In the Southwest Oncology Group phase II study S0108, patients with relapsed, aggressive non-Hodgkin's lymphoma were treated with single agent bevacizumab (Avastin), a recombinant monoclonal antibody directed against VEGF. Pretreatment tissue or bone marrow specimens were examined by immunohistochemistry (IHC) for expression of VEGF and its receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR). Circulating endothelial cells (CEC) and plasma levels of VEGF, VCAM, and bFGF were measured at baseline, week 8, and at disease progression. Currently, 45 patients have been enrolled in the study and 18 have had baseline lymphoma specimens submitted and adequate for analysis by IHC for expression of VEGF and its receptors. In 7 of 10 (70%) patients with diffuse large cell lymphoma, the tumors expressed VEGF and either or both VEGF receptors. There was 100% concordance between VEGF and receptor expression in these samples. In 7of 8 (88%) mantle cell specimens examined, VEGF expression was also observed. Expression of both VEGFR-1 and VEGFR-2 was observed in 6 (67%) of these specimens. While VEGF and VEGFR-1 expression was restricted to the malignant cells, VEGFR-2 was predominantly expressed on the endothelial cells in the lymphoma specimens, and in those cases where it was also expressed by the tumor cells it was typically at lower intensity. In 1 of 5 patients with serial lymphoma specimens, VEGF expression increased in the lymphoma cells during the course of bevacizumab therapy. There was a wide range in the plasma levels of VEGF, bFGF, VCAM, and CEC between patients. During the course of treatment, plasma VEGF levels decreased (p = 0.02), VCAM levels increased (p = 0.05), and bFGF and CEC levels remained relatively stable. CEC, VCAM, and bFGF levels did not correlate with VEGF expression in lymphoma samples but there was a trend for lymphomas with higher VEGF expression (+2 or higher) to have higher baseline plasma levels of VEGF (median VEGF level 471 pg/ml compared to 224 pg/ml). Accrual of samples continues and the results will be updated as the analyses are available. The high rate of concordance between VEGF and its receptors in diffuse large cell and mantle cell lymphomas suggests that an autocrine pathway may be involved in lymphoma pathogenesis and/or progression. In addition, these results provide a strong rationale for targeting the VEGF pathway in the treatment of these 2 histologic subtypes of aggressive non-Hodgkin's lymphoma.


We have integrated the observational capability of satellite remote sensing with plot-scale tree-ring data to upscale the evaluation of forest responses to drought. Satellite data, such as the normalized difference vegetation index (NDVI), can provide a spatially continuous measure with limited temporal coverage, while tree-ring width index (RWI) provides an accurate assessment with a much longer time series at local scales. Here, we explored the relationship between RWI and NDVI of three dominant species in the Southwestern United States (SWUS) and predicted RWI spatial distribution from 2001 to 2017 based on Moderate Resolution Imaging Spectroradiometer (MODIS) 1-km resolution NDVI data with stringent quality control. We detected the optimum time windows (around June–August) during which the RWI and NDVI were most closely correlated for each species, when the canopy growth had the greatest effect on growth of tree trunks. Then, using our upscaling algorithm of NDVI-based RWI, we were able to detect the significant impact of droughts in 2002 and in 2011–2014, which supported the validity of this algorithm in quantifying forest response to drought on a large scale.


The effect of fatty acids, monoglycerides, diglycerides and triglycerides (present or able to be generated in human milk by lipase activity) on the growth of anaerobic Bifidobacterium bifidum types a and b, Bifidobacterium infantis sp. infantis types a and b, and facultative Escherichia coli and Salmonella typhimurium were determined turbidimetrically. The fatty acids and monoglycerides tested inhibited the growth of the Bifidobacteria while the gram-negative E. coli and S. typhimurium proved more resistant. Triglycerides were not inhibitory to the bacteria tested, with some actually enhancing growth. Monolaurin and 2-monopalmitin proved to be the most potent inhibitors of Bjfidobacteria growth in the concentration ranges used.


A quick way to understand the "reverse mortgage" is to take most of what you know about the traditional mortgage lending process and turn it around. When a bank makes a reverse mortgage--more officially known as a "home equity conversion mortgage "--it sends monthly checks to the borrower, rather than vice-versa. Credit evaluation is unnecessary, in part because the members of the target market likely don't have the income necessary to pay the loan back. And if your bank goes into this business, chances are it will have the field to itself, unlike the fiercely competitive first- and second-mortgage businesses. Equity line with a twist Reverse mortgages are aimed at senior citizens who are house-rich but cashpoor. The loans enable them to draw on the equity they've built up in their homes without having to leave it. Unlike a home equity loan or credit line, however, reverse mortgages don't have to be paid back on a current basis. The lender typically looks to the eventual sale of the home for repayment of both principal and interest, although repayment can come from other sources as well. The concept of reverse mortgages has been around for some time, with some private lenders, notably insurance companies, launching their own programs. However, the idea became institutionalized when the federal government launched a pilot program m 1988 and when the Federal National Mortgage Association began buying certain loans originated by lenders under the Federal Housing Administration's program. (Fannie Mae is developing a purchase program for "conventional" reverse mortgages-- those not insured by FHA. The organization expects to roll out the program in early 1995.) The FHA program is a pilot effort, originally intended to expire in 1991. In 1990 Congress extended the pilot to Sept. 30, 1995, and raised the number of loans FHA could insure under the program ten-fold, to 25,000. Approximately 12,000 loans had been made under the program as of midyear, according to HUD, and it's estimated that Fannie Mae has purchased about a third of these. The American Association of Retired Persons, a major booster of the reverse mortgage concept, believes signs are good that the FHA program will be extended, with some modifications. Bank participation Reverse mortgages in some form are available in 43 states, according to AARP. However, one estimate puts the number of active reverse mortgage lenders at about 60, and only a handful of these organizations are banks or affiliates of banking companies. Historically, not many banks have explored becoming FHA-approved lenders, fearing massive government paperwork. Likewise, many banks aren't approved Fannie Mae lenders, although they can participate through correspondent programs, such as one offered by Wendover Funding, Inc., Greensboro, N.C. The firm, a subsidiary of State Street Bank and Trust Co., Boston, is the leading servicer for institutions making loans under FHA's program. In addition, even banks that have gotten into the business say that making reverse mortgages is so different from run-of-the mill mortgages that the origination and processing become challenging. From the start, the prospect for this type of loan has to get used to the idea. The reverse mortgage "is in conflict with their historic values," says Howard J. Levine, president and CEO of ARCS Mortgage, Inc. Today's senior citizens "were brought up to pay off their mortgage." ARCS, based in Calabasas, Calif., is the mortgage banking arm of The Bank of New York and has made about 70 loans under the program. ARCS sells its originations to Fannie Mae, assigning servicing to Wendover Funding. One lender notes that some of these prospects appreciate the opportunity to be counselled by HUD-approved agencies, while others, considering themselves experienced in home finances, become aggravated over having to go through what they consider an unnecessary stage. …


A new calibration of an OsO/sub 4/ absolute frequency grid is reported with an uncertainty less than 100 Hz in the 28/29 THz range (/spl delta/v/v/spl sim/3/spl times/10/sup -17/). A precedent determination has been performed fifteen years before, with uncertainties ranging from 50 Hz to 2 kHz. These OsO/sub 4/ transitions confer high metrological performances to CO/sub 2/ lasers when frequency locked on the third harmonic of the saturated resonances. We report also recent results on the stability of the BNM-LPTF CO/sub 2//OsO/sub 4/ optical frequency standard in terms of short-term stability of 3/spl times/10/sup -14//spl tau//sup - 1/2 / and long term stability of 2.4/spl times/10/sup -15/ for 3000 s of integration time. This result corresponds, to our knowledge, to the best stability achieved, up to now, in the optical domain.


"Letter from Birmingham Jail" was written on April 16, 1963, by Martin Luther King, Jr., the famous civil rights leader. The 1960s in America is usually called a decade that changed a nation. Some important social reform movements took place during this period. And it is also a special period for intellectual history which includes these main streams of American thought, such as puritan Christianity, revolutionary rationalism, and transcendentalism, pragmatism. Based on a close reading and a detailed analysis of the letter, we can find the traces of the influence of the American thought on Martin Luther King.


The social sciences have been investigating the processes of public opinion formation since the second half of the 19th century. From Tocqueville to Le Bon, from Toennies to Allport, from Lazarsfeld to Habermas, from Niklas Luhmann to Pierre Bourdieu, from Noelle-Neumann to Landowski. Among these authors, Lippmann stands out for his theoretical-practical orientation that anticipated themes and methodologies. Exactly one hundred years ago, in his best-known work Public Opinion (Lippmann 1922) he had opened the way to the inevitability of the construction of a world 'beyond the real', through the concept of 'pseudo-environment'.
The need for representation determines 'pseudo-environments', interstitial realities made up of stereotyped images and contents that the public interprets to construct shared imaginaries that do not adhere to reality: "The world outside and the picture in your head" (Lippmann 1992: 3).
Pseudo-environments enable decision-making and action, reducing complexity (Luhmann e De Giorgi 1992). This phenomenon anticipates the paradigm of hyper-reality, in the sense of Braudillard (1985), but also that of Second Life and the Meta-verse in the sense of Stephenson (1992).
Starting from Lippmann's vision, this proposed paper intends to recontextualize his thought in the light of the most recent theories of communication.


This chapter presents a comprehensive revision of the Helicellinae of Crete (Gastropoda: Hygromiidae) based on characters of the shell and the genitalia. The native fauna includes eleven Xerocrassa species, two Pseudoxerophila species and perhaps one Xeromunda species. One additional Xerocrassa species and six species of the genera Trochoidea, Xeropicta, Xerotricha, Microxeromagna and Cernuella were probably introduced by man to Crete. The distribution patterns of the endemic Xerocrassa and Pseudoxerophila species do not provide evidence for the hypothesis that these radiations were caused by the fragmentation of the region of present-day Crete into several palaeoislands in the late Miocene and Pliocene.


Over the past decade there has been mounting evidence of the significant role played by the myriad attributes of our city's built environments in shaping our health and well-being. This thesis hypothesizes that the constituent components of the built environment, especially the configuration and design of land uses and street networks governs the distribution of resources and services, configures the neighbourhood activity space, and thereby influences individual physical activity behaviours, social interactions, weight outcomes as well as mental health and well being. Enhanced accessibility to health-promoting community resources improves local opportunities for physical activity, thereby enhancing mobility, social interactions and independence as well as reducing isolation.
 The first section of this thesis conceptualizes the urban health niche as a novel holistic and spatially-explicit paradigm in public health and proposes a health niche model of healthy city. Based on the proposed paradigm and gathered research evidence, multilevel data sets pertaining to health, socio-economic, built and natural environment have been produced and integrated together to constitute the high resolution database, spatial Design Network Analysis for Urban Health (sDNA-UH). sDNA-UH has been developed for the assembly constituency of Caerphilly, South Wales enabling operationalization of the spatial elements of the proposed urban health niche. State-of-the-art spatial and network analysis techniques have been employed upon the UK Ordnance Survey Mastermap data layers to quantify the various facets of urban built environment in the form of built environment morphological metrics (morphometrics) with the potential to influence individual's health. Based on the developed sDNA-UH, a series of three empirical studies comprising multilevel cross-sectional and longitudinal models have been presented which examine the association between specific attributes of a built environment and health outcomes. Firstly, a two-part multi-level regression model was employed to examine the impact of built environment configuration upon psychological distress. Land use mix, density of amenities, local street-network general accessibility ('betweenness') and slope variability were identified as significant predictors. Secondly, the first long-term longitudinal evidence relating the built environment to change in obesity in older people identified land use mix, density of amenities street network accessibility and slope variability as significant predictors. The third study examined the health effects of differential accessibility of an individual's dwelling with respect to multiple service and facility catchments at multiple spatial scales. Dwelling level density, dwelling type, density of community services, street network movement potential expressed in terms of betweenness index as well as neighbourhood-level deprivation were identified as the significant parameters. The study reported significant differences in point estimates and level of significance when comparing the two spatial scales of 0.5 and 1.0 mile street network catchments.
 The empirical evidence thus generated lends support to the thesis' principal hypothesis that the built environment influences individual health behaviour and eventually health. The research concludes that optimized design and planning of urban built environments act as effective public health intervention in our goal of health-sustaining communities and a healthy city.


DNA intra-strand cross-link (ICL) agents are widely used in the treatment of cancer. ICLs are thought to form a link between the same strand (intra-strand) or complimentary strand (inter-strand) and thereby increase the stability of DNA, which forbids the processes like replication and transcription. As a result, cell death occurs. In this work, we have studied the enhanced stability of a double stranded DNA in the presence of ICLs and compared our findings with the results obtained in the absence of these links. Using atomistic simulations with explicit solvent, a force is applied along and perpendicular to the direction of the helix and we measured the rupture force and the unzipping force of DNA-ICL complexes. Our results show that the rupture and the unzipping forces increase significantly in the presence of these links. The ICLs bind to the minor groove of DNA, which enhance the DNA stabilisation. Such information may be used to design alternative drugs that can stall replication and transcription that are critical to a growing number of anticancer drug discovery efforts.


State-of-the-art stellar structure and evolution codes fail to adequately describe turbulent convection. For stars with convective envelopes such as red giants, this leads to an incomplete depiction of the surface layers. As a result, the predicted stellar oscillation frequencies are haunted by systematic errors, the so-called surface effect. Different empirically and theoretically motivated correction relations have been proposed to deal with this issue. In this paper, we compare the performance of these surface correction relations for red giant branch stars. For this purpose, we apply the different surface correction relations in asteroseismic analyses of eclipsing binaries and open clusters. In accordance with previous studies of main-sequence stars, we find that the use of different surface correction relations biases the derived global stellar properties, including stellar age, mass, and distance estimates. We, furthermore, demonstrate that the different relations lead to the same systematic errors for two different open clusters. Our results overall discourage from the use of surface correction relations that rely on reference stars to calibrate free parameters. Due to the demonstrated systematic biasing of the results, the use of appropriate surface correction relations is imperative to any asteroseismic analysis of red giants. Accurate mass, age, and distance estimates for red giants are fundamental when addressing questions that deal with the chemo-dynamical evolution of the Milky Way galaxy. In this way, our results also have implications for fields such as galactic archaeology that draw on findings from stellar physics.


Purified Ralstonia eutropha polyhydroxybutyrate (PHB) synthase from recombinant cells can exist as monomer and dimer. The polymerization reaction catalyzed by this enzyme displays a lag phase, which causes difficulties for kinetic and mechanistic characterization of the enzymatic polymerization reaction. In this study, we developed a method to eliminate the lag phase of PHB synthase by physical means, i.e., adding multihydroxyl compounds to the enzyme solution. This method allows us to recognize the nature of the lag phase as a physical rather than a chemical process. With such lag-phase-free-enzyme, the kinetic properties of the enzyme were investigated. The results indicate that 3-hydroxybutyryl-CoA (3HBCoA) is the optimal substrate for the enzyme. A slower catalytic rate and lower binding ability account for a lower reactivity of 3-hydroxyvaleryl-CoA (3HVCoA) compared to that of 3HBCoA. The change of hydroxyl group from the beta to the gamma position causes dramatic decreases in the binding ability of 4-hydroxybutyryl-CoA (4HBCoA). By using a dilution strategy and size exclusion chromatographic technique, the active form of the enzyme was identified to be the dimeric form. The number of catalytic sites in the dimeric form of the enzyme was examined by comparing the molecular weight of polyhydroxybutyrate as a function of substrate-to-enzyme ratio. The results suggest that the dimeric enzyme has only one catalytic site. A revised model of polymerization reaction catalyzed by R. eutropha PHB synthase is described.


Abstract We present high resolution simulations on the impact of ionizing radiation on turbulent molecular clouds. The combination of hydrodynamics, gravitational forces and ionization in the tree-SPH code iVINE naturally leads to the formation of elongated filaments and clumps, which are in excellent agreement with the pillars observed around HII regions. Including gravity the formation of a second generation of low-mass stars with surrounding protostellar disks is triggered at the tips of the pillars, as also observed. A parameter study allows us to determine the physical conditions under which irregular structures form and whether they resemble large pillars or a system of small, isolated globules.


Abstract 2980 Introduction: Deletion of chromosome 13, detected by conventional chromosome analysis (CC), has been suggested to be an independent indicator of poor prognosis in myeloma (MM). With the exception of a single study using conventional therapy this has not been confirmed in multicenter randomized controlled trials which have mostly used FISH analysis. We set out to assess the prognostic value of del(13) and compare its detection by FISH and CC. Methods: We have examined the effect of del(13) in a large multicenter randomized controlled phase III trial, MRC Myeloma IX (ISRCTN68454111), which tested the effect of induction therapy with a thalidomide combination in both an intensive (CTD vs CVAD prior to single HDM plus ASCT) and a non-intensive (CTDa vs MP) setting. From June 2003 to November 2007 samples from newly presenting MM patients were sent from hospitals throughout the UK to a central laboratory where CD138 purification for FISH was performed, with conventional cytogenetic culture(s), using unpurified cells, being set up wherever possible. Results: 1960 evaluable patients were entered into the trial (1111 intensive, 849 non-intensive) of which 1036 were evaluable for del(13) by FISH (613 intensive, and 423 non-intensive); del(13) was seen in 45% (470/1036) with a similar incidence in both pathways. With a median follow up of 3.7 years del(13) detected by FISH was associated with impaired OS (median, 42 vs 52 mo, p=0.004). The effect was stronger in the non-intensive pathway (median OS 25 vs 37 mo, p=0.001) than in the intensive one (median 58 mo vs not reached, p=0.095). However, this adverse prognostic impact was negated when the strong association of del(13) with the bad prognosis IGH translocations t(4;14), t(14;16) and t(14;20) (bad IGH) was taken into account. In comparison, 639 patients were evaluable for CC results (378 intensive, 261 non-intensive) with an overall abnormality rate of 35% (224/639). We note that the impact of detecting any abnormal karyotype was not significantly different from a normal/failed karyotype irrespective of intensive or non-intensive treatment being used (whole trial p=0.213, intensive p=0.249, non-intensive p=0.252) suggesting that the capacity to generate abnormal metaphases alone is not an adverse prognostic factor. Del(13) was seen in 45% of abnormal karyotype cases (102/224) and 16% of all cases tested for CC. Overall the detection of del(13) by CC was associated with an adverse prognostic effect on OS (median 34 vs 47 mo, p=0.039). However, the entire effect was in the non-intensive pathway (median 20 vs 34 mo, p=0.018) (Fig1A), with no detectable effect in the intensive pathway (median 69 vs not reached, p=0.679) (Fig1B). We addressed the impact of the treatment used, and in a comparison of the thalidomide and non-thalidomide regimes for all del(13) CC patients there was no significant impact on OS (p=0.538). However, in the non-intensive pathway there was a significant improvement in favour of thalidomide (median 33 vs 18 mo p=0.03). Multivariate analysis of the prognostic impact of genetic factors within abnormal metaphases showed that bad IGH (p=0.001), gain of 1q (p=0.001) and deletion of 17p (p=0.001) were the only independent prognostic factors. In further analyses including all FISH-detected abnormalities, the markers bad IGH (p Conclusions: We demonstrate that in a large multicenter trial carried out across the UK del 13 detected by FISH does not have adverse prognostic impact if its association with the poor prognosis translocations is taken into account. Similarly del(13) detected by CC is not an independent prognostic factor when bad IGH and gain of 1q are taken into acount. The trial shows that thalidomide improves the outcome for del(13) by CC in patients treated with conventional dose therapy. However, this beneficial effect of thalidomide is not enough to account for the lack of independent significance of this marker across the study. On the basis of these results we cannot recommend the use of conventional cytogenetic testing methods as a routine for patients entered into multicenter clinical trials. Disclosures: No relevant conflicts of interest to declare.


Acute exacerbations of chronic obstructive pulmonary disease (COPD) causing respiratory failure are associated with mortality rates of up to 26%. A new Royal College of Physicians guideline aims to impart standards and practical advice to those providing a non-invasive ventilation service for these patients. This article examines the guideline.


To facilitate resistance gene characterization in the present study, the pathogenicities of newly collected blast isolates from rice fields in the Philippines were characterized using international blast differential varieties consisting of 31 monogenic lines that target 24 resistance genes. To classify and designate the blast isolates, we used a new international blast designation system, which has been proposed as a suitable naming system for comparing blast races among different studies. A total of 23 rice blast isolates collected from the Philippines were classified into 16 pathotypes, which showed reaction patterns different from those seen in the standard isolates. Among the blast pathotypes, 11 had differentiating ability for four Pik alleles (Pik, Pik-m, Pik-h, and Pik-p) and Pi1, whereas the standard blast isolates from the Philippines were not able to differentiate these genes. In addition, several blast isolates were avirulent to IRBLt-K59, IRBL19-A, and Lijiangxintuanheigu, although the standard differential blast isolates were virulent to these lines. Moreover, two blast isolates were virulent to a monogenic line, IRBL9-W, which harbours Pi9 and was resistant to all standard differential blast isolates. By using the isolates avirulent to IRBL19-A, Pi19(t) was successfully mapped in the centromeric region on chromosome 12 with simple sequence repeat markers RM27937 and RM1337. These markers are useful for marker-assisted Pi19(t) introgression worldwide.


Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

The ovarian steroid hormones progesterone and estrogen play vital roles in the development of normal mammary gland and are likewise linked to mammary carcinogenesis via their receptors. Progesterone receptor (PR) is expressed as two isoforms, PR-A and PR-B, both in human and mouse. It has been reported that in human breast tumors the PR-A/PR-B expression ratio is altered. To further study the role of PR isoforms on mammary gland biology, transgenic mice carrying either an additional A form of PR (PR-A) or the B form of PR (PR-B) were generated. Both mice strains present abnormal development in their mammary glands. Overexpression of the A isoform of PR leads to increased side branching and multilayered ducts, while overexpressing the B isoform leads to limited ductal growth. The characteristics of mammary glands from these mice provide direct evidence that an aberration in the mechanisms regulating the differential expression of the two isoforms of PR can have major implications to mammary carcinogenesis and might affect the stem cell population of the gland.

Recent studies have shown that a hierarchy of mammary stem/progenitor cells exists among the mammary epithelium in both human and mouse and PR signaling has been shown to play a major role in the maintenance of the stem cell population. So far, however, the differential role of the PR isoforms in the regulation of the stem cell population in the breast has not been established. We propose that the altered ratio of PR A/B might affect the stem cell population expansion and self renewal in the mammary gland.

We found that mammary glands of mice overexpressing the B isoform presented a higher percentage of cells positive for stem cell markers (CD24+/CD29+) than those derived from PR-A and WT mice. Furthermore cells derived from PR-B mammary glands had increased mammosphere forming capacity compared to both PR-A and WT. Moreover, when mammosphere cultures were carried out in the presence of 4-OH-tamoxifen 10-8M, the number of mammospheres formed from mammary glands of WT and PR-A mice was reduced compared to control cultures treated with vehicle, whereas there were no differences for cultures derived from mammary glands of PR-B mice. Additionally, upon ovariectomy (OVX), mammary glands from PR-A and WT mice showed a higher percentage of cells positive for stem cell markers by flow cytometry, and increase mammosphere forming capacity than control sham mice, while in mammary glands derived from PR-B OVX mice neither parameters changed.

Our results suggest that the B isoform of PR, may play a predominant role in the maintenance of stem cell population of the mammary gland and in the development of hormone resistance given that ovarian regulation affected mammary glands of WT and PR-A mice, but not those derived from PR-B mice.

Citation Format: Maria S. Recouvreux, Rocio Sampayo, Marina Simian. Progesterone receptor isoform ratio regulates the stem cell population in the mouse mammary gland. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2240. doi:10.1158/1538-7445.AM2015-2240


Infants are discharged from intensive care nurseries with varied risk levels and care needs that require a multilevel resource network. This article describes a consultation model that evolved from the collaborative effort of two regional hospitals with state funding support. A hospital-based clinical nurse specialist provides consultation to community health nurses and other providers of local follow-up services. Individualized mentoring, group educational sessions, and program consultation are adapted to the practice level and resource needs in each urban and rural community.


We study various probabilistic and analytical properties of a class of degenerate diffusion operators arising in population genetics, the so-called generalized Kimura diffusion operators Epstein and Mazzeo [SIAM J. Math. Anal. 42 (2010) 568–608; Degenerate Diffusion Operators Arising in Population Biology (2013) Princeton University Press; Applied Mathematics Research Express (2016)]. Our main results are a stochastic representation of weak solutions to a degenerate parabolic equation with singular lower-order coefficients and the proof of the scale-invariant Harnack inequality for nonnegative solutions to the Kimura parabolic equation. The stochastic representation of solutions that we establish is a considerable generalization of the classical results on Feynman–Kac formulas concerning the assumptions on the degeneracy of the diffusion matrix, the boundedness of the drift coefficients and the a priori regularity of the weak solutions.


Cellular proteostasis is a highly dynamic process and is primarily carried out by the degradation tools of ubiquitin-proteasome system (UPS). Abnormalities in UPS function result in the accumulation of damaged or misfolded proteins which can form intra- and extracellular aggregated proteinaceous deposits leading to cellular dysfunction and/or death. Deposition of abnormal protein aggregates and the cellular inability to clear them have been implicated in the pathogenesis of a number of neurodegenerative disorders such as Alzheimer's and Parkinson's. Contrary to the upregulation of proteasome function in oncogenesis and the use of proteasome inhibition as a therapeutic strategy, activation of proteasome function would serve therapeutic objectives of treatment of neurodegenerative diseases. This review describes the current understanding of the role of the proteasome in neurodegenerative disorders and potential utility of proteasomal modulation therein.


Cold spraying has a high potential for building up thick coatings or structures, like for rapid prototyping or production of free-standing parts. This method is particularly interesting for high strength materials that are difficult to process or to shape, e.g. Titanium for special applications in aviation industries. In this contribution, the two major challenges are addressed: (I) optimizing mechanical properties by systematic variation of process parameters, and (ii) evaluating the influence of the spray angle with respect to complex geometries as requested by aviation industry. While in the past, high quality titanium coatings were only achieved using Helium as process gas, Nitrogen is used in this study to reduce costs. High deposition efficiencies of more than 95 % can be obtained and the coatings show very low porosities as well as high tensile strength of over 480 MPa. The influence of process conditions on the mechanical properties is discussed on the basis of coating microstructures, Micro Flat Tensile (MFT) and Tubular Coating Tensile tests (TCT-test).


AGES: 12–13 Everything we do (sense, move, feel, remember...) relies on the activity of neurons in the brain, the connections between them and their ability to change the strength of these connections. Astrocytes are a di erent type of brain cells previously thought to merely support the activity of neurons. Advanced tools allow us to artificially activate specific cells populations in specific brain areas. Using such tools, we found that astrocytes can independently strengthen the connections between neurons and improve memory. We show that this memory improvement is due to the ability of astrocytes to enhance only the activity of those neurons participating in learning. Our findings suggest that astrocytes are not merely support cells enabling memory, but they can actively change the function of neurons. The ability of astrocytes to enhance memory may serve as a basis for future treatments to improve normalmemory or help people who su er from memory loss.


Sphagnum peatlands or bogs in the Kosciuszko National Park ranging from montane to alpine in elevation were sampled on two occasions spanning a maximum interval of 32 years. Data analysed for individual samples (305 quadrats) clustered into consistent microhabitat (hummock/hollow) groups and subalpine/alpine subgroups. Quadrat data were aggregated for sites (13 bogs) and analysed for floristic trends over time. Cluster and ordination analyses showed a large change in a single montane bog, but relatively little composition (presence/absence) change for the subalpine and alpine bogs. Analyses of dominant species in alpine (three) and subalpine bogs (three) showed some temporal trends in cover. There appears to be an increase in the cover of Sphagnum and a decrease in shrub cover in the subalpine bogs over the 20–32 years. Changes in shrub cover in undisturbed subalpine sites are attributed to shrub senescence and lack of recruitment. Changes at a site with intensive ski field development (Smiggin Holes) were analysed separately and compared with adjacent sites with no such development. Sphagnum cover had not increased at this site and shrub decline was pronounced. Bare ground and ruderal species increased in cover whereas 13 native species that were originally recorded in 1959 were not re-recorded in 1991. The detection of vegetation change in bogs through monitoring is important for adaptive management of vegetation under intensive use.


This article investigates the socio-economic benefits of Home Based Enterprises (HBEs) within the settings of rural housing in Sirajganj, Bangladesh. Households' livelihood resources are engaged and affected widely by the HBEs and reciprocally the HBEs are also affected by them. Some households practice HBE only for their subsistence and some are involved for their household development. A major number of family members are engaged with the HBE. When HBE is practiced within the rural households, the livelihood receives some extended dimensions of socio-economic benefits. These benefits are studied for the six selected cases, identified as permanent and floating households. The selected case study HBEs are analyzed with reference to the analytical scale factors of livelihood resources. A comparison of the socio-economic benefits of the cases of permanent and floating homesteads context is drawn through the data analysis.


This paper presents a game that is developed to help the assessment of teaching and learning activities in a mechatronics course. The game is played with a mobile phone and it follows the dynamics of a 'treasure hunt' where participants follow a route and answer a series of questions that are encrypted in 2D barcodes. Participants interact with the game through a website; which allows to record various types of information related to the gameplay. In addition to gamifying the learning experience for students, the game allows the teacher to quantitatively assess the progression of the students and identify the topics that are challenging to comprehend.Copyright © 2014 by ASME


The classic electrochemical catalytic mechanism, often referred to as the EC' mechanism, is traditionally represented by the two reactions A + e <==> B (E(A/B)(0), k(A/B)(0), alpha(A/B)) and B + P <==> A + Q (K(eq), k(f), k(b)). Implicit in this mechanism is the additional heterogeneous electron transfer P + e <==> Q (E(P/Q)(0), k(P/Q)(0), alpha(P/Q)). To observe EC' behavior, the following conditions must be met (we focus on cyclic voltammetric responses): (1) E(P/Q)(0) > E(A/B)(0) (ensuring that K(eq) > 1), (2) k(P/Q)(0)c(P) exp[-alpha(P/Q)(F/RT)(E - E(P/Q)(0))]/(0.446c(A)(FD(A)|v|/RT)(1/2)) << 1 over the potential range of interest (ensuring that the reaction P + e <==> Q does not occur to any significant extent relative to the peak current for reaction A + e <==> B alone), (3) k(f)c(P)RT/F|v| > 1 (ensuring that the catalytic effect is significant). We offer arguments based on Marcus theory that when condition 2 is met, fulfilling condition 3 will be difficult. This could explain why EC' behavior is rare. In the present work we show that EC'-like cyclic voltammetric responses can be obtained even when P + e <==> Q is facile if D(P,Q) (the diffusion coefficient for the substrate-couple species P and Q) is much smaller than D(A,B) (the diffusion coefficient for the mediator-couple species A and B). When D(P,Q)/D(A,B) is sufficiently small, the system behavior becomes identical to that seen for the classical EC' system. We suggest that this "quasicatalytic" behavior should be considered when EC'-like behavior is observed and when the electrochemical system involves a substrate couple whose diffusion coefficients are much smaller than those of the mediator couple. As has been known for some time, when the diffusion coefficients of species A, B, P, and Q are identical (an assumption commonly made to simplify theoretical analysis) and when both heterogeneous electron transfers are reversible, the homogeneous kinetics have no effect on the cyclic voltammetric response--even though the distribution of species in the diffusion layer is dramatically altered.


Abstract A temperature-dependent in situ micro-FTIR and micro-Raman spectroscopic investigation was performed on powdered (FTIR, Raman) and single-crystal (Raman) lizardite-1T samples between room temperature and 819 °C. Between room temperature and 665 °C, the OH stretching bands shift to lower wavenumbers, demonstrating a weak expansion of the O3-H3…O2 interlayer distance. Band deconvolution of FTIR and Raman spectra at room temperature show differences in the number of bands in the OH stretching region with respect to group theory: four (FTIR) and six (Raman) OH stretching bands, respectively. This number reduces to four (Raman) at non-ambient temperatures either caused by LO-TO splitting, the presence of non-structural OH species or the presence of different lizardite polytypes and/or serpentine polymorphs as well as defects. During dehydroxylation, the evolution of the integrated intensity of the OH bands suggests a transport of hydrogen and oxygen as individual ions/molecule or OH-. A significant change in Raman spectra occurs between 639 and 665 °C with most lizardite peaks disappearing contemporaneously with the appearance of forsterite-related features and new, non-forsterite bands at 183, 350, and 670 cm-1. A further band appears at 1000 cm-1 at 690 °C. The long stability of Si-O-related bands indicates a delayed decomposition of the tetrahedral sheet with respect to the dehydroxylation of the octahedral sheet. Moreover, evidence for a small change in the ditrigonal distortion angle during heating is given. In general, all appearing non-forsterite-related frequencies are similar to Raman data of talc and this indicates the presence of a talc-like intermediate.


SUMMARY

New approaches to receiver function analyses at a suite of broad-band stations in the Coast Ranges of northern California identify rapid changes in crustal thickness accompanied by melt accumulation in the lower crust. These processes are associated with the northward migration of the Mendocino triple junction through the area over the past ∼8 Myr. By simultaneously solving for crustal thickness, Poisson's ratio and Moho strike and dip, we facilitate the application of receiver function analyses in areas of crustal complexity where data sets are sparse. We also introduce a straightforward approach to calculating the Vp/Vs velocity ratio of the seismogenic zone, which is used here to aid in the interpretation of results from the receiver function analysis. Results are consistent with triple junction related crustal modifications occurring in the plate motion direction in a narrow swath of crust between the Maacama and Bartlett Springs Faults. Crustal thicknesses decrease from over 35 km thick in Round Valley, south of the current triple junction location, to 20 km thick just 100 km further south, near Clear Lake. Major crustal thinning is localized to a narrow area of the crust around Redwood Valley, where the Moho dips approximately 17° to the northeast. This thinning may also be restricted to the lower crust rather than being evenly distributed throughout the crustal column. Coincident with these changes, melts are inferred in the lower crust from low velocity zones and elevated values of Poisson's ratio (σ≥ 0.32) at two seismic stations. These melts occur in the same area as melt bodies suggested in other seismological studies. Together these results provide the first detailed description of the crustal modifications—and the spatial extent of that deformation—associated with the passage of the Mendocino triple junction.


Ever since the early publication by Grayson, we have seen an increasing interest in decision-analysis in the oil and gas industry. There have been numerous studies and publications discussing methods and models for rational decision-making. Given the inherent limitations of intuition and heuristics, one might expect decision-makers to be delighted with the more consistent approach provided by rational decision-making techniques. Modern decision models can help process large amounts of information without losing valuable pieces. They never suffer from distraction, fatigue, boredom or random error. They are consistent, week after week. An important contributor of the complexity in decisionmaking stems from the fact that human beings are imperfect information processors, we are not always rational. Personal insights about uncertainty and preference can be both limiting and misleading, even while the individual making the judgments may demonstrate an amazing overconfidence. An awareness of human limitations is critical in developing good decision-making procedures. To our knowledge, very little has been published in the exploration & production literature on the "cognitive"; i.e., the "thinking", social, judgmental and emotional aspects of decision-making. Yet, in spite of these obvious advantages, people treat these with a nearly instinctive distaste. They are particularly resistant to the idea that simple models can validly make such subjective evaluations. For some, that resistance may stem simply from unfamiliarity with the statistics and probability involved. Many more, however, subscribe to the widespread assumption that human judgment is more discerning than a model. They are reluctant to believe that simple mathematical calculations can match the complexity of the human mind. "Take away an ordinary person's illusions," says Dr. Relling in Henrik Ibsen's Villanden, "and you take away happiness at the same time." Even today, after decades of research on the psychological aspects of judgment and decision-making, people continue to assume that intuition, repeated experience and their general intelligence will see them through. Unfortunately, intuition and repetition are unreliable teachers at best. Research shows that the less competent people are, the less likely they are to know it. Overconfidence is a deeply rooted human characteristic. Not only do most people tend to hold overly favorable views of their intellectual and interpersonal abilities, but those who are the least accomplished overestimate their performance and ability the most. In other words, those who most need training to improve their decision-making abilities are the least likely to recognize it. Instead, like drunken drivers who are certain that their reflexes are unimpaired, they proceed with the mistaken impression they are doing just fine. A particularly interesting aspect of human judgment and decision-making are the traps we unknowingly step into. Many decision-makers believe that intuition, repeated experience and their general intelligence will see them through. Unfortunately, as will be discussed in the paper, intuition and repetition are unreliable teachers at best. In this paper we will illustrate how a cognitive perspective can offer practical suggestions on how to deal with many 2 BRATVOLD, BEGG AND CAMPBELL SPE 77509 common problems in decision-making. The findings presented here are not novel and we have borrowed liberally from the pioneers and prominent researchers in the exploration of the minds of the decision-maker such as Kahneman and Tversky, Russo and Schoemaker, Thaler, March, and Plous. Yet, given the tendency of geo-scientists and engineers to focus on the "hard" elements of decision-making such as techniques and tools for quantifying uncertainty and risk, and not so much on the qualitative elements such as the cognitive and judgment aspects, we believe there is a need to broaden the understanding and appreciation of cognitive aspects. In this paper we are merely "touching the surface" of this field and we strongly encourage the interested reader to further explore this fascinating field by reading the original references. A good understanding of the behavioral elements of decisionmaking will lead to improved decision quality and, ultimately, to improved corporate performance. Good Decisions Process vs. Outcome Most decision makers focus on outcome. This is not surprising as most organizations reward – or penalize – people based on the outcomes of their decisions. Results are what matter. Indeed, many people believe that good outcomes are synonymous with a good process, that good outcomes necessarily imply that a good process was used. They often assume the converse is true as well: that a poor outcome necessarily signals a poor or incompetent process. Furthermore, if a company's or a managers track record is based on just a few "big" decisions instead of numerous small ones, a focus on outcomes carries the risk of rewarding good luck – or penalizing bad luck. The best hope for a good decision outcome is a good decision process. The main reason for this is that this forces the decision-makers to focus on what actually is under their control. Three things influence outcomes:


The electrocardiogram (EKG) is one of the most widely used diagnostic tests in clinical medicine and is generally considered to be an excellent means of detecting many important cardiac abnormalities. However, when the EKG is interpreted in the traditional manner, its diagnostic performance is not as good as clinicians might wish. For example, a recent study showed that three sets of commonly used traditional EKG criteria for inferior myocardial infarction (MI) had such low sensitivities that they missed between 66% and 96% of the MIs that they were supposed to detect. 1 In contrast, three different sets of vectorcardiographic (VCG) criteria for inferior MI exhibited much better diagnostic performances. The investigators found that the superior performance of the VCG was due to its ability to display information about the contour of the pathway followed by the electrical forces of ventricular depolarization. Despite the reported advantages of the VCG, it is


Sapphire, spinel, and ALON (aluminum oxynitride) have been identified as candidate dome materials for ultraviolet through 5 μm wavelength applications. They possess optical, mechanical, and thermal properties that are superior to those of currently used Irtran-1 domes. Optical performance of these materials in the visible wavelength region far exceeds that of Irtran-1, while infrared properties reported here vary from worse than to better than Irtran-1 domes. Reported in this paper are measurements of optical scatter and transmittance at 0.4762, 0.6471, and 3.39 μm, which represent a large range of values obtained on these materials in dome form. Processing changes over the last few years have produced improvements in both scatter and transmittance, provided that a good surface finish is maintained. Higher index of refraction will, of course, limit the ultimate transmittance for uncoated domes of these materials to slightly less than that of Irtran-1, which has also improved in the same time period. Calculations indicate maximum transmittance at 3.39 pm to be 0.95 to 0.96 for Irtran-1 and 0.87 to 0.88 for spinel, a difference of 0.08. Current measurements at the Naval Weapons Center confirm values of 0.88 for spinel, while the best Irtran-1 dome gave a value of less than 0.92.


Purpose
The purpose of this paper is to determine the principal organisational cultural dimensions that affect levels of post-merger integration (PMI) in Chinese acquisitions in Germany and to explore the relationship of these specific organisational cultural dimensions and levels of integration.

Design/methodology/approach
Data set were collected using a structured questionnaire given to Chinese and German managers and employees, who implemented/were responsible for the PMI in 12 Chinese acquisitions in Germany. A total of 120 questionnaires were distributed and there were 67 respondents, corresponding to a response rate of about 56 per cent. Principal components analysis, one-way ANOVA and bi-variate Spearman's correlation were applied to analyse the data.

Findings
Findings revealed that five organisational cultural dimensions (i.e. adaptability, consistency, involvement, balance and flexibility) were extracted to be the primary indicators affecting levels of integration in Chinese reverse mergers and acquisitions (M&As) in the German market. Further, adaptability emerged as the only predictor with a significant negative implication on predicting the degree of PMI that Chinese investors would initiate to integrate their acquired German subsidiaries.

Originality/value
This study is one of the few studies to consider the specific organisational cultural dimensions affecting the integration levels of reverse M&As and is the first study, to the best of our knowledge, to explore the correlations of specific corporate cultural dimensions and integration levels in emerging multinational enterprises' reverse M&As through quantitative research.


The chlamydospore is a distinctive morphological feature of the fungal pathogen Candida albicans that can be induced to form in oxygen-limited environments and has been reported in clinical specimens. Chlamydospores are not produced by the model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, so there is limited understanding of the pathways that govern their development. Here, the results of a forward genetic approach that begins to define the genetic control of chlamydospore formation are described. Six genes - ISW2, MDS3, RIM13, RIM101, SCH9 and SUV3 - are required for efficient chlamydospore formation, based on the phenotypes of homozygous insertion mutants and reconstituted strains. Mutations in ISW2, SCH9 and SUV3 completely abolish chlamydospore formation. Mutations in RIM13, RIM101 and MDS3 delay normal chlamydospore formation. The involvement of alkaline pH-response regulators Rim13p and Mds3p in chlamydospore formation is unexpected in view of the fact that chlamydospores in the inducing conditions used here are repressed in alkaline media.


Neurological disorders are now being more widely recognized as significant contributors to mortality and disability on a global scale. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provided the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. According to the findings of the study, the two largest contributors of neurological DALYs (disability-adjusted life-years) were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]). Stroke ranked first globally among neurological disorders in terms of age-standardised DALY rates in 19 of 21 world regions except in Australasia and Western Europe. Migraine ranked first in Australasia and Western Europe. Stroke burden rapidly increased up to the age of about 80 years, and was the dominant cause of neurological burden between ages 60 and 84 years, more so in males than females. Migraine and tension-type headaches were large contributors in young and middle-aged adults, with much higher numbers in females than males


Cryotherapy is the treatment of choice in the management of acute athletic injuries. Ice is readily available and simple to apply. The rationale for its use is based on well-defined physiologic observations. The application of heat is not indicated in the immediate treatment of acute athletic injuries. If applied early and injudiciously, heat may adversely affect resolution of the trauma and prolong the rehabilitation of the athlete.


Summary The presence of phosphotyrosine in proteins from washed rabbit platelets was demonstrated by electrophoresis and by alkali stability of phosphorylated polypeptides. The phosphotyrosine content increased about twofold by treating the platelets with PMA in spite of the fact that the specific activity of labeled ATP was unchanged. It was shown that phosphorylated proteins with apparent molecular weight of 48k, 53k and 250k were alkali-stable. Although phosphorylation of 48k protein in platelets was stimulated by 1 U thrombin as well as by 100 ng PMA, only the phosphorylated samples from PMA-treated platelets were alkali-stable. The 48k protein from platelets stimulated by PMA showed the fivefold increase of 32P-tyrosine content as compared with the control. Relatively lower increase of 32P-serine or 32P-threonine, 2- and 1.7-fold respectively, was thereby observed. The differences in time-sequence between 48k and 250k protein of total and alkali-stable phosphorylations suggested that tyrosine phosphorylation of 48k protein is the earliest event after the PM A-stimulation.


Politics is a process by which groups of people make group decisions. It is associated with social relations involving authority and power, for the greater good of society. The concept in itself is a useful and worthy one, and exists for a respectable cause and for the full and fair benefit of society. There are two impressions of politics - the honourable kind, and the tainted kind. The honourable kind is associated with statesmanship, protection and legacy.


A statistical analysis of observed oblique sounder lowest observed frequency (LOF) and predicted lowest usable frequency (LUF) was to assess the accuracy of the PROPHET algorithm QLOF version 2.0. A LOF data base of 1814 LOFs from 29 paths was established for the assessment. The data was screened into subsets to determine the effect of particular paths, universal and local time, sounder type, path length and orientation, season, month, sunspot number, and mid-path latitude. Version 2.0 had a bias of 0.55 MHz low, an rms error of 1.95 MHz, and a correlation coefficient with the observed data of 0.89. The rms error increases with increasing range. A higher residual was noted for the months of July through October. An increase in residual at midlatitude was noted. Reasons for these errors are given. A modification to the absorption index term which determines the latitudinal and seasonal variation is suggested.


A study of plasma polymerization of cyclopropylamine in a low-pressure cylindrical magnetron reactor is presented. Both experimental and numerical approaches are used to investigate thin film growth mechanisms and polymer film properties depending on the magnetic field strength. Combining both approaches enables the consistency of the numerical model to be checked while acquiring data for understanding the observed phenomena. Samples are first analyzed by x-ray photoelectron spectroscopy, time of flight secondary ion mass spectrometry, and ion beam analysis to illustrate the differences in degrees of chemical functionalization and cross-linking between the regions of high and low magnetic fields. 3D particle-in-cell Monte Carlo collision simulations are then performed to shed light on experimental results, after implementing a set of electron-cyclopropylamine collision cross sections computed using the R-matrix method. The simulations enable the main radicals produced in the discharge to be tracked by determining their production rates, how they diffuse in the plasma, and how they absorb on the reactor walls. Additionally, the cyclopropylamine ion (C3H7N+) behavior is followed to bring insights into the respective roles of ions and radicals during the plasma polymerization process.


The cost of downloading content from the Internet may be costly for mobile device users using its 3G connection, because the 3G connection cost to download data from the Internet is a function of the amount of data downloaded. This paper introduces an approach in which mobile devices, called peers, form an ad hoc network and share their downloaded content with others. As an example, spectators may want to collect/share information about players and game records in a stadium. In an art gallery, visitors may want to retrieve some background information about the displayed work from the nearby ad hoc network. In an outdoor class, a teacher may download today's topic files from the Internet, and all students may share the content with minimal or no cost paid. This is possible if mobile device has both a 3G interface and a wireless LAN interface. If the peers want to improve privacy md discourage traffic analysis when sharing content, this paper describes a low-delay anonymous connection between the sending peer and the receiving peer using two additional peers. Simulation results show that the transmission time overhead of the anonymous connection may increase 50% or less as the number of peers increase or the peers are scattered over the larger area.


Selection of optimal control samples is crucial in expression profiling tumor samples. To address this issue, we performed microarray expression profiling of control samples routinely used in head and neck squamous cell carcinoma studies: human bronchial and tracheal epithelial cells, squamous cells obtained by laser uvulopalatoplasty and tumor surgical margins. We compared the results using multidimensional scaling and hierarchical clustering versus tumor samples and laryngeal squamous cell carcinoma cell lines. A general observation from our study is that the analyzed cohorts separated according to two dominant factors: "malignancy", which separated controls from malignant samples and "cell culture-microenvironment" which reflected the differences between cultured and non-cultured samples. In conclusion, we advocate the use of cultured epithelial cells as controls for gene expression profiling of cancer cell lines. In contrast, comparisons of gene expression profiles of cancer cell lines versus surgical margin controls should be treated with caution, whereas fresh frozen surgical margins seem to be appropriate for gene expression profiling of tumor samples.


Aim Children with Pierre Robin Sequence (PRS) are at risk of early upper airway obstruction (UAO) and have increased prevalence of childhood obstructive sleep apnoea (OSA). Polysomnography is gold standard for OSA diagnosis and is used to objectively evaluate treatment modalities. This study defines its utility in PRS. Methods We retrospective reviewed case-notes and sleep study (SS) reports of 84 children with PRS (born 2004-2013). Sleep studies were performed as limited-channel cardiorespiratory studies with measurement of airflow (allowing confident detection of apnoea) and effort (allowing delineation of central versus obstructive events) in addition to SpO 2 . Scoring was in accordance with AASM standards. Results Management of UAO included prone positioning (36%), nasopharyngeal airway (51%), tongue-lip adhesion (4%) and tracheostomy (4%). 60% children (n=50) underwent SS (1-8 studies/child, mean 2.1), of whom 82% had abnormal studies. Syndromic PRS was highly predictive of abnormal SS (100% vs 76% in isolated PRS). 48% underwent SS aged l1 year (median 9d), of whom 98% had an abnormal study; 80% showed OSA and 18% central apnoeas alone. 23% underwent SS aged 1-6 years and 47% had an abnormal study (64% OSA, 36% central apnoeas). SS results guided the following interventions: NPA insertion/removal (n=16), caffeine therapy (n=2), home oxygen (n=2), overnight CPAP (n=3), adenotonsillectomy (n=2). Conclusions SS play an important role in PRS management, guiding decisions about airway support and timing of surgery, identifying OSA in older children, and demonstrating central apnoeas alone in a subset of patients. All of the above suggest that sleep diagnostics be considered an essential component of cleft services.


The article by Basnayake and Easterbrook on variation of global estimates for HBV, HCV and HIV co‐infection is a comprehensive study of cited World Health Organization (WHO) estimates in the literature between 2010 and 2014. The authors reviewed 488 articles published during this period and showed that a wide range of estimates have been quoted using different WHO estimates, and they attempt to set the record straight by listing the most recent/appropriate WHO estimates that should be used going forward.


This paper reviews different methodologies used for railroad capacity estimation and presents a user-friendly method to measure capacity. The objective of this paper is to use multivariate regression analysis to develop a continuous relation of the discrete parameters identified for capacity estimation. The algorithm developed in this paper can be used for managerial decision making regarding railroad capacity by various state agencies and state DOTs. This paper illustrates the relationship between the parameters and section capacities, which can be used to improve the throughput of the transportation system. The paper also illustrates the application of the model to estimate capacity of a statewide railroad network.


Many materials are used during a dental treatment, which can cause dental allergy in susceptible patients. Behind the immune response there are multistage biochemical processes, in which protein interactions can be investigated by directed evolutionary, phage display technique. Aim of this study is to determine the frequent amino acid sequences on polystyrene surface as dental base thermoplastic polymers by phage display technique. Positive control was streptavidin (Str) covered polymer, the negative control was bovine serum albumin blocked polystyrene. Based on our results it was found that the WLFNHPQ sequence is Str specific peptide in our system, because this variant has occurred repeatedly in three independent samples. The selected phages from the BSA blocked PS surface have contained some variants with some frequency. We demonstrated that peptides bond to PS surface. The most frequent peptide was FSGRPLP on untreated polystyrene surface. However allergy is not reported with the application of PS thermoplastic polymer. The reason of this can be the result of the applied technology, namely the injection moulded technique. In the antigen presentation the knowledge and blocking of the binding sites can help to discover and reduce the formation of allergic reactions. Based on our experiments it can be declared that our PS model system can be a good starting point in the recognition of other dental polymer peptide biding sites.


Measles virus (MV) causes small and large outbreaks in Iran. Molecular assays allow identifying and the sources of measles imported from neighboring countries. We carried out a phylogenetic analysis of measles virus circulating in Iran over the period 2010–2012. Specimens from suspected cases of measles were collected from different regions of Iran. Virus isolation was performed on urine and throat swabs. Partial nucleoprotein gene segments of MV were amplified by RT-PCR. PCR products of 173 samples were sequenced and analyzed. The median age of confirmed cases was 2 years. Among all confirmed cases, 32% had unknown vaccination status, 20% had been vaccinated, and 48% had not been vaccinated. Genotypes B3 and D8 (for the first time), H1 and D4 were detected mainly in unvaccinated toddlers and young children. Genotype B3 became predominant in 2012 and was closely related to African strains. H1 strains were also found in small and large outbreaks during 2012 but were not identical to Iranian H1-2009 strains. A majority of the Iranian D4 strains during 2010–2012 outbreaks were linked to the D4 strain identified in the Pakistan in 2007. We identified a single case in 2010 belonging to D8 genotype with 99.7% identity to Indian isolates. Although the vaccination program is currently good enough to prevent nationwide epidemics and successfully decreased measles incidence in Iran, the fraction of protected individuals in the population was not high enough to prevent continuous introduction of cases from abroad. Due to increasing number of susceptible individuals in some areas, sustained transmission of the newly introduced viral genotype remains possible.


Worldwide, about US$410 billion is spent every year to manage four billion tonnes of municipal solid wastes (MSW). Transport cost alone constitutes more than 50% of the total expenditure on solid waste management (SWM) in major cities of the developed world and the collection and transport cost is about 85% in the developing world. There is a need to improve the ability of the city administrators to manage the municipal solid wastes with least cost. Since 2000, new technologies such as geographical information system (GIS) and related optimization software have been used to optimize the haul route distances. The city limits of Chennai were extended from 175 to 426 km2 in 2011, leading to sub-optimum levels in solid waste transportation of 4840 tonnes per day. After developing a spatial database for the whole of Chennai with 200 wards, the route optimization procedures have been run for the transport of solid wastes from 13 wards (generating nodes) to one transfer station (intermediary before landfill), using ArcGIS. The optimization process reduced the distances travelled by 9.93%. The annual total cost incurred for this segment alone is Indian Rupees (INR) 226.1 million. Savings in terms of time taken for both the current and shortest paths have also been computed, considering traffic conditions. The overall savings are thus very meaningful and call for optimization of the haul routes for the entire Chennai.


Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

INTRODUCTION. The limitations of cellular models and xenograft for the identification of anti-neoplastic drugs are well known. The purpose of our study is to test the validity of a novel methodology to identify apoptotic cells in living mice genetically modified or pharmacologically treated to develop cancer.

METHODS AND RESULTS. The method presented here relies on the combined use of reporter mice engineered to express the luciferase gene ubiquitously (1-2) and modified luciferase substrates (Glo technology) where a pro-luciferin (VivoGlo Caspase-3/7) is converted into a luminogenic substrate only in the presence of the apoptotic enzymes Caspase-3/7 (3-4). The novel methodology was tested by inducing liver apoptosis in luciferase reporter mice by a single i.p. injection of D-galactosamine (D-GalN; 800mg/kg) and Lipopolysaccharide (LPS; 100μg/kg) shown to increase the number of apoptotic cells in the liver of 5-10 fold compared to vehicle-treated animals (5); 6 hours after LPS/D-GalN or vehicle administration, mice were treated i.p. with increasing doses (17-150mg/kg) of the VivoGlo Caspase-3/7 substrate (Z-DEVD-Aminoluciferin, Sodium Salt) and subjected to the bioluminescence in vivo imaging procedure. The in vivo imaging data obtained clearly show a dose-dependent increase of photon emission in the hepatic area of mice treated with D-GalN/LPS. No photon emission was observed in organs not affected by the apoptotic treatment. A complete analysis of pro-apoptotic effects induced by the treatment was carried out by ex vivo imaging acquisition of photon emission in several dissected tissues. This investigation confirmed that light emission observed in vivo was produced selectively by liver and adipose tissues. Finally, the presence of increased apoptotic cells in liver was also confirmed by western blot analysis and Caspase-3/7 enzymatic activity assay carried out on protein extracts.

CONCLUSIONS. The present study, by showing the power of modified luciferin substrates to label apoptotic cells in living animals, provides an important advancement over current imaging methodologies based on fluorescence, nuclear or magnetic resonance including: virtually null background, high sensitivity and simple instrumentation needed for the in vivo imaging measurement of the Caspase-3/7 activity. The present application carried out in reporter mice genetically engineered to develop specific cancers will open the way to novel, more predictive approaches for the study of anti-cancer treatments that will enable, for the first time, to measure drug efficacy in space and time providing relevant information to be rapidly translated to human therapy.

REFERENCES

1- Maggi et al. Trends Pharmacol Sci. 2004.

2- Maggi A and Ciana P Nat Rev Drug Discov. 2005.

3- Meisenheimer PL et al. Promega Notes 2008.

4- Kizaka-Kondoh S et al. Clin Cancer Res. 2009.

5- Nakama T et al. Hepatology. 2001.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4319.


In this note, a diiculty with the application of Hildebrandt's closed-form training algorithm for the neocognitron is reported. In applying this algorithm we have observed that S-cells frequently fail to respond to features that they have been trained to extract. We present results which indicate that this training vector rejection in an important factor in the overall classiication performance of the neocognitron trained using Hildebrandt's procedure.


The complex AC conductance of carbon-wax mixtures was measured as a function of angular frequency omega from 7 Hz to 100 kHz for different concentrations p of carbon near the percolation threshold pc. The scaling exponents x=0.72+or-0.01, y=0.23+or-0.05 were found to be remarkably close to the theoretical values expected from the intercluster polarization model. The characteristic frequency omega c at which the real part of the AC conductance deviates from its DC value scales with the DC conductance sigma DC as omega c approximately sigma DCz, where z approximately=1.1. The nature of the variation of loss tangent tan delta with frequency was studied in detail. It was found that tan delta went through a minimum at a frequency which increased with p. The increase of tan delta at higher frequencies cannot be explained by the usual RC model. The authors consider a modified version, the R-RC model in which a capacitor is always in series combination with a resistor, i.e. capacitors are lossy. This model is shown to reproduce the observed behaviour of tan delta and believed to be more realistic than the RC model hitherto considered in that series resistors may be a more effective representation of the dangling bonds in the system.


A case of pneumomediastinum following a minor blunt thoracic trauma is presented. As no underlying organic lesion could be found, the pathophysiology must have been that of a spontaneous pneumomediastinum, i.e. alveolar rupture with subsequent dissection of air along the bronchovascular sheats to the mediastinum. The pathophysiology, clinical presentation, diagnosis and treatment of the spontaneous pneumomediastinum are discussed. With regard to the treatment it seems most important not to be too aggressive, because spontaneous pneumomediastinum is a benign and self-limiting condition. Spontaneous regression within a week can be expected.


Due to the recent proliferation of hurricanes and heavy rains, occurrence probability of the collapse of river banks and overflow has increased and has brought about large loss of life and severe property damage in lowland. It is imperative information related to the collapse of levee and overflow systems, flood inundation ranges and overflow spots be generated. Real damage causes include flood waves; understanding streams of flood waves as they flow into the lowland is vitally important. The purpose of this study is to generate data that will protect life and the property of residents in damage areas. Flood analysis is preformed to prepare for emergency situations in lowland due to the collapse of dams and river banks due to extraordinary foods and severe rains. Additionally, through simulation and analysis related to flood distribution patterns in lowland, forecasted inundation depth and time, range of flood, and estimated size of damage expectation can be generated. Data targets include the Nam River watershed using the FLDWAV model. Calculating the water level in lowland and introducing flooding hydrograph are vital to success. This is all related to the collapse of river banks and takes into consideration analysis of flood waves and collapse patterns of river banks. Using this data to create a two-dimensional flood model and by examining flood wave transfer characteristics at the point of real bank collapse, progress can be made. Calculating the range of flood, inundation depth and time in lowland, comparing and reviewing results with actual data and flood marks that showed the goodness of fit is over 90% is key. Calculate the range of flood data by assuming extreme situation of 200 years frequency on the same region, these results are able to contribute establishment of flood damage mitigation measures.


This survey was designed to evaluate the factors affecting mental health and welfare in Australian anaesthetists and to investigate current sources of support. An electronic survey was sent to 500 randomly selected Fellows and trainees of the Australian and New Zealand College of Anaesthetists. Questions were related to: anxiety, stress, depression, substance misuse, self-medication, suicide, reporting illness, and help-seeking. Current psychological wellbeing was assessed using the Kessler Psychological Distress Scale (K10). A total of 191 completed surveys were received (a response rate of 38%): 26% had attended their general practitioner for mental health issues, of whom half had been diagnosed with a mental illness; 7% of all respondents were currently prescribed medication for this; 25% had previously self-prescribed psychoactive medication; 17% admitted to using alcohol to deal with stress, anxiety or depression; and 8% responded that mental illness had at some point impaired clinical care. Sixteen percent of all respondents reported previous suicidal ideation. Despite a low response rate, and the possibility of responder bias, the mental health of Australian anaesthetists would appear to be subject to common and persistent risk factors, many of which are well described in previous studies. We identify general practitioners as particularly valuable in targeting initiatives for improvements in mental health and welfare. The significant prevalence of suicidal ideation and reluctance to approach senior colleagues with concerns about mental health or welfare issues are specific causes for concern and suggest that further investigation, education and a potential review of support networks is required.


Abstract:This article explores the technological dimension of Shanghai's socialist transformation. It does so through a case study of the bicycle industry, tracing the industry's standardization and consolidation from the early 1950s to the 1960s. During this time, hundreds of independent bicycle factories merged into one state-owned manufacturing enterprise renowned for its celebrated bicycle brand: the Phoenix. By examining the archives of both the preconsolidation bicycle trade association and the postconsolidation state-owned factory, this study uncovers the critical role played by the social group labeled "middle and petty capitalists," many of whom were business owners with valuable technical know-how. Their integration into the new sociotechnological system eliminated the entrepreneur as an identity even as it valorized the role of "technician." Thus the party-state successfully assimilated both private assets and industrial expertise into the new socialist production regime.


[1] Neodymium (Nd) isotopes were measured on 181 samples of fossil fish teeth recovered from Oligocene to Miocene sections at Ocean Drilling Program Site 1090 (3700 m water depth) on Agulhas Ridge in the Atlantic sector of the Southern Ocean. A long-term decreasing trend toward less radiogenic Nd isotope compositions dominates the record. This trend is interrupted by shifts toward more radiogenic compositions near the early/late Oligocene boundary and the Oligocene/Miocene boundary. Overall, ɛNd values at Agulhas Ridge are more radiogenic than at other Atlantic locations, and are similar to those at Indian Ocean locations. The pattern of variability is remarkably similar to Nd isotope results from Walvis Ridge (South Atlantic) and Ninetyeast Ridge (Indian Ocean). In contrast, Agulhas Ridge and Maud Rise Nd isotope records do not show similar patterns over this interval. Results from this study indicate that deep water in the Atlantic flowed predominantly from north to south during the Oligocene and Miocene, and that export of Northern Component Water (NCW) to the Southern Ocean increased in the late Oligocene. There is also evidence for efficient exchange of deep waters between the Atlantic sector of the Southern Ocean and the Indian Ocean, although the direction of deep water flow is not entirely clear from these data. The shifts to more radiogenic Nd isotopic compositions most likely represent increases in the flux of Pacific waters through Drake Passage, and the timing of these events reflect development of a mature Antarctic Circumpolar Current (ACC). The relative timing of increased NCW export and ACC maturation support hypotheses that link deep water formation in the North Atlantic to the opening of Drake Passage.


A novel fiber optic moire interferometer has been developed and demonstrated. A He-Ne laser and three high birefringence fibers were used to configurate a fiber optic interferometer. The moire fringe patterns formed by the interferometer depend on the arrangement of three fiber ends. The experiment results and the intensity distribution function of the interference patterns are given.


Abstract The article investigates dependence of EDFA performance on its operating conditions. First of all, the impact of changes in channel spacing on the quality of the amplifier signal and on the desired EDFA configuration is observed – three different values of channel spacing are considered – 37.5 GHz, 50 GHz and 100 GHz. Afterwards, the impact of EDFA positioning on the quality of the amplified signal and the desired configuration is assessed. Three different EDFA positioning scenarios are considered – when the EDFA is used as a power booster, as an in-line amplifier and as a preamplifier. In all cases, such configuration of the EDFA is found that can ensure bit-error ratio (BER) values below 1·10−9 in all channels of the system. To assess the performance of the amplifiers, power penalty values are obtained in respect to identical transmission systems but without amplification.


Greening of the synthetic route for metal–organic frameworks (MOFs) has attracted much interest as a decisive step for practical industrial applications. For a more feasible process, employing waste plastic materials as a potential linker source for MOF synthesis is highly encouraging, combining a sustainable and environmentally friendly approach for scale-up production. The process is more economical when the whole MOF synthesis can be achieved based on waste metal and linker sources in the presence of green solvents derived from waste materials as well. Herein, we present a waste valorization approach for the preparation of MOFs based on different recycled polymer waste materials, MOFs based on waste metal sources, and MOFs based on the coupling of waste sources for both the organic ligand and metal center. This approach not only recycles discarded products but also produces high value-added costly materials for different applications.


Recent studies have shown that the chemokine stromal cell‐derived factor (SDF)‐1 and its receptor CXCR4 are involved in the metastatic process of colorectal cancer. The impact of SDF‐1 on the stimulated metastatic growth during hepatectomy‐associated liver regeneration is unknown. With the use of a heterotopic murine colon cancer model, we analyzed whether blockade of SDF‐1 inhibits angiogenesis and extrahepatic growth of colorectal cancer after liver resection. Functional neutralization of SDF‐1 by 1 mg/kg body weight anti‐SDF‐1 antibody only slightly delayed the initial tumor cell engraftment but also did not reduce the size of established extrahepatic tumors compared with controls. Tumor cell apoptosis was increased by anti‐SDF‐1 treatment only during the early 5–9‐day period of tumor cell engraftment, but was found significantly decreased during the late phase of tumor growth. The initial delay of tumor cell engraftment was associated with an increase of tumor capillary density and microvascular permeability. This was associated with an increased vascular endothelial growth factor (VEGF) expression and an enhanced tumor cell invasion of the neighboring tissue. In contrast to the neutralization of SDF‐1, blockade of the SDF‐1 receptors CXCR4 and CXCR7 significantly reduced tumor capillary density and tumor growth. Thus, our study indicates that neutralization of SDF‐1 after hepatectomy is not capable of inhibiting angiogenesis and growth of extrahepatic colorectal tumors, because it is counteracted by the compensatory actions through an alternative VEGF‐dependent pathway.


This paper discusses the performance improvement of a green building by optimization procedures and the influences of load characteristics on optimization. The green building is equipped with a self-sustained hybrid power system consisting of solar cells, wind turbines, batteries, proton exchange membrane fuel cell (PEMFC), electrolyzer, and power electronic devices. We develop a simulation model using the Matlab/SimPowerSystemTM and tune the model parameters based on experimental responses, so that we can predict and analyze system responses without conducting extensive experiments. Three performance indexes are then defined to optimize the design of the hybrid system for three typical load profiles: the household, the laboratory, and the office loads. The results indicate that the total system cost was reduced by 38.9%, 40% and 28.6% for the household, laboratory and office loads, respectively, while the system reliability was improved by 4.89%, 24.42% and 5.08%. That is, the component sizes and power management strategies could greatly improve system cost and reliability, while the performance improvement can be greatly influenced by the characteristics of the load profiles. A safety index is applied to evaluate the sustainability of the hybrid power system under extreme weather conditions. We further discuss two methods for improving the system safety: the use of sub-optimal settings or the additional chemical hydride. Adding 20 kg of NaBH4 can provide 63 kWh and increase system safety by 3.33, 2.10, and 2.90 days for the household, laboratory and office loads, respectively. In future, the proposed method can be applied to explore the potential benefits when constructing customized hybrid power systems.


The power deposition profile in the two-ion hybrid resonance heating regime in tokamaks is studied by including the modification of the minority ion velocity distribution. The Fokker-Planck equation and the kinetic wave equation are solved numerically in order to describe the time evolution of the velocity distribution and the deposition profile. The power that is transferred coUisionally to the electrons and majority ions from the minority ions is also calculated. Application to the JET plasma demonstrates strong electron heating near the plasma centre. Control of the deposition profile by varying the minority ion concentration and the magnitude of the magnetic field is also discussed.


The paper investigates high-Reynolds-number stationary instabilities in the boundary layer on a rotating disc. The investigation demonstrates that, in addition to the inviscid mode found by Gregory, Stuart & Walker (Phil. Trans. R. Soc. Lond. A 248, 155 (1955)) at high Reynolds numbers, there is a stationary short-wavelength mode. This mode has its structure fixed by a balance between viscous and Coriolis forces and cannot be described by an inviscid theory. The asymptotic structure of the wave-number and orientation of this mode is obtained, and a similar analysis is given for the inviscid mode. The expansion procedure provides the capacity of taking non-parallel effects into account in a self-consistent manner. The inviscid solution of Gregory et al. is modified to take account of viscous effects. The expansion procedure used is again capable of taking non-parallel effects into account. The results obtained suggest why the inviscid approach of Gregory et al. should give a good approximation to the experimentally measured orientation of the vortices. The results also explain partly why the inviscid analysis should not give such a good approximation to the wavenumber of the vortices. The asymptotic analysis of both modes provides a starting point for the corresponding nonlinear problems.


IntroductionNew Zealand's (NZ) Integrated Data Infrastructure (IDI) has rapidly expanded since our 2016 IPDLN conference update. Researchers have available a wide range of administrative and survey data. Even major earthquake damage to a Statistics NZ building in late 2016 has not halted progress with expanding the IDI and its usage.
Objectives and ApproachTo provide an update on the current state of the IDI and its use by the NZ research community.
To highlight some key areas that need further discussion because of the IDI's rapid growth, especially concerning :

Privacy, regulation and governance: how to make progress within appropriate regulatory constraints, especially around maintaining confidentiality, data sovereignty, data ethics and data security.
Capacity building: what are the best ways to build multidisciplinary skills for new IDI users, share code and knowledge and what types of networking options work best?
Cross-sectoral data linkage: to maximise the value of the IDI.

ResultsIn the last two years there has been a rapid expansion of external datalabs with access to the IDI (now around 33) and with the number of researchers using these datalabs (around 650). This has resulted in many useful research outputs; but it has also highlighted some areas that need more consideration including:

Data sovereignty: NZ needs to ensure a strong role of Māori (Indigenous NZers) in data governance to ensure that IDI data are used to maximise reduction in health and social inequalities.
Options for assisting new IDI users and exploring the best ways of sharing code, knowledge and networking.
To maximise value there needs more focus on use of cross-sectoral data linkage (to better understand the impact of social determinants on long-term health).

Conclusion/ImplicationsThere has been rapid expansion of the scope and use of the IDI in New Zealand. But to ensure the continuation of the success to date, even more attention needs to be paid to such issues as data governance and data protection.


Abstract:-In the context of "SwachhSarvekshan", the concept of waste management plays a very significant role in achieving the vision and mission of "Swachh Bharat Abhiyan", the clean mission of India. Waste, on one hand can become a factor undesirable, on the other and the most important angle, can contribute significantly to the national income as it has the potential to become a great source of income if put to use through recycling and reusing. The present research paper focusing on domestic waste highlights the software solution that was designed using MATLAB-GUI for using in accounting for revenues or losses generated during the administration of waste management, particularly at municipality level. Considering nine modules with nine parameters as one for each module, the software formulated assists in calculation of revenues generated out of recycled and reused waste, in a flash of a moment. The software will also provide a solution for re-planning the process of re-usage of waste, if any discrepancy is found between the budget amount and the actual costs incurred. The cumbersome managerial issues hitherto involved in various administrative processes for waste management find easy electronic solution in the software designed in the current research paper.


Background: Vibrio scophthalmi is an opportunistic bacterial pathogen, which is widely distributed in marine environment. Earlier studies have suggested that it is a normal microorganism in turbot gut. However, recent studies have confirmed that this bacterial strain can cause diseases in many different marine animals. Therefore, it is necessary to investigate its whole genome for better understanding its physiological and pathogenic mechanism.Results: In the present study, we obtained a pathogenic strain of V. scophthalmi from diseased half-smooth tongue sole (Cynoglossus semilaevis) and sequenced its whole genome. Its genome contained two circular chromosomes and two plasmids with a total size of 3,541,838 bp, which harbored 3,185 coding genes. Among these genes, 2,648, 2,298 and 1,915 genes could be found through annotation information in COG, Blast2GO and KEGG databases, respectively. Moreover, 10 genomic islands were predicted to exist in the chromosome I through IslandViewer online system. Comparison analysis in VFDB and PHI database showed that this strain had 334 potential virulence-related genes and 518 pathogen-host interaction-related genes. Although it contained genes related to four secretion systems of T1SS, T2SS, T4SS and T6SS, there was only one complete T2SS secretion system. Based on CARD database blast results, 180 drug resistance genes belonging to 27 antibiotic resistance categories were found in the whole genome of such strain. However, there were many differences between the phenotype and genotype of drug resistance.Conclusions: Based on the whole genome analysis, the pathogenic V. scophthalmi strain contained many types of genes related to pathogenicity and drug resistance. Moreover, it showed inconsistency between phenotype and genotype on drug resistance. These results suggested that the physiological mechanism might be complicated.


Newton's third law represents a certain symmetry in nature: Forces always occur in pairs, and one body cannot exert a force on another without experiencing a force itself. We sometimes refer to this law loosely as "action-reaction," where the force exerted is the action and the force experienced as a consequence is the reaction. Newton's third law has practical uses in analyzing the origin of forces and understanding which forces are external to a system.


Resolution of inflammation is an active process which is important for maintaining or restoring homeostasis in response to inflammatory insult. Failure in resolution results in persistent and chronic inflammation which increases the risk of cancer development. Efferocytosis, an essential part of resolution of inflammation, is defined as phagocytic removal of apoptotic cells, especially neutrophils, at the inflamed site, thereby preventing exposure of tissue to toxic intracellular components. It is carried out by a distinct group of phagocytes including anti-inflammatory macrophages (M2 type). Therefore, M2 macrophages represent a key component of the cellular proresolving mechanism and a potential factor for prevention of inflammation-associated cancer. Dysregulation, often overexpression, of c-Myc drives dedifferentiation of cancer cells to acquire capacity for self-renewal and metastasis, which accounts for poor prognosis in cancer patients. A cytoplasmic N-terminal part of full length c-Myc, termed Myc-nick, has been reported to promote differentiation of myoblasts. In the present study, we investigated whether Myc-nick is involved in M2 macrophage polarization and promotion of efferocytosis. We found that ectopic expression of Myc-nick in mouse bone marrow derived macrophages (BMDM) promoted the M2 macrophage polarization through upregulation of interleukin 10 (IL-10) and peroxisome proliferator activated receptor gamma (PPARγ). Furthermore, overexpression of exogenous Myc-nick in BMDM increased capture of apoptotic cells by BMDM through upregulation of a class of phosphatidyl serine (PS) receptors including T-cell immunoglobulin and mucin domain containing 4 (Timd4). PS constitutes one of 'eat-me' signals carried by apoptotic cells. PS receptors present on the surface of macrophages are important to recognize, engulf and finally clear apoptotic cells via phagocytosis. In addition, Myc-nick-induced efferocytosis was found to be tightly associated with K (lysine) acetyltransferase 2A (Kat2a/Gcn5). This may lead to the acetylation of transcription factors that regulate expression of PS receptor proteins. In conclusion, activation of M2 macrophages by Myc-nick facilitates efferocytosis and hence resolution of inflammation, and this may suppress inflammation-associated cancer progression. Citation Format: Xiancai Zhong, Ha-Na Lee, Young-Joon Surh. Myc-nick promotes efferocytosis through M2 macrophage polarization. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 825.


Ribociclib plus an aromatase inhibitor and ovarian function suppression is the preferred first-line option for pre-/perimenopausal women with hormone receptor-positive/human epidermal growth factor receptor-2-negative advanced or metastatic breast cancer. We opened an italian managed access program (MAP) that permitted access to ribociclib to selected patients and allowed to collect informative results on the clinical impact of the therapy. The MAP (April 2018–May 2020) included 64 premenopausal patients, with characteristics similar to those of the MONALEESA-7 trial. Of 57 patients with a known response, 48 (84.2%) achieved a clinical benefit (i.e., complete response, N = 7 (12.3%); partial response, N = 17 (29.8%); stable disease, N = 24 (42.1%)), while 9 (15.8%) experienced tumor progression. Some patients (N = 15–23.4%) needed ribociclib dose reduction because of adverse events. Thereafter, the treatment was well tolerated, and no new safety signals emerged. Our study is the first reported Italian real-world evidence of ribociclib effectiveness in premenopausal HR+/HER2− advanced breast cancer patients. Response and clinical benefit rates were particularly encouraging compared with those of the ribociclib group of MONALEESA-7. Our work confirms that ribociclib in combination with endocrine therapy is highly effective in the treatment of premenopausal HR+/HER2− advanced breast cancer patients with an expected safety profile.


Presented in this paper is a method that combines computer and human intelligence into a joint power to confront the intractability of assembly sequence planning. This method applies the theory of parameterized complexity to identify the source of complexity, and then separates and designates different tasks according to the strengths of autonomous planning and human reasoning for collaborative planning. The injection of human expertise via collaboration greatly helps to reduce the computational complexity of autonomous planning, and parameterized complexity analysis provides the much needed guideline for automated processes to decide when and what types of help are needed so that human intervention can be reduced to the minimum.


Pemphigus is an autoimmune disease affecting the skin and mucosae. Oral lesions are common and sometimes are the only manifestations of the disease. The clinical presentations of pemphigus might mimic other vesiculobullous lesions of the oral cavity. We report a case of a 60-year-old male patient who complained of erosive lesions in the oral cavity. The lesions were diagnosed as pemphigus based on histopathological examination and immunofluorescence findings. The patient did not respond to topical steroids and low doses of systemic steroids. Since the patient began developing dermatological manifestations, he was administered pulse steroid therapy. He is currently under observation and his clinical signs and symptoms show improvement, although he has developed hyperglycemia as a complication.