bluuebunny/crossref_metadata_2025 huggingface dataset:
Point-of-Care Testing for Hb A1c in the Management of Diabetes: A Systematic Review and Metaanalysis
Authors: Al-Ansary Lubna , Farmer Andrew , Hirst Jennifer , Roberts Nia , Glasziou Paul , Perera Rafael , Price Christopher P
Published: March 2011

BACKGROUND

The measurement of hemoglobin A1c (Hb A1c) is employed in monitoring of patients with diabetes. Use of point-of-care testing (POCT) for Hb A1c results at the time of the patient consultation potentially provides an opportunity for greater interaction between patient and caregiver, and more effective care.

OBJECTIVE

To perform a systematic review of current trials to determine whether POCT for Hb A1c, compared with conventional laboratory testing, improves outcomes for patients with diabetes.

METHODS

Searches were undertaken on 4 electronic databases and bibliographies from, and hand searches of, relevant journal papers. Only randomized controlled trials were included. The primary outcome measures were change in Hb A1c and treatment intensification. Metaanalyses were performed on the data obtained.

RESULTS

Seven trials were found. There was a nonsignificant reduction of 0.09% (95% CI −0.21 to 0.02) in the Hb A1c in the POCT compared to the standard group. Although data were collected on the change in proportion of patients reaching a target Hb A1c of <7.0%, treatment intensification and heterogeneity in the populations studied and how measures were reported precluded pooling of data and metaanalysis. Positive patient satisfaction was also reported in the studies, as well as limited assessments of costs.

CONCLUSIONS

There is an absence of evidence in clinical trial data to date for the effectiveness of POCT for Hb A1c in the management of diabetes. In future studies attention to trial design is needed to ensure appropriate selection and stratification of patients, collection of outcome measures, and action taken upon Hb A1c results when produced.
Sensitivity and specificity of the high fluorescent lymphocyte count-gate on the Sysmex XE-5000 hematology analyzer for detection of peripheral plasma cells
Authors: van Mirre Edwin , Vrielink Gert Jan , Tjon-a-Tsoi Nicole , Hendriks Henriët , de Kieviet Wim , ten Boekel Edwin
Published: March 2011

Background: Plasma cells are one of the end products of the B-lymphocyte mediated immune response. These cells normally reside in the bone marrow or some peripheral lymphoid tissues. Increased numbers of plasma cells in the blood, usually indicates pathology such as infection, auto-immunity or haematological malignancy. Therefore, the ability to measure plasma cells (PCs) on an automated cell analyzer might be advantageous.

Methods: The performance of the Sysmex XE-5000 leukocyte differential channel [high fluorescent lymphocyte count (HFLC) area] was evaluated for the ability to detect plasma cells in peripheral blood and compared to the detection of plasma cells by flow cytometric analyses.

Results: Our results show that the HFL count from the XE-5000 correlates (R2=0.8) with the number of PCs in peripheral blood, but detects PCs with moderate to good sensitivity (88.9%) and specificity (87.8%).

Conclusions: The Sysmex XE-5000 is suitable for screening blood samples for the presence of elevated number of plasma cells in peripheral blood, but the actual quantification needs to be confirmed by flow cytometry.
Performance evaluation of a multiplex assay for future use in biomarker discovery efforts to predict body composition
Authors: Bea Jennifer W. , Wright Nicole C. , Thompson Patricia , Hu Chengcheng , Guerra Stefano , Chen Zhao
Published: March 2011

Background: Interest in biomarker patterns and disease has led to the development of immunoassays that evaluate multiple analytes in parallel while using little sample. However, there are no current standards for multiplex configuration, validation, and quality. Thus, validation by platform, population, and question of interest is recommended. We sought to determine the best blood fraction for multiplex evaluation of circulating biomarkers in post-menopausal women, and to explore body composition phenotype discrimination by biomarkers.

Methods: Archived serum and plasma samples from a sample of healthy post-menopausal women with the highest (n=9) and lowest (n=11) percent lean mass, as determined by dual-energy X-ray absorptiometry, were used to measure 90 analytes using bead-based, suspension multiplex assays. Replicates of serum and plasma were analyzed in a random selection of four of these individuals.

Results: Ninety percent of the analytes were detectable for ≥50% of samples; when limited to these well detected analytes, mean replicate correlations for serum and plasma were 0.87 and 0.85, respectively. Serum had lower error rates discriminating phenotypes; seven serum vs. two plasma analytes discriminated extreme body phenotypes.

Conclusions: Serum and plasma performed similarly for the majority of the analytes. Serum showed a slight advantage in predicting extreme body composition phenotypes in postmenopausal women using parallel evaluation of analytes.
Human growth hormone (GH) immunoassay: standardization and clinical implications
Authors: Carrozza Cinzia , Lapolla Rosa , Canu Giulia , Annunziata Francesca , Torti Eleonora , Baroni Silvia , Zuppi Cecilia
Published: March 2011

Background: The poor comparability of growth hormone (GH) results obtained using commercially available methods, is partly due to standard preparations used in calibration. The system relies on the use of the International Reference Preparation (IRP) international standard (IS) 80/505, of human pituitary origin, containing all GH isoforms. Recently, a 22K recombinant GH isoform IRP IS 98/574 was commercialized. Our aim was to evaluate the influence of both calibrators on GH results.

Methods: GH concentration in 97 serum samples from children undergoing a growth hormone releasing hormone+arginine stimulation test was measured using Siemens IMMULITE electro-chemiluminescence method, calibrated with both IS 80/505 and IS 98/574 (GRH Growth hormone-Recombinant 98/574-kit).

Results: Comparison of our results obtained with the two sets of calibrators showed good correlation, although we found higher percentage variation (var%) than that stated by Siemens. The mean var% value was confirmed when all results were sub-divided into subgroups based on both high and low GH concentrations.

Conclusions: Since the GH assay is influenced by a variety of binding proteins, isoforms and conversion factors, standardization of the assay is strongly required. In Italy, the Agenzia Italiana del Farmaco 39 note provides GH laboratory values which are useful for therapy. On the basis of our results, we therefore propose to adjourn these GH values in order to ensure better management of patients with GH-related disorders.
Axonally Derived Neuregulin-1 Is Required for Remyelination and Regeneration after Nerve Injury in Adulthood
Authors: Fricker Florence R. , Lago Natalia , Balarajah Sharmili , Tsantoulas Christoforos , Tanna Shamil , Zhu Ning , Fageiry Samaher K. , Jenkins Mark , Garratt Alistair N. , Birchmeier Carmen , Bennett David L. H.
Published: March 2011

Neuregulin-1 (NRG1) plays a crucial role in axoglial signaling during the development of the peripheral nervous system, but its importance in adulthood after peripheral nerve injury remains unclear. We used single-neuron labeling with inducible Cre-mediated knock-out animals, which enabled visualization of a subset of adult myelinated sensory and motoneurons neurons in whichNrg1was inducibly mutated by tamoxifen treatment. In uninjured mice, NRG1-deficient axons and the associated myelin sheath were normal, and the neuromuscular junction demonstrated normal apposition of presynaptic and postsynaptic components. After sciatic nerve crush, NRG1 ablation resulted in severe defects in remyelination: axons were either hypomyelinated or had no myelin sheath. NRG1-deficient axons were also found to regenerate at a slower rate. After nerve injury, the neuromuscular junction was reinnervated, but excess terminal sprouting was observed. Juxtacrine Neuregulin-1 signaling is therefore dispensable for maintenance of the myelin sheath in adult animals but has a key role in reparative processes after nerve injury.
Behavioral and Synaptic Plasticity Are Impaired upon Lack of the Synaptic Protein SAP47
Authors: Saumweber Timo , Weyhersmüller Annika , Hallermann Stefan , Diegelmann Sören , Michels Birgit , Bucher Daniel , Funk Natalja , Reisch Dietmar , Krohne Georg , Wegener Stephanie , Buchner Erich , Gerber Bertram
Published: March 2011

The synapse-associated protein of 47 kDa (SAP47) is a member of a phylogenetically conserved gene family of hitherto unknown function. InDrosophila, SAP47 is encoded by a single gene (Sap47) and is expressed throughout all synaptic regions of the wild-type larval brain; specifically, electron microscopy reveals anti-SAP47 immunogold labeling within 30 nm of presynaptic vesicles. To analyze SAP47 function, we used the viable and fertile deletion mutantSap47156, which suffers from a 1.7 kb deletion in the regulatory region and the first exon. SAP47 cannot be detected by either immunoblotting or immunohistochemistry inSap47156mutants. These mutants exhibit normal sensory detection of odorants and tastants as well as normal motor performance and basic neurotransmission at the neuromuscular junction. However, short-term plasticity at this synapse is distorted. Interestingly,Sap47156mutant larvae also show a 50% reduction in odorant–tastant associative learning ability; a similar associative impairment is observed in a second deletion allele (Sap47201) and upon reduction of SAP47 levels using RNA interference. In turn, transgenically restoring SAP47 inSap47156mutant larvae rescues the defect in associative function. This report thus is the first to suggest a function for SAP47. It specifically argues that SAP47 is required for proper behavioral and synaptic plasticity in flies—and prompts the question whether its homologs are required for proper behavioral and synaptic plasticity in other species as well.
Disc1Point Mutations in Mice Affect Development of the Cerebral Cortex
Authors: Lee Frankie H. F. , Fadel Marc P. , Preston-Maher Kate , Cordes Sabine P. , Clapcote Steven J. , Price David J. , Roder John C. , Wong Albert H. C.
Published: March 2011

Disrupted-in-Schizophrenia 1 (DISC1) is a strong candidate gene for schizophrenia and other mental disorders. DISC1 regulates neurodevelopmental processes including neurogenesis, neuronal migration, neurite outgrowth, and neurotransmitter signaling. Abnormal neuronal morphology and cortical architecture are seen in human postmortem brain from patients with schizophrenia. However, the etiology and development of these histological abnormalities remain unclear. We analyzed the histology of twoDisc1mutant mice with point mutations (Q31L and L100P) and found a relative reduction in neuron number, decreased neurogenesis, and altered neuron distribution compared to wild-type littermates. Frontal cortical neurons have shorter dendrites and decreased surface area and spine density. Overall, the histology ofDisc1mutant mouse cortex is reminiscent of the findings in schizophrenia. These results provide further evidence thatDisc1participates in cortical development, including neurogenesis and neuron migration.
Changed Histone Acetylation Patterns in Normal-Appearing White Matter and Early Multiple Sclerosis Lesions
Authors: Pedre Xiomara , Mastronardi Fabrizio , Bruck Wolfgang , López-Rodas Gerardo , Kuhlmann Tanja , Casaccia Patrizia
Published: March 2011

The epigenetic identity of oligodendrocytes is modulated by posttranslational modifications of histones. Acetylation of histone H3 results from the balance between the activity of histone acetyltransferases (HATs) and histone deacetylases and modulates transcriptional activation. We have previously shown that, in rodents, histone deacetylation favors oligodendrocyte differentiation, whereas acetylation is associated with increased levels of transcriptional inhibitors of oligodendrocyte differentiation. Here, we report, in humans brains, a shift toward histone acetylation in the white matter of the frontal lobes of aged subjects and in patients with chronic multiple sclerosis (MS). Increased immunoreactivity for acetylated histone H3 was observed in the nuclei of NogoA+ oligodendrocytes in a subset of MS samples. These changes were associated with high levels of transcriptional inhibitors of oligodendrocyte differentiation (i.e.,TCF7L2,ID2, andSOX2) and higher HAT transcript levels (i.e.,CBP,P300) in female MS patients compared with non-neurological controls and correlated with disease duration. Chromatin immunoprecipitation from samples of MS patients revealed enrichment of acetyl-histone H3 at the promoter of the increased target genes (i.e.,TCF7L2). The data in chronic lesions contrasted with findings in early MS lesions, where a marked oligodendroglial histone deacetylation was observed. Together, these data suggest that histone deacetylation is a process that occurs at the early stages of the disease and whose efficiency decreases with disease duration.
Use-Dependent Hemispheric Balance
Authors: Avanzino Laura , Bassolino Michela , Pozzo Thierry , Bove Marco
Published: March 2011

In the human brain, homologous regions of the primary motor cortices (M1s) are connected through transcallosal fibers. Interhemispheric communication between the two M1s plays a major role in the control of unimanual hand movements, and the strength of this connection seems to be dependent on arm activity. For instance, a lesion in the M1 can induce an increase in the excitability of the intact M1 and an abnormal high inhibitory influence onto the damaged M1. This can be attributable to either the disuse of the affected limb or the overuse of the unaffected one. Here, to directly investigate cortical modifications induced by an abnormal asymmetric use of the two limbs, we studied both the excitability of the two M1s and transcallosal interaction between them in healthy subjects whose right hand was immobilized for 10 h. The left “not-immobilized” arm was completely free to move in one group of participants (G1) and limited in the other one (G2). We found that the non-use reduced the excitability of the left M1 and decreased the inhibitory influence onto the right hemisphere in the two groups. However, an increase in the excitability of right M1 and a deeper inhibitory interaction onto the left hemisphere were evident only in G1. Thus, modifications in the right M1 were not directly produced by the non-use but would depend on the overuse of the “not-immobilized” arm. Our findings suggest that the balance between the two M1s is strongly use dependent.
MicroRNA-9 Regulates Neurogenesis in Mouse Telencephalon by Targeting Multiple Transcription Factors
Authors: Shibata Mikihito , Nakao Hiromi , Kiyonari Hiroshi , Abe Takaya , Aizawa Shinichi
Published: March 2011

microRNA-9-2andmicroRNA-9-3double-mutant mice demonstrate thatmicroRNA-9(miR-9) controls neural progenitor proliferation and differentiation in the developing telencephalon by regulating the expression of multiple transcription factors. As suggested by our previous study, the Foxg1 expression was elevated, and the production of Cajal-Retzius cells and early-born neurons was suppressed in themiR-9-2/3double-mutant pallium. At embryonic day 16.5 (E16.5), however, the Foxg1 expression was no longer elevated. The expression of an AU-rich RNA-binding protein Elavl2 increased at E16.5, Elav2 associated withFoxg13′ untranslated region (UTR), and it countered theFoxg1suppression by miR-9. Later, progenitor proliferation was reduced in themiR-9-2/3double-mutant pallium with the decrease in Nr2e1 and Pax6 expression and the increase in Meis2 expression. The analyses suggest thatmicroRNA-9indirectly inhibitsPax6expression by suppressing Meis2 expression. In contrast, together with Elavl1 and Msi1,microRNA-9targetsNr2e1mRNA 3′ UTR to enhance the expression. Concomitantly, cortical layers were reduced, each cortical projection was malformed, and the tangential migration of interneurons into the pallium was impaired in themiR-9-2/3double mutants. miR-9 also targetsGsh23′ UTR, and Gsh2, as well as Foxg1, expression was elevated in themiR-9-2/3double-mutant subpallium. The subpallium progenitor proliferation was enhanced, and the development of basal ganglia including striatum and globus pallidus was suppressed. Pallial/subpallial boundary shifted dorsally, and the ventral pallium was lost. Corridor was malformed, and thalamocortical and corticofugal axons were misrouted in themiR-9-2/3double mutants.
Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase
Authors: Rodgers-Garlick Corinne I. , Armstrong Gary A. B. , Robertson R. Meldrum
Published: March 2011

Neural circuits are especially vulnerable to metabolic stress. The locust (Locusta migratoria) responds to anoxia by entering a coma during which neural and muscular systems shut down. During anoxic coma, arrest of the ventilatory central pattern generator is tightly correlated with an abrupt spreading depression (SD)-like increase in extracellular potassium concentration within the metathoracic neuropile. We examined the role of the AMP-activated protein kinase (AMPK), an evolutionarily conserved sensor of cellular energy status, in anoxia-induced ventilatory arrest and SD-like events in the locust. Perfusion of sodium azide (NaN3; mitochondrial toxin) induced SD, temporary coma, and profound changes in the ventilatory motor pattern characterized as a rapid rhythm before coma and a slower rhythm following recovery. AMPK activation using 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimicked the motor pattern changes induced by NaN3but did not induce SD and coma. The effects of NaN3on the ventilatory rhythm were reversed by perfusion of compound-C (AMPK inhibitor) or glucose, and the effects of AICAR were also reversed by compound-C, confirming the modulatory roles of AMPK and energy status. Ouabain-induced recurring SD was suppressed by inhibition of AMPK and exacerbated by its activation. We show that the motor pattern changes induced by metabolic stress are not the result of SD alone, but that AMPK is necessary and sufficient for these changes and that AMPK activity strongly influences susceptibility to SD.
Impaired Attention in the 3xTgAD Mouse Model of Alzheimer's Disease: Rescue by Donepezil (Aricept)
Authors: Romberg Carola , Mattson Mark P. , Mughal Mohamed R. , Bussey Timothy J. , Saksida Lisa M.
Published: March 2011

Several mouse models of Alzheimer's disease (AD) with abundant β-amyloid and/or aberrantly phosphorylated tau develop memory impairments. However, multiple non-mnemonic cognitive domains such as attention and executive control are also compromised early in AD individuals. Currently, it is unclear whether mutations in the β-amyloid precursor protein (APP) and tau are sufficient to cause similar, AD-like attention deficits in mouse models of the disease. To address this question, we tested 3xTgAD mice (which express APPswe, PS1M146V, and tauP301L mutations) and wild-type control mice on a newly developed touchscreen-based 5-choice serial reaction time test of attention and response control. The 3xTgAD mice attended less accurately to short, spatially unpredictable stimuli when the attentional demand of the task was high, and also showed a general tendency to make more perseverative responses than wild-type mice. The attentional impairment of 3xTgAD mice was comparable to that of AD patients in two aspects: first, although 3xTgAD mice initially responded as accurately as wild-type mice, they subsequently failed to sustain their attention over the duration of the task; second, the ability to sustain attention was enhanced by the cholinesterase inhibitor donepezil (Aricept). These findings demonstrate that familial AD mutations not only affect memory, but also cause significant impairments in attention, a cognitive domain supported by the prefrontal cortex and its afferents. Because attention deficits are likely to affect memory encoding and other cognitive abilities, our findings have important consequences for the assessment of disease mechanisms and therapeutics in animal models of AD.
Physiological Activation of Cholinergic Inputs Controls Associative Synaptic Plasticity via Modulation of Endocannabinoid Signaling
Authors: Zhao Yanjun , Tzounopoulos Thanos
Published: March 2011

Cholinergic neuromodulation controls long-term synaptic plasticity underlying memory, learning, and adaptive sensory processing. However, the mechanistic interaction of cholinergic, neuromodulatory inputs with signaling pathways underlying long-term potentiation (LTP) and long-term depression (LTD) remains poorly understood. Here, we show that physiological activation of muscarinic acetylcholine receptors (mAChRs) controls the size and sign of associative long-term synaptic plasticity via interaction with endocannabinoid signaling. Our findings indicate that synaptic or pharmacological activation of postsynaptic M1/M3 converts postsynaptic Hebbian LTP to presynaptic anti-Hebbian LTD in principal neurons of the dorsal cochlear nucleus (DCN). This conversion is also dependent on NMDA receptor (NMDAR) activation and rises in postsynaptic Ca2+. While NMDAR activation and Ca2+elevation lead to LTP, when these events are coordinated with simultaneous activation of M1/M3 mAChRs, anti-Hebbian LTD is induced. Anti-Hebbian LTD is mediated by a postsynaptic G-protein-coupled receptor intracellular signaling cascade that activates phospholipase C and that leads to enhanced endocannabinoid signaling. Moreover, the interaction between postsynaptic M1/M3 mAChRs and endocannabinoid signaling is input specific, as it occurs only in the parallel fiber inputs, but not in the auditory nerve inputs innervating the same DCN principal neurons. Based on the extensive distribution of cholinergic and endocannabinoid signaling, we suggest that their interaction may provide a general mechanism for dynamic, context-dependent modulation of associative synaptic plasticity.
The Gonadotropin-Releasing Hormone Cell-Specific Element Is Required for Normal Puberty and Estrous Cyclicity
Authors: Novaira Horacio J. , Yates Melissa , Diaczok Daniel , Kim Helen , Wolfe Andrew , Radovick Sally
Published: March 2011

Appropriate tissue-specific gene expression of gonadotropin-releasing hormone (GnRH) is critical for pubertal development and maintenance of reproductive competence. In these studies, a common element in the mouse GnRH (mGnRH) promoter, between −2806 and −2078 bp, is shown to mediate differential regulation of hypothalamic and ovarian mGnRH expression. To further characterize this region, we generated a knock-out mouse (GREKO−/−) with a deletion of the mGnRH promoter fragment between −2806 and −2078 bp. GnRH mRNA expression in the brain of GREKO−/−was less than the expression in wild-type mice; however, immunohistochemical analysis revealed no difference between the numbers of GnRH neurons among groups. GnRH mRNA expression in the ovary was fivefold higher in GREKO−/−. The immunohistochemical staining for GnRH in the ovary increased in surface epithelial and granulosa cells and also in the corpora lutea of GREKO−/−mice. The reproductive phenotype revealed that the mean day of vaginal opening was delayed, and additionally, there was a significant decrease in the length of proestrus and diestrus-metestrus phases of the estrous cycle, resulting in a shortened estrous cycle in GREKO−/−mice. This work supports the hypothesis that the region of the GnRH promoter contained between −2806 and −2078 bp acts as a cell-specific enhancer in the GnRH neuron and as a repressor in the ovary. Deletion of this regionin vivoimplicates the GnRH promoter in mediating pubertal development and periodic reproductive cycling, and forms the foundation to define the nuclear proteins important for puberty and estrous cycling in mammals.
Fractionating the Default Mode Network: Distinct Contributions of the Ventral and Dorsal Posterior Cingulate Cortex to Cognitive Control
Authors: Leech Robert , Kamourieh Salwa , Beckmann Christian F. , Sharp David J.
Published: March 2011

The posterior cingulate cortex (PCC) is a central part of the default mode network (DMN) and part of the structural core of the brain. Although the PCC often shows consistent deactivation when attention is focused on external events, anatomical studies show that the region is not homogeneous, and electrophysiological recordings in nonhuman primates suggest that it is directly involved in some forms of attention. We report a functional magnetic resonance imaging study of an attentionally demanding task (either a zero- or two-back working memory task). Standard subtraction analysis within the PCC shows a relative deactivation as task difficulty increases. In contrast, a dual-regression functional connectivity analysis reveals a clear dissociation between ventral and dorsal parts of the PCC. As task difficulty increases, the ventral PCC shows reduced integration within the DMN and less anticorrelation with the cognitive control network (CCN) activated by the task. The dorsal PCC shows an opposite pattern, with increased DMN integration and more anticorrelation. At rest, the dorsal PCC also shows functional connectivity with both the DMN and attentional networks. As expected, these results provide evidence that the PCC is involved in supporting internally directed thought, as the region is more highly integrated with the DMN at low task demands. In contrast, the task-dependent increases in connectivity between the dorsal PCC and the CCN are consistent with a role for this region in modulating the dynamic interaction between these two networks controlling the efficient allocation of attention.
Thalamocingulate Interactions In Performance Monitoring
Authors: Seifert Sebastian , von Cramon D. Yves , Imperati Davide , Tittgemeyer Marc , Ullsperger Markus
Published: March 2011

Performance monitoring is an essential prerequisite of successful goal-directed behavior. Research of the last two decades implicates the anterior midcingulate cortex (aMCC) in the human medial frontal cortex and frontostriatal basal ganglia circuits in this function. Here, we addressed the function of the thalamus in detecting errors and adjusting behavior accordingly. Using diffusion-based tractography, we found that, among the thalamic nuclei, the ventral anterior (VA) and ventral lateral anterior (VLa) nuclei have the relatively strongest connectivity with the aMCC. Patients with focal thalamic lesions showed diminished error-related negativity, behavioral error detection, and posterror adjustments. When the lesions specifically affected the thalamic VA/VLa nuclei, these effects were significantly pronounced, which was reflected by the complete absence of the error-related negativity. These results reveal that the thalamus, particularly its VA/VLa region, is a necessary constituent of the performance-monitoring network, anatomically well connected and functionally closely interacting with the aMCC.
Improving Visual Sensitivity with Subthreshold Transcranial Magnetic Stimulation
Authors: Abrahamyan Arman , Clifford Colin W. G. , Arabzadeh Ehsan , Harris Justin A.
Published: March 2011

We probed for improvement of visual sensitivity in human participants using transcranial magnetic stimulation (TMS). Stimulation of visual cortex can induce an illusory visual percept known as a phosphene. It is known that TMS, delivered at intensities above the threshold to induce phosphenes, impairs the detection of visual stimuli. We investigated how the detection of a simple visual stimulus is affected by TMS applied to visual cortex at or below the phosphene threshold. Participants performed the detection task while the contrast of the visual stimulus was varied from trial to trial according to an adaptive staircase procedure. Detection of the stimulus was enhanced when a single pulse of TMS was delivered to the contralateral visual cortex 100 or 120 ms after stimulus onset at intensities just below the phosphene threshold. No improvement in visual sensitivity was observed when TMS was applied to the visual cortex in the opposite hemisphere (ipsilateral to the visual stimulus). We conclude that TMS-induced neuronal activity can sum with stimulus-evoked activity to augment visual perception.
Sri Lanka in 2010
Authors: Uyangoda Jayadeva
Published: March 2011

The two key events of 2010 in Sri Lanka were the respective presidential and parliamentary elections, which enabled President Mahinda Rajapaksha's government to consolidate power in both the executive and legislative branches of the state in the post-civil war era. Regime priority has been toward political consolidation, rather than ethnic reconciliation and a political solution to potential ethnic tensions in the country.
Bangladesh in 2010
Authors: D'Costa Bina
Published: March 2011

Bangladesh in 2010 experienced a unique period in its domestic politics, and a boost in its bilateral and regional relationships. However, a fragile political system, poor human rights record, trade imbalances, and climate change vulnerabilities continued throughout the year and contributed to the everyday insecurities of the population.
Myanmar in 2010
Authors: Turnell Sean
Published: March 2011

The dominant issue in Myanmar throughout 2010 was the elections finally held on November 7. These were the culmination of the ruling junta's roadmap toward "disciplined democracy" but were neither free nor fair. A major development the same month was the release from house arrest of Daw Aung San Suu Kyi, which drew worldwide attention. Myanmar's economy continued to underperform.
The Philippines in 2010
Authors: Abinales Patricio N.
Published: March 2011

The new president of the Philippines, Benigno Aquino III, has to deal with the legacy of his predecessor, Gloria Macapagal-Arroyo. Her 10-year rule had the contradictory effect of stabilizing the economy but also bringing out the worst of a political process driven by patronage and anchored on the power and violence of political dynasties and warlords.
Indonesia in 2010
Authors: Kimura Ehito
Published: March 2011

Indonesia in 2010 saw reformers face off against entrenched interests in a series of high-profile battles as President Susilo Bambang Yudhoyono began his second term in office. While there appeared little to threaten the formal institutions of democracy, corruption continued to be an endemic problem. The economy posted impressive gains, and Indonesia's reputation abroad appeared solid.
Vietnam in 2010
Authors: Amer Ramses
Published: March 2011

During 2010, Vietnam's economy continued its recovery from the global recession. Politically, preparations for the Congress of the ruling Communist Party of Vietnam gained momentum. Vietnam's chairmanship of the Association of Southeast Asian Nations dominated in its foreign relations. China remained a major partner and a geo-strategic challenge.
Laos in 2010
Authors: Case William
Published: March 2011

Political contours changed little in Laos during 2010, leaving its single-party system in place. The economy continued to grow quickly, although not in ways that uplifted ordinary citizens. And deepening relations with China encouraged the government to open new channels to the United States.
North Korea in 2010
Authors: Beck Peter M.
Published: March 2011

The North killed 50 South Koreans in two audacious strikes, revved up its nuclear programs, and prepared for a third generation of Kim family rule. At the same time, a tight embrace of China still means hardship and hunger for millions of North Koreans.
Russia and the CIS in 2010
Authors: Wu Yu-Shan
Published: March 2011

Russia's semi-democratic system and fuel-driven state capitalism gradually recovered from the financial crisis. The Putin-Medvedev diarchy functioned reasonably well, although the two have not worked out a plan for political succession in 2012. On external relations, Russia improved ties with the U.S., and Kyrgyzstan's April revolution appeared a blessing.
Ivor Noël Hume: Historical Archaeologist
Authors: Hume Ivor Noël , Miller Henry M.
Published: March 2011

Ivor Noël Hume is one of the founders of historical archaeology in North America and has long championed the integration of documentary and archaeological evidence for understanding the past. As the chief archaeologist at Colonial Williamsburg for three decades, he directed numerous excavations and literally wrote the book on colonial artifacts. Committed to sharing research findings with the public, he led the way through varied publications and films and developed the first major exhibits about colonial archaeology in the United States. His most well-known project is the exploration and exhibition of the early seventeenth-century Virginia settlement of Martin's Hundred.
Quality of life in thyroid eye disease: impact of quality of care
Authors: Estcourt Stephanie , Quinn Anthony G , Vaidya Bijay
Published: March 2011

Thyroid eye disease (TED) is a chronic debilitating condition causing physical discomfort, facial disfigurement and impaired visual function. The physical consequences of TED could have a negative and lasting impact on patients' employment, hobbies and psychosocial function. In this review, we assess the evidence of the impact of TED on patients' quality of life (QOL) and also explore the effects of suboptimal quality of care on QOL of patients with this disease. It is hoped that recent initiatives, including the Amsterdam declaration, to raise the quality of care for patients with TED will help to improve their QOL.
Novel insights on imaging sex hormone-dependent tumourigenesis in vivo
Authors: Ramachandran Balaji , Stell Alessia , Maravigna Luca , Maggi Adriana , Ciana Paolo
Published: March 2011

Sex hormones modulate proliferation, apoptosis, migration, metastasis and angiogenesis in cancer cells influencing tumourigenesis from the early hyperplastic growth till the end-stage metastasis. Although decades of studies have detailed these effects at the level of molecular pathways, where and when these actions are needed for the growth and progression of hormone-dependent neoplasia is poorly elucidated. Investigation of the hormone influences in carcinogenesis in the spatio-temporal dimension is expected to unravel critical steps in tumour progression and in the onset of resistance to hormone therapies. Non-invasive in vivo imaging represents a powerful tool to follow in time hormone signalling in the whole body during tumour development. This review summarizes the tools currently available to follow hormone action in living organisms.
A differential autophagic response to hyperglycemia in the developing murine embryo
Authors: Adastra Katie L , Chi Maggie M , Riley Joan K , Moley Kelle H
Published: March 2011

Autophagy is critical to the process of development because mouse models have shown that lack of autophagy leads to developmental arrest during the pre-implantation stage of embryogenesis. The process of autophagy is regulated through signaling pathways, which respond to the cellular environment. Therefore, any alteration in the environment may lead to the dysregulation of the autophagic process potentially resulting in cell death. Using bothin vitroandin vivomodels to study autophagy in the pre-implantation murine embryo, we observed that the cells respond to environmental stressors (i.e. hyperglycemic environment) by increasing activation of autophagy in a differential pattern within the embryo. This upregulation is accompanied by an increase in apoptosis, which appears to plateau at high concentrations of glucose. The activation of the autophagic pathway was further confirmed by an increase in GAPDH activity in bothin vivoandin vitrohyperglycemic models, which has been linked to autophagy through the activation of theAtg12gene. Furthermore, this increase in autophagy in response to a hyperglycemic environment was observed as early as the oocyte stage. In conclusion, in this study, we provided evidence for a differential response of elevated activation of autophagy in embryos and oocytes exposed to a hyperglycemic environment.
An Optimal Weighted Aggregated Association Test for Identification of Rare Variants Involved in Common Diseases
Authors: Sul Jae Hoon , Han Buhm , He Dan , Eskin Eleazar
Published: March 2011

The advent of next generation sequencing technologies allows one to discover nearly all rare variants in a genomic region of interest. This technological development increases the need for an effective statistical method for testing the aggregated effect of rare variants in a gene on disease susceptibility. The idea behind this approach is that if a certain gene is involved in a disease, many rare variants within the gene will disrupt the function of the gene and are associated with the disease. In this article, we present the rare variant weighted aggregate statistic (RWAS), a method that groups rare variants and computes a weighted sum of differences between case and control mutation counts. We show that our method outperforms the groupwise association test of Madsen and Browning in the disease-risk model that assumes that each variant makes an equally small contribution to disease risk. In addition, we can incorporate prior information into our method of which variants are likely causal. By using simulated data and real mutation screening data of the susceptibility gene for ataxia telangiectasia, we demonstrate that prior information has a substantial influence on the statistical power of association studies. Our method is publicly available at http://genetics.cs.ucla.edu/rarevariants.
Focusing Transgene Expression in Drosophila by Coupling Gal4 With a Novel Split-LexA Expression System
Authors: Ting Chun-Yuan , Gu Stephanie , Guttikonda Sudha , Lin Tzu-Yang , White Benjamin H , Lee Chi-Hon
Published: March 2011

Here we report the development of a ternary version of the LexA::VP16/LexAop system in which the DNA-binding and trans-activating moieties are independently targeted using distinct promoters to achieve highly restricted, intersectional expression patterns. This Split LexA system can be concatenated with the Gal4/upstream activating sequence system to refine the expression patterns of existing Gal4 lines with minimal genetic manipulations.
Prion-Forming Ability of Ure2 of Yeasts Is Not Evolutionarily Conserved
Authors: Edskes Herman K , Engel Abbi , McCann Lindsay M , Brachmann Andreas , Tsai Huei-Fung , Wickner Reed B
Published: March 2011

[URE3] is a prion (infectious protein) of the Saccharomyces cerevisiae  Ure2p, a regulator of nitrogen catabolism. We show that wild S. paradoxus can be infected with a [URE3] prion, supporting the use of S. cerevisiae as a prion test bed. We find that the Ure2p of Candida albicans and C. glabrata also regulate nitrogen catabolism. Conservation of amino acid sequence within the prion domain of Ure2p has been proposed as evidence that the [URE3] prion helps its host. We show that the C. albicans Ure2p, which does not conserve this sequence, can nonetheless form a [URE3] prion in S. cerevisiae, but the C. glabrata Ure2p, which does have the conserved sequence, cannot form [URE3] as judged by its performance in S. cerevisiae. These results suggest that the sequence is not conserved to preserve prion forming ability.
Iron Balance in the Neonate
Authors: Cheng Carissa , Juul Sandra
Published: March 2011

Iron is essential for growth and development, and deficiency during gestation and infancy may have lifelong effects. Iron is necessary for oxygen transport, cellular respiration, myelination, neurotransmitter production, and cell proliferation. Iron deficiency may decrease hippocampal growth and alter oxidative metabolism, neurotransmitter concentrations, and fatty acid and myelination profiles throughout the brain. Excellent articles and reviews have been published on the effect of iron on cognitive development. This review highlights more recent findings, focusing on the role of iron in brain development during gestation and early life, and discusses implications for practice in the neonatal intensive care unit.
Thermal Analysis of Cw Laser Annealing Beyond the Melt Temperature
Authors: Kokorowski S A. , Olson G. L. , Hess L. D.
Published: March 2011

We present a thermal analysis which treats the problem of melting as it occurs during cw laser heating. Analytical expressions for sample temperature distributions are derived, and calculated results are compared to experimental measurements.
Time-Resolved Raman Scattering and Transmission Measurements During Pulsed Laser Annealing
Authors: Compaan A. , LO H. W. , Aydinli A. , Lee M. C.
Published: March 2011

Raman Scattering from a 7 nsec pulsed dye laser has been used to determine the onset of recrystallization following an 8 nsec dye laser excitation pulse in ion-implanted silicon. We find essentially complete recrystallization 59 nsec after the first excitation pulse and from Stokes-anti-Stokes ratios we find at 59 nsec a crystalline lattice temperature of 600 ± 200° C. Time-resolved transmission measurements at λ = 1.15 µm also demonstrate that no molten phase has occurred even though the usual reflectivity enhancement is observed.
Dislocation Nucleation, Growth and Suppression During Cw Laser Annealing of Silicon
Authors: Rozgonyi G.A. , Baumgart H. , Phillipp F.
Published: March 2011

Optical, X-ray and transmission electron microscopy plus preferential chemical etching have been used to examine the dislocations and lattice strain introduced during cw laser annealing of silicon. In addition to a substrate scanning mode we operate our cw Ar-ion laser in a “pulse” mode by using an electronically activated shutter located within the laser cavity. This permits accurate measurements to be made on isolated spots or large area scans with a dislocation density that can be deliberately varied. In particular we discuss surface slip traces, their component dislocations and resulting lattice strains, as well as submicron extrinsic dislocation loops which result from the condensation of ion-implantation produced interstitial silicon. Recommendations are presented for producing defect and strain-free material, as well as samples with specific densities of dislocations.
Laser Annealing of Defects in Vpe and Cz Grown Gallium Arsenide with a Pulsed Nd:Yag Laser
Authors: Mooney P. M. , Bourgoin J. C. , Icole J.
Published: March 2011

Gallium arsenide crystals, both VPE and Cz grown, were annealed with a pulsed Nd:YAG laser. Gold Schottky diodes were fabricated and defects were studied using the DLTS technique. The native defect E(0.83eV) was found to anneal while other electron traps, E(0.39eV) in both materials and E(0.30eV)in Cz material, remained after irradiation. A new trap, E(0.70eV), was observed after laser irradiation in both materials.

Cz GaAs samples implanted with both Ga and As were also laser annealed. The E(0.83eV) level was not observed after implantation. The E(0.30eV) trap and new levels, E(0.44eV) and E(0.6leV) were observed. C-V measurements and defect profiles indicate that the recrystallized layer is far from defect free.
Beam Annealing of Ion-Implanted Gaas and Inp
Authors: Fan J. C. C. , Chapman R. L. , Donnelly J. P. , Turner G. W. , Bozler C. O.
Published: March 2011

A scanned cw Nd: YAG laser was used to anneal ion-implanted GaAs and InP wafers. Measurements show that electrical activation is greater for p-type than for n-type dopants in GaAs, while in InP, the opposite is observed. A simple Fermi-level pinning model is presented to explain not only the electrical properties we have measured, but also those observed by other workers. We have fabricated GaAs and InP solar cells with junctions formed by ion implantation followed by laser annealing. The GaAs cells have much better conversion efficiencies than the InP cells, and this difference can be explained in terms of the model.
CW Laser Annealing of Low Dose Implants in GaAs
Authors: Nissim Yves I. , Gibbons James F.
Published: March 2011

The possibility of annealing low dose implants (≃ 1013cm-2) in GaAs using a cw scanning laser has been investigated. We have observed that above the threshold of laser-induced damage, a gallium oxide (3-Ga2O3) can be grown at laser scan speeds of 0.5mm/sec. The heat transferred to the substrate during the growth of the oxide is utilized to anneal low dose Si implanted layers. As suggested by sheet electrical measurements, close to complete activation of the implanted species is obtained.
Liquid Phase Recrystallization of InSb by CW Laser Irradiation
Authors: Lee D.H. , Olson G.L. , Hess L.D.
Published: March 2011

Indium antimonide can be recrystallized epitaxially in the liquid phase by a scanning cw argon ion laser beam for improvements in crystal quality, surface morphology and oxide interface properties. Selected area diffraction measurements, Auger sputter depth profiling and dispersive x-ray analysis indicate that crystallization occurs epitaxially, and stoichiometry is preserved in the laser processed regions. Complete elimination of all asperities present in the original polished surface was observed subsequent to laser irradiation. Scanning electron microscopy and mechanical stylus measurements of the lateral profile of the laser irradiated region revealed the presence of a slight surface contour (convex meniscus) with a maximum change in height of 700 Å across a 64 μm recrystallized strip. In contrast to previous work with other compound semiconductors (e.g., GaAs), these results with InSb indicate that cw laser-induced melting and subsequent liquid phase epitaxial recrystallization can be used to provide improved materials properties of particular compound semiconductors.
Laser-Annealed Gap Ohmic Contacts for High-Temperature Devices
Authors: Eknoyan O. , Van Der Hoeven W. , Richardson T. , Porter W.A.
Published: March 2011

The results of successful Nd:YAG laser annealed ohmic contacts on n-type GaP are reported. Comparisons on identical laser and thermal annealed contacts on the same substrates are performed. In addition aging investigations are also studied. The results indicate that laser annealed contacts have far superior electrical characteristics, much better surface morphology and are substantially more stable with aging than the same but thermally alloyed ones.
Laser Processing of Silicon for Advanced Microelectronic Devices and Circuits
Authors: Hess L.D. , Kokorowski S.A. , Olson G.L. , Yaron G.
Published: March 2011

Some of the basic requirements currently envisioned for advanced microelectronic devices and circuits are outlined and discussed in terms of fabrication techniques. Phenomenological aspects of laser processing of semiconductor materials are presented and related to the potential application of this technology for overcoming some of the fundamental limitations of conventional fabrication methods. Laser processing results obtained from a variety of siliconbased materials and test structures are presented and used to illustrate the unique features of the laser technique and the novel approach it brings to semiconductor device and circuit fabrication.
Pulsed Electron Beam Processing of Silicon Devices
Authors: Greenwald A. C. , Dolan R. P. , Tobin S. P.
Published: March 2011

Pulsed electron beams [1] were used to anneal ion-implanted diodes, transistors, and resistors. Devices were fabricated by patterning a thermal oxide on a silicon wafer, ion-implanting and pulse processing with the oxide in place, and then applying contacts. Oxide films over 0.3 micron thick were not damaged, and the silicon below these films was not melted by the pulsed electron beam. Low-dose (101311B+/cm2), implanted, pulse-annealed resistors showed no change in sheet resistance for oxide windows 2.5 to 50.0 microns wide. Diodes were fashioned with good forward and reverse I-V characteristics, with m=1.09 and IO=2.7×10−10 A/cm2 for I=IO exp(qV.mkT)−1 , when a low-temperature (550˚C, 1 hr), postpulse anneal was included in the process sequence. Both bipolar and FET types of transistors were fabricated. Results compare favorably with thermal annealing cycles.