33 research outputs found

    Management and Outcome of Cardiac and Endovascular Cystic Echinococcosis

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    Cardiac and vascular involvement are infrequent in classical cystic echinococcosis (CE), but when they occur they tend to present earlier and are associated with complications that may be life threatening. Cardiovascular CE usually requires complex surgery, so in low-income countries the outcome is frequently fatal. This case series describes the characteristics of cardiovascular CE in patients diagnosed and treated at a Tropical Medicine & Clinical Parasitology Center in Spain. A retrospective case series of 11 patients with cardiac and/or endovascular CE, followed-up over a period of 15 years (1995–2009) is reported. The main clinical manifestations included thoracic pain or dyspnea, although 2 patients were asymptomatic. The clinical picture and complications vary according to cyst location. Isolated cardiac CE may be cured after surgery, while endovascular extracardiac involvement is associated with severe chronic complications. CE should be included in the differential diagnosis of cardiovascular disease in patients from endemic areas. CE is a neglected disease and further studies are necessary in order to make more definite management recommendations for this rare and severe form of the disease. The authors propose a general approach based on cyst location: exclusively cardiac, endovascular or both

    Oxidative protein labeling in mass-spectrometry-based proteomics

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    Oxidation of proteins and peptides is a common phenomenon, and can be employed as a labeling technique for mass-spectrometry-based proteomics. Nonspecific oxidative labeling methods can modify almost any amino acid residue in a protein or only surface-exposed regions. Specific agents may label reactive functional groups in amino acids, primarily cysteine, methionine, tyrosine, and tryptophan. Nonspecific radical intermediates (reactive oxygen, nitrogen, or halogen species) can be produced by chemical, photochemical, electrochemical, or enzymatic methods. More targeted oxidation can be achieved by chemical reagents but also by direct electrochemical oxidation, which opens the way to instrumental labeling methods. Oxidative labeling of amino acids in the context of liquid chromatography(LC)–mass spectrometry (MS) based proteomics allows for differential LC separation, improved MS ionization, and label-specific fragmentation and detection. Oxidation of proteins can create new reactive groups which are useful for secondary, more conventional derivatization reactions with, e.g., fluorescent labels. This review summarizes reactions of oxidizing agents with peptides and proteins, the corresponding methodologies and instrumentation, and the major, innovative applications of oxidative protein labeling described in selected literature from the last decade

    Observation of Gravitational Waves from a Binary Black Hole Merger

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    On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of 1.0 × 10−21. It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1σ. The source lies at a luminosity distance of 410þ160 −180 Mpc corresponding to a redshift z ¼ 0.09þ0.03 −0.04 . In the source frame, the initial black hole masses are 36þ5 −4M⊙ and 29þ4 −4M⊙, and the final black hole mass is 62þ4 −4M⊙, with 3.0þ0.5 −0.5M⊙c2 radiated in gravitational waves. All uncertainties define 90% credible intervals. These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger

    Binary Black Hole Mergers in the first Advanced LIGO Observing Run

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    The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers. In this paper we present full results from a search for binary black hole merger signals with total masses up to 100M100 M_\odot and detailed implications from our observations of these systems. Our search, based on general-relativistic models of gravitational wave signals from binary black hole systems, unambiguously identified two signals, GW150914 and GW151226, with a significance of greater than 5σ5\sigma over the observing period. It also identified a third possible signal, LVT151012, with substantially lower significance, which has a 87% probability of being of astrophysical origin. We provide detailed estimates of the parameters of the observed systems. Both GW150914 and GW151226 provide an unprecedented opportunity to study the two-body motion of a compact-object binary in the large velocity, highly nonlinear regime. We do not observe any deviations from general relativity, and place improved empirical bounds on several high-order post-Newtonian coefficients. From our observations we infer stellar-mass binary black hole merger rates lying in the range 9240Gpc3yr19-240 \mathrm{Gpc}^{-3} \mathrm{yr}^{-1}. These observations are beginning to inform astrophysical predictions of binary black hole formation rates, and indicate that future observing runs of the Advanced detector network will yield many more gravitational wave detections

    Search for Gravitational Waves Associated with Gamma-Ray Bursts during the First Advanced LIGO Observing Run and Implications for the Origin of GRB 150906B

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    We present the results of the search for gravitational waves (GWs) associated with γ-ray bursts detected during the first observing run of the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). We find no evidence of a GW signal for any of the 41 γ-ray bursts for which LIGO data are available with sufficient duration. For all γ-ray bursts, we place lower bounds on the distance to the source using the optimistic assumption that GWs with an energy of 102Mc2{10}^{-2}{M}_{\odot }{c}^{2} were emitted within the 1616500500 Hz band, and we find a median 90% confidence limit of 71 Mpc at 150 Hz. For the subset of 19 short/hard γ-ray bursts, we place lower bounds on distance with a median 90% confidence limit of 90 Mpc for binary neutron star (BNS) coalescences, and 150 and 139 Mpc for neutron star–black hole coalescences with spins aligned to the orbital angular momentum and in a generic configuration, respectively. These are the highest distance limits ever achieved by GW searches. We also discuss in detail the results of the search for GWs associated with GRB 150906B, an event that was localized by the InterPlanetary Network near the local galaxy NGC 3313, which is at a luminosity distance of 5454 Mpc (z = 0.0124). Assuming the γ-ray emission is beamed with a jet half-opening angle 30\leqslant 30^\circ , we exclude a BNS and a neutron star–black hole in NGC 3313 as the progenitor of this event with confidence >99%. Further, we exclude such progenitors up to a distance of 102 Mpc and 170 Mpc, respectively

    Localization and broadband follow-up of the gravitational-wave transient GW150914

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    A gravitational-wave transient was identified in data recorded by the Advanced LIGO detectors on 2015 September 14. The event candidate, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the gravitational wave data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network Circulars, giving an overview of the participating facilities, the gravitational wave sky localization coverage, the timeline and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the electromagnetic data and results of the electromagnetic follow-up campaign will be disseminated in the papers of the individual teams

    Highly pathogenic Avian Influenza virus A/H5N1 infection in vaccinated meat duck flocks in the Mekong delta of Vietnam

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    We investigated episodes of suspected highly pathogenic avian influenza (HPAI)-like illness among 12 meat duck flocks in two districts in Tien Giang province (Mekong Delta, Vietnam) in November 2013. In total, duck samples from 8 of 12 farms tested positive for HPAI virus subtype A/haemagglutinin 5 and neuraminidase 1 (H5N1) by real-time RT-PCR. Sequencing results confirmed clade of 2.3.2.1.c as the cause of the outbreaks. Most (7/8) laboratory-confirmed positive flocks had been vaccinated with inactivated HPAI H5N1 clade 2.3.4 vaccines <6 days prior to onset of clinical signs. A review of vaccination data in relation to estimated production in the area suggested that vaccination efforts were biased towards larger flocks and that vaccination coverage was low [21.2% ducks vaccinated with two shots (range by district 7.4-34.9%)]. The low-coverage data, the experimental evidence of lack of cross-protection conferred by the currently used vaccines based on clade 2.3.4 together with the short lifespan of meat duck flocks (60-70 days), suggest that vaccination is not likely to be effective as a tool for control of H5N1 infection in meat duck flocks in the area

    Bifunctional fused polypeptide inhibits the growth and metastasis of breast cancer

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    Ai-Ling Liang,1–3,* Hai-Li Qian,4,* Ting-Ting Zhang,1–3 Ning Zhou,1–3 Hai-Juan Wang,4 Xi-Ting Men,4 Wei Qi,5 Ping-Ping Zhang,6 Ming Fu,4 Xiao Liang,4 Chen Lin,4 Yong-Jun Liu1–3 1Medical Molecular Diagnostics Key Laboratory of Guangdong, 2Department of Biochemistry and Molecular Biology, 3Department of Clinical Biochemistry, Guangdong Medical University, Dongguan, Guangdong, 4State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, 5Electroencephalogram Room, 6Department of Orthopedics, Guangdong Medical University Affiliated Hospital, Zhanjiang, Guangdong, People’s Republic of China *These authors contributed equally to this study Abstract: Breast cancer is the most common cancer and the leading cause of cancer-related death among women worldwide, with urgent need to develop new therapeutics. Targeted therapy is a promising strategy for breast cancer therapy. Stromal-derived factor-1/CXC chemokine receptor 4 (CXCR4) has been implicated in the metastasis of breast cancer, which renders it to be therapeutic target. This study aimed to evaluate the anticancer effect of fused TAT–DV1–BH3 polypeptide, an antagonist of CXCR4, and investigate the underlying mechanism for the cancer cell-killing effect in the treatment of breast cancer in vitro and in vivo. This results in a potent inhibitory effect of fused TAT–DV1–BH3 polypeptide on tumor growth and metastasis in nude mice bearing established MDA-MB-231 tumors. Fused TAT–DV1–BH3 polypeptide inhibited the proliferation of MDA-MB-231 and MCF-7 cells but did not affect that of HEK-293 cells. The fused TAT–DV1–BH3 polypeptide colocalized with mitochondria and exhibited a proapoptotic effect through the regulation of caspase-9 and -3. Furthermore, the fused TAT–DV1–BH3 polypeptide suppressed the migration and invasion of the highly metastatic breast cancer cell line MDA-MB-231 in a concentration-dependent manner. Notably, the DV1-mediated inhibition of the stromal-derived factor-1/CXCR4 pathway contributed to the antimetastasis effect, evident from the reduction in the level of phosphoinositide 3 kinase and matrix metalloproteinase 9 in MDA-MB-231 cells. Collectively, these results indicate that the apoptosis-inducing effect and migration- and invasion-suppressing effect explain the tumor regression and metastasis inhibition in vivo, with the involvement of caspase- and CXCR4-mediated signaling pathway. The data suggest that the fused TAT–DV1–BH3 polypeptide is a promising agent for the treatment of breast cancer, and more studies are warranted to fully elucidate the therapeutic targets and molecular mechanism. Keywords: bifunctional, fused polypeptide, CXCR4, breast cancer, apoptosis, transfe
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