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An enhanced dynamic ID-based authentication scheme for telecare medical information systems
No full textAbstractThe authentication schemes for telecare medical information systems (TMIS) try to ensure secure and authorized access. ID-based authentication schemes address secure communication, but privacy is not properly addressed. In recent times, dynamic ID-based remote user authentication schemes for TMIS have been presented to protect user’s privacy. The dynamic ID-based authentication schemes efficiently protect the user’s privacy. Unfortunately, most of the existing dynamic ID-based authentication schemes for TMIS ignore the input verifying condition. This makes login and password change phases inefficient. Inefficiency of the password change phase may lead to denial of service attack in the case of incorrect input in the password change phase. To overcome these weaknesses, we proposed a new dynamic ID-based authentication scheme using a smart card. The proposed scheme can quickly detect incorrect inputs which makes the login and password change phase efficient. We adopt the approach with the aim to protect privacy, and efficient login and password change phases. The proposed scheme also resists off-line password guessing attack and denial of service attack. We also demonstrate the validity of the proposed scheme by utilizing the widely-accepted BAN (Burrows, Abadi, and Needham) logic. In addition, our scheme is comparable in terms of the communication and computational overheads with relevant schemes for TMIS
Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model
No full textAbstractCurrently, there is no registered treatment for infections with emerging zoonotic coronaviruses like SARS- and MERS-coronavirus. We here report that in cultured cells low-micromolar concentrations of alisporivir, a non-immunosuppressive cyclosporin A-analog, inhibit the replication of four different coronaviruses, including MERS- and SARS-coronavirus. Ribavirin was found to further potentiate the antiviral effect of alisporivir in these cell culture-based infection models, but this combination treatment was unable to improve the outcome of SARS-CoV infection in a mouse model. Nevertheless, our data provide a basis to further explore the potential of Cyp inhibitors as host-directed, broad-spectrum inhibitors of coronavirus replication
Access to the substituted benzyl-1,2,3-triazolyl hesperetin derivatives expressing antioxidant and anticancer effects
No full textAbstractAzide–alkyne cycloaddition was attempted to generate a flavanone hesperetin based phenyl substituted 1,2,3-triazolyls as semi-synthetic natural product derivatives utilizing copper-catalyzed click chemistry. All final compounds were analyzed for their in vitro antioxidant abilities using DPPH and ABTS bioassay. Moreover, cancerous cell inhibitory prospect of titled compounds was screened against cervical cancer cell lines, HeLa and CaSki and an ovarian cancer cell line SK-OV-3 implementing SRB assay. Bearable toxicity of 6a-s was examined employing Madin–Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-s indicated remarkable antioxidant power in scavenging DPPH and ABTS+; particularly, an analog 6o with meta-methoxy substituent showed most potent radical scavenging activity, whereas scaffolds 6d with para-fluoro, 6k with ortho-methyl, and 6o with meta-methoxy performed excellently in inhibiting both the cervical cancer cell lines and analog 6q with meta-trifluoromethyl substituent expressed excellent sensitivity toward ovarian cancer cell line. From the structure–activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the phenyl ring attached to the triazole core may contribute to the anticipated antioxidant and anticancer action. Structure of final compounds was adequately confirmed exploring different spectroscopic techniques and elemental analysis in addition to the measurements of some physical properties
Safety of total laparoscopic modified radical hysterectomy with or without lymphadenectomy for endometrial cancer
No full textAbstractStudy objectiveIn order to reduce the risk of vaginal recurrence, we have chosen total laparoscopic modified radical hysterectomy instead of extrafascial hysterectomy in the treatment of endometrial cancer. The aim of this study was to assess the safety of this method.DesignRetrospective study of gynecological patients.SettingYokohama City University Medical Center, Yokohama, Japan.PatientsForty-nine patients who underwent total laparoscopic modified radical hysterectomy for the treatment of endometrial cancer at our hospital between December 2011 and September 2015.InterventionsTotal laparoscopic modified radical hysterectomy + bilateral salpingo-oophorectomy (n = 20), total laparoscopic modified radical hysterectomy + bilateral salpingo-oophorectomy + pelvic lymphadenectomy (n=18), or total laparoscopic modified radical hysterectomy + bilateral salpingo-oophorectomy + pelvic and para-aortic lymphadenectomy (n=11).Measurements and Main ResultsThe surgical outcomes were analyzed and compared to previous reports. The median operative time was 204 minutes (range, 99–504 minutes) and the median intraoperative blood loss was 150 mL (range, 0–680 mL). No patients needed a blood transfusion, conversion to laparotomy, or reoperation. Intra- and postoperative complications were observed in three patients and nine patients, respectively. The amount of blood loss and the incidence of complications in our study were almost identical to previous reports of laparoscopic hysterectomy. The operative time in our study was equivalent to previous reports of total laparoscopic modified radical hysterectomy.ConclusionTotal laparoscopic modified radical hysterectomy is safe and feasible for the treatment of early stage endometrial cancer. This procedure can be an alternative to total laparoscopic hysterectomy, especially when the uterus must be removed completely
The Shared Socioeconomic Pathways and their energy, land use, and greenhouse gas emissions implications: An overview
No full textAbstractThis paper presents the overview of the Shared Socioeconomic Pathways (SSPs) and their energy, land use, and emissions implications. The SSPs are part of a new scenario framework, established by the climate change research community in order to facilitate the integrated analysis of future climate impacts, vulnerabilities, adaptation, and mitigation. The pathways were developed over the last years as a joint community effort and describe plausible major global developments that together would lead in the future to different challenges for mitigation and adaptation to climate change. The SSPs are based on five narratives describing alternative socio-economic developments, including sustainable development, regional rivalry, inequality, fossil-fueled development, and middle-of-the-road development. The long-term demographic and economic projections of the SSPs depict a wide uncertainty range consistent with the scenario literature. A multi-model approach was used for the elaboration of the energy, land-use and the emissions trajectories of SSP-based scenarios. The baseline scenarios lead to global energy consumption of 400–1200 EJ in 2100, and feature vastly different land-use dynamics, ranging from a possible reduction in cropland area up to a massive expansion by more than 700 million hectares by 2100. The associated annual CO2 emissions of the baseline scenarios range from about 25 GtCO2 to more than 120 GtCO2 per year by 2100. With respect to mitigation, we find that associated costs strongly depend on three factors: (1) the policy assumptions, (2) the socio-economic narrative, and (3) the stringency of the target. The carbon price for reaching the target of 2.6W/m2 that is consistent with a temperature change limit of 2°C, differs in our analysis thus by about a factor of three across the SSP marker scenarios. Moreover, many models could not reach this target from the SSPs with high mitigation challenges. While the SSPs were designed to represent different mitigation and adaptation challenges, the resulting narratives and quantifications span a wide range of different futures broadly representative of the current literature. This allows their subsequent use and development in new assessments and research projects. Critical next steps for the community scenario process will, among others, involve regional and sectoral extensions, further elaboration of the adaptation and impacts dimension, as well as employing the SSP scenarios with the new generation of earth system models as part of the 6th climate model intercomparison project (CMIP6)
Chondroitin sulfate proteoglycans from salmon nasal cartilage inhibit angiogenesis
No full textAbstractBecause cartilage lacks nerves, blood vessels, and lymphatic vessels, it is thought to contain factors that inhibit the growth and development of those tissues. Chondroitin sulfate proteoglycans (CSPGs) are a major extracellular component in cartilage. CSPGs contribute to joint flexibility and regulate extracellular signaling via their attached glycosaminoglycan, chondroitin sulfate (CS). CS and CSPG inhibit axonal regeneration; however, their role in blood vessel formation is largely unknown. To clarify the function of CSPG in blood vessel formation, we tested salmon nasal cartilage proteoglycan (PG), a member of the aggrecan family of CSPG, for endothelial capillary-like tube formation. Treatment with salmon PG inhibited endothelial cell adhesion and in vitro tube formation. The anti-angiogenic activity was derived from CS in the salmon PG but not the core protein. Salmon PG also reduced matrix metalloproteinase expression and inhibited angiogenesis in the chick chorioallantoic membrane. All of these data support an anti-angiogenic role for CSPG in cartilage
c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium
No full textAbstractM cells reside within the follicle-associated epithelium (FAE) overlying the gut-associated lymphoid tissues. These unique phagocytic epithelial cells enable the mucosal immune system to sample antigens within the lumen of the intestine. The differentiation of M cells from uncommitted precursors in the FAE is dependent on the production of receptor activator of nuclear factor-κB ligand (RANKL) by subepithelial stromal cells. The ligation of a variety of cell surface receptors activates the nuclear factor-κB (NF-κB) family of transcription factors which in-turn induce the transcription of multiple target genes. RANKL-stimulation can stimulate the nuclear translocation of the NF-κB subunit c-Rel. We therefore used c-Rel-deficient mice to determine whether the differentiation and functional maturation of M cells in the Peyer’s patches was dependent on c-Rel. Our data show that c-Rel-deficiency does not influence the expression of RANKL or RANK in Peyer’s patches, or the induction of M-cell differentiation in the FAE. RANKL-stimulation in the differentiating M cells induces the expression of SpiB which is essential for their subsequent maturation. However, SpiB expression in the FAE was also unaffected in the absence of c-Rel. As a consequence, the functional maturation of M cells was not impaired in the Peyer’s patches of c-Rel-deficient mice. Although our data showed that the specific expression of CCL20 and ubiquitin D in the FAE was not impeded in the absence of c-Rel, the expression of ubiquitin D was dramatically reduced in the B cell-follicles of c-Rel-deficient mice. Coincident with this, we also observed that the status of follicular dendritic cells in the B cell-follicles was dramatically reduced in Peyer’s patches from c-Rel-deficient mice. Taken together, our data show that c-Rel is dispensable for the RANKL-mediated differentiation and functional maturation of M cells
Lifitegrast for the Treatment of Dry Eye Disease Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3)
No full textPurposeLifitegrast is a lymphocyte function–associated antigen-1 antagonist developed to reduce inflammation in dry eye disease (DED). We report the results of OPUS-3 (NCT02284516), a phase III study evaluating the efficacy and safety of lifitegrast versus placebo in participants with DED.DesignTwelve-week, phase III, randomized, double-masked, multicenter, placebo-controlled study.ParticipantsAdults aged ≥18 years with Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, corneal fluorescein staining score ≥2.0 (0–4 scale), eye dryness score (EDS) ≥40 (0–100 visual analogue scale [VAS]), and history of artificial tear use within 30 days of study entry.MethodsAfter a 14-day placebo run-in, participants were randomized 1:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days.Main Outcome MeasuresThe primary efficacy end point was change from baseline to day 84 in EDS. Key secondary efficacy end points were change from baseline to days 42 and 14 in EDS. Other secondary efficacy end points included additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photophobia, pain), ocular discomfort score (ODS), and safety/tolerability of lifitegrast versus placebo.ResultsIn the study, 711 participants were randomized: placebo, 356; lifitegrast, 355 (intention-to-treat [ITT] population). At day 84, lifitegrast-treated participants experienced significantly greater improvement from baseline in EDS versus those receiving placebo (treatment effect [TE], 7.16; 95% confidence interval [CI], 3.04–11.28; P = 0.0007). Mean changes from baseline in EDS also significantly favored lifitegrast on days 42 (TE, 9.32; 95% CI, 5.44–13.20; P < 0.0001) and 14 (TE, 7.85; 95% CI, 4.33–11.37; P < 0.0001). No statistically significant differences were observed in ODS between treatment groups at days 84, 42, or 14. A greater improvement was observed in lifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (nominal P = 0.0418), and eye discomfort (P = 0.0048) versus participants receiving placebo. Most treatment-emergent adverse events were mild to moderate in severity; no serious ocular adverse events were reported.ConclusionsLifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated
Low-field 1H NMR spectroscopy for distinguishing between arabica and robusta ground roast coffees
No full textAbstractThis work reports a new screening protocol for addressing issues of coffee authenticity using low-field (60MHz) bench-top 1H NMR spectroscopy. Using a simple chloroform-based extraction, useful spectra were obtained from the lipophilic fraction of ground roast coffees. It was found that 16-O-methylcafestol (16-OMC, a recognized marker compound for robusta beans) gives rise to an isolated peak in the 60MHz spectrum, which can be used as an indicator of the presence of robusta beans in the sample. A total of 81 extracts from authenticated coffees and mixtures were analysed, from which the detection limit of robusta in arabica was estimated to be between 10% and 20% w/w. Using the established protocol, a surveillance exercise was conducted of 27 retail samples of ground roast coffees which were labelled as “100% arabica”. None were found to contain undeclared robusta content above the estimated detection limit
Magmatic Cu-Ni-PGE-Au sulfide mineralisation in alkaline igneous systems: An example from the Sron Garbh intrusion, Tyndrum, Scotland
No full textAbstractMagmatic sulfide deposits typically occur in ultramafic-mafic systems, however, mineralisation can occur in more intermediate and alkaline magmas. Sron Garbh is an appinite-diorite intrusion emplaced into Dalradian metasediments in the Tyndrum area of Scotland that hosts magmatic Cu-Ni-PGE-Au sulfide mineralisation in the appinitic portion. It is thus an example of magmatic sulfide mineralisation hosted by alkaline rocks, and is the most significantly mineralised appinitic intrusion known in the British Isles. The intrusion is irregularly shaped, with an appinite rim, comprising amphibole cumulates classed as vogesites. The central portion of the intrusion is comprised of unmineralised, but pyrite-bearing, diorites. Both appinites and diorites have similar trace element geochemistry that suggests the diorite is a more fractionated differentiate of the appinite from a common source that can be classed with the high Ba-Sr intrusions of the Scottish Caledonides. Mineralisation is present as a disseminated, primary chalcopyrite-pyrite-PGM assemblage and a blebby, pyrite-chalcopyrite assemblage with significant Co-As-rich pyrite. Both assemblages contain minor millerite and Ni-Co-As-sulfides. The mineralisation is Cu-, PPGE-, and Au-rich and IPGE-poor and the platinum group mineral assemblage is overwhelmingly dominated by Pd minerals; however, the bulk rock Pt/Pd ratio is around 0.8. Laser ablation analysis of the sulfides reveals that pyrite and the Ni-Co-sulfides are the primary host for Pt, which is present in solid solution in concentrations of up to 22ppm in pyrite. Good correlations between all base and precious metals indicate very little hydrothermal remobilisation of metals despite some evidence of secondary pyrite and PGM. Sulfur isotope data indicate some crustal S in the magmatic sulfide assemblages. The source of this is unlikely to have been the local quartzites, but S-rich Dalradian sediments present at depth. The generation of magmatic Cu-Ni-PGE-Au mineralisation at Sron Garbh can be attributed to post-collisional slab drop off that allowed hydrous, low-degree partial melting to take place that produced a Cu-PPGE-Au-enriched melt, which ascended through the crust, assimilating crustal S from the Dalradian sediments. The presence of a number of PGE-enriched sulfide occurrences in appinitic intrusions across the Scottish Caledonides indicates that the region contains certain features that make it more prospective than other alkaline provinces worldwide, which may be linked the post-Caledonian slab drop off event. We propose that the incongruent melting of pre-existing magmatic sulfides or ‘refertilised’ mantle in low-degree partial melts can produce characteristically fractionated, Cu-PPGE-Au-semi metal bearing, hydrous, alkali melts, which, if they undergo sulfide saturation, have the potential to produce alkaline-hosted magmatic sulfide deposits