bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implicit invocation meets safe, implicit concurrency
Authors: Long Yuheng , Mooney Sean L. , Sondag Tyler , Rajan Hridesh 
Published: February 2011

Writing correct and efficient concurrent programs still remains a challenge. Explicit concurrency is difficult, error prone, and creates code which is hard to maintain and debug. This type of concurrency also treats modular program design and concurrency as separate goals, where modularity often suffers. To solve these problems, we are designing a new language that we call Panini. In this paper, we focus on Panini's asynchronous, typed events which reconcile the modularity goal promoted by the implicit invocation design style with the concurrency goal of exposing potential concurrency between the execution of subjects and observers.
Since modularity is improved and concurrency is implicit in Panini, programs are easier to reason about and maintain. The language incorporates a static analysis to determine potential conflicts between handlers and a dynamic analysis which uses the conflict information to determine a safe order for handler invocation. This mechanism avoids races and deadlocks entirely, yielding programs with a guaranteed deterministic semantics. To evaluate our language design and implementation we show several examples of its usage as well as an empirical study of program performance. We found that not only is developing and understanding Panini programs significantly easier compared to standard concurrent object-oriented programs, butt also performance of Panini programs is comparable to their equivalent hand-tuned versions written using Java's fork-join framework.
Incremental type-checking for type-reflective metaprograms
Authors: Miao Weiyu , Siek Jeremy G. 
Published: February 2011

Garcia introduces a calculus for type-reflective metaprogramming that provides much of the power and flexibility of C++ templates and solves many of its problems. However, one of the problems that remains is that the residual program is not type checked until after meta computation is complete. Ideally, one would like the type system of the metaprogram to also guarantee that the residual program will type check, as is the case in MetaML. However, in a language with type-reflective metaprogramming, type expressions in the residual program may be the result of meta computation, making the MetaML guarantee next to impossible to achieve.
In this paper we offer an approach to detecting errors earlier without sacrificing flexibility: we incrementally type check code fragments as they are created and spliced together during meta computation. The incremental type system is a variant of the gradual type system of Siek and Taha, in which we use type variables to represent type expressions that are not yet normalized and a new dynamic variation on existential types to represent residual code fragments. A type error in a code fragment is treated as a run-time error of the meta computation. We show that the incremental type checker can be implemented efficiently and we prove that if a well-typed metaprogram generates a residual program, then the residual program is also well-typed.
Notch1 in Bone Marrow–Derived Cells Mediates Cardiac Repair After Myocardial Infarction
Authors: Li Yuxin , Hiroi Yukio , Ngoy Soeun , Okamoto Ryuji , Noma Kensuke , Wang Chao-Yung , Wang Hong-Wei , Zhou Qian , Radtke Freddy , Liao Ronglih , Liao James K. 
Published: February 2011

Background—
The signaling mechanisms that regulate the recruitment of bone marrow (BM)–derived cells to the injured heart are not well known. Notch receptors mediate binary cell fate determination and may regulate the function of BM-derived cells. However, it is not known whether Notch1 signaling in BM-derived cells mediates cardiac repair after myocardial injury.

Methods and Results—

Mice with postnatal cardiac-specific deletion of Notch1 exhibit infarct size and heart function after ischemic injury that is similar to that of control mice. However, mice with global hemizygous deletion of Notch1 (N1
±
) developed larger infarct size and worsening heart function. When the BM of N1
±
mice were transplanted into wild-type (WT) mice, infarct size and heart function were worsened and neovascularization in the infarct border area was reduced compared with WT mice transplanted with WT BM. In contrast, transplantation of WT BM into N1
±
mice lessened the myocardial injury observed in N1
±
mice. Indeed, hemizygous deletion of Notch1 in BM-derived cells leads to decreased recruitment, proliferation, and survival of mesenchymal stem cells (MSC). Compared with WT MSC, injection of N1
±
MSC into the infarcted heart leads to increased myocardial injury whereas injection of MSC overexpressing Notch intracellular domain leads to decreased infarct size and improved cardiac function.

Conclusions—
These findings indicate that Notch1 signaling in BM-derived cells is critical for cardiac repair and suggest that strategies that increase Notch1 signaling in BM-derived MSC could have therapeutic benefits in patients with ischemic heart disease.
The Influence of Eastern Pacific Tropical Cyclone Remnants on the Southwestern United States
Authors: Ritchie Elizabeth A. , Wood Kimberly M. , Gutzler David S. , White Sarah R. 
Published: February 2011

Abstract
Forty-three eastern North Pacific tropical cyclone remnants with varying impact on the southwestern United States during the period 1992–2005 are investigated. Of these, 35 remnants (81%) brought precipitation to some part of the southwestern United States and the remaining 8 remnants (19%) had precipitation that was almost entirely restricted to Mexico, although cloud cover did advect over the southwestern United States in some of these cases. Although the tropical cyclone–strength winds rapidly diminish upon making landfall, these systems still carry a large quantity of tropical moisture and, upon interaction with mountainous topography, are found to drop up to 30% of the local annual precipitation.
Based on common rainfall patterns and large-scale circulation features, the tropical cyclones are grouped into five categories. These include a northern recurving pattern that is more likely to bring rainfall to the southwestern United States; a southern recurving pattern that brings rainfall across northern Mexico and the Gulf Coast region; a largely north and/or northwestward movement pattern that brings rainfall to the west coast of the United States; a group that is blocked from the southwest by a ridge, which limits rainfall to Mexico; and a small group of cases that are not clearly any of the previous four types. Composites of the first four groups are shown and forecasting strategies for each are described.
Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities
Authors: Wilber Andrew , Nienhuis Arthur W. , Persons Derek A. 
Published: February 2011

Abstract
In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical manifestations of both sickle cell disease and β-thalassemia. Understanding the normal process of loss of fetal globin expression and activation of adult globin expression could potentially lead to new therapeutic approaches for these hemoglobin disorders. Herein, we briefly review the history of the study of hemoglobin switching and then focus on recent discoveries in the field that now make new therapeutic approaches seem feasible in the future. Erythroid-specific knockdown of fetal gene repressors or enforced expression of fetal gene activators may provide clinically applicable approaches for genetic treatment of hemoglobin disorders that would benefit from increased fetal hemoglobin levels.
Promotion and maintenance of leukemia by ERG
Authors: Tsuzuki Shinobu , Taguchi Osamu , Seto Masao 
Published: February 2011

Abstract
The Ets-related gene (ERG) located on human chromosome 21 encodes a transcription factor and is thought to be causally related to Down syndrome–associated acute megakaryocytic leukemia in childhood. In clinical adult leukemia, however, increased expression of ERG is indicative of poor prognosis in T-cell acute lymphoblastic leukemia and cytogenetically normal acute myeloid leukemia, although the involvement of ERG in the development of adult leukemia remains elusive. Here, we show that forced expression of ERG in adult BM cells alters differentiation and induces expansion of T and erythroid cells and increases frequencies of myeloid progenitors in mouse BM transplantation models. The expanded T cells then develop T-cell acute lymphoblastic leukemia after acquisition of mutations in the Notch1 gene. Targeted expression of ERG into B cells also altered differentiation and promoted growth of precursor B cells. Overall, these findings suggest a general role of ERG in promoting growth of adult hematopoietic cells in various lineages. In line with this, shRNA-mediated silencing of ERG expression attenuated growth of human leukemia cell lines of various lineages. Thus, ERG is capable of promoting the development of leukemia and is crucial for its maintenance.
Effects of polymorphisms in ovine and caprine prion protein alleles on cell-free conversion
Authors: Eiden Martin , Soto Elizabeth Ortega , Mettenleiter Thomas C , Groschup Martin H 
Published: February 2011

Abstract
In sheep polymorphisms of the prion gene (PRNP) at the codons 136, 154 and 171 strongly influence the susceptibility to scrapie and bovine spongiform encephalopathy (BSE) infections. In goats a number of other gene polymorphisms were found which are suspected to trigger similar effects. However, no strong correlation between polymorphisms and TSE susceptibility in goats has yet been obtained from epidemiological studies and only a low number of experimental challenge data are available at present. We have therefore studied the potential impact of these polymorphisms in vitro by cell-free conversion assays using mouse scrapie strain Me7. Mouse scrapie brain derived PrPSc served as seeds and eleven recombinant single mutation variants of sheep and goat PrPC as conversion targets. With this approach it was possible to assign reduced conversion efficiencies to specific polymorphisms, which are associated to low frequency in scrapie-affected goats or found only in healthy animals. Moreover, we could demonstrate a dominant-negative inhibition of prion polymorphisms associated with high susceptibility by alleles linked to low susceptibility in vitro.
Prevalent de novo somatic mutations in superantigen genes of mouse mammary tumor viruses in the genome of C57BL/6J mice and its potential implication in the immune system
Authors: Lee Young-Kwan , Chiu Sophia , Chew Alex , Greenhalgh David G , Cho Kiho 
Published: February 2011

AbstractBackgroundSuperantigens (SAgs) of mouse mammary tumor viruses (MMTVs) play a crucial role in T cell selection in the thymus in a T cell receptor (TCR) Vβ-specific manner and SAgs presented by B cells activate T cells in the periphery. The peripheral T cell repertoire is dynamically shaped by the steady induction of T cell tolerance against self antigens throughout the lifespan. We hypothesize thatde novosomatic mutation of endogenous MMTV SAgs contributes to the modulation of the peripheral T cell repertoire.ResultsSAg coding sequences were cloned from the genomic DNAs and/or cDNAs of various tissues of female C57BL/6J mice. A total of 68 unique SAg sequences (54 translated sequences) were identified from the genomic DNAs of liver, lungs, and bone marrow, which are presumed to harbor only three endogenous MMTV loci (Mtv-8,Mtv-9, andMtv-17). Similarly, 69 unique SAg sequences (58 translated sequences) were cloned from the cDNAs of 18 different tissues. Examination of putative TCR Vβ specificity suggested that some of the SAg isoforms identified in this study have Vβ specificities different from the reference SAgs ofMtv-8,Mtv-9, orMtv-17.ConclusionThe pool of diverse SAg isoforms, generated byde novosomatic mutation, may play a role in the shaping of the peripheral T cell repertoire including the autoimmune T cell population.
Two novel types of hexokinases in the moss Physcomitrella patens
Authors: Nilsson Anders , Olsson Tina , Ulfstedt Mikael , Thelander Mattias , Ronne Hans 
Published: February 2011

AbstractBackgroundHexokinase catalyzes the phosphorylation of glucose and fructose, but it is also involved in sugar sensing in both fungi and plants. We have previously described two types of hexokinases in the mossPhyscomitrella. Type A, exemplified by PpHxk1, the major hexokinase inPhyscomitrella, is a soluble protein that localizes to the chloroplast stroma. Type B, exemplified by PpHxk2, has an N-terminal membrane anchor. Both types are found also in vascular plants, and localize to the chloroplast stroma and mitochondrial membranes, respectively.ResultsWe have now characterized all 11 hexokinase encoding genes inPhyscomitrella. Based on their N-terminal sequences and intracellular localizations, three of the encoded proteins are type A hexokinases and four are type B hexokinases. One of the type B hexokinases has a splice variant without a membrane anchor, that localizes to the cytosol and the nucleus. However, we also found two new types of hexokinases with no obvious orthologs in vascular plants. Type C, encoded by a single gene, has neither transit peptide nor membrane anchor, and is found in the cytosol and in the nucleus. Type D hexokinases, encoded by three genes, have membrane anchors and localize to mitochondrial membranes, but their sequences differ from those of the type B hexokinases. Interestingly, all moss hexokinases are more similar to each other in overall sequence than to hexokinases from other plants, even though characteristic sequence motifs such as the membrane anchor of the type B hexokinases are highly conserved between moss and vascular plants, indicating a common origin for hexokinases of the same type.ConclusionsWe conclude that the hexokinase gene family is more diverse inPhyscomitrella, encoding two additional types of hexokinases that are absent in vascular plants. In particular, the presence of a cytosolic and nuclear hexokinase (type C) setsPhyscomitrellaapart from vascular plants, and instead resembles yeast, where all hexokinases localize to the cytosol. The fact that all moss hexokinases are more similar to each other than to hexokinases from vascular plants, even though both type A and type B hexokinases are present in all plants, further suggests that the hexokinase gene family inPhyscomitrellahas undergone concerted evolution.
Evaluating clinic and community-based lifestyle interventions for obesity reduction in a low-income Latino neighborhood: Vivamos Activos Fair Oaks Program
Authors: Drieling Rebecca L , Ma Jun , Stafford Randall S 
Published: February 2011

Abstract

Background
Obesity exerts an enormous health impact through its effect on coronary heart disease and its risk factors. Primary care-based and community-based intensive lifestyle counseling may effectively promote weight loss. There has been limited implementation and evaluation of these strategies, particularly the added benefit of community-based intervention, in low-income Latino populations.

Design
The Vivamos Activos Fair Oaks project is a randomized clinical trial designed to evaluate the clinical and cost-effectiveness of two obesity reduction lifestyle interventions: clinic-based intensive lifestyle counseling, either alone (n = 80) or combined with community health worker support (n = 80), in comparison to usual primary care (n = 40). Clinic-based counseling consists of 15 group and four individual lifestyle counseling sessions provided by health educators targeting behavior change in physical activity and dietary practices. Community health worker support includes seven home visits aimed at practical implementation of weight loss strategies within the person's home and neighborhood. The interventions use a framework based on Social Cognitive Theory, the Transtheoretical Model of behavior change, and techniques from previously tested lifestyle interventions. Application of the framework was culturally tailored based on past interventions in the same community and elsewhere, as well as a community needs and assets assessment. The interventions include a 12-month intensive phase followed by a 12-month maintenance phase. Participants are obese Spanish-speaking adults with at least one cardiovascular risk factor recruited from a community health center in a low-income neighborhood of San Mateo County, California. Follow-up assessments occur at 6, 12, and 24 months for the primary outcome of percent change in body mass index at 24 months. Secondary outcomes include specific cardiovascular risk factors, particularly blood pressure and fasting glucose levels.

Discussion and Conclusions
If successful, this study will provide evidence for broad implementation of obesity interventions in minority populations and guidance about the selection of strategies involving clinic-based case management and community-based community health worker support.

Clinical Trial Registration
ClinicalTrials.gov: NCT01242683
Active protein aggregates induced by terminally attached self-assembling peptide ELK16 in Escherichia coli
Authors: Wu Wei , Xing Lei , Zhou Bihong , Lin Zhanglin 
Published: February 2011

Abstract

Background
In recent years, it has been gradually realized that bacterial inclusion bodies (IBs) could be biologically active. In particular, several proteins including green fluorescent protein, β-galactosidase, β-lactamase, alkaline phosphatase, D-amino acid oxidase, polyphosphate kinase 3, maltodextrin phosphorylase, and sialic acid aldolase have been successfully produced as active IBs when fused to an appropriate partner such as the foot-and-mouth disease virus capsid protein VP1, or the human β-amyloid peptide Aβ42(F19D). As active IBs may have many attractive advantages in enzyme production and industrial applications, it is of considerable interest to explore them further.

Results
In this paper, we report that an ionic self-assembling peptide ELK16 (LELELKLK)2 was able to effectively induce the formation of cytoplasmic inclusion bodies in Escherichia coli (E. coli) when attached to the carboxyl termini of four model proteins including lipase A, amadoriase II, β-xylosidase, and green fluorescent protein. These aggregates had a general appearance similar to the usually reported cytoplasmic inclusion bodies (IBs) under transmission electron microscopy or fluorescence confocal microscopy. Except for lipase A-ELK16 fusion, the three other fusion protein aggregates retained comparable specific activities with the native counterparts. Conformational analyses by Fourier transform infrared spectroscopy revealed the existence of newly formed antiparallel beta-sheet structures in these ELK16 peptide-induced inclusion bodies, which is consistent with the reported assembly of the ELK16 peptide.

Conclusions
This has been the first report where a terminally attached self-assembling β peptide ELK16 can promote the formation of active inclusion bodies or active protein aggregates in E. coli. It has the potential to render E. coli and other recombinant hosts more efficient as microbial cell factories for protein production. Our observation might also provide hints for protein aggregation-related diseases.
Immunization with different Pf AMA1 alleles in sequence induces clonal imprint humoral responses that are similar to responses induced by the same alleles as a vaccine cocktail in rabbits
Authors: Kusi Kwadwo A , Faber Bart W , van der Eijk Marjolein , Thomas Alan W , Kocken Clemens HM , Remarque Edmond J 
Published: February 2011

Abstract

Background
Antibodies to key Plasmodium falciparum surface antigens have been shown to be important effectors that mediate clinical immunity to malaria. The cross-strain fraction of anti-malarial antibodies may however be required to achieve
strain-transcending immunity. Such antibody responses against Plasmodium falciparum apical membrane antigen 1 (Pf AMA1), a vaccine target molecule that is expressed in both liver and blood stages of the parasite, can be elicited through immunization with a mixture of allelic variants of the parasite molecule. Cross-strain antibodies are most likely elicited against epitopes that are shared by the allelic antigens in the vaccine cocktail.

Methods
A standard competition ELISA was used to address whether the antibody response can be further focused on shared epitopes by exclusively boosting these common determinants through immunization of rabbits with different Pf AMA1 alleles in sequence. The in vitro parasite growth inhibition assay was used to further evaluate the functional effects of the broadened antibody response that is characteristic of multi-allele vaccine strategies.

Results
A mixed antigen immunization protocol elicited humoral responses that were functionally similar to those elicited by a sequential immunization protocol (p > 0.05). Sequential exposure to the different Pf AMA1 allelic variants induced immunological recall of responses to previous alleles and yielded functional cross-strain antibodies that would be capable of optimal growth inhibition of variant parasites at high enough concentrations.

Conclusions
These findings may have implications for the current understanding of the natural acquisition of clinical immunity to malaria as well as for rational vaccine design.
Developing a method to derive alcohol-attributable fractions for HIV/AIDS mortality based on alcohol's impact on adherence to antiretroviral medication
Authors: Gmel Gerrit , Shield Kevin D , Rehm Jürgen 
Published: February 2011

Abstract

Background
Alcohol consumption is causally linked to nonadherence to antiretroviral treatment that in turn causes an increase in HIV/AIDS mortality. This article presents a method to calculate the percentage of HIV/AIDS deaths attributable to alcohol consumption and the associated uncertainty.

Methods
By combining information on risk relations from a number of published sources, we estimated alcohol-attributable fractions (AAFs) of HIV/AIDS in a stepwise procedure. First, we estimated the effect of alcohol consumption on adherence to antiretroviral treatment, and then we combined this estimate with the impact of nonadherence on death. The 95% uncertainty intervals were computed by estimating the variance of the AAFs using Taylor series expansions of one and multiple variables. AAFs were determined for each of the five Global Burden of Disease regions of Africa, based on country-specific treatment and alcohol consumption data from 2005.

Results
The effects of alcohol on HIV/AIDS in the African Global Burden of Disease regions range from 0.03% to 0.34% for men and from 0% to 0.17% for women, depending on region and age category. The detrimental effect of alcohol consumption was statistically significant in every region and age category except for the North Africa/Middle East region.

Conclusions
Although the method has its limitations, it was shown to be feasible and provided estimates of the impact of alcohol use on the mortality outcome of HIV/AIDS.