An in situ Comparison of Electron Acceleration at Collisionless Shocks under Differing Upstream Magnetic Field Orientations

A leading explanation for the origin of Galactic cosmic rays is acceleration at high-Mach number shock waves in the collisionless plasma surrounding young supernova remnants. Evidence for this is provided by multi-wavelength non-thermal emission thought to be associated with ultrarelativistic electrons at these shocks. However, the dependence of the electron acceleration process on the orientation of the upstream magnetic field with respect to the local normal to the shock front (quasi-parallel/quasi-perpendicular) is debated. Cassini spacecraft observations at Saturn's bow shock have revealed examples of electron acceleration under quasi-perpendicular conditions, and the first in situ evidence of electron acceleration at a quasi-parallel shock. Here we use Cassini data to make the first comparison between energy spectra of locally accelerated electrons under these differing upstream magnetic field regimes. We present data taken during a quasi-perpendicular shock crossing on 2008 March 8 and during a quasi-parallel shock crossing on 2007 February 3, highlighting that both were associated with electron acceleration to at least MeV energies. The magnetic signature of the quasi-perpendicular crossing has a relatively sharp upstream–downstream transition, and energetic electrons were detected close to the transition and immediately downstream. The magnetic transition at the quasi-parallel crossing is less clear, energetic electrons were encountered upstream and downstream, and the electron energy spectrum is harder above ~100 keV. We discuss whether the acceleration is consistent with diffusive shock acceleration theory in each case, and suggest that the quasi-parallel spectral break is due to an energy-dependent interaction between the electrons and short, large-amplitude magnetic structures

The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

Plasma cholesterol levels and brain development in preterm newborns.

BackgroundTo assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns.MethodsSixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition.ResultsEarly plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.ConclusionsHigher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes

A genome-wide association study identifies multiple loci for variation in human ear morphology

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1

DNA immunization as a technology platform for monoclonal antibody induction

To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail

A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid

Amines are a fundamentally important class of biologically active compounds and the ability to manipulate their physicochemical properties through the introduction of fluorine is of paramount importance in medicinal chemistry. Current synthesis methods for the construction of fluorinated amines rely on air and moisture sensitive reagents that require special handling or harsh reductants that limit functionality. Here we report practical, catalyst-free, reductive trifluoroethylation reactions of free amines exhibiting remarkable functional group tolerance. The reactions proceed in conventional glassware without rigorous exclusion of either moisture or oxygen, and use trifluoroacetic acid as a stable and inexpensive fluorine source. The new methods provide access to a wide range of medicinally-relevant functionalized tertiary beta-fluoroalkylamine cores, either through direct trifluoroethylation of secondary amines or via a three-component coupling of primary amines, aldehydes and trifluoroacetic acid. A reduction of in situ-generated silyl ester species is proposed to account for the reductive selectivity observed

Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer. © 1999 Cancer Research Campaig

Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity

Type 2 diabetes mellitus (T2DM) is characterized by defects in both insulin sensitivity and glucose-stimulated insulin secretion (GSIS) and is often accompanied by obesity. In this study, we show that disruption of thioredoxin binding protein-2 (TBP-2, also called Txnip) in obese mice (ob/ob) dramatically improves hyperglycaemia and glucose intolerance, without affecting obesity or adipocytokine concentrations. TBP-2-deficient ob/ob mice exhibited enhanced insulin sensitivity with activated insulin receptor substrate-1/Akt signalling in skeletal muscle and GSIS in islets compared with ob/ob mice. The elevation of uncoupling protein-2 (UCP-2) expression in ob/ob islets was downregulated by TBP-2 deficiency. TBP-2 overexpression suppressed glucose-induced adenosine triphosphate production, Ca2+ influx and GSIS. In β-cells, TBP-2 enhanced the expression level and transcriptional activity of UCP-2 by recruitment of peroxisome proliferator-activated receptor-γ co-activator-1α to the UCP-2 promoter. Thus, TBP-2 is a key regulatory molecule of both insulin sensitivity and GSIS in diabetes, raising the possibility that inhibition of TBP-2 may be a novel therapeutic approach for T2DM

Epidemiological Features of Infantile Hypertrophic Pyloric Stenosis in Taiwanese Children: A Nation-Wide Analysis of Cases during 1997–2007

OBJECTIVE: To describe the epidemiological characteristics of infantile hypertrophic pyloric stenosis (IHPS) in ethnic Chinese children. MATERIALS AND METHODS: We reviewed the National Health Insurance claims database and analyzed data from children less than one year of age who had been diagnosed with IHPS (ICD-9-CM 750.5) and had undergone pyloromyotomy (ICD-9-CM 43.3). We analyzed the incidence, gender, age at diagnosis, length of hospital stay, seasonal variation and cost of IHPS from data collected between January 1997 and December 2007. RESULTS: A total of 1,077 infants met inclusion criteria, including 889 boys and 188 girls. The annual incidence of IHPS ranged from 0.30 to 0.47 per 1,000 live births with a mean incidence of 0.39 per 1,000 live births. Between 2002 and 2007, the incidence showed a declining trend (P = 0.025) with coincidentally increasing trends for both exclusive breastfeeding (P = 0.014) and breastfeeding plus bottle feeding (P = 0.004). The male-to-female rate ratio was dynamic and increased from 3.03 during the first two weeks of life to 8.94 during the 8(th) through 10th weeks of life. The overall male-to-female rate ratio was 4.30. The mean age at diagnosis was 43.1 ± 2.4 days. After analyzing the months of birth and hospital admission, no seasonal variation associated with IHPS was detected. The mean length of hospital stay was 8.28 ± 7.10 days. CONCLUSIONS: The incidence of IHPS in Taiwan, a country with a majority ethnic Chinese population, was lower than observed incidences in Caucasian populations living in Western countries. Breastfeeding campaigns and low maternal smoking rates may contribute to the lower incidence of IHPS in Taiwan. However, additional studies with longer follow-up periods are needed