bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of cAMP/PKA signaling cascade in vasopressin-induced trafficking of TRPC3 channels in principal cells of the collecting duct
Authors: Goel Monu , Zuo Cheng-Di , Schilling William P.
Published: January 2010

Transient receptor potential channels TRPC3 and TRPC6 are expressed in principal cells of the collecting duct (CD) along with the water channel aquaporin-2 (AQP2) both in vivo and in the cultured mouse CD cell line IMCD-3. The channels are primarily localized to intracellular vesicles, but upon stimulation with the antidiuretic hormone arginine vasopressin (AVP), TRPC3 and AQP2 translocate to the apical membrane. In the present study, the effect of various activators and inhibitors of the adenylyl cyclase (AC)/cAMP/PKA signaling cascade on channel trafficking was examined using immunohistochemical techniques and by biotinylation of surface membrane proteins. Both in vivo in rat kidney and in IMCD-3 cells, translocation of AQP2 and TRPC3 (but not TRPC6) was stimulated by [deamino-Cys1, d-Arg8]-vasopressin (dDAVP), a specific V2-receptor agonist, and blocked by [adamantaneacetyl1, O-Et-d-Tyr2, Val4, aminobutyryl6, Arg8,9]-vasopressin (AEAVP), a specific V2-receptor antagonist. In IMCD-3 cells, translocation of TRPC3 and AQP2 was activated by forskolin, a direct activator of AC, or by dibutyryl-cAMP, a membrane-permeable cAMP analog. AVP-, dDAVP-, and forskolin-induced translocation in IMCD-3 cells was blocked by SQ22536 and H89, specific inhibitors of AC and PKA, respectively. Translocation stimulated by dibutyryl-cAMP was unaffected by AEAVP but could be blocked by H89. AVP- and forskolin-induced translocation of TRPC3 in IMCD-3 cells was also blocked by two additional inhibitors of PKA, specifically Rp-cAMPS and the myristoylated inhibitor of PKA (m-PKI). Quantification of TRPC3 membrane insertion in IMCD-3 cells under each assay condition using a surface membrane biotinylation assay, confirmed the translocation results observed by immunofluorescence. Importantly, AVP-induced translocation of TRPC3 as estimated by biotinylation was blocked on average 95.2 ± 1.0% by H89, Rp-cAMPS, or m-PKI. Taken together, these results demonstrate that AVP stimulation of V2 receptors in principal cells of the CD causes translocation of TRPC3 to the apical membrane via stimulation of the AC/cAMP/PKA signaling cascade.
Early and prominent alterations in hemodynamics, signaling, and gene expression following renal ischemia in sickle cell disease
Authors: Juncos Julio P. , Grande Joseph P. , Croatt Anthony J. , Hebbel Robert P. , Vercellotti Gregory M. , Katusic Zvonimir S. , Nath Karl A.
Published: January 2010

Acute ischemic insults to the kidney are recognized complications of human sickle cell disease (SCD). The present study analyzed in a transgenic SCD murine model the early renal response to acute ischemia. Renal hemodynamics were profoundly impaired following ischemia in sickle mice compared with wild-type mice: glomerular filtration rate, along with renal plasma flow and blood flow rates, were markedly reduced, while renal vascular resistances were increased more than threefold in sickle mice following ischemia. In addition to these changes in renal hemodynamics, there were profound disturbances in renal signaling processes: phosphorylation of members of the MAPK and Akt signaling proteins occurred in the kidney in wild-type mice after ischemia, whereas such phosphorylation did not occur in the kidney in sickle mice after ischemia. ATP content in the postischemic kidney in sickle mice was less than half that observed in wild-type mice. Examination of the expression of candidate genes uncovered changes that may predispose to increased sensitivity of the kidney in sickle mice to ischemia: increased expression of inducible nitric oxide synthase and decreased expression of endothelial nitric oxide synthase, and increased expression of TNF-α. Inducibility of anti-inflammatory, cytoprotective genes, such as heme oxygenase-1 and IL-10, was not impaired in sickle mice after ischemia. We conclude that the kidney in SCD is remarkably vulnerable to acute ischemic insults. We speculate that such sensitivity of the kidney to ischemia in SCD may underlie the occurrence of acute kidney injury in patients with SCD and may set the stage for the emergence of chronic kidney disease in SCD.
Selective Excitatory Actions of DNQX and CNQX in Rat Thalamic Neurons
Authors: Lee Sang-Hun , Govindaiah G. , Cox Charles L.
Published: January 2010

The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from glutamatergic afferents from thalamocortical relay neurons and deep layer corticothalamic neurons, and they produce excitation via both N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Quinoxaline derivatives [e.g., 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] have routinely been used as non-NMDA receptor antagonists over the last two decades. In this study, we examined whether quinoxaline derivatives alter the intrinsic properties of thalamic neurons in light of recent findings indicating that these compounds can alter neuronal excitability in hippocampal and cerebellar neurons via transmembrane AMPA receptor (AMPAR) regulatory proteins (TARPs). Whole cell recordings were obtained from TRN and ventrobasal (VB) thalamic relay neurons in vitro. DNQX and CNQX produced a consistent depolarization in all TRN neurons tested. The depolarization persisted in tetrodotoxin and low Ca2+/high Mg2+conditions, suggesting a postsynaptic site of action. In contrast, DNQX and CNQX produced little or no change in VB thalamocortical relay neurons. The nonspecific ionotropic glutamate receptor antagonist, kynurenic acid, and the selective AMPAR antagonist, 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-y l)-benzenamine hydrochloride, blocked the DNQX-mediated depolarizations. Our results indicate that the DNQX- and CNQX-mediated depolarizations are mediated by AMPAR but not kainate receptors in TRN neurons. The AMPAR-positive allosteric modulator, trichloromethiazide, potentiated the DNQX-mediated depolarization in TRN neurons but did not unmask any excitatory actions of DNQX/CNQX in relay neurons. This selective action may not only reveal a differential TARP distribution among thalamic neurons but also may provide insight into distinct characteristics of AMPA receptors of thalamic neurons that could be exploited by future pharmacological development. Furthermore, these data suggest that quinoxaline derivatives could modulate synaptic transmission and alter neuronal excitability.
A Low-Affinity Antagonist Reveals Saturation and Desensitization in Mature Synapses in the Auditory Brain Stem
Authors: Chanda Soham , Xu-Friedman Matthew A.
Published: January 2010

Postsynaptic receptor desensitization has been observed to contribute to depression in immature synapses. However, it is not clear whether desensitization persists and causes depression in mature synapses. We investigate this issue at the endbulb of Held, the synapse made by auditory nerve (AN) fibers onto bushy cells (BCs) of the anteroventral cochlear nucleus, where depression could influence the processing of sound information. Experiments using cyclothiazide (CTZ) have implicated desensitization in endbulbs from postnatal day 16 (P16) to P21 mice, but application of γ-d-glutamylglycine (DGG) did not reveal desensitization in endbulbs >P22. To reconcile these findings, we have studied the effects of both CTZ and DGG on endbulbs from P5 to P40 CBA/CaJ mice. In paired-pulse protocols, both CTZ and DGG reduced depression in all ages at intervals <10 ms, consistent with their effects preventing desensitization. However, DGG increased depression at intervals >20 ms, consistent with DGG's use to prevent saturation. DGG application revealed receptor saturation even under conditions of very low release probability. Preventing desensitization by CTZ occluded the effects of DGG on desensitization and revealed the effects of saturation at short intervals. We developed an approach to separate DGG's effect on saturation from its effect on desensitization, which showed that desensitization has an impact during bursts of auditory nerve activity. Dynamic-clamp experiments indicated that desensitization can reduce BC spike probability and increase latency and jitter. Thus desensitization may affect sound processing in the mature auditory system.
Central Cholinesterase Inhibition Enhances Glutamatergic Synaptic Transmission
Authors: Kozhemyakin Maxim , Rajasekaran Karthik , Kapur Jaideep
Published: January 2010

Central cholinergic overstimulation results in prolonged seizures of status epilepticus in humans and experimental animals. Cellular mechanisms of underlying seizures caused by cholinergic stimulation remain uncertain, but enhanced glutamatergic transmission is a potential mechanism. Paraoxon, an organophosphate cholinesterase inhibitor, enhanced glutamatergic transmission on hippocampal granule cells synapses by increasing the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in a concentration-dependent fashion. The amplitude of mEPSCs was not increased, which suggested the possibility of enhanced action potential-dependent release. Analysis of EPSCs evoked by minimal stimulation revealed reduced failures and increased amplitude of evoked responses. The ratio of amplitudes of EPSCs evoked by paired stimuli was also altered. The effect of paraoxon on glutamatergic transmission was blocked by the muscarinic antagonist atropine and partially mimicked by carbachol. The nicotinic receptor antagonist α -bungarotoxin did not block the effects of paraoxon; however, nicotine enhanced glutamatergic transmission. These studies suggested that cholinergic overstimulation enhances glutamatergic transmission by enhancing neurotransmitter release from presynaptic terminals.
Human Sound-Localization Behavior Accounts for Ocular Drift
Authors: Van Grootel Tom J. , Van Opstal A. John
Published: January 2010

To generate an accurate saccade toward a sound in darkness requires a transformation of the head-centered sound location into an oculocentric motor command, which necessitates the use of an eye-in-head position signal. We tested whether this transformation uses a continuous representation of eye position by exploiting the property that the oculomotor neural integrator is leaky with a time constant of ∼20 s. Hence in complete darkness, the eyes tend to drift toward a neutral position. Alternatively, the spatial mapping stage could employ a sampled eye-position signal in which case drift will not be accounted for. Our data show that the sound location is accurately represented and that the transformation uses a dynamic eye-position signal. This signal, however, is slightly underestimated, leading to small systematic localization errors that tend to covary with the direction of eye position.
BOLD Responses in Human Auditory Cortex Are More Closely Related to Transient MEG Responses Than to Sustained Ones
Authors: Gutschalk Alexander , Hämäläinen Matti S. , Melcher Jennifer R.
Published: January 2010

Blood oxygen level dependent–functional magnetic resonance imaging (BOLD–fMRI) and magnetoencephalographic (MEG) signals are both coupled to postsynaptic potentials, although their relationship is incompletely understood. Here, the wide range of BOLD–fMRI and MEG responses produced by auditory cortex was exploited to better understand the BOLD–fMRI/MEG relationship. Measurements of BOLD and MEG responses were made in the same subjects using the same stimuli for both modalities. The stimuli, 24-s sequences of click trains, had duty cycles of 2.5, 25, 72, and 100%. For the 2.5% sequence, the BOLD response was elevated throughout the sequence, whereas for 100%, it peaked after sequence onset and offset and showed a diminished elevation in between. On the finer timescale of MEG, responses at 2.5% consisted of a complex of transients, including N1m, to each click train of the sequence, whereas for 100% the only transients occurred at sequence onset and offset between which there was a sustained elevation in the MEG signal (a sustained field). A model that separately estimated the contributions of transient and sustained MEG signals to the BOLD response best fit BOLD measurements when the transient contribution was weighted 8- to 10-fold more than the sustained one. The findings suggest that BOLD responses in the auditory cortex are tightly coupled to the neural activity underlying transient, not sustained, MEG signals.
Singing-Related Neural Activity Distinguishes Four Classes of Putative Striatal Neurons in the Songbird Basal Ganglia
Authors: Goldberg Jesse H. , Fee Michale S.
Published: January 2010

The striatum—the primary input nucleus of the basal ganglia—plays a major role in motor control and learning. Four main classes of striatal neuron are thought to be essential for normal striatal function: medium spiny neurons, fast-spiking interneurons, cholinergic tonically active neurons, and low-threshold spiking interneurons. However, the nature of the interaction of these neurons during behavior is poorly understood. The songbird area X is a specialized striato-pallidal basal ganglia nucleus that contains two pallidal cell types as well as the same four cell types found in the mammalian striatum. We recorded 185 single units in Area X of singing juvenile birds and, based on singing-related firing patterns and spike waveforms, find six distinct cell classes—two classes of putative pallidal neuron that exhibited a high spontaneous firing rate (>60 Hz), and four cell classes that exhibited low spontaneous firing rates characteristic of striatal neurons. In this study, we examine in detail the four putative striatal cell classes. Type-1 neurons were the most frequently encountered and exhibited sparse temporally precise singing-related activity. Type-2 neurons were distinguished by their narrow spike waveforms and exhibited brief, high-frequency bursts during singing. Type-3 neurons were tonically active and did not burst, whereas type-4 neurons were inactive outside of singing and during singing generated long high-frequency bursts that could reach firing rates over 1 kHz. Based on comparison to the mammalian literature, we suggest that these four putative striatal cell classes correspond, respectively, to the medium spiny neurons, fast-spiking interneurons, tonically active neurons, and low-threshold spiking interneurons that are known to reside in area X.
Controversies on Rituximab Therapy in Sjögren Syndrome-Associated Lymphoproliferation
Authors: Quartuccio Luca , Fabris Martina , Salvin Sara , Maset Marta , De Marchi Ginevra , De Vita Salvatore
Published: January 2010

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, and frequently accompanied by systemic symptoms. A subgroup of SS patients develops malignant B cell non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) type and very often located in the major salivary glands. Currently, there is a lack of evidence-based intervention therapy which may influence SS-related chronic inflammation and lymphoproliferation. B cells are involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of disease activity. Rituximab (RTX), a chimeric monoclonal antibody targeting the CD20 antigen on the B cell surface, has been successfully investigated in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome. Preliminary experiences of RTX therapy in SS patients with or without a lymphoproliferative disorder suggest that SS patients with more residual exocrine gland function might better benefit from RTX. Efficacy of RTX in SS-associated B-cell lymphoma, mainly in low-grade salivary gland lymphomas, remains an open issue.
Novel Influenza H1N1 in Pregnancy: A Report of Two Cases
Authors: Fridman Dmitry , Kuzbari Oumar , Minkoff Howard
Published: January 2010

Background. Pregnant women are a high-risk group for morbidity and mortality from influenza. During the current pandemic of H1N1 influenza, few cases of H1N1 have been reported in pregnancy.Cases. We report two cases of H1N1 influenza which occurred in single institution in the course of one month. The first patient developed acute respiratory distress syndrome, required intubation, and eventually died. The second patient had influenza H1N1 that did not have any major sequela.Conclusion. H1N1 influenza in pregnancy can be associated with severe complications. Widespread vaccination, when available, prompt diagnosis, and adequate treatment with antiviral medications when infection occurs are required.
The Venturia Apple Pathosystem: Pathogenicity Mechanisms and Plant Defense Responses
Authors: Jha Gopaljee , Thakur Karnika , Thakur Priyanka
Published: January 2010

Venturia inaequalis is the causal agent of apple scab, a devastating disease of apple. We outline several unique features of this pathogen which are useful for molecular genetics studies intended to understand plant‐pathogen interactions. The pathogenicity mechanisms of the pathogen and overview of apple defense responses, monogenic and polygenic resistance, and their utilization in scab resistance breeding programs are also reviewed.
Elastic Buckling Behaviour of a Four‐Lobed Cross Section Cylindrical Shell with Variable Thickness under Non‐Uniform Axial Loads
Authors: Khalifa Ahmed Mousa
Published: January 2010

The static buckling of a cylindrical shell of a four‐lobed cross section of variable thickness subjected to non‐uniform circumferentially compressive loads is investigated based on the thin‐shell theory. Modal displacements of the shell can be described by trigonometric functions, and Fourier′s approach is used to separate the variables. The governing equations of the shell are reduced to eight first‐order differential equations with variable coefficients in the circumferential coordinate, and by using the transfer matrix of the shell, these equations can be written in a matrix differential equation. The transfer matrix is derived from the nonlinear differential equations of the cylindrical shells by introducing the trigonometric series in the longitudinal direction and applying a numerical integration in the circumferential direction. The transfer matrix approach is used to get the critical buckling loads and the buckling deformations for symmetrical and antisymmetrical shells. Computed results indicate the sensitivity of the critical loads and corresponding buckling modes to the thickness variation of cross section and the radius variation at lobed corners of the shell.
Improved Label-Free LC-MS Analysis by Wavelet-Based Noise Rejection
Authors: Cappadona Salvatore , Nanni Paolo , Benevento Marco , Levander Fredrik , Versura Piera , Roda Aldo , Cerutti Sergio , Pattini Linda
Published: January 2010

Label-free LC-MS analysis allows determining the differential expression level of proteins in multiple samples, without the use of stable isotopes. This technique is based on the direct comparison of multiple runs, obtained by continuous detection in MS mode. Only differentially expressed peptides are selected for further fragmentation, thus avoiding the bias toward abundant peptides typical of data-dependent tandem MS. The computational framework includes detection, alignment, normalization and matching of peaks across multiple sets, and several software packages are available to address these processing steps. Yet, more care should be taken to improve the quality of the LC-MS maps entering the pipeline, as this parameter severely affects the results of all downstream analyses. In this paper we show how the inclusion of a preprocessing step of background subtraction in a common laboratory pipeline can lead to an enhanced inclusion list of peptides selected for fragmentation and consequently to better protein identification.
Near Optimum Power Control and Precoding under Fairness Constraints in Network MIMO Systems
Authors: Fodor Gábor , Johansson Mikael , Soldati Pablo
Published: January 2010

We consider the problem of setting the uplink signal-to-noise-and-interference (SINR) target and allocating transmit powers for mobile stations in multicell spatial multiplexing wireless systems. Our aim is twofold: to evaluate the potential of such mechanisms in network multiple input multiple output (MIMO) systems, and to develop scalable numerical schemes that allow real-time near-optimal resource allocation across multiple sites. We formulate two versions of the SINR target and power allocation problem: one for maximizing the sum rate subject to power constraints, and one for minimizing the total power needed to meet a sum-rate target. To evaluate the potential of our approach, we perform a semianalytical study inMathematicausing the augmented Lagrangian penalty function method. We find that the gain of the joint optimum SINR setting and power allocation may be significant depending on the degree of fairness that we impose. We develop a numerical technique, based on successive convexification, for real-time optimization of SINR targets and transmit powers. We benchmark our procedure against the globally optimal solution and demonstrate consistently strong performance in realistic network MIMO scenarios. Finally, we study the impact of near optimal precoding in a multicell MIMO environment and find that precoding helps to reduce the sum transmit power while meeting a capacity target.
Convergence Theorem Based on a New Hybrid Projection Method for Finding a Common Solution of Generalized Equilibrium and Variational Inequality Problems in Banach Spaces
Authors: Saewan Siwaporn , Kumam Poom , Wattanawitoon Kriengsak
Published: January 2010

The purpose of this paper is to introduce a new hybrid projection method for finding a common
element of the set of common fixed points of two relatively quasi‐nonexpansive mappings, the set of
the variational inequality for an α‐inverse‐strongly monotone, and the set of solutions of the generalized
equilibrium problem in the framework of a real Banach space. We obtain a strong convergence theorem
for the sequences generated by this process in a 2‐uniformly convex and uniformly smooth Banach space.
Base on this result, we also get some new and interesting results. The results in this paper generalize,
extend, and unify some well‐known strong convergence results in the literature.
Simultaneous Assessment of Unprocessed ProBNP
1-108
in Addition to Processed BNP32 Improves Identification of High-Risk Ambulatory Patients With Heart Failure
Authors: Dries Daniel L. , Ky Bonnie , Wu Alan H.B. , Rame J. Eduardo , Putt Mary E. , Cappola Thomas P.
Published: January 2010

Background—

B-type natriuretic peptide (BNP) is produced as a biologically inactive prohormone (proBNP
1-108
), processed, and released as an inactive amino acid N-terminal fragment (proBNP
1-76
) and a biologically active carboxyl-terminal fragment (proBNP
77-108
or BNP32). We hypothesized that simultaneous assessment of proBNP
1-108
and active BNP32, as an index of natriuretic peptide processing efficiency, would improve risk stratification in patients with chronic systolic heart failure.

Methods and Results—

We quantified plasma proBNP
1-108
and BNP32 in 756 participants in the Penn Heart Failure Study, a prospective cohort of outpatients with predominantly systolic heart failure. Cox models were used to determine the association between biomarker level at the time of study entry and incident risk of adverse cardiovascular outcomes. A significant amount of unprocessed proBNP
1-108
circulates in patients with systolic heart failure (median, 271 pg/mL; interquartile range, 65 to 825). Higher levels of proBNP
1-108
were associated with an increased risk of all-cause death or cardiac transplantation (adjusted hazard ratio, 4.9; 95% CI, 2.5 to 9.7;
P
<0.001, comparing third versus first proBNP
1-108
tertile). ProBNP
1-108
provided additive information to BNP32 risk assessment, particularly in patients with BNP32 less than the median of 125 pg/mL (adjusted hazard ratio, 1.4; 95% CI, 1.2 to 1.8;
P
<0.001 per doubling of proBNP
1-108
).

Conclusions—

Circulating proBNP
1-108
is independently associated with an increased risk of adverse cardiovascular outcomes in ambulatory patients with chronic systolic heart failure. The combined assessment of BNP32 and proBNP
1-108
provides additional information in determining risk of adverse clinical outcomes, particularly in patients with low BNP32 values that might otherwise be reassuring to the clinician.
« Toutefois, il n’y aura pas de nécessiteux chez toi » La stratégie argumentative de Deut. 15:1-11
Authors: Mukenge André Kabasele
Published: January 2010

By pointing out the apparent contradictions between verses 4, 7 and 11, the diachronic approach has often considered Deut. 15:1-11 as work from disparate sources. However a close reading that takes into account the rhetorical and stylistic effects as well as the syntactic arrangements of this pericope may reveal that we are in front of a coherent whole. The redactor anticipates the objections by introducing restrictions and prolepses, by using insistence formula (e.g. intensifying infinitive) to persuade the target audience, and by valuing the debtor, who is presented as a brother. All these are strategies for convincing the creditor to implement a difficult law.
David’s Sojourn in Keilah in Light of the Amarna Letters
Authors: Naaman Nadav
Published: January 2010

The article examines the story of David’s sojourn in Keilah (1 Sam. 23:1-13) in light of the episode of the sojourn of a band of ‘Apiru in the same city in the Amarna period. The biblical story is analyzed in the first part of the article, and is followed by a reconstruction of the 14th century BCE historical episode on the basis of some Amarna letters. The remarkable accord between the biblical and extra-biblical descriptions with regard to location and social conditions opens the way to a better understanding of both. The pro-Davidic character of the biblical story is evident from what the narrator includes in his story, as much as by what he left out. The extra-biblical source is the key to filling in the missing details that the narrator deliberately left out of his story.
The Hated Wife in Deuteronomic Law
Authors: Wells Bruce
Published: January 2010

In Deut 21:15-17, a father is required to grant the birthright to his biologically oldest son, when he has both a loved wife and a hated wife, and when the oldest son is the son of the hated wife. A common interpretation of this text is that it seeks to prevent fathers in general from demoting an eldest son and granting the birthright to a younger son. By contrast, this article argues that the text assumes that fathers had the right to demote their eldest and that they would continue to have this right. It suggests that the hated wife is one who has been arbitrarily demoted by her husband to a lower status within the household. Because of this action on the part of the husband, the text requires him to forfeit his right also to demote this woman’s son arbitrarily, a right he would otherwise have retained.
‘What Shall We Do with the Sabbath-Gatherer?’ A Narrative Approach to a ‘Hard Case’ in Biblical Law (Numbers 15:32-36)
Authors: Burnside Jonathan
Published: January 2010

This article puts forward an alternative reading of Num 15:32-36 which takes seriously the fact that the cognitive structures that go into reading the biblical Sabbath laws are narrative and visual, rather than semantic and literal. This ‘narrative’ reading sees ‘food production’ as the typical case of ‘work’ and sees ‘food production on the Sabbath’ as the ‘paradigm case’ of Sabbath-breaking. Against this background, Num 15:32-36 is a hard case because the Sabbath-gatherer’s behaviour is sufficiently far removed from the paradigm of food production to raise the question of whether the Sabbath laws could be used to resolve the problem. The uncertainty ensures that the case must be resolved by the parties concerned and since, unusually, God is the only offended party, only God can determine whether capital punishment applies and, if so, the form it should take. Ultimately, the offender’s behaviour is judged to be sufficiently close to the paradigm to deserve death because it evokes Israel’s experience of total servitude in Egypt. ‘Sabbath-gathering’ reflects a desire to return to the economic conditions associated with Pharaoh’s rule and thus signifies the rejection of YHWH’s lordship.
Complex Antiphony in David’s Lament and Its Literary Significance
Authors: Amzallag Nissim , Avriel Mikhal
Published: January 2010

The chiasma structure of David’s Lament (2 Sam 1:19-27), together with evidences of antiphonal performance of qinot in Israel, suggests that this dirge was performed antiphonally by two voices, the first (sense voice) singing all the verses in ascending order and the second (the anti-sense voice) responding by singing them in descending order. It is shown here that the matching of verses according to this setting (defined as cross-responsa) generates both complementary claims typical to antiphony, and new ‘composite meanings’ providing a new dimension to the poem as a whole. Since these features are difficultly fortuitous, it is concluded that the David’s lament was conceived to be performed antiphonally as a cross-responsa. This analysis reveals the existence of a complex but ignored dimension of ars poetica in ancient Israel.
Mothers', Fathers', and their Children's Perceptions and Reasoning about Nurturance and Self-Determination Rights
Authors: Cherney Isabelle
Published: January 2010

The present study investigated the development of autonomy by interviewing 47 ten-to- sixteen year-old adolescents and their parents from three US Midwestern cities about their perceptions of children's rights. The findings showed that on average, parents thought that their children would advocate for more rights than their children actually did. Mothers were more likely than fathers to believe that their child would advocate for self-determination rights. Older adolescents used more diverse reasoning categories than younger adolescents in their decision making. There was no age difference in the adolescents' support of nurturance and self-determination rights. Parents were generally given authority over moral consideration, but less over conventional and personal conventions. The results are discussed in the context of the development of personal autonomy and relatedness.
Evaluating the Children's Commissioner for Wales: Report of a Participatory Research Study
Authors: Hillman Joanne , Taylor Mathew , Pearson Toby , Cook Josey , Thomas Nigel , Crowley Anne , Pugh-Dungey Rhodri , France Hannah , Jenkins Cerys , Cook Mandy , Sawyers Ben
Published: January 2010

This article reports the results of an evaluation of the Children's Commissioner for Wales, which was planned and conducted with the active participation of children and young people. This article begins by giving the background to the evaluation and explaining the methods used. The findings are reported in relation to five key questions: (i) how well the Commissioner's office engages with children and young people; (ii) how much children and young people know about the Commissioner; (iii) what impact the Commissioner is having on policy and services for children and young people in Wales; (iv) how effective is the individual advice and support service; (v) whether the Commissioner has lived up to expectations. The article concludes with recommendations for the future development of the Commissioner's Office.
A Minor Matter? The Place of Young People in an EU Human Security Doctrine
Authors: Kuper Jenny
Published: January 2010

This article is a modified version of a paper written for the LSE-based 'Study Group on Europe's Security Capabilities'. It argues for the inclusion of children and young people as a specific constituency within a proposed new Human Security doctrine for EU military and peacekeeping interventions. The article outlines the importance of children/youth in relation to certain key principles of this Human Security approach, including the principles of: a) primacy of human rights; b) clear political authority; c) a 'bottom-up' approach, and d) multilateralism. It looks at a number of initiatives within the UN and EU that already recognise the importance of children and youth, and it concludes by suggesting strategies for raising the profile of children/youth in the proposed EU Human Security agenda.
Nordic Cooperation and the European Arrest Warrant: Intra-Nordic Extradition, the Nordic Arrest Warrant and Beyond
Authors: Mathisen Gjermund
Published: January 2010

For almost half a century, the Nordic countries have had a particular system of regional extradition. That system inspired and influenced the development of the European Arrest Warrant scheme at the turn of the millennium. Now, with the former Nordic system being replaced by a “Nordic Arrest Warrant”, the Nordic countries have in turn been inspired and influenced by the European Arrest Warrant scheme. In the future, it may be that the Nordic Arrest Warrant will inspire and influence further developments of the European Arrest Warrant scheme. The present article attempts an analysis of past and future interaction between developments on the Nordic level and the European Union level in this field.
United Nations Targeted Sanctions, the International Rule of Law and the European Court of Justice's Judgment in Kadi and al-Barakaat
Authors: Stenhammar Fredrik
Published: January 2010

This article analyzes the judgment of the European Court of Justice in the Kadi and al-Barakaat case from the perspective of international law and the rule of law among nations. The conclusions drawn are with regard to international law and thus not necessarily decisive for the application of domestic law and Community law to the issue of targeted United Nations (UN) sanctions. It is argued that targeted UN sanctions in the form of blacklisting and freezing of financial assets are lawful under applicable international law as a species of economic warfare. Even if, contrary to expectation, they were unlawful when first introduced, consent and active participation on part of the European states mean that they are in all likelihood precluded from protesting against them now. The European Community Court's judgment cannot affect the validity under international law of targeted UN sanctions. If it turns out that the UN sanctions can no longer be accommodated within Community law, which is an implication but by no means an immediate result of the judgment, it will be for each state to apply its national legislation and continue to implement the sanctions, disregarding Community law if necessary. This would be a serious test of the European states' professed devotion to international law.
The Use of Force: Sweden, the Jus ad Bellum and the European Security and Defence Policy
Authors: Österdahl Inger
Published: January 2010

This article explores the development of a doctrine of humanitarian intervention and responsibility to protect among Swedish policy-makers. The doctrine may or may not include an authorization by the United Nations (UN) Security Council as a necessary component. The article investigates how the new doctrine fits with the Swedish constitutional regulation of the use of force and how the evolution of the new Swedish view of the jus ad bellum interacts with the regulation of the use of force in the European Union (EU). The responsibility to protect answers to many of the concerns voiced in Parliament; the doctrine caters both to those who wish a basis for action independent of the Security Council and to those who are faithful to the UN. The parliamentary debates as well as government documents point to a developing political consensus that unilateral humanitarian intervention may be justified under certain exceptional circumstances. The argument that decisions should be made by the Security Council is difficult to maintain in the face of grave human suffering which would otherwise warrant action by the international community. The increasing ability and willingness to intervene internationally in Sweden and the EU leads to a further question, namely: For what will the force be used?
Special Protection: Article 20, Special Protection and Children's Rights Training in the Developing World?
Authors: Stevens Irene , Taylor Raymond
Published: January 2010

Article 20 of the UNCRC entitles young people in residential care to 'special protection.' This presents a challenge to States Parties concerned with how such protection can be achieved. It is suggested that one way to do this is through the establishment and delivery of meaningful training in children's rights. This paper describes the authors' experience of delivering a training programme on children's rights for staff working in Social Protection Centres in Vietnam. It provides a critical reflection on the broad emphasis of current children's rights training in the developing world and argues for more targeted research in this area.
Re-negotiating Personal Integrity in Finnish Child Welfare
Authors: Kouvonen Petra
Published: January 2010

By means of a semiotic analysis of various modalities, this article identifies two kinds of professional “speaking-images”—that of the legal adviser and the legal expert—and uses these to illustrate how deviant behaviour among children in child care custody is currently being framed. The data consist of comments on the new Finnish Child Welfare Act (LSL 417/2007) found in professional magazines in the field. The main finding is that the legal regulation of interventions in general might work to preserve child integrity. However, deviant acts of children, such as substance abuse, seem to be classified as risks that allow for a compulsory intervention.
Comparing Children's Rights: Introducing the Children's Rights Index
Authors: Gran Brian
Published: January 2010

Children's rights continue to be subject of international debates. Moving past these debates can be facilitated with an international measure of children's rights. This article introduces the Children's Rights Index, an international measure of children's rights for over 190 countries. The Children's Rights Index consists of two civil rights, two political rights, two social rights, and two economic rights. This article presents country scores on the Children's Rights Index, then examines whether children's rights vary by region and other differences, such as country wealth. It is hoped that the Children's Rights Index will provide evidence on children's rights important to the work of governments and nongovernmental organizations, as well as scholars and others concerned about children's welfare.
A Corpus-Based Sociolinguistic Study of Indefinite Article Forms in London English
Authors: Gabrielatos Costas , Torgersen Eivind Nessa , Hoffmann Sebastian , Fox Susan
Published: January 2010

This article reports on work carried out as part of the project Analysis of Spoken London English Using Corpus Tools, namely, an analysis of the use of indefinite article forms in spoken London English in a corpus of transcribed interviews, combining methodologies from sociolinguistics and corpus linguistics.The authors find a relatively high frequency of a before words beginning with a vowel, where Standard English will have an. Social factors, in particular speakers’ age, ethnicity, and place of residence, are more important than linguistic factors affecting the use of a before vowels. The authors argue that the indefinite article a before vowels forms part of Multicultural London English, along with other phonological and grammatical features that have previously been documented. The indefinite article a before vowels seems to have undergone a process of reallocation in which its status has been realigned, possibly because of an increase in social acceptance of nonstandard forms.
Long‐Term Changes in Cyclosporine Pharmacokinetics After Renal Transplantation in Children: Evidence for Saturable Presystemic Metabolism and Effect ofNR1I2Polymorphism
Authors: Fanta Samuel , Jönsson Siv , Karlsson Mats O. , Niemi Mikko , Holmberg Christer , Hoppu Kalle , Backman Janne T.
Published: January 2010

To improve cyclosporine dose individualization, the authors carried out a comprehensive analysis of the effects of clinical and genetic factors on cyclosporine pharmacokinetics in 176 children before and up to 16 years after renal transplantation. Pretransplantation test doses of cyclosporine were given intravenously and orally, followed by blood sampling for 24 hours. After transplantation, cyclosporine was quantified at trough, 2 hours postdose, or with dose‐interval curves. A 3‐compartment population pharmacokinetic model was used to describe the data. Cyclosporine oral bioavailability increased more than 1.5‐fold in the first month after transplantation, returning thereafter gradually to its initial value in 1 to 1.5 years. Moreover, older children receiving cyclosporine twice daily as the gelatin capsule microemulsion formulation had an about 1.25 to 1.3 times higher bioavailability than did the younger children receiving the liquid formulation thrice daily. In 91 children with genetic data after transplantation, patients carrying the NR1I2 g.‐25385C‐g.‐24381A‐g.‐205_‐200GAGAAG‐g.7635G‐g.8055C haplotype had about one‐tenth lower bioavailability, per allele, than did noncarriers (P = .039). The significance of the NR1I2 genotype warrants further study. In conclusion, by accounting for the effects of developmental factors (body weight), time after transplantation, and cyclosporine dosing frequency/formulation, it may be possible to improve individualization of cyclosporine dosing in children.
Single Therapeutic and Supratherapeutic Doses of Laropiprant, a Selective Prostaglandin D2 Receptor 1 Antagonist, Do Not Prolong the QTcF Interval in Healthy Volunteers
Authors: Luo Wen‐Lin , Crumley Tami , Ebel David , Atiee George J. , Royalty Jane , Johnson‐Levonas Amy O. , Wagner John , Lai Eseng
Published: January 2010

Laropiprant (LRPT), a prostaglandin D2 receptor‐1 antagonist shown to reduce niacin‐induced flushing symptoms, has been combined with niacin for treatment of dyslipidemia. This study evaluated the effects of LRPT (50 mg and 600 mg, respectively) on the QT interval with Fridericia's correction (QTcF). QTcF measurements were made over a 24‐hour period following administration of single‐dose moxifloxacin 400 mg, LRPT 50 mg, LRPT 600 mg, or placebo. The primary hypothesis was supported if the 90% confidence intervals (CIs) for the least squares (LS) mean differences between placebo and LRPT in change from baseline in QTcF interval were <10 milliseconds at every time point. The upper limits of the 90% CIs for LS mean differences from placebo in changes from baseline in QTcF intervals for LRPT 50 mg and 600 mg were <5 milliseconds at every time point. The lower limits of the 90% CIs for placebo‐adjusted LS mean changes from baseline in QTcF intervals for moxifloxacin exceeded 0 milliseconds at every time point, demonstrating the sensitivity of this assay to detect increases in the QTcF interval. In conclusion, single doses of LRPT 50 mg and 600 mg do not prolong the QTcF interval relative to placebo and are generally well tolerated.
Small business research: Time for a crisis-based view
Authors: Herbane Brahim
Published: January 2010

Small business and crisis management research are two established but largely uncoupled domains of study. Given the economic importance and vulnerability of a small businesses, closer attention is needed to understand how their owners think and act in relation to crisis management efforts in the event of business interruptions.This study highlights the relative absence of crisis management research in the small business literature and the absence of a small business focus in the crisis management literature, despite a rising tide of regulation and legislation that requires companies to have crisis/business continuity management arrangements in place. The study examines the understanding of, and resourcing and support for, crisis management using case studies from four UK small businesses. The resulting analysis illuminates four themes; understanding risks, three-dimensional crisis, learning from crisis, and stifled support systems. Furthermore, data suggest that owner-managers may frame risks in two ways — a ‘growth vulnerability paradox’ and the ‘risk elastic’ — while their understanding of crisis is conceptualized using a chronological approach to identify three key areas: crisis threat, crisis response, and crisis impact. The study concludes by asserting the need for a crisis-based view of small business research and proposes an agenda for future study.
The Basel II reform and the provision of finance for R & D activities in SMEs: An analysis of a sample of Italian companies
Authors: Scellato Giuseppe , Ughetto Elisa
Published: January 2010

In this article, we investigate the issue of the financing of R & D investments in SMEs in Italy with respect to the changes in the banking system, which are driven by the adoption of the new version of the Basel Capital Accord. Results from an instrumental variable (IV) probit model show a significant and large marginal effect of both indicators of R & D activity and R & D intensity on the probability that firms report unsatisfied credit needs. We find that the introduction of the new rules is likely to have a moderate impact on the capital requirements of banks when considering the possibility for a bank to pool together all the companies in its portfolio. However, we obtain an increase in capital requirements when we focus on the sub-sample of firms performing product innovation. In particular, the analysis suggests that the new rules on regulatory capital requirements might have a negative impact on lending conditions for those SMEs that are relatively younger, smaller and showing positive R & D expenditures.
Pharmacotechnological pitfalls of priming — possible source of microembolization during open heart surgery
Authors: Hejjel Laszlo , Szluka Gabor , Göbölös Laszlo , Szabados Sandor , Varga Tamas , Mayer Klara , Devay Attila , Foltan Maik , Ugocsai Peter , Philipp Alois
Published: January 2010

Objectives: Besides low mortality and morbidity rates in cardiac surgery, the associated cognitive dysfunction is the focus of interest. One possible reason is microembolisation. Methods and results: The authors analysed the crystallogenesis in the calcium-containing prime, inspired by their observation that the fluid sometimes becomes turbid during the priming process. Lactated Ringer-based prime solutions were tested, adding mannitol, NaHCO3, and heparin. The oxygenator was ventilated with compressed medical air. Samples were taken for dynamic light scattering particulate level analysis. The priming was furthermore modelled in the laboratory by mixing the components and then ventilating the mixture through with compressed air. Turbid solutions from the operating room contained 100-6500 nm crystals, while clear solutions contained 20-473 nm particles. In the model, continuous pH measurement showed pH 6.4-7.4 after blending the solutions, which then elevated the pH to 7.5-8.0 after ventilation with concomitant turbidity. The pH of the prime can be stabilized by the addition of ascorbic acid (1-2 mg/ml) and, also, the turbidity may be prevented. Conclusion: Ventilating the lactated Ringer-based calcium-containing primes after blending is not advisible because of alkalization and crystallogenesis. Ascorbic acid stabilizes the pH and prevents crystallogenesis in the prime. Pre-bypass filtration is recommended.