bluuebunny/crossref_metadata_2025 huggingface dataset:
Gemcitabine-loaded albumin nanospheres (GEM-ANPs) inhibit PANC-1 cells in vitro and in vivo
Authors: Li Ji , Di Yang , Jin Chen , Fu Deliang , Yang Feng , Jiang Yongjian , Yao Lie , Hao Sijie , Wang Xiaoyi , Subedi Sabin , Ni Quanxing
Published: April 2013

With the development of nanotechnology, special attention has been given to the nanomaterial application in tumor treatment. Here, a modified desolvation-cross-linking method was successfully applied to fabricate gemcitabine-loaded albumin nanospheres (GEM-ANPs), with 110 and 406 nm of mean diameter, respectively. The aim of this study was to assess the drug distribution, side effects, and antitumor activity of GEM-ANPs in vivo. The metabolic viability and flow cytometry analysis revealed that both GEM-ANPs, especially 406-nm GEM-ANPs, could effectively inhibit the metabolism and proliferation and promote the apoptosis of human pancreatic carcinoma (PANC-1) in vitro. Intravenous injection of 406-nm GEM-ANPs exhibited a significant increase of gemcitabine in the pancreas, liver, and spleen of Sprague–Dawley rats (p < 0.05). Moreover, no signs of toxic side effects analyzed by blood parameter changes were observed after 3 weeks of administration although a high dose (200 mg/kg) of GEM-ANPs were used. Additionally, in PANC-1-induced tumor mice, intravenous injection of 406-nm GEM-ANPs also could effectively reduce the tumor volume by comparison with free gemcitabine. With these findings, albumin nanosphere-loading approach might be efficacious to improve the antitumor activity of gemcitabine, and the efficacy is associated with the size of GEM-ANPs.
Random access transport capacity of multihop AF relaying: a throughput-reliability tradeoff
Authors: Lee Jaeyoung , Kim Sung-il , Kim Saejoon , Heo Jun
Published: April 2013

To determine the capacity of distributed wireless networks (i.e., ad hoc networks), the random access transport capacity was proposed as the average maximum rate of successful end-to-end transmission in the distance. In this article, we consider the random access transport capacity for multihop relaying to find the end-to-end throughput of a wireless ad hoc network, where each node relays the signal using an amplify-and-forward (AF) strategy. In particular, we analyze the exact outage probability for multihop AF relaying in the presence of both co-channel interference and thermal noise, where interferers are spatially distributed following a Poisson distribution. In our numerical results, it is observed that the maximum random access transport capacity is achieved at a specific spatial density of transmitting nodes due to the throughput-reliability tradeoff as the number of transmitting nodes (=interferers) increases. We compute the optimal spatial density of transmitting nodes that maximize their random access transport capacity. As a result, we can obtain the actual random access transport capacity of multihop AF relaying and predict the maximum number of transmitting nodes per unit area to maximize their performance.
Opportunities to investigate the effects of ivermectin mass drug administration on scabies
Authors: Engelman Daniel , Martin Diana L , Hay Roderick J , Chosidow Olivier , McCarthy James S , Fuller L Claire , Steer Andrew C
Published: April 2013

The recent article by Mohammed et al. demonstrates an impressive effect of ivermectin mass drug administration for lymphatic filariasis on the burden of scabies. Partnering scabies research within the evaluation and monitoring of Neglected Tropical Disease programmes could potentially increase our understanding of the epidemiology and control of scabies and its important bacterial complications.
Disruption of Reproductive Aging in Female and Male Rats by Gestational Exposure to Estrogenic Endocrine Disruptors
Authors: Walker Deena M. , Kermath Bailey A. , Woller Michael J. , Gore Andrea C.
Published: April 2013

Polychlorinated biphenyls (PCBs) are industrial contaminants and known endocrine-disrupting chemicals. Previous work has shown that gestational exposure to PCBs cause changes in reproductive neuroendocrine processes. Here we extended work farther down the life spectrum and tested the hypothesis that early life exposure to Aroclor 1221 (A1221), a mixture of primarily estrogenic PCBs, results in sexually dimorphic aging-associated alterations to reproductive parameters in rats, and gene expression changes in hypothalamic nuclei that regulate reproductive function. Pregnant Sprague Dawley rats were injected on gestational days 16 and 18 with vehicle (dimethylsulfoxide), A1221 (1 mg/kg), or estradiol benzoate (50 μg/kg). Developmental parameters, estrous cyclicity (females), and timing of reproductive senescence were monitored in the offspring through 9 months of age. Expression of 48 genes was measured in 3 hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV), arcuate nucleus (ARC), and median eminence (females only) by real-time RT-PCR. Serum LH, testosterone, and estradiol were assayed in the same animals. In males, A1221 had no effects; however, prenatal estradiol benzoate increased serum estradiol, gene expression in the AVPV (1 gene), and ARC (2 genes) compared with controls. In females, estrous cycles were longer in the A1221-exposed females throughout the life cycle. Gene expression was not affected in the AVPV, but significant changes were caused by A1221 in the ARC and median eminence as a function of cycling status. Bionetwork analysis demonstrated fundamental differences in physiology and gene expression between cycling and acyclic females independent of treatment. Thus, gestational exposure to biologically relevant levels of estrogenic endocrine-disrupting chemicals has sexually dimorphic effects, with an altered transition to reproductive aging in female rats but relatively little effect in males.
Detection of the Epidermal Growth Factor Receptor, Amphiregulin and Epiregulin in Formalin-Fixed Paraffin-Embedded Human Placenta Tissue by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging
Authors: Mahmoud Khaled , Cole Laura M. , Newton Jillian , Mohamed Sabah , Al-Enazi Maher , Quirke Phil , Clench Malcolm R
Published: April 2013

The study of the expression and the tissue distribution of the tyrosine kinase drug-target epidermal growth factor receptor (EGFR) is of interest in oncology as a marker of potential efficacy of treatment. It has been reported, however, that the response rates to anti-EGFR drugs are poorly linked to its expression. Clinical studies have also revealed a patient response correlation with the expression levels of two EGFR ligands; amphiregulin and epiregulin. Here, we report the development of a matrix-assisted laser desorption/ionisation mass spectrometry imaging methodology for the study of EGFR, epiregulin and amphiregulin distribution in formalin fixed paraffin embedded human placental tissue and a comparison to expression patterns obtained by immunohiostochemistry. Using on-tissue digests and imaging of specific peptides, the tissue distribution of these proteins has been obtained down to 30 μm spatial resolution.
Hybrid Capture 2 Test Results After an Initial Equivocal RLU/CO Value Are Dependent on Age
Authors: Elkins Camille T. , de Vries Christiaan E. , Stephens Julie , Suarez Adrian A.
Published: April 2013

The effect of age on Hybrid Capture 2 (HC2) tests initially falling within the equivocal range has not been determined. We identified 359 cervicovaginal liquid cytology specimens with initial equivocal values. First and second retest relative light units/cutoff (RLU/CO) values were compared for women of 3 different age groups (15–29, 30–49, and ≥50 years). The proportion of first retests with an RLU/CO of less than 1 increased with age (P < .001). Of the 56 second retests performed, only 4 had an RLU/CO of 1 or more. The proportion of “positive” HC2 results following the current HC2 algorithm decreased with increasing age (P < .001), showing that HC2 test results after an initial equivocal value are dependent on age. Follow-up demonstrated cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in 6 (5.9%) women 15 to 29 years old and in 5 (6.3%) women 30 to 49 years old. No CIN2+ was found on follow-up of 34 of 57 women 50 years and older. These results likely reflect human papillomavirus infection prevalence and question the use of identical cutoff values regardless of age for detection of CIN2+.
Failure of Current Laboratory Protocols to Detect Lot-to-Lot Reagent Differences: Findings and Possible Solutions
Authors: Algeciras-Schimnich Alicia , Bruns David E , Boyd James C , Bryant Sandra C , La Fortune Kristin A , Grebe Stefan KG
Published: April 2013

BACKGROUND

Maintaining consistency of results over time is a challenge in laboratory medicine. Lot-to-lot reagent changes are a major threat to consistency of results.

METHODS

For the period October 2007 through July 2012, we reviewed lot validation data for each new lot of insulin-like growth factor 1 (IGF-1) reagents (Siemens Healthcare Diagnostics) at Mayo Clinic, Rochester, MN, and the University of Virginia, Charlottesville, VA. Analyses of discarded patient samples were used for comparison of lots. For the same period, we determined the distributions of reported patient results for each lot of reagents at the 2 institutions.

RESULTS

Lot-to-lot validation studies identified no reagent lot as significantly different from the preceding lot. By contrast, significant lot-to-lot changes were seen in the means and medians of 105 668 reported patient IGF-I results during the period. The frequency of increased results increased nearly 2-fold to a high of 17%, without detectable changes in the underlying patient demographics. Retrospective statistical analysis indicated that lot-to-lot comparison protocols were underpowered and that validation studies for this assay required testing >100 samples to achieve 90% power to detect reagent lots that would significantly alter the distributions of patient results.

CONCLUSIONS

The number of test samples required for adequate lot-to-lot validation protocols is high and may be prohibitively large, especially for low-volume or complex assays. Monitoring of the distributions of patient results has the potential to detect lot-to-lot inconsistencies relatively quickly. We recommend that manufacturers implement remote monitoring of patient results from analyzers in multiple institutions to allow rapid identification of between-lot result inconsistency.
Bone Morphogenic Protein Signaling Is a Major Determinant of Dentate Development
Authors: Choe Youngshik , Kozlova Anastasiia , Graf Daniel , Pleasure Samuel J.
Published: April 2013

To understand life-long neurogenesis in the dentate gyrus (DG), characterizing dentate neural stem cells and the signals controlling their development are crucial. In the present study, we show that bone morphogenic protein (Bmp) signaling is a critical regulator of embryonic dentate development, required for initiating neurogenesis in embryonic DG progenitors and required for the establishment of dentate neural stem cells postnatally. We tested the hypothesis that Bmp signaling regulates dentate development in part by controlling the expression of Lef1, a Wnt responsive transcription factor expressed in dentate stem cells and absolutely required for dentate granule cell production. Bmp activation through the Acvr1 receptor induced Lef1 expression and neurogenesis in the embryonic DG. Ectopic expression of Bmp7 in the embryonic midline increased DG neurogenesis and inhibition of local Bmp signaling decreased embryonic DG neurogenesis. Mice with selective loss of Bmp expression due to defective meningeal development or with selective conditional deletion of meningeal Bmp7 also have dentate developmental defects. Conditional deletion of Activin receptor type I (Acvr1) or Smad4 (a downstream target nuclear effector of Bmp signaling) in DG neural stem cells resulted in defects in the postnatal subgranular zone and reduced neurogenesis. These results suggest that Acvr1-mediated meningeal Bmp signaling regulates Lef1 expression in the dentate, regulating embryonic DG neurogenesis, DG neural stem cell niche formation, and maintenance.
The Adhesion-GPCR BAI1 Regulates Synaptogenesis by Controlling the Recruitment of the Par3/Tiam1 Polarity Complex to Synaptic Sites
Authors: Duman Joseph G. , Tzeng Christopher P. , Tu Yen-Kuei , Munjal Tina , Schwechter Brandon , Ho Tammy Szu-Yu , Tolias Kimberley F.
Published: April 2013

Excitatory synapses are polarized structures that primarily reside on dendritic spines in the brain. The small GTPase Rac1 regulates the development and plasticity of synapses and spines by modulating actin dynamics. By restricting the Rac1-guanine nucleotide exchange factor Tiam1 to spines, the polarity protein Par3 promotes synapse development by spatially controlling Rac1 activation. However, the mechanism for recruiting Par3 to spines is unknown. Here, we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a synaptic adhesion GPCR that is required for spinogenesis and synaptogenesis in mice and rats. We show that BAI1 interacts with Par3/Tiam1 and recruits these proteins to synaptic sites. BAI1 knockdown results in Par3/Tiam1 mislocalization and loss of activated Rac1 and filamentous actin from spines. Interestingly, BAI1 also mediates Rac-dependent engulfment in professional phagocytes through its interaction with a different Rac1-guanine nucleotide exchange factor module, ELMO/DOCK180. However, this interaction is dispensable for BAI1's role in synapse development because a BAI1 mutant that cannot interact with ELMO/DOCK180 rescues spine defects in BAI1-knockdown neurons, whereas a mutant that cannot interact with Par3/Tiam1 rescues neither spine defects nor Par3 localization. Further, overexpression of Tiam1 rescues BAI1 knockdown spine phenotypes. These results indicate that BAI1 plays an important role in synaptogenesis that is mechanistically distinct from its role in phagocytosis. Furthermore, our results provide the first example of a cell surface receptor that targets members of the PAR polarity complex to synapses.
LHX2 Is Necessary for the Maintenance of Optic Identity and for the Progression of Optic Morphogenesis
Authors: Roy Achira , de Melo Jimmy , Chaturvedi Dhananjay , Thein Thuzar , Cabrera-Socorro Alfredo , Houart Corinne , Meyer Gundela , Blackshaw Seth , Tole Shubha
Published: April 2013

Eye formation is regulated by a complex network of eye field transcription factors (EFTFs), including LIM-homeodomain gene LHX2. We disrupted LHX2 function at different stages during this process using a conditional knock-out strategy in mice. We find that LHX2 function is required in an ongoing fashion to maintain optic identity across multiple stages, from the formation of the optic vesicle to the differentiation of the neuroretina. At each stage, loss ofLhx2led to upregulation of a set of molecular markers that are normally expressed in the thalamic eminence and in the anterodorsal hypothalamus in a portion of the optic vesicle or retina. Furthermore, the longer LHX2 function was maintained, the further optic morphogenesis progressed. Early loss of function caused profound mispatterning of the entire telencephalic-optic-hypothalamic field, such that the optic vesicle became mispositioned and appeared to arise from the diencephalic-telencephalic boundary. At subsequent stages, loss ofLhx2did not affect optic vesicle position but caused arrest of optic cup formation. IfLhx2was selectively disrupted in the neuroretina from E11.5, the neuroretina showed gross dysmorphology along with aberrant expression of markers specific to the thalamic eminence and anterodorsal hypothalamus. Our findings indicate a continual requirement for LHX2 throughout the early stages of optic development, not only to maintain optic identity by suppressing alternative fates but also to mediate multiple steps of optic morphogenesis. These findings provide new insight into the anophthalmic phenotype of theLhx2mutant and reveal novel roles for this transcription factor in eye development.
Molecular Mechanism of Constitutive Endocytosis of Acid-Sensing Ion Channel 1a and Its Protective Function in Acidosis-Induced Neuronal Death
Authors: Zeng Wei-Zheng , Liu Di-Shi , Duan Bo , Song Xing-Lei , Wang Xiang , Wei Dong , Jiang Wen , Zhu Michael X. , Li Yong , Xu Tian-Le
Published: April 2013

Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the peripheral and CNSs, which critically contribute to a variety of pathophysiological conditions that involve tissue acidosis, such as ischemic stroke and epileptic seizures. However, the trafficking mechanisms of ASICs and the related proteins remain largely unknown. Here, we demonstrate that ASIC1a, the main ASIC subunit in the brain, undergoes constitutive endocytosis in a clathrin- and dynamin-dependent manner in both mouse cortical neurons and heterologous cell cultures. The endocytosis of ASIC1a was inhibited by either the small molecular inhibitor tyrphostin A23 or knockdown of the core subunit of adaptor protein 2 (AP2) μ2 using RNA interference, supporting a clathrin-dependent endocytosis of ASIC1a. In addition, the internalization of ASIC1a was blocked by dominant-negative dynamin1 mutation K44A and the small molecular inhibitor dynasore, suggesting that it is also dynamin-dependent. We show that the membrane-proximal residues465LCRRG469at the cytoplasmic C terminus of ASIC1a are critical for interaction with the endogenous adaptor protein complex and inhibition of ASIC1a internalization strongly exacerbated acidosis-induced death of cortical neurons from wild-type but not ASIC1a knock-out mice. Together, these results reveal the molecular mechanism of ASIC1a internalization and suggest the importance of endocytic pathway in functional regulation of ASIC1a channels as well as neuronal damages mediated by these channels during neurodegeneration.
Decreased hippocampal mineralocorticoid:glucocorticoid receptor ratio is associated with low birth weight in female cynomolgus macaque neonates
Authors: Ong Shirlene X , Chng Keefe , Meaney Michael J , Buschdorf Jan P
Published: April 2013

During pregnancy, glucocorticoids transfer environmental signals to the growing brain and its associated neuroendocrine system to modulate their maturation and function during adolescence and adulthood. Increasedin uteroexposure to glucocorticoids is associated with impaired fetal growth resulting in low birth weight (LBW) and compromised neural development. The underlying molecular changes affecting brain development, however, are largely unknown. Here, we compared the relative mRNA expression of genes directly involved in glucocorticoid signaling in the hippocampus, amygdala, and cortex of female non-human primate neonates (Macaca fascicularis) of naturally occurring normal birth weight and LBW. We focused on the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) genes as well as that for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and found a significantly decreased MR:GR mRNA ratio in the hippocampus and lower expression of11β-HSD1in the amygdala associated with LBW. The MR:GR mRNA ratio in the amygdala and cortex was not associated with birth weight, reflecting tissue-specific effects. Protein quantification in the hippocampus confirmed our finding of a decreased hippocampal MR:GR ratio. Our data suggest that the MR:GR ratio in the hippocampus and the expression of11β-HSD1in the amygdala are associated with intrauterine growth restriction in non-human primates during early perinatal development.
Rezidensek és szakorvosok laparoscopos technikájának felmérése MENTOR® tréningboksz segítségével
Authors: Kakucs Tímea , Lukovich Péter , Dobó Noémi , Benkő Péter , Harsányi László
Published: April 2013

Absztrakt

Bevezetés: A laparoscopos technika betegen történő elsajátítása financiális és betegbiztonsági szempontból sem előnyös. A technika oktatására és elsajátítására jelenleg a tréningboksz tűnik a legmegfelelőbbnek, de a laparoscopos gyakorlattal már rendelkező szakorvosok technikájának mérésére és rezidensekkel történő összehasonlítására még kevés a releváns adat. Módszer: A SE I. sz. Sebészeti Klinikán 25 sebész és urológus szakorvost, illetve 30 rezidenst vizsgáltunk MENTOR® tréningbokszon egy kérdőív kitöltése után, melyben többek között rákérdeztünk a szakmai gyakorlatukra, korábbi tréningboksz-, virtuális szimulátor-, hangszer- és videojáték-használatukra. A vizsgált személyeknek 3, az Amerikai Sebész Társaság szakvizsgájához megkövetelt gyakorlatot (FLS) és 3 általunk meghatározott feladatot kellett el-végezniük meghatározott idő alatt. A statisztikai számításokhoz lineáris regresszióanalízist használtunk (ANOVA táblázat). Eredmények: A szakorvosok 16%-a, a rezidensek 6,66%-a tudta teljesíteni időkorláton belül az összes feladatot. A feladatok elvégzéséhez szükséges idő és a saját laparoscopos műtétek száma között szignifikáns (p < 0,05) kapcsolatot igazoltunk, míg a többi befolyásoló tényező és az idő között nem találtunk szignifikáns kapcsolatot. A résztvevők 66%-a az általunk készített feladatokat tartotta hasznosabbnak. Következtetések: Magyarországon jelenleg a rezidensek jellemzően a betegen sajátítják el a laparoscopos műtéti technikát, holott a tréningbokszok alkalmasak a szem-kéz koordináció, a kétkezesség begyakorlására, valamint az eszközhasználat megtanulására. Ezért szükség lenne szervezett gyakorlási lehetőségek biztosítására.
Volume growth of a powder snow avalanche
Authors: Louge Michel Y. , Turnbull Barbara , Carroll Cian
Published: April 2013

We contrast the frontal dynamics of dilute powder snow avalanches with the behavior of their tail. While the former can be regarded as a fast-moving eruption current dominated by synergistic material injection into a short head, the latter behaves as a nearly arrested dilute cloud of particles expanding by progressive incorporation of ambient air, or by entrainment of snow-cover material by late avalanches trailing well behind the front.
A Clinical Study and Short Term Outcome of the Patients Presented with Thyroiditis
Authors: Afrose Rafia , Ahasan H A M Najmul , Das Aparna , Banik Gobinda , Khan Abed Hussain , Shazzad Md. Nahiduzzamane , Siddique Ashfaque Ahmed , Khan Mohammad Ashik Imran , Chowdhury Mostofa Kamal
Published: April 2013

Background: Thyroiditis-inflammation of thyroid gland includes a group of individual disorders having many different clinical presentations, aetiopathogenesis and histology. Sometimes they are overlapping on their presentations. Objectives: To see the clinical biochemical profile and to observe a short term outcome of the patients presented with different types of thyroiditis. Materials & methods: 50 cases with clinical suspicion of thyroiditis were randomly selected. Clinical history, Physical examination and serum T3, T4, TSH was done in every patient and FNAC of thyroid gland & TMab (Thyroid microsomal antibody) was estimated in some. They were followed up at three monthly intervals with the measurement of TSH. Results: Cases were subdivided in to 3 groups. Among them subacute thyroiditis were 19 (38%), 26 (52%) were Hashimotos thyroiditis and 5(10%) were silent thyroiditis. The subacute group presented with features of hyperthyroidism, negligible RAIU (radioactive iodine uptake) and FNAC ( Fine Needle Aspiration Cytology) showed granulomatous thyroiditis. During follow up (57%) became hypothyroid at 3 months, (26%) euthyroid and (15%) in thyrotoxic state. After 9 months (87%) was hypothyroid and (5.26%) thyrotoxic. At 12 months (94%) was euthyroid and one thyrotoxic. Hashimotos group presented in hypothyroid state, RAIU test were variable. FNAC showed lymphocytic infiltration in all patients. They were found 100% hypothyroid after 1 year. Silent Thyroiditis group were in hyperthyroid state with negligible RAIU. After 12 month (60%) became euthyroid and (40%) remain hypothyroid. Conclusion: Thyroiditis has both thyrotoxic and hypothyroid phase but they are self limiting. So before giving specific therapy, thyroiditis must be excluded.DOI: http://dx.doi.org/10.3329/jom.v14i1.14532 J MEDICINE 2013; 14 : 23-27
Trends in the Diagnosis and Treatment of Chronic Hepatitis B in Karachi, Pakistan
Authors: Anjum Fakhsheena , Ghayas Sana , Shafi Viqas , Bashir Lubna , Naz Shazia
Published: April 2013

Aims: Aim of this study was to analyze diagnostic and therapeutic trends of physicians regarding Chronic Hepatitis B (CHB) in Karachi since Pakistan is endemic area for viral hepatitis B.Methods: A questionnaire was distributed to about 100 physicians / doctors in different hospitals of Karachi. The questionnaire assessed diagnostic trends, prescribing habits for Chronic Hepatitis B (CHB) treatment and patients monitoring and follow ups by the physician.Results: About 100 doctors from Karachi participated in the study (response rate: 72%). 34.72% doctors had experience of treating less than 10 patients per month. Majority of the doctors (79.16%) used HBsAg (anti-HBsAg seroconversion), (61.11%) used liver function tests (LFTs) and hepatitis B virus (HBV) DNA levels were used by doctors (47.22%) as diagnostic parameters for CHB. HBV-DNA levels were the most commonly used parameter to confirm diagnosis and was used by 86.11 % doctors. Treatment of CHB was started upon various indications i.e. 58.33% doctors used HBV DNA level when it is e20,000 IU/mL (105 copies/mL) ; 36.11% used HBV DNA when it is e 2000 IU/mL (104 copies/mL) and 29.16% doctors used Serum alanine aminotransferase (ALT) when it was elevated for 3-6 months. Most of the doctors (38.88%) had experience with Interferon alfa and Pegylated IFN-a 2a, (26.38%) with Lamivudine and (25%) with Entecavir. For treatment, 41.66% of doctors recommended Pegylated IFN-a 2a for HBeAg positive CHB patients whereas 22.22% of doctors treated HBeAg negative CHB Patients with Entecavir. HBV DNA levels and alanine aminotransferase (ALT) levels were most commonly used to monitor therapy by 73.61% and 52.77% doctors respectively. Frequency of follow-up was after 3 months by most of the doctors (63.88%). According to 23.61% doctors, 5 to 10% of patients required add- on treatment or switching from the previous regimen. According to most doctors (68.05%), polymerase chain reaction (PCR) - negativity was an important indication of improved response and outcome to anti-viral therapy.Conclusion: CHB management decision varies from physicians perspective and is not always based on scientific decision. Mostly doctors used HBV DNA level as indication for treatment when it is e 2000 IU/mL (104 copies/mL) and prescribed Interferon alfa and Pegylated IFN-a 2a to their patients. Monitoring of therapy was usually done by observing HBV DNA levels and alanine aminotransferase (ALT) levels of patients and frequency of follow-up was after 3 months by most of the doctors. Add- on treatment or switching is also required by some patients and improved response to treatment was assessed by PCR negativity. Management of CHB can be improved through CME (continual medical education) and practical training.DOI: http://dx.doi.org/10.3329/jom.v14i1.14538 J MEDICINE 2013; 14 : 57-61
National Professor Dr. Nurul Islam
Authors: Editor The
Published: April 2013

DOI: http://dx.doi.org/10.3329/jom.v14i1.14626 J MEDICINE 2013; 14 : 103
The Justice Ayre in the Border Sheriffdoms, 1493–1498
Authors: Armstrong Jackson W.
Published: April 2013

This article examines the administration of justice in the southern part of the kingdom during the first decade of James IV's reign. It does so through an analysis of the earliest surviving records of the justice ayre, for Lauder (1493), Jedburgh (1493), Jedburgh (1495), Selkirk (1495) and Peebles (1498). The character, intended purpose and provenance of the records is discussed. The function of the itinerant court is assessed, including how it worked with royal and seigneurial officials, and its relationship to regalian jurisdictions. The numbers of cases, outcomes and types of offences are examined, noting differences with the statutory record, especially with reference to the classification of theft and homicide. Comment is made on the process of pardon, highlighting the ways in which royal mercy could precede assythement, and the steps preliminary to remission. The extent to which a culture of private vengeance, feud and compensation can be detected in these records, and how this related to the ambitions and mechanisms of royal justice, underpins a cautiously pessimistic evaluation of this system.
The Economic Valuation and Commensuration of Cultural Resources: Financing and Monitoring the Swedish Culture Sector
Authors: Styhre Alexander
Published: April 2013

Economic sociology treats the process of valuation and commensuration of resources as socially-embedded practices determined by historical, cultural, and political conditions. Empirical studies of valuation and commensuration demonstrate that the practices of creating metrics, accounting procedures, and other forms of numerical representations that denote underlying resources are bound up with social interests and instituted beliefs. Recently, cultural resources and culture production have been advocated as key drivers of economic growth in what has been branded the “the creative economy.” At the same time, a lot of cultural resources and culture production are, historically, not strictly valued in terms of economic worth, instead being commonly regarded as having an intrinsic social value. Such norms disconnect cultural resources and economic worth, while much culture production is simultaneously being funded by welfare states, making the allocation of public funding a matter of professional expertise. This article reports on a study of how officers of a regional Culture Agency allocate regional culture budgets and monitor culture production via processes of valuation and commensuration. The study contributes to our understanding of how valuation and commensuration play a role in non-market or pseudo-market settings where both political interests and wider social interests are bound up with calculative practices.
Diving through Membranes: Molecular Cunning to Enforce the Endosomal Escape of Antibody-Targeted Anti-Tumor Toxins
Authors: Fuchs Hendrik , Bachran Christopher , Flavell David
Published: April 2013

Membranes are vital barriers by which cells control the flux of molecules and energy between their exterior and interior and also between their various intracellular compartments. While numerous transport systems exist for ions and small molecules, the cytosolic uptake of larger biological molecules and in particular antibody-targeted drugs, is a big challenge. Inducing leakage of the plasma membrane is unfavorable since the target cell specificity mediated by the antibody would likely be lost in this case. After binding and internalization, the antibody drug conjugates reach the endosomes. Thus, enforcing the endosomal escape of anti-tumor toxins without affecting the integrity of other cellular membranes is of paramount importance. Different strategies have been developed in the last decades to overcome endosomal accumulation and subsequent lysosomal degradation of targeted protein-based drugs. In this review we summarize the various efforts made to establish efficient techniques to disrupt the endosomal membrane barrier including the use of molecular ferries such as cell penetrating peptides or viral membrane fusion proteins, endosomal leakage inducing molecules such as saponins or monensin and physicochemical methods as represented by photochemical internalization.
L’application de la charte des services bancaires de base : Réflexion sur l’accès aux services bancaires et sur l’exercice de la citoyenneté économique
Authors: Caffet Marie-Christine
Published: April 2013

Low icome access to banking services in France

This article shows that, most of the time, only a few people are denied a deposit account : a recent study exhibited that only 5% of the requests were denied. The problem might be elsewhere, in the different banking services the low income are allowed access, or not.

JEL Classification : G21, G28, I30
Regulation and development of financial centres
Authors: Champarnaud François
Published: April 2013

Regulatory institutions have to protect investors and at the same time, maintain the competitivity of financial centers. They must control the security of intermediaries, the quality of the products, and the level of performance of technology. Cooperation and harmonization between international financial centers are some objectives that the main centers are trying to achieve.

JEL Classification : G18
Competition between stock exchanges and consequences for financial centres
Authors: Champarnaud François , Remay Vincent
Published: April 2013

This article deals with increased competition between financial centres, which leads to mergers, as is the case with Euronext. Due to technological changes, the concept of geographic location seems to fade away ; however, the financial centre becomes now a place where the actors accept to play by the same rules.

JEL Classification : G18, L19
The financial services industry : new environment, new Stakes
Authors: Landau Jean-Pierre , Tricou Jean
Published: April 2013

Banks’ strategies have been strongly affected by the increase of competition ; in Europe, a vast movement of mergers can be observed. In this context, a new conception of the financial center has appeared.

JEL Classification : G29
The location of investment banking business
Authors: Fleuriet Michel
Published: April 2013

Since 1998, there have been more foreign banks in France than French ones. Many of these banks are wholesale banks or investment banks. This article reviews the factors that lead banks to locate their investment banking activities in a particular market. The author mentions three factors. First, history, and this holds true for the role within Europe of London where the first bond and equity issues of any significance took place. The second factor is the location of clients, be they issuers or investors. In the author’s view, however, trading activities can be located anywhere. The third factor is the growth strategy model of investment banks. This model, called a « tubular strategy », is characterized by development in a particular business segment followed by an offshoot in another segment in synergy with the first one. This growth model leads banks to operate close to specific client bases. The author illustrates his point with the example of HSBC, the second largest bank in the world. This model also explains the strong presence of US banks in Europe and finally the location of non-French banks in France. In conclusion, the impact of new technologies on the location of investment banks is mentioned.

JEL Classification : G24, R38
4-Pyridylnitrene and 2-pyrazinylcarbene
Authors: Wentrup Curt , Reisinger Ales , Kvaskoff David
Published: April 2013

Both flash vacuum thermolysis (FVT) and matrix photolysis generate 2-diazomethylpyrazine (22) from 1,2,3-triazolo[1,5-a]pyrazine (24). FVT of 4-azidopyridine (18) as well as of 24 or 2-(5-tetrazolyl)pyrazine (23) affords the products expected from the nitrene, i.e., 4,4’-azopyridine and 2- and 3-cyanopyrroles. Matrix photolyses of both 18 and 24 result in ring expansion of 4-pyridylnitrene/2-pyrazinylcarbene to 1,5-diazacyclohepta-1,2,4,6-tetraene (20). Further photolysis causes ring opening to the ketenimine 27.
Un savoir faire entendre
Authors: Clavurier Vincent
Published: April 2013

Dans un travail précédent sur le lapsus auditif (Verhören) , je proposai de considérer le savoir-faire du psychanalyste comme un savoir- verhören , un savoir entendre de travers. Mais que s’agit-il d’entendre, et par qui ? Le pas supplémentaire que je propose aujourd’hui est de considérer ce savoir-faire à la fois comme un faire savoir et un savoir faire entendre. Cela entraîne une série de questions : où était ce savoir littéralement inouï avant d’être su ? Est-il découvert ou inventé ? Un détour par le savoir mathématique sera éclairant et nous fournira également un schème topologique (l’hélice et plus exactement la spire) dont le repérage des occurrences dans le champ de la psychanalyse révèle un autre aspect du savoir-faire de l’analyste, celui d’une pratique de lecture topologique. Mais parler de savoir-faire semble également en rabattre sur l’idée de savoir constitué et démontrable et on se demandera si la notion de preuve est du coup cliniquement pertinente. Dans le fil de cette question, reprenant l’appellation « science conjecturale » proposée par Lacan, nous nous interrogerons sur le rôle discutable de l’hypothèse dans le savoir-faire du psychanalyste.
Der Bann
Authors: Cambon Fernand
Published: April 2013

Deux conversations sur la singularité de la Corée-du-Nord associent un phénomène collectif d’une part à une sorte d’hypnose, d’autre part à une logique d’enfermement. Cela me donne l’idée d’étudier la convergence fréquente entre ces deux thématiques (par exemple le motif du « cercle magique »). Je suis alors renvoyé au mot allemand der Bann , dont la sémantique semble conjoindre les deux significations. (Ce mot a donné en français « le ban », à la sémantique nettement moins riche.) L’exploration de ce mot et des verbes afférents se révèle féconde. On se trouve alors face à un pouvoir, certes de vie et de mort, mais qui semble d’abord viser à inscrire et à projeter sa limite, réversible, dans un espace.
A practical study on the feasibility of alpha and gamma-tocopherol quantification for distinguishing Iberian pig feeding systems
Authors: Rey A. I. , Amazán D. , García-Casco J.
Published: April 2013

This study was undertaken to test the feasibility of using alpha and gamma-tocopherol quantification in fat and muscle to establish a correct classification of Iberian pigs according to their feeding background in practical situations. Samples were obtained over three different seasons from the four categories of pigs described in the Industry Quality Policy (FREE-OUT “bellota”; FREE-OUT-FEED “recebo”; FEEDOUT “campo”; and FEED-IN “cebo”). Linear discriminant functions were calculated with data obtained from seasons 1 and 2 and validated. The classification of fat and muscle samples from season 3 in the four feeding categories according to the calculated discriminant functions achieved an average of 76% success rate in distinguishing the true origin of pig samples. Quantification in muscle seemed to have higher prediction ability. Regression equations to quantify weight gained depending on the gamma-tocopherol concentration had higher R2 values for muscle than for fat (R2= 0.81 vs. 0.62). Merging of the feeding categories established by the Quality Policy could raise the accuracy of the alpha and gamma-tocopherol quantification method to up to between 89% and 98%.
Reproductive cycle of Glycymeris nummaria (Mollusca: Bivalvia) from Mali Ston Bay, Adriatic Sea, Croatia
Authors: Crnčević Marija , Peharda Melita , Ezgeta-Balić Daria , Pećarević Marijana
Published: April 2013

The reproductive cycle of the dog cockle, Glycymeris nummaria (Glycymerididae), was studied using specimens collected monthly from Mali Ston Bay, southeastern Adriatic Sea over the period from January to December 2010. We analysed sex ratios, gonad developmental stages, and oocyte diameters using standard histological techniques. There were no differences in the overall sex ratio and no difference in shell length with respect to sex. Results of a size-frequency analysis of oocyte diameters agreed with a qualitative analysis of gonadal developmental stages, confirming the occurrence of one annual spawning peak from May to July. A significant correlation was identified between mean gonad indices of males and females and condition index. This study provides the first data on the reproductive characteristics of G. nummaria, providing necessary information for the future sustainable management of its potential fishery.
A theoretical reflection on the implications of the philosophy of technology for classroompedagogy
Authors: Ankiewicz Piet
Published: April 2013

Learning programmes for technology education and its facilitation at chalk leveloften lack a scientifically founded, subject-based, philosophical framework. Matters arecomplicated by the fact that technology at school level is globally a developing subject withno existing equivalent academic discipline which can serve as a source of curriculumdevelopment and classroom pedagogy to rely upon in practice. The purpose of the article wasto do an investigation into a philosophical framework of technology that can be directive toclassroom pedagogy. The following research questions served as a departure point for thetheoretical reflection that underpinned the article, namely, (1) which aspects of a scientificallyfounded philosophical framework of technology can be directive to classroom pedagogy and(2) what are the implications of a philosophical framework of technology for specific aspectsof classroom pedagogy, for example instructional approaches, learning outcomes and learningcontent? In answer to the first research question, it was found that a philosophical frameworkof technology, based on the four modes of the manifestation of technology – namely as object,knowledge, activity, and volition – can be directive to classroom pedagogy. The teacher’schoice of learning outcomes, broad instructional approaches, strategies and skills, as well as thetypes of conceptual and procedural knowledge that should be taught, is closely related to thephilosophical underpinning of technology as phenomenon. In answer to the second researchquestion, teachers’ knowledge and understanding of a philosophical framework of technologycan support the specific choices that they must make regarding the learning outcomes, broadinstructional approaches, strategies and skills, as well as the types of conceptual and proceduralknowledge that should be taught – and hence become directive to classroom practice.
Eosinophil Apoptosis and Clearance in Asthma
Authors: Walsh Garry M.
Published: April 2013

Asthma is an increasingly common respiratory condition characterized by reversible airway obstruction, bronchial hyper-responsiveness and airway inflammation with a clear unmet need for more effective therapy. Eosinophilic asthma is a phenotype of the condition that features increased blood or sputum eosinophils whose numbers correlate with disease severity. Several lines of evidence are now emerging, which implicate increased persistence of eosinophils in the lungs of patients with asthma as a consequence of inhibition of and defects in the apoptotic process, together with impaired apoptotic cell removal mechanisms. This article will update our knowledge of the mechanisms controlling eosinophil apoptosis and clearance, together with evidence implicating defects in apoptosis and pro-inflammatory cell removal in asthma. Recent developments in novel therapies for asthma that target eosinophil apoptotic and/or clearance pathways will also be discussed.
Macrofaunal assemblages from mud volcanoes in the Gulf of Cadiz: abundance, biodiversity and diversity partitioning across spatial scales
Authors: Cunha M. R. , Rodrigues C. F. , Génio L. , Hilário A. , Ravara A. , Pfannkuche O.
Published: April 2013

Abstract. The Gulf of Cadiz is an extensive seepage area in the south Iberian margin (NE Atlantic) encompassing over 40 mud volcanoes (MVs) at depths ranging from 200 to 4000 m. The area has a long geologic history and a central biogeographic location with a complex circulation ensuring oceanographic connectivity with the Mediterranean Sea, equatorial and North Atlantic regions. The geodynamics of the region promotes a notorious diversity in the seep regime despite the relatively low fluxes of hydrocarbon-rich gases. We analyse quantitative samples taken during the cruises TTR14, TTR15 and MSM01-03 in seven mud volcanoes grouped into Shallow MVs (Mercator: 350 m, Kidd: 500 m, Meknès: 700 m) and Deep MVs (Captain Arutyunov: 1300 m, Carlos Ribeiro: 2200 m, Bonjardim: 3000 m, Porto: 3900 m) and two additional Reference sites (ca. 550 m). Macrofauna (retained by a 500 μm sieve) was identified to species level whenever possible. The samples yielded modest abundances (70–1567 individuals per 0.25 m2), but the local and regional number of species is among the highest ever reported for cold seeps. Among the 366 recorded species, 22 were symbiont-hosting bivalves (Thyasiridae, Vesicomyidae, Solemyidae) and tubeworms (Siboglinidae). The multivariate analyses supported the significant differences between Shallow and Deep MVs: The environmental conditions at the Shallow MVs make them highly permeable to the penetration of background fauna leading to high diversity of the attendant assemblages (H′: 2.92–3.94; ES(100): 28.3–45.0; J′: 0.685–0.881). The Deep MV assemblages showed, in general, contrasting features but were more heterogeneous (H′: 1.41–3.06; ES(100): 10.5–30.5; J′: 0.340–0.852) and often dominated by one or more siboglinid species. The rarefaction curves confirmed the differences in biodiversity of Deep and Shallow MVs as well as the convergence of the latter to the Reference sites. The Bray–Curtis dissimilarity demonstrated the high β-diversity of the assemblages, especially in pairwise comparisons involving samples from the Deep MVs. Diversity partitioning assessed for species richness, Hurlbert's expected number of species and Shannon–Wiener index confirmed the high β-diversity across different spatial scales (within MVs, between MVs, between Deep and Shallow MVs). We suggest that historical and contemporary factors with differential synergies at different depths contribute to the high α-, β- and γ-diversity of the mud volcano faunal assemblages in the Gulf of Cadiz.
Solute transport dynamics in small, shallow groundwater-dominated agricultural catchments: insights from a high-frequency, multisolute 10 yr-long monitoring study
Authors: Aubert A. H. , Gascuel-Odoux C. , Gruau G. , Akkal N. , Faucheux M. , Fauvel Y. , Grimaldi C. , Hamon Y. , Jaffrézic A. , Lecoz-Boutnik M. , Molénat J. , Petitjean P. , Ruiz L. , Merot P.
Published: April 2013

Abstract. High-frequency, long-term and multisolute measurements are required to assess the impact of human pressures on water quality due to (i) the high temporal and spatial variability of climate and human activity and (ii) the fact that chemical solutes combine short- and long-term dynamics. Such data series are scarce. This study, based on an original and unpublished time series from the Kervidy-Naizin headwater catchment (Brittany, France), aims to determine solute transfer processes and dynamics that characterise this strongly human-impacted catchment. The Kervidy-Naizin catchment is a temperate, intensive agricultural catchment, hydrologically controlled by shallow groundwater. Over 10 yr, five solutes (nitrate, sulphate, chloride, and dissolved organic and inorganic carbon) were monitored daily at the catchment outlet and roughly every four months in the shallow groundwater. The concentrations of all five solutes showed seasonal variations but the patterns of the variations differed from one solute to another. Nitrate and chloride exhibit rather smooth variations. In contrast, sulphate as well as organic and inorganic carbon is dominated by flood flushes. The observed nitrate and chloride patterns are typical of an intensive agricultural catchment hydrologically controlled by shallow groundwater. Nitrate and chloride originating mainly from organic fertilisers accumulated over several years in the shallow groundwater. They are seasonally exported when upland groundwater connects with the stream during the wet season. Conversely, sulphate as well as organic and inorganic carbon patterns are not specific to agricultural catchments. These solutes do not come from fertilisers and do not accumulate in soil or shallow groundwater; instead, they are biogeochemically produced in the catchment. The results allowed development of a generic classification system based on the specific temporal patterns and source locations of each solute. It also considers the stocking period and the dominant process that limits transport to the stream, i.e. the connectivity of the stocking compartment. This mechanistic classification can be applied to any chemical solute to help assess its origin, storage or production location and transfer mechanism in similar catchments.