1,053 research outputs found
Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.
Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5) bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines
Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with the ceramide analogue LCL29. Evidence from mouse squamous cell carcinomas
Photodynamic therapy (PDT) has been proven effective for treatment of several types of cancer. Photodynamic therapy alone, however, attains limited cures with some tumours and there is need for its improved efficacy in such cases. Sphingolipid (SL) analogues can promote tumour response in combination with anticancer drugs. In this study, we used mouse SCCVII squamous cell carcinoma tumours to determine the impact of Photofrin-PDT on the in vivo SL profile and the effect of LCL29, a C6-pyridinium ceramide, on PDT tumour response. Following PDT, the levels of dihydroceramides (DHceramides), in particular C20-DHceramide, were elevated in tumours. Similarly, increases in DHceramides, in addition to C20:1-ceramide, were found in PDT-treated SCCVII cells. These findings indicate the importance of the de novo ceramide pathway in Photofrin-PDT response not only in cells but also in vivo. Notably, co-exposure of SCCVII tumours to Photofrin-PDT and LCL29 led to enhanced tumour response compared with PDT alone. Thus, we show for the first time that Photofrin-PDT has a distinct signature effect on the SL profile in vitro and in vivo, and that the combined treatment advances PDT therapeutic gain, implying translational significance of the combination
Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer
<p>Abstract</p> <p>Background</p> <p>In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy.</p> <p>Methods</p> <p>Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. <it>p </it>values < 0.05 were considered to indicate statistical significance.</p> <p>Results</p> <p>Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter.</p> <p>Conclusion</p> <p>Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.</p
Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at TeV
Inclusive transverse momentum spectra of primary charged particles in Pb-Pb
collisions at = 2.76 TeV have been measured by the ALICE
Collaboration at the LHC. The data are presented for central and peripheral
collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross
section. The measured charged particle spectra in and GeV/ are compared to the expectation in pp collisions at the same
, scaled by the number of underlying nucleon-nucleon
collisions. The comparison is expressed in terms of the nuclear modification
factor . The result indicates only weak medium effects ( 0.7) in peripheral collisions. In central collisions,
reaches a minimum of about 0.14 at -7GeV/ and increases
significantly at larger . The measured suppression of high- particles is stronger than that observed at lower collision energies,
indicating that a very dense medium is formed in central Pb-Pb collisions at
the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98
Trends of obesity and abdominal obesity in Tehranian adults: a cohort study
<p>Abstract</p> <p>Background</p> <p>Considering the increasing trend of obesity reported in current data, this study was conducted to examine trends of obesity and abdominal obesity among Tehranian adults during a median follow-up of 6.6 years.</p> <p>Methods</p> <p>Height and weight of 4402 adults, aged 20 years and over, participants of the Tehran Lipid and Glucose Study (TLGS), were measured in 1999-2001(phase I) and again in 2002-2005(phase II) and 2006-2008 (phase III). Criteria used for obesity and abdominal obesity defined body mass index (BMI) ⼠30 and waist circumference ⼠94/80 cm for men/women respectively. Subjects were divided into10-year groups and the prevalence of obesity was compared across sex and age groups.</p> <p>Results</p> <p>The prevalence of obesity was 15.8, 18.6 and 21% in men and 31.5, 37.7 and 38.6% in women in phases I, II and III respectively (p < 0.001). The prevalence of abdominal obesity in men was 36.5, 57.2 and 63.3% and in women was 76.7, 83.8 and 83.6% in the three periods mentioned (p < 0.001). Men aged between 20-29 years had highest increase rates of obesity and abdominal obesity in phase III in comparison with phase I (with a respective rates of 2.2- and 3.3-fold). In both sexes, an increased trend was observed between phases I and II, whereas between phases II and III, this trend was observed in men, but not in women.</p> <p>Conclusion</p> <p>This study demonstrates alarming rises in the prevalences of both obesity and abdominal obesity in both sexes especially in young men, calling for urgent action to educate people in lifestyle modifications.</p
Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System
Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis
Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV
The inclusive cross section for production of isolated photons has been
measured in \pbarp collisions at GeV with the \D0 detector at
the Fermilab Tevatron Collider. The photons span a transverse energy ()
range from 7-49 GeV and have pseudorapidity . This measurement is
combined with to previous \D0 result at GeV to form a ratio
of the cross sections. Comparison of next-to-leading order QCD with the
measured cross section at 630 GeV and ratio of cross sections show satisfactory
agreement in most of the range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001
Two-pion Bose-Einstein correlations in central Pb-Pb collisions at = 2.76 TeV
The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb
collisions at TeV at the Large Hadron Collider is
presented. We observe a growing trend with energy now not only for the
longitudinal and the outward but also for the sideward pion source radius. The
pion homogeneity volume and the decoupling time are significantly larger than
those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/388
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
X-ray emission from the Sombrero galaxy: discrete sources
We present a study of discrete X-ray sources in and around the
bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival
Chandra observations with a total exposure of ~200 ks. With a detection limit
of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30
kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler
et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS
observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray
binaries (LMXBs). We quantify the differential luminosity functions (LFs) for
both the detected GC and field LMXBs, whose power-low indices (~1.1 for the
GC-LF and ~1.6 for field-LF) are consistent with previous studies for
elliptical galaxies. With precise sky positions of the GCs without a detected
X-ray source, we further quantify, through a fluctuation analysis, the GC LF at
fainter luminosities down to 1E35 erg/s. The derived index rules out a
faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent
findings in several elliptical galaxies and the bulge of M31. On the other
hand, the 2-6 keV unresolved emission places a tight constraint on the field
LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101
sources in the halo of Sombrero. The presence of these sources cannot be
interpreted as galactic LMXBs whose spatial distribution empirically follows
the starlight. Their number is also higher than the expected number of cosmic
AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray
surveys. We suggest that either the cosmic X-ray background is unusually high
in the direction of Sombrero, or a distinct population of X-ray sources is
present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres
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