The characterization of multidrug resistant type 1 S-fimbriated Escherichia coli from women with recurrent urinary tract infections (RUTIS) in Bangladesh

Background: Escherichia coli is a bacterial species that is most frequently associated with urinary tract infections (UTIs) worldwide. Recurrent UTIs (RUTIs) pose a major threat to health, especially in women. However, studies on the pathogenic potentials of E. coli isolates associated with RUTIs has yet to be done. The present study was designed to characterize the isolates of E. coli from women, suffering from repeated UTIs in Bangladesh.Methods: A total of 15 isolates of E. coli, collected from women with RUTIs in the Sylhet city of Bangladesh, were analyzed by a series of biochemical and molecular tests.Results: The PCR amplification of the mannose-resistant type 1 S-fimbriae gene (sfa1) confirmed all sfa1+ isolates of E. coli. In an antibiogram assay, all the isolates of E. coli were found to be completely resistant to at least five of the ten commercial antibiotics and drug resistance were found to be correlated with the weight of the RUTIs patient. Analysis of the 16S rRNA data of the two most drug-resistant and clinically significant isolates were found to be clustered with the drug-resistant UTI-causing E. coli isolates, circulated in India.Conclusions: This study could pave the way of RUTIs diagnosis and treatment strategy for women in Bangladesh.Keywords: RUTIs; E. coli; sfa1; multidrug-resistant isolates; 16S rRNA gene sequencing; correlation analysis

Pulsed combustion process for black liquor gasification

The objective of this project is to test an energy efficient, innovative black liquor recovery system on an industrial scale. In the MTCI recovery process, black liquor is sprayed directly onto a bed of sodium carbonate solids which is fluidized by steam. Direct contact of the black liquor with hot bed solids promotes high rates of heating and pyrolysis. Residual carbon, which forms as a deposit on the particle surface, is then gasified by reaction with steam. Heat is supplied from pulse combustor resonance tubes which are immersed within the fluid bed. A portion of the gasifier product gas is returned to the pulse combustors to provide the energy requirements of the reactor. Oxidized sulfur species are partially reduced by reaction with the gasifier products, principally carbon monoxide and hydrogen. The reduced sulfur decomposed to solid sodium carbonate and gaseous hydrogen sulfide (H{sub 2}S). Sodium values are recovered by discharging a dry sodium carbonate product from the gasifier. MTCI's indirectly heated gasification technology for black liquor recovery also relies on the scrubbing of H{sub 2}S for product gases to regenerate green liquor for reuse in the mill circuit. Due to concerns relative to the efficiency of sulfur recovery in the MTCI integrated process, an experimental investigation was undertaken to establish performance and design data for this portion of the system

Design, synthesis and biological evaluation of fused naphthofuro[3,2-c]quinoline-6,7,12-triones and pyrano[3,2-c]quinoline-6,7,8,13-tetraones derivatives as ERK inhibitors with efficacy in BRAF-mutant melanoma

Approximately 60% of human cancers exhibit enhanced activity of ERK1 and ERK2, reflecting their multiple roles in tumor initiation and progression. Acquired drug resistance, especially mechanisms associated with the reactivation of the MAPK (RAF/MEK/ERK) pathway represent a major challenge to current treatments of melanoma and several other cancers. Recently, targeting ERK has evolved as a potentially attractive strategy to overcome this resistance. Herein, we report the design and synthesis of novel series of fused naphthofuro[3,2-c] quinoline-6,7,12-triones 3a-f and pyrano[3,2-c]quinoline-6,7,8,13-tetraones 5a,b and 6, as potential ERK inhibitors. New inhibitors were synthesized and identified by different spectroscopic techniques and X-ray crystallography. They were evaluated for their ability to inhibit ERK1/2 in an in vitro radioactive kinase assay. 3b and 6 inhibited ERK1 with IC50s of 0.5 and 0.19 mu M, and inhibited ERK2 with IC50s of 0.6 and 0.16 mu M respectively. Kinetic mechanism studies revealed that the inhibitors are ATP-competitive inhibitors where 6 inhibited ERK2 with a K-i of 0.09 mu M. Six of the new inhibitors were tested for their in vitro anticancer activity against the NCI-60 panel of tumor cell lines. Compound 3b and 6 were the most potent against most of the human tumor cell lines tested. Moreover, 3b and 6 inhibited the proliferation of the BRAF mutant A375 melanoma cells with IC50s of 3.7 and 0.13 mu M, respectively. In addition, they suppressed anchorage-dependent colony formation. Treatment of the A375 cell line with 3b and 6 inhibited the phosphorylation of ERK substrates p-90RSK and ELK-1 and induced apoptosis in a dose dependent manner. Finally, a molecular docking study showed the potential binding mode of 3b and 6 within the ATP catalytic binding site of ERK2.Peer reviewe

Time-sensitive influence maximization in social networks

One of the fundamental issues in social networks is the influence maximization problem, where the goal is to identify a small subset of individuals such that they can trigger the largest number of members in the network. In real-world social networks, the propagation of information from a node to another may incur a certain amount of time delay; moreover, the value of information may decrease over time. So not only the coverage size, but also the propagation speed matters. In this paper, we propose the Time-Sensitive Influence Maximization (TSIM) problem, which takes into account the time dependence of the information value. Considering the time delay aspect, we develop two diffusion models, namely the Delayed Independent Cascade model and the Delayed Linear Threshold model. We show that the TSIM problem is NP-hard under these models but the spread function is monotone and submodular. Thus, a greedy approximation algorithm can achieve a 1 − 1/e approximation ratio. Moreover, we propose two time-sensitive centrality measures and compare their performance with the greedy algorithm.We evaluate our methods on four real-world datasets. Experimental results show that the proposed algorithms outperform existing methods, which ignore the decay of information value over time

Structural modifications in Bermuda grass [Cynodon dactylon (L.) Pers.] ecotypes for adaptation to environmental heterogeneity

IntroductionIt is well known that different ecotypes adopt different mechanisms to survive under environmental stress conditions. In this regard, each ecotype showed different type of modifications for their existence in a specific habitat that reflects to their ecological success.MethodsHere, differently adapted ecotypes of Bermuda grass [Cynodon dactylon (L.) Pers.] were collected to evaluate their differential structural and functional modifications that are specific to cope with environmental stress conditions. The soil that adheres ecotypes roots were highly saline in case of DF-SD (Derawar Fort-Saline Desert), UL-HS (Ucchali Lake-Hyper Saline) and G-SSA (Gatwala-Saline Semiarid) ecotypes. Soils of S- HS (Sahianwala-Hyper Saline), S-SW (Sahianwala-Saline Wetland) and PA-RF (Pakka Anna-Reclaimed Field) were basic (pH 9 to 10). Soils of UL-HS and PA- HS (Pakka Anna-Hyper Saline), KKL-S (Kalar Kahar Lake-Saline), BG-NS (Botanic Garden-Non Saline) and G-SSA were rich in organic matter, and soil of BG-NS and DF-SD were rich in minerals. Anatomical modifications were performed by using the free hand sectioning technique and light microscopy.Results and DiscussionDF-SD is one of the best ecotypes which showed anatomical modifications to cope with environmental changes. These modifications included stem cross-sectional area and leaf sheath thickness that contribute towards water storage, vascular tissues for proficient translocation of solutes and trichomes that provide resistance to water loss. On the other hand, sclerification in root is the only notable modification in the Gatwala Saline Semiarid (G-SSA) ecotype from saline arid habitat where rainfall is not as low as in the Cholistan Desert. Two ecotypes from hyper-saline wetlands, UL-HS and KL-HS showed increased number and size of vascular tissue, central cavity and sclerification in stem which are important for solutes conduction, water loss and salts bulk movement, respectively. The ecotype from reclaimed site was not much different from its counterpart from hyper-saline dryland. Overall, anatomical modifications to maintain water conservation are key mechanisms that have been identified as mediating stress tolerance in C. dactylon ecotypes

Conducting longitudinal research with older widows : Exploring personal communities through multiple methods

This article reports on the process of undertaking a longitudinal multiple methods study with older women experiencing the transition of later life widowhood. A series of three qualitative in depth interviews were conducted with twenty-six older widows in North Staffordshire, United Kingdom. Interviews included the use of personal community diagrams to identify the structure of personal communities, and Christmas and Christmas cards to further explore social relationships and practices during transition. Examples of cases are given to illustrate the findings derived from the methods employed. The cases demonstrate the diverse and often paradoxical nature of social relationships within similar networks

Human MLH1 Protein Participates in Genomic Damage Checkpoint Signaling in Response to DNA Interstrand Crosslinks, while MSH2 Functions in DNA Repair

DNA interstrand crosslinks (ICLs) are among the most toxic types of damage to a cell. For this reason, many ICL-inducing agents are effective therapeutic agents. For example, cisplatin and nitrogen mustards are used for treating cancer and psoralen plus UVA (PUVA) is useful for treating psoriasis. However, repair mechanisms for ICLs in the human genome are not clearly defined. Previously, we have shown that MSH2, the common subunit of the human MutSα and MutSβ mismatch recognition complexes, plays a role in the error-free repair of psoralen ICLs. We hypothesized that MLH1, the common subunit of human MutL complexes, is also involved in the cellular response to psoralen ICLs. Surprisingly, we instead found that MLH1-deficient human cells are more resistant to psoralen ICLs, in contrast to the sensitivity to these lesions displayed by MSH2-deficient cells. Apoptosis was not as efficiently induced by psoralen ICLs in MLH1-deficient cells as in MLH1-proficient cells as determined by caspase-3/7 activity and binding of annexin V. Strikingly, CHK2 phosphorylation was undetectable in MLH1-deficient cells, and phosphorylation of CHK1 was reduced after PUVA treatment, indicating that MLH1 is involved in signaling psoralen ICL-induced checkpoint activation. Psoralen ICLs can result in mutations near the crosslinked sites; however, MLH1 function was not required for the mutagenic repair of these lesions, and so its signaling function appears to have a role in maintaining genomic stability following exposure to ICL-induced DNA damage. Distinguishing the genetic status of MMR-deficient tumors as MSH2-deficient or MLH1-deficient is thus potentially important in predicting the efficacy of treatment with psoralen and perhaps with other ICL-inducing agents