Search for Higher Flavor Multiplets in Partial Wave Analyses

The possible existence of higher multi-quark flavor multiplets of baryons is investigated. We argue that the S-matrix should have poles with any quantum numbers, including those which are exotic. This argument provides a novel justification for the existence of hadrons with arbitrary exotic structure. Though it does not constitute a proof, there are still no theoretical arguments against exotics. We then consider KN and piN scattering. Conventional and modified partial-wave analyses provide several sets of candidates for correlated pairs (Theta1, Delta), each of which could label a related 27-plet. Properties of the pairs (masses, mass orderings, spin-parity quantum numbers) do not quite correspond to the current theoretical expectations. Decay widths of the candidates are either wider or narrower than expected. Possible reasons for such disagreements are briefly discussed.Comment: 12 pages, 1 figure; v2: references corrected; v3: minor changes, to appear in Eur.Phys.J.

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

AbstractHirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene–gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/− mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children

Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach

Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic variants have been previously reported to be causative of, or associated with, an increased risk for various types of cancer. Here, we adopted a next-generation sequencing approach in 11 members of two families of Greek descent to identify all genomic variants with the potential to predispose family members to cancer. Cross-comparison with data from the Human Gene Mutation Database identified a total of 571 variants, from which 47 % were disease-associated polymorphisms, 26 % disease-associated polymorphisms with additional supporting functional evidence, 19 % functional polymorphisms with in vitro/laboratory or in vivo supporting evidence but no known disease association, 4 % putative disease-causing mutations but with some residual doubt as to their pathological significance, and 3 % disease-causing mutations. Subsequent analysis, focused on the latter variant class most likely to be involved in cancer predisposition, revealed two variants of prime interest, namely MSH2 c.2732T>A (p.L911R) and BRCA1 c.2955delC, the first of which is novel. KMT2D c.13895delC and c.1940C>A variants are additionally reported as incidental findings. The next-generation sequencing-based family genomics approach described herein has the potential to be applied to other types of complex genetic disorder in order to identify variants of potential pathological significance

Search for CP Violation in the decays D+ -> K_S pi+ and D+ -> K_S K+

A high statistics sample of photo-produced charm from the FOCUS(E831) experiment at Fermilab has been used to search for direct CP violation in the decays D+->K_S pi+ and D+ -> K_S K+. We have measured the following asymmetry parameters relative to D+->K-pi+pi+: A_CP(K_S pi+) = (-1.6 +/- 1.5 +/- 0.9)%, A_CP(K_S K+) = (+6.9 +/- 6.0 +/- 1.5)% and A_CP(K_S K+) = (+7.1 +/- 6.1 +/- 1.2)% relative to D+->K_S pi+. The first errors quoted are statistical and the second are systematic. We also measure the relative branching ratios: \Gamma(D+->\bar{K0}pi+)/\Gamma(D+->K-pi+pi+) = (30.60 +/- 0.46 +/- 0.32)%, \Gamma(D+->\bar{K0}K+)/\Gamma(D+->K-pi+pi+) = (6.04 +/- 0.35 +/- 0.30)% and \Gamma(D+->\bar{K0}K+)/\Gamma(D+->\bar{K0}pi+) = (19.96 +/- 1.19 +/- 0.96)%.Comment: 4 pages, 3 figure

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

A measurement of branching ratios of D+D^+ and Ds+D^+_s hadronic decays to four-body final states containing a KSK_S

We have studied hadronic four-body decays of $D^+$ and $D^+_s$ mesons with a $K_S$ in the final state using data recorded during the 1996-1997 fixed-target run at Fermilab high energy photoproduction experiment FOCUS. We report a new branching ratio measurement of $\Gamma(D^+\to K_S K^-\pi^+\pi^+)/\Gamma(D^+\to K_S \pi^+\pi^+\pi^-)=0.0768\pm0.0041\pm0.0032$. We make the first observation of three new decay modes with branching ratios $\Gamma(D^+\to K_S K^+\pi^+\pi^-)/\Gamma(D^+\to K_S \pi^+\pi^+\pi^-)=0.0562\pm0.0039\pm0.0040$, \Gamma(D^+\to\K_S K^+ K^-\pi^+)/\Gamma(D^+\to K_S \pi^+\pi^+\pi^-)=0.0077\pm0.0015\pm0.0009, and $\Gamma(D^+_s\to K_S K^+\pi^+\pi^-)/\Gamma(D^+_s\to K_S K^-\pi^+\pi^+)=0.586\pm0.052\pm0.043$, where in each case the first error is statistical and the second error is systematic.Comment: 4 pages, 1 table, 2 figures, submitted to Physical Review Letter

Search for Λc+→pK+π−\Lambda_c^+ \to p K^+ \pi^- and Ds+→K+K+π−D_s^+ \to K^+ K^+ \pi^- Using Genetic Programming Event Selection

We apply a genetic programming technique to search for the double Cabibbo suppressed decays $\Lambda_c^+ \to p K^+ \pi^-$ and $D_s^+ \to K^+ K^+ \pi^-$. We normalize these decays to their Cabibbo favored partners and find $\text{BR}($\Lambda_c^+ \to p K^+ \pi^-$)/\text{BR}($\Lambda_c^+ \to p K^- \pi^+$) = (0.05 \pm 0.26 \pm 0.02)$ and $\text{BR}($D_s^+ \to K^+ K^+ \pi^-$)/\text{BR}($D_s^+ \to K^+ K^- \pi^+$) = (0.52\pm 0.17\pm 0.11)$ where the first errors are statistical and the second are systematic. Expressed as 90% confidence levels (CL), we find $< 0.46$ and $< 0.78$ respectively. This is the first successful use of genetic programming in a high energy physics data analysis.Comment: 10 page

A High Statistics Measurement of the Lambdac+ Lifetime

A high statistics measurement of the Lambdac+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat.) +/- 2.5 (syst.) fs from 8034 +/- 122 Lambdac -> pKpi decays represents a significant improvement over the present world average.Comment: Submitted to Physical Review Letter