bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward a 21st Century Social Contract
Authors: Ferenbach Carl , Pinney Chris 
Published: July 2012

This article makes the case for a new contract between business and government that will help us address the critical challenge of our time: the globalization of commerce, and its disruptive effects on labor, local communities, and the environment. The authors begin by showing how globalization has created a new playing field for government and business in which our current governance models and a social contract that proved remarkably effective during the 20th century can no longer ensure economic stability and social progress. While the private sector has for the most part demonstrated its ability to adapt and flourish in a global economy, governments have struggled, thanks in large part to complex decision‐making processes and centralized bureaucracies that were created in response to 20th‐century realities. The result has been ever more indebted nations and governments that have been unable to maintain the core foundation and social investments on which their economic competitiveness and the social well‐being of their citizens depend.Our challenge now is to create a new social contract between business and government that is equal to the challenges of a global economy. The authors identify a number of key issues that must be addressed in creating this new framework, and explore recent and emerging business leadership initiatives that are working to address them. These range from initiatives that encourage greater self‐regulation by business of its impact on society and the environment to those that explore ways for the private sector to help governments deliver services more cost effectively.As part of the fallout from the recent financial crisis, business, broadly speaking, no longer enjoys the level of public trust it once did, which has added significantly to the challenges it now faces in taking on greater social responsibility. To direct its considerable resources to the greater public good while continuing to produce a competitive return to shareholders will require a degree of innovation and leadership that many companies will find difficult. But without this increased participation of business and its leaders, it is hard to see how we will prosper in the increasingly uncertain future we now face.
Sustainability at Dow Chemical
Authors: Perkins Kathleen M. , Eccles Robert G. , Weick Mark 
Published: July 2012

Dow Chemical Company, which was founded in 1894, is now the second‐largest chemical company in the world. From the outset, the company has been committed to high‐technology research and commercial innovation in chemistry, advanced materials, and agro‐sciences. But if Dow's long history of innovation is impressive, the greatest change in the past few years has been the company's use of innovation to reinforce its commitment to sustainability. In 1996, the company produced its first set of 10‐year sustainability‐related goals. In an effort to meet such goals, the company invested a total of $1 billion in environmentally beneficial products such as new seeds and traits in Dow's AgroSciences business, solar shingles, and advanced battery technologies. Along with the social benefit of higher crop yields and reduced carbon emissions, the company's return on this investment has been estimated at $5 billion.The company was even more ambitious when setting its next set of 10‐year goals in 2006. In this statement, Dow's leadership aimed to create a culture that saw sustainability as a business opportunity from the perspective of a “triple bottom line”—a performance evaluation scheme focused on “people, planet, and profit” that construes success in terms of social benefits, environmental stewardship, and economic prosperity. Dow is now starting the process of developing its third set of 10‐year goals, with the aim of producing a plan that will ensure the viability of the company 50 years from now. With this end in mind, Dow's leaders understand their obligation to continue investing in the health and well‐being of their employees, their communities, and the environment while still creating value for their shareholders.
Antiemetic treatment for acute gastroenteritis in children: an updated Cochrane systematic review with meta-analysis and mixed treatment comparison in a Bayesian framework
Authors: Carter Ben , Fedorowicz Zbys 
Published: July 2012

ObjectiveTo assess the evidence for the safety and effectiveness of antiemetics on gastroenteritis-induced vomiting in children and adolescents.DesignSystematic review.Data SourcesThe Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE searched from 1980 to March 2012.MethodsMethods included comprehensive searches, data synthesis, meta-analysis and mixed treatment comparisons (MTC).Review methodsReference lists were checked, and missing or inconsistent data were sought from trial investigators. Randomised controlled trials comparing antiemetics in participants younger than 18 years and who were vomiting due to acute gastroenteritis. Four meta-analyses and three MTC were carried out.Results10 trials (1479 participants) and five treatments were included: dexamethasone, dimenhydrinate, granisetron, metoclopramide and ondansetron. There was clear evidence that ondansetron (oral or intravenous) compared with placebo increased the proportion of patients with cessation of vomiting (orally administered) (RR 1.44, 95% CI 1.29 to 1.61), reduced the immediate hospital admission rate (orally administered) (RR 0.40, 95% CI 0.19 to 0.83) and the need for intravenous rehydration therapy (orally administered) (RR 0.41, 95% CI 0.29 to 0.59). No significant difference was noted in the revisit rates, but ondansetron was associated with an increase in episodes of diarrhoea. There was no evidence for the use of dexamethasone or metoclopramide and limited evidence that dimenhydrinate or granisetron increased the cessation of vomiting. The MTC analysis suggested that ondansetron was the most likely treatment to stop the child vomiting. Nine studies were carried out in secondary care and one in primary care.ConclusionsThis systematic review used a method novel to this clinical area and found clear evidence that ondansetron was the most likely treatment to allow oral rehydration therapy to commence. Given the significance of these results, the authors urge healthcare policy makers to consider the wider use of ondansetron in secondary care. Furthermore, randomised controlled trials are needed to investigate the effectiveness of antiemetic treatment in primary care (including ambulatory care interventions).
Awaiting a New Era of Cancer Immunotherapy
Authors: Hong Cheng William , Zeng Qi 
Published: July 2012

Abstract
A major challenge in cancer therapy is the lack of specificity for cancer cells. Antibody-based therapies have better specificity and, thus, improved efficacy over standard chemotherapy regimens. Monoclonal antibodies (mAb) constitute the most rapidly growing class of human therapeutics and are proven agents for recognizing and destroying malignant cells. However, the development of antibody therapies has focused only on targeting extracellular (cell-surface or secreted) proteins rather than intracellular targets (within cells, such as phosphatases and/or kinases and transcription factors), because antibodies are generally believed to be too large to enter cells, resulting in a large untapped source of intracellular therapeutic targets. Recently, we presented evidence that suggests that intracellular proteins with high expression in cancer cells are useful targets for mAb-based or vaccination immunotherapies, thus challenging current understanding. Here, we further discuss the concept and future uses of these immunotherapies against a large pool of intracellular oncoproteins for cancer therapy. This line of research has the potential to vastly expand the field of antibody therapy and usher in a new era of cancer vaccines. Cancer Res; 72(15); 3715–9. ©2012 AACR.
Dual Targeting of the Akt/mTOR Signaling Pathway Inhibits Castration-Resistant Prostate Cancer in a Genetically Engineered Mouse Model
Authors: Floc'h Nicolas , Kinkade Carolyn Waugh , Kobayashi Takashi , Aytes Alvaro , Lefebvre Celine , Mitrofanova Antonina , Cardiff Robert D. , Califano Andrea , Shen Michael M. , Abate-Shen Cory 
Published: July 2012

Abstract
Although the prognosis for clinically localized prostate cancer is now favorable, there are still no curative treatments for castration-resistant prostate cancer (CRPC) and, therefore, it remains fatal. In this study, we investigate a new therapeutic approach for treatment of CRPC, which involves dual targeting of a major signaling pathway that is frequently deregulated in the disease. We found that dual targeting of the Akt and mTOR signaling pathways with their respective inhibitors, MK-2206 and ridaforolimus (MK-8669), is highly effective for inhibiting CRPC in preclinical studies in vivo using a refined genetically engineered mouse model of the disease. The efficacy of the combination treatment contrasts with their limited efficacy as single agents, since delivery of MK-2206 or MK-8669 individually had a modest impact in vivo on the overall tumor phenotype. In human prostate cancer cell lines, although not in the mouse model, the synergistic actions of MK-2206 and ridaforolimus (MK-8669) are due in part to limiting the mTORC2 feedback activation of Akt. Moreover, the effects of these drugs are mediated by inhibition of cellular proliferation via the retinoblastoma (Rb) pathway. Our findings suggest that dual targeting of the Akt and mTOR signaling pathways using MK-2206 and ridaforolimus (MK-8669) may be effective for treatment of CRPC, particularly for patients with deregulated Rb pathway activity. Cancer Res; 72(17); 4483–93. ©2012 AACR.
Cost effectivenes of erlotinib versus chemotherapy for first-line treatment of non small cell lung cancer (NSCLC) in fit elderly patients participating in a prospective phase 2 study (GFPC 0504)
Authors: Christos Chouaid , Hervé Le Caer , Chrystelle Locher , Cecile Dujon , Pascal Thomas , Jean Bernard Auliac , Isabelle Monnet , Alain Vergnenegre ,   and GFPC 0504 Team
Published: July 2012

Abstract

Background
The median age of newly diagnosed patients with non-small cell lung cancer (NSCLC) is 67 years, and one-third of patients are older than 75 years. Elderly patients are more vulnerable to the adverse effects of chemotherapy, and targeted therapy might thus be a relevant alternative. The objective of this study was to assess the cost-effectiveness of erlotinib followed by chemotherapy after progression, compared to the reverse strategy, in fit elderly patients with advanced NSCLC participating in a prospective randomized phase 2 trial (GFPC0504).

Methods
Outcomes (PFS and overall survival) and costs (limited to direct medical costs, from the third-party payer perspective) were prospectively collected until second progression. Costs after progression and health utilities (based on disease states and grade 3–4 toxicities) were derived from the literature.

Results
Median overall survival, QALY and total costs for the erlotinib-first strategy were respectively 7.1 months, 0.51 and 27 734 €, compared to 9.4 months, 0.52 and 31 688 € for the chemotherapy-first strategy. The Monte Carlo simulation demonstrates that the two strategies do not differ statistically.

Conclusion
In terms of cost effectiveness, in fit elderly patients with NSCLC, erlotinib followed by chemotherapy compares well with the reverse strategy.
Optimal pilot symbol power allocation under time-variant channels
Authors: Šimko Michal , Wang Qi , Rupp Markus 
Published: July 2012

Abstract
Nowadays, most wireless communication systems employ coherent demodulation on the receiver side. Under this circumstance, part of the available transmission resource is reserved and utilized for channel estimation, referred to as pilot symbols. In recent standards, for example long-term evolution (LTE), a certain adjustment is allowed for the power radiated on the pilot symbols. This additional degree of freedom creates space for a further optimization of the system performance. In this article, we consider an orthogonal frequency division multiplexing system and investigate how to distribute the available power between data symbols and pilot symbols under transmissions over time-variant channels so that the overall throughput is maximized. We choose the post-equalization signal-to-interference and noise ratio as the cost function and solve the problem analytically. Simulation results obtained by the Vienna LTE simulator are consistent with the analytical results. With an optimal power distribution between data and pilot symbols, a throughput increase of around 10% can be achieved compared to a system with evenly distributed power between data and pilot symbols.
Subcutaneous metastases from colon cancer: a case report
Authors: Lo Russo Giuseppe , Accarpio Fabio , Spinelli Gian Paolo , Miele Evelina , Borrini Francesco , Cerbone Linda , Stati Valeria , Prinzi Natalie , Strudel Martina , Sibio Simone , Tomao Silverio 
Published: July 2012

Abstract

Introduction
Dukes A stages of colorectal cancer are rarely reported to metastasize. Subcutaneous or skin metastases from colon cancer are rare events and usually indicate widespread disease.

Case presentation
We present the case of a 72-year-old Caucasian woman with Dukes A colorectal cancer at diagnosis and, three years later, a single secondary subcutaneous involvement with no other metastatic sites. The description of this case is supported by critical analysis of its clinical, radiological and pathological features. Our report illustrates that diagnosis can be difficult and controversial when relapse occurs in early stage patients and at uncommon sites.

Conclusion
The unusual and aggressive course of the reported disease stresses the importance of intensive follow-up in colorectal cancer patients with good prognostic factors.
Indian hedgehog gene transfer is a chondrogenic inducer of human mesenchymal stem cells
Authors: Steinert Andre F , Weissenberger Manuel , Kunz Manuela , Gilbert Fabian , Ghivizzani Steven C , Göbel Sascha , Jakob Franz , Nöth Ulrich , Rudert Maximilian 
Published: July 2012

Abstract
Introduction
To date, no single most-appropriate factor or delivery method has been identified for the purpose of mesenchymal stem cell (MSC)-based treatment of cartilage injury. Therefore, in this study we tested whether gene delivery of the growth factor Indian hedgehog (IHH) was able to induce chondrogenesis in human primary MSCs, and whether it was possible by such an approach to modulate the appearance of chondrogenic hypertrophy in pellet cultures in vitro.

Methods
First-generation adenoviral vectors encoding the cDNA of the human IHH gene were created by cre-lox recombination and used alone or in combination with adenoviral vectors, bone morphogenetic protein-2 (Ad.BMP-2), or transforming growth factor beta-1 (Ad.TGF-β1) to transduce human bone-marrow derived MSCs at 5 × 102 infectious particles/cell. Thereafter, 3 × 105 cells were seeded into aggregates and cultured for 3 weeks in serum-free medium, with untransduced or marker gene transduced cultures as controls. Transgene expressions were determined by ELISA, and aggregates were analysed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy.

Results
IHH, TGF-β1 and BMP-2 genes were equipotent inducers of chondrogenesis in primary MSCs, as evidenced by strong staining for proteoglycans, collagen type II, increased levels of glycosaminoglycan synthesis, and expression of mRNAs associated with chondrogenesis. IHH-modified aggregates, alone or in combination, also showed a tendency to progress towards hypertrophy, as judged by the expression of alkaline phosphatase and stainings for collagen type X and Annexin 5.

Conclusion
As this study provides evidence for chondrogenic induction of MSC aggregates in vitro via IHH gene delivery, this technology may be efficiently employed for generating cartilaginous repair tissues in vivo.
Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer
Authors: Byrski Tomasz , Dent Rebecca , Blecharz Pawel , Foszczynska-Kloda Malgorzata , Gronwald Jacek , Huzarski Tomasz , Cybulski Cezary , Marczyk Elzbieta , Chrzan Robert , Eisen Andrea , Lubinski Jan , Narod Steven A 
Published: July 2012

Abstract
Introduction
The purpose of this investigation was to evaluate the efficacy of cisplatin chemotherapy in BRCA1 mutation carriers with metastatic breast cancer.

Methods
In a phase II, open-label study, 20 patients with metastatic breast cancer who carried a mutation in BRCA1 were treated with cisplatin 75 mg/m2 intravenously every 3 weeks as part of a 21-day cycle for 6 cycles. Restaging studies to assess response were performed after cycles 2 and 6, and every three months thereafter.

Results
Between July 2007 and January 2009, 20 patients were enrolled. Baseline characteristics were as follows: 65% had prior adjuvant chemotherapy, 55% had prior chemotherapy for metastatic breast cancer; mean age was 48 years (ranges 32 to 70); 30% estrogen receptor (ER) or progesterone receptor (PR)+, 70% ER/PR/Human Epidermal Growth Factor Receptor 2 (HER2)- and 0% HER2+. Overall response rate was 80%; nine patients experienced a complete clinical response (45%) and seven experienced a partial response (35%). Overall survival was 80% at one year, 60% at two years and 25% at three years. Four of the 20 patients are alive four years after initiating treatment. The median time to progression was 12 months. The median survival from the start of cisplatinum treatment was 30 months. Cisplatin-related adverse events, including nausea (50%), anemia (5%) and neutropenia (35%) were mostly mild to moderate in severity.

Conclusions
This phase II study demonstrates that cisplatin chemotherapy has high activity in women with a BRCA1 mutation and metastatic breast cancer and is generally well tolerated.

Trial registration
This trial is registered retrospectively on the clinical trials website ClinicalTrials.gov. The identifier is NCT01611727.
Prolactin-induced protein mediates cell invasion and regulates integrin signaling in estrogen receptor-negative breast cancer
Authors: Naderi Ali , Meyer Michelle 
Published: July 2012

Abstract
Introduction
Molecular apocrine is a subtype of estrogen receptor (ER)-negative breast cancer that is characterized by a steroid-response gene signature. We have recently identified a positive feedback loop between androgen receptor (AR) and extracellular signal-regulated kinase (ERK) signaling in this subtype. In this study, we investigated the transcriptional regulation of molecular apocrine genes by the AR-ERK feedback loop.

Methods
The transcriptional effects of AR and ERK inhibition on molecular apocrine genes were assessed in cell lines. The most regulated gene in this process, prolactin-induced protein (PIP), was further studied using immunohistochemistry of breast tumors and xenograft models. The transcriptional regulation of PIP was assessed by luciferase reporter assay and chromatin immunoprecipitation. The functional significance of PIP in cell invasion and viability was assessed using siRNA knockdown experiments and the mechanism of PIP effect on integrin-β1 signaling was studied using immunoblotting and immunoprecipitation.

Results
We found that PIP is the most regulated molecular apocrine gene by the AR-ERK feedback loop and is overexpressed in ER-/AR+ breast tumors. In addition, PIP expression is regulated by AR-ERK signaling in xenograft models. These observations are explained by the fact that PIP is a target gene of the ERK-CREB1 pathway and is also induced by AR activation. Furthermore, we demonstrated that PIP has a significant functional role in maintaining cell invasion and viability of molecular apocrine cells because of a positive regulatory effect on the Integrin-ERK and Integrin-Akt signaling pathways. In fact, PIP-knockdown markedly decreases the phosphorylation of ERK, Akt, and CREB1. Importantly, PIP knockdown leads to a marked reduction of integrin-β1 binding to ILK1 and ErbB2 that can be reversed by the addition of fibronectin fragments.

Conclusions
We have identified a novel feedback loop between PIP and CREB1 mediated through the Integrin signaling pathway. In this process, PIP cleaves fibronectin to release fragments that activate integrin signaling, which in turn increases PIP expression through the ERK-CREB1 pathway. In addition, we demonstrated that PIP expression has a profound effect on cell invasion and the viability of molecular apocrine cells. Therefore, PIP signaling may be a potential therapeutic target in molecular apocrine breast cancer.
Diversification of a Protein Kinase Cascade: IME-2 Is Involved in Nonself Recognition and Programmed Cell Death in Neurospora crassa
Authors: Hutchison Elizabeth A , Bueche Joanna A , Glass N Louise 
Published: July 2012

Abstract
Kinase cascades and the modification of proteins by phosphorylation are major mechanisms for cell signaling and communication, and evolution of these signaling pathways can contribute to new developmental or environmental response pathways. The Saccharomyces cerevisiae kinase Ime2 has been well characterized for its role in meiosis. However, recent studies have revealed alternative functions for Ime2 in both S. cerevisiae and other fungi. In the filamentous fungus Neurospora crassa, the IME2 homolog (ime-2) is not required for meiosis. Here we determine that ime-2 interacts genetically with a transcription factor vib-1 during nonself recognition and programmed cell death (PCD). Mutations in vib-1 (Δvib-1) suppress PCD due to nonself recognition events; however, a Δvib-1 Δime-2 mutant restored wild-type levels of cell death. A role for ime-2 in the post-translational processing and localization of a mitochondrial matrix protein was identified, which may implicate mitochondria in N. crassa nonself recognition and PCD. Further, Δvib-1 strains do not produce extracellular proteases, but protease secretion reverted to near wild-type levels in a Δvib-1 Δime-2 strain. Mass spectrometry analysis revealed that the VIB-1 protein is phosphorylated at several sites, including a site that matches the IME-2 consensus. The genetic and biochemical data for ime-2 and vib-1 indicate that IME-2 is a negative regulator of VIB-1 and suggest parallel negative regulation by IME-2 of a cell death pathway in N. crassa that functions in concert with the VIB-1 cell death pathway. Thus, IME2 kinase function has evolved following the divergence of S. cerevisiae and N. crassa and provides insight into the evolution of kinases and their regulatory targets.