Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation of PhoP Protein Plays Direct Regulatory Role in Lipid Biosynthesis of Mycobacterium tuberculosis*

Background: PhoP is global regulator of Mycobacterium tuberculosis physiology. However, the role of phosphorylation of PhoP remains unknown. Results: PhoP activates complex lipid biosynthesis only upon phosphorylation. Conclusion: PhoP regulates lipid biosynthesis by a phosphorylation-dependent mechanism to contribute to morphology of the bacilli. Significance: This study sheds light on the unexplored role of phosphorylation of PhoP in regulating biosynthesis of lipids unique to M. tuberculosis. Mycobacterium tuberculosis PhoP is essential for virulence and intracellular growth of the tubercle bacilli. Genetic evidence suggests that PhoP regulates complex lipid biosynthesis, and absence of some of these lipid molecules in a phoP mutant partly accounts for its attenuated growth in macrophages and/or mice. To investigate the mechanism of regulation, here we demonstrate the essentiality of phosphorylation of PhoP in the regulation of complex lipid biosynthesis. We show that phosphorylated PhoP activates transcription of pks2 and msl3, gene(s) encoding polyketide β-ketoacyl synthases through direct DNA binding at the upstream regulatory region(s) of the target genes. Our results identify the genetic determinants recognized by PhoP and show that activation of target genes requires interaction(s) of the phosphorylated regulator at the cognate binding sites. The fact that these sites within the regulatory region of respective genes do not bind in vitro with either unphosphorylated or phosphorylation-deficient PhoP protein is consistent with phosphorylation-dependent assembly of the transcription initiation complex leading to in vivo transcriptional activation. Together, these results reveal so far unknown molecular mechanisms of how PhoP contributes to M. tuberculosis cell wall composition by regulating complex lipid biosynthesis.
Pulmonary Embolism following Operative Treatment of Ankle Fractures: A Report of Three Cases and Review of the Literature

The risks of thromboembolism following operative treatment of ankle fractures are deep vein thrombosis (DVT) and pulmonary embolism (PE). These are potentially life-threatening complications. Many orthopedic surgeons fail to appreciate the potential complications of thromboembolic events because of their rare and delayed occurrence in foot and ankle operations. The purpose of this report is to describe the potential for DVT and PE following ankle operations. We present three cases in which patients who underwent operative treatment of ankle fractures subsequently developed PE. We also review the literature on the prevalence of thrombosis, risk factors, methods of prophylaxis, and use of prophylaxis in surgical procedures of the lower extremity.
Value of Morning Home Blood Pressure as a Predictor of Decline in Renal Function in Patients with Chronic Kidney Disease

BACKGROUND Although blood pressure (BP) control is significantly associated with progression of chronic kidney disease (CKD), the influence of BP control based on home BP (HBP) measurement on the change in renal function in CKD patients is not fully defined. METHODS We recruited 137 patients with stage 3-5 CKD, who performed daily HBP measurements continuously. HBP was measured every morning and evening and data were obtained every 6 months in each patient with a follow-up of 32 +/- 5 months. The associations between BP data, other clinical variables and the change in estimated glomerular filtration rate (eGFR) were examined. RESULTS Mean morning BP, evening BP and clinic BP were 132.9/76.2, 128.5/72.5 and 129.4/69.1 mm Hg, respectively. There were significant correlations between mean morning systolic BP (SBP), mean evening SBP, mean clinic SBP and the change in eGFR (r = -0.318, -0.215, -0.174, p < 0.0001, <0.05, <0.05). Stepwise multivariate regression analysis demonstrated mean morning SBP and mean urinary protein excretion as independent predictors of the change in eGFR. CONCLUSION Morning SBP is a more significant predictor of decline in renal function than evening SBP or clinic SBP.
Overview of Existing Cartilage Repair Technology

Currently, autologous chondrocyte implantation and osteochondral grafting bridge the gap between palliation of cartilage injury and resurfacing via arthroplasty. Emerging technologies seek to advance first generation techniques and accomplish several goals including predictable outcomes, cost-effective technology, single-stage procedures, and creation of durable repair tissue. The biologic pipeline represents a variety of technologies including synthetics, scaffolds, cell therapy, and cell-infused matrices. Synthetic constructs, an alternative to biologic repair, resurface a focal chondral defect rather than the entire joint surface. Scaffolds are cell-free constructs designed as a biologic “net” to augment marrow stimulation techniques. Minced cartilage technology uses stabilized autologous or allogeneic fragments in 1-stage transplantation. Second and third generation cell-based methods include alternative membranes, chondrocyte seeding, and culturing onto scaffolds. Despite the promising early results of these products, significant technical obstacles remain along with unknown long-term durability. The vast array of developing technologies has exceptional promise and the potential to revolutionize the cartilage treatment algorithm within the next decade.
Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study

ObjectiveEstrogen plus progestin therapy (EPT) in postmenopausal women increases breast cancer risk and mammographic density to a higher extent than does estrogen therapy alone. Data from the randomized placebo-controlled Postmenopausal Estrogen/Progestinv Interventions trial showed that EPT-induced increases in serum estrone and estrone sulfate levels were positively correlated with increases in mammographic density. Here, after adjusting for serum estrone and estrone sulfate levels, we investigated the roles of posttreatment serum progestogen increase and of progesterone receptor gene (PGR) genetic variations on changes in mammographic density. MethodsWe measured the percent mammographic density and serum progestogen levels in 280 Postmenopausal Estrogen/Progestin Interventions trial participants randomized to EPT treatment. Analyses of genetic variations in PGR were limited to 260 white women for whom we successfully obtained PGR genotypes. We used linear regression analyses to determine how an increase in progestogen levels and PGR genetic variation influenced mammographic density change after EPT. ResultsThe increase in posttreatment serum progestogen level was positively associated with greater increases in mammographic density after adjustment for covariates (P trend = 0.044). Compared with women in the lowest quartile of serum progestogen level, women in the highest quartile experienced a 3.5% greater increase in mammographic density (P = 0.046). We did not find a strong indication that genetic variation in PGR was associated with mammographic density increase or modified the association with serum progestogen; however, confidence in these null findings is constrained by our small sample size. ConclusionsOur results suggest that higher serum progestogen levels resulting from EPT treatment lead to greater increases in mammographic density.
Corporate Debt Maturity and Stock Price Crash Risk

We find that firms with a larger proportion of short‐term debt have lower future stock price crash risk, consistent with short‐term debt lenders playing an effective monitoring role in constraining managers’ bad‐news‐hoarding behaviour. The inverse relationship between short‐maturity debt and future crash risk is more pronounced for firms that are harder to monitor due to weaker corporate governance, higher information asymmetry, and greater risk‐taking. These findings suggest that short‐term debt substitutes for other monitoring mechanisms in curbing managerial opportunism and reducing future crash risk. Our study implies that short‐maturity debt not only preserves creditors’ interests, but also protects shareholders’ wealth.
A novel low-leakage 8T differential SRAM cell

A novel low-leakage 8T differential SRAM cell is presented in 65nm bulk CMOS technology with the aim to address standby power consumption of embedded memories. The proposed cell supports differential read and write operation. HSPICE simulations incorporating process variation indicate that the proposed cell exhibits 84.8%, 44.8%, 42.6% and 27.0% less leakage under worst case conditions compared to 5T, 6T, 8T and 9T cells reported earlier in literature. With approximately 60% and 33% more area than the conventional 5T and the 6T cells and 11% less area than the 9T cell the proposed cell provides 3900.5× and 1.3× improvement in read static power noise margin compared to its 5T and 6T counterparts respectively under worst case conditions.
New species of Pheretima (Oligochaeta: Megascolecidae) from the Mt. Malindang Range, Mindanao Island, Philippines.

We provide descriptions, with illustrations of internal structures, for 18 new species of Pheretima from Mt. Malindang, Misamis Occidental Province, Mindanao Island, Philippines. Among the 18 species, 11 belong to the P. sangirensis species group, characterized by having a pair of spermathecal pores in the intersegmental furrow of 7/8 and lacking penial sheaths in the copulatory bursae: P. maculodorsalis n. sp. , P. tigris n. sp. , P. immanis n. sp. , P. lago n. sp. , P. nunezae n. sp. , P. boniaoi n. sp. , P. malindangensis n. sp. , P. misamisensis n. sp. , P. wati n. sp. , P. longiprostata n. sp. , and P. nolani n. sp. One species, P. longigula n. sp. , belongs to the P. montana species group, characterized by having a pair of spermathecal pores in the intersegmental furrow of 7/8 and penial sheaths in the copulatory bursae. Two species, P. vergrandis n. sp. and P. concepcionensis n. sp. , are monothecal. Three species, P. adevai n. sp. , P. lluchi n. sp. , and P. potonganensis n. sp. , belong to the P. darnleiensis species group, characterized by having either four or five pairs of spermathecae from vi to ix, with a fifth pair variably present in segment v. One species, P. subanensis n. sp. , is athecate. All species described here from the Mt. Malindang Range are probably native rather than introduced, and probably do not represent range extensions of species known from neighboring islands in Southeast Asia. We provide an identification key to the Pheretima species from Mt. Malindang.
Differential nucleolus organizer activity in normal and leukemic bone marrow

A cytochemical technique that uses silver nitrate staining has been used to study the nucleolus organizer activity in bone marrow cells from 13 patients with acute lymphocytic leukemia (ALL), 11 patients with chronic myelogenous leukemia (CML), 7 patients with acute myelogenous leukemia (AML), and 4 healthy persons. Our results indicate that the nucleolus organizer region (NOR) activity was significantly lower in the control group than in the ALL patients. The NOR activity level was significantly lower in both the CML patients in chronic phase and the AML patients than in the ALL group and similar to the control group. These disease‐related differences in NOR activity as detected by silver staining can be used as diagnostic procedure in evaluating human leukemias.
Influence of microbrush on efficacy of bonding into root canals.

PURPOSE Recently, several 'one-bottle' systems have been introduced for bonding into root canals. This study evaluated the influence of two brushes used as carriers of a primer-adhesive solution in the formation of resin tags, adhesive lateral branches and hybrid layer when used to bond fiber posts. MATERIALS AND METHODS Twenty root canal treated teeth, extracted for periodontal reasons, were selected for this study. The samples were randomly divided into two groups of 10 samples each: Group 1: Microbrush + One Step + Dual Link resin cement; Group 2: One Step + Dual Link resin cement. The adhesive system and resin cement were used strictly following manufacturers' instructions. The priming-adhesive solution of the 'one-bottle' system was light-cured before placing the resin cement and the post. Twenty translucent fiber posts were used. Then, root samples were processed for SEM observation. RESULTS The adhesive system showed resin dentin interdiffusion zone (RDIZ), resin tag and adhesive lateral branch formation. Microscopic examination of restored interfaces of Group 1 showed a higher % (P < 0.05) of RDIZ than those found in samples of Group 2. In Group 2 samples RDIZ morphology was well detectable and uniform in the first two thirds of root canals while in the apical third the RDIZ was not uniformly present while in Group 1 RDIZ was visible at the apical third too. No statistically significant differences were found among the two groups coronally and at the middle third, while the apical third of Group 1 showed significantly more resin tags than in Group 2. The characteristic reverse cone shape of resin tags was always noted in the coronal and middle third of the root canals of both groups and at the apical third of Group 1. In the apical third of Group 2 root canals, the resin tags showed a less uniform morphology and a shorter length than those found in the other observed thirds.
Dynamic radiation pattern diversity (DRPD) MIMO using CRLH leaky-wave antennas

This paper presents a dynamic radiation pattern diversity (DRPD) MIMO wireless system where the antennas radiation patterns are electronically controlled in real-time. The adopted antenna elements are composite right/left-handed (CRLH) microstrip leaky-wave (LW) antennas for which the beam direction can be electronically scanned in a continuous manner from backfire to endfire and the beam shape can be controlled. This system offers a tremendous amount of flexibility in tuning the channel transfer matrix to increase the system performance. Based on this architecture, we propose two simple radiation pattern control algorithms. The first one requires no feedback and averages out the channel fades while the second one requires a simple feedback at the receiver to select the beam pattern maximizing the performance metric. The capacity of both algorithms is derived and analyzed using Monte Carlo simulations. The results show that these algorithms significantly improve the wireless link outage performance in a slow fading environment and increase the diversity gain of a MIMO system for a fixed multiplexing gain.
Do acetylcholine receptor and striated muscle antibodies predict the presence of thymoma in patients with myasthenia gravis?

Introduction: Acetylcholine receptor (AChR) and striated muscle antibodies (StrAbs) are found frequently in myasthenia gravis (MG) patients with thymoma. In this study we aimed to determine the positive predictive value (PPV) and negative predictive value (NPV) of these antibodies for thymoma in patients with MG. Methods: Antibody findings, thymic histology, and onset age were reviewed for 1141 patients with MG. PPV and NPV of these antibodies for thymoma were determined. Results: The PPV of AChR binding antibodies plus StrAbs was highest (50.0%) with onset before the age of 40 years. The PPV of all antibodies was low (<9%) after age 40. Higher StrAb levels did not increase the PPV. The NPV of AChR binding antibodies was high (99.7%) for all ages. Conclusions: Patients without AChR binding antibody are not likely to have a thymoma. StrAbs and AChR binding antibodies are not diagnostic for thymoma, but in early‐onset MG their presence should raise the clinical suspicion for thymoma. Muscle Nerve 49: 30–34, 2014
The 216-nucleotide intron of the E1A pre-mRNA contains a hairpin structure that permits utilization of unusually distant branch acceptors

A recently characterized 216-nucleotide intron-splicing reaction occurs within the adenovirus E1A pre-mRNA through the use of three branch acceptor sites, located at 59, 55, and 51 nucleotides from the 3' splice site. To investigate the role of the cis-acting sequence elements in the selection of such unusually distant branch sites, transcripts differing in sequence downstream of the branch sites were analyzed for in vitro splicing. Initial results suggested that secondary structure could be involved in the use of distant branch sites. The involvement of a hairpin structure, including a nine-G C-base-pair stem, was supported by the results of site-directed mutagenesis analyses. Mutations that destroyed or weakened this hairpin resulted in an inefficient splicing reaction. In contrast, complementary mutation or deletion of two bulges, which involved a restoration or reinforcement of the hairpin, resulted in a reactivation or improvement of the splicing efficiency, respectively. Therefore, we conclude that the hairpin structure shortens the operational distance between the 3' splice site and the branch acceptors and brings the branch sites into the branch-permissive window, 18 to 40 nucleotides upstream of the 3' splice site. Our results confirm the importance of the constraint of distance for the splicing reaction and show that this constraint may be overcome by means of a stable hairpin formation.
Microbial Diversity and Heterogeneity in Sandy Subsurface Soils

ABSTRACT Microbial community diversity and heterogeneity in saturated and unsaturated subsurface soils from Abbott's Pit in Virginia (1.57, 3.25, and 4.05 m below surface) and Dover Air Force Base in Delaware (6.00 and 7.50 m below surface) were analyzed using a culture-independent small-subunit (SSU) rRNA gene (rDNA)-based cloning approach. Four to six dominant operational taxonomic units (OTUs) were identified in 33 to 100 unique SSU rDNA clones (constituting about 40 to 50% of the total number of SSU rDNA clones in the clone library) from the saturated subsurface samples, whereas no dominant OTUs were observed in the unsaturated subsurface sample. Less than 10% of the clones among samples from different depths at the same location were identical, and the proportion of overlapping OTUs was lower for the samples that were vertically far apart than for adjacent samples. In addition, no OTUs were shared between the Abbott's Pit and Dover samples. The majority of the clones (80%) had sequences that were less than 5% different from those in the current databases. Phylogenetic analysis indicated that most of the bacterial clones were affiliated with members of the Proteobacteria family (90%), gram-positive bacteria (3%), and members of the Acidobacteria family (3%). Principal component analysis revealed that samples from different geographic locations were well separated and that samples from the same location were closely grouped together. In addition, the nonsaturated subsurface samples from Abbott's Pit clustered together and were well separated from the saturated subsurface soil sample. Finally, the overall diversity of the subsurface samples was much lower than that of the corresponding surface soil samples.
Carboxypeptidase-G 2 Rescue in Cancer Patients with Delayed Methotrexate Elimination after High-dose Methotrexate Therapy

High-dose methotrexate (HDMTX) is a component of many cancer treatment regimens. Despite careful management, delayed renal clearance, followed by extremely high serum levels with potentially life-threatening toxicity can occur. In the present study, we report our results of carboxypeptidase-G 2 (CPDG 2 ) rescue in 8 patients with delayed methotrexate elimination and renal impairment after HDMTX therapy for lymphoma or osteosarcoma. A dose of 50 U/kg CPDG 2 was administered. MTX plasma levels decreased rapidly and recovery of renal function was observed in all patients. No patient developed severe WHO grade 4 MTX toxicity. CPDG 2 provides an alternative route of MTX elimination by converting it to inactive and non-toxic metabolites. CPDG 2 rescue was well tolerated, safe and very effective in preventing severe or life-threatening MTX toxicity.
Prolonged antibiotics for purulent bronchiectasis in children and adults.

BACKGROUND The vicious cycle hypothesis for bronchiectasis predicts that bacterial colonisation of the respiratory tract perpetuates inflammatory change. This damages the mucociliary escalator preventing bacterial clearance and allowing the persistence of pro-inflammatory mediators. Conventional treatment with physiotherapy and intermittent antibiotics are felt to improve the condition of bronchiectasis patients although there are no conclusive data showing that these interventions influence the natural history of the condition. Various strategies have been tried to interrupt this cycle of infection and inflammation and one of these is to prolong antibiotic treatment in the hope of allowing the airway mucosa to heal. OBJECTIVES This systematic review brings together the evidence and where possible presents a meta-analysis of the data available to answer the question 'Does treatment with prolonged courses of antibiotics influence the outcome in purulent bronchiectasis? ' SEARCH STRATEGY The Cochrane Airways Group trials register and reference lists of identified articles were searched. Searches were current as of January 2007. SELECTION CRITERIA Randomised trials looking at the use of prolonged antibiotic therapy in the treatment of bronchiectasis compared with either placebo or usual care. DATA COLLECTION AND ANALYSIS Trial quality was assessed and data extraction was carried out by the reviewers independently. Study authors were contacted for missing information. MAIN RESULTS Nine trials met the inclusion criteria, recruiting a total of 378 participants. Antibiotics were given for between 4 weeks and one year. Only limited meta-analysis was possible due to the diversity of outcomes in the trials. Response rates showed significant effects in favour of prolonged antibiotic treatment (Peto OR (95% CI), 3.37 (1.60 to 7.09)). Conversely for exacerbation rates there was no significant difference between prolonged antibiotics and placebo (Peto OR (95% CI), 0.96 (0.27 to 3.46)). For withdrawals there was no significant difference between treatment and placebo management (Peto OR (95% CI), 1.06 (0.42 to 2.65)). Data for lung function showed no significant benefit in favour of antibiotic treatment (% predicted FEV1 mean difference -1.05 % (95% CI -6.93 to 4.83)). AUTHORS' CONCLUSIONS The evidence available shows a small benefit for the use of prolonged antibiotics in the treatment of bronchiectasis. This review is limited by the diversity of the trials. Further randomised controlled trials with adequate power and standardised end points are required.