Chemoselective oxidation of aryl organoboron systems enabled by boronic acid-selective phase transfer

We report the direct chemoselective Brown-type oxidation of aryl organoboron systems containing two oxidizable boron groups. Basic biphasic reaction conditions enable selective formation and phase transfer of a boronic acid trihydroxyboronate in the presence of boronic acid pinacol (BPin) esters, while avoiding speciation equilibria. Spectroscopic investigations validate a base-promoted phase-selective discrimination of organoboron species. This phenomenon is general across a broad range of organoboron compounds and can also be used to invert conventional protecting group strategies, enabling chemoselective oxidation of BMIDA species over normally more reactive BPin substrates. We also demonstrate the selective oxidation of diboronic acid systems with chemoselectivity predictable a priori. The utility of this method is exemplified through the development of a chemoselective oxidative nucleophile coupling

Serial characterisation of monocyte and neutrophil function after lung resection.

OBJECTIVES: The primary aim of this prospective study was to perform a comprehensive serial characterisation of monocyte and neutrophil function, circulating monocyte subsets, and bronchoalveolar lavage (BAL) fluid after lung resection. A secondary aim was to perform a pilot, hypothesis-generating evaluation of whether innate immune parameters were associated with postoperative pneumonia. METHODS: Forty patients undergoing lung resection were studied in detail. Blood monocytes and neutrophils were isolated preoperatively and at 6, 24 and 48 h postoperatively. BAL was performed preoperatively and immediately postoperatively. Monocyte subsets, monocyte responsiveness to lipopolysaccharide (LPS) and neutrophil phagocytic capacity were quantified at all time points. Differential cell count, protein and cytokine concentrations were measured in BAL. Pneumonia evaluation at 72 h was assessed using predefined criteria. RESULTS: After surgery, circulating subsets of classical and intermediate monocytes increased significantly. LPS-induced release of proinflammatory cytokines from monocytes increased significantly and by 48 h a more proinflammatory profile was found. Neutrophil phagocytosis demonstrated a small but significant fall. Factors associated with postoperative pneumonia were: increased release of specific proinflammatory and anti-inflammatory cytokines from monocytes; preoperative neutrophilia; and preoperative BAL cell count. CONCLUSIONS: We conclude that postoperative lung inflammation is associated with specific changes in the cellular innate immune response, a better understanding of which may improve patient selection and prediction of complications in the future

Speciation control during Suzuki-Miyaura cross-coupling of haloaryl and haloalkenyl MIDA boronic esters

Boronic acid solution speciation can be controlled during the Suzuki-Miyaura cross-coupling of haloaryl MIDA boronic esters to enable the formal homologation of boronic acid derivatives. The reaction is contingent upon control of the basic biphase and is thermodynamically driven: temperature control provides highly chemoselective access to either BMIDA adducts at room temperature or BPin products at elevated temperature. Control experiments and solubility analyses have provided some insight into the mechanistic operation of the formal homologation process

Disease Status and Pubertal Stage Predict Improved Growth in Anti-TNF Therapy for Pediatric Inflammatory Bowel Disease

Background: Growth failure is well-recognised in pediatric Inflammatory Bowel Disease (PIBD; <18 years). We aimed to examine whether anti-Tumor Necrosis Factor (TNF) therapy improves growth in a PIBD population-based cohort. Methods: A retrospective review of all Scottish children receiving anti-TNF (infliximab (IFX) and adalimumab (ADA)) from 2000-2012 was performed; height was collected at: 12 months before anti-TNF (T-12), start (T0) and 12 (T+12) months after anti-TNF. Results: 93/201 treated with IFX and 28/49 for ADA had satisfactory growth data; 66 had full pubertal data. Univariate analysis demonstrated early pubertal stages (Tanner 1-3 n = 44 vs. T4-5 n = 22), disease remission, disease duration >=2 years and duration of IFX >=12 months were associated with improved linear growth for IFX; for ADA only improvement was seen in Tanner 1-3. For IFX, Tanner 1-3 median [DELTA] ht SDS -0.3 (-0.7,0.2) at T0 changed to 0.04 (-0.5, 0.7) at T+12 (p < 0.001) vs -0.01 (-0.5, 0.9) at T0 in T4-5 changed to -0.01 (-0.4, 0.2) at T+12 (p > 0.05). For IFX disease duration >=2 year, median [DELTA] ht SDS was -0.13 (-0.6, 0.3) at T0 then 0.07 (-0.3, 0.6) at T+12 (p < 0.001). Remission improved [DELTA] ht SDS (median [DELTA] ht SDS -0.14 (-0.6, 0.3) at T0 to 0.17 (-0.2, 0.7) at T+12 (p > 0.001)). Multiple regression analysis demonstrated corticosteroid usage at T0 predicted improved [DELTA] ht SDS at T+12 for IFX and ADA. Conclusions: Anti-TNF therapy is more likely to be associated with growth improvement when used at earlier stages of puberty with remission a key growth-promoting strategy in Paediatric Crohn's disease

Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation.

BACKGROUND: We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR(+)CD14(++)CD16(+)cells) and inducible PMLC (iPMLC, HLA-DR(+)CD14(++)CD16(-) cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. METHODS: iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. RESULTS: rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. CONCLUSIONS: These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation

Scale-Invariant Gravity: Geometrodynamics

We present a scale-invariant theory, conformal gravity, which closely resembles the geometrodynamical formulation of general relativity (GR). While previous attempts to create scale-invariant theories of gravity have been based on Weyl's idea of a compensating field, our direct approach dispenses with this and is built by extension of the method of best matching w.r.t scaling developed in the parallel particle dynamics paper by one of the authors. In spatially-compact GR, there is an infinity of degrees of freedom that describe the shape of 3-space which interact with a single volume degree of freedom. In conformal gravity, the shape degrees of freedom remain, but the volume is no longer a dynamical variable. Further theories and formulations related to GR and conformal gravity are presented. Conformal gravity is successfully coupled to scalars and the gauge fields of nature. It should describe the solar system observations as well as GR does, but its cosmology and quantization will be completely different.Comment: 33 pages. Published version (has very minor style changes due to changes in companion paper

Next-generation sequencing for HLA typing of class I loci

<p>Abstract</p> <p>Background</p> <p>Comprehensive sequence characterization across the MHC is important for successful organ transplantation and genetic association studies. To this end, we have developed an automated sample preparation, molecular barcoding and multiplexing protocol for the amplification and sequence-determination of class I HLA loci. We have coupled this process to a novel HLA calling algorithm to determine the most likely pair of alleles at each locus.</p> <p>Results</p> <p>We have benchmarked our protocol with 270 HapMap individuals from four worldwide populations with 96.4% accuracy at 4-digit resolution. A variation of this initial protocol, more suitable for large sample sizes, in which molecular barcodes are added during PCR rather than library construction, was tested on 95 HapMap individuals with 98.6% accuracy at 4-digit resolution.</p> <p>Conclusions</p> <p>Next-generation sequencing on the 454 FLX Titanium platform is a reliable, efficient, and scalable technology for HLA typing.</p

A cascade Suzuki-Miyaura/Diels-Alder protocol : exploring the bifunctional utility of vinyl Bpin

Funding: Industrial CASE studentship awarded from EPSRC and GlaxoSmithKline. The authors thank the EPSRC, GlaxoSmithKline, and the University of St Andrews for studentship funding (DLC), and the University of St Andrews and the EPSRC UK National Mass Spectrometry Facility at Swansea University for analyses.Cascade reactions are an important strategy in reaction design, allowing streamlining of chemical synthesis. Here we report a cascade Suzuki-Miyaura/Diels-Alder reaction, employing vinyl Bpin as a bifunctional reagent in two distinct roles: as an organoboron nucleophile for cross- coupling and as a Diels-Alder dienophile. Merging these two reactions enables a rapid and operationally simple synthesis of functionalized carbocycles in good yield. The effect of the organoboron subtype on Diels- Alder regioselectivity was investigated and post-synthetic modifications were carried out on a model substrate. The potential for a complementary Heck/Diels-Alder process was also assessed.PostprintPeer reviewe

Incidental diagnosis of diseases on un-enhanced helical computed tomography performed for ureteric colic

BACKGROUND: Patients presenting in the emergency room with flank pain suggestive of acute ureteric colic may have alternative underlying conditions mimicking ureteric stones. An early diagnosis and appropriate treatment for other causes of flank pain is important. The majority of centers around the world are increasingly using un-enhanced helical CT (UHCT) for evaluation of ureteric colic. This study was conducted to determine the incidence and spectrum of significant incidental diagnoses established or suggested on UHCT performed for suspected renal/ureteric colic. METHODS: Urologist and radiologist reviewed 233 consecutive UHCT, performed for suspected renal/ureteral colic along with assessment of the medical records. Radiological diagnoses of clinical entities not suspected otherwise were analyzed. All other relevant radiological, biochemical and serological investigations and per-operative findings were also noted. RESULTS: Ureteral calculi were identified in 148 examinations (64%), findings of recent passage of calculi in 10 (4%) and no calculus in 75 examinations (32%). Overall the incidental findings (additional or alternative diagnosis) were found in 28 (12%) CT scans. Twenty (71%) of these diagnoses were confirmed by per-operative findings, biopsy, and other radiological and biochemical investigations or on clinical follow up. CONCLUSION: A wide spectrum of significant incidental diagnoses can be identified on UHCT performed for suspected renal/ureteral colic. In the present series of 233 consecutive CT examinations, the incidence of incidental diagnosis was 12%

‘Whether you are gay or straight, I don’t like to see effeminate dancing’: effeminophobia in performance-level ballroom dance

This article discusses recent responses to performances of same-sex male ballroom dancing in order to consider the subtle difference which can exist between homophobia and effeminophobia. Given that the world of performance-level ballroom dancing is a gay-friendly environment, in which many participants are openly gay identified, this article will argue that a discourse of effeminophobia, rather than homophobia, underpins the world of performance-level ballroom dance. Performance-level ballroom dance is often read as camp not only because it represents exaggerated gender roles but because its official technique requires that the male dancer synthesise codes of masculinity and femininity in his dancing. What protects the gender-dissident male ballroom dancer from being read as effeminate is that he is paired with a female body performing excessive femininity. Without the foil of the hyper-feminine female partner, the same-sex couple draws attention to the fact that the male ballroom dancer is not dancing as a man but in accordance with ballroom’s queer construction of masculinity. Given that performance-level dance has struggled for so many years to be viewed as masculine sport, practitioners may, quite understandably, be anxious about any representation which suggests that ballroom dance may be an effeminate activity