bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteins from the Wnt pathway are involved in the pathogenesis and progression of mammary phyllodes tumours
Authors: Karim R Z , Gerega S K , Yang Y H , Horvath L , Spillane A , Carmalt H , Scolyer R A , Lee C S 
Published: October 2009

Background:The Wnt pathway is important in cell signalling transduction and is involved in the pathogenesis of multiple tumour types. A comprehensive analysis of the expression of Wnt signalling pathway proteins in mammary phyllodes tumours (PTs) has not been previously performed.Aims:To evaluate the immunohistochemical expression of Wnt pathway proteins in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome.Methods:65 PTs (34 benign, 23 borderline and 8 malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemical stains were performed on tissue microarrays for β-catenin, Wnt1, Wnt5a, SFRP4 and E-cadherin. Stroma and epithelium were scored separately.Results:Stromal cytoplasmic Wnt5a and SFRP4 expression showed significant progressive increases in expression with increasing grade (p = 0.002 and p = 0.02 respectively). Epithelial membranous and stromal nuclear β-catenin, epithelial cytoplasmic Wnt1 and epithelial E-cadherin all also showed increasing expression with increasing tumour grade, however, the differences were not significant. Disease-free survival was significantly decreased (p = 0.0017) with positive epithelial E-cadherin staining.Conclusions:Results suggest that alterations in the Wnt pathway are important in the progression and in the epithelial and stromal interactions in PTs. They have important implications for understanding the pathogenesis of these uncommon but clinically important tumours.
If your pearls of wisdom fall in a forest…
Authors: Westfall Ralph 
Published: October 2009

Introduction

The idea of doing things that can improve something is an extremely popular concept in American culture. For example, I found the phrase,
make a difference
, in 129 million Web pages in a Yahoo! search in July 2009. The concept typically applies to impacts at local levels because, until recently, few people had opportunities to do things that could positively affect substantial numbers of people throughout the country in which they live or even throughout the world.

After dot com bubble burst, many investors found that the slogan that "the Internet changes everything" did not apply to many of the requirements for having a successful business. However the Internet really does provide opportunities for those who create knowledge to share it with more people who can use it to advantage, and share it more quickly than through other means.

Of course, this potential capability to share materials is limited by people's abilities to find useful information in the billions of pages on the Internet. Yahoo reported indexing over 19 billion pages in 2005. (Perhaps responding to criticism of the estimates,
1
the leading search engine companies no longer publish counts of pages indexed. Although no one really knows how big the "haystack" is, the simile about "finding a needle" is quite applicable to the Internet.)

Nevertheless there are two aspects of innovative materials that work in favor of their being found:
• The goals of search engine companies.
• The nature of knowledge.
Strictly declarative specification of sophisticated points-to analyses
Authors: Bravenboer Martin , Smaragdakis Yannis 
Published: October 2009

We present the DOOP framework for points-to analysis of Java programs. DOOP builds on the idea of specifying pointer analysis algorithms declaratively, using Datalog: a logic-based language for defining (recursive) relations. We carry the declarative approach further than past work by describing the full end-to-end analysis in Datalog and optimizing aggressively using a novel technique specifically targeting highly recursive Datalog programs.
As a result, DOOP achieves several benefits, including full order-of-magnitude improvements in runtime. We compare DOOP with Lhotak and Hendren's PADDLE, which defines the state of the art for context-sensitive analyses. For the exact same logical points-to definitions (and, consequently, identical precision) DOOP is more than 15x faster than PADDLE for a 1-call-site sensitive analysis of the DaCapo benchmarks, with lower but still substantial speedups for other important analyses. Additionally, DOOP scales to very precise analyses that are impossible with PADDLE and Whaley et al.'s bddbddb, directly addressing open problems in past literature. Finally, our implementation is modular and can be easily configured to analyses with a wide range of characteristics, largely due to its declarativeness.
Optimizing programs with intended semantics
Authors: von Dincklage Daniel , Diwan Amer 
Published: October 2009

Modern object-oriented languages have complex features that cause programmers to overspecify their programs. This overspecification hinders automatic optimizers, since they must preserve the overspecified semantics. If an optimizer knew which semantics the programmer intended, it could do a better job.
Making a programmer clarify his intentions by placing assumptions into the program is rarely practical. This is because the programmer does not know which parts of the programs' overspecified semantics hinder the optimizer. Therefore, the programmer has to guess which assumption to add. Since the programmer can add many different assumptions to a large program, he will need to place many such assumptions before he guesses right and helps the optimizer.
We present IOpt, a practical optimizer that uses a specification of the programmers' intended semantics to enable additional optimizations. That way, our optimizer can significantly improve the performance of a program. We present case studies in which we use IOpt to speed up two programs by a factor of 2.

To make specifying the intended semantics practical, IOpt communicates with the programmer. IOpt identifies which assumptions the programmer
should
place, and where he should place them. IOpt ranks each assumption by (i) the likelyhood that the assumption conforms to the programmers' intended semantics and (ii) how much the assumption will help IOpt improve the programs' performance. IOpt proposes ranked assumptions to the programmer, who just picks those that conform to his intended semantics.With this approach, IOpt keeps the programmers' specification burden low. In our case studies, programmers had to add just a few assumptions to realize significant performance speedups.
Another Look at Interannual-to-Interdecadal Variations of the East Asian Winter Monsoon: The Northern and Southern Temperature Modes
Authors: Wang Bin , Wu Zhiwei , Chang Chih-Pei , Liu Jian , Li Jianping , Zhou Tianjun 
Published: October 2009

Abstract
This study investigates the causes of interannual-to-interdecadal variability of the East Asian (EA; 0°–60°N, 100°–140°E) winter monsoon (EAWM) over the past 50 yr (1957–2006). The winter mean surface air temperature variations are dominated by two distinct principal modes that together account for 74% of the total temperature variance. The two modes have notably different circulation structures and sources of variability. The northern mode, characterized by a westward shift of the EA major trough and enhanced surface pressure over central Siberia, represents a cold winter in the northern EA resulting from cold-air intrusion from central Siberia. The southern mode, on the other hand, features a deepening EA trough and increased surface pressure over Mongolia, representing a cold winter south of 40°N resulting from cold-air intrusion from western Mongolia. The cold northern mode is preceded by excessive autumn snow covers over southern Siberia–Mongolia, whereas the cold southern mode is preceded by development of La Niña episodes and reduced snow covers over northeast Siberia. These remarkably different spatiotemporal structures and origins are primarily associated with interannual variations. On the decadal or longer time scale their structures are somewhat similar and are preceded by similar autumn sea surface temperature anomalies over the North Atlantic and tropical Indian Ocean. The two modes found for the EA region also represent the winter temperature variability over the entire Asian continent. Thus, study of the predictability of the two modes may shed light on understanding the predictable dynamics of the Asian winter monsoon.
Acute Psychiatric Disorders in Foreign Domestic Workers in Hong Kong: a Pilot Study
Authors: Lau Phyllis W.L. , Cheng Judy G.Y. , Chow Dickson L.Y. , Ungvari G.S. , Leung C.M. 
Published: October 2009

Aim: To explore the psychopathology of foreign domestic workers (FDWs) who had an acute psychiatric disorder in Hong Kong. Method: This was a retrospective chart review. Demographic and clinical data were extracted from case records of FDWs who were admitted for the first time as inpatients for psychiatric treatment to three regional hospitals of the same catchment area in Hong Kong between 2000 and 2004. Relevant socio-demographic data on local FDWs and the general population of Hong Kong were obtained from local government departments. Results: Twenty-seven Filipino and 14 Indonesian FDWs presenting with their first and so far only psychiatric admission were identified. There were significantly more FDWs who were single or never married in the sample. Filipino FDWs tended to fall ill after 4 years of service in Hong Kong while the corresponding figure for Indonesian FDWs was 2 years. Indonesian FDWs were older and had less access to social and medical services than their Filipino counterparts. Home sickness and marital problems were more commonly identified as stressors rather than workrelated difficulties. Acute and Transient Psychotic Disorder (ICD-10) was diagnosed in over 60% of the subjects, making FDWs two times more vulnerable than local women of similar age for this illness. Conclusions: FDWs constitute a vulnerable group in terms of psychiatric morbidity. Concerted political, social and psychological efforts would be require to alleviate the distress faced by this particularly disadvantaged subset of female expatriates.
Developing a set of ancestry-sensitive DNA markers reflecting continental origins of humans
Authors: Kersbergen Paula , van Duijn Kate , Kloosterman Ate D , den Dunnen Johan T , Kayser Manfred , de Knijff Peter 
Published: October 2009

Abstract

Background
The identification and use of Ancestry-Sensitive Markers (ASMs), i.e. genetic polymorphisms facilitating the genetic reconstruction of geographical origins of individuals, is far from straightforward.

Results
Here we describe the ascertainment and application of five different sets of 47 single nucleotide polymorphisms (SNPs) allowing the inference of major human groups of different continental origin. For this, we first used 74 cell lines, representing human males from six different geographical areas and screened them with the Affymetrix Mapping 10K assay. In addition to using summary statistics estimating the genetic diversity among multiple groups of individuals defined by geography or language, we also used the program STRUCTURE to detect genetically distinct subgroups. Subsequently, we used a pairwise FST ranking procedure among all pairs of genetic subgroups in order to identify a single best performing set of ASMs. Our initial results were independently confirmed by genotyping this set of ASMs in 22 individuals from Somalia, Afghanistan and Sudan and in 919 samples from the CEPH Human Genome Diversity Panel (HGDP-CEPH)

Conclusion
By means of our pairwise population FST ranking approach we identified a set of 47 SNPs that could serve as a panel of ASMs at a continental level.
Tetrapisispora phaffii killer toxin is a highly specific β-glucanase that disrupts the integrity of the yeast cell wall
Authors: Comitini Francesca , Mannazzu Ilaria , Ciani Maurizio 
Published: October 2009

AbstractBackgroundKiller yeasts have been used to combat contaminating wild yeasts in food, to control pathogenic fungi in plants, and in the medical field, to develop novel antimycotics for the treatment of human and animal fungal infections. Among these killer yeasts,Tetrapisispora phaffii(formerly known asKluyveromyces phaffii) secretes a glycoprotein known as Kpkt that is lethal to spoilage yeasts under winemaking conditions. In the present study, the mode of action of Kpkt, and the specific damage produced by this toxin on sensitive yeasts is investigated.ResultsThe use of castanospermine, a β-glucanase inhibitor, demonstrated that β-glucanase activity is essential for the Kpkt killer activityin vivo. Accordingly, Kpkt has no killer activity on either sensitive yeast spheroplasts or whole sensitive cells in the presence of isosmothic medium (0.8 molar sorbitol). Kpkt induces ultrastructural modifications in the cell wall of sensitive strains, as shown by confocal microscopy, laser-scanning electron microscopy, and atomic force microscopy. The Kpkt killer action is mediated by the glucidic portion of the toxin. This, in turn, appears to be involved both in the stronger cytocidal activity and in the selectivity for the sensitive strain shown by Kpkt compared to laminarinase.ConclusionCollectively, these data indicate that the mode of action of Kpkt is directed towards the disruption of cell-wall integrity, and that this is mediated by a highly specific β-glucanase activity. In this, Kpkt differs from other microbial β-glucanases that do not show killer activities.
Influence of the calcium concentration in the presence of organic phosphorus on the physicochemical compatibility and stability of all-in-one admixtures for neonatal use
Authors: Ribeiro Daniela de Oliveira , Lobo Bianca Waruar , Volpato Nádia Maria , da Veiga Venício Féo , Cabral Lúcio Mendes , de Sousa Valeria Pereira 
Published: October 2009

Abstract

Background
Preterm infants need high amounts of calcium and phosphorus for bone mineralization, which is difficult to obtain with parenteral feeding due to the low solubility of these salts. The objective of this study was to evaluate the physicochemical compatibility of high concentrations of calcium associated with organic phosphate and its influence on the stability of AIO admixtures for neonatal use.

Methods
Three TPN admixture formulas were prepared in multilayered bags. The calcium content of the admixtures was adjusted to 0, 46.5 or 93 mg/100 ml in the presence of a fixed organic phosphate concentration as well as lipids, amino acids, inorganic salts, glucose, vitamins and oligoelements at pH 5.5. Each admixture was stored at 4°C, 25°C or 37°C and evaluated over a period of 7 days. The physicochemical stability parameters evaluated were visual aspect, pH, sterility, osmolality, peroxide formation, precipitation, and the size of lipid globules.

Results
Color alterations occurred from the first day on, and reversible lipid film formation from the third day of study for the admixtures stored at 25°C and 37°C. According to the parameters evaluated, the admixtures were stable at 4°C; and none of them presented precipitated particles due to calcium/phosphate incompatibility or lipid globules larger than 5 μm, which is the main parameter currently used to evaluate lipid emulsion stability. The admixtures maintained low peroxide levels and osmolarity was appropriate for parenteral administration.

Conclusion
The total calcium and calcium/phosphorus ratios studied appeared not to influence the physicochemical compatibility and stability of AIO admixtures.
Combined treatment with lexatumumab and irradiation leads to strongly increased long term tumour control under normoxic and hypoxic conditions
Authors: Marini Patrizia , Junginger Dorothea , Stickl Stefan , Budach Wilfried , Niyazi Maximilian , Belka Claus 
Published: October 2009

AbstractPurposeThe combination of ionizing radiation with the pro-apoptotic TRAIL receptor antibody lexatumumab has been shown to exert considerable synergistic apoptotic effects in vitro and in short term growth delay assays. To clarify the relevance of these effects on local tumour control long-term experiments using a colorectal xenograft model were conducted.Materials and methodsColo205-xenograft bearing NMRI (nu/nu) nude mice were treated with fractionated irradiation (5× 3 Gy, d1-5) and lexatumumab (0.75 mg/kg, d1, 4 and 8). The tumour bearing hind limbs were irradiated with graded single top up doses at d8 under normoxic (ambient) and acute hypoxic (clamped) conditions. Experimental animals were observed for 270 days. Growth delay and local tumour control were end points of the study. Statistical analysis of the experiments included evaluation of tumour regrowth and local tumour control.ResultsCombined treatment with irradiation and lexatumumab led to a pronounced tumour regrowth-delay when compared to irradiation alone. The here presented long-term experiments revealed a highly significant rise of local tumour control for normoxic (ambient) (p = 0. 000006) and hypoxic treatment (p = 0. 000030).ConclusionOur data show that a combination of the pro-apoptotic antibody lexatumumab with irradiation reduces tumour regrowth and leads to a highly increased local tumour control in a nude mouse model. This substantial effect was observed under ambient and more pronounced under hypoxic conditions.
Prognostic and Predictive Value of HER2 Extracellular Domain in Metastatic Breast Cancer Treated With Lapatinib and Paclitaxel in a Randomized Phase III Study
Authors: Finn Richard S. , Gagnon Robert , Di Leo Angelo , Press Michael F. , Arbushites Michael , Koehler Maria 
Published: October 2009

Purpose The HER2 extracellular domain (ECD) is enzymatically cleaved from the cell membrane. Shed ECD in serum has been studied as both prognostic and predictive markers. Lapatinib is a dual inhibitor of HER2 and epidermal growth factor receptor kinases. We examined the prognostic and predictive role of HER2 ECD in a randomized trial of paclitaxel with placebo or lapatinib in women with HER2-negative or -unknown breast cancer. Patients and Methods Patients (n = 579) with newly diagnosed metastatic breast cancer (MBC) were randomly assigned to paclitaxel with placebo or lapatinib. HER2 status was determined centrally. ECD was centrally measured by enzyme linked immunoassay in available samples at baseline (b; n = 472), week 9, and every 12 weeks thereafter. Results were correlated to overall response rate (ORR) and progression-free survival (PFS). Results Elevated baseline ECD (bECD) levels (≥ 16 ng/mL) did not predict HER2 tumor status (sensitivity, 62%; specificity, 75%). In HER2-negative tumors, elevated bECD was not correlated with improved efficacy for lapatinib plus paclitaxel versus placebo plus paclitaxel (ORR: odds ratio, 1.6; 95% CI, 0.1 to 3.8; P = .365; PFS: hazard ratio, 0.94; 95% CI, 0.60 to 1.47; P = .797). ECD levels tended to decrease over time when bECD was elevated. ECD conversion from low to high was associated with worse PFS. Converting from high to low was associated with a better PFS. A consistently low ECD level had better PFS than a consistently elevated ECD. All associations were found to be independent of lapatinib. Conclusion HER2 bECD does not predict lapatinib benefit in patients with HER2-negative MBC. Changes in ECD status correlates with patient outcome regardless of treatment given. Measuring HER2 ECD is not currently recommended for predicting benefit to lapatinib.
Dose Finding and Early Efficacy Study of Gemcitabine Plus Capecitabine in Combination With Bevacizumab Plus Erlotinib in Advanced Pancreatic Cancer
Authors: Starling Naureen , Watkins David , Cunningham David , Thomas Janet , Webb Janine , Brown Gina , Thomas Karen , Oates Jacqui , Chau Ian 
Published: October 2009

Purpose This study evaluated safety and efficacy of chemotherapy (gemcitabine plus capecitabine) plus bevacizumab/erlotinib in advanced pancreatic cancer because dual epidermal growth factor receptor/vascular endothelial growth factor blockade has a rational biologic basis in this malignancy. Patients and Methods Patients with untreated, unresectable, locally advanced or metastatic pancreatic carcinoma were enrolled onto one of the following four sequential dose levels (DLs) of escalating capecitabine doses (days 1 to 21): DL1, 910 mg/m2; DL2, 1,160 mg/m2; DL3, 1,400 mg/m2; or DL4, 1,660 mg/m2. Doses of coadministered gemcitabine (1,000 mg/m2 on days 1, 8, and 15), bevacizumab (5 mg/kg on days 1 and 15), and erlotinib (100 mg/d) every 28 days (up to six cycles) were fixed. Using a 3+3 study design, dose-limiting toxicity (DLT) was assessed in cycle 1. Results Twenty assessable patients were enrolled (DL1, n = 8; DL2, n = 3; DL3, n = 6; and DL4, n = 3); 97 cycles were administered. Median age was 63 years (range, 33 to 77 years), and male-to-female ratio was 10:10. Performance status was 0 and 1 in two and 17 patients, respectively; and nine and 11 patients had locally advanced and metastatic disease, respectively. DLT occurred in one patient at DL1 (grade 3 epistaxis) and two patients at DL4 (grade 3 diarrhea and grade 3 skin rash > 7 days). Common grade 3 and 4 toxicities (10% to 20%) were diarrhea, hand-foot syndrome, stomatitis, and skin rash. Grade 3 lethargy and grade 3 or 4 neutropenia occurred in 40% and 45% of patients, respectively. No GI perforation, grade 3 GI hemorrhage/hypertension, or pneumonitis occurred. Ten partial responses were observed. Median overall and progression-survival times (all patients) were 12.5 and 9.0 months, respectively. Conclusion The maximum-tolerated dose of capecitabine was 1,660 mg/m2. The recommended capecitabine dose in this cytotoxic doublet/biologic doublet regimen is 1,440 mg/m2; this regimen is under evaluation in an ongoing phase II study.
Randomized Phase II Study of Gemcitabine Administered at a Fixed Dose Rate or in Combination With Cisplatin, Docetaxel, or Irinotecan in Patients With Metastatic Pancreatic Cancer: CALGB 89904
Authors: Kulke Matthew H. , Tempero Margaret A. , Niedzwiecki Donna , Hollis Donna R. , Kindler Hedy L. , Cusnir Michael , Enzinger Peter C. , Gorsch Stefan M. , Goldberg Richard M. , Mayer Robert J. 
Published: October 2009

Purpose The relative value of gemcitabine-based combination chemotherapy therapy and prolonged infusions of gemcitabine in patients with advanced pancreatic cancer remains controversial. We explored the efficacy and toxicity of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in a multi-institutional, randomized, phase II study. Patients and Methods Patients with metastatic pancreatic cancer were randomly assigned to one of the following four regimens: gemcitabine 1,000 mg/m2 on days 1, 8, and 15 with cisplatin 50 mg/m2 on days 1 and 15 (arm A); gemcitabine 1,500 mg/m2 at a rate of 10 mg/m2/min on days 1, 8, and 15 (arm B); gemcitabine 1,000 mg/m2 with docetaxel 40 mg/m2 on days 1 and 8 (arm C); or gemcitabine 1,000 mg/m2 with irinotecan 100 mg/m2 on days 1 and 8 (arm D). Patients were observed for response, toxicity, and survival. Results Two hundred fifty-nine patients were enrolled onto the study, of whom 245 were eligible and received treatment. Anticipated rates of myelosuppression, fatigue, and expected regimen-specific toxicities were observed. The overall tumor response rates were 12% to 14%, and the median overall survival times were 6.4 to 7.1 months among the four regimens. Conclusion Gemcitabine/cisplatin, fixed dose rate gemcitabine, gemcitabine/docetaxel, and gemcitabine/irinotecan have similar antitumor activity in metastatic pancreatic cancer. In light of recent negative randomized studies directly comparing several of these regimens with standard gemcitabine, none of these approaches can be recommended for routine use in patients with this disease.