Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.

Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes

Use of health related quality of life tools in upper gastrointestinal surgery

The objective of this article is to review the literature and discuss the various tools used in upper gastrointestinal surgery for the measurement of health related quality of life (HR-QOL) and highlights various outcome variables that affect the HR-QOL among patients of common upper gastrointestinal disorders. The paper reviews HR-QOL articles published in the last 25 years on different upper gastrointestinal curative or palliative procedures. The paper used an HR-QOL method, which is a questionnaire, which is utilized to assess the changes in the health status of patients after a surgical intervention. These surveys are of increasingly importance, as health care providers are challenged to justify treatment approaches and rationale for any surgical intervention. These HR-QOL tools are very helpful for the evaluation of subjective outcome of common upper gastrointestinal surgical procedures like Gastrointestinal Quality of Life Index (GIQLI) and Quality of life in reflux and dyspepsia (QOLRAD) for Nissen fundoplication, Spitzer\'s QOL index for gastrectomy, Short Form 36 (SF-36) for achalasia and GIQLI for peptic ulcer disease. The paper concludes that use of validated and reliable health instruments in upper gastrointestinal surgery is directed at measuring the impact in a reproducible and valid fashion. Curative or palliative procedures should be offered to the patients of upper gastrointestinal disorders after the assessment by HR-QOL tools. As the impairment of functions that may occur after different operations vary considerably, an operation-specific assessment of HR-QOL for each type of surgical procedure is becoming an essential principle to follow in a successful healthcare system.African Journal of Health Sciences Vol. 15 (1&2) 2008: pp. 14-2

U-Pb geochronology and petrogenesis of peraluminous granitoids from northern Indian plate in NW Pakistan: Andean type orogenic signatures from the early Paleozoic along the northern Gondwana

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe pre-Himalayan peraluminous magmatic event along the northern margin of Indian plate in north-western Pakistan has been investigated leading to a correlation with the magmatic evolution in other Himalayan and northern Gondwana regions. The two mica granites from Utla and Mansehra regions of NW Pakistan are dominantly megacrystic, strongly peraluminous (A/CNK > 1.1) and intruded by aplitic dykes and quartz rich veins. U-Pb zircon dating by SIMS reveals their emplacement during the early Paleozoic, ranging from 476 Ma to 480 Ma. These granites are enriched in light rare-earth elements (LREEs) and show similar REE patterns with negative Eu anomalies. Geochemical modelling indicates that these granites were derived mainly from the partial melting of pelitic sources followed by the evolution of melt via fractional crystallization of feldspars, biotite, muscovite, apatite, and/or zircon, with the aplite dykes representing the very last fractionation product. Based on their compositions, source rock characteristics and U-Pb geochronology, we assign these to the regional association of other Cambro-Ordovician granitoids from the Himalayas and northern Gondwana terranes. Due to these similarities alongside other metamorphic, stratigraphic and geochemical evidence, an early Paleozoic Andean-type orogenic event is proposed for the genesis of these granitoids where the process could have been initiated by the subduction of the Proto-Tethys oceanic lithosphere beneath the northern Gondwana continental margin.The principal author acknowledges the financial assistance provided by the Commonwealth Scholarship Commission, United Kingdom

Convergence of defect energetics calculations

Determination of the chemical and spectroscopic natures of defects in materials such as hexagonal boron nitride (h-BN) remains a serious challenge for both experiment and theory. To establish basics needs for reliable calculations, we consider a model defect $V_N N_B$ in h-BN in which a boron-for-nitrogen substitution is accompanied by a nitrogen vacancy, examining its lowest-energy transition, (1)2B1 to (1)2A1. This provides a relatively simple test system as open-shell and charge-transfer effects, that are difficult to model and can dominate defect spectroscopy, are believed to be small. We establish calculation convergence with respect to sample size using both cluster and 2D-periodic models, convergence with respect to numerical issues such as use of plane-wave or Gaussian-basis-set expansions, and convergence with respect to the treatment of electron correlation. The results strongly suggest that poor performance of computational methods for defects of other natures arise through intrinsic methodological shortcomings

Preparation of Photoactive Transition-Metal Layered Double Hydroxides (LDH) to Replace Dye-Sensitized Materials in Solar Cells

This work highlights the use of Fe-modified MgAl-layered double hydroxides (LDHs) to replace dye and semiconductor complexes in dye-sensitized solar cells (DSSCs), forming a layered double hydroxide solar cell (LDHSC). For this purpose, a MgAl-LDH and a Fe-modified MgAl LDH were prepared. X-ray diffraction spectroscopy (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) spectroscopy were used to analyze the structural properties, morphology, and success of the Fe-modification of the synthesized LDHs. Ultraviolet-visible (UV-Vis) absorption spectroscopy was used to analyze the photoactive behavior of these LDHs and compare it to that of TiO2 and dye-sensitized TiO2. Current-voltage (I–V) solar simulation was used to determine the fill factor (FF), open circuit voltage (VOC), short circuit current (ISC), and efficiency of the LDHSCs. It was shown that the MgFeAl-LDH can act as a simultaneous photoabsorber and charge separator, effectively replacing the dye and semiconductor complex in DSSCs and yielding an efficiency of 1.56%

Specialist paediatric palliative care services: what are the benefits?

Background The number of children and young people (CYP) living with life-limiting and life-threatening conditions is rising. Paediatric palliative care is a relatively new aspect of healthcare, the delivery of which is variable, with a wide range of healthcare and voluntary sector providers involved. Policy recommendations are for Specialist Paediatric Palliative Care (SPPC) services to be supported by a physician with specialist training. Aim To examine the research evidence regarding the distinct benefits of SPPC services, with ‘Specialist Paediatric Palliative Care’ defined as palliative care services supported by a specialist physician. Method Systematic review of studies of SPPC services published in English from 1980 to 2016. Keyword searches were carried out in medical databases (Cochrane, PubMed, EMBASE, CINAHL and AMED) and a narrative synthesis. Results Eight studies were identified, most of which were retrospective surveys undertaken within single institutions; three were surveys of bereaved parents and three were medical notes reviews. Together they represented a heterogeneous body of low-level evidence. Cross-cutting themes suggest that SPPC services improve the quality of life and symptom control and can impact positively on place of care and family support. Conclusions Current evidence indicates that SPPC services contribute beneficially to the care and experience of CYP and their families, but is limited in terms of quantity, methodological rigour and generalisability. Further research is necessary given the significant workforce and resource implications associated with policy recommendations about the future provision of SPPC and to address the need for evidence to inform the design and delivery of SPPC services