bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolution of Transnational Environmental Law: Four Cases in Historical Perspective
Authors: Sand Peter H. 
Published: April 2012

AbstractThis essay places transnational environmental law in an epistemological context. Starting from the general concept of ‘transnational law’ and the specific environmental dimension of ‘international administrative law’, four case histories are presented to illustrate the integrant approach of transnational environmental law. The cases – all arising in the1970s – deal with transboundary problems of aircraft noise, ocean dumping, river pollution, and marine protected areas. In addition to traditional aspects of public international law in the environmental field, they typically interface with questions of administrative law, private international law, criminal law, and human rights law. The essay advocates a new focus on mechanisms for participation by civil society in the operation and implementation of transnational environmental law.
MMFPh: a maximal motif finder for phosphoproteomics datasets
Authors: Wang Tuobin , Kettenbach Arminja N. , Gerber Scott A. , Bailey-Kellogg Chris 
Published: April 2012

Abstract
Motivation: Protein phosphorylation, driven by specific recognition of substrates by kinases and phosphatases, plays central roles in a variety of important cellular processes such as signaling and enzyme activation. Mass spectrometry enables the determination of phosphorylated peptides (and thereby proteins) in scenarios ranging from targeted in vitro studies to in vivo cell lysates under particular conditions. The characterization of commonalities among identified phosphopeptides provides insights into the specificities of the kinases involved in a study. Several algorithms have been developed to uncover linear motifs representing position-specific amino acid patterns in sets of phosphopeptides. To more fully capture the available information, reduce sensitivity to both parameter choices and natural experimental variation, and develop more precise characterizations of kinase specificities, it is necessary to determine all statistically significant motifs represented in a dataset.
Results: We have developed MMFPh (Maximal Motif Finder for Phosphoproteomics datasets), which extends the approach of the popular phosphorylation motif software Motif-X (Schwartz and Gygi, 2005) to identify all statistically significant motifs and return the maximal ones (those not subsumed by motifs with more fixed amino acids). In tests with both synthetic and experimental data, we show that MMFPh finds important motifs missed by the greedy approach of Motif-X, while also finding more motifs that are more characteristic of the dataset relative to the background proteome. Thus MMFPh is in some sense both more sensitive and more specific in characterizing the involved kinases. We also show that MMFPh compares favorably to other recent methods for finding phosphorylation motifs. Furthermore, MMFPh is less dependent on parameter choices. We support this powerful new approach with a web interface so that it may become a useful tool for studies of kinase specificity and phosphorylation site prediction.
Availability: A web server is at www.cs.dartmouth.edu/~cbk/
Contact: cbk@cs.dartmouth.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Altered immunoregulatory profile during anti-tumour necrosis factor treatment of patients with inflammatory bowel disease
Authors: Grundström J , Linton L , Thunberg S , Forsslund H , Janczewska I , Befrits R , van Hage M , Gafvelin G , Eberhardson M 
Published: April 2012

SummaryInflammatory bowel disease (IBD) can be treated effectively by anti-tumour necrosis factor (TNF) therapy. We set out to investigate the unclear immunoregulatory mechanisms of the treatment. Thirty-four patients with IBD treated with anti-TNF were included. Lymphocytes from peripheral blood and intestinal biopsies were analysed by flow cytometry. Regulation of antigen-stimulated proliferation was analysed by blocking of interleukin (IL)-10, transforming growth factor (TGF)-β or depletion of CD25+ cells in peripheral blood mononuclear cell cultures. No changes in CD4+CD25+, CD25+TNF-RII+ or CD4+CD25+forkhead box protein 3 (FoxP3+) T cells could be observed in peripheral blood after, in comparison to before, 6 weeks of treatment. The suppressive ability of CD4+CD25+ cells did not change. There was an initial decrease of CD4+CD25+ cells in intestinal mucosa after 2 weeks of treatment, followed by an increase of these cells from weeks 2 to 6 of treatment (P &lt; 0·05). This was accompanied by an increased percentage of CD69+ cells among these cells after 6 weeks of treatment compared to before treatment (P &lt; 0·01). There was also an increase of mucosal T helper type1 cells from weeks 2 to 6 (P &lt; 0·05). In addition, CD25+TNF-RII+ cells in the mucosa were decreased after 6 weeks of treatment compared to before treatment (P &lt; 0·05). Before treatment, peripheral blood mononuclear cell baseline proliferation was increased when IL-10 was blocked (P &lt; 0·01), but not after. In CD25+ cell-depleted cultures proliferation increased after treatment (P &lt; 0·05). Our data indicate that anti-TNF treatment leads to an induction of effector T cells. Anti-TNF therapy has no significant impact on regulatory T cells in IBD, although the composition of regulatory T cell subsets may change during treatment.
Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)-infected and HIV-negative CD4 T lymphocytopenic patients
Authors: Lim H , Kane L , Schwartz J B , Hesdorffer C S , Deeks S G , Greig N , Ferrucci L , Goetzl E J 
Published: April 2012

SummarySuppressed T cell functions in human immunodeficiency virus (HIV) infection were identified and corrected by lenalidomide in middle-aged HIV-infected patients. Chemotaxis of T cells from HIV-infected men (n = 6, mean 43 years) to sphingosine 1-phosphate (S1P) and CCL21 was significantly lower than that of HIV-negative men (n = 6, mean 41 years), and was enhanced significantly up to control levels by 100 and 1000 nM lenalidomide. Generation of interleukin (IL)-2, but not interferon (IFN)-γ, by T cells of middle-aged HIV-infected men was significantly lower than that for controls and was increased significantly by 10–1000 nM lenalidomide up to a maximum of more than 300%. CD4 and CD8 T cells isolated from healthy middle-aged men and reconstituted in vitro at a low CD4 : CD8 ratio typical of HIV infection had depressed chemotaxis to S1P, but not CCL21, and generation of IL-2, but not IFN-γ. Significant enhancement of chemotaxis to S1P and CCL21was induced by 100–1000 nM lenalidomide only for normal T cells at a low CD4 : CD8 ratio. T cells from HIV-negative middle-aged CD4 T lymphocytopenic patients (n = 3), with a CD4 : CD8 ratio as low as that of HIV-infected patients, had similarly diminished chemotaxis to S1P and CCL21, and depressed generation of IL-2, but not IFN-γ. Lenalidomide at 30–1000 nM significantly enhanced chemotaxis to S1P and IL-2 generation for T cells from HIV-negative CD4 T lymphocytopenic patients as from HIV-infected patients, with less effect on CCL21-elicited chemotaxis and none for IFN-γ generation. Defects in functions of T cells from middle-aged HIV-infected men are partially attributable to CD4 T lymphocytopenia and are corrected by lenalidomide.
Stability of tallgrass prairie during a 19‐year increase in growing season precipitation
Authors: Collins Scott L. , Koerner Sally E. , Plaut Jennifer A. , Okie Jordan G. , Brese Daniel , Calabrese Laura B. , Carvajal Alejandra , Evansen Ryan J. , Nonaka Etsuko 
Published: April 2012

Summary1. Precipitation is considered to be a key driver of ecosystem processes in mesic grasslands, and climate models predict changes in the amount and intensity of precipitation under future global change scenarios. Although most experimental rainfall studies decrease precipitation, seasonal rainfall is predicted to increase in the northern Great Plains under climate change.2. We analysed changes in community composition and structure of upland and lowland native tallgrass prairie in central Kansas, USA, subjected to 19 years of irrigation designed to eliminate moisture stress throughout the growing season.3. Irrigation had limited effects on species richness in both upland and lowland prairie. Total cover increased significantly and consistently with irrigation in drier uplands and in more mesic lowlands. Abundance of rhizomatous, tall, perennial species as well as C3forbs increased with irrigation.4. The strongest response to irrigation came within the dominant functional type, C4perennial grasses.Panicum virgatumbecame the dominant species in irrigated lowlands, whereasAndropogon gerardiiremained the dominant species in irrigated uplands and in control plots. Overall, irrigation had less effect on community composition and structure than other known drivers of grassland structure and function.5. In comparison with other studies, our results demonstrate that water addition has less of an impact than fire, grazing or nitrogen addition on composition and dynamics in this mesic grassland. The strongest response to long‐term irrigation occurredwithinthe dominant functional type: tall, perennial, rhizomatous, C4grasses. Thus, functional redundancy will buffer this ecosystem from potential increases in rainfall due to climate change. Finally, our results highlight the limited utility of qualitative functional traits to predict how this mesic grassland will respond to climate change.
Study of correlation between maternal fatigue and uterine contraction pattern in the active phase of labour
Authors: Ebrahimzadeh Samira , Golmakani Nahid , Kabirian Maryam , Shakeri Mohhamad T 
Published: April 2012

Aims and objectives.  To evaluate the correlation between maternal fatigue and uterine contraction pattern at the beginning of the active phase of labour.Background.  Fatigue is one of the most common complaints in pregnant women that often continues until delivery. Maternal fatigue prolongs the labour process and increases the rate of cesarian section. Studies on the pattern of uterine contractions have shown that the length of the fall time is longer in prolonged labours than in normal deliveries.Design.  A cross‐sectional study.Methods.  This study was conducted on 100 primiparous women who were referred to Ommolbanin Hospital (Mashhad, Iran) in 2011. Maternal fatigue was assessed at the beginning of the active phase of labour. Then, the pattern of uterine contractions was monitored for 30 minutes by an external tocodynamometer. The F/R ratio was determined by measuring the time for a contraction to return to its baseline from its peak and the time for a contraction to rise to its peak. The data were analysed by chi‐square and anova tests.Results.  The results showed that there was a significant relationship between maternal fatigue and uterine contraction pattern. The F/R ratio was increased with increase in fatigue severity.Conclusions.  Fatigue causes changes in the pattern of uterine contractions. The return time of a contraction from its peak to its baseline (fall) is increased with increase in fatigue severity.Relevance to clinical practice.  Offering strategies to prevent tiredness and reduce the related fatigue complications.
Bypassing proximal health care facilities for acute care: a survey of patients in a Ghanaian Accident and Emergency Centre
Authors: Yaffee A. Q. , Whiteside L. K. , Oteng R. A. , Carter P. M. , Donkor P. , Rominski S. D. , Kruk M. E. , Cunningham R. M. 
Published: April 2012

AbstractObjective  To characterise the population that presents to the Accident and Emergency Centre (AEC) at Komfo Anokye Teaching Hospital (KATH) and to identify risk factors associated with bypassing proximal care facilities.Methods  A structured questionnaire was verbally administered to patients presenting to the AEC over 2 weeks. The questionnaire focused on the use of health care resources and characteristics of current illness or injury. Measures recorded include demographics, socioeconomic status, chief complaint, transportation and mobility, reasons for choosing KATH and health care service utilisation and cost.Results  The total rate of bypassing proximal care was 33.9%. On multivariate analysis, factors positively associated with bypassing included age older than 38 years (OR: 2.18, P 0.04) and prior visits to facility (OR 2.88, P 0.01). Bypassers were less likely to be insured (OR 0.31, P 0.01), to be seeking care due to injury (OR 0.42, P 0.03) and to have previously sought care for the problem (OR 0.10, P < 0.001).Conclusions  Patients who bypass facilities near them to seek care at an urban AEC in Ghana do so for a combination of reasons including familiarity with the facility, chief complaint and insurance status. Understanding bypassing behaviour is important for guiding health care utilisation policy decisions and streamlining cost‐effective, appropriate access to care for all patients.
Neuromodulation of Pelvic Visceral Pain: Review of the Literature and Case Series of Potential Novel Targets for Treatment
Authors: Hunter Corey , Davé Nimish , Diwan Sudhir , Deer Timothy 
Published: April 2012

AbstractChronic pelvic pain (CPP) is complex and often resistant to treatment. While the exact pathophysiology is unknown, the pain states resultant from conditions such as interstitial cystitis and the like yield patients with a presentation that bears a striking similarity to neuropathic syndromes that are known to respond to neuromodulation. While there has been past success using the sacral region as a target for spinal cord stimulation (SCS) to treat these patients, there remains to be a consensus on the optimal location for lead placement. In this article, the authors discuss the potential etiology of CPP, examine the current literature on lead placement for SCS as a method of treatment, as well as present several cases where novel lead placement was successfully employed.
Surfaces of Longing. Cosmopolitan Aspiration and Frustration in Egypt
Authors: SCHIELKE SAMULI 
Published: April 2012

AbstractOne of the most ambiguous outcomes of globalization has been the emergence of a large class of people who subscribe to global trends in religion, consumerism, nationalism, sports and popular culture, without having access to the mobility nor the symbolic capital that are associated with cosmopolitanism. This sense of aspiration is far from ephemeral. It is material, it has shape, surface, and form. This photo essay attempts to connect this sensual presence of images, and materials with the sense of longing and discontent involved in looking out to the world from the vantage point of underprivileged social milieus in Egypt.
A scaling transformation for classifier output based on likelihood ratio: Applications to a CAD workstation for diagnosis of breast cancer
Authors: Horsch Karla , Pesce Lorenzo L. , Giger Maryellen L. , Metz Charles E. , Jiang Yulei 
Published: April 2012

Purpose:The authors developed scaling methods that monotonically transform the output of one classifier to the “scale” of another. Such transformations affect the distribution of classifier output while leaving the ROC curve unchanged. In particular, they investigated transformations between radiologists and computer classifiers, with the goal of addressing the problem of comparing and interpreting case‐specific values of output from two classifiers.Methods:Using both simulated and radiologists' rating data of breast imaging cases, the authors investigated a likelihood‐ratio‐scaling transformation, based on “matching” classifier likelihood ratios. For comparison, three other scaling transformations were investigated that were based on matching classifier true positive fraction, false positive fraction, or cumulative distribution function, respectively. The authors explored modifying the computer output to reflect the scale of the radiologist, as well as modifying the radiologist's ratings to reflect the scale of the computer. They also evaluated how dataset size affects the transformations.Results:When ROC curves of two classifiers differed substantially, the four transformations were found to be quite different. The likelihood‐ratio scaling transformation was found to vary widely from radiologist to radiologist. Similar results were found for the other transformations. Our simulations explored the effect of database sizes on the accuracy of the estimation of our scaling transformations.Conclusions:The likelihood‐ratio‐scaling transformation that the authors have developed and evaluated was shown to be capable of transforming computer and radiologist outputs to a common scale reliably, thereby allowing the comparison of the computer and radiologist outputs on the basis of a clinically relevant statistic.
Mouse Tissues that Undergo Neoplastic Progression after K-Ras Activation Are Distinguished by Nuclear Translocation of phospho-Erk1/2 and Robust Tumor Suppressor Responses
Authors: Parikh Neha , Shuck Ryan L. , Nguyen Thuy-Ai , Herron Alan , Donehower Lawrence A. 
Published: April 2012

Abstract
Mutation of K-Ras is a frequent oncogenic event in human cancers, particularly cancers of lungs, pancreas, and colon. It remains unclear why some tissues are more susceptible to Ras-induced transformation than others. Here, we globally activated a mutant oncogenic K-Ras allele (K-RasG12D) in mice and examined the tissue-specific effects of this activation on cancer pathobiology, Ras signaling, tumor suppressor, DNA damage, and inflammatory responses. Within 5 to 6 weeks of oncogenic Ras activation, mice develop oral and gastric papillomas, lung adenomas, and hematopoietic hyperproliferation and turn moribund. The oral, gastric, and lung premalignant lesions display activated extracellular signal–regulated kinases (Erk)1/2 and NF-κB signaling as well as activated tumor suppressor and DNA damage responses. Other organs such as pancreas, liver, and small intestine do not exhibit neoplastic progression within 6 weeks following K-RasG12D activation and do not show a potent tumor suppressor response. Even though robust Erk1/2 signaling is activated in all the tissues examined, the pErk1/2 distribution remains largely cytoplasmic in K-RasG12D–refractory tissues (pancreas, liver, and intestines) as opposed to a predominantly nuclear localization in K-RasG12D–induced neoplasms of lung, oral, and gastric mucosa. The downstream targets of Ras signaling, pElk-1 and c-Myc, are elevated in K-RasG12D–induced neoplastic lesions but not in K-RasG12D–refractory tissues. We propose that oncogenic K-Ras–refractory tissues delay oncogenic progression by spatially limiting the efficacy of Ras/Raf/Erk1/2 signaling, whereas K-Ras–responsive tissues exhibit activated Ras/Raf/Erk1/2 signaling, rapidly form premalignant tumors, and activate potent antitumor responses that effectively prevent further malignant progression. Mol Cancer Res; 10(6); 845–55. ©2012 AACR.
Circulating Women as Objects of Trade in Malay Historical Texts
Authors: Hashim Ruzy Suliza , Tahir Ungku Maimunah Mohd , Jalaluddin Nor Hashimah , Mohamad Zulkarnaen 
Published: April 2012

AbstractIn this paper, we shall discuss ‘circulating women’ as objects of trade based on the corpus of three historical texts such as The Malay Annals (Sejarah Melayu) and Misa Melayu Perak. Barbara Andaya (2006:104) has cogently argued that “Southeast Asia is an attractive laboratory to investigate women’s economic roles” especially in the early modern period. By focusing on issues related to marriage and slave trade, we look specifically at the movements of women in the chronicles. Whether they were consorts, concubines and maids-in-waiting in the Malay courts, the traffic of women showed an intricate web of social exchange where symmetrical and asymmetrical reciprocity took place in various political situations of the day. By showing these exchanges, we unveil an aspect of women and trade in early modern Southeast Asia where women were involved in boosting male prestige and power, political hierarchy, social identity and legitimacy.
Investigating the Mechanisms of Diurnal Rainfall Variability Using a Regional Climate Model
Authors: Evans Jason P. , Westra Seth 
Published: April 2012

Abstract
This study investigates the ability of a regional climate model (RCM) to simulate the diurnal cycle of precipitation over southeast Australia, to provide a basis for understanding the mechanisms that drive diurnal variability. When compared with 195 observation gauges, the RCM tends to simulate too many occurrences and too little intensity for precipitation events at the 3-hourly time scale. However, the overall precipitation amounts are well simulated and the diurnal variability in occurrences and intensities are generally well reproduced, particularly in spring and summer. In terms of precipitation amounts, the RCM overestimated the diurnal cycle during the warmer months but was reasonably accurate during winter. The timing of the maxima and minima was found to match the observed timings well. The spatial pattern of diurnal variability in the Weather Research and Forecasting model outputs was remarkably similar to the observed record, capturing many features of regional variability. The RCM diurnal cycle was dominated by the convective (subgrid scale) precipitation. In the RCM the diurnal cycle of convective precipitation over land corresponds well to atmospheric instability and thermally triggered convection over large areas, and also to the large-scale moisture convergence at 700 hPa along the east coast, with the strongest diurnal cycles present where these three mechanisms are in phase.
A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR
Authors: Torikai Hiroki , Reik Andreas , Liu Pei-Qi , Zhou Yuanyue , Zhang Ling , Maiti Sourindra , Huls Helen , Miller Jeffrey C. , Kebriaei Partow , Rabinovitch Brian , Lee Dean A. , Champlin Richard E. , Bonini Chiara , Naldini Luigi , Rebar Edward J. , Gregory Philip D. , Holmes Michael C. , Cooper Laurence J. N. 
Published: April 2012

Abstract
Clinical-grade T cells are genetically modified ex vivo to express a chimeric antigen receptor (CAR) to redirect specificity to a tumor associated antigen (TAA) thereby conferring antitumor activity in vivo. T cells expressing a CD19-specific CAR recognize B-cell malignancies in multiple recipients independent of major histocompatibility complex (MHC) because the specificity domains are cloned from the variable chains of a CD19 monoclonal antibody. We now report a major step toward eliminating the need to generate patient-specific T cells by generating universal allogeneic TAA-specific T cells from one donor that might be administered to multiple recipients. This was achieved by genetically editing CD19-specific CAR+ T cells to eliminate expression of the endogenous αβ T-cell receptor (TCR) to prevent a graft-versus-host response without compromising CAR-dependent effector functions. Genetically modified T cells were generated using the Sleeping Beauty system to stably introduce the CD19-specific CAR with subsequent permanent deletion of α or β TCR chains with designer zinc finger nucleases. We show that these engineered T cells display the expected property of having redirected specificity for CD19 without responding to TCR stimulation. CAR+TCRneg T cells of this type may potentially have efficacy as an off-the-shelf therapy for investigational treatment of B-lineage malignancies.