847 research outputs found
Rapid Progression of Low-Grade Cervical Dysplasia into Invasive Cancer during Natalizumab Treatment for Relapsing Remitting Multiple Sclerosis
A 25-year-old patient treated for relapsing remitting multiple sclerosis (RRMS) with natalizumab had a rapid progression of a low grade squamous intraepithelial lesion to a FIGO stage 1B1 squamous cell carcinoma of the uterine cervix within 2 years. She was treated with radical hysterectomy and pelvic lymphadenectomy and subsequently developed a vault recurrence within 2 years. The recurrence was treated with definitive synchronous chemo-radiotherapy and she has been disease free for 7 years. This case and existing evidence on increased risk of developing cervical dysplasia under natalizumab show that MS patients under immunosuppressive therapy require close annual cervical screening with immediate investigation of abnormal test results
Composition and luminescence studies of InGaN epilayers grown at different hydrogen flow rates
Indium gallium nitride (In(x)Ga(1-x)N) is a technologically important material for many optoelectronic devices, including LEDs and solar cells, but it remains a challenge to incorporate high levels of InN into the alloy while maintaining sample quality. A series of InGaN epilayers was grown with different hydrogen flow rates (0-200 sccm) and growth temperatures (680-750 °C) to obtain various InN fractions and bright emission in the range 390-480 nm. These 160-nm thick epilayers were characterized through several compositional techniques (wavelength dispersive x-ray spectroscopy, x-ray diffraction, Rutherford backscattering spectrometry) and cathodoluminescence hyperspectral imaging. The compositional analysis with the different techniques shows good agreement when taking into account compositional gradients evidenced in these layers. The addition of small amounts of hydrogen to the gas flow at lower growth temperatures is shown to maintain a high surface quality and luminescence homogeneity. This allowed InN fractions of up to ~16% to be incorporated with minimal peak energy variations over a mapped area while keeping a high material quality
MALDI Imaging Mass Spectrometry (MALDI-IMS)âApplication of Spatial Proteomics for Ovarian Cancer Classification and Diagnosis
MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review
In-House Packed Porous Graphitic Carbon Columns for Liquid Chromatography-Mass Spectrometry Analysis of N-Glycans
Protein glycosylation is a common post-translational modification that modulates biological processes such as the immune response and protein trafficking. Altered glycosylation profiles are associated with cancer and inflammatory diseases, as well as impacting the efficacy of therapeutic monoclonal antibodies. Consisting of oligosaccharides attached to asparagine residues, enzymatically released N-linked glycans are analytically challenging due to the diversity of isomeric structures that exist. A commonly used technique for quantitative N-glycan analysis is liquid chromatography-mass spectrometry (LC-MS), which performs glycan separation and characterization. Although many reversed and normal stationary phases have been utilized for the separation of N-glycans, porous graphitic carbon (PGC) chromatography has become desirable because of its higher resolving capability, but is difficult to implement in a robust and reproducible manner. Herein, we demonstrate the analytical properties of a 15 cm fused silica capillary (75 ¾m i.d., 360 ¾m o.d.) packed in-house with Hypercarb PGC (3 ¾m) coupled to an Agilent 6550 Q-TOF mass spectrometer for N-glycan analysis in positive ion mode. In repeatability and intermediate precision measurements conducted on released N-glycans from a glycoprotein standard mixture, the majority of N-glycans reported low coefficients of variation with respect to retention times (â¤4.2%) and peak areas (â¤14.4%). N-glycans released from complex samples were also examined by PGC LC-MS. A total of 120 N-glycan structural and compositional isomers were obtained from formalin-fixed paraffin-embedded ovarian cancer tissue sections. Finally, a comparison between early- and late-stage formalin-fixed paraffin-embedded ovarian cancer tissues revealed qualitative changes in the Îą2,3- and Îą2,6-sialic acid linkage of a fucosylated bi-antennary complex N-glycan. Although the Îą2,3-linkage was predominant in late-stage ovarian cancer, the alternate Îą2,6-linkage was more prevalent in early-stage ovarian cancer. This study establishes the utility of in-house packed PGC columns for the robust and reproducible LC-MS analysis of N-glycans
Exploring the Immunoproteome for Ovarian Cancer Biomarker Discovery
Most scientific efforts towards early detection of ovarian cancer are commonly focused on the discovery of tumour-associated antigens (TAA). Autologous antibodies against TAA, however, may serve as more sensitive diagnostic markers. They circulate in the blood before TAA and are usually more abundant than the TAAs themselves as a result of amplification through the humoral immune response. Accumulating evidence also suggests that a humoral response already exists during malignant transformation when aberrant gene expression is translated into premalignant cellular changes. This article reviews the current knowledge about autoantibodies against TAA in ovarian cancer and presents current immunoproteomic approaches for their detection
Measurements of branching fraction ratios and CP-asymmetries in suppressed B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^- decays
We report the first reconstruction in hadron collisions of the suppressed
decays B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^-, sensitive to the
CKM phase gamma, using data from 7 fb^-1 of integrated luminosity collected by
the CDF II detector at the Tevatron collider. We reconstruct a signal for the
B^- -> D(-> K^+ pi^-)K^- suppressed mode with a significance of 3.2 standard
deviations, and measure the ratios of the suppressed to favored branching
fractions R(K) = [22.0 \pm 8.6(stat)\pm 2.6(syst)]\times 10^-3, R^+(K) =
[42.6\pm 13.7(stat)\pm 2.8(syst)]\times 10^-3, R^-(K)= [3.8\pm 10.3(stat)\pm
2.7(syst]\times 10^-3, as well as the direct CP-violating asymmetry A(K) =
-0.82\pm 0.44(stat)\pm 0.09(syst) of this mode. Corresponding quantities for
B^- -> D(-> K^+ pi^-)pi^- decay are also reported.Comment: 8 pages, 1 figure, accepted by Phys.Rev.D Rapid Communications for
Publicatio
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
Search for anomalous t t-bar production in the highly-boosted all-hadronic final state
A search is presented for a massive particle, generically referred to as a
Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are
sufficiently massive to produce highly Lorentz-boosted top quarks, which yield
collimated decay products that are partially or fully merged into single jets.
The analysis uses new methods to analyze jet substructure, providing
suppression of the non-top multijet backgrounds. The analysis is based on a
data sample of proton-proton collisions at a center-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits
in the range of 1 pb are set on the product of the production cross section and
branching fraction for a topcolor Z' modeled for several widths, as well as for
a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any
enhancement in t t-bar production beyond expectations of the standard model for
t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version
includes a minor typo correction that will be submitted as an erratu
Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV
A search for new physics is presented based on an event signature of at least
three jets accompanied by large missing transverse momentum, using a data
sample corresponding to an integrated luminosity of 36 inverse picobarns
collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector
at the LHC. No excess of events is observed above the expected standard model
backgrounds, which are all estimated from the data. Exclusion limits are
presented for the constrained minimal supersymmetric extension of the standard
model. Cross section limits are also presented using simplified models with new
particles decaying to an undetected particle and one or two jets
Combined search for the quarks of a sequential fourth generation
Results are presented from a search for a fourth generation of quarks
produced singly or in pairs in a data set corresponding to an integrated
luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in
2011. A novel strategy has been developed for a combined search for quarks of
the up and down type in decay channels with at least one isolated muon or
electron. Limits on the mass of the fourth-generation quarks and the relevant
Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a
simple extension of the standard model with a sequential fourth generation of
fermions. The existence of mass-degenerate fourth-generation quarks with masses
below 685 GeV is excluded at 95% confidence level for minimal off-diagonal
mixing between the third- and the fourth-generation quarks. With a mass
difference of 25 GeV between the quark masses, the obtained limit on the masses
of the fourth-generation quarks shifts by about +/- 20 GeV. These results
significantly reduce the allowed parameter space for a fourth generation of
fermions.Comment: Replaced with published version. Added journal reference and DO
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