bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Combined Scratch and Nanoindentation Experiments on Soda‐Lime‐Silica Glass
Authors: Bandyopadhyay Payel , Dey Arjun , Mukhopadhyay Anoop K. 
Published: February 2012

Many advanced applications of glass demand fabrication of engineering parts of utmost dimensional precision which require very accurate grinding and polishing that involves controlled removal of glass. Despite the wealth of literature, however; the mechanism of material removal in glass grinding and polishing is still far from well understood. For instance, it is not known at all to what extent the mechanical properties are compromised inside a scratch groove so as to optimize the machining parameters. Therefore, to develop better understanding about the mechanism of material removal, a series of combined nanoindentation and single pass scratch experiments were conducted on a commercially available soda‐lime‐silica glass as a function of various normal loads (2–20 N) and scratch speeds (0.1–1 mm/s). It was found that the nanohardness and Young's modulus at the local microstructural length scale inside the scratch groove could decrease quite dramatically (~30% to 70%) depending on the combination of load and scratching speed. Further, the tribological properties, the severity and the spatial density of damage evolution were sensitive to the normal loads, scratching speeds, and tensile stresses. Extensive scanning electron microscopy leads to interesting observations on material removal mechanisms. These observations were explained by the theoretical predictions of a model for a brittle, microcracked solid.
Catastrophic worries in mothers of adolescents with internalizing disorders
Authors: Triantafyllou Kalliopi , Cartwright‐Hatton Sam , Korpa Terpsichori , Kolaitis Gerasimos , Barrowclough Christine 
Published: February 2012

Objectives. This study investigates worrying in mothers of adolescents with internalizing disorders, and tests the hypothesis that these mothers will produce a greater number of worries with higher catastrophic content compared to control groups.Design. Differences in worry steps and in catastrophic content of worries were investigated in a cross‐sectional, between groups design, employing a clinical internalizing group, a clinical control, and a non‐referred control group.Methods. Twenty‐five mothers of adolescents with internalizing disorders, 24 mothers of adolescents with externalizing disorders, and 28 mothers with non‐referred adolescents participated in two interviews about their ‘real’ pre‐existing worries and their worries in response to a hypothetical situation.Results. The internalizing group produced both a greater number of worry steps and a higher catastrophic content when they talked about their ‘real’ worries, compared to both control groups. They also produced a greater number of worry steps in response to a hypothetical situation compared to the other two groups. The number of worry steps and the level of catastrophic content of ‘real’ worries were associated with adolescent depression and anxiety. Additionally, the number of worry steps and the level of catastrophic content of worries in response to a hypothetical situation were related to adolescent depression. The number of worry steps in ‘real’ worries and the level of catastrophic content in hypothetical worries were also associated with maternal depressive symptoms.Conclusions. Mothers of adolescents with internalizing disorders may worry more catastrophically about their children than other mothers.
Mechanics of myosin function in white muscle fibres of the dogfish, Scyliorhinus canicula
Authors: Park‐Holohan S. , Linari M. , Reconditi M. , Fusi L. , Brunello E. , Irving M. , Dolfi M. , Lombardi V. , West T. G. , Curtin N. A. , Woledge R. C. , Piazzesi G. 
Published: February 2012

Key points
Muscle force and shortening are generated by a structural change called the working stroke in myosin motor proteins that cross‐link the myosin and actin filaments in muscle.
Precise values for two key parameters of the myosin motor – its mechanical stiffness and the size of the working stroke at low load – were previously only available from one type of muscle in one species, fast twitch muscles of the frog, so it was not clear how generally applicable these values were.
We show that in dogfish fast muscle the low‐load working stroke is the same as in frog muscle, but the myosin motor stiffness is smaller.
The results provide new insights into how the molecular properties of myosin motors in different muscle types and species may be adapted for different muscle functions.
Postsynaptic mechanisms of CO2 responses in parafacial respiratory neurons of newborn rats
Authors: Onimaru Hiroshi , Ikeda Keiko , Kawakami Kiyoshi 
Published: February 2012

Key points
The central chemoreceptors for respiratory control in the medulla sense changes in CO2 concentration and regulate respiratory activity.
Neurons that express a transcription factor, Phox2b, in the parafacial region of the rostral and ventrolateral medulla are excited by hypercapnic stimulation and are proposed to play an important role in central chemoreception.
In this study, we show evidence that Phox2b‐expressing parafacial neurons in neonatal rats were sensitive to hypercapnia via direct action on the postsynaptic membrane without contribution of putative presynaptic or other calcium‐dependent components.
Since these parafacial neurons are also a part of the respiratory rhythm generator in neonates, they are essential for postnatal survival, which is probably due to their contribution to central chemoreception as well as respiratory rhythm generation.
Safety and Efficacy of GSK2248761, a Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor, in Treatment-Naive HIV-1-Infected Subjects
Authors: Zala Carlos , St. Clair Marty , Dudas Kathleen , Kim Joseph , Lou Yu , White Scott , Piscitelli Steve , Dumont Etienne , Pietropaolo Keith , Zhou Xiao-Jian , Mayers Douglas 
Published: February 2012

ABSTRACT

GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. Two phase I/IIa, double-blind, randomized, placebo-controlled studies investigated the antiviral activity, safety, and pharmacokinetics (PK) of several doses of GSK2248761 monotherapy in treatment-naive HIV-infected subjects. In the initial study, 10 subjects (8 active and 2 placebo) per dose received sequentially descending GSK2248761 monotherapy regimens of 800, 400, 200, and 100 mg QD for 7 days. Because a dose-response relationship was not identified, a second study examined a lower, 30-mg QD dose in 8 subjects (6 active and 2 placebo). Adverse events, viral load (VL), PK, and reverse transcriptase mutations were assessed and combined for analysis. Treatment with GSK2248761 for 7 days was well tolerated with no serious adverse events or discontinuations. The mean VL reductions from baseline on day 8 were 0.97, 1.87, 1.84, 1.81, and 1.78 log
10
copies/ml for GSK2248761 doses of 30, 100, 200, 400, and 800 mg QD, respectively. GSK2248761 PK (maximum drug concentration in serum [
C
max
], area under the plasma concentration-time curve from 0 h to the end of the dosing interval [AUC
0-τ
], and concentration at the end of the dosing interval [
C
τ
]) increased proportionally over the dose range of 30 to 800 mg QD. The relationship between short-term VL change and GSK2248761 PK was best described by a maximum-effect (
E
max
) model using
C
τ
(
E
max
= 2.0; 50% effective concentration [EC
50
] = 36.9 ng/ml). No NNRTI resistance mutations emerged during the study. GSK2248761 at 100 to 800 mg QD for 7 days was well tolerated, demonstrated potent antiviral activity in treatment-naive HIV-infected subjects, and had favorable PK and resistance profiles. GSK2248761 is no longer in clinical development.
Campylobacter jejuni Disrupts Protective Toll-Like Receptor 9 Signaling in Colonic Epithelial Cells and Increases the Severity of Dextran Sulfate Sodium-Induced Colitis in Mice
Authors: O'Hara Jennifer R. , Feener Troy D. , Fischer Carrie D. , Buret Andre G. 
Published: February 2012

ABSTRACT

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with a dysregulated immune response to commensal bacteria in susceptible individuals. The relapse of IBD may occur following an infection with
Campylobacter jejuni
. Apical epithelial Toll-like receptor 9 (TLR9) activation by bacterial DNA is reported to maintain colonic homeostasis. We investigated whether a prior
C. jejuni
infection disrupts epithelial TLR9 signaling and increases the severity of disease in a model of mild dextran sulfate sodium (DSS) colitis in mice. In a further attempt to identify mechanisms, T84 monolayers were treated with
C. jejuni
followed by a TLR9 agonist. Transepithelial resistance (TER) and dextran flux across confluent monolayers were monitored. Immunohistochemistry, Western blotting, and flow cytometry were used to examine TLR9 expression. Mice colonized by
C. jejuni
lacked any detectable pathology; however, in response to low levels of DSS, mice previously exposed to
C. jejuni
exhibited significantly reduced weight gain and increased occult blood and histological damage scores. Infected mice treated with DSS also demonstrated a significant reduction in levels of the anti-inflammatory cytokine interleukin-25.
In vitro
studies indicated that apical application of a TLR9 agonist enhances intestinal epithelial barrier function and that this response is lost in
C. jejuni
-infected monolayers. Furthermore, infected cells secreted significantly more CXCL8 following the basolateral application of a TLR9 agonist. Surface TLR9 expression was reduced in
C. jejuni
-infected monolayers subsequently exposed to a TLR9 agonist. In conclusion, infection by
C. jejuni
disrupts TLR9-induced reinforcement of the intestinal epithelial barrier, and colonization by
C. jejuni
increases the severity of mild DSS colitis.
Retinoic Acid/Alpha-Interferon Combination Inhibits Growth and Promotes Apoptosis in Mantle Cell Lymphoma through Akt-Dependent Modulation of Critical Targets
Authors: Dal Col Jessica , Mastorci Katy , Faè Damiana Antonia , Muraro Elena , Martorelli Debora , Inghirami Giorgio , Dolcetti Riccardo 
Published: February 2012

Abstract
Mantle cell lymphoma (MCL) is characterized by a profound deregulation of the mechanisms controlling cell-cycle progression and survival. We herein show that the combination of 9-cis-retinoic acid (RA) and IFN-α induces marked antiproliferative and proapoptotic effects in MCL cells through the modulation of critical targets. Particularly, IFN-α enhances RA-mediated G0–G1 cell accumulation by downregulating cyclin D1 and increasing p27Kip1 and p21WAF1/Cip1 protein levels. Furthermore, RA/IFN-α combination also induces apoptosis by triggering both caspases-8 and -9 resulting in Bax and Bak activation. In particular, RA/IFN-α treatment downregulates the antiapoptotic Bcl-xL and Bfl-1 proteins and upregulates the proapoptotic BH3-only Noxa protein. Sequestration of Mcl-1 and Bfl-1 by upregulated Noxa results in the activation of Bid, and the consequent induction of apoptosis is inhibited by Noxa silencing. Noxa upregulation is associated with nuclear translocation of the FOXO3a transcription factor as consequence of RA/IFN-α–induced Akt inhibition. Pharmacologic suppression of Akt, but not of TORC1, increases Noxa protein levels and downregulates Bfl-1 protein supporting the conclusion that the inhibition of the Akt pathway, the resulting FOXO3a activation and Noxa upregulation are critical molecular mechanisms underlying RA/IFN-α—dependent MCL cell apoptosis. These results support the potential therapeutic value of RA/IFN-α combination in MCL management. Cancer Res; 72(7); 1825–35. ©2012 AACR.
Workplace-Based Breast Cancer Screening Intervention in China
Authors: Ma Grace X. , Yin Lihong , Gao Wanzhen , Tan Yin , Liu Ran , Fang Carolyn , Ma Xiang S. 
Published: February 2012

AbstractBackground: Breast cancer continues to be the primary cause of death among East and Southeast Asian women. Although China, the most populous country in the world, is experiencing unprecedented economic growth, its health care system has yet to benefit from the current economic prosperity. Indeed, studies have shown a consistent increase in breast cancer rates among Chinese women over the past two decades in the absence of breast cancer screening guidelines.Methods: The primary objective of this study was to examine the impact of a workplace intervention on increasing breast cancer screening rates. The study was implemented at eight worksites in Nanjing, four of which were assigned to the intervention group (n = 232) and four to the control group (n = 221). The intervention group received breast cancer education and screening navigation. The control group was provided with general cancer education and received a delayed intervention after completion of the study. Study measures were completed at pre- and postprogram and at 6-month follow-up to assess uptake of mammography.Results: Baseline mammography use was low among both intervention and control groups. However, exposure to the workplace intervention dramatically increased the uptake of mammography from 10.3% at baseline to 72.6% at 6-month follow-up in the intervention group (P &lt; 0.001).Conclusions: Findings provide preliminary evidence that the implementation of a comprehensive workplace breast cancer screening intervention program in China can lead to increased uptake of mammography. These data may help facilitate the development of theory-based workplace cancer prevention programs and screening guidelines in China.Impact: A workplace-based multifaceted intervention could have a strong impact in breast cancer prevention and early detection among women in China. Cancer Epidemiol Biomarkers Prev; 21(2); 358–67. ©2011 AACR.
Variation in Age at Cancer Diagnosis in Familial versus Nonfamilial Barrett's Esophagus
Authors: Chak Amitabh , Chen Yanwen , Vengoechea Jaime , Canto Marcia I. , Elston Robert , Falk Gary W. , Grady William M. , Guda Kishore , Kinnard Margaret , Markowitz Sanford , Mittal Sumeet , Prasad Ganapathy , Shaheen Nicholas , Willis Joseph E. , Barnholtz-Sloan Jill S. 
Published: February 2012

Abstract
Background: Genetic influences may be discerned in families that have multiple affected members and may manifest as an earlier age of cancer diagnosis. In this study, we determine whether cancers develop at an earlier age in multiplex Familial Barrett's Esophagus (FBE) kindreds, defined by 3 or more members affected by Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC).
Methods: Information on BE/EAC risk factors and family history was collected from probands at eight tertiary care academic hospitals. Age of cancer diagnosis and other risk factors were compared between nonfamilial (no affected relatives), duplex (two affected relatives), and multiplex (three or more affected relatives) FBE kindreds.
Results: The study included 830 nonfamilial, 274 duplex, and 41 multiplex FBE kindreds with 274, 133, and 43 EAC and 566, 288, and 103 BE cases, respectively. Multivariable mixed models adjusting for familial correlations showed that multiplex kindreds were associated with a younger age of cancer diagnosis (P = 0.0186). Median age of cancer diagnosis was significantly younger in multiplex compared with duplex and nonfamilial kindreds (57 vs. 62 vs. 63 years, respectively, P = 0.0448). Mean body mass index was significantly lower in multiplex kindreds (P = 0.0033), as was smoking (P &lt; 0.0001), and reported regurgitation (P = 0.0014).
Conclusions: Members of multiplex FBE kindreds develop EAC at an earlier age compared with nonfamilial EAC cases. Multiplex kindreds do not have a higher proportion of common risk factors for EAC, suggesting that this aggregation might be related to a genetic factor.
Impact: These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds. Cancer Epidemiol Biomarkers Prev; 21(2); 376–83. ©2011 AACR.
Spin-Labeling Magnetic Resonance Imaging Detects Increased Myocardial Blood Flow After Endothelial Cell Transplantation in the Infarcted Heart
Authors: Zhang Hualei , Qiao Hui , Frank Rachel S. , Huang Bin , Propert Kathleen J. , Margulies Susan , Ferrari Victor A. , Epstein Jonathan A. , Zhou Rong 
Published: February 2012

Background—
We quantified absolute myocardial blood flow (MBF) using a spin-labeling MRI (SL-MRI) method after transplantation of endothelial cells (ECs) into the infarcted heart. Our aims were to study the temporal changes in MBF in response to EC transplantation and to compare regional MBF with contractile function (wall motion) and microvascular density.

Methods and Results—

We first validated the SL-MRI method with the standard microsphere technique in normal rats. We then induced myocardial infarction in athymic rats and injected 5 million ECs (human umbilical vein endothelial cells) suspended in Matrigel or Matrigel alone (vehicle) along the border of the blanched infarcted area. At 2 weeks after myocardial infarction, MBF averaged over the entire slice (
P
=0.038) and in the infarcted region (
P
=0.0086) was significantly higher in EC versus vehicle group; the greater MBF was accompanied by an increase of microvasculature density in the infarcted region (
P
=0.0105 versus vehicle). At 4 weeks after myocardial infarction, MBF in the remote region was significantly elevated in EC-treated hearts (
P
=0.0277); this was accompanied by increased wall motion in this region assessed by circumferential strains (
P
=0.0075). Intraclass correlation coefficients and Bland-Altman plot revealed a good reproducibility of the SL-MRI method.

Conclusions—
MBF in free-breathing rats measured by SL-MRI is validated by the standard color microsphere technique. SL-MRI allows quantification of temporal changes of regional MBF in response to EC treatment. The proof-of-principle study indicates that MBF is a unique and sensitive index to evaluate EC-mediated therapy for the infarcted heart.
Down-regulated expression of hsa-miR-181c in Fanconi anemia patients: implications in TNFα regulation and proliferation of hematopoietic progenitor cells
Authors: Río Paula , Agirre Xabier , Garate Leire , Baños Rocío , Álvarez Lara , San José-Enériz Edurne , Badell Isabel , Casado José A. , Garín Marina , Prósper Felipe , Bueren Juan A. 
Published: February 2012

AbstractFanconi anemia (FA) is an inherited genetic disorder associated with BM failure and cancer predisposition. In the present study, we sought to elucidate the role of microRNAs (miRNAs) in the hematopoietic defects observed in FA patients. Initial studies showed that 3 miRNAs, hsa-miR-133a, hsa-miR-135b, and hsa-miR-181c, were significantly down-regulated in lymphoblastoid cell lines and fresh peripheral blood cells from FA patients. In vitro studies with cells expressing the luciferase reporter fused to the TNFα 3′-untranslated region confirmed in silico predictions suggesting an interaction between hsa-miR-181c and TNFα mRNA. These observations were consistent with the down-regulated expression of TNFα mediated by hsa-miR-181c in cells from healthy donors and cells from FA patients. Because of the relevance of TNFα in the hematopoietic defects of FA patients, in the present study, we transfected BM cells from FA patients with hsa-miR-181c to evaluate the impact of this miRNA on their clonogenic potential. hsa-miR-181c markedly increased the number and size of the myeloid and erythroid colonies generated by BM cells from FA patients. Our results offer new clues toward understanding the biologic basis of BM failure in FA patients and open new possibilities for the treatment of the hematologic dysfunction in FA patients based on miRNA regulation.
Functional analysis of hepatitis B virus pre-s deletion variants associated with hepatocellular carcinoma
Authors: Lin Chih-Ming , Wang Gen-Ming , Jow Guey-Mei , Chen Bing-Fang 
Published: February 2012

Abstract

Background
Naturally occurring pre-S deletion mutants have been identified in hepatitis B carriers and shown to be associated with the development of hepatocellular carcinoma. The phenotypes of these pre-S deletion genomes remain unclear, and they were investigated in this study.

Methods
The pre-S deletion genomes: (1) pre-S1 deletion, (2) deletion spanning pre-S1 and pre-S2, (3) pre-S2 N-terminal deletion, and (4) pre-S2 internal deletion were constructed and analyzed by transfection into Huh-7 cells.

Results
Functional analyses reveal that these mutants were divided into two groups: S promoter deletion and non-S promoter deletion variants. Compared with the wild-type genome, S promoter deletion variants led to an inverse ratio of pre-S1 mRNA and pre-S2/S mRNA, and intracellular accumulation of surface proteins. An interesting finding is that a small amount of L proteins was detected in the medium from S promoter deletion variant-transfected cells. Non-S promoter deletion variants conversely displayed a wild-type like mRNA and protein pattern. The secretion of surface proteins from non-S promoter deletion variants was inhibited less than from S promoter deletion variant. Immunofluorescence analysis showed mutant surface proteins colocalized with ER and exhibited an atypical distribution: granular staining pattern in the S-promoter deletion variants and perinuclear staining pattern in the non-S promoter deletion variants.

Conclusion
This study shows that these pre-S deletion genomes exhibit two different phenotypes in mRNA transcription, surface protein expression and secretion. This diversity seems to result from the deletion of S promoter rather than result from the deletion of pre-S1 or pre-S2.