis and its prediction that retroviral budding represents exploitation of a pre-existing cellular pathway of intercellular vesicle trafficking.
Nutritional Alterations Associated With HIV Infection

&NA;Nutritional alterations are common in HIV infection. Early studies documented weight loss and protein depletion, a finding associated with body cell mass depletion in untreated patients. The application of highly active antiretroviral therapy has led to a decreased incidence of malnutrition, although altered body fat distribution and metabolic alterations, including hyperlipidemia and insulin resistance, are common sequelae. The development of malnutrition is multifactorial and occurs through changes in caloric intake, nutrient absorption, or energy expenditure. Clinically, malnutrition develops as a result of either starvation or cachexia. Other hormonal and endocrinologic alterations include hypercortisolemia and hypogonadism. The rationale for providing nutritional support to AIDS patients is based upon the assumptions that nutrition status can be improved and that such improvements have clinical benefits. The results of hypercaloric feeding studies, including the use of appetite stimulants, indicate that weight gain is possible but that the weight gained is predominantly fat. In contrast, anabolic agents and resistance training exercise have been shown to promote body cell mass repletion and skeletal muscle gain. Cytokine inhibitors also have been evaluated for the treatment of wasting in HIV infection. Development of combination therapies, preventive therapies, and efficient and cost‐effective therapies are current tasks in the field.
Managing DS Records from the Parent via CDS/CDNSKEY

RFC 7344 specifies how DNS trust can be maintained across key rollovers in-band between parent and child. This document elevates RFC 7344 from Informational to Standards Track. It also adds a method for initial trust setup and removal of a secure entry point. Changing a domain's DNSSEC status can be a complicated matter involving multiple unrelated parties. Some of these parties, such as the DNS operator, might not even be known by all the organizations involved. The inability to disable DNSSEC via in-band signaling is seen as a problem or liability that prevents some DNSSEC adoption at a large scale. This document adds a method for in-band signaling of these DNSSEC status changes. This document describes reasonable policies to ease deployment of the initial acceptance of new secure entry points (DS records). It is preferable that operators collaborate on the transfer or move of a domain. The best method is to perform a Key Signing Key (KSK) plus Zone Signing Key (ZSK) rollover. If that is not possible, the method using an unsigned intermediate state described in this document can be used to move the domain between two parties. This leaves the domain temporarily unsigned and vulnerable to DNS spoofing, but that is preferred over the alternative of validation failures due to a mismatched DS and DNSKEY record.
Depletion of Pre-16 S rRNA in Starved Escherichia coli Cells

Specific hybridization assays for intermediates in rRNA synthesis (pre-rRNA) may become useful for monitoring the growth activity of individual microbial species in complex natural systems. This possibility depends upon the assumption that rRNA processing in microbial cells continues after growth and pre-rRNA synthesis cease, resulting in drainage of the pre-rRNA pool. This is not the case in many eukaryotic cells, but less is known about the situation in bacteria. Therefore, we used DNA probes to measure steady-state cellular pre-16S rRNA pools during growth state transitions in Escherichia coli. Pre-16S rRNA became undetectable when cells entered the stationary phase on rich medium and was replenished upon restoration of favorable growth conditions. These fluctuations were of much greater magnitude than concurrent fluctuations in the mature 16S rRNA pool. The extent of pre-16S rRNA depletion depended upon the circumstances limiting growth. It was significantly more pronounced in carbon-energy-starved cells than in nitrogen-starved cells or in cells treated with energy uncouplers. In the presence of the transcriptional inhibitor rifampin, rates of pre-16S rRNA depletion in carbon-energy-starved cells and nitrogen-starved cells were similar, suggesting that the difference between these conditions resides primarily at the level of pre-rRNA synthesis. Chloramphenicol, which inhibits the final steps in rRNA maturation, halted pre-16S rRNA depletion under all conditions. The data show that E. coli cells continue to process pre-rRNA after growth and rrn operon transcription cease, leading to drainage of the pre-rRNA pool. This supports the feasibility of using pre-rRNA-targeted probes to monitor bacterial growth in natural systems, with the caveat that patterns of pre-rRNA depletion vary with the conditions limiting growth.
CD4+CD28null T lymphocytes resemble CD8+CD28null T lymphocytes in their responses to IL‐15 and IL‐21 in HIV‐infected patients

HIV‐infected individuals suffer from accelerated immunologic aging. One of the most prominent changes during T lymphocyte aging is the accumulation of CD28null T lymphocytes, mainly CD8+ but also CD4+ T lymphocytes. Enhancing the functional properties of these cells may be important because they provide antigen‐specific defense against chronic infections. The objective of this study was to compare the responses of CD4+CD28null and CD8+CD28null T lymphocytes from HIV‐infected patients to the immunomodulatory effects of cytokines IL‐15 and IL‐21. We quantified the frequencies of CD4+CD28null and CD8+CD28null T lymphocytes in peripheral blood from 110 consecutive, HIV‐infected patients and 25 healthy controls. Patients showed increased frequencies of CD4+CD28null and CD8+CD28null. Both subsets were positively correlated to each other and showed an inverse correlation with the absolute counts of CD4+ T lymphocytes. Higher frequencies of HIV‐specific and CMV‐specific cells were found in CD28null than in CD28+ T lymphocytes. Activation of STAT5 by IL‐15 and STAT3 by IL‐21 was higher in CD28null compared with CD28+ T lymphocytes. Proliferation, expression of CD69, and IFN‐γ production in CD28null T lymphocytes were increased after treatment with IL‐15, and IL‐21 potentiated most of those effects. Nevertheless, IL‐21 alone reduced IFN‐γ production in response to anti‐CD3 stimulation but increased CD28 expression, even counteracting the inhibitory effect of IL‐15. Intracytoplasmic stores of granzyme B and perforin were increased by IL‐15, whereas IL‐21 and simultaneous treatment with the 2 cytokines also significantly enhanced degranulation in CD4+CD28null and CD8+CD28null T lymphocytes. IL‐15 and IL‐21 could have a role in enhancing the effector response of CD28null T lymphocytes against their specific chronic antigens in HIV‐infected patients.
Triple mode dielectric-loaded cavity band pass filter

This paper presents a compact triple mode band pass filter (BPF) using dielectric-loaded cylindrical cavity that allows the realization of three transmission zeros. This class of triple mode resonator utilizes the degenerate TE11 modes and the single TM01 mode. Coupling structure is based on choosing the proper resonator height and input/output feeding probe position (angle Ø) to achieve the desired perturbation between the degenerate modes. Therefore, no additional space nor coupling screws is needed. A three-pole BPF is designed to verify this approach at 2.08 GHz centre frequency with bandwidth of 42 MHz at -20 dB return loss. The introduced triple mode resonator can be used as a building block in the design of diplexers and sophisticated higher-order filters.
Down-Regulates CHK 1 through p 21 and the Retinoblastoma Protein

Both fission yeast and mammalian cells require the function of the checkpoint kinase CHK1 for G2 arrest after DNA damage. The tumor suppressor p53, a well-studied stress response factor, has also been shown to play a role in DNA damage G2 arrest, although in a manner that is probably independent of CHK1. p53, however, can be phosphorylated and regulated by both CHK1 as well as another checkpoint kinase, hCds1 (also called CHK2). It was therefore of interest to determine whether reciprocally, p53 affects either CHK1 or CHK2. We found that induction of p53 either by diverse stress signals or ectopically using a tetracycline-regulated promoter causes a marked reduction in CHK1 protein levels. CHK1 downregulation by p53 occurs as a result of reduced CHK1 RNA accumulation, indicating that repression occurs at the level of transcription. Repression of CHK1 by p53 requires p21, since p21 alone is sufficient for this to occur and cells lacking p21 cannot downregulate CHK1. Interestingly, pRB is also required for CHK1 downregulation, suggesting the possible involvement of E2F-dependent transcription in the regulation of CHK1. Our results identify a new repression target of p53 and suggest that p53 and CHK1 play interdependent and complementary roles in regulating both the arrest and resumption of G2 after DNA damage.
Power Doppler and spectral Doppler measurements of knee-joint synovitis in rheumatoid arthritis patients with superficial pattern signals and in those with deep pattern signals

Power Doppler and spectral Doppler ultrasonography were used to scan 127 knee joints of 72 patients with rheumatoid arthritis (RA). Synovial effusion thickness and synovial proliferation (pannus) thickness, as well as the flow signal diameter, were measured on ultrasonogram prints of the power Doppler using digital calipers. In addition, color-flow signal grades on power Doppler and the resistance index (RI) values on spectral Doppler were evaluated. The values of these five variables were compared among 58 joints with superficial pattern flow signals and 69 joints with deep pattern flow signals. Compared with the joints with deep pattern signals, the joints with superficial pattern signals had significantly higher mean values of effusion thickness (P < 0.0001) and flow signal grades (P < 0.0001), and significantly lower mean RI (P < 0.0001). On the other hand, the joints with deep pattern signals had a significantly higher value of signal diameter (P = 0.0125) and had a trend to higher value of pannus thickness (P = 0.079) as well. Significant correlations were observed between effusion thickness and signal grades (P < 0.0001); effusion thickness and RI (P < 0.0001); signal diameter and pannus thickness (P = 0.0102); signal diameter and RI (P < 0.0001); and signal grades and RI (P < 0.0001). The ultrasonographic measurements of synovitis in RA patients provide valuable information on synovial inflammation.
ProViz: a tool for explorative 3-D visualization and template matching in electron tomograms

Visual understanding is a key aspect when studying electron tomography data-sets, aside quantitative assessments such as registration of high-resolution structures. We here present the free software tool ProViz (Protein Visualization) for visualisation and template matching in electron tomograms of biological samples. The ProViz software contains methods and tools which we have developed, adapted and computationally optimised for easy and intuitive visualisation and analysis of electron tomograms with low signal-to-noise ratio. ProViz complements existing software in the application field and serves as an easy and convenient tool for a first assessment and screening of the tomograms. It provides enhancements in three areas: (1) improved visualisation that makes connections as well as intensity differences between and within objects or structures easier to see and interpret, (2) interactive transfer function editing with direct visual result feedback using both piecewise linear functions and Gaussian function elements, (3) computationally optimised template matching and tools to visually assess and interactively explore the correlation results. The visualisation capabilities and features of ProViz are demonstrated on various biological volume data-sets: bacterial filament structures in vitro, a desmosome and the transmembrane cadherin connections therein in situ, and liposomes filled with doxorubicin in solution. The explorative template matching is demonstrated on a synthetic IgG data-set.