bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone modification enhances the effectiveness of IL-13 receptor targeted immunotoxin in murine models of human pancreatic cancer
Authors: Fujisawa Toshio , Joshi Bharat H , Puri Raj K 
Published: April 2011

Abstract

Background
Interleukin-13 Receptor α2 (IL-13Rα2) is a tumor-associated antigen and target for cancer therapy. Since IL-13Rα2 is heterogeneously overexpressed in a variety of human cancers, it would be highly desirable to uniformly upregulate IL-13Rα2 expression in tumors for optimal targeting.

Methods
We examined epigenetic regulation of IL-13Rα2 in a murine model of human pancreatic cancer by Bisulfite-PCR, sequencing for DNA methylation and chromatin immunoprecipitation for histone modification. Reverse transcription-PCR was performed for examining changes in IL-13Rα2 mRNA expression after treatment with histone deacetylase (HDAC) and c-jun inhibitors. In vitro cytotoxicity assays and in vivo testing in animal tumor models were performed to determine whether HDAC inhibitors could enhance anti-tumor effects of IL-13-PE in pancreatic cancer. Mice harboring subcutaneous tumors were treated with HDAC inhibitors systemically and IL-13-PE intratumorally.

Results
We found that CpG sites in IL-13Rα2 promoter region were not methylated in all pancreatic cancer cell lines studied including IL-13Rα2-positive and IL-13Rα2-negative cell lines and normal cells. On the other hand, histones at IL-13Rα2 promoter region were highly-acetylated in IL-13Rα2-positive but much less in receptor-negative pancreatic cancer cell lines. When cells were treated with HDAC inhibitors, not only histone acetylation but also IL-13Rα2 expression was dramatically enhanced in receptor-negative pancreatic cancer cells. In contrast, HDAC inhibition did not increase IL-13Rα2 in normal cell lines. In addition, c-jun in IL-13Rα2-positive cells was expressed at higher level than in negative cells. Two types of c-jun inhibitors prevented increase of IL-13Rα2 by HDAC inhibitors. HDAC inhibitors dramatically sensitized cancer cells to immunotoxin in the cytotoxicity assay in vitro and increased IL-13Rα2 in the tumors subcutaneously implanted in the immunodeficient animals but not in normal mice tissues. Combination therapy with HDAC inhibitors and immunotoxin synergistically inhibited growth of not only IL-13Rα2-positive but also IL-13Rα2-negative tumors.

Conclusions
We have identified a novel function of histone modification in the regulation of IL-13Rα2 in pancreatic cancer cell lines in vitro and in vivo. HDAC inhibition provides a novel opportunity in designing combinatorial therapeutic approaches not only in combination with IL-13-PE but with other immunotoxins for therapy of pancreatic cancer and other cancers.
Optical identification of electronic state levels of an asymmetric InAs/InGaAs/GaAs dot-in-well structure
Authors: Zhou Xiaolong , Chen Yonghai , Xu Bo 
Published: April 2011

AbstractWe have studied the electronic state levels of an asymmetric InAs/InGaAs/GaAs dot-in-well structure, i.e., with an In0.15Ga0.85As quantum well (QW) as capping layer above InAs quantum dots (QDs), via temperature-dependent photoluminescence, photo-modulated reflectance, and rapid thermal annealing (RTA) treatments. It is shown that the carrier transfer via wetting layer (WL) is impeded according to the results of temperature dependent peak energy and line width variation of both the ground states (GS) and excited states (ES) of QDs. The quenching of integrated intensity is ascribed to the thermal escape of electron from the dots to the complex In0.15Ga0.85As QW + InAs WL structure. Additionally, as the RTA temperature increases, the peak of PL blue shifts and the full width at half maximum shrinks. Especially, the intensity ratio of GS to ES reaches the maximum when the energy difference approaches the energy of one or two LO phonon(s) of InAs bulk material, which could be explained by phonon-enhanced inter-sublevels carrier relaxation in such asymmetric dot-in-well structure.PACS: 73.63.Kv; 73.61.Ey; 78.67.Hc; 81.16.Dn
Organic nanofibers integrated by transfer technique in field-effect transistor devices
Authors: Tavares Luciana , Kjelstrup-Hansen Jakob , Thilsing-Hansen Kasper , Rubahn Horst-Günter 
Published: April 2011

AbstractThe electrical properties of self-assembled organic crystalline nanofibers are studied by integrating these on field-effect transistor platforms using both top and bottom contact configurations. In the staggered geometries, where the nanofibers are sandwiched between the gate and the source-drain electrodes, a better electrical conduction is observed when compared to the coplanar geometry where the nanofibers are placed over the gate and the source-drain electrodes. Qualitatively different output characteristics were observed for top and bottom contact devices reflecting the significantly different contact resistances. Bottom contact devices are dominated by contact effects, while the top contact device characteristics are determined by the nanofiber bulk properties. It is found that the contact resistance is lower for crystalline nanofibers when compared to amorphous thin films. These results shed light on the charge injection and transport properties for such organic nanostructures and thus constitute a significant step forward toward a nanofiber-based light-emitting device.
Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction
Authors: Peng Jing , He Fang , Zhang Ciliu , Deng Xiaolu , Yin Fei 
Published: April 2011

Abstract

Background
Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC) isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC) barrier dysfunction.

Methods
Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL). RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER). p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability.

Results
We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA) transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER.

Conclusions
Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF-α signaling to RhoA, and that this plays a critical role in signaling F-actin rearrangement and barrier dysfunction in BMECs.
Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy
Authors: Bratland Åse , Dueland Svein , Hollywood Donal , Flatmark Kjersti , Ree Anne H 
Published: April 2011

Abstract

Background
In early-phase studies with targeted therapeutics and radiotherapy, it may be difficult to decide whether an adverse event should be considered a dose-limiting toxicity (DLT) of the investigational systemic agent, as acute normal tissue toxicity is frequently encountered with radiation alone. We have reanalyzed the toxicity data from a recently conducted phase 1 study on vorinostat, a histone deacetylase inhibitor, in combination with pelvic palliative radiotherapy, with emphasis on the dose distribution within the irradiated bowel volume to the development of DLT.

Findings
Of 14 eligible patients, three individuals experienced Common Terminology Criteria of Adverse Events grade 3 gastrointestinal and related toxicities, representing a toxicity profile vorinostat has in common with radiotherapy to pelvic target volumes. For each study patient, the relative volumes of small bowel receiving radiation doses between 6 Gy and 30 Gy at 6-Gy intervals (V6-V30) were determined from the treatment-planning computed tomography scans. The single patient that experienced a DLT at the second highest dose level of vorinostat, which was determined as the maximum-tolerated dose, had V6-V30 dose-volume estimates that were considerably higher than any other study patient. This patient may have experienced an adverse radiation dose-volume effect rather than a toxic effect of the investigational drug.

Conclusions
When reporting early-phase trial results on the tolerability of a systemic targeted therapeutic used as potential radiosensitizing agent, radiation dose-volume effects should be quantified to enable full interpretation of the study toxicity profile.

Trial registration
ClinicalTrials.gov: NCT00455351
Sex Differences in Lipid and Lipoprotein Metabolism: It's Not Just about Sex Hormones
Authors: Wang Xuewen , Magkos Faidon , Mittendorfer Bettina 
Published: April 2011

AbstractIt is commonly thought that sex hormones are important regulators of plasma lipid kinetics and are responsible for sexual dimorphism in the plasma lipid profile. Here we discuss the findings from studies evaluating lipid and lipoprotein kinetics in men and women in the context of what we know about the effects of exogenous sex hormone administration, and we conclude that it is more complicated than that. It has become clear that normal physiological alterations in the hormonal milieu (i.e. due to menopause or throughout the menstrual cycle) do not significantly affect plasma lipid homeostasis. Furthermore, parenterally administered estrogens have either no effect or only very small beneficial effects, whereas orally administered estrogens raise plasma triglyceride concentrations—a phenomenon that is not consistent with the observed sex differences and likely results from the hepatic “first-pass effect.” The effects of progestogens and androgens mimic only in part the differences in plasma lipids between men and women. Thus, the underlying physiological modulators of plasma lipid metabolism responsible for the differences between men and women remain to be elucidated.
Performance of a Dynamic Dew Point Method for Moisture Isotherms of Clays
Authors: Likos William J. , Lu Ning , Wenszel Wentz 
Published: April 2011

Abstract
Laboratory tests were conducted to assess the performance of a dynamic equilibrium method for rapidly measuring water vapor sorption isotherms of clays and clayey soils. Emphasis was placed on quantifying temperature stability, measurement reproducibility, establishing a recommended testing protocol, and comparing dynamically generated isotherms with those obtained using a conventional equilibrium method. Adsorption-desorption loops for water activity (aw) or relative humidity ranging from 0.03 to 0.95 and containing as many as 140 discrete measurements were obtained using the dynamic method in 12–24 h. Far less intensive sorption isotherms using the equilibrium method required ∼600 h (25 days). Measurement reproducibility was within 6 % of the full-scale range. Water contents measured using the dynamic method at aw less than 0.60 compared excellently with values measured using the equilibrium system and are within 10 to 15 % of the full-scale range at higher activity. Comparisons between total suction characteristic curves obtained using the dynamic system and the equilibrium system suggest a practical total suction measurement range from about 100 000 to 400 000 kPa for a wide range of clay types.
ASTM Round-Robin on Creep-Fatigue and Creep Behavior of P91 Steel
Authors: Kalyanasundaram V. , Saxena A. , Narasimhachary S. , Dogan B. 
Published: April 2011

Abstract
The American Society for Testing and Materials (ASTM), through its Committee E08 on Fatigue and Fracture subcommittee E08.05 on Creep-Fatigue Crack Formation, has recently developed a new standard for creep-fatigue testing (ASTM E2714-09). This paper describes the plans and preliminary results from a round-robin being presently conducted in support and verification of this new standard. The choice of the test material (ASTM Grade P91), the design of the round-robin test matrix, and a machining plan for the specimens are described. The results of microstructural analysis, tensile testing, and creep deformation and rupture testing are also presented along with some preliminary results from creep-fatigue testing. A new analytical model for representing the creep deformation characteristics of this material is also presented and evaluated using the creep data generated as part of the round-robin program. The results of the round-robin creep-fatigue testing will be used to make appropriate modifications to the test standard.
Topological modeling of reconstructive phase transitions through periodic hyperbolic surfaces: the β-quartz to keatite type transition
Authors: Bieri-Gross Barbara , Nesper Reinhard 
Published: April 2011

Abstract
The reconstructive transition β-quartz to keatite is evaluated by employing symmetry-adapted hyperbolic surfaces, i.e. periodic equi-surfaces (PES) as structural trial models. The PES descriptors reveal a transition model very close to the one discussed by Li et al. We can show that this model is associated with only a small shift of the principal structure factors in reciprocal space. We derive an intermediate structure halfway between quartz and keatite of P21 symmetry through symmetry considerations and group-subgroup relations. Atomic shifts are given. It is shown that topological modeling of reconstructive phase transitions by means of periodic hyperbolic surface descriptors is a valuable extension to MD methods in exploring possible transition coordinates. As the PES-method works strictly under symmetry control along group-subgroup relations it allows for a rationalization of both global structural changes and local chemical variations. The whole transition is described by means of only one significant set of structure factors for quartz and two sets for keatite.
Double sequence spaces defined by a modulus
Authors: Savaş Ekrem , Patterson Richard 
Published: April 2011

Abstract
This paper begins with new definitions for double sequence spaces. These new definitions are constructed, in general, by combining modulus function and nonnegative four-dimensional matrix. We use these definitions to establish inclusion theorems between various sequence spaces such as: If A = (a
m,n,k,l) be a nonnegative four-dimensional matrix such that $$
\mathop {\sup }\limits_{m,n} \sum\limits_{k,l = 0,0}^{\infty ,\infty } {a_{m,n,k,l} < \infty }
$$ and let f be a modulus, then ω″(A, f) ⊂ ω″∞(A, f) and ω″0(A, f) ⊂ ω″∞(A, f).
New Treatment Resources of Traumatic Thoracolumbar Burst Fractures - Minimally Invasive Open Anterior Column Reconstruction: our Initial Experience
Authors: Briuks Kalvis , Ruks Kaspars , Puce Andris , Jumtins Andris 
Published: April 2011

New Treatment Resources of Traumatic Thoracolumbar Burst Fractures - Minimally Invasive Open Anterior Column Reconstruction: our Initial Experience
Introduction. Thoracolumbal burst fracture is a common pathology in spinal trauma surgery. Most important for the understanding and treatment spinal injuries is to recognize spinal stability or instability as for unstable injuries stabilisation is recommended. Posterior only stabilisation leads to a high incidence of implant failure and re-kyphosis in the long-term, and patients with implant failure have moderate-to-severe pain. 80-85% of axial forces on the spine are transmitted via the anterior vertebral column. The aim of the procedure is to restore anatomical alignment and integrity to unstable or destroyed segments of the anterior column of the thoracic and lumbar spine. An open minimally invasive surgical approach is used to minimise surgical trauma and to reduce perioperative and postoperative morbidity Aim of the Study. We analyzed our initial experience in spinal anterior column stabilization for thoracolumbar burst fractures. Materials and methods. We have reviewed first 37 patients with thoracolumbar burst fracture wich have undergone anterior column stabilization in the Department of Spine Surgery of Trauma and Orthopaedic hospital between september 2007- september 2010. Results. We initially reported a series of 37 consecutive patients (14 women, 23 men) who were treated with minimally invasive open surgery to the anterior column between september 2007 and september 2010. There were 5 fractures of the thoracic spine (T4-10),17 fractures involving the thoracolumbar junction (T11-L1) and 15 fractures of the lumbar spine (L2-4). The most affected level was L1 (11 patients). In 5 cases anterior and posterior surgery were performed in one day. In 4 patients a right-sided mini-thoracotomy and 1 left sided minithoracotomy was performed to access the midthoracic spine (T4-8), a left-sided mini-thoracotomy to reach the thoracolumbar junction (T9-L1) was used in 14 patients and a retroperitoneal minilateral approach was used in 18 patients for lumbar spine intervention (L2-L4). Allogenous iliac crest bone was harvested in 11 patients and iliac crest autografts in 1 patient. Expandable (Synex) cages were used for vertebral reconstruction in 9 patients, but expandable (Obelisc) cages were used in 8 patients, nonexpandable mesh cages(DePuy) were used in 2 cases, tricortical iliac crest bone plus screw and rod system Expedium anterior (DePuy) - in 12 patients. Tricortical iliac crest bone or expandable cage plus locking compression plate (Synthes) in 3 patients. Conclusions. Our initial experience encourages us to continue this type of operation as it proved to be a safe for patients, the stability of the spine is much higher and anterior column stabilisation protects the spine.
Role of Human Skin Antimicrobial Peptides in Psoriasis
Authors: Mozeika Elga , Pilmane Mara , Kisis Janis 
Published: April 2011

Role of Human Skin Antimicrobial Peptides in Psoriasis
Introduction. Psoriasis is a chronic inflammatory skin disease with various biochemical, immunologic and vascular changes, and a vague relationship to nervous system function. Skin defends the body by rapidly setting an innate immune response and providing a swift first-line defense against infection or injury. Hundreds of naturally occurring antimicrobial peptides have been discovered and it has been shown that psoriatic epidermis expresses high levels of host defense proteins. Aim of the Study. To evaluate human antimicrobial peptides in correlation with inflammation level in skin biopsy material of psoriatic lesions. Materials and methods. We evaluated 9 psoriasis patients and 1 healthy volunteer. Skin biopsies were obtained from using the routine punch biopsy method. All tissue specimens were stained with hematoxylin and eosin and by immunochemistry for human β defensin 2, PGP 9.5, MMP2. The intensity of immunostaining was graded semiquantitatively. For apoptosis evaluation, we used TUNEL method. Results. We found a distinct inflammatory cell infiltration with diffusive character in subepithelial layer, epithelium and hair follicle outer epithelial sheath. Defensin-containing cell number, PGP 9.5-containing nerve fibers and number of MMP2 positive macrophages, fibroblasts and epitheliocytes varied from few to abundant in the visual field. Apoptosis affected epithelial cells, connective tissue cells and inflammatory cells focally. Conclusions. Histological findings vary from marked inflammatory cell infiltration to granulation tissue. Psoriatic lesions of patients with no previous active psoriasis treatment feature marked activation of defensin, matrix metalloproteinase, apoptosis and neuropeptides-containing innervation. In skin of psoriasis patients with long-term ineffective treatment psoriatic lesions show abundance of positive structures of defensin, matrix metalloproteinase and neuropeptides-containing innervation. Close correlation between expression of defensin-containing cells, apoptotic cells, and inflammation in the skin was found suggesting about possible stimulation of AMPs and apoptosis by specific inflammation.
Tumefactive Multiple Sclerosis Mimicking Neoplasm
Authors: Elsone Liene , Platkajis Ardis , Karelis Guntis , Dzelzite Sarmite , Murzina Maira 
Published: April 2011

Tumefactive Multiple Sclerosis Mimicking Neoplasm
Acute demyelination may present as a rapidly expanding space-occupying or tumefactive lesion (TDL). Tumefactive demyelinating lesions are misdiagnosed quite frequently and can result in unnecessary and potentially harmful surgical resection, radiation or toxic chemotherapeutic interventions therapy. Systematic literature review from available articles and abstracts in PubMed database was summarized in purpose to describe typical presentation and diagnostically challenging features of TDL. One clinical case report presenting tumor-like lesion of the brain, when the diagnosis of TDL was established, is added as an illustrative material.
Severe Deep Neck Space Infection and Bilateral Pneumonia of Odontogenic Origin: a Case Report
Authors: Dobele Ilze , Kragis Gints , Salms Girts , Apse Peteris 
Published: April 2011

Severe Deep Neck Space Infection and Bilateral Pneumonia of Odontogenic Origin: a Case Report
Severe deep neck infections (DNIs) are potential complications of odontogenic pathology. DNIs affecting perimandibular space have a high prevalence and their etiologic and therapeutic aspects have been discussed. Early diagnosis and aggressive antimicrobial and surgical treatment are essential to successfully treat cervical abscesses and compromised upper airways of odontogenic origin. We report the case of life threatening pathology involving perimandibular, retropharyngeal spaces and bilateral pneumonia.