bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia
Authors: Ataga Kenneth I. , Smith Wally R. , De Castro Laura M. , Swerdlow Paul , Saunthararajah Yogen , Castro Oswaldo , Vichinsky Elliot , Kutlar Abdullah , Orringer Eugene P. , Rigdon Greg C. , Stocker Jonathan W. 
Published: January 2008

AbstractSenicapoc, a novel Gardos channel inhibitor, limits solute and water loss, thereby preserving sickle red blood cell (RBC) hydration. Because hemoglobin S polymerization is profoundly influenced by intracellular hemoglobin concentration, senicapoc could improve sickle RBC survival. In a 12-week, multicenter, phase 2, randomized, double-blind, dose-finding study, we evaluated senicapoc's safety and its effect on hemoglobin level and markers of RBC hemolysis in sickle cell anemia patients. The patients were randomized into 3 treatment arms: placebo; low-dose (6 mg/day) senicapoc; and high-dose (10 mg/day) senicapoc. For the primary efficacy end point (change in hemoglobin level from baseline), the mean response to high-dose senicapoc treatment exceeded placebo (6.8 g/L [0.68 g/dL] vs 0.1 g/L [0.01 g/dL], P < .001). Treatment with high-dose senicapoc also produced significant decreases in such secondary end points as percentage of dense RBCs (−2.41 vs −0.08, P < .001); reticulocytes (−4.12 vs −0.46, P < .001); lactate dehydrogenase (−121 U/L vs −15 U/L, P = .002); and indirect bilirubin (−1.18 mg/dL vs 0.12 mg/dL, P < .001). Finally, senicapoc was safe and well tolerated. The increased hemoglobin concentration and concomitant decrease in the total number of reticulocytes and various markers of RBC destruction following senicapoc administration suggests a possible increase in the survival of sickle RBCs. This study is registered at http://clinicaltrials.gov as NCT00040677.
Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components
Authors: Alici Evren , Sutlu Tolga , Björkstrand Bo , Gilljam Mari , Stellan Birgitta , Nahi Hareth , Quezada Hernan Concha , Gahrton Gösta , Ljunggren Hans-Gustaf , Dilber M. Sirac 
Published: January 2008

AbstractMultiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied. Here, we explored the possibility of expanding NK cells from the peripheral blood of 7 newly diagnosed, untreated MM patients, using good manufacturing practice (GMP)–compliant components. After 20 days of culture, the number of NK cells from these patients had expanded on average 1600-fold. Moreover, expanded NK cells showed significant cytotoxicity against primary autologous MM cells, yet retained their tolerance against nonmalignant cells. Based on these findings, we propose that autologous NK cells expanded ex vivo deserve further attention as a possible new treatment modality for MM.
Differential expression of wild-type and mutant NMMHC-IIA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders
Authors: Kunishima Shinji , Hamaguchi Motohiro , Saito Hidehiko 
Published: January 2008

AbstractMYH9 disorders such as May-Hegglin anomaly are characterized by macrothrombocytopenia and cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, the gene for nonmuscle myosin heavy chain-IIA (NMMHC-IIA). We examined the expression of mutant NMMHC-IIA polypeptide in peripheral blood cells from patients with MYH9 5770delG and 5818delG mutations. A specific antibody to mutant NMMHC-IIA (NT629) was raised against the abnormal carboxyl-terminal residues generated by 5818delG. NT629 reacted to recombinant 5818delG NMMHC-IIA but not to wild-type NMMHC-IIA, and did not recognize any cellular components of normal peripheral blood cells. Immunofluorescence and immunoblotting revealed that mutant NMMHC-IIA was present and sequestrated only in inclusion bodies within neutrophils, diffusely distributed throughout lymphocyte cytoplasm, sparsely localized on a diffuse cytoplasmic background in monocytes, and uniformly distributed at diminished levels only in large platelets. Mutant NMMHC-IIA did not translocate to lamellipodia in surface activated platelets. Wild-type NMMHC-IIA was homogeneously distributed among megakaryocytes derived from the peripheral blood CD34+ cells of patients, but coarse mutant NMMHC-IIA was heterogeneously scattered without abnormal aggregates in the cytoplasm. We show the differential expression of mutant NMMHC-IIA and postulate that cell-specific regulation mechanisms function in MYH9 disorders.
Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via Carma1 for NF-κB and MAPK activation to selectively control cytokine production
Authors: Gross Olaf , Grupp Christina , Steinberg Christian , Zimmermann Stephanie , Strasser Dominikus , Hannesschläger Nicole , Reindl Wolfgang , Jonsson Helena , Huo Hairong , Littman Dan R. , Peschel Christian , Yokoyama Wayne M. , Krug Anne , Ruland Jürgen 
Published: January 2008

AbstractNatural killer (NK) cells are innate immune cells that mediate resistance against viruses and tumors. They express multiple activating receptors that couple to immunoreceptor tyrosine-based activation motif (ITAM)–containing signaling chains for downstream cell activation. Ligation of activating NK-cell receptors induces NK-cell cytotoxicity and cytokine release. How these distinct events are selectively controlled is not well defined. Here we report the identification of a specific signaling pathway that operates downstream of the ITAM-coupled NK-cell receptors NK1.1, Ly49D, Ly49H, and NKG2D. Using primary NK cells from Bcl10−/−, Malt1−/−, Carma1−/−, and Card9−/− mice, we demonstrate a key role for Bcl10 signalosomes in the activation of canonical NF-κB signaling as well as JNK and p38 MAPK upon NK-cell triggering. Bcl10 directly cooperates with Malt1 and depends on Carma1 (Card11) but not on Card9 for NK-cell activation. These Bcl10-dependent cascades selectively control cytokine and chemokine production but do not affect NK-cell differentiation or killing. Thus, we identify a molecular basis for the segregation of NK-cell receptor–induced signals for cytokine release and target cell killing and extend the previously recognized roles for CARD-protein/Bcl10/Malt1 complexes in ITAM receptor signaling in innate and adaptive immune cells.
Ly49 C/I-dependent NKT cell-derived IL-10 is required for corneal graft survival and peripheral tolerance
Authors: Watte C M , Nakamura T , Lau C H , Ortaldo J R , Stein-Streilein J 
Published: January 2008

AbstractSimilar to their activity on NK cells, Ly49 molecules play a pivotal role in influencing how NKT cells respond. It is known that Ly49 C/I is an inhibitory receptor capable of down-modulating proliferation, IFN-γ response, and cytotoxic activity in cells that express it. In a model of peripheral tolerance induced via the eye, we observed that Ly49 C/I-positive, invariant NKT cells were required. To test if the NK inhibitory receptor functionally contributed to tolerance development, we used blocking antibody, in vivo and in vitro, to interfere with the development of antigen-specific suppression. A result of blocking ligation of Ly49 C/I inhibitory receptor prevented NKT cell production of IL-10 and the subsequent development of tolerance. Ly49 C/I-blocking antibodies also prevented corneal graft survival, a phenomenon dependent on eye-induced tolerance. Furthermore, in the presence of TCR stimulation, cross-linking of Ly49 C/I on CD4+ NKT cells stimulated an increase in IL-10 mRNA and a decrease in IFN-γ. The concept of Ly49 inhibitory receptors regulating immune reactivity to self by regulating immune activity of individual cells is thus expanded to include a role for the inhibitory receptors in the more global process of peripheral tolerance to foreign antigens.
Barriers to the provision of needle-exchange services: a qualitative study in community pharmacies
Authors: Hall Susan , Matheson Catriona 
Published: January 2008

Abstract

Objective
To investigate the attitudes of pharmacists to the provision of needle-exchange services (NES) at community pharmacies and, if barriers exist, explore means by which they may be overcome.

Setting
Twenty-one community pharmacies across Grampian in North East Scotland during May and June 2005.

Method
Semi-structured face-to-face interviews conducted with 24 pharmacists.

Key findings
Newly identified barriers included the negative influence of security staff, a local policy against NES provision and a lack of awareness of other services available for drug users.

Conclusion
Training packages for all health professionals working with drug users and awareness training for security staff are required if the identified barriers are to be overcome. ‘Hands-on’ training and experience of NES for pharmacists and their staff should be available. Suggestions made by pharmacists for NES provision in general practitioner surgeries or community hospitals and the development of automated services should be considered.
Development, implementation and evaluation of a pilot project to deliver interventions on alcohol issues in community pharmacies
Authors: Fitzgerald Niamh , McCaig Dorothy J , Watson Hazel , Thomson David , Stewart Derek C 
Published: January 2008

Abstract

Objective
The aim was to evaluate the feasibility and acceptability of the provision of brief interventions on alcohol misuse in community pharmacies. The objectives were to: train community pharmacists to initiate discussion of alcohol consumption with targeted pharmacy clients and screen, intervene or refer as appropriate; and to explore with pharmacists and clients the feasibility, acceptability and perceived value of screening and delivering the intervention.

Setting
Eight community pharmacies in Greater Glasgow.

Method
After a two-day training course for pharmacists (n = 9) and one day for pharmacy assistants (n = 13), the eight pharmacies recruited clients over 3 months. Standardised protocols were prepared to screen clients for hazardous or harmful drinking using the Fast Alcohol Screening Tool (FAST) and to guide the intervention. Clients were recruited from specific target groups and via posters highlighting the service. Following completion of the recruitment phase, pharmacists and clients were followed up by the research team, using a combination of focus groups and semi-structured telephone interviews.

Key findings
During the study period 70 clients were recruited, 30 screened as drinking hazardously (42.9%) and 7 (10%) screened positive for harmful drinking. Interventions commonly included explanation of sensible drinking and units in clients' preferred drinks (n = 33), feedback on screening and risks to health (n = 27) and discussion of pros and cons of current drinking pattern and link with presenting issue (n = 23). Of the 40 clients agreeing to be followed up, 19 could be contacted and most were generally positive about the experience. On follow-up the pharmacists were positive and felt the project worthwhile and, importantly, noted no strong negative reactions from clients.

Conclusion
This project has been successful in training community pharmacists to discuss alcohol with 70 clients. Further work is required to test the generalisability of our findings and to measure the impact on alcohol consumption.
Nanoscale surface chemistry in self- and directed-assembly of organic molecules on solid surfaces and synthesis of nanostructured organic architectures
Authors: Tao Feng 
Published: January 2008

Abstract
This article briefly reviews the interplay of weak noncovalent interactions involved in the formation of self-assembled monolayers of organic molecules and the strong chemical binding in directed-assembly of organic molecules on solid surfaces. For a self-assembled monolayer, each molecule involves at least three categories of weak interactions, including molecule-substrate interactions, molecule-molecule interactions in a lamella, and molecule-molecule interactions between two adjacent lamellae. Basically, molecule-substrate interactions play a major role in determining molecular configuration. Molecule-molecule interactions, particularly the interactions of molecular ending functional groups between two adjacent lamellae, such as hydrogen bonds, play a dominant role in determining the molecular packing pattern in a monolayer. These weak interactions may induce or influence molecular chirality. This understanding at the atomic scale allows us to design 2D nanostructured organic materials via precisely manipulating these weak noncovalent interactions. Compared to the self-assembled monolayer formed via weak noncovalent interactions, the structure of directed-assembled monolayer/multilayers formed through strong chemical bonds is significantly dependent on the geometric arrangement and reactivity of active sites on the solid surface. In contrast to the significant role of weak intermolecular interactions in determining molecular packing in a self-assembled monolayer, strong chemical binding between molecules and reactive sites of a substrate plays a major role in determining the molecular packing pattern in a directed-assembly monolayer. Controllable chemical attachment between organic functional groups and reactive sites of the solid surface is crucial for the formation of a highly oriented organic monolayer and the following multilayer.
My Career Chapter: Guidance Counsellors' Appraisal of Its Suitability for Adolescents
Authors: McIlveen Peter , Patton Wendy , Hoare P. Nancey 
Published: January 2008

AbstractThis article presents an investigation into the properties of a new narrative technique for career assessment and counselling, ‘My Career Chapter: A Dialogical Autobiography’. This technique is used to facilitate clients' construction of a meaningful career-related autobiography. Previous research indicates the usefulness of My Career Chapter for adult clients and its alignment with recommendations for the development and application of qualitative assessment and counselling techniques. This study specifically commences research into the technique's applicability for adolescents. A focus group, comprised of guidance counselling professionals whose work primarily pertained to the needs of adolescents, found that there is potential to develop a version of My Career Chapter that is suitable for adolescents.
Mesenchymal Stem Cells Effectively Deliver an Oncolytic Adenovirus to Intracranial Glioma
Authors: Sonabend Adam M. , Ulasov Ilya V. , Tyler Matthew A. , Rivera Angel A. , Mathis James M. , Lesniak Maciej S. 
Published: January 2008

AbstractGene therapy represents a promising treatment alternative for patients with malignant gliomas. Nevertheless, in the setting of these highly infiltrative tumors, transgene delivery remains a challenge. Indeed, viral vehicles tested in clinical trials often target only those tumor cells that are adjacent to the injection site. In this study, we examined the feasibility of using human mesenchymal stem cells (hMSC) to deliver a replication-competent oncolytic adenovirus (CRAd) in a model of intracranial malignant glioma. To do so, CRAds with a chimeric 5/3 fiber or RGD backbone with or without CXCR4 promoter driving E1A were examined with respect to replication and toxicity in hMSC, human astrocytes, and the human glioma cell line U87MG by quantitative polymerase chain reaction and membrane integrity assay. CRAd delivery by virus-loaded hMSC was then evaluated in vitro and in an in vivo model of mice bearing intracranial U87MG xenografts. Our results show that hMSC are effectively infected by CRAds that use the CXCR4 promoter. CRAd-CXCR4-RGD had the highest replication, followed by CRAd-CXCR4–5/3, in hMSC, with comparable levels of toxicity. In U87MG tumor cells, CRAd-CXCR4–5/3 showed the highest replication and toxicity. Virus-loaded hMSC effectively migrated in vitro and released CRAds that infected U87MG glioma cells. When injected away from the tumor site in vivo, hMSC migrated to the tumor and delivered 46-fold more viral copies than injection of CRAd-CXCR4–5/3 alone. Taken together, these results indicate that hMSC migrate and deliver CRAd to distant glioma cells. This delivery strategy should be explored further, as it could improve the outcome of oncolytic virotherapy for glioma.Disclosure of potential conflicts of interest is found at the end of this article.
Notch Signaling Through Jagged-1 Is Necessary to Initiate Chondrogenesis in Human Bone Marrow Stromal Cells but Must Be Switched off to Complete Chondrogenesis
Authors: Oldershaw Rachel A. , Tew Simon R. , Russell Amanda M. , Meade Kate , Hawkins Robert , McKay Tristan R. , Brennan Keith R. , Hardingham Timothy E. 
Published: January 2008

Abstract
We investigated Notch signaling during chondrogenesis in human bone marrow stromal cells (hMSC) in three-dimensional cell aggregate culture. Expression analysis of Notch pathway genes in 14-day chondrogenic cultures showed that the Notch ligand Jagged-1 (Jag-1) sharply increased in expression, peaking at day 2, and then declined. A Notch target gene, HEY-1, was also expressed, with a temporal profile that closely followed the expression of Jag-1, and this preceded the rise in type II collagen expression that characterized chondrogenesis. We demonstrated that the shut-down in Notch signaling was critical for full chondrogenesis, as adenoviral human Jag-1 transduction of hMSC, which caused continuous elevated expression of Jag-1 and sustained Notch signaling over 14 days, completely blocked chondrogenesis. In these cultures, there was inhibited production of extracellular matrix, and the gene expression of aggrecan and type II collagen were strongly suppressed; this may reflect the retention of a prechondrogenic state. The JAG-1-mediated Notch signaling was also shown to be necessary for chondrogenesis, as N-[N-(3,5-difluorophenacetyl-l-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) added to cultures on days 0–14 or just days 0–5 inhibited chondrogenesis, but DAPT added from day 5 did not. The results thus showed that Jag-1-mediated Notch signaling in hMSC was necessary to initiate chondrogenesis, but it must be switched off for chondrogenesis to proceed.
Disclosure of potential conflicts of interest is found at the end of this article.
Abnormal Pressure Detection and Wellbore Stability Evaluation in Carbonate Formations of East Sichuan, China
Authors: Qiuguo Li , Heliot Denis , Liangxiao Zhao , Yuxin Chen 
Published: January 2008

Abstract
Today although various methods have been developed for effective overpressure detection in sand/shale formations, pore pressure detection in carbonates is still a difficult problem. As the topic of this paper, we studied the structurally complex, fractured, gas-bearing carbonate formations in East Sichuan, China, to develop both pore pressure detection and wellbore stability evaluation methods to address current drilling problems. A pore pressure detection method based on relationships between the ratio of compressional and shear wave velocity (Vp/Vs) and vertical effective stress, Poisson's ratio and vertical effective stress was developed. The interpretation results obtained from this method, which are also an important parameter for wellbore stability evaluation, are good in comparison to measured pore pressure. As for wellbore stability evaluation, the methodologies implemented in a commercial software (ROXAN*) were applied to the log data of three wells in the field. Field mechanical data and rock mechanical properties test results on cores were used to develop correlations adapted to the specific situations of East Sichuan and to build a mechanical earth model. Rock strengths and geostresses were calibrated with laboratory measurements and FMI images to establish realistic mechanical parameters for the 3D linear poroelastic model. The comparison between the predicted shear/tensile failures under the mud weight used in the three wells and the borehole failure indications from FMI images provided reasonable calibration factors for rock strengths. Together with other wellbore stability managing techniques and tools, the stable mud weight ranges derived from the wellbore stability planning for a new well can optimize drilling efficiency greatly.
Subsea Downhole Motion Compensator: Field History, Enhancements, and the Next Generation
Authors: Durst Doug , Luke Mike 
Published: January 2008

Abstract
Since its successful debut in the North Sea, the Subsea Downhole Motion Compensator (SDMC™) has performed flawlessly in numerous milling runs in recent Latin America and North Sea projects. During one North Sea project, rig heave resulted in downtime during nonmilling runs. However, during milling runs in which the SDMC was used, there was no downtime spent waiting on weather (WOW), even when rig heave was as high as 13 ft.
Design enhancements to the SDMC include increased allowable operating loads, the addition of a landing ring, and an automatic downhole reset feature. Benefits to the operator and driller are as follows:
ability to safely sustain larger operating loads by accommodating greater rig heave longer operating life of high-wear internal parts, achieved by the sacrificial landing ring, which protects the wear bushing during planned or unplanned milling operations ease of handling, resulting in greater safety and more efficient operations overall rig-time savings
The next-generation SDMC offers the operator many additional capabilities and features, and improved operational performance. The tool is completely automatic: from the time that the SDMC makes initial downhole contact (landed position) on the wear bushing, it is never necessary to return it to the surface. The tool is fully resettable at the wellhead for each complete stroke of the piston, and it continually strokes new pipe through the tool without being retrieved from the wellhead. Virtually unlimited stands of drillpipe may be installed conventionally on the rig floor and fed through the rotary table and through the SDMC to perform unlimited exploration, drilling, and completion operations without any downtime spent WOW.
This paper introduces the operating principles and new design features of the SDMC. It also recaps case histories of successful jobs that resulted in cost savings and reduced downtime for the operator.
Research and Development of Advanced Coiled Tubing
Authors: Urayama T. , Yonezawa T. , Hamada M. , Sugino M. , Takabe H. , Ikeda A. 
Published: January 2008

Abstract
This paper describes Joint Industry Project (JIP) DEA107, in which BP, AMOCO, Eni S.p.A. Divisione Agip, Scottish Enterprise Operations and Japan National Oil Corporation (JNOC) participated. The objectives of this project were to investigate and report low cycle fatigue phenomena of coiled tubing, to present a rational fatigue life prediction model for coiled tubing and to develop an advanced coiled tubing which could be applied to coiled tubing drilling of deep wells. In this paper, the effect of various factors on cyclic bending performance of parent coiled tubing materials is predicted first in relation to ballooning and low cycle fatigue phenomena. Then corrosion and low cycle fatigue phenomena of coiled tubing after long-term exposure in a mud environment is also discussed. Next, fatigue performance and improvement of circumferential joining techniques are discussed. Finally, a trial section of advanced coiled tubing of 2-3/8-inch outer diameter (O.D.) and 0.190-inch wall thickness (W.T.) with total length of 3000 feet was manufactured by means of joining short lengths of seamless tubing using the amorphous diffusion bonding (ADB) technique. A coiled tubing drilling test at the JNOC Kashiwazaki test field in Japan was completed successfully using this advanced coiled tubing.