bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sir Joseph Barcroft: one victorian physiologist's contributions to a half century of discovery
Authors: Longo Lawrence D. 
Published: May 2015

AbstractDuring the first half of the 20th Century, Joseph Barcroft, KBE, FRS of Cambridge University became a world leader in respiratory physiology. He determined the role of neural stimulation in the oxygen consumption of several organs, established many of the factors that regulate the binding of oxygen to haemoglobin, explored the determinants of a human's acclimatization to high altitude and developed the field of fetal cardiovascular physiology. Chair of the Cambridge Department of Physiology from 1925 to 1937, he served as a consultant and member of many UK governmental committees. During World War I, he led a British research unit exploring the effects of poisonous gases on pulmonary function and related problems. In addition to his almost 300 publications, several of his monographs are considered as classics.
Operating Experience of General Electric Gas Turbines
Authors: McLean H. D. 
Published: May 2015

A review is made of all General Electric Company Gas Turbines installed and operated previous to January 1, 1958. The gas turbines are reviewed with respect to application, fuels burned, fired hours, and miscellaneous features. Each different basic design is briefly described, with date of first operation and total number installed given. Gas turbine failures that have occurred in operation are discussed.
Availability, reliability, and use factors are given. A brief review of published articles by gas turbine owners and operators is made. Problems that have occurred in eight and one-half years of operation are discussed, and solutions are given. Maintenance requirements and life of gas-path parts are discussed.
A brief description of future activity, new basic designs, new features, and new installations is included.
Anthropometrics of Italian Senior Male Rugby Union Players: From Elite to Second Division
Authors: Fontana Federico Y. , Colosio Alessandro , De Roia Gabriela F. , Da Lozzo Giorgio , Pogliaghi Silvia 
Published: May 2015

Anthropometric evaluation of athletes is necessary to optimize talent identification and player development.

Objectives:
To provide a specific anthropometric reference database of senior male rugby players competing at different levels in the southern European region.

Design:
Cross-sectional.

Methods:
In 362 professional players (25 ± 4 y; 138 Italian national team, 97 first-division, and 127 second-division national championships) the authors measured mass, stature, and percentage body fat (plicometry). Mean, SD, and coefficient of variation were calculated for forwards and backs and for positional subgroups. Binomial logistic regression and receiver-operating-characteristic curve were performed to assess which variables best predicted level assignment (international vs national level).

Results:
For all competitive levels forwards were significantly heavier and taller and had a larger percentage body fat and fat-free mass than backs. The lower the competitive level, the higher the within-role variability observed; furthermore, players in a specific positional subgroup were lighter, shorter, and fatter and had less fat-free mass. Fat-free mass is the variable that best predicts the likelihood of being classified as an international or national player (cutoff value 79.54 kg).

Conclusions:
The data confirm the specificity in the physical requirements of rugby in individual playing positions at all competitive levels and document significant differences among elite and 1st- and 2nd-division players in the same positional role. These differences may reflect the variable technical abilities, selection, training practices, and requirements of the game among these categories.
Genome Sequence of a Novel Iflavirus from the Leafhopper
Graminella nigrifrons
Authors: Chen Yuting , Liu Sijun , Bonning Bryony C. 
Published: May 2015

ABSTRACT

A novel iflavirus was discovered from the transcriptome of the leafhopper
Graminella nigrifrons
. The assembled virus genome has 9,700 nucleotides (nt) and encodes a 3,035-amino-acid polyprotein. Sanger sequencing was used to confirm the sequence encoding the polyprotein and indicated a genome length of 9,617 nt with a polyadenylated tail.
Whole-Genome Sequence of an Epidemic Strain of Burkholderia pseudomallei vgh07 in Taiwan
Authors: Chen Yao-Shen , Lin Hsi-Hsun , Hsueh Pei-Tan , Liu Pei-Ju , Ni Wen-Fan , Chung Wan-Chia , Lin Chih-Peng , Chen Ya-Lei 
Published: May 2015

ABSTRACT

Here, we report the complete genome sequence of
B. pseudomallei
vgh07. This is an epidemic strain that was isolated from a melioidosis patient with arthro-osteomyelitis in Taiwan.
Genome Sequence of Classical Swine Fever Virus Genotype 1.1 with a Genetic Marker of Attenuation Detected in a Continuous Porcine Cell Line
Authors: Tomar N. , Gupta A. , Arya R. S. , Somvanshi R. , Sharma V. , Saikumar G. 
Published: May 2015

ABSTRACT
The complete genome sequencing and analysis of a classical swine fever virus (CSFV) detected in a porcine kidney cell line revealed a close relationship with genotype 1.1 viruses circulating in India and China. The presence of consecutive T insertions in the 3′ untranslated region (UTR), as seen in vaccine strains of CSFV, suggested some degree of attenuation.
Complete Genome Sequence of a Coxsackievirus A16 Strain, Isolated from a Fatal Case in Shenzhen, Southern China, in 2014
Authors: Chen Long , Yang Hong , Feng Qian-Jin , Yao Xiang-Jie , Zhang Hai-Long , Zhang Ren-Li , He Ya-Qing 
Published: May 2015

ABSTRACT
We determined the complete genome sequence of a coxsackievirus A16 strain (CVA16/SZ29/CHN/2014) from a fatal case in Shenzhen, southern China, in 2014. The strain was assigned to subgenotype B1b based on phylogenetic analysis of the VP1 gene.
First Insights into the Genome of the
N
-Methylhydantoin-Degrading
Clostridium
sp. Strain FS41 (DSM 6877)
Authors: Poehlein Anja , Bandera Adrian , Horne Deborah , Maier Joachim , Pawlowicz David , Siebert Verena , Daniel Rolf 
Published: May 2015

ABSTRACT

Clostridium
sp. strain FS41 (DSM 6877) is a strictly anaerobic and Gram-positive spindle-shaped rod. This spore-forming bacterium is able to degrade
N
-methylhydantoin, with
N
-carbamoylsarcosine and sarcosine as intermediates. The genome consists of one replicon (6.28 Mb) and harbors 5,735 predicted protein-coding genes.
Draft Genome Sequences of Histamine-Producing Photobacterium kishitanii and Photobacterium angustum, Isolated from Albacore (
Thunnus alalunga
) and Yellowfin (
Thunnus albacares
) Tuna
Authors: Bjornsdottir-Butler Kristin , McCarthy Susan A. , Dunlap Paul V. , Timme Ruth E. , Benner Ronald A. 
Published: May 2015

ABSTRACT

Histamine-producing bacteria are responsible for scombrotoxin (histamine) fish poisoning, a leading cause of fish poisoning in the United States. We report here the draft genome sequences of four histamine-producing (HP)
Photobacterium kishitanii
strains and nine HP
Photobacterium angustum
strains isolated from tuna.
Activation of Toxin-Antitoxin System Toxins Suppresses Lethality Caused by the Loss of σ
E
in Escherichia coli
Authors: Daimon Yasushi , Narita Shin-ichiro , Akiyama Yoshinori 
Published: April 2015

ABSTRACT

σ
E
, an alternative σ factor that governs a major signaling pathway in envelope stress responses in Gram-negative bacteria, is essential for growth of
Escherichia coli
not only under stressful conditions, such as elevated temperature, but also under normal laboratory conditions. A mutational inactivation of the
hicB
gene has been reported to suppress the lethality caused by the loss of σ
E
.
hicB
encodes the antitoxin of the HicA-HicB toxin-antitoxin (TA) system; overexpression of the HicA toxin, which exhibits mRNA interferase activity, causes cleavage of mRNAs and an arrest of cell growth, while simultaneous expression of HicB neutralizes the toxic effects of overproduced HicA. To date, however, how the loss of HicB rescues the cell lethality in the absence of σ
E
and, more specifically, whether HicA is involved in this process remain unknown. Here we showed that simultaneous disruption of
hicA
abolished suppression of the σ
E
essentiality in the absence of
hicB
, while ectopic expression of wild-type HicA, but not that of its mutant forms without mRNA interferase activity, restored the suppression. Furthermore, HicA and two other mRNA interferase toxins, HigB and YafQ, suppressed the σ
E
essentiality even in the presence of chromosomally encoded cognate antitoxins when these toxins were overexpressed individually. Interestingly, when the growth media were supplemented with low levels of antibiotics that are known to activate toxins,
E. coli
cells with no suppressor mutations grew independently of σ
E
. Taken together, our results indicate that the activation of TA system toxins can suppress the σ
E
essentiality and affect the extracytoplasmic stress responses.

IMPORTANCE
σ
E
is an alternative σ factor involved in extracytoplasmic stress responses. Unlike other alternative σ factors, σ
E
is indispensable for the survival of
E. coli
even under unstressed conditions, although the exact reason for its essentiality remains unknown. Toxin-antitoxin (TA) systems are widely distributed in prokaryotes and are composed of two adjacent genes, encoding a toxin that exerts harmful effects on the toxin-producing bacterium itself and an antitoxin that neutralizes the cognate toxin. Curiously, it is known that inactivation of an antitoxin rescues the σ
E
essentiality, suggesting a connection between TA systems and σ
E
function. We demonstrate here that toxin activation is necessary for this rescue and suggest the possible involvement of TA systems in extracytoplasmic stress responses.
High-Frequency Targetable EGFR Mutations in Sinonasal Squamous Cell Carcinomas Arising from Inverted Sinonasal Papilloma
Authors: Udager Aaron M. , Rolland Delphine C.M. , McHugh Jonathan B. , Betz Bryan L. , Murga-Zamalloa Carlos , Carey Thomas E. , Marentette Lawrence J. , Hermsen Mario A. , DuRoss Kathleen E. , Lim Megan S. , Elenitoba-Johnson Kojo S.J. , Brown Noah A. 
Published: May 2015

Abstract
Inverted sinonasal papilloma (ISP) is a locally aggressive neoplasm associated with sinonasal squamous cell carcinoma (SNSCC) in 10% to 25% of cases. To date, no recurrent mutations have been identified in ISP or SNSCC. Using targeted next-generation sequencing and Sanger sequencing, we identified activating EGFR mutations in 88% of ISP and 77% of ISP-associated SNSCC. Identical EGFR genotypes were found in matched pairs of ISP and associated SNSCC, providing the first genetic evidence of a biologic link between these tumors. EGFR mutations were not identified in exophytic or oncocytic papillomas or non–ISP-associated SNSCC, suggesting that the ISP/SNSCC spectrum is biologically distinct among sinonasal squamous tumors. Patients with ISP harboring EGFR mutations also exhibited an increased progression-free survival compared with those with wild-type EGFR. Finally, treatment of ISP-associated carcinoma cells with irreversible EGFR inhibitors resulted in inactivation of EGFR signaling and growth inhibition. These findings implicate a prominent role for activating EGFR mutations in the pathogenesis of ISP and associated SNSCC and rationalize consideration of irreversible EGFR inhibitors in the therapy of these tumors. Cancer Res; 75(13); 2600–6. ©2015 AACR.
Building a Funded Research Program in Cancer Health Disparities: Considerations for Young Investigators
Authors: Ochs-Balcom Heather M. , Phillips Lynette S. , Nichols Hazel B. , Martinez Elena , Thompson Beti , Ojeifo John , Rebbeck Timothy R. 
Published: May 2015

Abstract
A workshop entitled “Building a funded research program in cancer health disparities” was held at the 38th Annual American Society of Preventive Oncology (ASPO) Meeting. Organized by the Junior Members Interest Group, the session addressed topics relevant to career development for cancer disparities investigators. Such considerations include the development of research programs on a backdrop of existing multi- and transdisciplinary teams, recognizing opportunities for advancing their research, given the growth of consortia-related research, and development of effective community-based partnerships. Key strategies for developing a sustainable career in cancer health disparities in the current environment include the need to effectively engage with communities, appreciate the value of team science and develop cross-discipline collaborations, and navigate the use and utility of consortia for disparities research. Academic considerations related to earning tenure and promotion that may be faced by the junior investigator in cancer health disparities were also discussed. This report may serve to both educate and provide lessons for early-stage investigators who wish to tackle complex scientific questions while developing their careers in cancer health disparities. Cancer Epidemiol Biomarkers Prev; 24(5); 882–5. ©2015 AACR.
IL2 Inducible T-cell Kinase, a Novel Therapeutic Target in Melanoma
Authors: Carson Craig C. , Moschos Stergios J. , Edmiston Sharon N. , Darr David B. , Nikolaishvili-Feinberg Nana , Groben Pamela A. , Zhou Xin , Kuan Pei Fen , Pandey Shaily , Chan Keefe T. , Jordan Jamie L. , Hao Honglin , Frank Jill S. , Hopkinson Dennis A. , Gibbs David C. , Alldredge Virginia D. , Parrish Eloise , Hanna Sara C. , Berkowitz Paula , Rubenstein David S. , Miller C. Ryan , Bear James E. , Ollila David W. , Sharpless Norman E. , Conway Kathleen , Thomas Nancy E. 
Published: May 2015

Abstract
Purpose: IL2 inducible T-cell kinase (ITK) promoter CpG sites are hypomethylated in melanomas compared with nevi. The expression of ITK in melanomas, however, has not been established and requires elucidation.
Experimental Design: An ITK-specific monoclonal antibody was used to probe sections from deidentified, formalin-fixed paraffin-embedded tumor blocks or cell line arrays and ITK was visualized by IHC. Levels of ITK protein differed among melanoma cell lines and representative lines were transduced with four different lentiviral constructs that each contained an shRNA designed to knockdown ITK mRNA levels. The effects of the selective ITK inhibitor BI 10N on cell lines and mouse models were also determined.
Results: ITK protein expression increased with nevus to metastatic melanoma progression. In melanoma cell lines, genetic or pharmacologic inhibition of ITK decreased proliferation and migration and increased the percentage of cells in the G0–G1 phase. Treatment of melanoma-bearing mice with BI 10N reduced growth of ITK-expressing xenografts or established autochthonous (Tyr-Cre/Ptennull/BrafV600E) melanomas.
Conclusions: We conclude that ITK, formerly considered an immune cell–specific protein, is aberrantly expressed in melanoma and promotes tumor development and progression. Our finding that ITK is aberrantly expressed in most metastatic melanomas suggests that inhibitors of ITK may be efficacious for melanoma treatment. The efficacy of a small-molecule ITK inhibitor in the Tyr-Cre/Ptennull/BrafV600E mouse melanoma model supports this possibility. Clin Cancer Res; 21(9); 2167–76. ©2015 AACR.
Synergistic Leukemia Eradication by Combined Treatment with Retinoic Acid and HIF Inhibition by EZN-2208 (PEG-SN38) in Preclinical Models of PML-RARα and PLZF-RARα–Driven Leukemia
Authors: Coltella Nadia , Valsecchi Roberta , Ponente Manfredi , Ponzoni Maurilio , Bernardi Rosa 
Published: May 2015

Abstract
Purpose: Retinoic acid-arsenic trioxide (ATRA-ATO) combination therapy is the current standard of care for patients with acute promyelocytic leukemia (APL) carrying the oncogenic fusion protein PML-RARα. Despite the high cure rates obtained with this drug combination, resistance to arsenic is recently emerging. Moreover, patients with APL carrying the PLZF-RARα fusion protein are partially resistant to ATRA treatment. Hypoxia-inducible factor-1α (HIF-1α) activation has been recently reported in APL, and EZN-2208 (PEG-SN38) is a compound with HIF-1α inhibitory function currently tested in clinical trials. This study investigates the effect of EZN-2208 in different preclinical APL models, either alone or in combination with ATRA.
Experimental Design: Efficacy of EZN-2208 in APL was measured in vitro by assessing expression of HIF-1α target genes, cell migration, clonogenicity, and differentiation, vis a vis the cytotoxic and cytostatic effects of this compound. In vivo, EZN-2208 was used in mouse models of APL driven by PML-RARα or PLZF-RARα, either alone or in combination with ATRA.
Results: Treatment of APL cell lines with noncytotoxic doses of EZN-2208 causes dose-dependent downregulation of HIF-1α bona fide target genes and affects cell migration and clonogenicity in methylcellulose. In vivo, EZN-2208 impairs leukemia progression and prolongs mice survival in APL mouse models. More importantly, when used in combination with ATRA, EZN-2208 synergizes in debulking leukemia and eradicating leukemia-initiating cells.
Conclusions: Our preclinical data suggest that the combination ATRA-EZN-2208 may be tested to treat patients with APL who develop resistance to ATO or patients carrying the PLZF-RARα fusion protein. Clin Cancer Res; 21(16); 3685–94. ©2015 AACR.
AMG 595, an Anti-EGFRvIII Antibody–Drug Conjugate, Induces Potent Antitumor Activity against EGFRvIII-Expressing Glioblastoma
Authors: Hamblett Kevin J. , Kozlosky Carl J. , Siu Sophia , Chang Wesley S. , Liu Hua , Foltz Ian N. , Trueblood Esther S. , Meininger David , Arora Taruna , Twomey Brian , Vonderfecht Steven L. , Chen Qing , Hill John S. , Fanslow William C. 
Published: May 2015

Abstract
Epidermal growth factor receptor variant III (EGFRvIII) is a cancer-specific deletion mutant observed in approximately 25% to 50% of glioblastoma multiforme (GBM) patients. An antibody drug conjugate, AMG 595, composed of the maytansinoid DM1 attached to a highly selective anti-EGFRvIII antibody via a noncleavable linker, was developed to treat EGFRvIII-positive GBM patients. AMG 595 binds to the cell surface and internalizes into the endo-lysosomal pathway of EGFRvIII-expressing cells. Incubation of AMG 595 with U251 cells expressing EGFRvIII led to potent growth inhibition. AMG 595 treatment induced significant tumor mitotic arrest, as measured by phospho-histone H3, in GBM subcutaneous xenografts expressing EGFRvIII. A single intravenous injection of AMG 595 at 17 mg/kg (250 μg DM1/kg) generated complete tumor regression in the U251vIII subcutaneous xenograft model. AMG 595 mediated tumor regression in the D317 subcutaneous xenograft model that endogenously expresses EGFRvIII. Finally, AMG 595 treatment inhibited the growth of D317 xenografts orthotopically implanted into the brain as determined by magnetic resonance imaging. These results demonstrate that AMG 595 is a promising candidate to evaluate in EGFRvIII-expressing GBM patients. Mol Cancer Ther; 14(7); 1614–24. ©2015 AACR.
Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models
Authors: Hu Chaoxin , Dadon Tikva , Chenna Venugopal , Yabuuchi Shinichi , Bannerji Rajat , Booher Robert , Strack Peter , Azad Nilofer , Nelkin Barry D. , Maitra Anirban 
Published: May 2015

Abstract
KRAS is activated by mutation in the vast majority of cases of pancreatic cancer; unfortunately, therapeutic attempts to inhibit KRAS directly have been unsuccessful. Our previous studies showed that inhibition of cyclin-dependent kinase 5 (CDK5) reduces pancreatic cancer growth and progression, through blockage of the centrally important RAL effector pathway, downstream of KRAS. In the current study, the therapeutic effects of combining the CDK inhibitor dinaciclib (SCH727965; MK-7965) with the pan-AKT inhibitor MK-2206 were evaluated using orthotopic and subcutaneous patient-derived human pancreatic cancer xenograft models. The combination of dinaciclib (20 mg/kg, i.p., three times a week) and MK-2206 (60 mg/kg, orally, three times a week) dramatically blocked tumor growth and metastasis in all eight pancreatic cancer models examined. Remarkably, several complete responses were induced by the combination treatment of dinaciclib and MK-2206. The striking results obtained in these models demonstrate that the combination of dinaciclib with the pan-AKT inhibitor MK-2206 is promising for therapeutic evaluation in pancreatic cancer, and strongly suggest that blocking RAL in combination with other effector pathways downstream from KRAS may provide increased efficacy in pancreatic cancer. Based on these data, an NCI–CTEP-approved multicenter phase I clinical trial for pancreatic cancer of the combination of dinaciclib and MK-2206 (NCT01783171) has now been opened. Mol Cancer Ther; 14(7); 1532–9. ©2015 AACR.
Abstract 1108: B-cell lymphoma-derived exosomes are reservoirs of inhibitors of apoptosis
Authors: Bennit Heather R. Ferguson , Valenzuela Malyn M. Asuncion , Jutzy Jessica S. , Wall Nathan R. 
Published: May 2015

Abstract
B-cells, along with other normal and cancerous cells, secrete 50-150 nm vesicles called exosomes. Exosomes carry proteins, mRNA, and miRNA that can be functional upon cellular uptake and are often specific to cell of origin, offering potential as disease biomarkers. Our lab has identified within exosomes from solid tumor cells a cancer-specific protein, Survivin, which is a member of the Inhibitors of Apoptosis (IAP) family. Whether Survivin and other IAP family members such as XIAP, cIAP1 or cIAP2 are also expressed in exosomes from hematopoietic malignancies is yet to be determined. In this study, we aim to investigate the exosomes released from B-cell lymphoma cells and determine the IAP content under basal and sublethal stress conditions. Three human non EBV-transformed B-cell lymphoma lines developed at Wayne State University were used. WSU-FSCCL (follicular small cleaved cell), WSU-DLCL-2 (diffuse large cell), and WSU-WM (Waldenstrom Macroglobulinemia) represent different levels of aggressiveness. Cells were cultured for 24 or 48 hours before exosome isolation from the conditioned media using either ultracentrifugation on a sucrose cushion or ExoQuick (System Biosciences). Sublethal levels of UV irradiation were determined for each cell line by analyzing DNA content by propidium iodide staining with a FACSCalibur. Protein quantity of exosomes was measured using a BCA assay, and protein content was studied using Western blotting. Corresponding gene expression was identified using RT-PCR. Here we report IAP protein and mRNA (except XIAP) within exosomes from basal cells. We are currently probing exosomes from stressed cells for comparison. We hypothesize that the IAP exosomal profile may change under stressed conditions. The specificity and variability in exosomal content offers capabilities not only as disease biomarkers, but also in the immunomodulating activity of exosomes which have shown roles in both stimulating and inhibiting the immune system, We have found evidence that exosomal Survivin plays an immune role in skewing Th1/Th2 populations and decreasing cytotoxic function. Changes in exosome content between basal and stressed cells may have roles in the immunomodulation of the tumor microenvironment which facilitates the evasion of lymphoma cells to immune destruction, as well as possible prognostic benefit as to whether treatments are being effective or detrimental.
Citation Format: Heather R. Ferguson Bennit, Malyn M. Asuncion Valenzuela, Jessica S. Jutzy, Nathan R. Wall. B-cell lymphoma-derived exosomes are reservoirs of inhibitors of apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1108. doi:10.1158/1538-7445.AM2014-1108