Integrated Analysis of Production Potential and Profitability of a Horizontal Well in the Lower Glen Rose Formation, Maverick County, Texas

The U.S. Department of Energy/Morgantown Energy Technology Center (DOE/METC) awarded a contract in 1991 to Prime Energy Corporation (PEC) to demonstrate the benefit of using horizontal wells to recover gas from low permeability formations. The project area was located in the Chittim field of Maverick County, Texas. The Lower Glen Rose Formation in the Chittim field was a promising horizontal well candidate based on the heterogenous nature of the reservoir (suggested by large well-to-well variances in reserves) and the low percentage of economical vertical wells. Since there was substantial evidence of reservoir heterogeneity, it was unknown whether the selected, wellsite would penetrate a reservoir with the desired properties for a horizontal well. Thus, an integrated team was formed to combine geologic analysis, seismic interpretation, reservoir engineering, reservoir simulation, and economic assessment to analyze the production potential and profitability of completing a horizontal well in the Lower Glen Rose formation

Constraints From b→sγb \to s\gamma on the Left-Right Symmetric Model

Recent results from the CLEO Collaboration on both inclusive and exclusive radiative $B$ decays are used to constrain the parameter space of two versions of the Left-Right Symmetric Model. In the first scenario, when the left- and right-handed Cabibbo-Kobayashi-Maskawa mixing matrices are equal, $V_L=V_R$, the radiative $B$ decay data is shown to lead to strong bounds on the $W_L-W_R$ mixing angle that are quite insensitive to either the top quark or $W_R$ mass. The second scenario examined is that of Gronau and Wakaizumi wherein $b$-quark decays proceed only via right-handed currents and $V_L$ and $V_R$ are quite distinct. For this model, the combined constraints from Tevatron $W_R$ searches, the $B$ lifetime, and radiative $B$ decays lead to a very highly restricted allowed range for the $W_L-W_R$ mixing angle.Comment: 16 pages, 9 figures(not included), LaTex, SLAC-PUB-642

Src Binds Cortactin Through An Sh2 Domain Cystine-Mediated Linkage

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature

This is an accepted manuscript of an article published by Elsevier in Journal of Thermal Biology on 18/07/2017, available online: https://doi.org/10.1016/j.jtherbio.2017.07.006 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Ltd The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n  =  24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.Published versio

Regulation of anti-apoptotic signaling by Kruppel-like factors 4 and 5 mediates lapatinib resistance in breast cancer

The Kruppel-like transcription factors (KLFs) 4 and 5 (KLF4/5) are coexpressed in mouse embryonic stem cells, where they function redundantly to maintain pluripotency. In mammary carcinoma, KLF4/5 can each impact the malignant phenotype, but potential linkages to drug resistance remain unclear. In primary human breast cancers, we observed a positive correlation between KLF4/5 transcript abundance, particularly in the human epidermal growth factor receptor 2 (HER2)-enriched subtype. Furthermore, KLF4/5 protein was rapidly upregulated in human breast cancer cells following treatment with the HER2/epidermal growth factor receptor inhibitor, lapatinib. In addition, we observed a positive correlation between these factors in the primary tumors of genetically engineered mouse models (GEMMs). In particular, the levels of both factors were enriched in the basal-like tumors of the C3(1) TAg (SV40 large T antigen transgenic mice under control of the C3(1)/prostatein promoter) GEMM. Using tumor cells derived from this model as well as human breast cancer cells, suppression of KLF4 and/or KLF5 sensitized HER2-overexpressing cells to lapatinib. Indicating cooperativity, greater effects were observed when both genes were depleted. KLF4/5-deficient cells had reduced basal mRNA and protein levels of the anti-apoptotic factors myeloid cell leukemia 1 (MCL1) and B-cell lymphoma-extra large (BCL-XL). Moreover, MCL1 was upregulated by lapatinib in a KLF4/5-dependent manner, and enforced expression of MCL1 in KLF4/5-deficient cells restored drug resistance. In addition, combined suppression of KLF4/5 in cultured tumor cells additively inhibited anchorage-independent growth, resistance to anoikis and tumor formation in immunocompromised mice. Consistent with their cooperative role in drug resistance and other malignant properties, KLF4/5 levels selectively stratified human HER2-enriched breast cancer by distant metastasis-free survival. These results identify KLF4 and KLF5 as cooperating protumorigenic factors and critical participants in resistance to lapatinib, furthering the rationale for combining anti-MCL1/BCL-XL inhibitors with conventional HER2-targeted therapies

Integrated analysis of production potential and profitability of a horizontal well in the Lower Glen Rose Formation, Maverick County, Texas

The U.S. Department of Energy/Morgantown Energy Technology Center (DOE/METC) awarded a contract in 1991 to Prime Energy Corporation (PEC) to demonstrate the benefit of using horizontal wells to recover gas from low permeability formations. The project area was located in the Chittim field of Maverick County, Texas. The Lower Glen Rose Formation in the Chittim field was a promising horizontal well candidate based on the heterogenous nature of the reservoir (suggested by large well-to-well variances in reserves) and the low percentage of economical vertical wells. Since there was substantial evidence of reservoir heterogeneity, it was unknown whether the selected, wellsite would penetrate a reservoir with the desired properties for a horizontal well. Thus, an integrated team was formed to combine geologic analysis, seismic interpretation, reservoir engineering, reservoir simulation, and economic assessment to analyze the production potential and profitability of completing a horizontal well in the Lower Glen Rose formation

Cortactin Phosphorylated by ERK1/2 Localizes to Sites of Dynamic Actin Regulation and Is Required for Carcinoma Lamellipodia Persistence

Tumor cell motility and invasion is governed by dynamic regulation of the cortical actin cytoskeleton. The actin-binding protein cortactin is commonly upregulated in multiple cancer types and is associated with increased cell migration. Cortactin regulates actin nucleation through the actin related protein (Arp)2/3 complex and stabilizes the cortical actin cytoskeleton. Cortactin is regulated by multiple phosphorylation events, including phosphorylation of S405 and S418 by extracellular regulated kinases (ERK)1/2. ERK1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the Arp2/3 regulator neuronal Wiskott-Aldrich syndrome protein (N-WASp), promoting actin polymerization and enhancing tumor cell movement.In this report we have developed phosphorylation-specific antibodies against phosphorylated cortactin S405 and S418 to analyze the subcellular localization of this cortactin form in tumor cells and patient samples by microscopy. We evaluated the interplay between cortactin S405 and S418 phosphorylation with cortactin tyrosine phosphorylation in regulating cortactin conformational forms by Western blotting. Cortactin is simultaneously phosphorylated at S405/418 and Y421 in tumor cells, and through the use of point mutant constructs we determined that serine and tyrosine phosphorylation events lack any co-dependency. Expression of S405/418 phosphorylation-null constructs impaired carcinoma motility and adhesion, and also inhibited lamellipodia persistence monitored by live cell imaging.Cortactin phosphorylated at S405/418 is localized to sites of dynamic actin assembly in tumor cells. Concurrent phosphorylation of cortactin by ERK1/2 and tyrosine kinases enables cells with the ability to regulate actin dynamics through N-WASp and other effector proteins by synchronizing upstream regulatory pathways, confirming cortactin as an important integration point in actin-based signal transduction. Reduced lamellipodia persistence in cells with S405/418A expression identifies an essential motility-based process reliant on ERK1/2 signaling, providing additional understanding as to how this pathway impacts tumor cell migration

Reliability of infrared thermography in skin temperature evaluation of wheelchair users

To examine the reliability of infrared thermography (IRT) in wheelchair users (WCUs), as a noninvasive and risk-free technique to detect the natural thermal radiation emitted by human skin and to allow subsequent interpretations of temperature distributions

Predicting the spatial and temporal dynamics of species interactions in Fagus sylvatica and Pinus sylvestris forests across Europe

The productivity and functioning of mixed-species forests often differs from that of monocultures. However, the magnitude and direction of these differences are difficult to predict because species interactions can be modified by many potentially interacting climatic and edaphic conditions, stand structure and previous management. Process-based forest growth models could potentially be used to disentangle the effects of these factors and thereby improve our understanding of mixed forest functioning while facilitating their design and silvicultural management. However, to date, the predicted mixing effects of forest growth models have not been compared with measured mixing effects. In this study, 26 sites across Europe, each containing a mixture and monocultures of Fagus sylvatica and Pinus sylvestris, were used to calculate mixing effects on growth and yield and compare them with the mixing effects predicted by the forest growth model 3-PGmix. The climate and edaphic conditions, stand structures and ages varied greatly between sites. The model performed well when predicting the stem mass and total mass (and mixing effects on these components), with model efficiency that was usually >0.7. The model efficiency was lower for growth or smaller components such as foliage mass and root mass. The model was also used to predict how mixing effects would change along gradients in precipitation, temperature, potential available soil water, age, thinning intensity and soil fertility. The predicted patterns were consistent with measurements of mixing effects from published studies. The 3-PG model is a widely used management tool for monospecific stands and this study shows that 3-PGmix can be used to examine the dynamics of mixed-species stands and determine how they may need to be managed.This article is based upon work from COST Action EuMIXFOR, supported by COST (European Cooperation in Science and Technology). Funding for the Czech Republic site was provided by the MŠMT projects COST CZ – LD14063 and LD14074. All contributors thank their national funding institutions and the forest owners for agreeing to establish the plots and to measure and analyse data from the plots. The first author was funded by a Heisenberg Fellowship (FO 791/4-1) from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). Mário Pereira was supported by European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT – Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013 as well as by project Interact-Integrative Research in Environment, Agro-Chain and Technology, NORTE-01-0145-FEDER-000017, research line BEST, co-financed by FEDER/NORTE 2020

Growth and yield of mixed versus pure stands of Scots pine (Pinus sylvestris L. ) and European beech (Fagus sylvatica L.) analysed along a productivity gradient through Europe

Mixing of complementary tree species may increase stand productivity, mitigate the effects of drought and other risks, and pave the way to forest production systems which may be more resource-use efficient and stable in the face of climate change. However, systematic empirical studies on mixing effects are still missing for many commercially important and widespread species combinations. Here we studied the growth of Scots pine (Pinus sylvestris L.) and European beech (Fagus sylvatica L.) in mixed versus pure stands on 32 triplets located along a productivity gradient through Europe, reaching from Sweden to Bulgaria and from Spain to the Ukraine. Stand inventory and taking increment cores on the mainly 60-80 year-old trees and 0.02-1.55 ha sized, fully stocked plots provided insight how species mixing modifies the structure, dynamics and productivity compared with neighbouring pure stands. In mixture standing volume (+12 %), stand density (+20 %), basal area growth (+12 %), and stand volume growth (+8 %) were higher than the weighted mean of the neighbouring pure stands. Scots pine and European beech contributed rather equally to the overyielding and overdensity. In mixed stands mean diameter (+20 %) and height (+6 %) of Scots pine was ahead, while both diameter and height growth of European beech were behind (−8 %). The overyielding and overdensity were independent of the site index, the stand growth and yield, and climatic variables despite the wide variation in precipitation (520-1175 mm year−1), mean annual temperature (6-10.5 °C), and the drought index by de Martonne (28-61 mm °C−1) on the sites. Therefore, this species combination is potentially useful for increasing productivity across a wide range of site and climatic conditions. Given the significant overyielding of stand basal area growth but the absence of any relationship with site index and climatic variables, we hypothesize that the overyielding and overdensity results from several different types of interactions (light-, water-, and nutrient-related) that are all important in different circumstances. We discuss the relevance of the results for ecological theory and for the ongoing silvicultural transition from pure to mixed stands and their adaptation to climate change.The networking in this study has been sup-ported by COST Action FP1206 EuMIXFOR. All contributors thanktheir national funding institutions to establish, measure, and analysedata from the triplets. The first author also thanks the BayerischenStaatsforsten (BaySF) for supporting the establishment of the plots,the Bavarian State Ministry for Nutrition, Agriculture, and Forestryfor permanent support of the project W 07 ‘‘Long-term experimentalplots for forest growth and yield research’’ (# 7831-22209-2013) andthe German Science Foundation for providing the funds for the pro-jects PR 292/12-1 ‘‘Tree and stand-level growth reactions on droughtin mixed versus pure forests of Norway spruce and European beech’’.Thanks are also due to Ulrich Kern for the graphical artwork, and totwo anonymous reviewers for their constructive criticism