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Introducing the multi-faceted teaching experiment

A mathematics classroom is comprised of many mathematicians with varying understanding of mathematics knowledge, including the teacher, students and sometimes researchers. To align with this conceptualisation of knowledge and understanding, the multi-faceted teaching experiment will be introduced as an approach to study all classroom participants’ interactions with the shared knowledge of mathematics. Drawing on the experiences of a large curriculum project, it is claimed that, unlike a multi-tiered teaching experiment, the multi-faceted teaching experiment provides a research framework that allows for the study of mathematicians’ building of knowledge in a classroom without privileging the experience of any one participant

The structure of Serratia marcescens Lip, a membrane-bound component of the type VI secretion system

The high-resolution crystal structure of S. marcescens Lip reveals a new member of the transthyretin family of proteins. Lip, a core component of the type VI secretion apparatus, is localized to the outer membrane and is positioned to interact with other proteins forming this complex system

Advanced power sources for space missions

Approaches to satisfying the power requirements of space-based Strategic Defense Initiative (SDI) missions are studied. The power requirements for non-SDI military space missions and for civil space missions of the National Aeronautics and Space Administration (NASA) are also considered. The more demanding SDI power requirements appear to encompass many, if not all, of the power requirements for those missions. Study results indicate that practical fulfillment of SDI requirements will necessitate substantial advances in the state of the art of power technology. SDI goals include the capability to operate space-based beam weapons, sometimes referred to as directed-energy weapons. Such weapons pose unprecedented power requirements, both during preparation for battle and during battle conditions. The power regimes for these two sets of applications are referred to as alert mode and burst mode, respectively. Alert-mode power requirements are presently stated to range from about 100 kW to a few megawatts for cumulative durations of about a year or more. Burst-mode power requirements are roughly estimated to range from tens to hundreds of megawatts for durations of a few hundred to a few thousand seconds. There are two likely energy sources, chemical and nuclear, for powering SDI directed-energy weapons during the alert and burst modes. The choice between chemical and nuclear space power systems depends in large part on the total duration during which power must be provided. Complete study findings, conclusions, and eight recommendations are reported

Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK–TssFG subcomplex

Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival bacteria or eukaryotic cells. However, the mechanism of the T6SS is incompletely understood. In the present study, we investigated a conserved component of the T6SS, TssK, using the antibacterial T6SS of Serratia marcescens as a model system. TssK was confirmed to be essential for effector secretion by the T6SS. The native protein, although not an integral membrane protein, appeared to localize to the inner membrane, consistent with its presence within a membrane-anchored assembly. Recombinant TssK purified from S. marcescens was found to exist in several stable oligomeric forms, namely trimer, hexamer and higher-order species. Native-level purification of TssK identified TssF and TssG as interacting proteins. TssF and TssG, conserved T6SS components of unknown function, were required for T6SS activity, but not for correct localization of TssK. A complex containing TssK, TssF and TssG was subsequently purified in vitro, confirming that these three proteins form a new subcomplex within the T6SS. Our findings provide new insight into the T6SS assembly, allowing us to propose a model whereby TssK recruits TssFG into the membrane-associated T6SS complex and different oligomeric states of TssK may contribute to the dynamic mechanism of the system

Radio Polarimetry of the ELAIS N1 Field: Polarized Compact Sources

We present deep polarimetric observations at 1420 MHz of the European Large Area ISO Survey North 1 region (ELAIS N1) as part of the Dominion Radio Astrophysical Observatory Planck Deep Fields project. By combining closely spaced aperture synthesis fields, we image a region of 7.43 square degrees to a maximum sensitivity in Stokes Q and U of 78 microJy/beam, and detect 786 compact sources in Stokes I. Of these, 83 exhibit polarized emission. We find that the differential source counts (log N - log p) for polarized sources are nearly constant down to p > 500 microJy, and that these faint polarized radio sources are more highly polarized than the strong source population. The median fractional polarization is (4.8 +/- 0.7)% for polarized sources with Stokes I flux density between 1 and 30 mJy; approximately three times larger than sources with I > 100 mJy. The majority of the polarized sources have been identified with galaxies in the Spitzer Wide Area Infrared Extragalactic Survey (SWIRE) image of ELAIS N1. Most of the galaxies occupy regions in the IRAC 5.8/3.6 micron vs. 8.0/4.5 micron color-color diagram associated with dusty AGNs, or with ellipticals with an aging stellar population. A few host galaxies have colors that suggests significant PAH emission in the near-infrared. A small fraction, 12%, of the polarized sources are not detected in the SWIRE data. None of the polarized sources in our sample appears to be associated with an actively star-forming galaxy.Comment: 28 pages, 8 Figures. Figures 2 and 3 as separate gif images. Accepted for publication in the Astrophysical Journa

Quality of hospital care for sick newborns and severely malnourished children in Kenya: A two-year descriptive study in 8 hospitals

BACKGROUND: Given the high mortality associated with neonatal illnesses and severe malnutrition and the development of packages of interventions that provide similar challenges for service delivery mechanisms we set out to explore how well such services are provided in Kenya. METHODS: As a sub-component of a larger study we evaluated care during surveys conducted in 8 rural district hospitals using convenience samples of case records. After baseline hospitals received either a full multifaceted intervention (intervention hospitals) or a partial intervention (control hospitals) aimed largely at improving inpatient paediatric care for malaria, pneumonia and diarrhea/dehydration. Additional data were collected to: i) examine the availability of routine information at baseline and their value for morbidity, mortality and quality of care reporting, and ii) compare the care received against national guidelines disseminated to all hospitals. RESULTS: Clinical documentation for neonatal and malnutrition admissions was often very poor at baseline with case records often entirely missing. Introducing a standard newborn admission record (NAR) form was associated with an increase in median assessment (IQR) score to 25/28 (22-27) from 2/28 (1-4) at baseline. Inadequate and incorrect prescribing of penicillin and gentamicin were common at baseline. For newborns considerable improvements in prescribing in the post baseline period were seen for penicillin but potentially serious errors persisted when prescribing gentamicin, particularly to low-birth weight newborns in the first week of life. Prescribing essential feeds appeared almost universally inadequate at baseline and showed limited improvement after guideline dissemination. CONCLUSION: Routine records are inadequate to assess newborn care and thus for monitoring newborn survival interventions. Quality of documented inpatient care for neonates and severely malnourished children is poor with limited improvement after the dissemination of clinical practice guidelines. Further research evaluating approaches to improving care for these vulnerable groups is urgently needed. We also suggest pre-service training curricula should be better aligned to help improve newborn survival particularly

Experience developing national evidence-based clinical guidelines for childhood pneumonia in a low-income setting - making the GRADE?

BACKGROUND: The development of evidence-based clinical practice guidelines has gained wide acceptance in high-income countries and reputable international organizations. Whereas this approach may be a desirable standard, challenges remain in low-income settings with limited capacity and resources for evidence synthesis and guideline development. We present our experience using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for the recent revision of the Kenyan pediatric clinical guidelines focusing on antibiotic treatment of pneumonia. METHODS: A team of health professionals, many with minimal prior experience conducting systematic reviews, carried out evidence synthesis for structured clinical questions. Summaries were compiled and distributed to a panel of clinicians, academicians and policy-makers to generate recommendations based on best available research evidence and locally-relevant contextual factors. RESULTS: We reviewed six eligible articles on non-severe and 13 on severe/very severe pneumonia. Moderate quality evidence suggesting similar clinical outcomes comparing amoxicillin and cotrimoxazole for non-severe pneumonia received a strong recommendation against adopting amoxicillin. The panel voted strongly against amoxicillin for severe pneumonia over benzyl penicillin despite moderate quality evidence suggesting clinical equivalence between the two and additional factors favoring amoxicillin. Very low quality evidence suggesting ceftriaxone was as effective as the standard benzyl penicillin plus gentamicin for very severe pneumonia received a strong recommendation supporting the standard treatment. CONCLUSIONS: Although this exercise may have fallen short of the rigorous requirements recommended by the developers of GRADE, it was arguably an improvement on previous attempts at guideline development in low-income countries and offers valuable lessons for future similar exercises where resources and locally-generated evidence are scarce

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs