Miracle-dz/UniFAR-FTUs huggingface dataset:
Down-Regulation of Bax-Interacting Factor 1 in Human Pancreatic Ductal Adenocarcinoma

Objective: Bax-interacting factor 1 (Bif-1) protein plays a critical role in apoptosis, mitochondrial morphogenesis, and autophagy, and its loss promotes tumorigenesis. The role of Bif-1 in pancreatic cancer has not been studied. Methods: We determined Bif-1 expression in 82 human pancreatic ductal adenocarcinomas (PDCs) and in 82 nonmalignant pancreatic specimens (NMPs), using immunohistochemistry and tissue microarray. Bif-1 immunostain was semiquantitatively scored on a scale of 0 to 9. Results: Bif-1 scores in NMP were either 6 or 9, with lower scores in only 19 (23.2%) of 82 NMPs. Low Bif-1 expression (score <6) was found in 37 (45.1%) of 82 PDCs, a proportion significantly greater than that found in NMP (P = 0.005). The expression of Bif-1 was twice as likely to be low in PDC as in NMP (relative risk = 1.95, 95% confidence interval, 1.23-3.09). Kaplan-Meier survival estimates showed no difference in survival between patients with low and high Bif-1 expression (P = 0.21, log-rank test). Conclusions: The expression of Bif-1 is downregulated in a subset of PDC. This novel finding is in agreement with the tumor suppressor function of Bif-1. The lack of association between Bif-1 expression and patient survival may be best explained by the complexity of carcinogenesis.
Probabilistic error analysis of encrypted transmission for safety-related railway applications

The paper deals with the problem of probabilistic error analysis of an encrypted transmission used within safety-related control system for applications with increasing safety integrity level (SIL). The requirements to cryptographic block code in safety-related communications for railway application are describe. The main part is oriented to description of mathematical apparatus for the error probability of the cryptography block code for the communication system on the end-to-end with GSM-R communication channel. The practical results are related with the quantitative evaluation of an average error probability of the cryptography code for several lengths of safety - related message which are expanded with determination of the cryptography degradation with using GMSK modulation scheme.
A 46 $\mu \text{W}$ 13 b 6.4 MS/s SAR ADC With Background Mismatch and Offset Calibration

A 6.4 MS/s 13 b ADC with a low-power background calibration for DAC mismatch and comparator offset errors is presented. Redundancy deals with DAC settling and facilitates calibration. A two-mode comparator and 0.3 fF capacitors reduce power and area. The background calibration can directly detect the sign of the dynamic comparator offset error and the DAC mismatch errors and correct both of them simultaneously in a stepwise feedback loop. The calibration achieves 20 dB spur reduction with little area and power overhead. The chip is implemented in 40 nm CMOS and consumes 46 $\mu \text{W}$ from a 1 V supply, and achieves 64.1 dB SNDR and a FoM of 5.5 fJ/conversion-step at Nyquist.
A role for tungsten in the biology of Campylobacter jejuni: tungstate stimulates formate dehydrogenase activity and is transported via an ultra‐high affinity ABC system distinct from the molybdate transporter

The food‐borne pathogen Campylobacter jejuni possesses no known tungstoenzymes, yet encodes two ABC transporters (Cj0300–0303 and Cj1538–1540) homologous to bacterial molybdate (ModABC) uptake systems and the tungstate transporter (TupABC) of Eubacterium acidaminophilum respectively. The actual substrates and physiological role of these transporters were investigated. Tryptophan fluorescence spectroscopy and isothermal titration calorimetry of the purified periplasmic binding proteins of each system revealed that while Cj0303 is unable to discriminate between molybdate and tungstate (KD values for both ligands of 4–8 nM), Cj1540 binds tungstate with a KD of 1.0 ± 0.2 pM; 50 000‐fold more tightly than molybdate. Induction‐coupled plasma mass spectroscopy of single and double mutants showed that this large difference in affinity is reflected in a lower cellular tungsten content in a cj1540 (tupA) mutant compared with a cj0303c (modA) mutant. Surprisingly, formate dehydrogenase (FDH) activity was decreased ∼50% in the tupA strain, and supplementation of the growth medium with tungstate significantly increased FDH activity in the wild type, while inhibiting known molybdoenzymes. Our data suggest that C. jejuni possesses a specific, ultra‐high affinity tungstate transporter that supplies tungsten for incorporation into FDH. Furthermore, possession of two MoeA paralogues may explain the formation of both molybdopterin and tungstopterin in this bacterium.
Characteristics of placebo responses in medical treatment of premenstrual syndrome.

OBJECTIVE This study characterizes the responses to placebo medication of patients with premenstrual syndrome (PMS) who were randomly assigned in controlled treatment trials. Possible predictors of placebo response were also examined. METHOD Subjects from two randomized controlled trials were pooled. The 101 subjects met defined criteria for severe PMS, remained eligible after 1 month of single-blind placebo lead-in treatment, and were randomly assigned to 3 months of double-blind placebo treatment. Improvement in the current study was defined as a decrease of at least 50% in premenstrual symptom score from the pretreatment baseline. RESULTS At endpoint, 20 (20%) of the placebo-treated subjects showed sustained improvement, 18 of these in at least 3 of the 4 months of placebo medication. Another 42% of subjects partially improved, and 39% were clearly unimproved throughout the study period. CONCLUSIONS Some patients with severe PMS experience significant and sustained improvement with placebo medication, but the majority report only partial or no improvement. Patients who sustain improvement for at least 2 consecutive months are likely to remain improved, indicating the importance of nondrug factors in clinical care.
Should Dual-Energy Computed Tomography Pulmonary Angiography Replace Single-Energy Computed Tomography Pulmonary Angiography in Pregnant and Postpartum Patients?

Objective The study aims to compare single-energy (SE) and dual-energy (DE) computed tomography pulmonary angiography (CTPA) for evaluation of suspected pulmonary embolism in pregnant and postpartum patients. Materials and Methods Our study included 59 CTPA performed in pregnant/postpartum women (study group) comprised of 38 SE-CTPA and 21 DE-CTPA. The control group of 21 age- and weight-matched nonpregnant/nonpostpartum women underwent DE-CTPA. Two radiologists assessed pulmonary arterial enhancement, image quality, and artifacts. &kgr; Test and analysis of variance were performed. Results Fourteen of 38 pregnant/postpartum women (37%) had suboptimal SE-CTPA compared with just 10% (2/21) suboptimal DE-CTPA studies (P = 0.02). Mean Hounsfield unit (HU) in the pulmonary trunk was 550 ± 68 HU in the DE-CTPA pregnant/postpartum group and 245 ± 12 HU in the SE-CTPA (P < 0.001). The mean volume computed tomography dose index in the pregnant/postpartum patients for DE-CTPA and SE-CTPA were 9 ± 2 and 19 ± 8 mGy, respectively (P < 0.001). Conclusions Dual-energy CTPA substantially increased arterial enhancement for evaluation of pulmonary embolism in pregnant and postpartum women compared with SE-CTPA.
Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins.

BACKGROUND Previous twin studies of asthma and allergy implicate both genetic and environmental factors in disease risk, but few have related the occurrence of clinical disease to objective markers of allergic sensitization in twins. OBJECTIVE We sought to investigate the concordance and interrelationships of self-reported allergic disease and total and aeroallergen-specific IgE levels within pairs of British adult female twins. METHODS Three hundred forty monozygotic and 533 dizygotic pairs, aged 18 to 72 years, completed questionnaires about allergic disease. Of these, 282 monozygotic and 270 dizygotic pairs were tested for total IgE and specific IgE to Der p 1, mixed grass pollen, and cat dander by means of fluoroimmunoassay. RESULTS Concordance rates for all variables were higher for monozygotic than for dizygotic twins, significantly (P < .05) so for hay fever, eczema, and specific IgE positivity but not (P > .05) for self-reported asthma or allergies. Within-pair correlations of log-transformed IgE were 0.59 for monozygotic twins and 0.29 for dizygotic twins, implying heritability of 60%. Within both monozygotic and dizygotic pairs discordant for hay fever or reported allergies, the affected twin had significantly higher total and specific IgE levels. Within pairs who were doubly discordant for 3 allergic diseases, associations between diseases were of similar strength for monozygotic and dizygotic pairs. CONCLUSIONS These results confirm that genetic factors influence susceptibility to aeroallergen sensitization and clinical allergic disease. However, genetically identical twins are often discordant in their expression of atopy, suggesting a substantial modifying role for environmental factors.
Rotavirus vaccine administered parenterally induces protective immunity

We performed experiments to determine whether parenteral immunization with SA11 rotavirus can induce active protective immunity in a rabbit model of rotavirus infection. After one or two intramuscular injections of 1 ml of live or formalin-inactivated SA11 virus, we evaluated the mucosal and serologic immune response and protection from challenge with a high dose of live, virulent rabbit (Ala) rotavirus. Inactivated SA11 virus preparations, evaluated by enzyme-linked immunosorbent assay (ELISA) with a panel of VP4- and VP7-specific neutralizing and nonneutralizing monoclonal antibodies, did not show a loss of epitopes from the inactivation procedure compared with live virus. Administration of two doses of vaccine, one at zero days postvaccination (DPV) and a booster shot at 49 DPV, followed by challenge at 71 DPV with 3.5 x 10(5) PFU of Ala virus resulted in protection from challenge. None of the two-dose virus-vaccinated rabbits shed virus after challenge, while virus shedding was detected in all control rabbits (P = 0.001, Fisher's exact two-tailed test). Differences in total serum immunoglobulin (Ig) antirotavirus ELISA titers (P < 0.05, Wilcoxon's rank sum test) were observed between groups vaccinated with virus in aluminum phosphate or Freund's adjuvant but not between groups vaccinated with live or inactivated virus in either adjuvant. All rabbits given two doses of vaccine had detectable antirotavirus intestinal antibody of the IgG, but not IgA, isotype. After challenge, fourfold or greater increases in intestinal IgG antibody responses were observed in three rabbits, whereas all controls and all but one virus-vaccinated rabbit had an intestinal IgA antibody response. In contrast, vaccination of rabbits with one dose of SA11 followed by challenge at 21 DPV did not protect from challenge; no difference in the mean number of days of virus shedding between any of the vaccinated groups and controls was observed. A serologic, but not a mucosal, antibody response was observed after the one-dose vaccination regimen. Differences in serologic antibody titers were not observed between any of the one-dose virus-vaccinated groups. These data indicate that parenteral vaccination with two, but not one, doses of rotavirus in either Freund's adjuvant or aluminum phosphate can induce active protection from challenge. (ABSTRACT TRUNCATED AT 400 WORDS)
Panton-Valentine Leukocidin (PVL)-Positive Health Care-Associated Methicillin-Resistant Staphylococcus aureus Isolates Are Associated with Skin and Soft Tissue Infections and Colonized Mainly by Infective PVL-Encoding Bacteriophages

ABSTRACT The emergence of Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA) is a public health concern worldwide. PVL is associated with community-associated MRSA and is linked to skin and soft tissue infections (SSTIs). However, PVL genes have also been detected in health care-associated (HA) MRSA isolates. The diseases associated with PVL-positive HA-MRSA isolates and the distributions of PVL-encoding bacteriophages in HA-MRSA have not been determined. In this study, a total of 259 HA-MRSA strains isolated between 2009 and 2012 in China from inpatients with SSTIs, pneumonia, and bacteremia were selected for molecular typing, including staphylococcal cassette chromosome mec typing, multilocus sequence typing, and staphylococcal protein A gene typing. The PVL genes and PVL bacteriophages in the MRSA isolates were characterized by PCR. Among the tested MRSA isolates, 28.6% (74/259) were PVL positive. The high prevalence of PVL-carrying HA-MRSA was observed to be associated with SSTIs but not with pneumonia or bacteremia. The PVL-positive HA-MRSA isolates were colonized mainly by infective PVL phages, namely, Φ7247PVL, ΦSLT, and ΦSa2958. The distribution of PVL-carrying bacteriophages differed geographically. Our study highlights the potential risk of the emergence of multidrug-resistant HA-MRSA strains with increased virulence.
Effects of granulocyte and granulocyte-macrophage colony-stimulating factors in a neutropenic murine model of trichosporonosis

We produced disseminated trichosporonosis in a neutropenic murine model with Trichosporon asahii, which was identified by DNA relatedness analysis. We then assessed the efficacy of granulocyte colony-stimulating factor (G-CSF) (30 to 100 microg/kg of body weight per day) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.8 to 2 microg/kg x day). The administration of G-CSF either before or after infection improved the survival rate from less than 25% up to 100% (P < 0.05). The effects of G-CSF on organ clearance and histological examinations were most remarkable in the lungs. The levels of tumor necrosis factor alpha (TNF-alpha) in bronchoalveolar lavage fluid (BALF) of neutropenic and G-CSF-pretreated mice were 60 +/- 6 ng/ml and 18 +/- 6 pg/ml, respectively, at 24 h after infection. Immunohistologically, alveolar macrophages proved to be the main source of TNF-alpha in BALF. GM-CSF increased neutrophil counts less significantly than did G-CSF and increased the lethality (P < 0.05) with a high level of TNF-alpha in BALF. Expecting to inhibit TNF-alpha, we administered anti-TNF-alpha intraperitoneally at the dose completely inhibiting TNF-alpha in plasma (2 x 10(4) U), but the TNF-alpha level in BALF and the lethality increased. Though the number of neutrophils at the early stage of infection appeared to be the most critical, the results suggest that other host defense mechanisms, such as TNF-alpha overproduction in the lungs, have an important role in the prognosis of trichosporonosis.
Histone H4 Acetylation Differentially Modulates Arginine Methylation by an in Cis Mechanism*

Histone H4 undergoes extensive post-translational modifications (PTMs) at its N-terminal tail. Many of these PTMs profoundly affect the on and off status of gene transcription. The molecular mechanism by which histone PTMs modulate genetic and epigenetic processes is not fully understood. In particular, how a PTM mark affects the presence and level of other histone modification marks needs to be addressed and is essential for better understanding the molecular basis of histone code hypothesis. To dissect the interplaying relationship between different histone modification marks, we investigated how individual lysine acetylations and their different combinations at the H4 tail affect Arg-3 methylation in cis. Our data reveal that the effect of lysine acetylation on arginine methylation depends on the site of acetylation and the type of methylation. Although certain acetylations present a repressive impact on PRMT1-mediated methylation (type I methylation), lysine acetylation generally is correlated with enhanced methylation by PRMT5 (type II dimethylation). In particular, Lys-5 acetylation decreases the activity of PRMT1 but increases that of PRMT5. Furthermore, circular dichroism study and computer simulation demonstrate that hyperacetylation increases the content of ordered secondary structures at the H4 tail region. These findings provide new insights into the regulatory mechanism of Arg-3 methylation by H4 acetylation and unravel the complex intercommunications that exist between different the PTM marks in cis. The divergent activities of PRMT1 and PRMT5 with respect to different acetyl-H4 substrates suggest that type I and type II protein-arginine methyltransferases use distinct molecular determinants for substrate recognition and catalysis.
Channel Formation by the Glycosylphosphatidylinositol-anchored Protein Binding Toxin Aerolysin Is Not Promoted by Lipid Rafts*

Glycosylphosphatidylinositol-anchored proteins may be concentrated in membrane microdomains (lipid rafts) that are also enriched in cholesterol and sphingolipids. The glycosyl anchor of these proteins is a specific, high affinity receptor for the channel-forming protein aerolysin. We wished to determine if the presence of rafts promotes the activity of aerolysin. Treatment of T lymphocytes with methyl-β-cyclodextrin, which destroys lipid rafts by sequestering cholesterol, had no measurable effect on the sensitivity of the cells to aerolysin; nor did similar treatment of erythrocytes decrease the rate at which they were lysed by the toxin. We also studied the rate of aerolysin-induced channel formation in liposomes containing glycosylphosphatidylinositol-anchored placental alkaline phosphatase, which we show is a receptor for aerolysin. In liposomes containing sphingolipids as well as glycerophospholipids and cholesterol, most of the enzyme was Triton X-100-insoluble, indicating that it was localized in rafts, whereas in liposomes prepared without sphingolipids, all of the enzyme was soluble. Aerolysin was no more active against liposomes containing rafts than against those that did not. We conclude that lipid rafts do not promote channel formation by aerolysin.
Survival following salvage therapy for primary refractory peripheral T‐cell lymphomas (PTCL)

Optimal salvage therapy for primary refractory peripheral T‐cell lymphomas (PTCL) and the role of hematopoietic stem cell transplant (SCT) remain poorly defined. We conducted a retrospective review of clinical outcomes and prognostic factors in a single‐center cohort of 93 patients with primary refractory PTCL, defined as progression during first‐line therapy or relapse within 6 months of its completion. Clinical outcomes were poor in this population, with median event‐free survival (EFS) of 3.5 months, median overall survival (OS) of 9.1 months, and 34% 3‐year survival. Outcomes were comparable in patients who progressed through first‐line therapy and patients who achieved CR/PR and subsequently relapsed within 6 months. A majority exhibited high‐risk features and had intermediate to high risk IPI, which correlated with inferior outcomes. There was no difference in outcomes between patients who received single‐agent salvage regimens and patients who underwent traditional, multi‐agent salvage regimens. Thus, participation in well‐designed clinical trials should be encouraged in this population. Additionally, there may be a trend toward improved EFS and OS in patients who underwent autologous or allogeneic SCT compared to patients who achieved CR or PR but were not transplanted.
Post surgery circulating free tumor DNA is a predictive biomarker for relapse of lung cancer

Cancer cells release DNA fragments into plasma as circulating free DNA (cfDNA). However, quantitative measurement of tumor‐derived DNA in cfDNA remains challenge. The purpose of this study was to quantitatively assess tumor‐derived DNA in lung cancer patients. By optimizing competitive allele‐specific TaqMan PCR (CAST‐PCR), we assessed the copy number of mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) alleles in the pre/post surgery plasma of 168 lung cancer patients. An absolute quantitative PCR method was developed to assess the number of total cfDNA. All mutations detected in tumors were also found in the plasma after surgery. At the time of 30 days after surgery, EGFR mutation of circulating cell‐free DNA was detected only in two patients who recurred in 4 months after surgery. Compared to that of normal control at 30 days after surgery, five patients who recurred in 4 months had significantly higher circulating cell‐free DNA (P < 0.001), whereas six patients who recurred after 4 months (P = 0.207) and five patients without recurrence (P = 0.901) demonstrated significantly lower circulating cell‐free DNA. Our findings suggest that cfDNA analysis in plasma is an alternative and supplement to tissue analysis and hold promise for clinical application. Stratification of patients according to cfDNA levels at 30 days after surgery might be helpful in selecting lung cancer patients for adjuvant therapy after surgery.
Langhans giant cells from M. tuberculosis‐induced human granulomas cannot mediate mycobacterial uptake

Tuberculosis is characterized by a tight interplay between Mycobacterium tuberculosis (M. tb) and host cells within granulomas. These cellular aggregates restrain M. tb spreading but do not kill all bacilli, which persist for years. A more detailed investigation of the interaction between M. tb and granuloma cells is needed to improve our understanding of this persistence and to explain the physiopathology of tuberculosis. In the present study, a recently developed in vitro human model of tuberculous granulomas has been used to analyse the modulation of granuloma cell differentiation by M. tb, in comparison to poorly virulent mycobacteria, which do not persist. It is reported that whilst all mycobacteria species induce granuloma formation, only M. tb triggers the differentiation of granuloma macrophages into very large multinucleated giant cells (MGCs) that are unable to mediate any bacterial uptake. This loss of function is not due to cell quiescence, as MGCs still display NADPH oxidase activity, but it correlates with decreased expression of phagocytosis receptors. This phenomenon is specific for the virulent species of M. tuberculosis complex, as poorly virulent species only induce the formation of small multinucleated cells (MCs) with conserved mycobacterial uptake ability, which never reach the MGC differentiation stage. The phenotype of MGCs thus strongly resembles mature dendritic cells with a loss of microbial uptake ability, despite conserved antigen presentation. In M. tb‐induced granulomas, MGCs thus seem to be devoted to the destruction of bacilli that have been ingested in previous differentiation stages, ie in macrophages and MCs. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.