bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoparticle‐Induced Exosomes Target Antigen‐Presenting Cells to Initiate Th1‐Type Immune Activation
Authors: Zhu Motao , Tian Xin , Song Xiao , Li Yiye , Tian Yanhua , Zhao Yuliang , Nie Guangjun 
Published: June 2012

AbstractThe mechanisms associated with the induction of systemic immune responses by nanoparticles are not fully understood, but their elucidation is critical to address safety issues associated with the broader medical application of nanotechnology. In this study, a key role of nanoparticle‐induced exosomes (extracellularly secreted membrane vesicles) as signaling mediators in the induction of T helper cell type 1 (Th1) immune activation is demonstrated. In vivo exposure to magnetic iron oxide nanoparticles (MIONs) results in significant exosome generation in the alveolar region of Balb/c mice. These act as a source of nanoparticle‐induced, membrane‐bound antigen/signaling cargo, which transfer their components to antigen‐presenting cells (APCs) in the reticuloendothelial system. Through exosome‐initiated signals, immature dendritic cells (iDCs) undergo maturation and differentiation to the DC1 subtype, while macrophages go through classical activation and differentiation to the M1 subtype. Simultaneously, iDCs and macrophages release various Th1 cytokines (including interleukin‐12 and tumor necrosis factor α) driving T‐cell activation and differentiation. Activated APCs (especially DC1 and M1 subtypes) consequently prime T‐cell differentiation towards a Th1 subtype, thereby resulting in an orchestrated Th1‐type immune response. Th1‐polarized immune activation is associated with delayed‐type hypersensitivity, which might underlie the long‐term inflammatory effects frequently associated with nanoparticle exposure. These studies suggest that nanoparticle‐induced exosomes provoke the immune activation and inflammatory responses that can accompany nanoparticle exposure.
Der Gasballast
Authors: Henning Hinrich 
Published: June 2012

AbstractNachdem Gaede durch seine rotierende Quecksilberhochvakuumpumpe den Einzug der Vakuumtechnik in die industrielle Produktion geebnet hat, sind in weiteren zehn Jahren von ihm die Molekularpumpe und die Diffusionspumpe erfunden worden. In beiden verwendet er jeweils einen physikalischen Effekt erstmals für die Vakuumerzeugung. Auf dem langen Weg zur Konstruktion von zuverlässigen Hochvakuumpumpen erweist sich die Molekularpumpe — vorerst! — als zu empfindlich. Der Einsatz von Feinvakuumpumpen weitet sich mehr und mehr aus, die ölgedichteten rotierenden Pumpen sind aber für das Absaugen von Dämpfen aller Art auf Dauer störanfällig. Auch die „Chemikerpumpe”︁ von Leybold hilft dem Übel nicht ab. Erst Ende 1935 kann Gaede die Erfindung des Gasballasts zum Patent anmelden und damit eine bis heute wichtige Verbesserung an Feinvakuumpumpen schaffen.
Fragment library design considerations
Authors: Boyd Susan M. , Turnbull Andrew P. , Walse Björn 
Published: June 2012

AbstractAs fragment‐based drug design has become established as a standard component of the drug discovery armory, the design of fragment libraries has evolved according to the practicalities of detection methods, synthetic elaboration, and intended use of the libraries. Through experience, several companies have iteratively designed and redesigned their fragment libraries to these ends, and have reported their findings to aid in future library design. Here, some of these libraries are described and various empirical design considerations are reviewed. Design criteria for future directions in fragment library design are considered, such as targeting of membrane‐bound targets or disruption of protein–protein interactions.This article is categorized under:

Computer and Information Science > Chemoinformatics
The Reaction of Cyclohexanone Azine with PCl3. Synthesis of Annulated Dichlorodiazaphosphole and its Unusual Transannulation
Authors: Kornev Alexander N. , Gorak Olga Y. , Lukoyanova Olga V. , Sushev Vyacheslav V. , Panova Julia S. , Baranov Evgenii V. , Fukin Georgy K. , Ketkov Sergei Y. , Abakumov Gleb A. 
Published: June 2012

AbstractThe N, N′‐annulated dichlorodiazaphosphole 1 was prepared in 55 % yield by the reaction of cyclohexanone azine (c‐HA) with two equivalents of PCl3 in pyridine. Compound 1 revealed one‐dimensional chains in crystal with short intermolecular interactions [3.194(1) Å] between phosphorus atoms of adjacent molecules. Treatment of c‐HA with MeLi (2 equiv. in Et2O) followed by addition of PCl3 gave 1 in 33 % yield. An amount of c‐HA isomerizes in these conditions to form corresponding hexahydroindazole derivative 3, which further reacts with 1 to give diazaphosphole 5 as transannulation product. Copper monochloride forms an (1:1) adduct with 5, which was characterized by its X‐ray crystal structure. Only one equivalent of PCl3 reacts with c‐HA in Et2O/Et3N mixture to form diazaphospholium chloride 2 and hexahydroindazole 3.
Na3B3O3F6: Synthesis, Crystal Structure, and Ionic Conductivity
Authors: Cakmak Güliz , Pilz Thomas , Jansen Martin 
Published: June 2012

AbstractCrystalline Na3B3O3F6 was synthesized from H3BO3 and NaBF4 at 623 K, alternatively NaBO2 can be reacted with NaBF4 at 673 K. The title compound (C2/c, a = 11.866(7), b = 6.901(4), c = 9.367(6) Å, β = 113.724(9)°) contains the cyclo‐fluorooxotriborate anion B3O3F63–, which displays a planar B3O3 ring. Within the margins of experimental error, its point group symmetry is D3h. Layers of fluorinated boroxine rings and sodium atoms are stacked in an alternating manner in parallel to the ab plane. The novel sodium fluorooxoborate is a poor sodium ion conductor with conductivities of 8.7 × 10–5 and 3.6 × 10–3 S·cm–1 at 523 and 623 K, respectively.
Apparent diffusion coefficient measurements in the differentiation between benign and malignant lesions: a systematic review
Authors: Vermoolen M. A. , Kwee T. C. , Nievelstein R. A. J. 
Published: June 2012

Abstract
Objectives
To systematically review the value of apparent diffusion coefficient (ADC) measurement in the differentiation between benign and malignant lesions.

Methods
A systematic search of the Medline/Pubmed and Embase databases revealed 109 relevant studies. Quality of these articles was assessed using the Quality Assessment of the Studies of Diagnostic Accuracy Included in Systematic Reviews (QUADAS) criteria. Reported ADC values of benign and malignant lesions were compared per organ.

Results
The mean quality score of the reviewed articles was 50%. Comparison of ADC values showed marked variation among studies and between benign and malignant lesions in various organs. In several organs, such as breast, liver, and uterus, ADC values discriminated well between benign and malignant lesions. In other organs, such as the salivary glands, thyroid, and pancreas, ADCs were not significantly different between benign and malignant lesions.

Conclusion
The potential utility of ADC measurement for the characterisation of tumours differs per organ. Future well-designed studies are required before ADC measurements can be recommended for the differentiation of benign and malignant lesions. These future studies should use standardised acquisition protocols and provide complete reporting of study methods, to facilitate comparison of results and clinical implementation of ADC measurement for tumour characterisation.
Promoting protective factors for young adolescents: ABCD Parenting Young Adolescents Program randomized controlled trial
Authors: Burke Kylie , Brennan Leah , Cann Warren 
Published: June 2012

ABSTRACTThis study examined the efficacy of a program for parents of young adolescents combining behavioral family intervention with acceptance‐based strategies. 180 parents were randomly allocated to a 6‐session group ABCD Parenting Young Adolescent Program or wait‐list condition. Completer analysis indicated parents in the intervention reported significantly higher adolescent prosocial behaviors (p = 0.020), lower conduct problems (p = 0.048) and total difficulties (p = 0.041). These parents also reported lower stress associated with adolescent moodiness (p = 0.032), parent life‐restriction (p < 0.001), adult‐relations (p < 0.001), social isolation (p = 0.012), incompetence/guilt (p < 0.001), lower stress in the parenting domain (p < 0.001) and lower overall stress (p = 0.003) relative to the control condition following the intervention period. No other statistically significant differences were evident (p < 0.05). Results of intention‐to‐treat analyses were similar. Greater reliable clinically significant change was also achieved for the intervention condition. Participants reported high satisfaction with all elements of the ABCD program. Results suggest the program may assist parents of young adolescents to promote or maintain protective factors in their families. Australian and New Zealand Clinical Trials Registry: ANZCTRN12609000194268.
EXPLAINING THE LEGAL EFFECTS OF RECOGNITION
Authors: Vidmar Jure 
Published: June 2012

AbstractRecognition in contemporary international law is generally seen as a declaratory act. This is indeed the only plausible explanation in situations where a new State emerges consensually and in the absence of territorial illegality. Unilateral secession and territorial illegality, however, create different legal circumstances in which the applicable rules of international law imply and even presuppose that (collective) recognition could have constitutive effects. This article therefore suggests that the interpretation of the legal nature of recognition and non-recognition should not start on the premise that recognition always merely acknowledges the fact of the emergence of a new State. This is not to say that States cannot exist without being recognized. Rather, the legal effects of recognition may depend on the mode of a certain (attempt at) State creation.
Failing constitutionalism: From political legalism to defective empowerment
Authors: MAZMANYAN ARMEN 
Published: June 2012

AbstractThe recent wave of popular uprisings in the Middle East and Northern Africa has sparked a renewed attention to democratization across the world. One of many intriguing questions in this context is whether this trend will be spread globally and will flash another wave of democratization among some regions and countries where democratic euphoria has faded away. Another intriguing question is whether this new wave, in the Middle East or elsewhere, will take a constitutional path or will evolve through undemocratic and unconstitutional channels. In this light, it looks perfectly timely to discuss the lessons from and the modern prospects of building constitutional democracies in post-Soviet countries.This article offers perspectives on challenges facing post-Soviet higher courts in the effort to promote constitutional democracy in their countries. While it argues that there are many such challenges and that their roots are mostly deep in the political culture, selected and discussed are some specific instances which starkly expose the patterns of constitutional perversion and the most relevant limitations facing post-Soviet courts in our days. The solutions to these are seen in the incremental process of institutional learning hence the article suggests some designer strategies which may help moving along this process.The first section outlines what appears to be a peculiar vision of constitutionalism as embedded in respective societies and assesses this entrenched concept against accepted accounts of Western constitutionalism. The second section discusses some specific challenges to development of constitutionalism in post-Soviet countries, concentrating on inherited mindset and legal culture, as well as corrupt political technologies and flaws in the design of constitutional courts. The third section discusses two illustrative cases before higher tribunals to demonstrate what courts face in the courtroom when confronting the described challenges.
Proportionality and freedom—An essay on method in constitutional law
Authors: PERJU VLAD 
Published: June 2012

AbstractThis article presents a functional explanation of why proportionality has become one of the most successful legal transplants in contemporary constitutional law. It argues that proportionality helps judges mitigate what Robert Cover called the ‘inherent difficulty presented by the violence of the state’s law acting upon the free interpretative process’. More than alternative methods, proportionality calibrates the violence that the justification of state coercion inflicts on private (non-official) jurisgenerative interpretative processes in constitutional cases. The first three sections show, through an analysis of different constitutional styles which I label Doric, Ionic and Corinthian, how proportionality seeks to place a non-deontological conception of rights within a categorical structure of formal legal analysis. This method aims to synthesize fidelity to form and institutional structure (thesis) with ‘fact-sensitivity’ to contexts in which specific controversies arise (antithesis). Proportionality positions judges vis-à-vis the parties and the parties in relation to one another differently from other constitutional methods. The next sections distinguish between constitutional perception and reality. While the normative appeal of proportionality can be traced to the perception of its integrative aims, in reality, judicial technique does not entirely live up to those aims. Proportionality succumbs to pressures from the centrifugal forces of universalism and particularism that it seeks to integrate. The final section draws on the works of Kant and Arendt and discusses the implications of an approach to constitutional method such as that reflected in the advent of proportionality for the project of constitutionalism more generally.
A functional interaction between the MAGUK protein hDlg and the gap junction protein connexin 43 in cervical tumour cells
Authors: MacDonald Alasdair I. , Sun Peng , Hernandez-Lopez Hegel , Aasen Trond , Hodgins Malcolm B. , Edward Michael , Roberts Sally , Massimi Paola , Thomas Miranda , Banks Lawrence , Graham Sheila V. 
Published: June 2012

Gap junctions, composed of Cxs (connexins), allow direct intercellular communication. Gap junctions are often lost during the development of malignancy, although the processes behind this are not fully understood. Cx43 is a widely expressed Cx with a long cytoplasmic C-terminal tail that contains several potential protein-interaction domains. Previously, in a model of cervical carcinogenesis, we showed that the loss of gap junctional communication correlated with relocalization of Cx43 to the cytoplasm late in tumorigenesis. In the present study, we demonstrate a similar pattern of altered expression for the hDlg (human discs large) MAGUK (membrane-associated guanylate kinase) family tumour suppressor protein in cervical tumour cells, with partial co-localization of Cx43 and hDlg in an endosomal/lysosomal compartment. Relocalization of these proteins is not due to a general disruption of cell membrane integrity or Cx targeting. Cx43 (via its C-terminus) and hDlg interact directly in vitro and can form a complex in cells. This novel interaction requires the N- and C-termini of hDlg. hDlg is not required for Cx43 internalization in W12GPXY cells. Instead, hDlg appears to have a role in maintaining a cytoplasmic pool of Cx43. These results demonstrate that hDlg is a physiologically relevant regulator of Cx43 in transformed epithelial cells.
The Association of Intervertebral Disk Degeneration on MRI and Low Back Pain: A Population-Based Study
Authors: Samartzis D. , Karppinen J. , Luk K. , Cheung K. 
Published: June 2012

Introduction According to previous studies, the presence of disk degeneration based on MRI and its association with low back pain (LBP) remains questionable. However, such studies were not population-based and/or entailed various methodological limitations, and should be interpreted with caution. Therefore, as part of the largest radiographic and clinical population-based study of the lumbar spine, this study addressed the association of disk degeneration as noted on MRI with the presence and severity of LBP. Materials and Methods Sagittal T2-weighted MRIs of the lumbar spine were obtained of 2702 adult Southern Chinese. Radiographic evaluation entailed the presence of disk degeneration based on the Schneiderman et al criteria. An overall degenerative disk disease score (range: 0 to 15) was obtained and represented the global severity of disk degeneration. Additional assessment of spine pathology/abnormalities, LBP, visual analog scale (VAS) pain scores, and subject demographics were performed. Based on various modifiable and nonmodifiable risk factors associated with LBP, a LBP profile was assessed. Results There were 1614 females and 1088 males (mean age = 42 years). A low back profile was identified, noting younger individuals, females, and Modic changes to be highly associated with the reporting of LBP and although there was an increasing trend of workload severity associated with LBP it was not a significant factor. Individuals with disk degeneration had a higher prevalence and increased likelihood of LBP than individuals without disk degeneration (OR: 1.45; 95% CI, 1.12–1.87; p2 = 0.95) and LBP (DDD = 0 (ref), adjusted OR = 1.4 at 1 to 2 DDD; OR = 1.7 at 3 to 4 DDD; OR = 2.0 at 5 to 6 DDD; OR = 3.4 at >7 DDD; p). Further subgroup analysis suggested that the association of disk degeneration with LBP may be demographically influenced (e.g., age). Conclusion This large-scale study noted that disk degeneration based on MRI is significantly associated with LBP. The “global severity” of disk degeneration was found to increase the risk of having LBP. These findings support that the study of disk degeneration on MRI is clinically relevant. In addition, a LBP profile in a Chinese population was established. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Combination of MRI and 99mTc-NTP 15-5 Scintigraphy for the Assessment of Intervertebral Disk Degeneration and Tissue Engineering
Authors: Colombier P. , Clouet J. , Miot-Noirault E. , Vidal A. , Cachin F. , Vinatier C. , Fusellier M. , Fellah B. H. , Gauthier O. , Chezal J. M. , Grimandi G. , Guicheux J. 
Published: June 2012

Introduction Intervertebral disk degeneration is one of the leading causes of low back pain. The development of regenerative cell-based biotherapies for degenerated IVD has recently been contemplated. To evaluate the preclinical relevance of such therapies, animal models combined with longitudinal imaging methods such as MRI are currently used. However, facing the limitations of MRI and to further decipher the early process of IVD degeneration, innovative radio imaging approaches are considered promising. In this context, we were interested in determining whether a scintigraphic imaging approach using a specific proteoglycan radiotracer (99mTc-NTP 15-5) could be instrumental to assess the biofunctionality of IVD extracellular matrix. Materials and Methods New Zealand white rabbits (1-, 6-, 12- and 30-month-old; n = 3 for each age) were used. Early aging of lumbar IVD was determined by MRI and scintigraphic analysis. MRI images were analyzed using T2-weighted signal intensity (T2wsi) and scored according to the Pfirrmann grading. In a first set of experiments, scintigraphic analyses were performed to assess the kinetic distribution in 12-month old rabbits. Ratio IVD on muscle fixation was measured. The distribution of 99 mTc-NTP-15-5 in IVD was evaluated by in vivo scintigraphic imaging (BigSpace Gamma Imager) on three rabbits of each age. Results MRI assessments of rabbit IVDs reveal as a function of age, a grading decrease in IVD signal intensity (T2wsi) associated with an increase in Pfirrmann grade. These data indicate the existence of an aging/degeneration process of rabbit IVD. As a function of escalating ages, a differential uptake of 99 mTc-NTP 15-5 in IVD was observed. Uptake was maximal at 1 month of age, and was followed by a dramatic decrease as early as 6 months (approximately 50% of radioactive signal). After 6 months, the intensity of decrease was less pronounced (approximately 10% of radioactive signal). Conclusion These in vivo results highlight the interest of combining 99 mTc-NTP-15-5 scintigraphic imaging of proteoglycans with MRI. Whereas MRI T2wsi reflects the hydration level, 99 mTc-NTP-15-5 scintigraphy allowed the functional assessment of IVD at the proteoglycan level. Such multi-imaging approach could be useful for the longitudinal study of engineered IVD following the intradiscal transplantation of mesenchymal stem cells using an injectable biomaterial. In addition, the use of scintigraphy imaging in human should be paid further attention particularly to detect the early IVD degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
The Effect of Scoliosis Correction on Sexual Function of Women with Adolescent Idiopathic Scoliosis
Authors: Schroeder J. E. , Michaeli T. , Luria M. , Barzilay Y. , Hasharoni A. , Kaplan L. 
Published: June 2012

Introduction In the past decades, there has been an increasing interest in quality of life assessment after treatment of adolescent idiopathic scoliosis. Scoliosis affects young patients many of them women that deal with the scoliosis and surgical treatment for the rest of their life. The effect of scoliosis correction on sexual function has yet to be assessed. The female sexual function index (FSFI) is a validated tool for the assessment of sexual function in women. Materials and Methods Women (over the age of 18) under the age of 40, who underwent uncomplicated posterior scoliosis correction for idiopathic adolescent scoliosis, were assessed for sexual function via the FSFI. The scores retained were compared to the general population data in the following five categories: desire, sexual arousal, lubrication, orgasm, and satisfaction and pain. Results A total of 22 women responded to the questioner. The average age was 28 (range: 19 to 38). Time from surgery was 8.2 years (range: 2 to 17 years). All patients underwent uncomplicated posterior spine fusion, without the need of secondary interventions. The Cobb angle correction in the surgery was 55 degrees (range: 40 to 70). The average FSFI score was 24.2 (range:17.5 to 29.1) (normal score over 26.5). Patients scored within the normal range in sexual desire, pain during intercourse, and lubrication. A decreased score was noted in sexual arousal, orgasms, and satisfaction, when compared to normal population values. Conclusion Female patients, who underwent correction of scoliosis due to AIS, have a decreased sexual function, many years after the surgery when compared to the general population. This is due to a decreased arousal, orgasms, and a decreased sexual satisfaction. A distinction still needs to be made if this is due to the scoliosis or the correction. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared