Multiple deprotonation of primary aromatic diamines by LiAlH4.

Reaction of LiAlH4 with 1,2-phenylenediamine (1H4) in THF results in formation of the metallocyclic amido-/imido complex [{Al(1H2)}2{Al(1H)2}2][Li(THF)2]4 (3), while in the presence of various Lewis base ligands 1,8-diaminonaphthalene (2H4) gives the amido-('ate') complexes [Al(2H2)2](-)[Li(LL')](+) [L = THF, L' = PMDETA (N,N,N',N',N''-pentamethyldiethylenetriamine) (4); L = L' = TMEDA (N,N,N',N'-tetramethylethylenediamine) (5)]. The latter complexes provide evidence of intermediates in the proposed reaction pathway for formation of the cyclic framework of the tetraanion [{Al(1H2)}2{Al(1H)2}2](4-) of 3.We thank the EU (ERC Advanced Investigator Grant for D.S.W.), the EU (R.J.L. and L.K.A.). We also thank Dr. J. E. Davies for collecting X-ray data on 3, 4 and 5.This is the author accepted manuscript. The final version is available via RSC at http://pubs.rsc.org/en/Content/ArticleLanding/2015/DT/c4dt03802a#!divAbstract

Coordinations between gene modules control the operation of plant amino acid metabolic networks

<p>Abstract</p> <p>Background</p> <p>Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results.</p> <p>Results</p> <p>Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes.</p> <p>Conclusion</p> <p>Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.</p

Predictors of Lost to Follow-Up among Children with Type 2 Diabetes

Background/Aims: Youth with type 2 diabetes (T2D) have poor compliance with medical care. This study aimed to determine which demographic and clinical factors differ between youth with T2D who receive care in a pediatric diabetes center versus youth lost to follow-up for >18 months. Methods: Data were analyzed from 496 subjects in the Pe­diatric Diabetes Consortium registry. Enrollment variables were selected a priori and analyzed with univariable and multivariable logistic regression models. Results: After a median of 1.3 years from enrollment, 55% of patients were lost to follow-up. The final model included age, race/ethnicity, parent education, and estimated distance to study site. The odds ratio (99% confidence interval) of loss to follow-up was 2.87 (1.34, 6.16) for those aged 15 to <18 years versus those aged 10 to <13 years and 6.57 (2.67, 16.15) for those aged ≥18 years versus those aged 10 to <13 years. Among patients living more than 50 miles from the clinic, the odds ra tio of loss to follow-up was 3.11 (1.14, 8.49) versus those living within 5 miles of the site. Conclusion: Older adolescents with T2D are more likely to be lost to follow-up, but other socioeconomic factors were not significant predictors of clinic follow-up

CFD Investigation on Fluid Flow Analysis in Fluid Separator

The analysis of fully developed flow in the two fluid separators is an important issue in the industry such as production, processing, and petrochemical. The role of the two fluid separator is to separate two different fluid by using an appropriate mechanism without changing the quality. In this study, we have reviewed different mechanisms of two fluid separations such as gravity sedimentation, centrifugation, and electro kinetics, etc. The current work focuses on the design aspect of a fluid separator with respect to geometry and thermal design. CFD has been used to simulate flow in a fluid separator and its results have been verified experimentally. Flow rates used in the simulation have different values in interval 0.1 LPM. The study shows the best performance of fluid separator with respect to shape and flow rates. The given work helps to co-relate various design of separator in the industry with laboratory separators

Integrated stratigraphy of the Priabonian (upper Eocene) Urtsadzor section, Armenia

The transition from the Bartonian to the Priabonian, as traditionally understood, has long been associated with a series of extinctions and originations in several microfossil groups. The planktonic foraminifer genus Morozovelloides and large species of Acarinina suffered a rapid global extinction, as did many radiolarians. Calcareous nannofossils show several assemblage changes including the acme beginning of Cribrocentrum erbae and the lowest and highest occurrences of Chiasmolithus oamaruensis and C. grandis respectively. In shallow water environments, larger foraminifera also show an extinction among large species of Nummulites, as well as the first occurrences of the stratigraphically important genus Spiroclypeus. However, the correlation between shallow and deep water records remains uncertain, as do the mechanisms driving these biotic events. Here we present the results of a new integrated stratigraphical study (calcareous nannofossils, planktonic foraminifera, larger benthic foraminifera, and low-resolution magnetostratigraphy) of the Urtsadzor section in south-western Armenia which appears to be continuous through this interval. The Urtsadzor section consists of calcareous siltstones rich in micro- and nannofossils, with interbedded limestones containing abundant larger benthic foraminifera. Our new data enable us to correlate larger foraminiferal events with global plankton biostratigraphy, in a section outside of southwest Europe where most previous correlations have been based. At Urtsadzor, the large Nummulites species of N. millecaput-group are present throughout the whole section but decrease in abundance toward the top. The first occurrence of Spiroclypeus, also occurs in the upper part of the section, marking the SBZ 18/19 boundary. These events are associated with the phylogenetic development of the Nummulites fabianii and Heterostegina reticulata lineages. However, the calcareous plankton biostratigraphy indicates the section is well within the Priabonian; within planktonic foraminiferal Zones E14 and E15 and calcareous nannoplankton Zones CNE 18 and CNE 19. These results indicate larger foraminiferal events occur well above the planktonic foraminiferal extinction level and nannofossil assemblage changes indicating the events are not synchronous across groups, with implications for biostratigraphy and recognition of the basal Priabonian in different depositional settings and regions

Computer simulation of glioma growth and morphology

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion

Typology of Environment-Related Provisions in Regional Trade Agreements

The last 25 years have witnessed a rapid increase in regional trade agreements (RTAs). Although RTAs generally aim at lowering tariff and non-tariff trade barriers, an increasing number of trade agreements extend their scope to cover specific policy areas such as environmental protection and sustainable development. This paper establishes a comprehensive typology and quantitative analysis of environment-related provisions included in RTAs. The analysis covers all the RTAs currently into force that have been notified to the WTO between 1957 and May 2016, namely 270 trade agreements. While environmental exceptions, along with environmental cooperation continue to be the most common types of environment-related provisions, many other different types of provisions are incorporated in an increasing number of RTAs. The common feature of all environment-related provisions, including environmental exceptions, is their heterogeneity in terms of structure, language and scope

Tumor Invasion of Salmonella enterica Serovar Typhimurium Is Accompanied by Strong Hemorrhage Promoted by TNF-α

BACKGROUND:Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS:We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization. CONCLUSION:Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria

High Interstitial Fluid Pressure Is Associated with Tumor-Line Specific Vascular Abnormalities in Human Melanoma Xenografts

PURPOSE: Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurability and high metastatic frequency in human melanoma xenografts and with poor survival after radiation therapy in cervical cancer patients. Abnormalities in tumor vascular networks have been identified as an important cause of elevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphological properties of tumor vascular networks. MATERIALS AND METHODS: A-07-GFP and R-18-GFP human melanomas growing in dorsal window chambers in BALB/c nu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamine isothiocyanate-labeled dextran. IFP was measured in the center of the tumors using a Millar catheter. Angiogenic profiles of A-07-GFP and R-18-GFP cells were obtained with a quantitative PCR array. RESULTS: High IFP was associated with low growth rate and low vascular density in A-07-GFP tumors, and with high growth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks, while R-18-GFP tumors showed more organized vascular networks with supplying arterioles in the tumor center and draining venules in the tumor periphery. Furthermore, A-07-GFP and R-18-GFP cells differed substantially in angiogenic profiles. A-07-GFP tumors with high IFP showed high geometric resistance to blood flow due to high vessel tortuosity. R-18-GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries. CONCLUSIONS: High IFP in A-07-GFP and R-18-GFP human melanoma xenografts was primarily a consequence of high blood flow resistance caused by tumor-line specific vascular abnormalities