bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of secondary neutron dose in proton therapy resulting from the use of a tungsten alloy MLC or a brass collimator system
Authors: Diffenderfer Eric S. , Ainsley Christopher G. , Kirk Maura L. , McDonough James E. , Maughan Richard L. 
Published: October 2011

Purpose:To apply the dual ionization chamber method for mixed radiation fields to an accurate comparison of the secondary neutron dose arising from the use of a tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system for defining the shape of a therapeutic proton field.Methods:Hydrogenous and nonhydrogenous ionization chambers were constructed with large volumes to enable measurements of absorbed doses below 10–4 Gy in mixed radiation fields using the dual ionization chamber method for mixed‐field dosimetry. Neutron dose measurements were made with a nominal 230 MeV proton beam incident on a closed tungsten alloy MLC and a solid brass block. The chambers were cross‐calibrated against a 60Co‐calibrated Farmer chamber in water using a 6 MV x‐ray beam and Monte Carlo simulations were performed to account for variations in ionization chamber response due to differences in secondary neutron energy spectra.Results:The neutron and combined proton plus γ‐ray absorbed doses are shown to be nearly equivalent downstream from either a closed tungsten alloy MLC or a solid brass block. At 10 cm downstream from the distal edge of the collimating material the neutron dose from the closed MLC was (5.3 ± 0.4) × 10− 5 Gy/Gy. The neutron dose with brass was (6.4 ± 0.7) × 10− 5 Gy/Gy. Further from the secondary neutron source, at 50 cm, the neutron doses remain close for both the MLC and brass block at (6.9 ± 0.6) × 10− 6 Gy/Gy and (6.3 ± 0.7) × 10− 6 Gy/Gy, respectively.Conclusions:The dual ionization chamber method is suitable for measuring secondary neutron doses resulting from proton irradiation. The results of measurements downstream from a closed tungsten alloy MLC and a brass block indicate that, even in an overly pessimistic worst‐case scenario, secondary neutron production in a tungsten alloy MLC leads to absorbed doses that are nearly equivalent to those seen from brass collimators. Therefore, the choice of tungsten alloy in constructing the leaves of a proton MLC is appropriate, and does not lead to a substantial increase in the secondary neutron dose to the patient compared to that generated in a brass collimator.
Immunization with Ehrlichia P28 Outer Membrane Proteins Confers Protection in a Mouse Model of Ehrlichiosis
Authors: Crocquet-Valdes Patricia A. , Thirumalapura Nagaraja R. , Ismail Nahed , Yu Xuejie , Saito Tais B. , Stevenson Heather L. , Pietzsch Colette A. , Thomas Sunil , Walker David H. 
Published: October 2011

ABSTRACT

The obligately intracellular bacterium
Ehrlichia chaffeensis
that resides in mononuclear phagocytes is the etiologic agent of human monocytotropic ehrlichiosis (HME). HME is an emerging and often life-threatening, tick-transmitted infectious disease in the United States. Effective primary immune responses against
Ehrlichia
infection involve generation of
Ehrlichia
-specific gamma interferon (IFN-γ)-producing CD4
+
T cells and cytotoxic CD8
+
T cells, activation of macrophages by IFN-γ, and production of
Ehrlichia
-specific antibodies of the Th1 isotype. Currently, there are no vaccines available against HME. We evaluated the ability of 28-kDa outer membrane proteins (P28-OMP-1) of the closely related
Ehrlichia muris
to stimulate long-term protective memory T and B cell responses and confer protection in mice. The spleens of mice vaccinated with
E. muris
P28-9, P28-12, P28-19, or a mixture of these three P28 proteins (P28s) using a DNA prime-protein boost regimen and challenged with
E. muris
had significantly lower bacterial loads than the spleens of mock-vaccinated mice. Mice immunized with P28-9, P28-12, P28-19, or the mixture induced
Ehrlichia-
specific CD4
+
Th1 cells. Interestingly, mice immunized with P28-14, orthologs of which in
E. chaffeensis
and
E. canis
are primarily expressed in tick cells, failed to lower the ehrlichial burden in the spleen. Immunization with the recombinant P28-19 protein alone also significantly decreased the bacterial load in the spleen and liver compared to those of the controls. Our study reports, for the first time, the protective roles of the
Ehrlichia
P28-9 and P28-12 proteins in addition to confirming previous reports of the protective ability of P28-19. Partial protection induced by immunization with P28-9, P28-12, and P28-19 against
Ehrlichia
was associated with the generation of
Ehrlichia-
specific cell-mediated and humoral immune responses.
Identification and Analysis of Papillomavirus E2 Protein Binding Sites in the Human Genome
Authors: Võsa Liisi , Sudakov Aleksander , Remm Maido , Ustav Mart , Kurg Reet 
Published: October 2011

ABSTRACT
Papillomavirus E2 protein is required for the replication and maintenance of viral genomes and transcriptional regulation of viral genes. E2 functions through sequence-specific binding to 12-bp DNA motifs—E2 binding sites (E2BS)—in the virus genome. Papillomaviruses are able to establish persistent infection in their host and have developed a long-term relationship with the host cell in order to guarantee the propagation of the virus. In this study, we have analyzed the occurrence and functionality of E2BSs in the human genome. Our computational analysis indicates that most E2BSs in the human genome are found in repetitive DNA regions and have G/C-rich spacer sequences. Using a chromatin immunoprecipitation approach, we show that human papillomavirus type 11 (HPV11) E2 interacts with a subset of cellular E2BSs located in active chromatin regions. Two E2 activities, sequence-specific DNA binding and interaction with cellular Brd4 protein, are important for E2 binding to consensus sites. E2 binding to cellular E2BSs has a moderate or no effect on cellular transcription. We suggest that the preference of HPV E2 proteins for E2BSs with A/T-rich spacers, which are present in the viral genomes and underrepresented in the human genome, ensures E2 binding to specific binding sites in the virus genome and may help to prevent extensive and possibly detrimental changes in cellular transcription in response to the viral protein.
A Novel Cyanophage with a Cyanobacterial Nonbleaching Protein A Gene in the Genome
Authors: Gao E-Bin , Gui Jian-Fang , Zhang Qi-Ya 
Published: October 2011

ABSTRACT

A cyanophage, PaV-LD, has been isolated from harmful filamentous cyanobacterium
Planktothrix agardhii
in Lake Donghu, a shallow freshwater lake in China. Here, we present the cyanophage's genomic organization and major structural proteins. The genome is a 95,299-bp-long, linear double-stranded DNA and contains 142 potential genes. BLAST searches revealed 29 proteins of known function
in
cyanophages, cyanobacteria, or bacteria. Thirteen major structural proteins ranging in size from 27 kDa to 172 kDa were identified by SDS-PAGE and mass-spectrometric analysis. The genome lacks major genes that are necessary to the tail structure, and the tailless PaV-LD has been confirmed by an electron microscopy comparison with other tail cyanophages and phages. Phylogenetic analysis of the major capsid proteins also reveals an independent branch of PaV-LD that is quite different from other known tail cyanophages and phages. Moreover, the unique genome carries a nonbleaching protein A (NblA) gene (open reading frame [ORF]
022L
), which is present in all phycobilisome-containing organisms and mediates phycobilisome degradation. Western blot detection confirmed that
022L
was expressed after PaV-LD infection in the host filamentous cyanobacterium. In addition, its appearance was companied by a significant decline of phycocyanobilin content and a color change of the cyanobacterial cells from blue-green to yellow-green. The biological function of PaV-LD
nblA
was further confirmed by expression in a model cyanobacterium via an integration platform, by spectroscopic analysis and electron microscopy observation. The data indicate that PaV-LD is an exceptional cyanophage of filamentous cyanobacteria, and this novel cyanophage will also provide us with a new vision of the cyanophage-host interactions.
Molecular Pathways: Osteoclast-Dependent and Osteoclast-Independent Roles of the RANKL/RANK/OPG Pathway in Tumorigenesis and Metastasis
Authors: Dougall William C. 
Published: October 2011

Abstract
Receptor activator of nuclear factor-kappa B ligand (RANKL) is a TNF ligand superfamily member that is essential for the formation, activation, and function of osteoclasts. RANKL functions via its cognate receptor RANK, and it is inhibited by the soluble decoy receptor osteoprotegerin (OPG). In skeletal metastases, the ratio of RANKL to OPG is upregulated, which leads to increased osteoclast-mediated bone destruction. These changes in the bone microenvironment not only compromise the structural integrity of bone, leading to severe clinical morbidities, but have also been implicated in establishment of de novo bone metastasis and the progression of existing skeletal tumors. Evaluation of RANKL inhibitors, including the fully human anti-RANKL antibody denosumab, in patients with cancer has shown reductions in tumor-induced bone resorption activity and successful management of skeletal complications of bone metastases. RANKL also functions as a major paracrine effector of the mitogenic action of progesterone in mouse mammary epithelium, and it has a role in ovarian hormone-dependent expansion and regenerative potential of mammary stem cells. RANKL inhibition attenuates mammary tumorigenesis and pulmonary metastases in mouse models. These data suggest that the contribution of progesterone to increased mammary cancer incidence is mediated, at least in part, by RANKL-dependent changes in the mammary epithelium; RANKL also directly promotes distant metastases. In summary, the antitumor and antimetastatic effects of RANKL inhibition can occur by at least 2 distinct mechanisms, one in the bone via osteoclast-dependent effects, and the second via direct effects on the tumor cells of various origins and/or mammary epithelium. Clin Cancer Res; 18(2); 326–35. ©2011 AACR.
Curcumin Induces the Differentiation of Myeloid-Derived Suppressor Cells and Inhibits Their Interaction with Cancer Cells and Related Tumor Growth
Authors: Tu Shui Ping , Jin Huanyu , Shi Jin Dong , Zhu Li Ming , Suo Ya , Lu Gang , Liu Anna , Wang Timothy C. , Yang Chung S. 
Published: October 2011

Abstract
Myeloid-derived suppressor cells (MDSC) accumulate in the spleen and tumors and contribute to tumor growth, angiogenesis, and progression. In this study, we examined the effects of curcumin on the activation and differentiation of MDSCs, their interaction with human cancer cells, and related tumor growth. Treatment with curcumin in the diet or by intraperitoneal injection significantly inhibited tumorigenicity and tumor growth, decreased the percentages of MDSCs in the spleen, blood, and tumor tissues, reduced interleukin (IL)-6 levels in the serum and tumor tissues in a human gastric cancer xenograft model and a mouse colon cancer allograft model. Curcumin treatment significantly inhibited cell proliferation and colony formation of cancer cells and decreased the secretion of murine IL-6 by MDSCs in a coculture system. Curcumin treatment inhibited the expansion of MDSCs, the activation of Stat3 and NF-κB in MDSCs, and the secretion of IL-6 by MDSCs, when MDSCs were cultured in the presence of IL-1β, or with cancer cell- or myofibroblast-conditioned medium. Furthermore, curcumin treatment polarized MDSCs toward a M1-like phenotype with an increased expression of CCR7 and decreased expression of dectin 1 in vivo and in vitro. Our results show that curcumin inhibits the accumulation of MDSCs and their interaction with cancer cells and induces the differentiation of MDSCs. The induction of MDSC differentiation and inhibition of the interaction of MDSCs with cancer cells are potential strategies for cancer prevention and therapy. Cancer Prev Res; 5(2); 205–15. ©2011 AACR.
The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation
Authors: Pietschmann Matthias F. , Niethammer Thomas R. , Horng Annie , Gülecyüz Mehmet F. , Feist-Pagenstert Isa , Jansson Volkmar , Müller Peter E. 
Published: October 2011

Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI.
Treatment Options for Low Back Pain in Athletes
Authors: Petering Ryan C. , Webb Charles 
Published: October 2011

Context: Low back pain is one of the most common medical presentations in the general population. It is a common source of pain in athletes, leading to significant time missed and disability. The general categories of treatment for low back pain are medications and therapies. Evidence acquisition: Relevant studies were identified through a literature search of MEDLINE and the Cochrane Database from 1990 to 2010. A manual review of reference lists of identified sources was also performed. Results: It is not clear whether athletes experience low back pain more often than the general public. Because of a aucity of trials with athlete-specific populations, recommendations on treatments must be made from reviews of treatments for the general population. Several large systemic reviews and Cochrane reviews have compiled evidence on different modalities for low back pain. Superficial heat, spinal manipulation, nonsteroidal anti-inflammatory medications, and skeletal muscle relaxants have the strongest evidence of benefit. Conclusions: Despite the high prevalence of low back pain and the significant burden to the athletes, there are few clearly superior treatment modalities. Superficial heat and spinal manipulation therapy are the most strongly supported evidence-based therapies. Nonsteroidal anti-inflammatory medications and skeletal muscle relaxants have benefit in the initial management of low back pain; however, both have considerable side effects that must be considered. Athletes can return to play once they have recovered full range of motion and have the strength to prevent further injury.
Transcript profiling reveals expression differences in wild-type and glabrous soybean lines
Authors: Hunt Matt , Kaur Navneet , Stromvik Martina , Vodkin Lila 
Published: October 2011

Abstract

Background
Trichome hairs affect diverse agronomic characters such as seed weight and yield, prevent insect damage and reduce loss of water but their molecular control has not been extensively studied in soybean. Several detailed models for trichome development have been proposed for Arabidopsis thaliana, but their applicability to important crops such as cotton and soybean is not fully known.

Results
Two high throughput transcript sequencing methods, Digital Gene Expression (DGE) Tag Profiling and RNA-Seq, were used to compare the transcriptional profiles in wild-type (cv. Clark standard, CS) and a mutant (cv. Clark glabrous, i.e., trichomeless or hairless, CG) soybean isoline that carries the dominant P1 allele. DGE data and RNA-Seq data were mapped to the cDNAs (Glyma models) predicted from the reference soybean genome, Williams 82. Extending the model length by 250 bp at both ends resulted in significantly more matches of authentic DGE tags indicating that many of the predicted gene models are prematurely truncated at the 5' and 3' UTRs. The genome-wide comparative study of the transcript profiles of the wild-type versus mutant line revealed a number of differentially expressed genes. One highly-expressed gene, Glyma04g35130, in wild-type soybean was of interest as it has high homology to the cotton gene GhRDL1 gene that has been identified as being involved in cotton fiber initiation and is a member of the BURP protein family. Sequence comparison of Glyma04g35130 among Williams 82 with our sequences derived from CS and CG isolines revealed various SNPs and indels including addition of one nucleotide C in the CG and insertion of ~60 bp in the third exon of CS that causes a frameshift mutation and premature truncation of peptides in both lines as compared to Williams 82.

Conclusion
Although not a candidate for the P1 locus, a BURP family member (Glyma04g35130) from soybean has been shown to be abundantly expressed in the CS line and very weakly expressed in the glabrous CG line. RNA-Seq and DGE data are compared and provide experimental data on the expression of predicted soybean gene models as well as an overview of the genes expressed in young shoot tips of two closely related isolines.
Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1
Authors: Moehler Markus , Sieben Maike , Roth Susanne , Springsguth Franziska , Leuchs Barbara , Zeidler Maja , Dinsart Christiane , Rommelaere Jean , Galle Peter R 
Published: October 2011

Abstract

Background
Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric, colorectal, cervix and pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents or targeted agents could be combined with the oncolytic and immunostimmulatory properties of H-1PV.

Methods
Using human ex vivo models we evaluated the biological and immunological effects of H-1PV-induced tumor cell lysis alone or in combination with chemotherapeutic or targeted agents in human melanoma cells +/- characterized human cytotoxic T-cells (CTL) and HLA-A2-restricted dendritic cells (DC).

Results
H-1PV-infected MZ7-Mel cells showed a clear reduction in cell viability of >50%, which appeared to occur primarily through apoptosis. This correlated with viral NS1 expression levels and was enhanced by combination with chemotherapeutic agents or sunitinib. Tumor cell preparations were phagocytosed by DC whose maturation was measured according to the treatment administered. Immature DC incubated with H-1PV-induced MZ7-Mel lysates significantly increased DC maturation compared with non-infected or necrotic MZ7-Mel cells. Tumor necrosis factor-α and interleukin-6 release was clearly increased by DC incubated with H-1PV-induced SK29-Mel tumor cell lysates (TCL) and was also high with DC-CTL co-cultures incubated with H-1PV-induced TCL. Similarly, DC co-cultures with TCL incubated with H-1PV combined with cytotoxic agents or sunitinib enhanced DC maturation to a greater extent than cytotoxic agents or sunitinib alone. Again, these combinations increased pro-inflammatory responses in DC-CTL co-cultures compared with chemotherapy or sunitinib alone.

Conclusions
In our human models, chemotherapeutic or targeted agents did not only interfere with the pronounced immunomodulatory properties of H-1PV, but also reinforced drug-induced tumor cell killing. H-1PV combined with cisplatin, vincristine or sunitinib induced effective immunostimulation via a pronounced DC maturation, better cytokine release and cytotoxic T-cell activation compared with agents alone. Thus, the clinical assessment of H-1PV oncolytic tumor therapy not only alone but also in combination strategies is warranted.
Higher incidence of perineal community acquired MRSA infections among toddlers
Authors: McCullough Alexis C , Seifried Melissa , Zhao Xiaochen , Haase Jeffrey , Kabat William J , Yogev Ram , Blumenthal Robert M , Mukundan Deepa 
Published: October 2011

AbstractBackgroundA six-fold increase in pediatric MRSA infections, prompted us to examine the clinical profile of children with MRSA infections seen at Mercy Children's Hospital, Toledo, Ohio and to characterize the responsible strains.MethodsRecords were reviewed of pediatric patients who cultured positive for MRSA from June 1 to December 31, 2007. Strain typing by pulsed field gel electrophoresis (PFT) and DiversiLab, SCCmectyping, and PCR-basedlukSF-PVgene (encodes Panton-Valentine leukocidin), arginine catabolic mobile element (ACME) andcap5 gene detection was performed.ResultsChart review of 63 patients with MRSA infections revealed that 58(92%) were community acquired MRSA (CAMRSA). All CAMRSA were skin and soft tissue infections (SSTI). Twenty five (43%) patients were aged < 3 yrs, 19(33%) aged 4-12 and 14(24%) aged 13-18. Nineteen (76%) of those aged < 3 yrs had higher incidence of perineal infections compared to only 2(11%) of the 4-12 yrs and none of the 13-18 yrs of age. Infections in the extremities were more common in the older youth compared to the youngest children. Overall, there was a significant association between site of the infection and age group (Fisher's Exact p-value < 0.001). All CAMRSA were USA300 PFT, clindamycin susceptible, SCCmectype IVa andlukSF-PV genepositive. Nearly all contained ACME and about 80% werecap5 positive. Of the 58 USA300 strains by PFT, 55(95%) were also identified as USA300 via the automated repetitive sequence-based PCR method from DiversiLab.ConclusionsCAMRSA SSTI of the perineum was significantly more common among toddlers and that of the extremities in older children. The infecting strains were all USA300 PFT. Further studies are needed to identify the unique virulence and colonization characteristics of USA300 strains in these infections.