bluuebunny/crossref_metadata_2025 huggingface dataset:
Unified variation modeling of sheet metal assembly considering rigid and compliant variations
Authors: Cai Na , Qiao Lihong , Anwer Nabil
Published: May 2014

Variation modeling of sheet metal assemblies is quite critical when specifying and verifying the geometric and dimensional requirements of parts. However, sheet metal parts’ compliant behavior makes the variation modeling approach more complex when coupling both rigid variation in the in-plane direction and compliant variation in the out-of-plane direction. In order to completely model the overall three-dimensional variation of sheet metal assembly, a unified variation modeling approach considering both rigid and compliant variations is proposed in this article. Four types of coordinate systems are defined. In the in-plane direction, homogeneous transformation matrix is used to describe the position and orientation relationships between assembly elements, and differential motion vector is used to represent rigid variation. In the out-of-plane direction, a vector composed of the deviations of selected key characteristic points is used to represent compliant variation, and the method of influence coefficients is adopted to analyze compliant variation. The overall three-dimensional variation of sheet metal assembly is the superposition of both in-plane rigid variation and out-of-plane compliant variation. Three types of variation sources that are fixture locators’ deviations, datum features’ deviations and joint features’ deviations are considered here. A case study is presented to illustrate the proposed approach.
Kinematic analysis and design of a novel 6-degree of freedom parallel robot
Authors: Hui DU , Feng GAO , Yang PAN
Published: May 2014

A novel 3-UP3R parallel mechanism with six degree of freedoms is proposed in this paper. One most important advantage of this mechanism is that the three translational and three rotational motions are partially decoupled: the end-effector position is only determined by three inputs, while the rotational angles are relative to all six inputs. The design methodology via GF set theory is brought out, using which the limb type can be determined. The mobility of the end-effector is analyzed. After that, the kinematic and velocity models are formulated. Then, workspace is studied, and since the robot is partially decoupled, the reachable workspace is also the dexterous workspace. In the end, both local and global performances are discussed using conditioning indexes. The experiment of real prototype shows that this mechanism works well and may be applied in many fields.
Is one-time carbon monoxide intoxication harmless? Evaluation by argyrophilic nucleolar-organizing regions staining method
Authors: Çolakoğlu S , Saritas A , Eroz R , Oktay M , Yaykasli KO , Akoz A , Kaya E , Kandis H
Published: May 2014

In carbon monoxide (CO) poisoning, CO affects the oxygen-carrying capacity of the hemoglobin molecule. Nucleolar-organizing regions (NORs) are genetic loci on chromosomes that are composed of ribosomal DNA and proteins. NORs can be stained with silver. A total of 18 rats were exposed to CO in three different concentrations (1000, 3000, and 5000 ppm) with 6 rats as controls. The animals were euthanized 7 days after CO intoxication. Lung tissues were taken, embedded in paraffin blocks, and sectioned at 5 μm thickness. Argyrophilic nucleolar-organizing region (AgNOR) staining was carried out. One hundred nuclei per individual were evaluated, and total AgNOR number per total nuclear number and total AgNOR area per nuclear area (TAA/NA) for each nucleus were analyzed. The CO exposure groups had significantly higher TAA/NA values and AgNOR numbers than the control group ( p < 0.05). Although the differences between 1000 ppm and the other two CO-exposed groups were meaningful ( p < 0.05) in the TAA/NA values, there were no differences among the CO exposure groups for the AgNOR number ( p > 0.05). The increase in TAA/NA value depends on the increase in the CO exposure. Significant correlations between both the AgNOR values and histopathological scoring methods were found. Therefore, AgNOR staining method may be used as an indirect indicator for evaluating the degree of cell damage rate.
A literature review on the mediation of sociolinguistic style in television and cinematic fiction: Sustaining the ideology of authenticity
Authors: Stamou Anastasia G
Published: May 2014

A shift of contemporary sociolinguistic research towards media and pop cultural discourse has been observed (e.g. Lopez, 2009; Meek, 2006). Despite the proliferation of studies, there has not been a systematic attempt to chart this field of research. In the light of this, in the present article I review research on the representations of sociolinguistic style in TV and film fictional discourse. The review reveals that although the epistemology of social construction has privileged the analysis of fictional data, the paradigm upon which most of the reviewed studies have drawn remains a traditional one. Similarly, a view of fiction as a reflection of sociolinguistic style is still a dominant conceptual framework from which many researchers tend to interpret their analyses. In conclusion, it is suggested that this research strand tends to confirm the ‘artificiality’ of fiction, by eventually sustaining the ideology of sociolinguistic authenticity.
Parentheticals and the presentation of multipersonal consciousness: A stylistic analysis of Mrs Dalloway
Authors: Cui Yaxiao
Published: May 2014

The presentation of consciousness in Mrs Dalloway has long been a focus of study, and many scholars have investigated Woolf’s narrative techniques in this regard, especially her use of Free Indirect Style. However, most of the existing studies mainly concentrate on the consciousness presentation of individual characters. Few studies have provided adequate accounts concerning the arrangement of the shifting narrative viewpoints and the linguistic mechanism that facilitates the ‘multipersonal representation of consciousness’ in this novel (Auerbach, 2003 [1953]: 536). This article attempts to fill this research gap by examining the use of parentheticals in Mrs Dalloway. The syntactic independence of a parenthetical gives it a degree of freedom to digress from its host, which makes this construction a convenient device to bring in new sources of consciousness and thus shift the narrative viewpoint from one character to another. The frequent viewpoint shifts subvert the convention of adhering to a single coherent narrative point of view. Meanwhile, using parentheticals allows Woolf to present multiple points of view within a short stretch of text, even within a single sentence. In this way, a sense of simultaneity is created. Distinct sources of consciousness are brought closer to each other; the very boundaries between individual minds seem to be blurred.
Third-Party Allocation of Rewards
Authors: Kazemi Ali , Törnblom Kjell
Published: May 2014

The present study shows that categorization of reward recipients into different entities affects distributive preferences by third-party non-recipient allocators. Rewards were allocated more equally to members of one group than to members of two dyads or to independent recipients. Moreover, allocators who were explicitly requested to allocate rewards justly were more egalitarian than those who were not requested to do so. More interestingly, rewards were allocated more equally between members in each of two dyads and between independent recipients, when a just allocation request was made, than when such a request was not made. This implies that a request for just allocation modifies the effects of recipient entity categorization toward more equal reward allocations.
Palliative Sedation
Authors: Gurschick Lauren , Mayer Deborah K. , Hanson Laura C.
Published: May 2014

Purpose:

To describe the suggested clinical practice of palliative sedation as it is presented in the literature and discuss available guidelines for its use.

Methods:

CINAHL, PubMed, and Web of Science were searched for publications since 1997 for recommended guidelines and position statements on palliative sedation as well as data on its provision. Keywords included palliative sedation, terminal sedation, guidelines, United States, and end of life. Inclusion criteria were palliative sedation policies, frameworks, guidelines, or discussion of its practice, general or oncology patient population, performance of the intervention in an inpatient unit, for humans, and in English. Exclusion criteria were palliative sedation in children, acute illness, procedural, or burns, and predominantly ethical discussions.

Results:

Guidelines were published by American College of Physicians-American Society of Internal Medicine (2000), Hospice and Palliative Nurses Association (2003), American Academy of Hospice and Palliative Medicine (2006), American Medical Association (2008), Royal Dutch Medical Association (2009), European Association for Palliative Care (2009), National Hospice and Palliative Care Organization (2010), and National Comprehensive Cancer Network (2012). Variances throughout guidelines include definitions of the practice, indications for its use, continuation of life-prolonging therapies, medications used, and timing/prognosis.

Recommendations:

The development and implementation of institutional-based guidelines with clear stance on the discussed variances is necessary for consistency in practice. Data on provision of palliative sedation after implementation of guidelines needs to be collected and disseminated for a better understanding of the current practice in the United States.
Sofosbuvir
Authors: Rose Lucia , Bias Tiffany E. , Mathias Clinton B. , Trooskin Stacey B. , Fong Jeffrey J.
Published: May 2014

Objective: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). Data Sources: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. Study Selection and Data Extraction: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. Data Synthesis: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. Conclusion: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..
Sensory Nerve Dysfunction and Hallux Valgus Correction
Authors: Jastifer James R. , Coughlin Michael J. , Doty Jesse F. , Stevens Faustin R. , Hirose Christopher , Kemp Travis J.
Published: May 2014

Background:

Sensory nerve dysfunction in patients with hallux valgus has been described as both a symptom of the deformity and a complication of the treatment. The purpose of this study was to quantify nerve dysfunction in hallux valgus patients and to prospectively evaluate whether the trauma of surgery or the correction of the deformity had any effect on the sensory nerve function.

Methods:

Fifty-seven consecutive feet undergoing operative correction for hallux valgus were prospectively enrolled. Preoperative and 3-, 6-, and 24-month postoperative clinical, radiographic, and detailed sensory examinations were completed. For the sensory examination, a Semmes-Weinstein 5.07 monofilament was used to establish, if present, a geometric area of sensory deficit about the hallux. This area was traced onto calibrated graphing paper and processed with imaging software. A total of 48/57 (84%) went on to complete 24 months of follow-up.

Results:

Preoperative sensory area deficit improved by a mean of 529 mm2 at 24-month follow-up. The mean preoperative sensory deficit area was 688 mm2 (SD 681 mm2, range: 0 to 2885 mm2) and 24-month postoperative sensory deficit area was 159 mm2 (SD 329 mm2, range: 0 to 1463 mm2). No clinically significant correlation existed between deficit and clinical outcome measures.

Conclusions:

This study showed that preoperative sensory deficits exist, and can improve up to 24 months after operative correction of the hallux valgus deformity. This supports the concept that sensory deficit in hallux valgus is at least partially caused by a reversible injury to the sensory nerves, not necessarily a complication of surgery.

Level of Evidence:

Level IV, case series.
Response of a half-car model with optimal magnetorheological damper parameters
Authors: Prabakar Ramia Sridaran , Sujatha Chandramohan , Narayanan Sadagopan
Published: May 2014

In this paper, control of the stationary response of a half-car model with a magnetorheological (MR) damper moving over a random road is considered. The MR damper is characterized using Bingham and modified Bouc–Wen models whose parameters are determined optimally using a multi-objective optimization technique and nondominated sorting genetic algorithm II. The multi-objective optimization problem is solved by minimizing the difference between the root mean square sprung mass acceleration, the sum of the front and rear suspension strokes and the sum of the front and rear road holding response of the half-car model with the MR damper, and those of an active suspension system based on linear quadratic regulator (LQR) control. The control force of the MR damper suspension is constrained to lie within ±5% of the control force corresponding to the active suspension system based on LQR control. It is observed that the MR damper suspension systems with optimal parameters perform an order of magnitude better than the passive suspension and perform as well as active suspensions with limited state feedback, and closer to the performance of fully active suspensions. In the case of MR damper suspensions, the vehicle response statistics are obtained using the equivalent linearization method and verified by Monte Carlo simulation.
Zinc-Excess Intake Causes the Deterioration of Renal Function Accompanied by an Elevation in Systemic Blood Pressure Primarily Through Superoxide Radical-Induced Oxidative Stress
Authors: Yanagisawa Hiroyuki , Miyazaki Takashi , Nodera Makoto , Miyajima Yuka , Suzuki Takashi , Kido Takamasa , Suka Machi
Published: May 2014

Using rats fed 22 g/d of a control diet containing 0.005% zinc (Zn) or 2 Zn-excess diets containing 0.05% or 0.2% Zn for 4 weeks, we examined the mechanisms involved in the deterioration of renal function induced by Zn-excess intake. An increase in Zn intake elevated mean blood pressure (BP) and reduced renal blood flow (RBF) and inulin clearance in a dose-dependent manner. This decline in inulin clearance may be derived from a fall in RBF. Administration of the nitric oxide (NO) synthase inhibitor, Nω-nitro-l-arginine methyl ester, markedly increased mean BP and significantly decreased RBF in the 3 groups of rats. Administration of the exogenous superoxide radical (OO−) scavenger, tempol, significantly decreased mean BP and substantially increased RBF in all groups of rats. These observations suggest that both an elevation in systemic BP and a reduction in RBF seen in the 2 Zn-excess diet groups result from a decrease in the action of the vasodilator, NO, through the formation of peroxynitrite based on the nonenzymatic reaction of NO and increased OO−. Indeed, the activity of the endogenous OO− scavenger, copper/Zn-superoxide dismutase, was significantly reduced in the vessel wall of rats fed 2 Zn-excess diets versus a control diet. 8-Hydroxy-2′-deoxyguanosine formation caused by OO− generation was notably elevated in the kidneys of rats fed 2 Zn-excess diets relatively to rats fed a control diet. Thus, Zn-excess intake leads to the aggravation of renal function concomitantly with an increase in systemic BP predominantly through the oxidative stress caused by OO−.
Hypo-osmotic Shock-Induced Subclinical Inflammation of Skin in a Rat Model of Disrupted Skin Barrier Function
Authors: Kishi Chihiro , Minematsu Takeo , Huang Lijuan , Mugita Yuko , Kitamura Aya , Nakagami Gojiro , Yamane Takumi , Yoshida Mikako , Noguchi Hiroshi , Funakubo Megumi , Mori Taketoshi , Sanada Hiromi
Published: May 2014

Aging disrupts skin barrier function and induces xerosis accompanied by pruritus. In many cases, elderly patients complain of pruritus during skin hygiene care, a condition called aquagenic pruritus of the elderly (APE). To date, the pathophysiology and mechanism of action of APE have not been elucidated. We conducted the present study to test the hypothesis that hypo-osmotic shock of epidermal cells induces skin inflammation and elongation of C-fibers by nerve growth factor β (NGFβ) as a basic mechanism of APE. The dorsal skin of HWY rats, which are a model for disrupted skin barrier function, was treated with distilled water (hypotonic treatment [Hypo] group) or normal saline (isotonic treatment [Iso] group) by applying soaked gauze for 7 days. Untreated rats were used as a control (no-treatment [NT] group). Histochemical and immunohistochemical analyses revealed inflammatory responses in the epidermis and the dermal papillary layer in the Hypo group, while no alterations were observed in the Iso or NT groups. Induction of expression and secretion of NGFβ and elongation of C-fibers into the epidermis were found in the Hypo group. In contrast, secretion of NGFβ was significantly lower and elongation of C-fibers was not observed in the Iso group. These results suggest that hypo-osmotic shock–induced inflammatory reactions promote hypersensitivity to pruritus in skin with disrupted barrier function.
Does risk stratification decrease the risk of natalizumab-associated PML? Where is the evidence?
Authors: Cutter Gary R , Stüve Olaf
Published: May 2014

The use of natalizumab has likely been limited by its association with progressive multifocal leukoencephalopathy (PML), an infection caused by the human polyomavirus John Cunningham (JC). Three factors were recently identified that contribute to the overall risk of natalizumab-associated PML: (1) Positive serostatus for anti-JCV antibodies, (2) prior use of immunosuppressants, and (3) duration of natalizumab therapy. This risk stratification algorithm has not led to a reduction in the incidence of PML in natalizumab-treated patients with multiple sclerosis between April 2010 and February 2014. This observation may appear perplexing, as treatment duration and JCV serostatus are modifiable risk factors. Potential reasons for the lack of success of companion diagnostics that determine the overall risk of natalizumab-associated PML are discussed.
Media convergence
Authors: Mishra Smeeta
Published: May 2014

This article explores the views of Indian journalists on media convergence in a context where the print media is thriving and Internet penetration is relatively low. Findings show that many journalists do not view convergence as a matter of survival as the print media remains robust. The lack of a strong revenue model for multimedia journalism also contributes to dampening enthusiasm about convergence among many journalists. However, forms of tactical convergence such as cross promotion of content among outlets owned by the same media conglomerate are becoming common. Coordination among journalists working on multiple platforms is more visible in the case of breaking news events than other areas. The desirability of multi-platform delivery by the same reporter is strongly contested among Indian journalists. Overall, journalists working at smaller organizations are more supportive of convergence than those working for large ones with an established reputation in a particular medium. Finally, the study indicates that any effort at introducing convergence in Indian newsrooms must take into account the strength and reach of the print media in the country.
Proper handling of bullet evidence in trauma patients
Authors: Masteller Michael A , Prahlow Adam , Walsh Mark M , Thomas Scott G , Wolfenbarger Ray , Prahlow Joseph A
Published: May 2014

Gunshot-related trauma varies in frequency around the world; however, every trauma center should be prepared for and capable of dealing with patients who have sustained gunshot injuries. While the appropriate medical and surgical treatment of gunshot injuries is the goal of the trauma center, many gunshot cases involve situations that have various criminal and/or other forensic concerns. As such, healthcare providers in trauma centers need to be aware of important evidence issues related to gunshot injuries. This paper provides basic information and guidelines for healthcare providers regarding the appropriate identification, documentation, collection, and preservation of forensic evidence in gunshot injury cases.
Management of a Patient With Faciocervical Burns and Inhalational Injury Due to Hydrofluoric Acid Exposure
Authors: Yuanhai Zhang , Xingang Wang , Liangfang Ni , Chunmao Han
Published: May 2014

Hydrofluoric acid, a highly dangerous substance, can cause tissue damage and systemic toxicity by its unique mechanisms. Many cases of severe faciocervical burns due to hydrofluoric acid exposure are lethal. Herein, we present a case of 37-year-old man who suffered from hydrofluoric acid burns to his face, anterior neck, lips, and nasal cavity. On admission, this patient coughed with much sputum, and the chest auscultation detected rough breath sounds, wheezes, and very weak heart sounds, indicating possible inhalation injury. This case highlights the extreme complexity of managing this kind of injury. Timely and accurate wound treatment and respiratory tract care, as well as active systematic support treatment, played vital roles in the management of this patient.
Moderation Effect of Job Involvement on the Relationship Between Organizational Commitment and Job Satisfaction
Authors: Tiwari Vivek , Singh S. K.
Published: May 2014

The present study investigates the impact that Job Satisfaction (JS) has on the Organizational Commitment (OC) level of industrial workers and also finds out whether Job Involvement (JI) moderates the relationship between JS and OC. The study has been conducted on 600 employees belonging to different departments of Diesel Locomotive Works (DLW), which is one of the public sector giants of India. Relationship between JS and OC has been established with the help of a 2 × 2 factorial design, and moderation effect of JI on the relationship between JS and OC has been checked with the help of hierarchical multiple regression analysis. The results of the investigation have come out with the findings that OC is positively related to JS. Also, JI does moderate the relationship between JS and OC but in a negative way, and the impact has been found to be weak.
Mainstreaming cold spray – push for applications
Authors: Champagne V. K. , Helfritch D. J.
Published: May 2014

Modern cold spray, first implemented 30 years ago, has since expanded rapidly in system designs and applications. While initially considered to be a method to deposit a ductile metal coating onto another metal, subsequent innovations in design and use have allowed new applications to areas as diverse as medical and electronics. This paper describes some new methods and applications that are currently being developed. Twenty-four new applications are presented, chosen to represent the diversity of actual and potential uses of cold spray technology.
Studies on electroless nickel boride coating on boron carbide particles
Authors: Deepa J. P. , Rajan T. P. D. , Pavithran C. , Pai B. C.
Published: May 2014

Ni–B alloy deposits were successfully formed over alkali surface treated boron carbide by electroless technique and the effects of processing parameters such as reduction bath pH, temperature and post-heat treatment were investigated. Microstructural studies show remarkable changes in structural morphology from mesh-like structure to platelet type Ni–B coating. The main Ni–B phases observed were NiB, Ni2B, Ni3B and Ni4B3. An effective Ni–B alloy coating with better surface characteristics was formed at pH 8 under 75°C reaction bath temperature in the presence of bath stabiliser. The post-heat treatment of Ni–B coated particles under varying bath reaction temperatures at 400°C showed remarkable Ni–B phase transformation from metastable NiB and Ni2B to stable crystalline Ni3B phase. The NiB coated particle shows lower particle–matrix interfacial reaction, better wettability and enhanced dispersion in aluminium composites compared to uncoated particles.
Templated growth of PFO-DBT nanorod bundles by spin coating: effect of spin coating rate on the morphological, structural, and optical properties
Authors: Fakir Muhamad Saipul , Supangat Azzuliani , Sulaiman Khaulah
Published: May 2014

In this study, the spin coating of template-assisted method is used to synthesize poly[2,7-(9,9-dioctylfluorene)-alt-4,7-bis(thiophen-2-yl)benzo-2,1,3-thiadiazole] (PFO-DBT) nanorod bundles. The morphological, structural, and optical properties of PFO-DBT nanorod bundles are enhanced by varying the spin coating rate (100, 500, and 1,000 rpm) of the common spin coater. The denser morphological distributions of PFO-DBT nanorod bundles are favorably yielded at the low spin coating rate of 100 rpm, while at high spin coating rate, it is shown otherwise. The auspicious morphologies of highly dense PFO-DBT nanorod bundles are supported by the augmented absorption and photoluminescence.
Persistence properties of solutions to the dissipative 2-component Degasperis-Procesi system
Authors: Ming Sen , Yang Han , Yong Ls
Published: May 2014

The persistence properties of solutions to the dissipative 2-component Degasperis-Procesi system are investigated. We find that if the initial data with their derivatives of the system exponentially decay at infinity, then the corresponding solution also exponentially decays at infinity.

MSC:35G25, 35L15, 35Q58.
Employment of the Triple Helix concept for development of regenerative medicine applications based on human pluripotent stem cells
Authors: Sartipy Peter , Björquist Petter
Published: May 2014

Using human pluripotent stem cells as a source to generate differentiated progenies for regenerative medicine applications has attracted substantial interest during recent years. Having the capability to produce large quantities of human cells that can replace damaged tissue due to disease or injury opens novel avenues for relieving symptoms and also potentially offers cures for many severe human diseases. Although tremendous advancements have been made, there is still much research and development left before human pluripotent stem cell derived products can be made available for cell therapy applications. In order to speed up the development processes, we argue strongly in favor of cross‐disciplinary collaborative efforts which have many advantages, especially in a relatively new field such as regenerative medicine based on human pluripotent stem cells. In this review, we aim to illustrate how some of the hurdles for bringing human pluripotent stem cell derivatives from bench‐to‐bed can be effectively addressed through the establishment of collaborative programs involving academic institutions, biotech industries, and pharmaceutical companies. By taking advantage of the strengths from each organization, innovation and productivity can be maximized from a resource perspective and thus, the chances of successfully bringing novel regenerative medicine treatment options to patients increase.
Influence of alpine mountain climate of Bavaria on patients with atopic diseases: studies at the Environmental Research Station Schneefernerhaus (UFS ‐ Zugspitze) – a pilot study
Authors: Eberlein Bernadette , Huss‐Marp Johannes , Pfab Florian , Fischer Rainald , Franz Regina , Schlich Michele , Leibl Maria , Allertseder Veronika , Liptak Jarmila , Kriegisch Marie , Hennico Romain , Latotski Julia , Ebner von Eschenbach Cordula , Darsow Ulf , Buters Jeroen , Behrendt Heidrun , Huber Rudolf , Ring Johannes
Published: May 2014

Mountain and maritime climate therapy takes advantage of specific climatic conditions to treat chronic allergic diseases. It was the aim of the study to investigate effects of a 5 day sojourn on atopic diseases at the highest German mountain. In this pilot study 18 patients with grass pollen‐induced rhinoconjunctivitis, atopic ezcema or asthma and 11 non‐allergic controls were included. Skin physiology parameters, changes of the respiratory and nasal functions, subjective symptoms and blood parameters were measured during a 5‐day observation period in the Environmental Research Station Schneefernerhaus (UFS) at the moderate altitude mountain region (Zugspitze; 2650 m alt.) compared to a low altitude area (Munich; 519 m alt.). Several of the skin physiology parameters changed significantly during the observation period (decrease of skin hydration, increase of skin smoothness, skin roughness, skin scaliness and pH‐value). In patients with atopic eczema, the SCORAD (Severity Scoring of Atopic Dermatitis) and the scores of the DIELH (Deutsches Instrument zur Erfassung der Lebensqualität bei Hauterkrankungen) did not change significantly. Histamine induced itch decreased significantly. Parameters of nasal function did not change significantly. Several lung parameters showed a slight, but statistically significant improvement (forced expiratory volume in one second/volume capacity [FEV1/VC], peak expiratory flow [PEF], maximum expiratory flow at 50% of vital capacity [MEF 50], maximal mid‐expiratory flow between 25% and 75% of vital capacity [MMFEF 25/75]), whereas the vital capacity (VC) decreased significantly. ECP (eosinophil cationic protein) in the serum and parameters of blood count changed significantly. These results show that the benefit of a moderate altitude mountain climate sojourn over a period of 5 days differs in depending on the atopic disease. Especially asthma parameters and itching of the skin improved. It would be interesting to assess the parameters during longer observation periods in alpine climate.
Genetic and pharmacologic inhibition of Tpl2 kinase is protective in a mouse model of ventilator-induced lung injury
Authors: Kaniaris Evangelos , Vaporidi Katerina , Vergadi Eleni , Theodorakis Emmanuel E , Kondili Eumorfia , Lagoudaki Eleni , Tsatsanis Christos , Georgopoulos Dimitris
Published: May 2014

Background

Mechanical stress induced by injurious ventilation leads to pro-inflammatory cytokine production and lung injury. The extracellular-signal-regulated-kinase, ERK1/2, participates in the signaling pathways activated upon mechanical stress in the lungs to promote the inflammatory response. Tumor progression locus 2 (Tpl2) is a MAP3kinase that activates ERK1/2 upon cytokine or TLR signaling, to induce pro-inflammatory cytokine production. The role of Tpl2 in lung inflammation, and specifically in the one caused by mechanical stress has not been investigated. The aim of the study was to examine if genetic or pharmacologic inhibition of Tpl2 could ameliorate ventilator-induced lung injury.

Methods

Adult male wild-type and Tpl2-deficient mice were ventilated with normal or high tidal volume for 4 h. Additional wild-type mice were treated with a Tpl2 inhibitor either before or 30 min after initiation of high tidal ventilation. Non-ventilated mice of both genotypes served as controls. The development of lung injury was evaluated by measuring lung mechanics, arterial blood gases, concentrations of proteins, IL-6, and MIP-2 in bronchoalveolar lavage fluid (BALF) and by lung histology. Data were compared by Kruskal-Wallis non-parametric test and significance was defined as p < 0.05.

Results

Mechanical ventilation with normal tidal volume induced a mild increase of IL-6 in BALF in both strains. High tidal volume ventilation induced lung injury in wild-type mice, characterized by decreased lung compliance, increased concentrations of proteins, IL-6 and MIP-2 in BALF, and inflammatory cell infiltration on histology. All indices of lung injury were ameliorated in Tpl2-deficient mice. Wild-type mice treated with the Tpl2 inhibitor, either prior of after the initiation of high tidal volume ventilation were protected from the development of lung injury, as indicated by preserved lung compliance and lower BALF concentrations of proteins and IL-6, than similarly ventilated, untreated wild-type mice.

Conclusions

Genetic and pharmacologic inhibition of Tpl2 is protective in a mouse model of ventilator-induced lung injury, ameliorating both high-permeability pulmonary edema and lung inflammation.
Polarity gene alterations in pure invasive micropapillary carcinomas of the breast
Authors: Gruel Nadège , Benhamo Vanessa , Bhalshankar Jaydutt , Popova Tatiana , Fréneaux Paul , Arnould Laurent , Mariani Odette , Stern Marc-Henri , Raynal Virginie , Sastre-Garau Xavier , Rouzier Roman , Delattre Olivier , Vincent-Salomon Anne
Published: May 2014

Introduction

Pure invasive micropapillary carcinoma (IMPC) is a special type of breast carcinoma characterised by clusters of cells presenting polarity abnormalities. The biological alterations underlying this pattern remain unknown.

Methods

Pangenomic analysis (n = 39), TP53 (n = 43) and PIK3CA (n = 41) sequencing in a series of IMPCs were performed. A subset of cases was also analysed with whole-exome sequencing (n = 4) and RNA sequencing (n = 6). Copy number variation profiles were compared with those of oestrogen receptors and grade-matched invasive ductal carcinomas (IDCs) of no special type.

Results

Unsupervised analysis of genomic data distinguished two IMPC subsets: one (Sawtooth/8/16) exhibited a significant increase in 16p gains (71%), and the other (Firestorm/Amplifier) was characterised by a high frequency of 8q (35%), 17q (20% to 46%) and 20q (23% to 30%) amplifications and 17p loss (74%). TP53 mutations (10%) were more frequently identified in the amplifier subset, and PIK3CA mutations (4%) were detected in both subsets. Compared to IDC, IMPC exhibited specific loss of the 6q16-q22 region (45%), which is associated with downregulation of FOXO3 and SEC63 gene expression. SEC63 and FOXO3 missense mutations were identified in one case each (2%). Whole-exome sequencing combined with RNA sequencing of IMPC allowed us to identify somatic mutations in genes involved in polarity, DNAH9 and FMN2 (8% and 2%, respectively) or ciliogenesis, BBS12 and BBS9 (2% each) or genes coding for endoplasmic reticulum protein, HSP90B1 and SPTLC3 (2% each) and cytoskeleton, UBR4 and PTPN21 (2% each), regardless of the genomic subset. The intracellular biological function of the mutated genes identified by gene ontology analysis suggests a driving role in the clinicopathological characteristics of IMPC.

Conclusion

In our comprehensive molecular analysis of IMPC, we identified numerous genomic alterations without any recurrent fusion genes. Recurrent somatic mutations of genes participating in cellular polarity and shape suggest that they, together with other biological alterations (such as epigenetic modifications and stromal alterations), could contribute to the morphological pattern of IMPC. Though none of the individual abnormalities demonstrated specificity for IMPC, whether their combination in IMPC may have a cumulative effect that drives the abnormal polarity of IMPC needs to be examined further with in vitro experiments.
Using a pseudo-steady-state flow equation and 4D seismic traveltime shifts for estimation of pressure and saturation changes
Authors: Witsker Sandra Ok Soon , Landrø Martin , Avseth Per
Published: May 2014

Pressure and saturation changes cause a change in seismic P-wave velocity resulting in a shift in 4D traveltime. A discrimination between both effects is important to enhance reservoir management decisions. We explored the possibility of linking the fields of reservoir engineering and 4D seismic. A simple inversion scheme based on a reservoir engineering flow equation for pore pressure predictions combined with the Hertz-Mindlin and Gassmann rock-physics models to discriminate pressure and saturation effects from 4D time shifts was presented. To account for no-flow reservoir boundaries, the pseudo-steady-state flow equation giving the pressure distribution was extended with a superpositioning method. During the inversion, three parameters were determined by a nonlinear, least-squares fitting method: the thickness of the hydrocarbon column, the pressure at the well position, and its decay rate away from the well. We successfully tested our approach on a synthetic and a field data case, where the [Formula: see text] injection well at the Snøhvit field, Norway, served as a good example to demonstrate our method. We observed a good correlation between simulation and inversion in our synthetic study. Our theory was limited to homogeneous reservoir conditions and produces spatially low frequent outputs. To apply the model in complex fields, such as at Snøhvit, we introduced a spatially varying Mindlin-exponent over the field and used the theory as an heuristic model assuming that a variation of the Mindlin-exponent takes a change in pressure sensitivity into account. This assumption provided the possibility to indirectly include heterogeneities in grain sorting and porosity variation and improved the model significantly. We see the advantage of our method in its fast and direct implementation to study first-order effects of pressure and saturation behavior on time-lapse seismic data using a simple inversion algorithm instead of computationally intensive simulations.
BAG6 regulates the quality control of a polytopic ERAD substrate
Authors: Payapilly Aishwarya , High Stephen
Published: May 2014

BAG6 participates in protein quality control and we address its role during endoplasmic reticulum associated degradation (ERAD) using the polytopic membrane protein OpD. Both BAG6 knockdown and BAG6 overexpression delay OpD degradation, however, our data suggest these two perturbations are mechanistically distinct. Hence, BAG6 knockdown correlates with reduced OpD polyubiquitination, yet BAG6 overexpression increases polyubiquitinated OpD. The UBL- and BAG-domains of exogenous BAG6 are dispensable for OpD stabilisation and enhanced levels of polyubiquitinated OpD. Thus, whilst endogenous BAG6 normally promotes OpD degradation, exogenous BAG6 expression delays it; we speculate that over expressed BAG6 subunits may associate with the endogenous BAG6 complex, resulting in a dominant negative effect that inhibits its function. Interestingly cellular levels of BAG6 also correlate with total steady state polyubiquitination, with Rpn10 overexpression showing a similar effect. These findings suggest that perturbations to the levels of ubiquitin binding proteins can impact upon cellular ubiquitin homeostasis. We propose that exogenous BAG6 perturbs the function of the BAG6 complex at a stage beyond substrate recognition and polyubiquitination, most likely the BAG6-dependent delivery of OpD to the proteasome.
The extent of error-prone replication-restart by homologous recombination is controlled by Exo1 and checkpoint proteins
Authors: Tsang Ellen , Miyabe Izumi , Iraqui Ismail , Zheng Jiping , Lambert Sarah A. E. , Carr Antony M.
Published: May 2014

Genetic instability, a hallmark of cancer, can occur when the replication machinery encounters a barrier. The intra-S phase checkpoint maintains stalled replication forks in a replication-competent configuration by phosphorylating replisome components and DNA repair proteins to prevent forks from catastrophically collapsing. Here we report a novel Chk1- and Cds1Chk2-independent function for Rad3ATR, the core S. pombe checkpoint sensor kinase: Rad3ATR regulates the association of recombination factors with collapsed forks thus limiting their genetic instability. We further reveal antagonistic roles for Rad3ATR and the 9-1-1 clamp: Rad3ATR restrains MRN- and Exo1-dependent resection while the 9-1-1 complex promotes Exo1 activity. Interestingly the MRN complex, but not its nuclease activity, promotes resection and the subsequent association of recombination factors at collapsed forks. The biological significance of this regulation is revealed by the observation that Rad3ATR prevents Exo1-dependent genome instability upstream a collapsed fork without affecting the efficiency of recombination-mediated replication-restart. We propose the interplay between Rad3ATR and the 9-1-1 clamp functions to fine-tune the balance between the need for recovery of replication via recombination and the risk of increased genome instability.
Sources and Resources
Authors: Howe Cathy
Published: May 2014

This paper reports on the first UK Knowledge Mobilisation Forum, held in mixed reality on 3–4 February 2014. This forum brought together 70 delegates from 15 sectors under the theme of ‘making connections matter’. Highly participatory and academically credible, the forum combined a form of ‘open space’ participation with presentations from respected speakers on topics as diverse as design, fiction writing and community-university coproduction. The forum has been described as ‘a hallmark event’. It was rated as excellent or good by 85% of attendees, and there is demand for it to become an annual event. It will be held next in Edinburgh in 2015.
Pretreatment MicroRNA Level and Outcome in Sorafenib-treated Hepatocellular Carcinoma
Authors: Gyöngyösi Benedek , Végh Éva , Járay Balázs , Székely Eszter , Fassan Matteo , Bodoky György , Schaff Zsuzsa , Kiss András
Published: May 2014

Sorafenib represents the first effective targeted therapy for advanced stage hepatocellular carcinoma (HCC); however, adequate patient stratification regarding sorafenib-responsiveness is still missing. Our aim was to analyse the association between the pretreatment microRNA profile of HCC and patient survival under sorafenib treatment. Total RNA was extracted from diagnostic fine-needle aspiration biopsy (FNAB) cytological smears of 20 advanced stage HCC patients collected between June 2008 and July 2012. All patients underwent sorafenib administration after FNA. Clinicopathological and survival data were recorded. Fourteen frequently deregulated miRNAs in HCC (miR-17-5p, miR-18a, miR-21, miR-34a, miR-122, miR-195, miR-210, miR-214, miR-221, miR-222, miR-223, miR-224, miR-140, miR-328) were tested by qRT-PCR. NormFinder software was used to select proper miR (mir-140) as a reference. Satisfactory amount of total RNA was obtained from all the considered samples (mean 10.8 ± 9.3 µg, range 0.2–32.2 µg). Among the analysed miRNAs, high miR-214 expression was associated with smaller tumor size ( p=0.019), whereas high miR-17-5p expression correlated with better Eastern Cooperative Oncology Group performance status ( p=0.003). The survival analysis revealed that high miR-224 expression was associated with increased progression-free and overall survival (PFS p=0.029; OS p=0.012). Pretreatment microRNA profiling, especially miR-224 expression, might serve as an ancillary tool for the better assessment of expected survival rates for patients under sorafenib treatment.
The Whitewash Committee of 1914: The Knights of Columbus, Freemasonry and anti-Catholicism in California
Authors: Kendall Adam G.
Published: May 2014

This essay explores and contextualizes the rising anti-Catholic sentiment during the 1910s found within American fraternal societies, particularly Freemasonry, in addition to its condemnation by the Catholic Church. The study is illustrated by the public controversy involving the so-called Masonic Whitewash Committee of 1914–15, which included prominent grand officers of the California Grand Lodge (some of whom were later involved in the 1921 California Ku Klux Klan controversy) that investigated an alleged oath of the Knights of Columbus entered into the 1913 United States Congressional Record. The oath was determined by this unofficial committee to be fallacious (as had countless others, including Congress), and its conclusion set off a nationwide controversy within the fraternal and public press as a defense for what was believed to be Catholic infiltration of institutions at all levels of American society. The California Grand Lodge joined in the condemnation, claiming the committee’s use of Masonic titles gave the false impression that it was officially sanctioned by the governing body. To make matters worse for the committee, their report was also admitted into the 1915 Congressional Record by Congressman William Kettner, the then Grand Marshal for the Grand Lodge.

Allegations of favoring Catholic political candidates, along with the ‘whitewashing’ of the committee’s actions via fraternal politicking and character assassination were played out in the era’s infamous anti-Catholic newspapers. The essay seeks to demonstrate that this little-known conflict is in fact one of many footnotes that characterized anti-Catholic nativism and hyper-patriotism during the 1910s, as well as highlighting the Catholic defense of their own contribution to the American way of life. This paper also illustrates the distinct and important role fraternal organizations and their members played as arbiters and, sometimes, challengers of social trends.
Attention must be paid: Andy Warhol, John Cage and Gertrude Stein
Authors: Powers Edward D.
Published: May 2014

This essay traces the impact of Gertrude Stein’s signature strategies of repetition with a difference and of divided, yet mutually reinforcing, attention, which she called ‘insistence’ and ‘genius’, respectively, on Pop artist Andy Warhol and, among his colleagues into the early 1960s, on avant-garde composer John Cage, most notably. By challenging the conventional ascription of the artist’s affective or psychological depth to the artwork’s surface, Stein’s twin concepts of insistence and genius resisted not merely what cultural critics typically nutshell as the ‘depth model’ but even its heteronormativity and its corollary interpretation of queerness as a symptom. For both Stein and Warhol, moreover, at the root of this pair of techniques was the impact of automatism, which Stein only experimented with while in college, yet Warhol actually practiced from the advent of his Pop art in 1961. By focusing on how Warhol’s reproductive techniques embodied Stein’s view of automatism as a gestural practice – one that is neither reducible to writing nor, otherwise, a significant vehicle for linguistic meaning – I aim to inscribe what is routinely dismissed as Warhol’s accidental formalism within a discourse not of artistic indifference but, to the contrary, of queer resistance.
On Sampled Time and Intermedial Space: Postproduction, Video Installation and Christian Marclay’s The Clock
Authors: Bouman Margot
Published: May 2014

Like other postproduction work by contemporary artists and purveyors of popular culture, the videos of artist, musician and composer Christian Marclay use accumulations of cultural data extracted from thousands of films (and television shows) as raw material for the diegesis. What sets Marclay’s installation The Clock (2010) apart from other installations and films in this category is the interrelationship established between its postproduction aesthetic and its specific display conditions. By matching on-screen time with actual time in a carefully designed exhibition context, The Clock simultaneously reifies the psychosomatic transformation of the moviegoer identified by Roland Barthes and dismantles the hermetic nature of the cinematic apparatus. In so doing, Marclay mobilizes latent aspects of video installation to produce new phenomenological experiences and reorganize the relationship between aesthetics and everyday life.