bluuebunny/crossref_metadata_2025 huggingface dataset:
Traumatic Superior Mesenteric Arteriovenous Fistula and Aortic Pseudoaneurysm 20 Years after Repair
Authors: Bikk Andras , Rosenthal David , Kohlman Michael , Lai Kin Man , Wellons Eric D.
Published: February 2011

A case of traumatic superior mesenteric arteriovenous fistula (SMAVF) and aortic pseudoaneurysm successfully treated by a unique combination of operative and endovascular techniques with a 20-year follow-up is reviewed. After 20 years, the patient presented with an aortoenteric fistula, which was managed with a cryopreserved aortic interposition graft. In this report, we review the evolution of the treatment for traumatic SMAVF and aortic pseudoaneurysm and the current management of aortoenteric fistula.
Successful Surgical Management of Pelvic Congestion and Lower Extremity Swelling Owing to Absence of Infrarenal Inferior Vena Cava
Authors: Zhou Wei , Rosenberg Wade , Lumsden Alan , Li James
Published: February 2011

Absence of isolated infrarenal inferior vena cava (IVC) is a rare condition documented in only a few published cases and typically treated with anticoagulation. We herein describe successful surgical management of the isolated infrarenal IVC absence in a healthy 35-year-old woman who presented with disabling pelvic congestion. An ascending venogram showed the absence of infrarenal IVC with a large left ovarian vein draining pelvic collateral vessels to the normal left renal vein and suprarenal IVC. The patient was successfully treated with a common femoral vein to the suprarenal IVC bypass using a bifurcated polytetrafluoroethylene graft, with rapid symptom resolution, and remained symptom free 6 months later. This is the first reported case describing a surgical strategy for isolated infrarenal IVC absence in a symptomatic patient.
Diagnosis and laparoscopic surgery in the female form of persistent Müllerian duct syndrome
Authors: Letourneau Karen , Lawrence Patrick , McTavish Gordon , Kirkpatrick Iain
Published: February 2011

Persistent Müllerian duct syndrome (PMDS) is a rare anomaly characterized by the presence of a combination of Müllerian derivatives, including a uterus, fallopian tubes, cervix or vagina in otherwise normally differentiated men. The female form of PMDS is particularly uncommon, making up only 5–10% of the 150 reported cases. In this case, PMDS was not diagnosed until the patient was well into the fifth decade of life. He presented with haematuria and haematospermia and was referred for sonographic examination. During the transrectal prostate ultrasound examination the Müllerian remnants were discovered, including uterus, cervix and vagina. In this report we describe the sonographic and magnetic resonance appearances of PMDS and discuss management via laproscopic hysterectomy and bilateral ovotestectomy.
Contrast-enhanced ultrasound compared with multislice computed tomography for endovascular aneurysm repair surveillance
Authors: Clevert D-A , Sommer W H , Meimarakis G , Kopp R , Weidenhagen R , Reiser M
Published: February 2011

Endoleaks after endovascular aneurysm repair (EVAR) are commonly encountered and present a diagnostic challenge in the follow-up after EVAR. Contrast-enhanced ultrasound (CEUS) is a new promising method in the diagnosis and follow-up of endoleaks. CEUS with SonoVue® allows a more rapid and non-invasive diagnosis. This review describes the aetiology, classification and importance of different types of endoleaks and compares CEUS findings with multislice computed tomography angiography, thus demonstrating the usefulness of CEUS in this clinical situation.
Technical tip: duplex surveillance for deep vein thrombosis post endoluminal venous procedures
Authors: Samuel N , Smith G E , Wolstenhulme S , Chetter I C
Published: February 2011

Duplex ultrasound imaging of the venous system has become the procedure of choice to evaluate the technical success post endoluminal ablative procedures and in the diagnosis of proximal leg DVT, which may occur as a rare complication. The purpose of this technical tip is to highlight the information that could be gathered by stepwise assessment of the deep venous system including the junctions with simple B-mode and Doppler colour flow imaging for the presence of an acute thrombus. This technique in turn may obviate the need for distal augmentation manoeuvres that is often used to demonstrate filling within the venous lumen and hence preclude potential iatrogenic thrombo-embolism.
Practical applications of ultrasound: getting the best out of your ultrasound machine
Authors: Venables Heather
Published: February 2011

Recently, there has been an explosion in the use of ultrasound outside the confines of the conventional imaging department. Many specialties are waking up to the huge potential for focused ultrasound and ultrasound guidance for interventions. Unfortunately, to date, very few formal ultrasound courses are available or accessible to specialist groups. The result is, in some cases, the purchase and use of ultrasound equipment by individuals with little or no training. A good understanding of the basic physics of ultrasound is helpful, but this is of little real value unless the operator can apply this in practice. When faced with a technically challenging examination, users need to be able to fit together their knowledge of underlying principles, an awareness of what each equipment control does and an appreciation of why the scan may be difficult. The aim of this paper is to provide clinicians who are new to ultrasound with an overview of key equipment controls and to indicate how these can be optimized.
Relation between Angle of Attack and Atmospheric Ice Accretion on Large Wind Turbine's Blade
Authors: Virk Muhammad S. , Homola Matthew C. , Nicklasson Per J.
Published: February 2011

A numerical study of wind turbine blade profile's angle of attack variation on atmospheric ice accretion near the blade tip section was performed. Three dimensional computational fluid dynamics (CFD) based numerical analyses were carried out using NACA 64618 blade profile at five different angles of attack ranging from −5 to +7.5 degrees. Based upon the flow field calculations and the super cooled water droplet collision efficiency, the rate and shape of accreted ice was simulated for both rime and glaze ice conditions. The results show that atmospheric icing is less severe at lower angles of attack, both in terms of local ice mass and relative ice thickness.
Grid Integration of Distributed Generation—Consequences on Node Voltage under Grid Perturbations
Authors: Vinothkumar K. , Selvan M. P.
Published: February 2011

Wind generators are very popular in most parts of the world as distributed generations (DG) owing to their technological advancement for grid integration, minimal environmental impact and free abundant availability. These wind generators usually employ induction machine for their electric power conversion due to its control simplicity and robustness in construction. The power output of such induction generator based wind turbine generator system (WTGS), depends on the node voltage and frequency of the connected radial distribution system (RDS). The node voltages of RDS are however subject to change due to variations in loading conditions. Therefore, a requirement arises to analyze the resulting mutual effect on the node voltages of RDS embedded with DG during such grid perturbations. Hence, the consequences of DG on the node voltages of RDS under anticipated small grid perturbations such as slow variation in grid frequency and connected loads are presented in this paper. The analysis is carried out on a practical Indian 25 bus radial distribution system embedded with different types of DG. From the results presented, it is observed that RDS embedded with fixed speed stall regulated WTGS are largely prone to voltage deviations at all nodes.
Experimental Comparison of Performances of Grid Connected Small Wind Energy Conversion Systems
Authors: Arifujjaman Md , Iqbal M. T. , Quaicoe J. E.
Published: February 2011

This paper presents an experimental comparative study of performances in terms of efficiency on two possible grid connected small wind turbine systems. One of the systems is based on Permanent Magnet Generator (PMG) and the other system is based on Wound Rotor Induction Generator (WRIG). The Power Conditioning System (PCS) for grid connection of the PMG-based system requires a rectifier, boost converter and a grid-tie inverter, while the WRIG-based system employs a rectifier, a switch and an external resistance in the rotor side with the stator directly connected to the grid. Experimental test benches for both systems are implemented using Wind Turbine Emulator (WTE) and Maximum Power Point Tracking (MPPT) control strategy. The procedure for calculate the PCS losses, energy capture and energy loss is presented. The expected efficiency of the systems is investigated for wind distributions at eight sites in Newfoundland and Labrador. It is shown that a WRIG-based system could provide 5% higher efficiency in contrast to a PMG-based system and could be an optimum alternative in the small wind energy domain.
Vibration Monitoring of Wind Turbine Blade using Fiber Bragg Grating
Authors: Fattahi S. J. , Zabihollah A. , Zareie S.
Published: February 2011

Rapid growth in generating power from wind turbines led to application of long laminated composite blades. However, as the length of blades increases, the risk of failure due to excessive vibration increases. Therefore, a reliable wind power generator requires an efficient and accurate, yet economical structural health monitoring system to detect vibration and apply a reliable control to prevent from unpredicted failure. This paper presents an optimal, low cost and continuous vibration monitoring system for laminated composite blades using Fiber Bragg Grating (FBG). Utilizing a layerwise displacement theory, the Finite Element (FEM) model has been developed for the wind turbine blade. The optomechanical relations between strains and FBG wavelength shift have been presented to study the dynamic of a wind turbine blade. The reflected spectrum caused by modal displacement, interrogated by WDM method has been studied for vibration control. Numerical examples have been presented to compare the FEM and FBG results which show a very good agreement for the first 3 vibration modes.
Robustly Optimal Contra-Rotating HAWT
Authors: Farthing S. P.
Published: February 2011

The contra-torquing Horizontal Axis Wind Turbine (HAWT) is optimised. The two rotor actuator discs are sheets of equal and opposite bound vorticity which induce a swirl crosswind flow between them, halved at the discs and nil outside them. The optimal circulation is constant radially and the power is the Betz limit.

Aft at blade speed of 1/3 windspeeed, the optimum apparent wind is straight ahead; the axial velocity change and thrust both reverse; and the product of lift coefficient by solidity is 2. If this aft value is realistically held at 2 for lower speed ratios, then the product climbs to 2 for the front rotor which becomes identical to the optimum single HAWT at zero speed ratio, where the contra combination has 3.56 times the starting torque and zero net thrust.

The design lift coefficients that robustly maintain the optimum as the windspeed varies slightly are given for a typical stalling blade section for the single HAWT, as well as the greater ones for the aft contra rotor and smaller for the fore rotor above the 1/3 speed ratio of reversing aft thrust. But the apparent wind difference dominates to make the aft robust design pitch considerably greater than the fore (and single) towards the 1/3 ratio. A contra-torquing stator is shown to best follow a rotor.
Distributed Health Monitoring System for Zhanjiang Bay Bridge
Authors: Cao Yinghong , Zhang Yi , Zhao Yang , Wang Ming L.
Published: February 2011

Zhanjiang Bay Bridge is a cable-stayed bridge with a main span of 480 m. In order to verify the structural properties and monitor its behavior in service and extreme conditions, a Distributed Bridge Health Monitoring System (DBHMS) was installed when the bridge opened to traffic in December 2006. Based on the analysis of the bridge's behavior, the DBHMS was designed to be a concise monitoring system with a minimum of 60 sensors to monitor the key parameters. The entire system was designed as a three-layer structure consisting of sensors, substations, and a server. The system reliability was improved by distributing part of the data processing from the central server into substations located at the bridge. Practical structural behavior identification techniques, including virtual channel, three-level warning system, and data statistics, were developed for the real-time health monitoring of this bridge. Some analysis of the data collected during these two years showed the efficiency of this system in detecting the bridge's abnormal behaviors under the excitation of temperature, traffic load, and a typhoon.
Damage Detection and Autonomous Repair System Coordination
Authors: Huston Dryver , Hurley David , Gollins Kenneth , Gervais Anthony , Ziegler Tim
Published: February 2011

Self-repairing structural systems offer potentially extended performance ranges and lifetimes when compared to conventional systems without self-healing capability. Self-healing materials where damage directly initiates a repair response without supervisory coordination have been used for automotive and aeronautical applications for over a century. Integrating sensing and supervisory control technologies with self-healing can further extend the safety and reliability of critical components and structures. Laboratory scale test beds were created to illustrate the benefits of a coupled system. A thermal-healing polymer embedded with resistive heating wires acts as the sensing-healing material. The impedance, capacitance, and resistance between and across heating wires both detect and assess damage. Once damage had been detected, repairs were initiated, monitored through completion and terminated. This proof-of-concept prototype can likely be expanded and improved with alternative sensor options, sensing-healing materials, and system architecture.
The Yield of an Open Innovation Arena for Occupational Health and Safety Ideas in the Swedish Construction Industry
Authors: Andersson E. Roland , Lundblad Jan , Jansson Bjarne
Published: February 2011

The rationale behind our approach was that product innovations in occupational health and safety originate from radical innovation processes where ideas are tested naturally before any rational decisions are made. Our thesis therefore was that an open and subsidized radical innovation arena might counteract today's development imperfections and also be profitable to the society as a whole. In this study we critically scrutinized the implementation of such a publically open arena in the Swedish construction industry, which is an area with large costs for accidents and injuries. We used a two-step action research approach in order to compare the efficiency of a general arena (Innovation Stockholm) with a specialised health and safety arena, given the same radical supporting style and entrepreneurial culture. Our results confirmed our thesis: both arenas produced successful innovations and were profitable to the society as a whole. The specialised arena even doubled the efficiency for an idea to be in the market after 2 years: from 0.1 ideas to 0.25 ideas. In a general perspective we believe that our findings can contribute to the discussion on the “Open innovation” concept and how to reorganize the established “Science Park” innovation model.
On The Distortional Buckling, Post-Buckling And Strength of Cold-Formed Steel Lipped Channel Columns Under Fire Conditions
Authors: Landesmann Alexandre , Camotim Dinar
Published: February 2011

This paper reports the available results of an ongoing shell finite element investigation on the distortional buckling, post-buckling and ultimate strength behaviour of cold-formed steel lipped channel columns (centrally compressed members) subjected to high temperatures typically caused by fire conditions. Two column collapse situations are dealt with, corresponding to different loading strategies: (i) application of an increasing compressive load to columns subjected to a constant (uniform) temperature distribution, in order to obtain failure loads, and (ii) application of a progressive temperature raise to axially compressed column, in order to obtain failure temperatures - the latter approach provides a more realistic simulation of fire conditions. The steel material behaviour at high temperatures is described by the constitutive model prescribed in Eurocode 3 for cold-formed steel. After validating the numerical model adopted, through the comparison with results of simulations reported in the literature and based on experimentally obtained stress-strain laws, the paper presents numerical results concerning lipped channel columns made of various steel grades under fire conditions - they consist of (i) non-linear equilibrium paths, yielded by steady state and transient column analyses, and (ii) the corresponding failure loads/stresses and temperatures.
Behaviour of R.C. Beams Under Elevated Temperature
Authors: Jayasree G. , Lakshmipathy M. , Santhanaselvi S.
Published: February 2011

Concrete is subjected to elevated temperature for short duration, long duration and cyclic heating on many occasions. The dramatic fire accidents/incidents have renewed the interest in the area of research on concrete subjected to elevated temperature. From the literature review it is found that the experimental data which simulate the conditions of structural elements in stressed conditions when exposed to fire are scarce. The work presents a study on the residual characteristics of R.C. beams subjected to elevated temperature under unstressed and stressed conditions. The R.C beams were of size 120mm×120mm×1500mm and designed with single and double reinforcement and referenced as Type I and Type II respectively. M20 grade of concrete was used in casting the beams. The temperatures were kept as 100°C, 200°C, 300°C, 400°C and 500°C and the duration of exposure was 4 hours. The specimens were cooled in air and the residual properties were tested by conducting two point bending test on R.C. beams and their behavioral parameters were studied in comparison with beams tested under normal (room) temperature conditions. The extent of damage suffered measured by the damage factor was about 32 % for Type I beams and about 48% for the Type II beams tested under unstressed test condition when exposed to 500°C; whereas it is to an extent of 33% for Type I beams and 49% for Type II beams in stressed test condition for the same exposed temperature. The degradation in initial stiffness was nearly 57% and 49% for Type I and Type II beams in unstressed test and 54% and 73% respectively for stressed test when exposed to 500°C. The degradation in stiffness at 50% of ultimate load was nearly 36% and 35% for Type I and Type II beams in unstressed test and 49% and 76.6% respectively for stressed test when exposed to 500°C. The ultimate load of R.C. beams tested in stressed condition were marginally 5% lower than the beams under unstressed test condition.
Structural Performance of Slim Beam Floor System in Fire
Authors: Choi Sengkwan , Ali Faris , Nadjai Ali , Han Sanghoon , Choi Joungyoon
Published: February 2011

This paper presents a numerical study to predict the in-fire performance of slim floor system, composed of asymmetric steel beam, deep steel decking and in-situ concrete slab. The reliability of the proposed numerical model was verified by comparison with experimental results obtained for 4.2m beam tests. A pilot study was also conducted to examine the effect of the cross sectional modification of the steel section on performance enhancement of the model in fire.
Alternatives to Sodium Amobarbital in the Wada Test
Authors: Patel Akta , Wordell Cindy , Szarlej Dorata
Published: February 2011

Objective:

To review the literature and identify alternatives to sodium amobarbital for use in the Wada test.

Data Sources:

A search of PubMed (1960-October 2010) was performed using the following key words alone or in combination: Wada test, intracarotid amobarbital procedure, intracarotid, intraarterial, sodium amobarbital, methohexital, Brevital, pentobarbital, etomidate, propofol, and alternative anesthetics. References of the identified articles were reviewed for relevant information.

Study Selection and Data Extraction:

All articles in English identified from the data sources were evaluated. Review included comparative, prospective, and retrospective studies along with case series and case reports.

Data Synthesis:

Methohexital, pentobarbital, etomidate, and propofol have all been studied as alternatives to sodium amobarbital in the Wada test. Four controlled experimental trials, 1 uncontrolled experimental trial, 6 retrospective chart reviews, and 2 case reports were reviewed. Methohexital, pentobarbital, and propofol required a second injection due to their short duration of action. Etomidate was studied as a bolus injection followed by a continuous infusion until the critical speech and memory tests were administered, which differed from the standard Wada test procedure. Patients had an increased risk of seizures with methohexital, whereas 1 patient developed transient respiratory depression immediately after receiving pentobarbital. Furthermore, propofol caused increased tone with twitching and rhythmic movements, which interfered with the completion of the Wada test for 1 patient. All authors concluded that these agents were equivalent to amobarbital for the Wada test.

Conclusions:

Methohexital, pentobarbital, etomidate, and propofol are viable alternatives to sodium amobarbital for use in the Wada test, but each has shortcomings.
Authorship and Characteristics of Articles in Pharmacy Journals: Changes Over a 20-Year Interval
Authors: Dotson Bryan , McManus Kevin P , Zhao Jing J , Whittaker Peter
Published: February 2011

Background:

To our knowledge, no studies have evaluated authorship patterns and characteristics of articles in pharmacy journals,

Objective:

To investigate changes over a 20-year period in authorship and characteristics of articles in pharmacy journals.

Methods:

All articles published in the American Journal of Health-System Pharmacy, The Annals of Pharmacotherapy, and Pharmacotherapy in 1989, 1999, and 2009 were reviewed. Data collected for each article included article type, number of authors, number of physician authors, whether any author was affiliated with a pharmaceutical company, and source of funding.

Results:

The number of articles included was 574 in 1989, 659 in 1999, and 589 in 2009. The mean number of authors per article increased from 2.5 in 1989 to 2.8 in 1999 and 3.6 in 2009 (p< 0.001). Conversely, the proportion of articles with a single author decreased from 35% in 1989 to 23% in 1999 and 11 % in 2009 (p < 0.001), while the proportion of multi-authored articles (>6 authors) increased from 2% in 1989 to 3% in 1999 and 9% in 2009 (p < 0.001). A physician author was listed on 25% of papers in 1989, which increased to 38% in 1999 and 41% in 2009 (p < 0.001). Among research articles with declared funding from industry, there was an increase over time in reported author affiliation with an industry sponsor (10% of articles in 1989, 17% in 1999, and 66% in 2009; p < 0.001).

Conclusions:

Significant changes in authorship patterns and characteristics of articles were observed from 1989 to 2009. We found an increase in the number of authors per article over time, with fewer single-author papers now published. The explanations for the changes are likely multifactorial, including increased pressure to publish, increased research complexity, and inappropriate authorship. To prevent inappropriate author-number inflation and to preserve authorship's meaning and value, authors should adhere to the criteria for authorship from the International Committee of Medical Journal Editors.
Health-Care Policy 2011: Implications for Pharmacists
Authors: Matzke Gary R
Published: February 2011

Objective:

The enactment of the Patient Protection and Affordable Care Act of 2010 set the stage for a new era. The 2010 Congressional election results and recent court rulings challenging the constitutionality of various provisions of the Act suggest that implementation will be anything but straightforward. The proposed changes in health insurance, along with modifications in current reimbursement models, will alter the health-care environment. It is important for pharmacists to be aware of these opportunities and the resultant changes in public expectations. It is with these considerations in mind that The Annals announces the creation of a Health Care Policy expert panel to initiate commentary and discussion regarding health-care policy issues of relevance to the pharmacy community.
School Vouchers in a Climate of Political Change
Authors: Sutton Lenford C. , King Richard A.
Published: February 2011

Legal scrutiny of school voucher policies initially focused on the establishment clause concerning with allocating public dollars to schools sponsored by religious organizations. In recent years, advocates asserted that the exclusion of faith-based organizations from voucher plans that permit expenditures in secular private organizations violates equal protection and free exercise guarantees. In addition to legal arguments is today's imperative to reform education in ways that promote safe and effective learning environments. Proponents contend that open competition would place healthy pressure on both public and private schools, thus improving outcomes for all children. In contrast, opponents point to the diversion of tax dollars from public schools to support efforts to privatize and abandon the common school just to advance the interests of a small segment of the population. They also view voucher plans as highly divisive in fostering government entanglement with churches and serving as a catalyst for re-segregating public schools. The framework for initial analyses in this article is the evolution of voucher plans, including a historical account of the social unrest that increased demand for public support of privately sponsored schooling through the early 20th century. The perspective shifts from social and economic contexts to state and federal constitutional bases for legal challenges and the reluctance of courts to embrace free exercise and equal protection claims of voucher advocates. Next, there is a description of the legal strategies available to today's voucher rivals in the aftermath of Zelman v. Simmons-Harris (2002), which effectively eliminated federal barriers to voucher expansion. The final section describes the parallel course of early school finance lawsuits and our forecast of school voucher litigation in tandem with a discussion of the political struggles around school choice which offer the most promise for influencing judicial outcomes in state courts nationwide.
Biotinylated Probe Isolation of Targeted Gene Region Improves Detection of T790M Epidermal Growth Factor Receptor Mutation via Peptide Nucleic Acid–Enriched Real-Time PCR
Authors: Li Jin , Jänne Pasi A , Makrigiorgos G Mike
Published: February 2011

BACKGROUND

The presence of the EGFR (epidermal growth factor receptor) T790M mutation in tumor tissue or body fluids from patients treated with EGFR tyrosine kinase inhibitors may indicate the onset of resistance to treatment. It is important to identify this mutation as early as possible so that treatment can be modified accordingly or potential side effects of further treatment can be avoided. This requirement calls for high detection sensitivity. Peptide nucleic acids (PNAs) are used as PCR clamps to inhibit amplification of wild-type DNA during PCR cycling, thereby enriching for rare mutations such as T790M. We describe a modification that improves the detection limit of PNA-clamp methods by at least 20-fold.

METHODS

We enriched the target by exposing genomic DNA to an EGFR exon 20–specific biotinylated oligonucleotide, followed by binding to streptavidin beads. We then prepared serial dilutions of the isolated target DNA containing the T790M mutation by mixing with wild-type DNA and then performed PNA clamp–based, real-time TaqMan PCR. For comparison, we performed PNA clamp–based PCR directly on genomic DNA.

RESULTS

Whereas the detection limit for PNA clamp–based PCR performed directly on genomic DNA is 1 mutant allele in 1000 wild-type alleles, conducting the assay with biotinylated oligonucleotide–enriched target DNA improved the detection limit to 1 mutant allele in 40 000 wild-type alleles. A possible explanation for the improvement in detection is that biotin-based target isolation efficiently eliminates wild-type DNA; therefore, fewer erroneous amplifications of wild-type DNA can occur early during the PCR.

CONCLUSIONS

Combining target molecule isolation via a biotinylated probe with PNA-enriched TaqMan real-time PCR provides a major improvement for detecting the EGFR T790M resistance mutation.
Cystatins: a versatile family
Authors: Esposito Veronica , Temussi Piero A.
Published: February 2011

Cystatins are small proteins, typically composed of 100–120 amino acids, which together with similar proteins devoid of inhibitory properties, belong to a cystatin ‘superfamily’. Cystatins can do more than just inhibit proteases: two important aspects described here are aggregation properties linked to misfolding diseases and the unique ability of monellin, a plant cystatin, to elicit sweet taste. The explanation of the puzzling phenomenon of ‘sweet proteins’ required an in-depth structural study of monellin, also regarding the causes of the high thermal stability of its single chain structure. The detailed mechanisms by which cystatins aggregate could be relevant in the study of misfolding diseases involving cystatins. They are reviewed here with emphasis on 3D domain swapping, typical of aggregating cystatins. While studying monellin, we noticed that it aggregates in a conventional way, probably through the cross-β spine mechanism. However, several cystatins derived from oryzacystatin_I to emulate the taste behavior of monellin aggregate via different mechanisms.
MAPKs in development: insights from Dictyostelium signaling pathways
Authors: Hadwiger Jeffrey A. , Nguyen Hoai-Nghia
Published: February 2011

Mitogen activated protein kinases (MAPKs) play important roles in the development of eukaryotic organisms through the regulation of signal transduction pathways stimulated by external signals. MAPK signaling pathways have been associated with the regulation of cell growth, differentiation, and chemotaxis, indicating that MAPKs contribute to a diverse set of developmental processes. In most eukaryotes, the diversity of external signals is likely to far exceed the diversity of MAPKs, suggesting that multiple signaling pathways might share MAPKs. Do different signaling pathways converge before MAPK function or can MAPKs maintain signaling specificity through interactions with specific proteins? The genetic and biochemical analysis of MAPK pathways in simple eukaryotes such asDictyosteliumoffers opportunities to investigate functional specificity of MAPKs in G-protein-mediated signal transduction pathways. This review considers the regulation and specificity of MAPK function in pathways that controlDictyosteliumgrowth and development.
Functional Reorganization of the Brain in Humans Following Spinal Cord Injury: Evidence for Underlying Changes in Cortical Anatomy
Authors: Henderson Luke A. , Gustin Sylvia M. , Macey Paul M. , Wrigley Paul J. , Siddall Philip J.
Published: February 2011

Loss of somatosensory drive results in functional reorganization of the primary somatosensory cortex (SI). While the phenomenon of functional cortical reorganization is well established, it remains unknown whether in humans, functional reorganization results from changes in brain anatomy, or simply reflects an unmasking of already existing dormant synapses. In 20 subjects with complete thoracic spinal cord injuries (SCIs) and 23 controls, we used functional and structural magnetic resonance imaging to determine whether SI reorganization was associated with changes in SI anatomy. SCI resulted in a significant SI reorganization, with the little finger representation moving medially toward the lower body representation (i.e., area of sensory loss). Furthermore, although SCI was associated with gray matter volume loss in the lower body representation, this loss was minimized as reorganization increased. That is, the greater the medial shift in little finger representation, the greater the gray matter preservation in the lower body representation. In addition, in the region of greatest SI reorganization (little finger), fractional anisotropy was correlated with SI reorganization. That is, as SI reorganization increased, the extent of aligned structures decreased. Finally, although thalamocortical fibers remained unchanged, the ease and direction of water movement within the little finger representation was altered, being directed more toward the midline in SCI subjects. These data show that SI reorganization following SCI is associated with changes in SI anatomy and provide compelling evidence that SI reorganization in humans results from the growth of new lateral connections, and not simply from the unmasking of already existing lateral connections.
Dynamic Causal Modeling of Subcortical Connectivity of Language
Authors: David Olivier , Maess Burkhard , Eckstein Korinna , Friederici Angela D.
Published: February 2011

Subcortical–cortical interactions in the language network were investigated using dynamic causal modeling of magnetoencephalographic data recorded during auditory comprehension. Participants heard sentences that either were correct or contained violations. Sentences containing violations had syntactic or prosodic violations or both. We show that a hidden source, modeling magnetically silent deep nuclei, is required to explain the data best. This is in line with recent brain imaging studies and intracranial recordings suggesting an involvement of subcortical structures in language processing. Here, the processing of syntactic and prosodic violations elicited a global increase in the amplitude of evoked responses, both at the cortical and subcortical levels. As estimated by Bayesian model averaging, this was accompanied by various changes in cortical-cortical and subcortical–cortical connectivity. The most consistent findings in relation to violations were a decrease of reentrant inputs to Heschl's gyrus (HG) and of transcallosal lateral connections. These results suggest that in conditions where one hemisphere detects a violation, possibly via fast thalamocortical (HG) loops, the intercallosal connectivity is reduced to allow independent processing of syntax (left hemisphere) and of prosody (right hemisphere). This study is the first demonstration in cognitive neuroscience that subcortical–cortical loops can be empirically investigated using noninvasive electrophysiological recordings.
Spontaneous Electrical Activity in the Human Fetal CortexIn Vitro
Authors: Moore Anna R. , Zhou Wen-Liang , Jakovcevski Igor , Zecevic Nada , Antic Srdjan D.
Published: February 2011

Our knowledge about the developing human cerebral cortex is based on the analysis of fixed postmortem material. Here we use electrical recordings from unfixed human postmortem tissue to characterize the synaptic physiology and spontaneous network activity of pioneer cortical neurons (“subplate neurons”). Our electrophysiological experiments show that functional glutamate or GABA ionotropic receptors are expressed on human subplate (SP) neurons as early as 20 gestational weeks. Extracellular (synaptic) stimulations evoked postsynaptic potentials in a very small fraction of SP neurons, suggesting that functional synaptic contacts are rare at midgestation. Although synaptic inputs were scarce, we regularly observed spontaneous (unprovoked) electrical activity among human SP neurons, comprised of sustained plateau depolarizations and bursts of action potential firing, which resembled cortical UP and DOWN states in the adult neocortex. Plateau depolarizations and bursts of action potential firing are thought to depend on the mature morphology and physiology of adult cortical network. However, our current data reveal that similar cortical rhythm is generated by a very immature ensemble of human fetal neurons. In the relative absence of sensory inputs, as in developmentin utero, or in slow-wave sleep (i.e., throughout the entire lifespan), the spontaneous slow oscillatory pattern (UP and DOWN states) is a fundamental aspect of human cortical physiology.
Role for Reelin in Neurotransmitter Release
Authors: Hellwig Sabine , Hack Iris , Kowalski Janina , Brunne Bianka , Jarowyj Joel , Unger Andreas , Bock Hans H. , Junghans Dirk , Frotscher Michael
Published: February 2011

The extracellular matrix molecule Reelin is known to control neuronal migration during development. Recent evidence suggests that it also plays a role in the maturation of postsynaptic dendrites and spines as well as in synaptic plasticity. Here, we aimed to address the question whether Reelin plays a role in presynaptic structural organization and function. Quantitative electron microscopic analysis of the number of presynaptic boutons in the stratum radiatum of hippocampal region CA1 did not reveal differences between wild-type animals and Reelin-deficientreelermutant mice. However, additional detailed analysis showed that the number of presynaptic vesicles was significantly increased in CA1 synapses ofreelermutants. To test the hypothesis that vesicle fusion is altered inreeler, we studied proteins known to control transmitter release. SNAP25, a protein of the solubleN-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, was found to be significantly reduced inreelermutants, whereas other SNARE complex proteins remained unaltered. Addition of recombinant Reelin to organotypic slice cultures of reeler hippocampi substantially rescued not only SNAP25 protein expression levels but also the number of vesicles per bouton area indicating a role for Reelin in presynaptic functions. Next, we analyzed paired-pulse facilitation, a presynaptic mechanism associated with transmitter release, and observed a significant decrease at CA1 synapses ofreelermutants when compared with wild-type animals. Together, these novel findings suggest a role for Reelin in modulating presynaptic release mechanisms.
Origin and Determination of Inhibitory Cell Lineages in the Vertebrate Retina
Authors: Jusuf Patricia R. , Almeida Alexandra D. , Randlett Owen , Joubin Kathy , Poggi Lucia , Harris William A.
Published: February 2011

Multipotent progenitors in the vertebrate retina often generate clonally related mixtures of excitatory and inhibitory neurons. The postmitotically expressed transcription factor, Ptf1a, is essential for all inhibitory fates in the zebrafish retina, including three types of horizontal and 28 types of amacrine cell. Here, we show that specific types of inhibitory neurons arise from the cell-autonomous influence of Ptf1a in the daughters of fate-restricted progenitors, such as Ath5 or Vsx1/2-expressing progenitors, and that in the absence of Ptf1a, cells that would have become these specific inhibitory subtypes revert to the histogenetically appropriate excitatory subtypes of the same lineage. Altered proportions of amacrine subtypes respecified by the misexpression of Ptf1a in the Ath5 lineage suggest that Ath5-expressing progenitors are biased, favoring the generation of some subtypes more than others. Yet the full array of inhibitory cell subtypes in Ath5 mutants implies the existence of Ath5-independent factors involved in inhibitory cell specification. We also show that an extrinsic negative feedback on the expression of Ptf1a provides a control mechanism by which the number of any and all types of inhibitory cells in the retina can be regulated in this lineage-dependent way.
Presenilin-1 Regulates Neural Progenitor Cell Differentiation in the Adult Brain
Authors: Gadadhar Archana , Marr Robert , Lazarov Orly
Published: February 2011

Presenilin-1 (PS1) is the catalytic core of the aspartyl protease γ-secretase. Previous genetic studies using germ-line deletion ofPS1and conditional knock-out mice demonstrated that PS1 plays an essential role in neuronal differentiation during neural development, but it remained unclear whether PS1 plays a similar role in neurogenesis in the adult brain. Here we show that neural progenitor cells infected with lentiviral vectors-expressing short interfering RNA (siRNA) for the exclusive knockdown of PS1 in the neurogenic microenvironments, exhibit a dramatic enhancement of cell differentiation. Infected cells differentiated into neurons, astrocytes and oligodendrocytes, suggesting that multipotentiality of neural progenitor cells is not affected by reduced levels of PS1. Neurosphere cultures treated with γ-secretase inhibitors exhibit a similar phenotype of enhanced cell differentiation, suggesting that PS1 function in neural progenitor cells is γ-secretase-dependent. Neurospheres infected with lentiviral vectors expressing siRNA for the targeting of PS1 differentiated even in the presence of the proliferation factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), suggesting that PS1 dominates EFG and bFGF signaling pathways. Reduction of PS1 expression in neural progenitor cells was accompanied by a decrease in EGF receptor and β-catenin expression level, suggesting that they are downstream essential transducers of PS1 signaling in adult neural progenitor cells. These findings suggest a physiological role for PS1 in adult neurogenesis, and a potential target for the manipulation of neural progenitor cell differentiation.
Tau-Induced Defects in Synaptic Plasticity, Learning, and Memory Are Reversible in Transgenic Mice after Switching Off the Toxic Tau Mutant
Authors: Sydow Astrid , Van der Jeugd Ann , Zheng Fang , Ahmed Tariq , Balschun Detlef , Petrova Olga , Drexler Dagmar , Zhou Lepu , Rune Gabriele , Mandelkow Eckhard , D'Hooge Rudi , Alzheimer Christian , Mandelkow Eva-Maria
Published: February 2011

This report describes the behavioral and electrophysiological analysis of regulatable transgenic mice expressing mutant repeat domains of human Tau (TauRD). Mice were generated to express TauRDin two forms, differing in their propensity for β-structure and thus in their tendency for aggregation (“pro-aggregant” or “anti-aggregant”) (Mocanu et al., 2008). Only pro-aggregant mice show pronounced changes typical for Tau pathology in Alzheimer's disease (aggregation, missorting, hyperphosphorylation, synaptic and neuronal loss), indicating that the β-propensity and hence the ability to aggregate is a key factor in the disease. We now tested the mice with regard to neuromotor parameters, behavior, learning and memory, and synaptic plasticity and correlated this with histological and biochemical parameters in different stages of switching TauRDon or off. The mice are normal in neuromotor tests. However, pro-aggregant TauRDmice are strongly impaired in memory and show pronounced loss of long-term potentiation (LTP), suggesting that Tau aggregation specifically perturbs these brain functions. Remarkably, when the expression of human pro-aggregant TauRDis switched on for ∼10 months and off for ∼4 months, memory and LTP recover, whereas aggregates decrease moderately and change their composition from mixed human plus mouse Tau to mouse Tau only. Neuronal loss persists, but synapses are partially rescued. This argues that continuous presence of amyloidogenic pro-aggregant TauRDconstitutes the main toxic insult for memory and LTP, rather than the aggregates as such.
Dorsal Radial Glial Cells Have the Potential to Generate Cortical Interneurons in Human But Not in Mouse Brain
Authors: Yu Xiaojing , Zecevic Nada
Published: February 2011

Radial glial (RG) cells, in the neocortical ventricular/subventricular zone (VZ/SVZ), generate cortical projection neurons both in rodents and humans, but whether they can also generate cortical interneurons is not clear. We demonstrated both on cryosections and in cell cultures that in the human VZ/SVZ, cells can be double labeled with RG markers and calretinin (CalR) and GABA, markers that suggest interneuronal lineage. We examined in more detail the cell fate of human RG cells isolated from the VZ/SVZ at midterm. After 24 h, no CalR+or GABA+cells were seen in cultures, whereas 5–10% cells expressed Nkx2.1 and Dlx, two ventral transcription factors. CalR+and GABA+cells were apparent for the first time after 3 din vitro, and their number increased in subsequent days, consistent with the gradual transition of RG cells into CalR+or GABA+cells. Indeed, the progeny of genetically labeled RG cells could be immunolabeled with antibodies to CalR and GABA or ventral transcription factors (Nkx2.1+, Dlx+). In contrast to humans, in the embryonic mouse, similar experiments showed that only RG cells isolated from the subpallium (ganglionic eminence) generate CalR+or GABA+cells, whereas this was not the case with RG cells isolated from the pallium. These findings support the idea that human, but not mouse, dorsal RG cells have the potential to generate various subtypes of neocortical interneurons. Multiple progenitors and sites of cortical interneuron origin in human might be an evolutionary adaptation underlying brain expansion and the increased complexity of cortical circuitry in humans.
Endogenous GABA Levels in the Pontine Reticular Formation Are Greater during Wakefulness than during Rapid Eye Movement Sleep
Authors: Vanini Giancarlo , Wathen Bradley L. , Lydic Ralph , Baghdoyan Helen A.
Published: February 2011

Studies using drugs that increase or decrease GABAergic transmission suggest that GABA in the pontine reticular formation (PRF) promotes wakefulness and inhibits rapid eye movement (REM) sleep. Cholinergic transmission in the PRF promotes REM sleep, and levels of endogenous acetylcholine (ACh) in the PRF are significantly greater during REM sleep than during wakefulness or non-REM (NREM) sleep. No previous studies have determined whether levels of endogenous GABA in the PRF vary as a function of sleep and wakefulness. This study tested the hypothesis that GABA levels in cat PRF are greatest during wakefulness and lowest during REM sleep. Extracellular GABA levels were measured during wakefulness, NREM sleep, REM sleep, and the REM sleep-like state (REMNeo) caused by microinjecting neostigmine into the PRF. GABA levels varied significantly as a function of sleep and wakefulness, and decreased significantly below waking levels during REM sleep (−42%) and REMNeo(−63%). The decrease in GABA levels during NREM sleep (22% below waking levels) was not statistically significant. Compared with NREM sleep, GABA levels decreased significantly during REM sleep (−27%) and REMNeo(−52%). Comparisons of REM sleep and REMNeorevealed no differences in GABA levels or cortical EEG power. GABA levels did not vary significantly as a function of dialysis site within the PRF. The inverse relationship between changes in PRF levels of GABA and ACh during REM sleep indicates that low GABAergic tone combined with high cholinergic tone in the PRF contributes to the generation of REM sleep.