Proponents of making, particularly those in the West (Anderson 2012; Gershenfeld 2005), have been promoting a generalized idea of maker practice and education across the globe. Examples include international standards in the form of the Fab Charter and the exclusion of local maker presenters during the first editions of the Maker Faire Shenzhen in China. Such strategies work to highlight the dominant narrative of making within the cultural localities of the Silicon Valley and the East Coast of North America. But what happens, when the social, economic, and cultural conditions of the West do not apply to the making practices of other places, even in what is widely understood as the West? How are locally-based practices, traditions, and pedagogies shaping the adoption of this maker model? In this paper, we draw on observations and analyses from our distinct ethnographic research on maker practices, makerspaces, and their communities across North America and Europe. Spanning five years and conducted in nine countries, our methods were primarily qualitative including data gathered through observation, interviews, and attendance of maker-related events. One of us has been examining the presumably disruptive qualities of "alternative" maker practices. This has resulted in explorations of makerspaces in US public libraries, feminist hacker groups, and repair collectives and their potentially emancipatory impact on marginalized communities. The other author has been charting the influence of maker practices and technologies on professional design work. This research has led to questioning the ideas of de-professionalization and deconstruction of boundaries between lay and professional practice. Our mutual point of entry into our distinct but intersecting studies, which we share with other research on maker practices and cultures (Lindtner et al. 2016; Lindtner & Li 2017), is a disapproval of the Western technosolutionism programmed into maker narratives. While some of the observed making manifests Western ideas on the surface, we have also encountered how different—even Western— makerspaces and fab labs have reintroduced culturally contingent local features to discern themselves from innovation-driven technological objectives. Examples include, for instance, slöjd traditions in the work approaches of Danish designer-makers and pedagogical techniques such as the Montessori approach in DIY care projects in Italy. This position paper shares several instances of making and makerspaces framed by local attributes and histories—and while it does not cover postcolonial sites, it still reveals that a general trope of the West is also imprecise. Thereby we hope to contribute to an ongoing rearticulation and intervention into the dominant presence of the Silicon Valley-model of maker practice (Lindtner & Lin 2017). References: Anderson, Chris. 2013. Makers: the New Industrial Revolution. New York: Crown Business. Gershenfeld, Neil. 2005. Fab: The Coming Revolution on Your Desktop–From Personal Computers to Personal Fabrication. New York: Basic Books. Lindtner, Silvia, Shaowen Bardzell, and Jeffrey Bardzell. 2016. "Reconstituting the Utopian Vision of Making: HCI After Technosolutionism." In: Proceedings of the 2016 CHI Conference on Human Factors in Computing Systems (CHI '16), 1390-1402. Lindtner, Silvia, and Cindy Lin. 2017. "Making and Its Promises." CoDesign, 13(2), 70-82.


The basement membrane (BM), of which laminin is a major glycoprotein component, is an important barrier to tumour cells which must be breeched before metastatic spread can occur. We have compared the pattern of laminin expression in a range of benign and malignant breast lesions to better understand the process of tumour progression. A total of 162 cases of breast samples, comprising 18 fibroadenomas, 22 cases of fibrocystic disease, 96 cases of invasive ductal carcinoma and 26 carcinomas with intraductal components, were evaluated for laminin expression by a standard immunoperoxidase method on formalin-fixed, paraffin-embedded histological sections, using a commercial antibody against human laminin. The pattern of laminin expression was charted as follows: Type I, > 70% of BM complete/continuous; Type II, > 70% of BM moderately disrupted; Type III, > 70% of BM completely disrupted. The Type I pattern was observed in all cases of fibroadenoma and fibrocystic diseases, and in 77% of intraductal carcinoma components. Various patterns of BM disruption were observed in invasive ductal carcinoma. Severity of BM disruption correlated with histological grade of the carcinomas (P < 0.001). Small-sized tumours, those without lymphatic invasion and lymph node-negative tumours showed more complete patterns of laminin expression. The current study suggests that tumour cells with high histological grade possess an enhanced capacity to disrupt the basement membrane, an important step in the metastatic process. The detection of BM disruption by immunohistochemical staining for laminin is technically easy and may be usefully applied for the differentiation of in situ and microinvasive carcinoma.


The Chulitna terrane is an enigmatic, fault-bounded package of mid-Paleozoic to early Mesozoic sedimentary rocks and volcanics that are exotic to North America and show no clear affi nity with any of the other allochthonous terranes in southern Alaska. Geologic mapping and geochemical analyses of Triassic strata from the Chulitna terrane indicate Triassic rifting of a Devonian volcanic arc and development of an asymmetric basin that was later deformed in the Cretaceous within the broadly defi ned suture between the Wrangellia composite terrane and the Mesozoic margin of North America. The structure of the region consists of an overturned synclinorium that verges southeast, Triassic strata in the core of the syncline, and basement rocks exposed in the hanging walls of a series of out-of-syncline thrusts on the southeastern, upright limb. The basement of the complex consists of serpentinite, vesicular fl ows of basaltic andesite with minor pillow lavas, and volcanic debris with blocks of andesite and minor Devonian red chert. From southeast to northwest, there are systematic changes in the facies associated with Triassic strata that overlie this basement. To the southeast, the basement is unconformably overlain by bedded sedimentary breccias that consist of subangular clasts of basement lithologies, including red chert, serpentinite, and andesite. Further to the northwest, in the hanging wall of a more rearward thrust, the red-bed strata consist of conglomerate intermixed with siltstone and cross-bedded sandstone. In the northwest on the overturned limb of the syncline, the red beds are composed of siltstone and sandstone interfi ngered with limestone. There is an overall increase in the thickness of the red-bed unit from southeast to northwest. On the northwestern limb of the syncline, the red beds overlie a 1500-m-thick basalt sequence with columnar jointed fl ows and pillow basalts interbedded with limestone. Geochemical analyses of clinopyroxene phenocrysts in the basalts show similarities with island-arc basalts, suggesting that volcanism was related to early rifting of an oceanic arc. A marine sandstone unit overlies the entire red-bed package along a fl ooding surface and thins to the southeast. These results are consistent with Triassic deposition within a rifted volcanic arc, an upland erosion surface to the southeast, and increasing thickness of the Triassic section toward a basin-bounding fault in the northwest. This basin was initially ~18 km wide prior to accretion along the Mesozoic margin of North America, which resulted in southeast-vergent folding and 30% shortening.


The temporal stability and the analysis reproducibility of nutrient concentration of leaf blades and petioles of Vitis vinifera L. cv. Tempranillo were evaluated at a vineyard representing the soil and climate conditions within the AOC Rioja region of Spain. Leaf blade and petiole were sampled throughout the growing season and analyzed for N, P, K, Ca, Mg, Fe, Mn, Zn, Cu, and B concentrations. For reproducibility of the analyses, leaf blade had a lower percent coeffcient of variation (%CV) of total N, and K than petiole, while petiole had a lower %CV than leaf blade for B. Phosphorus and Mg had similar %CV in blade and petiole at flowering, while blade had lower %CV at veraison for both nutrients. Calcium, Mn, and Fe had similar %CV in both tissues throughout the growing season. Seasonal changes of nutrient concentration in leaves confirmed the need for specific reference values for both leaf blades and petioles in each phenological stage. In general, nutrient concentration trends throughout the growing season showed short periods without differences between consecutive samplings near the 100% capfall phenological stage, while no statistical differences were found between samples obtained at any time throughout veraison. Results suggest that blade could be a more appropriate tissue for total N and K evaluation, whereas petiole is more appropriate for B evaluation. Calcium, Mn, and Fe will have a similar accuracy in both tissues at any phenological stage. While P and Mg had similar reproducibility in blade and petiole at flowering, blade seems be a better tissue for P and Mg nutritional diagnosis at veraison.


A precipitated iron Fischer−Tropsch (F−T) catalyst (100 Fe/3 Cu/4 K/16 SiO2 on mass basis) was tested in a stirred tank slurry reactor under reaction conditions representative of industrial practice using CO-rich synthesis gas (260 °C, 1.5−2.2 MPa, H2/CO = 2/3). Repeatability of performance and reproducibility of catalyst preparation procedure were successfully demonstrated on a laboratory scale. Catalyst productivity was increased by operating at higher synthesis pressure while maintaining a constant contact time in the reactor and through the use of different catalyst pretreatment procedures. In one of the tests (run SA-2186), the catalyst productivity was 0.86 (g hydrocarbons/g Fe/h) at syngas conversion of 79%, methane selectivity of 3% (weight percent of total hydrocarbons produced), and C5+ hydrocarbon selectivity of 83 wt %. This represents a substantial improvement in productivity in comparison to state-of-the-art iron F−T catalysts. This catalyst is ideally suited for production of high-quality d...


AZD3229 demonstrates pan-KIT/PDGFRα activity in several preclinical models and is a promising agent for the treatment of GIST. Getting the GIST of treatment Gastrointestinal stromal tumor, or GIST, can be targeted by inhibiting KIT and platelet-derived growth factor α (PDGFRα). Unfortunately, the therapeutic effects do not always last, as the tumors develop resistance mutations that are not susceptible to existing drugs. Banks et al. report the design of AZD3229, a compound that combines selectivity for KIT and PDGFRα with broad activity against a variety of disease-causing mutations. Its selectivity decreases the risk of off-target toxicity, which has been a problem for multiple other KIT/PDGFRα inhibitors. AZD3229 showed promising activity and safety in a range of drug-resistant GIST mouse models, suggesting its potential for clinical translation. Gastrointestinal stromal tumor (GIST) is the most common human sarcoma driven by mutations in KIT or platelet-derived growth factor α (PDGFRα). Although first-line treatment, imatinib, has revolutionized GIST treatment, drug resistance due to acquisition of secondary KIT/PDGFRα mutations develops in a majority of patients. Second- and third-line treatments, sunitinib and regorafenib, lack activity against a plethora of mutations in KIT/PDGFRα in GIST, with median time to disease progression of 4 to 6 months and inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) causing high-grade hypertension. Patients with GIST have an unmet need for a well-tolerated drug that robustly inhibits a range of KIT/PDGFRα mutations. Here, we report the discovery and pharmacological characterization of AZD3229, a potent and selective small-molecule inhibitor of KIT and PDGFRα designed to inhibit a broad range of primary and imatinib-resistant secondary mutations seen in GIST. In engineered and GIST-derived cell lines, AZD3229 is 15 to 60 times more potent than imatinib in inhibiting KIT primary mutations and has low nanomolar activity against a wide spectrum of secondary mutations. AZD3229 causes durable inhibition of KIT signaling in patient-derived xenograft (PDX) models of GIST, leading to tumor regressions at doses that showed no changes in arterial blood pressure (BP) in rat telemetry studies. AZD3229 has a superior potency and selectivity profile to standard of care (SoC) agents—imatinib, sunitinib, and regorafenib, as well as investigational agents, avapritinib (BLU-285) and ripretinib (DCC-2618). AZD3229 has the potential to be a best-in-class inhibitor for clinically relevant KIT/PDGFRα mutations in GIST.


This repository includes a description of the files needed to replicate the findings reported in 'Talking Politics on Social Media' by Rolf Fredheim and Alfred Moore --README.txt --anon.Rdata Rdata file containing deidentified commenting data needed to reproduce main figures and findings reported in the paper. --reproduction.py script used to identify reason-giving, agreement, disagreement, and insults. This script requires Python 2, version 2.5 or higher, and the modules codecs, ner, pyenchant, re, and urllib2. --suppMat.Rmd: R markdown file used to generate the supplementary materials. It includes examples of comments identified as positive matches, as well as the code necessary to recreate figures, statistical tests, etc. This script requires the following packages: data.table, ggthemes, ggplot2, gridExtra, knitr, Rmisc, and scales. The supplementary materials were compiled through Rstudio 0.99.484 on a computer running Ubuntu 14.04 with a full installation of TeX and Pandoc. TeX set up for debian based systems: apt-get install libcairo2-dev pandoc textlive texlive-latex-extra texlive-fonts-extra texlive-xetex


A spindle matrix has been proposed to help organize and stabilize the microtubule spindle during mitosis, though molecular evidence corroborating its existence has been elusive. In Drosophila, we have cloned and characterized a novel nuclear protein, skeletor, that we propose is part of a macromolecular complex forming such a spindle matrix. Skeletor antibody staining shows that skeletor is associated with the chromosomes at interphase, but redistributes into a true fusiform spindle structure at prophase, which precedes microtubule spindle formation. During metaphase, the spindle, defined by skeletor antibody labeling, and the microtubule spindles are coaligned. We find that the skeletor-defined spindle maintains its fusiform spindle structure from end to end across the metaphase plate during anaphase when the chromosomes segregate. Consequently, the properties of the skeletor-defined spindle make it an ideal substrate for providing structural support stabilizing microtubules and counterbalancing force production. Furthermore, skeletor metaphase spindles persist in the absence of microtubule spindles, strongly implying that the existence of the skeletor-defined spindle does not require polymerized microtubules. Thus, the identification and characterization of skeletor represents the first direct molecular evidence for the existence of a complete spindle matrix that forms within the nucleus before microtubule spindle formation.


Mehmed, A., Enchev, S. & Bozhimirov, S. (2021). Assessment of initial material for stevia selection (Stevia rebaudiana B.). Bulg. J. Agric. Sci., 27 (3), 536–540 The leaves of South American plant – Stevia (Stevia rebaudiana B.) contain low-calorie but highly effective glycosides (stevioside and rebaudiside) that are extracted as a commercial product, which is 300 to 320 times sweeter than sugar and can be safely used by diabetics. The enhanced interest in stevia cultivation (Stevia rebaudiana Bertoni) as a source for natural, non-calorific sweeteners requires constant enrichment of the gene pool of initial material for the selection. Propagation of stevia is carried out by seeds, vegetative and in vitro methods. Seed germination is usually very poor, and vegetative propagation by cutting the stem requires large stocks of stems, and therefore this method is limited. An alternative approach to successfully replicate and maintain stevia is to use in vitro methods. The soil and climatic conditions in Bulgaria also allow the successful cultivation of S. rebaudiana B., but due to its high sensitivity to low temperatures, stevia in Bulgaria is only grown as an annual plant. The current study was carried out in 2017 in Agricultural Institute – Shumen (Bulgaria). The used selection material in this study is seedlings of 33 origins, obtained by 3 different methods: from seeds, from stem cuttings and in vitro propagation. Around May 10th when the danger of frosts has passed, the plants are planted in the field at 50/30cm distance. The selection materials Stevia differ in the evaluated morphological and productive traits. From the comparative tests, the most perspective for effective production were the seedlings from in vitro regenerates. A tendency was established for more stable yields in some stabilized populations as a result of prolonged selection. Based on dry mass yield, the R-3 population was most productive – 115 g. The method for obtaining seedlings did not have a significant effect on the height trait of the plants. An evaluation of the gene pool of Agricultural Institute – Shumen was made and the perspective stevia origins for fresh and dry leaf mass production were selected.


Landscape painting has played a significant role in shaping practices of nature appreciation in Western and Chinese cultures. Both cultures have also seen the recent emergence of philosophical views of nature appreciation that stress the importance of ecological understanding. However, these philosophical views differ in their response to the influence of the landscape painting tradition: whereas Western approaches have largely been critical, Chinese ecoaestheticians have embraced it. In this paper, we explore this difference and argue that it is not explained by differences between Western and Chinese art but by differences in Western and Chinese philosophers' conceptions of ecology. We further argue that, even granting these differing conceptions of ecology, consideration of the problematic aspects of the landscape painting tradition remains a pressing concern for ecoaesthetics.


Beekeeping has a major economic importance, because these have an important role in most crops pollination that are destined for seed production. This study is part of the first researches realised on canola culture, in Romania and was observed the evolution of honeybees family, before and after the application of pesticides, which represents a stress factor. After seven days from the treatment application the number of honeybees identified at the entry in the beehive decreased sudden, from a maximum number of 367 honeybees registered at the beehive entrance at the beginning of researches to a minimum number of 77 honeybees, and after 14 days from the pesticides application, the number of identified honeybees started to increase till 323 honeybees. The witness had a slight increase during the entire measurement period, at the beginning of the study it had a maximum of 330 honeybees at the beehive entrance and in the second week of observation the maximum recorded value was of 512 honeybees at 12 o'clock. In the third week of observations in the control variant the maximum number of honeybees recorded was of 605, honeybees identified at 12 o'clock. Based on these observations we have noticed that in the three studied variants the number of honeybees in the control variant where no pesticides had been used, has been throughout the entire period higher than in the two studied variants and where insecticides had been applied for protecting the canola culture. Therefore we can say that the honeybees in the first area suffered more because of insecticide used in canola culture. Number of bees found in the first area was less than in the second area, and also was less than the control area where the bees did not suffer at all, and have had steady growth throughout the flowering period of rape culture. The second area has the smallest amount of honey. To prevent these negative aspects, occurs the necessity of friendly relations between the beekeepers in pastoral and farmers cultivators of canola, for avoid negative phenomena that can happen during collecting.


PURPOSE
The German Retina.net ROP registry and its Europe-wide successor, the EU-ROP registry, collect data from patients treated for ROP. This analysis compares input parameters of these two registries to establish a procedure for joint analyses of different registry data using exemplary datasets from the two registries.

METHODS
Exemplary datasets from the two databases over a 1-year period each (German Retina.net ROP Registry, 2011, 22 infants; EU-ROP Registry, 2021, 44 infants) were compared. The parameters documented in the two databases were aligned and analysed regarding demographic parameters, treatment modalities, complications within first 24 h and retreatments.

RESULTS
The current analysis showed that data can be aligned for joint analyses with some adjustments within the data structure. The registry with more detailed data collection (EU-ROP) needs to be reduced regarding granularity in order to align the different registries, as the registry with lower granularity determines the level of analyses that can be performed in a comparative approach. In the exemplary datasets, we observed that the overall most common ROP severity in both registries was zone II, 3+ (2011: 70.5%; 2021: 65%), with decreasing numbers of clock hours showing preretinal neovascularisations (2011: 10-12 clock hours in 29% of cases, 2021: 4-6 clock hours in 38%). The most prevalent treatment method was laser coagulation in 2011 (75%) and anti-VEGF therapy in 2021 (86.1%). Within the anti-VEGF group, all patients were treated with bevacizumab in 2011 and with ranibizumab in 2021. Retreatment rates were comparable in 2011 and 2021.

CONCLUSION
Data from two different ROP registries can be aligned and jointly analysed. The analysis reveals a paradigm shift in treatment modalities, from predominantly laser to anti-VEGF, and within the anti-VEGF group from bevacizumab to ranibizumab in Germany. In addition, there was a trend towards earlier treatment in 2021.


One incentive for developing the alphavirus Sindbis virus as a vector for the expression of heterologous proteins is the very high level of viral structural proteins that accumulates in infected cells. Although replacement of the structural protein genes by a heterologous gene should lead to an equivalent accumulation of the heterologous protein, the Sindbis virus capsid protein is produced at a level 10- to 20-fold higher than that of any foreign protein. Chimeric mRNAs which contain the first 275 nucleotides of the Sindbis virus 26S mRNA fused to the lacZ gene are also translated at the higher level. The enhancing sequences, located downstream of the AUG codon that initiates translation of the capsid protein, have a predicted hairpin-like structure; deletions in this region destroy the activity. These sequences enhance translation in infected cells but have the opposite effect in uninfected cells. Furthermore, translation of this RNA in infected cells is suppressed by a second viral RNA lacking the hairpin-like structure, but translation of the latter RNA is not affected. We propose that the hairpin-like structure presents a barrier to the movement of the ribosomes during translation of mRNA. In infected cells, under conditions in which this mRNA is essentially the only RNA being translated, a slowdown in the transit of the ribosomes gives factors present at low concentrations a chance to bind to the translation complex and permits a high level of functional complexes to be formed. In uninfected cells and in infected cells translating two different viral subgenomic mRNAs, a pause in the movement of the ribosomes along the RNA is no longer an advantage, because the required factors are now usurped by other translation complexes.


Diverse coastal seaweed communities dominated by perennial fucoids become replaced by species-poor turfs of annual algae throughout the Baltic Sea. A large-scale field survey and factorial field experiments indicated that grazers maintain the fucoid community through selective consumption of annual algae. Interactive effects between grazers and dormant propagules of annual algae, stored in a 'marine seed bank', determine the response of this system to anthropogenic nutrient loading. Nutrients override grazer control and accelerate the loss of algal diversity in the presence but not in the absence of a propagule bank. This implies a novel role of propagule banks for community regulation and ecosystem response to marine eutrophication.


Serotonin plays a key role in mood or affect, and dysfunction of the serotonin system has been linked to depression in humans and animal models. Depression appears prior to or coincident with overt symptoms of Alzheimer's disease (AD) in about 50% of patients, and some experts consider it a risk factor for the development of AD. In addition, AD is more prevalent in women, who also show increased incidence of depression. Indeed, it has been proposed that mechanisms underlying depression overlap the mechanisms thought to hasten AD. Women undergo ovarian failure and cessation of ovarian steroid production in middle age and the postmenopausal period correlates with an increase in the onset of depression and AD. This laboratory has examined the many actions of ovarian steroids in the serotonin system of non-human primates using a rhesus macaque model of surgical menopause with short or long-term estradiol (E) or estradiol plus progesterone (E+P) replacement therapy. In this mini-review, we present a brief synopsis of the relevant literature concerning AD, depression, and serotonin. We also present some of our data on serotonin neuron viability, the involvement of the caspase-independent pathway, and apoptosis-inducing factor in serotonin-neuron viability, as well as gene expression related to neurodegeneration and neuron viability in serotonin neurons from adult and aged surgical menopausal macaques. We show that ovarian steroids, particularly E, are crucial for serotonin neuron function and health. In the absence of E, serotonin neurons are endangered and deteriorating toward apoptosis. The possibility that this scenario may proceed or accompany AD in postmenopausal women seems likely.


Data Envelopment Analysis is a linear programming technique for assessing the efficiency and productivity of decision making units (DMUs). Over the last decade, DEA has gained considerable attention as a managerial tool for measuring performance. The flexibility in selecting the weights in standard DEA models deters the comparison among DMUs on a common base. Moreover, these weights are unsuitable to measure the preferences of a decision maker (DM). For dealing with these two difficulties simultaneously; we use preference common weights. This paper uses preference common weights for time-series evaluations to calculate the global Malmquist productivity index (MPI) so that the productivity of changes of all DMUs have a common basis for comparison, and DM's preference information is incorporated in calculating global MPI.


Conventional liquefied natural gas (LNG) cargo vessels are imposed with tank-fill limitations as precautions to prevent structural damage and stability-loss due to high-impact sloshing, enforcing cargo volume-fills to be lower than 10% or higher than 70% of the tank height. The restrictions, however, limit commercial operations, specifically when handling spot trades and offshore loading/unloading at multiple ports along a shipping route. The study puts forward a computational fluid dynamic (CFD) sloshing analysis of partially-filled chamfered rectangular tanks undergoing sinusoidal oscillatory kinetics with the use of the explicit volume-of-fluid and non-iterative time-advancement schemes. Establishing a 20% to 60% fill-range, the sloshing dynamics were acknowledged within an open-bore, partitioned, and perforated-partitioned tank when oscillating at frequencies of 0.5 Hz and 1 Hz. The overall torque and static pressure induced on the tank walls were investigated. High-impact slamming at the tank roof occurred at 40% and 60% fills, however, the implementation of the partition and perforated-partition barriers successfully reduced the impact due to suppression and dissipation of the wave dynamics.


We propose a system that can record driving events and detect unsafe driving behaviors. Three sensors, an engine control unit (ECU) reader, a 3-axis accelerometer, and a camera are used, in which they represent the car, the passenger, and the driverpsilas perspective. Our system combines data from these three sensors with a fuzzy inference system to identify an event of hazardous driving. The output of the system is the driving risk level ranging from 1 to 3, where 1 is the safest. The output of the system was verified by comparison with a questionnaire from three passengers in a test run experiment.


Background Providing teaching on non-technical skills, or 'human factors', is of increasing interest to healthcare professionals, yet it is rarely universally taught. Teams continue to make human errors despite technical expertise and knowledge, compromising patient safety. Our aim was to design a one-day, multi-professional, multidisciplinary course to teach, practice and apply non-technical and team-working skills in emergency situations through simulated scenarios in a safe, open, environment. Methodology To cater for different clinical settings, and the various teams therein operating, the course would provide a common teaching 'stem' of morning lectures, case studies and team-working exercises, with speciality themed afternoon simulated scenarios to practice these. So far, we have developed 'A-TEAMS: Advanced Teamworking in Emergency and Acute Medical Situations', set in the emergency department, and 'S-TEAMS' the surgical equivalent, set in theatre. During simulation, professionals stay within their normal role to keep the experience as realistic as possible. Teams are encouraged to focus on skills such as communication strategies, situational awareness and the use of prompts, eg checklists, to improve team-working. A thorough debrief with highly experienced senior clinicians follows. Results Over 150 healthcare professionals have completed the course thus far. All participants felt the course had a clear structure and that learning objectives were explicit. 95% felt the scenarios had good or excellent relevance to clinical practice. 100% found the course useful and would recommend it to their colleagues. Longer-term data (up to 18 months post course completion) revealed 98% of participants had incorporated the non-technical skills learnt into clinical practice. Potential impact There is a real demand and enthusiasm for developing non-technical skills within modern healthcare. A training course which includes simulation, focusing on human factors in a multiprofessional and multidisciplinary environment will improve not only team-working, but the culture in general and, ultimately, patient safety. References Flin R, O'Connor P, Crichton M.' Safety at te Sharp End', First Ed, 2008, Ashgate Publishing Ltd Flin R, Maran N. 'Identifying and Training Non-technical Skills for Teams in Acute Medicine'. Quality and Safety in Healthcare 2004;3:i80–i84 Yule et al. 'Non technical skills for surgeons in the operating room: a review of literature'. Surgery 2006;39;6:140–149 Andersen et al. 'Identifying Non-technical Skills and Barriers for Improvement in Cardiac Arrest Teams'. Resuscitation 2010;81;6:695–702


Plasma turbulence associated with the creation of an artificial dust layer in the Earth's ionosphere is investigated. Two scenarios are considered for plasma irregularity generation as dust is injected at an oblique angle across the magnetic field. The first is a shear-driven plasma instability due to inhomogeneities in the boundary layer between the injected charged dust layer and the background plasma. This begins to appear at very early times relative to the release of the dust into the plasma, which is on the order of or less than the dust charging time period. The second mechanism is free streaming of the dust relative to the background plasma, which produces irregularities at times much longer than the dust charging period and also longer than the dust plasma period. Although both mechanisms are shown to produce turbulence in the lower hybrid frequency range, the resulting irregularities have important differences in their physical characteristics. A comparison between the processes is made to determine the consequences for upcoming observations. Both processes are shown to have the possibility to generate turbulence after the release of dust for the regimes of upcoming space experiments over a range of timescales.


Banggai cardinal fish (Pterapogonkauderni, Koumans 1933) is uncommon example of a marine fish with distributed in small range area while being in highly exploited. This fish is in high demand as an ornamental fish. However, the information on the number of density is limited. An underwater visual fish census survey was conducted in June to July 2010 at 18 fishing sites around Banggai archipelago to estimate the density of the stock and assess the impact of fishing and habitat on density. The areas are divided into three main islands, namely Banggai Island, Peleng Island, Toropot-Tumbak-Labobo Island. The lowest density index of the P. kauderni recorded at Kindandal village on Peleng Island, 0.014 fish/m2while the highest abundance index of 3.0 fish/m2 found at Toropot village at Toropot Island. In three survey sites (Bonebaru and Toropot villages) where the fishing activities are still ongoing, the density has declined compared to the survey conducted in 2004. Majority of the villages in Peleng Island have lower density compared with the other islands probably due to the degradation of microhabitat of P. kauderni. In many cases, microhabitat degradation might be as a result of collection of sea urchins and sea anemone for consumption by local community.


We have employed a genetic approach to study the resistance of tomato to the phytopathogenic bacterium Pseudomonas syringae pv tomato. Resistance to P. s. tomato depends upon expression of the Pto locus in tomato, which encodes a protein with similarity to serine/threonine protein kinases and recognizes pathogen strains expressing the avirulence gene avrPto. Eleven tomato mutants were isolated with altered resistance to P. s. tomato strains expressing avrPto. We identified mutations both in the Pto resistance locus and in a new locus designated Prf (for Pseudomonas resistance and fenthion sensitivity). The genetic approach allowed us to dissect the roles of these loci in signal transduction in response to pathogen attack. Lines carrying mutations in the Pto locus vary 200-fold in the degree to which they are susceptible to P. s. tomato strains expressing avrPto. The pto mutants retain sensitivity to the organophosphate insecticide fenthion; this trait segregates with Pto in genetic crosses. This result suggested that contrary to previous hypotheses, the Pto locus controls pathogen recognition but not fenthion sensitivity. Interestingly, mutations in the prf locus result in both complete susceptibility to P. s. tomato and insensitivity to fenthion, suggesting that Prf plays a role in tomato signaling in response to both pathogen elicitors and fenthion. Because pto and prf mutations do not alter recognition of Xanthomonas campestris strains expressing avrBsP, an avirulence gene recognized by all tested tomato cultivars, Prf does not play a general role in disease resistance but possibly functions specifically in resistance against P. s. tomato. Genetic analysis of F2 populations from crosses of pto and prf homozygotes indicated that the Pto and Prf loci are tightly linked.


We study the behavior of strategic customers in an open-routing service network with multiple stations. When a customer enters the network, she is free to choose the sequence of stations that she visits, with the objective of minimizing her expected total system time. For the two-station game with deterministic service times, we prove that the game is supermodular. By applying the supermodularity result, we observe that strategic customers "herd," i.e., in equilibrium all customers choose the same route. We then identify a broad class of learning rules --- which includes both fictitious play and Cournot best-response --- that converges to herding in finite time. We also find that the herding behavior is prevalent in many other open-routing service networks, including those with stochastic service times and those with more than two stations.


In the present study, the effect of various weight fractions of graphene nanoplatelet (GPL) on flexural fatigue behavior of epoxy polymer has been investigated at room temperature and generally the temperature was monitored on the surface of specimen during each test. The flexural stiffness of grapheme nano-platelet/epoxy nanocomposites at 0.1, 0.25 and 0.5 wt. % as a main effective parameter on flexural bending fatigue was considered. The samples were implemented to different displacement fatigue amplitudes and it led to the known bending strength ratio. Finally, the flexural fatigue responses of graphene nano-platelet/epoxy nanocomposites at mentioned graphene contents were taken into account. The experimental results show that the addition of 0.25 wt. % of graphene nano-platelet on fatigue life was more effective in comparison with 0.1 and 0.5 wt. % epoxy graphene nanocomposites. According to the addition of graphene nano-platelets, a remarkable increase in fatigue life of epoxy was observed. For instance, at the bending strength ratio equal to 43% by adding 0.1, 0.25 and 0.5 wt. % of graphene into epoxy resin, 22.4, 27.4 and 17 times improvement in flexural bending fatigue life of the neat epoxy were observed, respectively.


Strong fatigue during sustained operations is difficult to quantify because of its complex nature and large inter-individual differences. The most evident and unambiguous sign is the occurrence of microsleep (MS) events. We aimed at detecting MS utilizing computational intelligence methods. Our analysis was based on biosignal and video recordings of 10 healthy young adults who completed 14 sessions over two nights in our real-car driving simulation lab. Visual scoring by trained raters led to 2,290 examples of MS. Only evident events accompanied by prolonged eyelid closures, roving eye movements, head noddings, major driving incidents, and drift-out-of-lane accidents were regarded as MS. All other cases with signs of fatigue were regarded as dubious. The same amount of counterexamples (Non-MS) where continued driving was still possible were picked out from the recordings. Non-MS and MS examples covered only 15% of the whole time. Support-Vector Machines were utilized as classifiers and were adapted to these two classes of examples. If such classifiers were applied consecutively, then 100% of time is covered. Validation analysis demonstrated that the classifier gained high selectivity and high specificity. Based on this complete coverage, the percentage of MS in a predefined time span can be calculated. This measure was highly correlated to deteriorations in driving performance and to subjective self-ratings of sleepiness. We conclude that reliable detection of MS is possible despite large intra- and inter-individual differences in behaviour and in biosignal characteristics. Therefore, the percentage of detected MS gives an objective measure of strong driver fatigue.


The aim of this study was to record the length-weight relationship parameters and condition factors for some commercially important fish of Bushehr coastal waters of Persian Gulf. The length-weight relationships were calculated for five species caught during fishing surveys using different types of fishing gears (trawls, pots and gill net with different mesh size) during April 2008 to December 2010. The b value ranged between 2.733 for Argyrops spinifer and 3.03 for Epinephelus coioides . The coefficient of determination (r2) was very significant for all the species. Relative weight had significant differences (Kruskal-Wallis test, P<0.001) with best performance by E. coioides. This results show that this range size of specimens in these populations apparently do not reach and surpass 100% of mean weight. In this study, length-weight relationships and condition factors are reported for the first time for A. spinifer, Pomadasys kaakan and Lutjanus malabaricus from the Persian Gulf and for Lethrinus nebulosus and Lutjanus malabaricus ruber which has not been previously recorded in the Iranian waters. Key words : Length-weight relationships, condition factor, relative weight, Persian Gulf.


Future necessity of implement several levels of design is established. The most important variables which defined the behavior of structures under seismic actions are identified and their influence in the structural behavior is analyzed in order to obtain the risk spectra associated to a specific seismic hazard and structural vulnerability. Thus the assessment of the seismic demand associated to any level of performance, which can be used either to design new structures or evaluate existent structures.


Federated learning (FL) is a collaborative machine learning technique to train a global model (GM) without obtaining clients' private data. The main challenges in FL are statistical diversity among clients, limited computing capability among clients' equipment, and the excessive communication overhead between the server and clients. To address these challenges, we propose a novel sparse personalized FL scheme via maximizing correlation (FedMac). By incorporating an approximated l1 -norm and the correlation between client models and GM into standard FL loss function, the performance on statistical diversity data is improved and the communicational and computational loads required in the network are reduced compared with nonsparse FL. Convergence analysis shows that the sparse constraints in FedMac do not affect the convergence rate of the GM, and theoretical results show that FedMac can achieve good sparse personalization, which is better than the personalized methods based on the l2 -norm. Experimentally, we demonstrate the benefits of this sparse personalization architecture compared with the state-of-the-art personalization methods (e.g., FedMac, respectively, achieves 98.95%, 99.37%, 90.90%, 89.06%, and 73.52% accuracy on the MNIST, FMNIST, CIFAR-100, Synthetic, and CINIC-10 datasets under non-independent and identically distributed (i.i.d.) variants).


Dynamic binary translator (DBT) is typically used for software migration or binary code optimization. In this paper, we describe the design and implementation of a multi-sources and multi-targets DBT–CrossBit, which aims at fast migrating existing executable source code from one platform to another alien target platform with lower cost. In order to support code translation among multi-sources and multi-targets better, a new intermediate instruction set– VInst, which is independent of any specific machine instructions, has been introduced. Unlike many other existing DBTs which directly translate the binary code of one instruction set architecture (ISA) to another ISA, CrossBit first converts source binary code to VInst specifications, and then transforms them into target platform code, using a granularity of a basic block (BB) as the unit of translation. Additionally, to address the performance issue, we adopt several generic optimization methods to optimize the translated code. Finally, our experimental result indicates that, for the SPECint2000 benchmarks, CrossBit's performance is pleasant and can meet the design requirement. Keywords-DBT; intermediate instruction; CrossBit; basic block;


Abstract. Modern eddy covariance (EC) systems collect high-frequency data (10–20 Hz)
via digital outputs of instruments.
This is an important evolution with respect to the traditional and widely
used mixed analog/digital systems, as fully digital systems help overcome
the traditional limitations of transmission reliability, data quality, and
completeness of the datasets. However, fully digital acquisition introduces a new problem for guaranteeing
data synchronicity when the clocks of the involved devices themselves cannot
be synchronized, which is often the case with instruments providing data via
serial or Ethernet connectivity in a streaming mode. In this paper, we
suggest that, when assembling EC systems "in-house", aspects related to
timing issues need to be carefully considered to avoid significant flux
biases. By means of a simulation study, we found that, in most cases, random timing
errors can safely be neglected, as they do not impact fluxes significantly.
At the same time, systematic timing errors potentially arising in
asynchronous systems can effectively act as filters leading to significant
flux underestimations, as large as 10 %, by means of attenuation of
high-frequency flux contributions. We characterized the transfer function of
such "filters" as a function of the error magnitude and found cutoff
frequencies as low as 1 Hz, implying that synchronization errors can
dominate high-frequency attenuations in open- and enclosed-path EC systems.
In most cases, such timing errors neither be detected nor characterized
a posteriori. Therefore, it is important to test the ability of traditional
and prospective EC data logging systems to assure the required synchronicity
and propose a procedure to implement such a test relying on readily
available equipment.


In multigigahertz integrated-circuit design, the extra energy loss caused by conductor surface roughness in metallic interconnects and packagings is more evident than ever before and demands explicit consideration for accurate prediction of signal integrity and energy consumption. Existing techniques based on analytical approximation, despite simple formulations, suffer from restrictive valid ranges, namely, either small or large roughness/frequencies. In this paper, we propose a robust and efficient numerical-simulation methodology applicable to evaluating general surface roughness, described by parameterized stochastic processes, across a wide frequency band. Traditional computation-intensive electromagnetic simulation is avoided via a tailored scalar-wave modeling to capture the power loss due to surface roughness. The spectral stochastic collocation method is applied to construct the complete statistical model. Comparisons with full wave simulation as well as existing methods in their respective valid ranges then verify the effectiveness of the proposed approach.


The objective of this study was to evaluate the simplification of design procedures for continuous post-tensioned members using an average-tendon stress as opposed to the current-design procedure of using a variable-tendon stress at different design control points along the length of a tendon profile. This report evaluates the tendon stress distribution due to frictional effects during jacking and seating of several tendon profiles. Measured strand stress values along the tendon profile are compared to predicted theoretical stress values. After seating, the redistribution of strand stresses was observed to determine the magnitude of tendon stress equalization and the necessary time period for redistribution to occur. The results of laboratory and field experimental studies are summarized in this report.


MicroRNAs (miRNAs/miRs) serve an important role in the regulation of carcinogenic pathways. RCC is the most prevalent kidney cancer that occurs in adults. miRNAs have gained increasing attention due to their association with RCC tumorigenesis, serving as biomarkers for early detection and progression monitoring, and as potential targets for molecular therapy. Upregulation of miRNA-142-3p has been previously identified in RCC tissues by microarray profile, however, its expression and function in RCC have not yet been validated. In the present study, quantitative polymerase chain reaction was performed to quantify the relative expression of miR-142-3p in 53 paired RCC and adjacent normal tissues. Furthermore, wound healing, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays were performed to analyze the impacts of miR-142-3p on cellular migration, proliferation and apoptosis. The results demonstrated that miR-142-3p was significantly upregulated in RCC tissues compared with adjacent normal tissues. Downregulation of miR-142-3p, induced by chemically synthesized miR-142-3p inhibitor, significantly suppressed cell migration and proliferation, and promoted cell apoptosis in 786-O and ACHN cells, supporting the theory that miR-142-3p may function as an oncogene in RCC. The potential clinical significance of miR-142-3p, as a biomarker and therapeutic target, provides rationale for further investigation into the miR-142-3p-mediated molecular pathway and how it is associated with RCC development.


Single phase natural circulation loops are widely used passive systems in heat transfer applications. Since achievement of stable flow and highly efficient heat transfer is the main concern of recent studies, effects of geometry and the working fluid on the single phase natural circulation loops' performance are getting attention. In this study, aspect ratio and pipe diameter effect on thermo-hydraulic performance of mini SPNCLs (SPNCmLs) has been investigated numerically by developing a 3D steady model. Water based Al2O3 nanofluid (1, 2, 3 vol. %) was used as a working fluid. Performance and characteristics of the loop for different working fluids is evaluated by using temperature distributions, mass flow rates and derived non-dimensional parameters. It is shown that pipe diameter effect on the heat transfer performance is more significant compared to aspect ratio. Moreover, nanofluids have higher temperatures and thus effectiveness values compared to water. In order to generalize the SPNCmL performance Num and Ress correlations were developed within the accuracy of ±10%.


The emergence of perovskite solar cells (PSCs) recently has brought new hope to the solar cell industry due to their incredible improvement of the power conversion efficiency (PCE), which can now exceed 20.0% within seven years of tremendous research. The efficiency and stability of PSCs depend strongly on the morphology and type of materials selected as the electron transport layer (ETL) in the device. In this review, the functions of the ETL based on titania (TiO2) in n–i–p architecture PSCs, including planar heterojunction and mesoporous-structured devices, are reviewed in terms of the device performance and stability. Studies found that the application of suitable fabrication techniques and manipulation of the nanostructural properties of TiO2 are crucial factors in ameliorating the short-circuit current density, JSC, and fill factor, FF, of PSCs. On top of that, the effect of substituting TiO2 with other potential inorganic materials like zinc oxide (ZnO), tin oxide (SnO2), ternary metal oxides, and metal sulphides, as well as organic semiconductors including fullerene, graphene, and ionic liquids, towards the photovoltaic properties and stability of the devices are also elaborated and discussed. Meanwhile, the utilization of non-electron transport layers (non-ETLs), such as alumina (Al2O3) and zirconia (ZrO2), as the mesoporous scaffold in PSCs is found to enhance the open-circuit voltage, VOC, of the devices.


Protein kinases Aurora A, B, and C play essential roles during mitosis and cell division, are frequently elevated in cancer, and represent attractive targets for therapeutic intervention. TAK-901 is an investigational, multitargeted Aurora B kinase inhibitor derived from a novel azacarboline kinase hinge-binder chemotype. TAK-901 exhibited time-dependent, tight-binding inhibition of Aurora B, but not Aurora A. Consistent with Aurora B inhibition, TAK-901 suppressed cellular histone H3 phosphorylation and induced polyploidy. In various human cancer cell lines, TAK-901 inhibited cell proliferation with effective concentration values from 40 to 500 nmol/L. Examination of a broad panel of kinases in biochemical assays revealed inhibition of multiple kinases. However, TAK-901 potently inhibited only a few kinases other than Aurora B in intact cells, including FLT3 and FGFR2. In rodent xenografts, TAK-901 exhibited potent activity against multiple human solid tumor types, and complete regression was observed in the ovarian cancer A2780 model. TAK-901 also displayed potent activity against several leukemia models. In vivo biomarker studies showed that TAK-901 induced pharmacodynamic responses consistent with Aurora B inhibition and correlating with retention of TAK-901 in tumor tissue. These preclinical data highlight the therapeutic potential of TAK-901, which has entered phase I clinical trials in patients within a diverse range of cancers. Mol Cancer Ther; 12(4); 460–70. ©2013 AACR.


This study analyzes the suitability of agricultural lands with risk of abandonment for restoration to suitable habitats for animal species of conservation interest. As a case study, the main focus was on olive plantations (Olea europaea L.) of mountainous areas of Southern Spain and the Iberian lynx (Lynx pardinus Temminck, 1827). The method weighs the judgement of experts on the effect of landscape elements on the habitat via an analytic hierarchy process and spots areas most suitable for restoration through geographical information systems. The results suggest that the edge of major agricultural areas and areas with natural vegetation adjacent to the Natural Park of Sierra de Cardena and Montoro would be most suitable for restoration of the lynx habitat. The precise location of olive groves suitable for restoration are discussed, as revealed by experts" decision-making processes. The main interest of the study relies on the potential of the method to combine territorial analysis with biological requirements of endangered species to facilitate their dispersal.


Surface samples were collected from three sections across the newly exposed shores of the Dead Sea. Analysis of the water content of the sediments as well as the Cl and SO 4 concentrations of the sediment solutions was conducted in order to check the effect of leaching by rain on the sediments. In all cross sections decrease in salinity and chlorinity with time of exposure was observed and was taken to represent the leaching effect of rain. High salinities near the shore reflect input of sea spray. Only the dssl0 cross section represents conditions unperturbed by the upwelling of groundwater and thus enables one to assess the effects of rain leaching only. The spray zone in the dss10 case dominates the sediment solutions up to 12 m from the shore line (equivalent to an exposure period of 3 years). From then on salinity decreases until constant salinities are reached at a distance of 27 m from the shore line corresponding to about 9 years of exposure, at a [Cl -- ] c oncentration of 0.3 eq/l. In the other cross sections (dss3, dss9) the effect of groundwater input (of saline/fresh type) was more significant than the effect of rain in adding/ removing salts from the sediments and therefore the pattern of decrease in salinity with time was perturbed. Relatively constant gypsum concentrations in the sediments in all cross sections indicate that the amount of rain that passed through the sediments in the last 50-60 years was not sufficient to cause a significant dissolution of gypsum.


Laser ablation coupled to multicollector inductively coupled plasma mass spectrometry (LA-MC-ICPMS) allows accurate and precise isotope ratio determination of solid samples in a quasi-nondestructive manner, making the technique interesting for isotopic provenance studies of valuable historical artifacts. In order to enable LA-MC-ICPMS analysis of objects that cannot be transported to the laboratory for analysis, a portable laser ablation sampling device was applied. Ablated material was collected on filters, which were subsequently analyzed in the laboratory by means of MC-ICPMS. Filters were analyzed by: (I) acid digestion followed by solution nebulization MC-ICPMS and (II) fast scanning filter ablation coupled to MC-ICPMS. For both procedures, the analytical performance was investigated for lead isotope ratio measurements in ceramics, lead ore (galena) and the metallic lead standard NIST SRM 981. Filter digestion followed by solution analysis allowed determination of lead isotope ratios with external precisions of better than 0.10‰. Mass-dependent deviations towards lighter isotope ratios of 0.10‰ per u were observed for metallic lead, which indicates to a low extent isotopic fractionation during the sampling procedure. Filter ablation coupled to MC-ICPMS resulted in reduced precision compared to the solution measurements. However, it enabled straightforward simultaneous isotopic and elemental analysis by splitting the carrier gas flow to a MC-ICPMS and quadrupole ICPMS. In summary, portable LA sampling followed by MC-ICPMS analysis was shown to enable lead isotope ratio determinations of objects in the field with an analytical performance similar to a laboratory-based analysis. The approach was applied to lead isotope provenancing of ancient Chinese ceramics.


As the number of online communities (OCs) continues to increase, it is critical for an OC to satisfy users' needs in order to encourage and retain their voluntary participation and contribution over time. Consistent with the IS Success model, we argue that information quality and system quality are two important antecedents of OC user satisfaction. However, little IS research has systematically examined quality issues and their impacts in the OC context. To bridge the gap, we empirically investigate the impacts of information quality and system quality on user satisfaction in one of the largest travel OCs. Based on the IS quality literature, we develop a measurement model by incorporating different dimensions of information quality and system quality. Given the uniqueness of OCs, this study enriches our understanding of why and how information and system quality matter in an OC. It also provides insights for OC design and management.


Studying the structure and composition of solid-state materials on the atomic scale has become nearly routine in transmission electron microscopy with the development of novel electron optics and electron sources. In particular, with spatial resolutions better than 0.1 nm and energy resolution smaller than 100 meV, the stoichiometry, bonding, and coordination can now be examined on similar scales. Aberration-corrected scanning transmission electron microscopy and electron energy-loss spectroscopy (EELS) have played a crucial role in identifying charge ordering, valence, and as spin state transitions in transition metal perovskite oxides. In this letter, we investigate the effects of ever-decreasing electron-probe sizes on the measured near-edge fine-structure of the transition metal core-loss edge using EELS. We find that for certain transition metal perovskites, the position of the electron probe with respect to the atomic column is crucial in determining the correct valence state. Several reasons for the observed position-sensitive EELS fine-structure are discussed.


: Aerobic, thermophilic composting is a widely practiced method for disposal of organic wastes. The wastes which are composted include biosolids from waste water treatment plants (WWTP), and biowastes (food scraps and yardwaste). Important hygiene issues are involved in composting since many potential pathogens may be present in the fresh wastes. In this study, the survival of Salmonella and Escherichia coli is examined during aerobic composting of municipal solid wastes, municipal wastewater sludge and biowastes. A laboratory compost was prepared by inoculating with 10(7) Salmonella typhimurium Q and Escherichia coli B. In both industrial and laboratory trials, gene probes were used to determine at what time during the composting and at what temperature these bacteria became undetectable. It was observed that Salmonella and E. coli survived for 59 days at about 60 degrees C in an industrial compost. The bacteria became undetectable after the temperature decreased from 62 degrees C to about 40 degrees C in the compost curing. The bench scale trials showed that E. coli B survived for at least 9 days at 60-70 degrees C in a biowaste (food waste) compost or a waste water sludge compost. Salmonella typhimurium Q survived for at least 9 days over 60 degrees C in the food biowaste compost and at least 5 days in the waste water sludge compost. Data collected show that the temperature or the time of high temperature is difficult to correlate to the destruction of the pathogen, Salmonella, or the pathogen indicator, E. coli. These results suggest that the mechanism for removal of these microorganisms during aerobic composting is complex and not simply the result of a thermal physical environment.


Abstract This study presents zircon fission track data from the Bucovinian nappe stack (northern part of the Inner Eastern Carpathians, Rodna Mountains) and a neighbouring part of the Biharia nappe system (Preluca massif) in order to unravel the thermal history of the area and its structural evolution by integrating the fission track data with published data on the tectonic and sedimentary evolution of the area. The increase of metamorphic temperatures towards the SW detected by the zircon fission track data suggests SW-wards increasing tectonic overburden (up to at least 15 km) and hence top NE thrusting. Sub-greenschist facies conditions during the Alpine metamorphic overprint only caused partial annealing of fission tracks in zircon in the external main chain of the Central Eastern Carpathians. Full annealing of zircon points to at least 300 °C in the more internal elements (Rodna Mountains and Preluca massif). The zircon fission track central and single grain ages largely reflect Late Cretaceous cooling and exhumation. A combination of fission track data and stratigraphic constraints points to predominantly tectonic differential exhumation by some 7-11 km, connected to massive Late Cretaceous extension not yet detected in the area. Later events such as the latest Cretaceous ("Laramian") juxtaposition of the nappe pile with the internal Moldavides, causing exhumation by erosion, re-burial by sedimentation and tectonic loading during the Cenozoic had no impact on the zircon fission track data; unfortunately it prevented a study of the low temperature part of the Late Cretaceous exhumation history.


In the Canes Venatici cloud, eighteen dwarf irregular galaxies were observed in B; V bands at the Nordic Optical Telescope under a seeing of one arc- sec. Most of the galaxies having radial velocities V0 < 500 km/s have been resolved into stars for the rst time. The galaxy distances were derived based on photome- try of their brightest blue stars. Distances to some of the galaxies: UGC 6782, UGC 7131 and, probably, K 215, which are located at the CVn southern edge, were es- timated to be about 15 Mpc, which is typical of the Virgo cluster outskirts. For two LSB galaxies, K 200 and K 215, the distances may be overestimated, probably be- cause of a lack of young massive stars. For the remaining galaxies: UGC 7559, UGC 7599, UGC 7605, UGC 7639, UGC 7698, UGCA 290, UGCA 292, UGC 7866, UGC 8024, UGC 8638, UGC 8651, UGC 8760, and UGC 8833 the estimated distances range from 2.3 to 8.0 Mpc, indicating their actual membership in the CVn cloud. Several objects studied here (UGC 7605, UGC 7639, UGC 8638, UGC 8833) have a well-resolved bluish core and regular yellow outer parts, which may point to composite (new and old) populations. The galaxy UGCA 292 = CVn dwA has unusual global parameters: (B V )T=+0.08, MT = 11:4, M(HI)=LB =6 M=L andM(HI)=MT =0 :7, being, perhaps, one of the youngest known objects in the Local Universe.


Florida is a site of critical inquiry and figures prominently in the US American imaginary. The Sunshine State sets the stage for broader conversations about cultural difference, climate change, and participatory democracy. Contributors to this special issue apply the canonical circuit of culture model to address the interrelated nature of culture and power. They provide methodologically thick, fleshy interpretive analyses that privilege experiential, experimental, and embodied approaches to take seriously Florida cultural politics, people, and popular forms.


Migraine is a very common disorder occurring in 20% of women and 6% of men. Central neuronal hyperexcitability is proposed to be the putative basis for the physiological disturbances in migraine. Since there are no consistent structural disturbances in migraine, physiological and psychophysical studies have provided insight into the underlying mechanisms. This is a review of the neurophysiological studies which have provided an insight to migraine pathogenesis supporting the theory of hyperexcitability.


A novel material with coexisting switchable nonlinear optical (NLO) and dielectric properties, [trimethylchloromethyl ammonium]2[ZnCl4] [(TMCM)2-ZnCl4], which undergoes two reversible solid state phase transitions at 337 K (Tc1) and 258 K (Tc2), respectively, has been successfully synthesized and grown as block crystals. Exceptionally, variable-temperature X-ray single crystal structural analyses of (TMCM)2-ZnCl4 reveal that the unusual space group changes from P212121 at 223 K to P21/c between Tc2 and Tc1 to Pmcn above Tc1. As expected, the dielectric value of (TMCM)2-ZnCl4 exhibits two remarkable step-like enlargements around Tc1 and Tc2, indicating that it exhibits a low dielectric state, an intermediate dielectric state and a high dielectric state. In particular, the second harmonic generation (SHG) efficiency shows a sharp step-like increase from almost zero to 0.47, and its SHG activities in a high-NLO state can be recovered after several cycles without any attenuation. The transitions of (TMCM)2-ZnCl4 could be intrinsically ascribed to the sequential order–disorder transformations of both the cations and anions. All these results demonstrate its potential application as a switchable and tunable molecular dielectric and NLO material.


The use of multiple traits for drought study affirms the complexity of drought tolerance in cowpea. Despite the availability of several traits for drought tolerance evaluation, the rapid screening technique used by many scientists for seedling drought in wooden boxes is the simplest method for screening large populations. The objective of this study was to select drought tolerant cowpea recombinant lines developed from a drought tolerant and susceptible parent using the wooden box screening technique. Two hundred Recombinant Inbred Lines (RILS) an F2:6 generation were used for the study. The parents were drought tolerant line crossed with susceptible line. Screening was done in wooden boxes and plants stressed for 4 weeks and in two sessions. Leaf wilting, relative water content, chlorophyll content during stress, and recovery from drought data were taken. Results from this study showed significant differences (p < 0.05) for relative chlorophyll content for the 4 weeks of water stress and relative water content taken on the second week of water stress for all 200 inbred lines, but no significant differences were observed for the parental checks. Relative water contents taken for RILS during water-stress ranged between 70-20% for drought tolerant and drought susceptible lines respectively. The parental lines used as checks both had relative water contents of 60%. Relative water content for the second experiment ranged between 74-22% for tolerant and susceptible RILS respectively. About 12 inbred lines consistently performed well for recovery, 13 RILS were susceptible. RILS that maintained a higher relative water and chlorophyll contents, with high proportion of survived seedlings were 11. Potential seedling drought tolerant RILS have been identified.

 Key words:  Cowpea, leaf wilting, chlorophyll, recombinant inbred lines, drought tolerance, relative water content.


There probably are few diseases known to man which have caused as much speculation regarding their treatment as erysipelas. Standard textbooks and current medical literature allude to many forms of therapy, among which are well known local applications such as sulphonated bitumen, N. F., zinc stearate, magnesium sulphate, alcohol glycerin, mercurochrome-220 soluble, phenol, lead water, mercuric chloride, picric acid and iodine in various combinations. In addition whole blood, serums, leukocytic extracts and vaccine have all been exploited. Recently Alquier 1 and others have advocated the use of ultraviolet radiation. The multiplicity and variability in methods of treatment in a given disease probably indicate an uncertainty as to the value of all of these therapeutic procedures and the lack of uniform success following their employment only stresses the fact that the disease in question is more or less self limited. Erysipelas stands out as a striking example of this group of diseases,


OBJECTIVE
To study the effect and safety of intensive phototherapy in the treatment of neonatal hyperbilirubinemia.

METHODS
A total of 144 neonates with neonatal hyperbilirubinemia were randomly and prospectively divided into intensive phototherapy group and conventional phototherapy group, with 72 neonates in each group. The therapeutic effect and incidence of complications were compared between the two groups.

RESULTS
Within 12 hours after phototherapy, the total serum bilirubin level in the intensive phototherapy group was significantly lower than in the conventional phototherapy group (P<0.05), and the intensive phototherapy group had a significantly greater reduction in serum bilirubin level than the conventional phototherapy group (P<0.05). The intensives phototherapy group had a significantly shorter time of phototherapy than the conventional phototherapy group (P<0.05). The incidence rates of fever, diarrhea, rash, and hypocalcemia and reductions in blood calcium and hemoglobin levels after phototherapy showed no significant differences between the two groups.

CONCLUSIONS
During the initial stage of phototherapy, intensive phototherapy can quickly and effectively reduce the serum level of bilirubin in neonates with neonatal hyperbilirubinemia. It can also shorten the total phototherapy time, and does not increase the incidence of adverse events. Therefore, it is superior to conventional phototherapy.


Background: Plantar fasciitis is the most common cause of heel pain. Sonography has been proposed for early and differential diagnosis of heel pain. Materials and Methods: The study was performed on patients with plantar fasciitis (n=40). After completing the demographic data, the pain intensity was measured using Visual Analogue Scale (VAS); foot and ankle function by Foot and Ankle Ability Measure (FAAM) tests. In addition, ultrasonography of plantar fascia was performed. The t test and Pearson correlation were used for analysis. Results: The Mean for plantar fascia thickness was 4.7±0.42 mm. A significant inverse correlation was observed between pain intensity during the day with foot limitation in daily activities (P=0.001) and during the exercise (P=0.017). A significant inverse correlation was found between morning foot pain and restrictions in daily activities (P=0.008). Plantar fascia thickness had no significant correlation with the variables studied. However, in women plantar fascia thickness had a direct and significant correlation with BMI (P=0.002). Conclusion: Despite a significant correlation between plantar fascia thickness and BMI in women, no correlation was found between plantar fascia thickness with other variables. Therefore, weight loss in patients, particularly women, may reduce the thickness and symptoms of the condition.


The increase in velocity, volume, and complexity of the data generated by the upcoming LCLS-II upgrade presents a considerable challenge for data acquisition, data processing, and data management. These systems face formidable challenges due to the extremely high data throughput, hundreds of GB/s to multi-TB/s, generated by the detectors at the experimental facilities and to the intensive computational demand for data processing and scientific interpretation. The LCLS-II Data System offers a fast, powerful, and flexible architecture that includes a feature extraction layer designed to reduce the data volumes by at least one order of magnitude while preserving the science content of the data. Innovative architectures are required to implement this reduction with a configurable approach that can adapt to the multiple science areas served by LCLS. In order to increase the likelihood of experiment success and improve the quality of recorded data, a real-time analysis framework provides visualization and graphically-configurable analysis of a selectable subset of the data on the timescale of seconds. A fast feedback layer offers dedicated processing resources to the running experiment in order to provide experimenters feedback about the quality of acquired data within minutes. We will present an overview of the LCLS-II Data System architecture with an emphasis on the Data Reduction Pipeline (DRP) and online monitoring framework.


A leaf turning red in the fall makes for a much greater mystery than a leaf turning yellow does. The yellowing signals simply a dropping of veils because the yellow pigment has lain hidden in the leaf during its long, green summer. When summer ends and the green pigments break down, the yellow shines through. Reds, however, don't loll around all summer. A leaf with only a few weeks left to hang on its tree summons its faltering resources for a burst of bright-red-pigment making.


Interactions between the basolateral amygdala (BLA) and the nucleus accumbens (NAc) mediate reward-related processes that are modulated by mesoaccumbens dopamine (DA) transmission. The present in vivo electrophysiological study assessed: (1) changes in the firing probability of submaximal BLA-evoked single neuronal firing activity in the NAc after tetanic stimulation of the BLA, and (2) the functional roles of DA and NMDA receptors in these processes. Tetanic stimulation of the BLA potentiated BLA-evoked firing activity of NAc neurons for a short duration (∼25 min). This short-term potentiation was associated with an increase in DA oxidation currents that was monitored with chronoamperometry. Systemic or iontophoretic application before BLA tetanus of the D1 receptor antagonist SCH23390, but not the D2 receptor antagonist sulpiride, abolished the potentiation of BLA-evoked NAc activity, whereas administration of SCH23390 3 min after tetanus had no effect. However, systemic administration of the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), either before or after BLA tetanus, abolished the potentiation of BLA-evoked firing of NAc neurons. These data suggest that higher-frequency activity in BLA efferents can autoregulate their excitatory influence over neural activity of NAc neurons by facilitating the release of DA and activating both DA D1and NMDA receptors. This may represent a cellular mechanism that facilitates approach behaviors directed toward reward-related stimuli that are mediated by BLA–NAc circuitries.


Abstract Numerous industrial processes such as conveying, fluidizing and handling involve two-phase (fluid-solids) flows. Investigation of the two-phase flow mechanisms have importance in both industrial manufacturing processes and natural phenomenon such as dust storms, erosion, air pollution and soil deposition in rivers and ocean flows. One of the most significant parameters for designing two-phase (fluid-solids) flow conveying systems is the fluid velocity magnitude. Inaccurate determination of the fluid velocity can lead to high energy consumption, particle attrition, pipe erosion and in some cases pipe blockage. This work reviews numerous studies presented in the literature concerning various threshold velocities in horizontal two-phase (fluid-solids) flow systems. The threshold velocities include: incipient motion, pickup from a layer of particles, pickup from hill-shape particle deposits, boundary saltation and minimum pressure velocity. Most of the studies were conducted in pneumatic and hydraulic conveying systems and large-scale wind tunnels systems. As each threshold velocity characterizes a transition between two or more flow regimes and mode of particle movement, all possible flow regimes of the particle-fluid horizontal conveying systems are present first. Then the threshold velocity models and correlations are analyzed and compared. The theoretical models are compared for the forces and torque vectors taken into account for various threshold conditions and particle package geometry. In addition, the main parameters influencing the pickup and saltation mechanisms and the dimensionless numbers are reviewed. Finally, four threshold velocities are used to characterize a generalized flow regime diagram for horizontal conveying systems. This diagram makes a significant contribution to researching and designing two-phase flow systems. For example, the diagram may assist in the transition conditions between dilute and stratified flow regimes. However, more theoretical and empirical research is required to discover all the possible states of horizontal systems.


The "reasonable person" plays an important role in English and American criminal law, but not in German criminal law. The comparative view yields a number of differences (for example, with respect to negligent crimes, errors about justifying circumstances, and excuses like duress). Besides analyzing such differences, the article examines the legitimate role of social expectations in criminal law (which stand behind references to the "reasonable person") beyond the details of different legal systems. It concludes that one must distinguish judgments about wrongdoing from judgments about personal responsibility. The former are shaped by social expectations, while personal responsibility needs to be evaluated with a view to the individual offender.


Consumers hold landraces in high esteem and often consider that breeding programs lead to a loss of sensory quality, although consumers' opinions have not been scientifically confirmed. As a model case of study we recorded seed sensory traits in six inbred common bean lines classified in the market class Fabada obtained by backcrossing and/or pedi- gree selection (to change the plant architecture and increase resistances) and then cultivated in two environments in two consecutive years. A sensory panel noted differences among all the inbreds, but only the introduction of the gene fin (determinate growth habit) seemed to be associated to a loss of quality (rougher seed coat and lower percentage of whole beans after cooking). As theoretically expected, changes in sensory traits were smaller in inbreds obtained through simple backcrossing than in those obtained through pedigree selection after inbred crossing. Large differences in sensory traits due to environmental factors were also recorded (similar to the genetic effects in magnitude), especially soil type and rainfall around flowering. These results make it highly recommendable to evaluate sensory attributes in the course of breeding programs to ensure that the sensory quality is not lost. Given the importance of the environmental component in the phenotypic variation of the sensory traits studied, crop location and management also appear as key factors for the obtainment of optimum products.


Transient faults became an increasing issue in the past few years as smaller geometries of newer, highly miniaturized, silicon manufacturing technologies brought to the mass-market failure mechanisms traditionally bound to niche markets as electronic equipments for avionic, space or nuclear applications. This chapter presents the origin of transient faults, it discusses the propagation mechanism, it outlines models devised to represent them and finally it discusses the state-of-the-art design techniques that can be used to detect and correct transient faults. The concepts of hardware, data and time redundancy are presented, and their implementations to cope with transient faults affecting storage elements, combinational logic and IP-cores (e.g., processor cores) typically found in a System-on-Chip are discussed


The study of 34 suicides who were in treatment in an ambulatory psychiatric service reveals a predominance of psychotics. Critical description of the treatment, the psychological factors leading up to the suicide (importance of professional conflicts) and the attitude of the physicians. Relationship between the depressive state and the presuicide syndrome. Remarks on foreseeing suicide and on the psychological repercussions on the psychiatrist.


With the discovery of optical fiber there was a widespread revolution in the field of communication. Optical fiber communication offers high data rate, security, flexibility, higher bandwidth etc. However factors such as dispersion, attenuation, scattering etc., greatly hampers it'sperformance. Moreover it's dispersion that severely damages the high speed data transmission in optical fiber. Dispersion causes the pulse to spread as it travels along the fiber and causing interference. There are various methods for dispersion compensation. This research is done to emphasize the effect of dispersion and how to overcome it by using FBG. Fiber Bragg Grating is one of the widely used technology to compensate dispersion in optical fiber communication and here we have used FBG to compensate dispersion in a 80Gb/s WDM network using NRZ modulator at transmitter side and the results thus obtained are compared. The value of Q-factor, eye height and bit error rate (BER) is determined for each and every channel and their values are compared.


Background and Aims : Morphological awareness is one of the dimensions of metalinguistic awareness and is defined as the ability to manipulate morphemes that make up the word and knowledge of the rules of word formation. Previous studies have shown that morphological awareness contributes to literacy achievement. The purpose of the present study was to review the literature available in the context of morphological awareness and its relevance to the accuracy and comprehension of reading in different languages. Materials and Methods : Studies conducted between 1995 and 2017 and published in the Springer, Google scholar, ASHA, Science Direct, PubMed international databases as well as domestic dissertations and journals in Magiran and SID databases were searched. Descriptive-analytic studies that could answer the research question were included in the study. The search was performed using the following keywords: morphological awareness, reading ability, reading accuracy, reading comprehension, and educational achievement. The results of 18 articles are presented in the current review study. Conclusion : The results showed that children with better scores in the morphological awareness test show better results in reading comprehension. In languages such as English, morphological awareness helps to distinguish between words and thus help reading accuracy, but not in Greek. It seems that the relationship between morphological awareness and reading accuracy is different between different languages, according to language properties such as transparency.


Transcriptional networks regulate cell fate decisions, which occur at the level of individual cells. However, much of what we know about their structure and function comes from studies averaging measurements over large populations of cells, many of which are functionally heterogeneous. Such studies conceal the variability between cells and so prevent us from determining the nature of heterogeneity at the molecular level. In recent years, many protocols and platforms have been developed that allow the high throughput analysis of gene expression in single cells, opening the door to a new era of biology. Here, we discuss the need for single cell gene expression analysis to gain deeper insights into the transcriptional control of cell fate decisions, and consider the insights it has provided so far into transcriptional regulatory networks in development.


Diabetes-related neuropathic ulcers located at the plantar aspect of the hallux interphalangeal joint are often chronic or recurrent and frequently become complicated by osteomyelitis. Once infected, treatment will typically involve hallux amputation. Although intended as a definitive procedure, amputation of the first toe is not desirable from a cosmetic or functional standpoint and often leads to transfer ulcers at adjacent locations of the foot. Reconstructive wound surgery, combined with limited bone resection, is possible if the infection is caught early before the local tissue and bone have become necrotic. In addition to neuropathy, biomechanical issues, including ankle equinus, hallux limitus, hallux extensus, and hallux valgus, predispose patients with diabetes mellitus to developing plantar hallux ulcers. We commonly employ a proximal based unilobed plantar rotational flap combined with hallux interphalangeal joint arthroplasty as an alternative to hallux amputation. We present a typical case with long-term follow-up to highlight our flap protocol, including patient selection criteria, flap design, surgical technique, bone resection and biopsy pearls, staging timeline, and a typical postoperative course. Periodic follow-up during the next 72 months for unrelated conditions allowed long-term monitoring with no recurrence of osteomyelitis or subsequent amputation. The foot remained ulcer free 6 years later. The benefits of this surgical approach include complete excision of the ulcer, adequate exposure for bone resection, early bone biopsy before the spread of infection or necrosis of local tissue, flap coverage with viable soft tissue, and partial offloading of mechanical pressure at the plantar interphalangeal joint.


: Progressive osseous heteroplasia (POH) is an ultrarare genetic condition of progressive ectopic ossification. Most cases of POH are caused by heterozygous inactivating mutations of GNAS , the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase. POH is part of a spectrum of related genetic disorders, including Albright hereditary osteodystrophy, pseudohypoparathyroidism, and primary osteoma cutis, that share common features of superficial ossification and association with inactivating mutations of GNAS . The genetics, diagnostic criteria, supporting clinical features, current management, and prognosis of POH are reviewed here, and emerging therapeutic strategies are discussed.


We study the uplink control signaling in 3GPP-Long Term Evolution (LTE) systems. Specifically, we propose a precoding method that uses complex-field coding (CFC) to improve the performance of the PUCCH format 2 control signaling. In the case of perfect channel state information (CSI) at the receiver and with a single receive antenna, the proposed method offers significant gains compared to the coding currently used in 3GPP-LTE. However the gains are marginal with two receive antennas. In order to examine the impact of channel estimation errors, we also derive the optimal detector for the case of imperfect receiver CSI, both for conventional coding and for the proposed CFC method.


Clinical trials are increasingly "offshored" to developing countries. Many participants in these trials can plausibly be regarded as victims of deep structural injustices, e.g. severe avoidable poverty and lack of access to healthcare. This chapter discusses whether patients who benefit from drugs developed among the global poor have any special responsibility to remedy their unjust circumstances. More precisely, it examines whether such a responsibility can be grounded in the fact that these patients are beneficiaries of injustice. Finding no justification for singling out this group, the author ends by exploring the idea that the responsibility to remedy structural injustice is a more widely shared one.


AIM
To evaluate neoangiogenesis in patients with colon cancer by two fluorescently labeled antibodies on fresh biopsy samples imaged with confocal laser endomicroscopy (CLE).

METHODS
CLE is an imaging technique for gastrointestinal endoscopy providing in vivo microscopy at subcellular resolution. An important question in validating tumor angiogenesis is what proportion of the tumor vascular network is represented by pre-existing parent tissue vessels and newly formed vessels. CD105 (endoglin) represents a proliferation-associated endothelial cell adhesion molecule. In contrast to pan-endothelial markers, such as CD31, CD105 is preferentially expressed in activated endothelial cells that participate in neovascularization. Thus, we evaluated CD105 and CD31 expression from samples of ten patients with primary rectal adenocarcinoma, using a dedicated endomicroscopy system. A imaging software was used to obtain the Z projection of the confocal serial images from each biopsy sample previously combined into stacks. Vascular density and vessel diameters were measured within two 50 μm x 475 μm rectangular regions of interest centered in the middle of each image in the horizontal and vertical direction. The results were averaged over all the patients and were expressed as the mean ± SE.

RESULTS
The use of an anti-CD105 antibody was found to be suitable for the detection of blood vessels in colon cancer. Whereas anti-CD31 antibodies stained blood vessels in both normal and pathologic colon equally, CD105 expression was observed primarily in malignant lesions, with little or no expression in the vessels of the normal mucosa (244.21 ± 130.7 vessels/mm(3) in only four patients). The average diameter of anti-CD105 stained vessels was 10.97 ± 0.6 μm in tumor tissue, and the vessel density was 2787.40 ± 134.8 vessels/mm(3). When using the anti-CD31 antibody, the average diameter of vessels in the normal colon tissue was 7.67 ± 0.5 μm and the vessel density was 3191.60 ± 387.8 vessels/mm(3), while in the tumors we obtained an average diameter of 10.88 ± 0.8 μm and a vessel density of 4707.30 ± 448.85 vessels/mm(3). Thus, there were more vessels stained with CD31 than CD105 (P < 0.05). The average vessel diameter was similar for both CD31 and CD105 staining. A qualitative comparison between CLE vs immunohistochemistry lead to similar results.

CONCLUSION
Specific imaging and quantification of tumor microvessels are feasible in human rectal cancer using CLE examination and CD105 immunostaining of fresh tissue samples.


Abstract. We have studied the relationship between the long-term interannual variability in large-scale meteorology in western North Africa – the largest and most active dust source worldwide – and Saharan dust export in summer, when enhanced dust mobilization in the hyper-arid Sahara results in maximum dust impacts throughout the North Atlantic. We address this issue by analyzing 28 years (1987–2014) of summer averaged dust concentrations at the high-altitude Izana observatory (~ 2400 m a.s.l.) on Tenerife, and satellite and meteorological reanalysis data. The summer meteorological scenario in North Africa (aloft 850 hPa) is characterized by a high over the the subtropical Sahara and a low over the tropics linked to the monsoon. We measured the variability of this high–low dipole-like pattern in terms of the North African dipole intensity (NAFDI): the difference of geopotential height anomalies averaged over the subtropics (30–32° N, Morocco) and the tropics (10–13° N, Bamako region) close to the Atlantic coast (at 5–8° W). We focused on the 700 hPa standard level due to dust export off the coast of North Africa tending to occur between 1 and 5 km a.s.l. Variability in the NAFDI is associated with displacements of the North African anticyclone over the Sahara and this has implications for wind and dust export. The correlations we found between the 1987–2014 summer mean of NAFDI with dust at Izana, satellite dust observations and meteorological re-analysis data indicate that increases in the NAFDI (i) result in higher wind speeds at the north of the Inter-Tropical Convergence Zone that are associated with enhanced dust export over the subtropical North Atlantic, (ii) influence the long-term variability of the size distribution of exported dust particles (increasing the load of coarse dust) and (iii) are associated with enhanced rains in the tropical and northern shifts of the tropical rain band that may affect the southern Sahel. Interannual variability in NAFDI is also connected to spatial distribution of dust over the North Atlantic; high NAFDI summers are associated with major dust export (linked to winds) in the subtropics and minor dust loads in the tropics (linked to higher rainfall), and vice versa. The evolution of the summer NAFDI values since 1950 to the present day shows connections to climatic variability (through the Sahelian drought, ENSO (El Nino–Southern Oscillation) and winds) that have implications for dust export paths. Efforts to anticipate how dust export may evolve in future decades will require a better understanding of how the large-scale meteorological systems represented by the NAFD will evolve.


Despite significant efforts, the clinical mechanism of action of hypomethylating agents such as 5-azacytidine (5-aza) is still poorly understood. 5-aza is currently indicated for the treatment of patients with myelodysplastic syndrome (MDS). While 5-aza has achieved good single-agent activity in acute myeloid leukemia (AML), complete response rates remain low when used as a single agent. In a recent report aimed at identifying rational therapeutic combinations with 5-aza, Bogenberger and colleagues identified multiple BCL-2 family member/BH3-containing therapeutic targets, which synergize with 5-aza when inhibited genetically or pharmacologically. The CDK9 inhibitor, alvocidib, has achieved significant improvement in complete response rates of newly diagnosed AML patients when administered before cytarabine and mitoxantrone (FLAM regimen) in a randomized multi-center Phase 2 trial when compared to 7+3 standard of care treatment. Recent reports suggest that the transcriptional repression of key anti-apoptotic proteins (eg., MCL-1) mediated by alvocidib9s CDK9 inhibition, drive the pro-apoptotic activity of alvocidib in the FLAM regimen. We, therefore, hypothesized that alvocidib and 5-aza would synergize therapeutically in the treatment of AML by means of transcriptional repression of MCL-1 and sensitization to 5-aza. In this report, we demonstrate that treatment of AML cell lines with alvocidib inhibits both mRNA and protein expression of MCL-1 in a time and concentration-dependent fashion. Pre-treatment of cells with alvocidib, to repress MCL-1 expression prior to 5-aza treatment, reduced the 5-aza cell viability EC50 more than 2.5-fold, from 1.8 µM to 0.6 µM in MV4-11 cells. The alvocidib/5-aza combination also resulted in synergistic increases in caspase activity relative to either single agent within the combination, at multiple dose levels. Therefore, following reports suggesting inhibition of BCL-2 family members including MCL-1, sensitizes cells to 5-aza, our data suggest that the alvocidib/5-aza combination may constitute a viable therapeutic regimen. We also conclude that a CDK9 inhibitor/5-aza combination may be an effective clinical approach for the treatment of AML. Disclosures Kim:Tolero Pharmaceuticals: Employment. Soh:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Lee:Tolero Pharmaceuticals: Employment. Peterson:Tolero Pharmaceuticals: Employment. Whatcott:Tolero Pharmaceuticals: Employment. Siddiqui-Jain:Tolero Pharmaceuticals: Employment. Weitman:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Warner:Tolero Pharmaceuticals: Employment.


1. Section of the posterior two-thirds of the corpus callosum eliminates almost completely the response of superior colliculus (SC) neurons to stimulation of the contralateral eye in split-chiasm cats. On the contrary, the responsiveness of SC neurons to stimulation of the contralateral eye is not abolished by a transection of the posterior and tectal commissures leaving the corpus callosum intact. The callosal section also reduces the number of SC receptive fields abutting the vertical meridian in the ipsilateral eye of split-chiasm cats. 2. In cats with intact optic pathways, a similar callosal section abolishes the SC representation of the ipsilateral visual field in the ipsilateral eye and also reduces the number of receptive fields adjoining the vertical meridian in the same eye. In the contralateral eye, the SC representation of the ipsilateral visual field is reduced in extension to about one-fifth of that seen in cats with intact commissures. 3. The results suggest that the corpus callosum is the main pathway for cross-midline communication of visual information at not only the cortical, but also the midbrain level. The corpus callosum may subserve this function because it contains uninterrupted crossed corticotectal projections or because it transmits visual information from one hemisphere to contralateral cortical areas projecting ipsilaterally to SC. The latter hypothesis is more likely but, in any case, the findings imply that the lack of interhemispheric transfer of visual learning in cats with a chiasmatic and callosal section may depend on a midline disconnection of both subcortical and cortical visual centers. 4. The corpus callosum is also responsible for the representation of the ipsilateral visual field of the ipsilateral eye in the cat SC. The SC representation of the ipsilateral visual field in the contralateral eye is due, in minimal part, to direct retinotectal connections from temporal retina and, for the largest part, to the corpus callosum. 5. Finally, the corpus callosum contributes to the representation of the contralateral visual field near the vertical meridian of the temporal retina in both split-chiasm and normal cats. This is probably due to the scarcity of direct retinotectal projections from this part of the retina and to their supplementation by corticotectal neurons influenced by the callosal afferents.