bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overweight and obesity in Norwegian children: Secular trends in weight‐for‐height and skinfolds
Authors: Júlíusson PB , Roelants M , Eide GE , Hauspie R , Waaler PE , Bjerknes R 
Published: October 2007

AbstractAim: The prevalence of overweight and obesity in paediatric populations has been rapidly increasing in many countries over the past decades. The aims of the present study were to provide new data on weight‐for‐height and skinfolds, and to compare these to growth references for children between 3 and 17 years, collected in the same city between 1971 and 1974.Material: The present study is based on cross‐sectional data of 4115 children (2086 boys and 2029 girls) aged 4–15 years measured in 2003–6.Results: Overall, 18.0% of the boys and 20.1% of the girls were above the 90th weight‐for‐height percentile of the 1971–1974 references, 8.0% and 7.2% were above the 97.5th percentile, indicating an upward shift in weight‐for‐height. An even more prominent increase was observed for skinfold thicknesses; for triceps skinfolds about 30% of the boys and 28% of the girls were above the 90th percentile of the 1971–1974 references, and corresponding values for subscapular skinfolds were 26.5% and 25.9%. Using international cut‐off values for body mass index, the overall prevalence of overweight and obesity was 12.5% and 2.1% in boys, and 14.8% and 2.9% in girls.Conclusions: Our study has demonstrated a significant increase in weight‐for‐height in Norwegian children over the last 30 years, and that these changes are caused by an increase in fat tissue, as shown by skinfold measurements. The current prevalence of overweight and obesity is comparable to recent estimates from most Western and Northern European countries.
Infants admitted to a neonatal intensive care unit: parental psychological status at 9 months
Authors: Carter Janet D , Mulder Roger T , Frampton Christopher M A , Darlow Brian A 
Published: October 2007

AbstractAim: This paper reports on the 9‐month follow‐up of parents who had an infant admitted to neonatal intensive care unit (NICU) compared to parents of full‐term health infants. The psychological status of the parent groups is compared and factors associated with status change are examined.Methods: Prospective longitudinal study of random sample of 447 parents (mother and father with an infant admitted to the NICU and 189 parents (mother and father) with term infant not requiring NICU admission. Parents' depression and anxiety symptoms were assessed at infant birth and 9 months later.Results: The increased levels of depression and anxiety symptoms evident in NICU parents after their infant's birth were no longer apparent by 9 months. Higher initial symptom severity and perceived quality of the couple relationship were most commonly associated with improvement. Other factors related to symptoms change were number of baby hospitalizations for fathers and being in the NICU, age and living with the infant's father or mother.Conclusion: For the majority of parents having an infant admitted to the NICU does not result in ongoing psychological distress.
Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin
Authors: Freemark Michael 
Published: October 2007

AbstractAim: In a previous study we showed that metformin reduced BMI z‐scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6‐month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines.Methods: The 6‐month trial was randomized, double blinded and placebo controlled; a total of 14 metformin‐treated (500 mg bid) and 15 placebo‐treated subjects completed the study. There were no dietary restrictions.Results: In obese adolescents fed ad libitum, metformin (a) prevented the rise in ALT concentrations that were observed in placebo‐treated subjects at the 3 to 5 month time‐points (p < 0.05); (b) reduced (p < 0.01) the percentage of all ALT values exceeding 40 U/L; and (c) caused a modest (10%) but statistically significant (p < 0.05) reduction in serum ALT in Caucasian subjects. Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study but reduced their fasting insulin concentrations from 26.1 to 19.5 μU/mL (p < 0.05).Conclusions: Our findings suggest that metformin might reduce the rates or severity of liver dysfunction in selected high‐risk adolescents.
McErlang
Authors: Fredlund Lars-Åke , Svensson Hans 
Published: October 2007

We present a model checker for verifying distributed programs written in the Erlang programming language. Providing a model checker for Erlang is especially rewarding since the language is by now being seen as a very capable platform for developing industrial strength distributed applications with excellent failure tolerance characteristics. In contrast to most other Erlang verification attempts, we provide support for a very substantial part of the language. The model checker has full Erlang data type support, support for general process communication, node semantics (inter-process behave subtly different from intra-process communication), fault detection and fault tolerance through process linking, and can verify programs written using the OTP Erlang component library (used by most modern Erlang programs).
As the model checking tool is itself implemented in Erlang we benefit from the advantages that a (dynamically typed) functional programming language offers: easy prototyping and experimentation with new verification algorithms, rich executable models that use complex data structures directly programmed in Erlang, the ability to treat executable models interchangeably as programs (to be executed directly by the Erlang interpreter) and data, and not least the possibility to cleanly structure and to cleanly combine various verification sub-tasks. In the paper we discuss the design of the tool and provide early indications on its performance.
Adding delimited and composable control to a production programming environment
Authors: Flatt Matthew , Yu Gang , Findler Robert Bruce , Felleisen Matthias 
Published: October 2007

Operators for delimiting control and for capturing composable continuations litter the landscape of theoretical programming language research. Numerous papers explain their advantages, how the operators explain each other (or don't), and other aspects of the operators' existence. Production programming languages, however, do not support these operators, partly because their relationship to existing and demonstrably useful constructs - such as exceptions and dynamic binding - remains relatively unexplored.
In this paper, we report on our effort of translating the theory of delimited and composable control into a viable implementation for a production system. The report shows how this effort involved a substantial design element, including work with a formal model, as well as significant practical exploration and engineering.
The resulting version of PLT Scheme incorporates the expressive combination of delimited and composable control alongside dynamic-wind, dynamic binding, and exception handling. None of the additional operators subvert the intended benefits of existing control operators, so that programmers can freely mix and match control operators.
Evaluating high-level distributed language constructs
Authors: Nyström Jan , Trinder Phil , King David 
Published: October 2007

The paper investigates the impact of high level distributed programming language constructs on the engineering of realistic software components. Based on reengineering two non-trivial telecoms components, we compare two high-level distributed functional languages, Erlang and GdH, with conventional distributed technologies C++/CORBA and C++/UDP.
We investigate several aspects of high-level distributed languages including the impact on code size of high-level constructs. We identify three language constructs that primarily contribute to the reduction in application size and quantify their impact. We provide the first evidence based on analysis of a substantial system to support the widely-held supposition that high-level constructs reduce programming effort associated with specifying distributed coordination. We investigate whether a language with sophisticated high-level fault tolerance can produce suitably robust components, and both measure and analyse the additional programming effort needed to introduce robustness. Finally, we investigate some implications of a range of type systems for engineering distributed software.
User-friendly functional programming for web mashups
Authors: Ennals Rob , Gay David 
Published: October 2007

MashMaker is a web-based tool that makes it easy for a normal user to create web mashups by browsing around, without needing to type, or plan in advance what they want to do.
Like a web browser, Mashmaker allows users to create mashups by browsing, rather than writing code, and allows users to bookmark interesting things they find, forming new widgets - reusable mashup fragments. Like a spreadsheet, MashMaker mixes program and data and allows ad-hoc unstructured editing of programs.
MashMaker is also a modern functional programming language with non-side effecting expressions, higher order functions, and lazy evaluation. MashMaker programs can be manipulated either textually, or through an interactive tree representation, in which a program is presented together with the values it produces.
In order to cope with this unusual domain, MashMaker contains a number of deviations from normal function languages. The most notable of these is that, in order to allow the programmer to write programs directly on their data, all data is stored in a single tree, and evaluation of an expression always takes place at a specific point in this tree, which also functions as its scope.
Feedback directed implicit parallelism
Authors: Harris Tim , Singh Satnam 
Published: October 2007

In this paper we present an automated way of using spare CPU resources within a shared memory multi-processor or multi-core machine. Our approach is (
i
) to profile the execution of a program, (
ii
) from this to identify pieces of work which are promising sources of parallelism, (
iii
) recompile the program with this work being performed speculatively via a work-stealing system and then (
iv
) to detect at run-time any attempt to perform operations that would reveal the presence of speculation.

We assess the practicality of the approach through an implementation based on GHC 6.6 along with a limit study based on the execution profiles we gathered. We support the full Concurrent Haskell language compiled with traditional optimizations and including I/O operations and synchronization as well as pure computation. We use 20 of the larger programs from the 'nofib' benchmark suite. The limit study shows that programs vary a lot in the parallelism we can identify: some have none, 16 have a potential 2x speed-up, 4 have 32x. In practice, on a 4-core processor, we get 10-80% speed-ups on 7 programs. This is mainly achieved at the addition of a second core rather than beyond this.
This approach is therefore not a replacement for manual parallelization, but rather a way of squeezing extra performance out of the threads of an already-parallel program or out of a program that has not yet been parallelized.
Faster laziness using dynamic pointer tagging
Authors: Marlow Simon , Yakushev Alexey Rodriguez , Peyton Jones Simon 
Published: October 2007

In the light of evidence that Haskell programs compiled by GHC exhibit large numbers of mispredicted branches on modern processors, we re-examine the "tagless" aspect of the STG-machine that GHC uses as its evaluation model.
We propose two tagging strategies: a simple strategy called semi-tagging that seeks to avoid one common source of unpredictable indirect jumps, and a more complex strategy called dynamic pointer-tagging that uses the spare low bits in a pointer to encode information about the pointed-to object. Both of these strategies have been implemented and exhaustively measured in the context of a production compiler, GHC, and the paper contains detailed descriptions of the implementations. Our measurements demonstrate significant performance improvements (14% for dynamic pointer-tagging with only a 2% increase in code size), and we further demonstrate that much of the improvement can be attributed to the elimination of mispredicted branch instructions.
As part of our investigations we also discovered that one optimisation in the STG-machine, vectored-returns, is no longer worthwhile and we explain why.
Call-pattern specialisation for Haskell programs
Authors: Peyton Jones Simon 
Published: October 2007

User-defined data types, pattern-matching, and recursion are ubiquitous features of Haskell programs. Sometimes a function is called with arguments that are statically known to be in constructor form, so that the work of pattern-matching is wasted. Even worse, the argument is sometimes freshly-allocated, only to be immediately decomposed by the function.
In this paper we describe a simple, modular transformation that specialises recursive functions according to their argument "shapes". We describe our implementation of this transformation in the Glasgow Haskell Compiler, and give measurements that demonstrate substantial performance improvements: a worthwhile 10% on average, with a factor of 10 in particular cases.
Discovery and Pharmacologic Characterization of CP-724,714, a Selective ErbB2 Tyrosine Kinase Inhibitor
Authors: Jani Jitesh P. , Finn Richard S. , Campbell Mary , Coleman Kevin G. , Connell Richard D. , Currier Nicolas , Emerson Erling O. , Floyd Eugenia , Harriman Shawn , Kath John C. , Morris Joel , Moyer James D. , Pustilnik Leslie R. , Rafidi Kristina , Ralston Sherry , Rossi Ann Marie K. , Steyn Stefanus J. , Wagner Larry , Winter Steven M. , Bhattacharya Samit K. 
Published: October 2007

AbstractAmplification and overexpression of erbB2 (Her-2/neu) proto-oncogene has been linked to human malignancies including tumors of the breast, ovary, and stomach. It has been implicated in tumor growth, sensitivity to standard chemotherapy, prognosis of patients, and disease-free survival. Although the clinical use of trastuzumab (Herceptin) has prolonged the survival of breast cancer patients with erbB2-overexpressing tumors, there is an urgent need for more potent and orally bioavailable small-molecule inhibitors. CP-724,714 is a potent inhibitor of erbB2 receptor autophosphorylation in intact cells and is currently undergoing phase I clinical trials. Here, we describe the effects of CP-724,714 in vitro and in vivo in human breast cancer models. CP-724,714 is selective for inhibiting growth of HER2-driven cell lines. In addition, we show that it induces G1 cell cycle block in erbB2-overexpressing BT-474 human breast carcinoma cells and inhibits erbB2 autophosphorylation in xenografts when administered p.o. to athymic mice. It induces a marked reduction of extracellular signal–regulated kinase and Akt phosphorylation, tumor cell apoptosis, and release of caspase-3. P.o. administration (q.d. or b.i.d.) of CP-724,714 inhibits the growth of erbB2-overexpressing tumors in athymic mice without overt adverse effects. [Cancer Res 2007;67(20):9887–93]
Proteasome Inhibition Up-regulates p53 and Apoptosis-Inducing Factor in Chondrocytes Causing Severe Growth Retardation in Mice
Authors: Zaman Farasat , Menendez-Benito Victoria , Eriksson Emma , Chagin Andrei S. , Takigawa Masaharu , Fadeel Bengt , Dantuma Nico P. , Chrysis Dionisios , Sävendahl Lars 
Published: October 2007

Abstract
Proteasome inhibitors (PI), a novel class of anticancer drugs, are relatively well tolerated and have recently been introduced into the clinic for the treatment of multiple myeloma. The tumor selectivity and low toxicity of PIs are surprising, given the crucial role of the ubiquitin/proteasome system in a multitude of cellular processes. Here, we show that systemic administration of PIs specifically impairs the ubiquitin/proteasome system in growth plate chondrocytes. Importantly, young mice displayed severe growth retardation during treatment as well as 45 days after the cessation of treatment with clinically relevant amounts of MG262 (0.2 μmol/kg body weight/injection) or bortezomib (1.0 mg/kg body weight/injection). Dysfunction of the ubiquitin/proteasome system was accompanied by the induction of apoptosis of stem-like and proliferative chondrocytes in the growth plate. These results were recapitulated in cultured fetal rat metatarsal bones and chondrocytic cell lines (rat, human). Apoptosis was associated with up-regulation of the proapoptotic molecules, p53 and apoptosis-inducing factor (AIF), both in vitro and in vivo. In addition to the observation that AIF is expressed in the growth plate, we also provide evidence that AIF serves as a direct target protein for ubiquitin, thus explaining its prominent up-regulation upon proteasome inhibition. Suppression of p53 or AIF expression with small interfering RNAs partly rescued chondrocytes from proteasome inhibition–induced apoptosis (35% and 41%, respectively). Our observations show that proteasome inhibition may selectively target essential cell populations in the growth plate causing significant growth failure. These findings could have important implications for the use of proteasome inhibitors in the treatment of childhood cancer. [Cancer Res 2007;67(20):10078–86]
Interleukin-4 Cytotoxin Therapy Synergizes with Gemcitabine in a Mouse Model of Pancreatic Ductal Adenocarcinoma
Authors: Shimamura Takeshi , Royal Richard E. , Kioi Mitomu , Nakajima Atsushi , Husain Syed R. , Puri Raj K. 
Published: October 2007

Abstract
Targeting cell surface receptors with cytotoxins or immunotoxins provides a unique opportunity for tumor therapy. Here, we show the efficacy of the combination therapy of gemcitabine with an interleukin-4 (IL-4) cytotoxin composed of IL-4 and truncated Pseudomonas exotoxin in animal models of pancreatic ductal adenocarcinoma (PDA). We have observed that 42 of 70 (60%) tumor samples from patients with PDA express moderate- to high-density surface IL-4 receptor (IL-4R), whereas normal pancreatic samples express no or low-density IL-4R. IL-4 cytotoxin was specifically and highly cytotoxic [50% protein synthesis inhibition (IC50) ranging from &gt;0.1 to 13 ng/mL] to six of eight pancreatic cancer cell lines, whereas no cytotoxicity (IC50 &gt;1,000 ng/mL) was observed in normal human pancreatic duct epithelium cells, fibroblasts, and human umbilical vein endothelial cells (HUVEC). We also showed that IL-4 cytotoxin in combination with gemcitabine exhibited synergistic antitumor activity in vitro. To confirm synergistic antitumor activity in vivo and monitor precise real-time disease progression, we used a novel metastatic and orthotopic mouse model using green fluorescent protein–transfected cancer cells and whole-body imaging system. The combination of both agents caused complete eradication of tumors in 40% of nude mice with small established PDA tumors. In addition, combined treatment significantly prolonged the survival of nude mice bearing day 14 advanced distant metastatic PDA tumors. Similar results were observed in mice xenografted with PDA obtained from a patient undergoing surgical resection. These results indicate that IL-4 cytotoxin combined with gemcitabine may provide effective therapy for the treatment of patients with PDA. [Cancer Res 2007;67(20):9903–12]
Complex N-Glycan and Metabolic Control in Tumor Cells
Authors: Mendelsohn Richard , Cheung Pam , Berger Lloyd , Partridge Emily , Lau Ken , Datti Alessandro , Pawling Judy , Dennis James W. 
Published: October 2007

Abstract
Golgi β1,6N-acetylglucosaminyltransferase V (Mgat5) produces β1,6GlcNAc-branched complex N-glycans on cell surface glycoproteins that bind to galectins and promote surface residency of glycoproteins, including cytokine receptors. Carcinoma cells from polyomavirus middle T (PyMT) transgenic mice on a Mgat5−/− background have reduced surface levels of epidermal growth factor (EGF) and transforming growth factor-β (TGF-β) receptors and are less sensitive to acute stimulation by cytokines in vitro compared with PyMT Mgat5+/+ tumor cells but are nonetheless tumorigenic when injected into mice. Here, we report that PyMT Mgat5−/− cells are reduced in size, checkpoint impaired, and following serum withdrawal, fail to down-regulate glucose transport, protein synthesis, reactive oxygen species (ROS), and activation of Akt and extracellular signal-regulated kinase. To further characterize Mgat5+/+ and Mgat5−/− tumor cells, a screen of pharmacologically active compounds was done. Mgat5−/− tumor cells were comparatively hypersensitive to the ROS inducer 2,3-dimethoxy-1,4-naphthoquinone, hyposensitive to tyrosine kinase inhibitors, to Golgi disruption by brefeldin A, and to mitotic arrest by colcemid, hydroxyurea, and camptothecin. Finally, regulation of ROS, glucose uptake, and sensitivities to EGF and TGF-β were rescued by Mgat5 expression or by hexosamine supplementation to complex N-glycan biosynthesis in Mgat5−/− cells. Our results suggest that complex N-glycans sensitize tumor cells to growth factors, and Mgat5 is required to balance responsiveness to growth and arrest cues downstream of metabolic flux. [Cancer Res 2007;67(20):9771–80]
Fms-like Tyrosine Kinase 3 Ligand Stimulation Induces MLL-Rearranged Leukemia Cells into Quiescence Resistant to Antileukemic Agents
Authors: Furuichi Yoshiyuki , Goi Kumiko , Inukai Takeshi , Sato Hiroki , Nemoto Atsushi , Takahashi Kazuya , Akahane Koshi , Hirose Kinuko , Honna Hiroko , Kuroda Itaru , Zhang Xiaochun , Kagami Keiko , Hayashi Yasuhide , Harigaya Kenichi , Nakazawa Shinpei , Sugita Kanji 
Published: October 2007

Abstract
Fms-like tyrosine kinase 3 (FLT3) is highly expressed in acute lymphoblastic leukemia with the mixed-lineage leukemia (MLL) gene rearrangement refractory to chemotherapy. We examined the biological effect of FLT3-ligand (FL) on 18 B-precursor leukemic cell lines with variable karyotypic abnormalities, and found that nine of nine MLL-rearranged cell lines with wild-type FLT3, in contrast to other leukemic cell lines, are significantly inhibited in their proliferation in a dose-dependent manner by FL. This inhibition was due to induction of the G0-G1 arrest. A marked up-regulation of p27 by suppression of its protein degradation and an abrogation of constitutive signal transducers and activators of transcription 5 phosphorylation were revealed in arrested leukemia cells after FL stimulation. Importantly, FL treatment rendered not only cell lines but also primary leukemia cells with MLL rearrangement resistant to chemotherapeutic agents. MLL-rearranged leukemia cells adhering to the bone marrow stromal cell line, which expresses FL as the membrane-bound form, were induced to quiescent state resistant to chemotherapeutic agents, but their chemosensitivity was significantly restored in the presence of neutralizing anti-FL antibody. The FL/FLT3 interaction between leukemia cells and bone marrow stromal cells expressing FL at high levels should contribute, at least in part, to persistent minimal-residual disease of MLL-rearranged leukemia in bone marrow. [Cancer Res 2007;67(20):9852–61]