bluuebunny/crossref_metadata_2025_split huggingface dataset:
Raman Spectroscopic Signatures of Echovirus 1 Uncoating
Authors: Ruokola Päivi , Dadu Elina , Kazmertsuk Artur , Häkkänen Heikki , Marjomäki Varpu , Ihalainen Janne A. 
Published: May 2014

ABSTRACT
In recent decades, Raman spectroscopy has entered the biological and medical fields. It enables nondestructive analysis of structural details at the molecular level and has been used to study viruses and their constituents. Here, we used Raman spectroscopy to study echovirus 1 (EV1), a small, nonenveloped human pathogen, in two different uncoating states induced by heat treatments. Raman signals of capsid proteins and RNA genome were observed from the intact virus, the uncoating intermediate, and disrupted virions. Transmission electron microscopy data revealed general structural changes between the studied particles. Compared to spectral characteristics of proteins in the intact virion, those of the proteins of the heat-treated particles indicated reduced α-helix content with respect to β-sheets and coil structures. Changes observed in tryptophan and tyrosine signals suggest an increasingly hydrophilic environment around these residues. RNA signals revealed a change in the environment of the genome and in its conformation. The ionized-carbonyl vibrations showed small changes between the intact virion and the uncoating intermediate, which points to cleavage of salt bridges in the protein structure during the uncoating process. In conclusion, our data reveal distinguishable Raman signatures of the intact, intermediate, and disrupted EV1 particles. These changes indicate structural, chemical, and solute-solvent alterations in the genome and in the capsid proteins and lay the essential groundwork for investigating the uncoating of EV1 and related viruses in real time.

IMPORTANCE
In order to combat virus infection, we need to know the details of virus uncoating. We present here the novel Raman signatures for opened and intact echovirus 1. This gives hope that the signatures may be used in the near future to evaluate the ambient conditions in endosomes leading to virus uncoating using, e.g., coherent anti-Stokes Raman spectroscopy (CARS) imaging. These studies will complement structural studies on virus uncoating. In addition, Raman/CARS imaging offers the possibility of making dynamic live measurements
in vitro
and in cells which are impossible to measure by, for example, cryo-electron tomography. Furthermore, as viral Raman spectra can be overwhelmed with various contaminants, our study is highly relevant in demonstrating the importance of sample preparation for Raman spectroscopy in the field of virology.
Implementation of a neuromuscular training programme in female adolescent football: 3-year follow-up study after a randomised controlled trial
Authors: Lindblom Hanna , Waldén Markus , Carlfjord Siw , Hägglund Martin 
Published: May 2014

BackgroundNeuromuscular training (NMT) has been shown to reduce anterior cruciate ligament injury rates in highly structured clinical trials. However, there is a paucity of studies that evaluate implementation of NMT programmes in sports.AimTo evaluate the implementation of an NMT programme in female adolescent football 3 years after a randomised controlled trial (RCT).MethodsCross-sectional follow-up after an RCT using the Reach, Effectiveness, Adoption, Implementation, and Maintenance Sports Setting Matrix (RE-AIM SSM) framework. Questionnaires were sent to the Swedish Football Association (FA), to eight district FAs and coaches (n=303) that participated in the RCT in 2009, and coaches who did not participate in the RCT but were coaching female adolescent football teams during the 2012 season (n=496).ResultsResponse rates were 100% among the FAs, 57% among trial coaches and 36% among currently active coaches. The reach of the intervention was high, 99% of trial coaches (control group) and 91% of current coaches were familiar with the programme. The adoption rate was 74% among current coaches, but programme modifications were common among coaches. No district FA had formal policies regarding implementation, and 87% of current coaches reported no club routines for programme use. Maintenance was fairly high; 82% of trial coaches from the intervention group and 68% from the control group still used the programme.ConclusionsReach and adoption of the programme was high among coaches. However, this study identified low programme fidelity and lack of formal policies for its implementation and use in clubs and district FAs.
A coronary heart disease prediction model: the Korean Heart Study
Authors: Jee Sun Ha , Jang Yangsoo , Oh Dong Joo , Oh Byung-Hee , Lee Sang Hoon , Park Seong-Wook , Seung Ki-Bae , Mok Yejin , Jung Keum Ji , Kimm Heejin , Yun Young Duk , Baek Soo Jin , Lee Duk Chul , Choi Sung Hee , Kim Moon Jong , Sung Jidong , Cho BeLong , Kim Eung Soo , Yu Byung-Yeon , Lee Tae-Yong , Kim Jong Sung , Lee Yong-Jin , Oh Jang-Kyun , Kim Sung Hi , Park Jong-Ku , Koh Sang Baek , Park Sat Byul , Lee Soon Young , Yoo Cheol-In , Kim Moon Chan , Kim Hong-Kyu , Park Joo-sung , Kim Hyeon Chang , Lee Gyu Jang , Woodward Mark 
Published: May 2014

ObjectiveThe objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score.DesignA prospective cohort study within a national insurance system.Setting18 health promotion centres nationwide between 1996 and 2001 in Korea.Participants268 315 Koreans between the ages of 30 and 74 years without CHD at baseline.Outcome measureNon-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI).ResultsThe optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3–6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort.ConclusionsThe present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.
The impact of gastrostomy in motor neurone disease: challenges and benefits from a patient and carer perspective
Authors: Stavroulakis Theocharis , Baird Wendy O , Baxter Susan K , Walsh Theresa , Shaw Pamela J , McDermott Christopher J 
Published: May 2014

ObjectivesThis study explores the experience of gastrostomy insertion from the perspective of the patients and their informal carers. Gastrostomy feeding is commonly used to support motor neurone disease (MND) patients with dysphagia. However, there is lack of information describing patient and carer experiences following gastrostomy insertion. The effect of gastrostomy on quality of life for these patients and their family is currently not well understood.MethodsRetrospective qualitative exploration using semistructured interviews with patients and their informal carers to elicit in-depth descriptions of their experiences and views following gastrostomy.Results27 patients consented to the study; of these, 23 underwent a successful gastrostomy. 10 patients and 8 carers were interviewed, approximately 3 months following a successful gastrostomy. Participants described clinical complications, practical issues, time restrictions imposed by strict feeding regimens and psychological issues, which adversely impacted on quality of life. However, the establishment of a safe alternative route for feeding and medication, and the reduced worry over difficult meals and weight loss, were described by all as outweighing these negative impacts. Participants also described having received education/training on gastrostomy feeding both in hospital and in the community, which helped them to cope during the transition from oral to gastrostomy feeding.ConclusionsThis study highlights the challenges and benefits of gastrostomy as well as the importance of education and information provision. Emphasis should be given to education before and after insertion along with support and care in the community. While the significant impact of gastrostomy on patients and carers should not be underestimated, the potential benefits were described as outweighing these concerns.
Supervision and risk of unintentional injury in young children
Authors: Schnitzer Patricia G , Dowd M Denise , Kruse Robin L , Morrongiello Barbara A 
Published: May 2014

ObjectiveAssess the association between caregiver supervision and acute unintentional injury in young children; evaluate whether lower levels of supervision result in more severe injury.MethodsA case cross-over study was conducted. Parents of children aged ≤4 years whose injuries required emergency department (ED sample) treatment or admission to the hospital (inpatient sample) were interviewed. Information on supervision (3 dimensions: proximity, attention, continuity) at the time of injury and 1 h before the injury (control time) was collected. An overall supervision score was created; a higher score indicates closer supervision. Hospital admission served as a proxy for injury severity. ORs and 95% CIs were calculated.ResultsInterviews were completed by 222 participants; 50 (23%) were in the inpatient sample. For each supervision dimension the inpatient sample had higher odds of injury, indicating effect modification requiring separate analyses for inpatient and ED samples. For both samples, proximity ‘beyond reach’ was associated with the highest odds of injury; compared with 1 h before injury, children were more likely to be beyond reach of their caregiver at the time of injury (inpatient sample: OR 11.5, 95% CI 2.7 to 48.8; ED sample: OR 2.9, 95% CI 1.8 to 4.9). Children with lower supervision scores had the greatest odds of injury (inpatient sample: OR 8.0, 95% CI 2.4 to 26.6; ED sample: OR 3.3, 95% CI 1.9 to 5.6).ConclusionsLower levels of adult supervision are associated with higher odds of more severe injury in young children. Proximity is the most important supervision dimension for reducing injury risk.
Structural, stability and electronic properties of C15-AB2 (A = Ti, Zr; B = Cr) intermetallic compounds and their hydrides: An ab initio study
Authors: Sarhaddi Reza , Arabi Hadi , Pourarian Faiz 
Published: May 2014

The structural, stability and electronic properties of C15- AB 2 ( A = Ti , Zr ; B = Cr ) isomeric intermetallic compounds were systematically investigated by using density functional theory (DFT) and plane-wave pseudo-potential (PW-PP) method. The macroscopic properties including the lattice constant, bulk modulus and stability for these compounds were studied before and after hydrogenation. For parent compounds, the enthalpy of formation was evaluated with regard to their bulk modules and electronic structures. After hydrogenation of compounds at different interstitial tetrahedral sites ( A 2 B 2, A 1 B 3, B 4), a volume expansion was found for hydrides. The stability properties of hydrides characterized the A 2 B 2 sites as the site preference of hydrogen atoms for both compounds. The Miedema's "reverse stability" rule is also satisfied in these compounds as lower the enthalpy of formation for the host compound, the more stable the hydride. Analysis of microscopic properties (electronic structures) after hydrogenation at more stable interstitial site ( A 2 B 2) shows that the H atoms interact stronger with the weaker (or non) hydride forming element B (Cr) than the hydride forming element A ( Ti/Zr ). A correlation was also found between the stability of the hydrides and their electronic structure: the deeper the hydrogen band, the less stable the hydride.
Several Dynamical Properties for a Nonlinear Shallow Water Equation
Authors: Yong Ls , Yan Haibo 
Published: May 2014

A nonlinear third order dispersive shallow water equation including the Degasperis‐Procesi model is investigated. The existence of weak solutions for the equation is proved in the space L1(R)∩BV (R) under certain assumptions. The Oleinik type estimate and L2N(R)  (N is a natural number) estimate for the solution are obtained.
β-Catenin Activation in a Novel Liver Progenitor Cell Type Is Sufficient to Cause Hepatocellular Carcinoma and Hepatoblastoma
Authors: Mokkapati Sharada , Niopek Katharina , Huang Le , Cunniff Kegan J. , Ruteshouser E. Cristy , deCaestecker Mark , Finegold Milton J. , Huff Vicki 
Published: May 2014

Abstract
Hepatocellular carcinoma (HCC) was thought historically to arise from hepatocytes, but gene expression studies have suggested that it can also arise from fetal progenitor cells or their adult progenitor progeny. Here, we report the identification of a unique population of fetal liver progenitor cells in mice that can serve as a cell of origin in HCC development. In the transgenic model used, mice carry the Cited1-CreERTM-GFP BAC transgene in which a tamoxifen-inducible Cre (CreERTM) and GFP are controlled by a 190-kb 5′ genomic region of Cited1, a transcriptional coactivator protein for CBP/p300. Wnt signaling is critical for regulating self-renewal of progenitor/stem cells and has been implicated in the etiology of cancers of rapidly self-renewing tissues, so we hypothesized that Wnt pathway activation in CreERTM-GFP+ progenitors would result in HCC. In livers from the mouse model, transgene-expressing cells represented 4% of liver cells at E11.5 when other markers were expressed, characteristic of the hepatic stem/progenitor cells that give rise to adult hepatocytes, cholangiocytes, and SOX9+ periductal cells. By 26 weeks of age, more than 90% of Cited1-CreERTM-GFP;Ctnnb1ex3(fl) mice with Wnt pathway activation developed HCC and, in some cases, hepatoblastomas and lung metastases. HCC and hepatoblastomas resembled their human counterparts histologically, showing activation of Wnt, Ras/Raf/MAPK, and PI3K/AKT/mTOR pathways and expressing relevant stem/progenitor cell markers. Our results show that Wnt pathway activation is sufficient for malignant transformation of these unique liver progenitor cells, offering functional support for a fetal/adult progenitor origin of some human HCC. We believe this model may offer a valuable new tool to improve understanding of the cellular etiology and biology of HCC and hepatoblastomas and the development of improved therapeutics for these diseases. Cancer Res; 74(16); 4515–25. ©2014 AACR.
Analysis of Chemotherapeutic Response in Ovarian Cancers Using Publicly Available High-Throughput Data
Authors: Bosquet Jesus Gonzalez , Marchion Douglas C. , Chon HyeSook , Lancaster Johnathan M. , Chanock Stephen 
Published: May 2014

Abstract
A third of patients with epithelial ovarian cancer (OVCA) will not respond to standard treatment. The determination of a robust signature that predicts chemoresponse could lead to the identification of molecular markers for response as well as possible clinical implementation in the future to identify patients at risk of failing therapy. This pilot study was designed to identify biologic processes affecting candidate pathways associated with chemoresponse and to create a robust gene signature for follow-up studies. After identifying common pathways associated with chemoresponse in serous OVCA in three independent gene-expression experiments, we assessed the biologic processes associated with them using The Cancer Genome Atlas (TCGA) dataset for serous OVCA. We identified differential copy-number alterations (CNA), mutations, DNA methylation, and miRNA expression between patients that responded to standard treatment and those who did not or recurred prematurely. We correlated these significant parameters with gene expression to create a signature of 422 genes associated with chemoresponse. A consensus clustering of this signature identified two differentiated clusters with unique molecular patterns: cluster 1 was significant for cellular signaling and immune response (mainly cell-mediated); and cluster 2 was significant for pathways involving DNA-damage repair and replication, cell cycle, and apoptosis. Validation through consensus clustering was performed in five independent OVCA gene-expression experiments. Genes were located in the same cluster with consistent agreement in all five studies (κ coefficient ≥ 0.6 in 4). Integrating high-throughput biologic data have created a robust molecular signature that predicts chemoresponse in OVCA. Cancer Res; 74(14); 3902–12. ©2014 AACR.
Therapeutic Efficacy of an Fc-Enhanced TCR-like Antibody to the Intracellular WT1 Oncoprotein
Authors: Veomett Nicholas , Dao Tao , Liu Hong , Xiang Jingyi , Pankov Dmitry , Dubrovsky Leonid , Whitten Joseph A. , Park Sun-Mi , Korontsvit Tatyana , Zakhaleva Victoria , Casey Emily , Curcio Michael , Kharas Michael G. , O'Reilly Richard J. , Liu Cheng , Scheinberg David A. 
Published: May 2014

AbstractPurpose: RMFPNAPYL (RMF), a Wilms' tumor gene 1 (WT1)–derived CD8 T-cell epitope presented by HLA-A*02:01, is a validated target for T-cell–based immunotherapy. We previously reported ESK1, a high avidity (Kd &lt; 0.2 nmol/L), fully-human monoclonal antibody (mAb) specific for the WT1 RMF peptide/HLA-A*02:01 complex, which selectively bound and killed WT1+ and HLA-A*02:01+ leukemia and solid tumor cell lines.Experimental Design: We engineered a second-generation mAb, ESKM, to have enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) function due to altered Fc glycosylation. ESKM was compared with native ESK1 in binding assays, in vitro ADCC assays, and mesothelioma and leukemia therapeutic models and pharmacokinetic studies in mice. ESKM toxicity was assessed in HLA-A*02:01+ transgenic mice.Results: ESK antibodies mediated ADCC against hematopoietic and solid tumor cells at concentrations below 1 μg/mL, but ESKM was about 5- to 10-fold more potent in vitro against multiple cancer cell lines. ESKM was more potent in vivo against JMN mesothelioma, and effective against SET2 AML and fresh ALL xenografts. ESKM had a shortened half-life (4.9 days vs. 6.5 days), but an identical biodistribution pattern in C57BL/6J mice. At therapeutic doses of ESKM, there was no difference in half-life or biodistribution in HLA-A*02:01+ transgenic mice compared with the parent strain. Importantly, therapeutic doses of ESKM in these mice caused no depletion of total WBCs or hematopoetic stem cells, or pathologic tissue damage.Conclusions: The data provide proof of concept that an Fc-enhanced mAb can improve efficacy against a low-density, tumor-specific, peptide/MHC target, and support further development of this mAb against an important intracellular oncogenic protein. Clin Cancer Res; 20(15); 4036–46. ©2014 AACR.
Semi-Mechanistic Pharmacokinetic/Pharmacodynamic Modeling of the Antitumor Activity of LY2835219, a New Cyclin-Dependent Kinase 4/6 Inhibitor, in Mice Bearing Human Tumor Xenografts
Authors: Tate Sonya C. , Cai Shufen , Ajamie Rose T. , Burke Teresa , Beckmann Richard P. , Chan Edward M. , De Dios Alfonso , Wishart Graham N. , Gelbert Lawrence M. , Cronier Damien M. 
Published: May 2014

Abstract
Purpose: Selective inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) represents a promising therapeutic strategy. However, despite documented evidence of clinical activity, limited information is available on the optimal dosing strategy of CDK4/6 inhibitors. Here, we present an integrated semi-mechanistic pharmacokinetic/pharmacodynamic model to characterize the quantitative pharmacology of LY2835219, a CDK4/6 inhibitor, in xenograft tumors.
Experimental Design: LY2835219 plasma concentrations were connected to CDK4/6 inhibition and cell-cycle arrest in colo-205 human colorectal xenografts by incorporating the biomarkers, phospho-(ser780)-Rb, topoisomerase II α, and phosphohistone H3, into a precursor-dependent transit compartment model. This biomarker model was then connected to tumor growth inhibition (TGI) by: (i) relating the rate of tumor growth to mitotic cell density, and (ii) incorporating a concentration-dependent mixed cytostatic/cytotoxic effect driving quiescence and cell death at high doses. Model validation was evaluated by predicting LY2835219-mediated antitumor effect in A375 human melanoma xenografts.
Results: The model successfully described LY2835219-mediated CDK4/6 inhibition, cell-cycle arrest, and TGI in colo-205, and was validated in A375. The model also demonstrated that a chronic dosing strategy achieving minimum steady-state trough plasma concentrations of 200 ng/mL is required to maintain durable cell-cycle arrest. Quiescence and cell death can be induced by further increasing LY2835219 plasma concentrations.
Conclusions: Our model provides mechanistic insight into the quantitative pharmacology of LY2835219 and supports the therapeutic dose and chronic dosing strategy currently adopted in clinical studies. Clin Cancer Res; 20(14); 3763–74. ©2014 AACR.
A High-Affinity, High-Stability Photoacoustic Agent for Imaging Gastrin-Releasing Peptide Receptor in Prostate Cancer
Authors: Levi Jelena , Sathirachinda Ataya , Gambhir Sanjiv S. 
Published: May 2014

Abstract
Purpose: To evaluate the utility of targeted photoacoustic imaging (PAI) in providing molecular information to complement intrinsic functional and anatomical details of the vasculature within prostate lesion.
Experimental Design: We developed a PAI agent, AA3G-740, that targets gastrin-releasing peptide receptor (GRPR), found to be highly overexpressed in prostate cancer. The binding specificity of the agent was evaluated in human prostate cancer cell lines, PC3 and LNCaP, and antagonist properties determined by cell internalization and intracellular calcium mobilization studies. The imaging sensitivity was assessed for the agent itself and for the PC3 cells labeled with agent. The in vivo stability of the agent was determined in human plasma and in the blood of living mice. The in vivo binding of the agent was evaluated in PC3 prostate tumor models in mice, and was validated ex vivo by optical imaging.
Results: AA3G-740 demonstrated strong and specific binding to GRPR. The sensitivity of detection in vitro indicated suitability of the agent to image very small lesions. In mice, the agent was able to bind to GRPR even in poorly vascularized tumors leading to nearly 2-fold difference in photoacoustic signal relative to the control agent.
Conclusions: The ability to image both vasculature and molecular profile outside the blood vessels gives molecular PAI a unique advantage over currently used imaging techniques. The imaging method presented here can find application both in diagnosis and in image-guided biopsy. Clin Cancer Res; 20(14); 3721–9. ©2014 AACR.