Simulations of a Line W-based observing system for the Atlantic meridional overturning circulation

In a series of observing system simulations, we test whether the Atlantic meridional overturning circulation (AMOC) can be observed based on the existing Line W deep western boundary array. We simulate a Line W array, which is extended to the surface and to the east to cover the basin to the Bermuda Rise. In the analyzed ocean circulation model ORCA025, such an extended Line W array captures the main characteristics of the western boundary current. Potential trans-basin observing systems for the AMOC are tested by combining the extended Line W array with a mid-ocean transport estimate obtained from thermal wind "measurements" and Ekman transport to the total AMOC (similarly to Hirschi et al., Geophys Res Lett 30(7):1413, 2003). First, we close Line W zonally supplementing the western boundary array with several "moorings" in the basin (Line W-32A degrees N). Second, we supplement the western boundary array with a combination of observations at Bermuda and the eastern part of the RAPID array at 26A degrees N (Line W-B-RAPID). Both, a small number of density profiles across the basin and also only sampling the eastern and western boundary, capture the variability of the AMOC at Line W-32A degrees N and Line W-B-RAPID. In the analyzed model, the AMOC variability at both Line W-32A degrees N and Line W-B-RAPID is dominated by the western boundary current variability. Away from the western boundary, the mid-ocean transport (east of Bermuda) shows no significant relation between the two Line W-based sections and 26A degrees N. Hence, a Line W-based AMOC estimate could yield an estimate of the meridional transport that is independent of the 26A degrees N RAPID estimate. The model-based observing system simulations presented here provide support for the use of Line W as a cornerstone for a trans-basin AMOC observing system

Hyaluronan Binding Motifs of USP17 and SDS3 Exhibit Anti-Tumor Activity

BACKGROUND: We previously reported that the USP17 deubiquitinating enzyme having hyaluronan binding motifs (HABMs) interacts with human SDS3 (suppressor of defective silencing 3) and specifically deubiquitinates Lys-63 branched polyubiquitination of SDS3 resulting in negative regulation of histone deacetylase (HDAC) activity in cancer cells. Furthermore, USP17 and SDS3 mutually interact with each other to block cell proliferation in HeLa cells but the mechanism for this inhibition in cell proliferation is not known. We wished to investigate whether the HABMs of USP17 were responsible for tumor suppression activity. METHODOLOGY/PRINCIPAL FINDINGS: Similarly to USP17, we have identified that SDS3 also has three consecutive HABMs and shows direct binding with hyaluronan (HA) using cetylpyridinium chloride (CPC) assay. Additionally, HA oligosaccharides (6-18 sugar units) competitively block binding of endogenous HA polymer to HA binding proteins. Thus, administration of HA oligosaccharides antagonizes the interaction between HA and USP17 or SDS3. Interestingly, HABMs deleted USP17 showed lesser interaction with SDS3 but retain its deubiquitinating activity towards SDS3. The deletion of HABMs of USP17 could not alter its functional regulation on SDS3-associated HDAC activity. Furthermore, to explore whether HABMs in USP17 and SDS3 are responsible for the inhibition of cell proliferation, we investigated the effect of USP17 and SDS3-lacking HABMs on cell proliferation by soft agar, apoptosis, cell migration and cell proliferation assays. CONCLUSIONS: Our results have demonstrated that these HABMs in USP17 and its substrate SDS3 are mainly involved in the inhibition of anchorage-independent tumor growth

Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

<p>Abstract</p> <p>Background</p> <p>Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.</p> <p>Methods</p> <p>The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.</p> <p>Results</p> <p>ECI carrying a chitobiose unit, ECI-(GlcNAc) ₂, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)₃(GlcNAc)₂], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)₂.</p> <p>Conclusions</p> <p>Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.</p

Mobile Phone Data for Children on the Move: Challenges and Opportunities

Today, 95% of the global population has 2G mobile phone coverage and the number of individuals who own a mobile phone is at an all time high. Mobile phones generate rich data on billions of people across different societal contexts and have in the last decade helped redefine how we do research and build tools to understand society. As such, mobile phone data has the potential to revolutionize how we tackle humanitarian problems, such as the many suffered by refugees all over the world. While promising, mobile phone data and the new computational approaches bring both opportunities and challenges. Mobile phone traces contain detailed information regarding people's whereabouts, social life, and even financial standing. Therefore, developing and adopting strategies that open data up to the wider humanitarian and international development community for analysis and research while simultaneously protecting the privacy of individuals is of paramount importance. Here we outline the challenging situation of children on the move and actions UNICEF is pushing in helping displaced children and youth globally, and discuss opportunities where mobile phone data can be used. We identify three key challenges: data access, data and algorithmic bias, and operationalization of research, which need to be addressed if mobile phone data is to be successfully applied in humanitarian contexts.Comment: 13 pages, book chapte

Healthcare Barriers of Refugees Post-resettlement

The majority of refugees spend the greater part of their lives in refugee camps before repatriation or resettlement to a host country. Limited resources and stress during residence in refugee camps can lead to a variety of acute and chronic diseases which often persist upon resettlement. However, for most resettled refugees little is known about their health needs beyond a health assessment completed upon entry. We conducted a qualitative pilot-study in San Diego County, the third largest area in California, USA for resettling refugees, to explore health care access issues of refugees after governmental assistance has ended. A total of 40 guided in-depth interviews were conducted with a targeted sample of informants (health care practitioners, employees of refugee serving organizations, and recent refugee arrivals) familiar with the health needs of refugees. Interviews revealed that the majority of refugees do not regularly access health services. Beyond individual issues, emerging themes indicated that language and communication affect all stages of health care access—from making an appointment to filling out a prescription. Acculturation presented increased stress, isolation, and new responsibilities. Additionally, cultural beliefs about health care directly affected refugees’ expectation of care. These barriers contribute to delayed care and may directly influence refugee short- and long-term health. Our findings suggest the need for additional research into contextual factors surrounding health care access barriers, and the best avenues to reduce such barriers and facilitate access to existing services

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis

Gender-related differences in physiologic color space: a functional transcranial Doppler (fTCD) study

Simultaneous color contrast and color constancy are memory processes associated with color vision, however, the gender-related differences of 'physiologic color space' remains unknown. Color processing was studied in 16 (8 men and 8 women) right-handed healthy subjects using functional transcranial Doppler (fTCD) technique. Mean flow velocity (MFV) was recorded in both right (RMCA) and left (LMCA) middle cerebral arteries in dark and white light conditions, and during color (blue and yellow) stimulations. The data was plotted in a 3D quadratic curve fit to derive a 'physiologic color space' showing the effects of luminance and chromatic contrasts. In men, wavelength-differencing of opponent pairs (yellow-blue) was adjudged by changes in the RMCA MFV for Yellow plotted on the Y-axis, and the RMCA MFV for Blue plotted on the X-axis. In women, frequency-differencing for opponent pairs (blue-yellow) was adjudged by changes in the LMCA MFV for Yellow plotted on the Y-axis, and the LMCA MFV for Blue plotted on the X-axis. The luminance effect on the LMCA MFV in response to white light with the highest luminous flux, was plotted on the (Z - axis), in both men and women. The 3D-color space for women was a mirror-image of that for men, and showed enhanced color constancy. The exponential function model was applied to the data in men, while the logarithmic function model was applied to the data in women. Color space determination may be useful in the study of color memory, adaptive neuroplasticity, cognitive impairment in stroke and neurodegenerative diseases

Quantitative Proteomic and Interaction Network Analysis of Cisplatin Resistance in HeLa Cells

Cisplatin along with other platinum based drugs are some of the most widely used chemotherapeutic agents. However drug resistance is a major problem for the successful chemotherapeutic treatment of cancer. Current evidence suggests that drug resistance is a multifactorial problem due to changes in the expression levels and activity of a wide number of proteins. A majority of the studies to date have quantified mRNA levels between drug resistant and drug sensitive cell lines. Unfortunately mRNA levels do not always correlate with protein expression levels due to post-transcriptional changes in protein abundance. Therefore global quantitative proteomics screens are needed to identify the protein targets that are differentially expressed in drug resistant cell lines. Here we employ a quantitative proteomics technique using stable isotope labeling with amino acids in cell culture (SILAC) coupled with mass spectrometry to quantify changes in protein levels between cisplatin resistant (HeLa/CDDP) and sensitive HeLa cells in an unbiased fashion. A total of 856 proteins were identified and quantified, with 374 displaying significantly altered expression levels between the cell lines. Expression level data was then integrated with a network of protein-protein interactions, and biological pathways to obtain a systems level view of proteome changes which occur with cisplatin resistance. Several of these proteins have been previously implicated in resistance towards platinum-based and other drugs, while many represent new potential markers or therapeutic targets