Csd

The liquid antisolvent (LAS) precipitation process for production of ultra-fine particles has been widely researched for a last few decades. In LAS process, precipitation of solute is achieved by decreasing the solvent power for the solute dissolved in a solution. This is done by addition of a non-solvent for solute called as antisolvent. The method is applicable for a wide range of materials such as pharmaceutical ingredients, inorganic compounds, polymers and proteins. In this work, efforts have been made to review the use of LAS for precipitation and stabilization of ultrafine particles of poorly water soluble drugs. The main focus of this review is on the strategies for controlling particle size, size distribution, and stabilization of ultrafine particles using polymers and surfactants. Process intensification of LAS process using ultrasound and rapid mixing devices has also been discussed in detail.

Stress, a common if unpredictable life event, can have pronounced effects on physiology and behavior. Individuals show wide variation in stress susceptibility and resilience, which are only partially explained by variations in coding genes. Developmental programing of the hypothalamic-pituitary-adrenal stress axis provides part of the explanation for this variance. Epigenetic approaches have successfully helped fill the explanatory gaps between the influences of gene and environment on stress responsiveness, and differences in the sequelae of stress across individuals and generations. Stress and the stress axis interacts bi-directionally with epigenetic marks within the brain. It is now clear that exposure to stress, particularly in early life, has both acute and lasting effects on these marks. They in turn influence cognitive function and behavior, as well as the risk for suicide and psychiatric disorders across the lifespan and, in some cases, unto future generations.

Brain neuronal dysfunction has been implicated in pathogenesis of migraine but direct evidence is lacking. Scintillating scotoma of migraine is generally believed to originate at the visual cortex. While cortical spreading depression is a relatively late physiological alteration in migraine, its protective role in neuronal ischaemia is increasingly being recognized. Atenolol, nadolol, or verapamil prevent migraine but do not readily cross the blood–brain barrier or critically influence any brain or peripheral neuronal function. Typical migraine headache, aura, or scintillating scotoma has not been reported following enucleation or evisceration of the eye. In humans, pain and temperature fibres from only the ophthalmic division of the trigeminal nerve reach the upper cervical spinal segments. Pain in migraine attacks including occipital and nuchal discomfort reflects selective involvement of the ophthalmic nerve. Photophobia is largely a retinal reflex involving the ophthalmic division of the trigeminal nerve. Key clinical features of the migrainous scintillating scotoma are consistent with retinal origin. Spreading depression in the retina is well-established. A subtle regional ocular sympathetic deficit prevails in migraine patients and possibly impairs regulation of intraocular choroidal blood volume and intraocular pressure. Several first-line migraine prophylactic agents lower the intraocular pressure. The neuro-ophthalmological basis for a monocular origin of migrainous scintillating scotomata due to mechanical deformation of the posterior segment of the corneo-scleral envelope consequent to choroidal venous congestion and rise in intraocular pressure is presented. Study of distribution and displaceability of the migrainous scintillating scotoma can settle its site of origin. Headache of migraine possibly arises from a similar mechanical deformation of the anterior eye segment followed by antidromic discharge in the trigeminovascular system. Lateralizing negative deficits such as homonymous hemianopia probably reflect vasospastic complications of migraine. A rational explanation for the most characteristic clinical features of migraine and a new template to elucidate the pharmacological basis of anti-migraine drugs is offered.

Dredging is the sub aqueous or underwater excavation of rocks and soil. The purpose of this research is to  analyze the present volume of dredging in India and to identify the actual requirement of dredging volume and the dredging fleet in India. The first phase of the study involves the identification of actual amount of capital and maintenance dredging being undertaken in India and the present available fleet of dredgers in the Public and private sector. The second phase involves the study on how various players get into this business and the final phase involves possible strategic methods of improving the capacity and meeting the dredging requirement. A possible alliance between the dredging majors with the help of govt. policies aiming in capacity creation for undertaking commercial dredging activities are also presented.

Delayed ischemic neurologic deficit (DIND) is a serious and poorly understood complication of aneurysmal subarachnoid hemorrhage. Although advances in treatment have improved prognosis for these patients, long-term clinical outcomes remain disappointing. Historically, angiographic vasospasm was thought to result in a DIND, although an increasing body of evidence suggests that this is an oversimplification, because interventions that have effectively targeted angiographic vasospasm have not improved outcome. Consequently, the relationship between angiographic vasospasm and neurologic outcome may be associative rather than causative. Although our understanding of the underlying molecular processes and pathophysiology is improving, responsible mediators or pathways have yet to be identified. The aim of this review is to summarize the key historical events that have helped shape our understanding of the pathophysiology of this phenomenon (microcirculation, autoregulation, microthrombosi...

The human Y-box protein 1 (YB-1) is a member of the Y-box protein family, a class of proteins involved in transcriptional and translational regulation of a wide range of genes. Here, we report the solution structure of the cold-shock domain (CSD) of YB-1, which is thought to be responsible for nucleic acid binding. It is the ®rst structure solved of a eukaryotic member of the cold-shock protein family and consists of a closed ®ve-stranded anti-parallel b-barrel capped by a long¯exible loop. The structure of CSD is similar to the OB-fold and a comparison with bacterial cold-shock proteins shows that its structural properties are conserved from bacteria to man. Our data suggest the presence of a DNAbinding site consisting of a patch of positively charged and aromatic residues on the surface of the b-barrel. Further, it is shown that CSD, which has a preference for binding single-stranded pyrimidine-rich sequences, binds weakly and hardly speci®cally to DNA. Binding af®nities reported for intact YB-1 indicate that domains other than the CSD play a role in DNA binding of YB-1.

The range of target structures in the fifth international blind test of crystal structure prediction was extended to include a highly flexible molecule, (benzyl-(4-(4-methyl-5-(p-tolylsulfonyl)-1,3-thiazol-2-yl)phenyl)carbamate, as a challenge representative of modern pharmaceuticals. Two of the groups participating in the blind test independently predicted the correct structure. The methods they used are described and contrasted, and the implications of the capability to tackle molecules of this complexity are discussed.

Explosive activity at Mt. Etna from July 19 to August 7, 2001, provides a good case study to investigate the causes of the transitions between style of basaltic explosion. In this period, a new vent, located at 2550 m above sea level on the southern flank of the volcano, exhibited three types of activities that followed one another: initial ash and steam explosions with the emission of radial jets, of hydromagmatic origin; intermediate fire fountaining and Strombolian explosions, due to magma vesiculation; and finally, sustained to pulsing ash explosions, caused by overpressurization of the degassed and cooling top of the magma column. The activities produced two end-members of juvenile ash in the size range 0.4–0.1 mm: (1) brown, fluidal- to irregular-shaped, vesicular sideromelane glass particles, and (2) microcrystalline, blocky, poorly vesicular tachylite particles. Component analysis of the ash reveals a gradual decrease in the abundance of sideromelane, replaced by tachylite, in the transition from the Strombolian to the final ash explosion activity. Dense blocks with irregular, variable surface textures also characterize the products of the late pulsing ash explosions. Petrographic, chemical, and crystal size distribution analyses, together with morphological evidences, indicate that sideromelane quenched earlier than tachylite during the final stage of magma evolution. In fact, the groundmass of tachylite formed by subsequent crystallization of magma, possibly at lower temperature and under different degassing conditions. We hypothesize that sideromelane formed in the central part of the volcanic conduit, where the buoyant rise of gas bubbles caused a higher magma ascent velocity, which did not allow time for vesicle to escape or collapse before fragmentation. Conversely, tachylite crystallized at the margins of the conduit, where slow-moving magma accumulated, temperature was lower, and vesicle collapsed, forming a network of cracks favorable to permeable gas flow. Reduced magma emission rate at the end of the Strombolian phase caused an increase in the thickness of the peripheral degassed magma zone, until it formed a plug at the top of the conduit, and activity gradually shifted to pulsing ash explosions. These were driven by repeated explosions of the overpressurized plug, in a small-scale, vulcanian-like, explosive process. We suggest that the relative abundance of sideromelane and tachylite ash particles in basaltic explosion products may provide information on the evolution of velocity gradients within magma flux.

Cortical spreading depression (CSD) is a reversible electrophysiological phenomenon that is not associated with tissue damage under normal blood supply. The induction of CSD during ischemia causes an increase in tissue damage, while pre-conditioning with CSD decreases the damage induced by a subsequent episode of ischemia. The mechanisms underlying these effects are not clear. Because the production of reactive oxygen species (ROS) is involved in tissue damage during ischemia-reperfusion, the aim of the present study was to evaluate the effects of CSD on superoxide production (O 2 − ), on hydrogen peroxide (H 2 O 2 ) production and on superoxide dismutase (SOD) activity in the cerebral cortex. CSD was induced by KCl application on the cortical surface in rats. O 2 − production was evaluated using dihydroethidium (DHE) that is oxidized to the fluorescent dye ethidium (HEt) by O 2 − . The extracellular level of H 2 O 2 was evaluated by microdialysis sampling and HPLC analysis. SOD activity was evaluated with a histochemical assay. The results showed an increase in H 2 O 2 production, an increase in SOD activity and a decrease in O 2 − concentration 1 h after CSD induction. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m w w w . e l s e v i e r . c o m / l o c a t e / b r a i n r e s

Weakly electric fish orient, hunt and communicate by emitting electrical pulses, enabling them to discriminate objects, conspecifics and prey. In addition to the electrosensory modality-although dominating in importance in these fishes-other modalities, like vision, play important roles for survival. The visual system of Gnathonemus petersii, a member of the family mormyridae living in West African blackwater streams shows remarkable specializations: Cone photoreceptors are grouped in bundles within a light reflecting tapetum lucidum, while the rods are also bundled but located at the back within a light-scattering guanine layer. Such an organization does not improve light sensitivity nor does it provide high spatial resolution. Thus, the function of the grouped retinal arrangement for the visual performance of the fish remains unclear. Here we investigated the contrast sensitivity of the temporal transfer properties of the visual system of Gnathonemus. To do so, we analyzed visual evoked potentials in the optic tectum and tested the critical flicker fusion frequency in a behavioral paradigm. Results obtained in Gnathonemus are compared to results obtained with goldfish (Carassius auratus), revealing differences in the filter characteristics of their visual systems: While goldfish responds best to low frequencies, Gnathonemus responds best at higher frequencies. The visual system of goldfish shows characteristics of a low-pass filter while the visual system of Gnathonemus has characteristics of a band-pass filter. Furthermore we show that the visual system of Gnathonemus is more robust towards contrast reduction as compared to the goldfish. The grouped retina might enable Gnathonemus to see large, fast moving objects even under low contrast conditions. Due to the fact that the electric sense is a modality of limited range, it is tempting to speculate that the retinal specialization of Gnathonemus petersii might be advantageous for predator avoidance even when brightness differences are small.

The csdA, csdB and iscS genes encoding for cysteine desulfurase enzymatic activities in Escherichia coli were independently inactivated and potassium tellurite sensitivity, determined for each of the resulting mutant clones, was found to be iscS > csdB > csdA. Structural genes encoding for each of the wild-type cysteine desulfurases were cloned into a vector containing the regulated ara promoter and further introduced into the mutant strains. Desulfurase-deficient cells transformed with homolog or paralog desulfurase genes and grown in arabinose-amended media restored their basal tellurite resistance. While csdB gene complemented the auxotrophy of csdB and iscS mutants for nicotinic acid, the iscS gene only complemented the auxotrophy of iscS cells for thiamine. Introduction of the csdA gene into the desulfurase-deficient strains did not change tellurite resistance or nutritional requirement patterns of the recipient cells. Complementation analysis could not be performed under anaerobic conditions because the three mutants did not show tellurite hypersensitivity. These results indicate that oxidative stress is involved in tellurite toxicity in E. coli. (C.C. Vásquez). eral cellular processes . Tellurite anions seem to enter the cell through phosphate transporters [33] and can be reduced, at least in part, by the enzyme nitrate reductase at the inner leaflet of the cytoplasmic membrane, thus providing Escherichia coli with a basal level of resistance to potassium tellurite . Tellurite could also be reduced inside the cell by other apparently non-related enzymatic activities , by cytosolic glutathione and/or other reduced thiols generating metallic tellurium (Te 0 ) as well as, most probably, superoxide anions .

Isochoric measurements were taken for the R23 + CO 2 system for both the two-phase and the superheated vapor regions. The isochoric experiment covered a temperature range from 253 to 353 K and a pressure range from 1590 to 5880 kPa. The data in the two-phase region enabled VLE parameters to be derived using a flash method with the Carnahan-Starling-De Santis equation of state (EoS); in addition, the dew point for each isochore was found from the intersection of P-T sequences. The two derived parameters were compared with each other and a good consistency was found. The VLE data for the R23 + CO 2 system were compared with results in the literature and a fair degree of agreement was found. The measured system showed positive deviation from Raoult's law that increases with rising of temperature. The P-V-T-x data in the superheated region were compared with the REFPROP 6.01 estimate for a wider temperature range than was previously measured by the Burnett method. The values predicted by the REFPROP 6.01 software show a positive deviation of about 0.4% in the comparison with the experimental data.

Certain beverages contribute energy, protein, vitamins, and minerals. North American adolescents have shifted their beverage intake from predominantly milk to predominantly sugary beverages. Intake of these sugary beverages, in sufficient quantity, may increase the risk of bone fractures, may contribute to obesity, and may lead to tooth decay. This study evaluated the effectiveness of a schoolnutrition education program (Fluids Used Effectively for Living) on nutrition knowledge, attitude, and self-reported behavior of grade 9 students in Saskatchewan, Canada. Two classes of grade 9 students, 1 (n = 33) in a high school in Saskatoon (n = 33) and 1 (n = 24) in a large high school in Prince Albert, Saskatchewan, received the peer educator intervention. Two other classes in the 2 cities (n = 24 and n = 24, respectively) were controls. Six sessions of Fluids Used Effectively for Living nutrition education were delivered by using 2 peer educator models (multiple and single), and the intervention was delivered in a 45-minute weekly class session over a 6-week period. After the intervention, students in these 2 peer educator classes decreased their sugary beverage intake significantly, which was sustained for 3 months. Students in the control self-taught class increased their juice intake at the end of the year. The significant decrease of juice and sugary beverage intakes in the single model peer educator class disappeared after Bonferroni correction. Carbonated sugary beverage intake of students in the control self-taught classes declined, but it was not sustainable at the 3-month follow-up. A peer educator school-based nutrition education approach can lead to a decrease in sugary beverage intake in high school children.

The 1973 eruption of Eldfell volcano, Iceland, appears to have been a short, simple event, but textural and geochemical evidence suggest that it may have had three different magmatic components. The first-erupted fissure magmas were chemically evolved, rich in plagioclase (∼18%) and had shallow, straight crystal size distribution (CSD) curves. The early lavas were less evolved chemically, had lower plagioclase contents (∼ 13%) and steeper, slightly concave up CSDs. The late lavas were chemically similar to the early lavas, but even richer in plagioclase than the initial magmas (∼ 24%) and had the steepest CSDs. There was no chemical evidence for plagioclase fractionation, but compositional diversity could be produced by clinopyroxene fractionation which must have occurred at depth. We propose that the eruption started with old, coarsened (Ostwald ripened) magma left over from a previous eruption, possibly that which produced Surtsey Island ten years earlier. The early flows may be mixtures of small amounts of this old magma with a new, low crystallinity, uncoarsened magma or a completely new magma. The late flows are another new magma from depth, chemically similar to the early flows, but which has grown plagioclase under increasing saturation (undercooling) perhaps during its ascent. All three magmatic components may have originated from the same parent, but had varying degrees of clinopyroxene fractionation, plagioclase nucleation and growth, and coarsening.

The range of target structures in the fifth international blind test of crystal structure prediction was extended to include a highly flexible molecule, (benzyl-(4-(4-methyl-5-(p-tolylsulfonyl)-1,3-thiazol-2-yl)phenyl)carbamate, as a challenge representative of modern pharmaceuticals. Two of the groups participating in the blind test independently predicted the correct structure. The methods they used are described and contrasted, and the implications of the capability to tackle molecules of this complexity are discussed.

Explosive activity at Mt. Etna from July 19 to August 7, 2001, provides a good case study to investigate the causes of the transitions between types of basaltic explosion. In this period, a new vent, located at 2550 m above sea level on the southern flank of the volcano, exhibited three types of activities that followed one another: initial ash and steam explosions with the emission of radial jets, of hydromagmatic origin; intermediate fire fountaining and Strombolian explosions, due to magma vesiculation; and finally, sustained to pulsing ash explosions, caused by overpressurization of the degassed and cooling top of the magma column. The activities produced two end-members of juvenile ash in the size range 0.4 -0.1 mm: (1) brown, fluidalto irregular-shaped, vesicular sideromelane glass particles, and (2) microcrystalline, blocky, poorly vesicular tachylite particles. Component analysis of the ash reveals a gradual decrease in the abundance of sideromelane, replaced by tachylite, in the transition from the intermediate Strombolian to the final ash explosion activity. Dense blocks with irregular, variable surface textures also characterize the products of the pulsing ash explosions. Petrographic, chemical, and crystal size distribution analyses, together with morphological evidences, indicate that sideromelane quenched earlier than tachylite during the final stage of magma evolution. In fact, the groundmass of tachylite formed by subsequent crystallization of magma, possibly at lower temperature and under different degassing conditions. We hypothesize that sideromelane formed in the central part of the volcanic conduit, where the buoyant rise of gas bubbles caused a higher magma ascent velocity, which did not allow time for vesicle to escape or collapse before fragmentation. Conversely, tachylite crystallized at the margins of the conduit, where slowmoving magma accumulated, temperature was lower, and vesicle collapsed, forming a network of cracks favorable to permeable gas flow. Reduced magma emission rate at the end of the Strombolian phase caused an increase in the thickness of the peripheral degassed magma zone, until it formed a plug at the top of the conduit, and activity gradually shifted to pulsing ash explosions. These were driven by repeated explosions of the overpressurized plug, in a small-scale, vulcanian-like, explosive process. We suggest that the relative abundance of sideromelane and tachylite ash particles in basaltic explosion products may provide information on the evolution of velocity gradients within magma flux. D

Roundabout 1 (Robo1) is the cognate receptor for secreted axon guidance molecule, Slits, which function to direct cellular migration during neuronal development and angiogenesis. The Slit2eRobo1 signaling is modulated by heparan sulfate, a sulfated linear polysaccharide that is abundantly expressed on the cell surface and in the extracellular matrix. Biochemical studies have further shown that heparan sulfate binds to both Slit2 and Robo1 facilitating the ligandereceptor interaction. The structural requirements for heparan sulfate interaction with Robo1 remain unknown. In this report, surface plasmon resonance (SPR) spectroscopy was used to examine the interaction between Robo1 and heparin and other GAGs and determined that heparin binds to Robo1 with an affinity of w650 nM. SPR solution competition studies with chemically modified heparins further determined that although all sulfo groups on heparin are important for the Robo1eheparin interaction, the N-sulfo and 6-O-sulfo groups are essential for the Robo1eheparin binding. Examination of differently sized heparin oligosaccharides and different GAGs also demonstrated that Robo1 prefers to bind full-length heparin chains and that GAGs with higher sulfation levels show increased Robo1 binding affinities.

Eight protein crystal structures, which have been refined against X-ray diffraction data extending to atomic resolution, 1.2 A or better, were inspected using four different validation tools, PROCHECK, PROVE, SQUID and WHATCHECK. Two general questions were addressed. (1) Do the structures imply changes in "expected" stereochemical properties and are the target values used for restraints in the validation programs and the refinement protocol appropriate? (2) Can errors in models be detected and how reliable are the coordinates after refinement? Preliminary analysis by members of the network led to modifications both to the validation programs and to the refinement protocols. The results of the final analyses are reported here. Apparent discrepancies in cell dimensions were identified. Most stereochemical properties are shown to be more tightly clustered than for lower resolution analyses. In contrast the omega angle has a wider distribution. The validation software is gener...

1 We would like to thank the members of the ESCB-CESR Task Force 1 who carried out the fact-fi nding exercise on national regulations, the results of which we used in Chapter 5. Special thanks go to Mrs Jennifer Boneham of the UK Financial Services Authority and to Mr Marc Peters of the Commission bancaire, fi nancière et des assurances/Commissie voor het Bank-, Financie-en Assurantiewezen (CBFA) of Belgium for their contributions and comments. We are also indebted to an anonymous referee who provided us with very useful comments as well as suggestions on how to improve the presentation of the paper. The views expressed by the authors do not necessarily refl ect those of the European Central Bank.

Problem statement: Ultra Wide Band (UWB) technology has attracted many researchers' attention due to its advantages and its great potential for future applications. The physical layer standard of Multi-band Orthogonal Frequency Division Multiplexing (MB-OFDM) UWB system is defined by ECMA International. In this standard, the data sampling rate from the analog-to-digital converter to the physical layer is up to 528 M sample sec −1. Therefore, it is a challenge to realize the physical layer especially the components with high computational complexity in Very Large Scale Integration (VLSI) implementation. Fast Fourier Transform (FFT) block which plays an important role in MB-OFDM system is one of these components. Furthermore, the execution time of this module is only 312.5 ns. Therefore, if employing the traditional approach, high power consumption and hardware cost of the processor will be needed to meet the strict specifications of the UWB system. The objective of this study was to design an Application Specific Integrated Circuit (ASIC) FFT processor for this system. The specification was defined from the system analysis and literature research. Approach: Based on the algorithm and architecture analysis, a novel Genetic Algorithm (GA) based Canonical Signed Digit (CSD) Multiplier less 128-point FFT processor and its inverse (IFFT) for MB-OFDM UWB systems had been proposed. The proposed pipelined architecture was based on the modified Radix-2 2 algorithm that had same number of multipliers as that of the conventional Radix-2 2. However, the multiplication complexity and the ROM memory needed for storing twiddle factors coefficients could be eliminated by replacing the conventional complex multipliers with a newly proposed GA optimized CSD constant multipliers. The design had been coded in Verilog HDL and targeted Xilinx Virtex-II FPGA series. It was fully implemented and tested on real hardware using Virtex-II FG456 prototype board and logic analyzer. Results: From the synthesis reports, the proposed GA optimized CSD constant complex multiplier achieved 79 and 50% equivalent gates and latency efficiency when compared to the conventional complex multiplier. Conclusion: As a conclusion, we successfully implemented 128-points FFT/IFFT processor with the proposed architecture that can meet the requirement of MB-OFDM UWB system with higher throughput and less area compared to conventional architecture.

During the last 30 years the scope of biocatalysis has been expanding due to the advances in several technological fields. Diverse techniques as structural enzyme improvement (e.g. protein engineering, direct evolution), engineering approaches (e.g. ionic liquids, supercritical fluids) and physical stabilization (e.g. immobilization, CLEAS) have been developed, which in combination are powerful tools to improve biotransformation and to synthesize new products. In the present work, recent advances in biocatalysis are reviewed.

In this solution crystallization study, a population balance model that predicts the crystal size distribution (CSD) is used for targeting, by optimization, the product mean size and the coefficient of variation of the final CSD. The model is robust over a wide range of conditions and predicts the effects of heating during a batch since the kinetics of dissolution have been identified and incorporated into the model. The dynamic temperature profile and the initial seed size distribution are optimized while the initial seed induction time is conferred through knowledge of saturation conditions. This is quite a highly developed method that provides a systematic approach towards optimal operation. Results from optimizations under different objective functions are presented and validated experimentally.

Replication of hepatitis C virus (HCV) requires host cell factors, such as cyclophilin A (CypA). CypA binds to HCV's nonstructural protein (NS)5A to promote replication of viral RNA. CypA antagonists, such as cyclosporines, are potent inhibitors of HCV replication. NS2 modulates sensitivity of HCV to cyclosporines. We investigated why cyclosporines require NS2 to increase their inhibitory effect and how they block HCV replication. METHODS: We determined replication fitness and sensitivity of various HCV replicons, containing or lacking NS2, to cyclosporine and other direct-acting antiviral agents. We also analyzed the effects of cyclosporine on membranous web formation by electron microscopy. RESULTS: NS2-5B replicons of genotype 2a (JFH1), but not genotype 1b, had increased sensitivity to cyclosporine. This difference was lost with replicationattenuated NS3-5B JFH1 RNAs, showing that cyclosporine sensitivity is linked to reduced replication fitness of NS2containing HCV RNAs. Fitness also determined sensitivity to a nucleoside analogue and an NS5A inhibitor, but not to telaprevir. Cyclosporine blocked de novo formation of the membranous web, but had little effect on established membranous replication factories. This block was prevented by cyclosporine resistance mutations in NS5A. CONCLUSIONS: Cleavage at the NS2/3 junction is a rate-limiting step in replication of particular HCV isolates and determines their sensitivity to CypA inhibitors. These drugs target de novo formation of the membranous web and RNA replication.

We investigated the influence of hyperoxirt (ruteritil p0, 446 i 43 mmHg) and hyperglycemia (blood glucose 19.4 ~nnwl/l) WI somatosensory stimulation (whisker deflection) employing laser Doppler flowmctry (LDF). Our aim wuz to tcht the hypothcsih that ;I possible substrate-sensing mechunism for gh~cose and oxygen contributes to the coupling between cortictil activity and regional ccrehrnl blood flow (ICBF) in order to match increased demand with substrates. In addition. we looked at the influence of hyperglycemiu (blood glucose 17.9 mmol/l) and hypercapnia (arterial pC02 62 mmHg) OJI rCBF (LDF) and regionul cerebral blood oxygenation changes (tCB0) in the even stronger metabolic stimulus of cortical spreading depression (CSD). For the latter we employed the new non-invasive technique of neur infrared spectroscopy (NIRS). All experiments were done using chlomlose/urethane-anesthetized rats. Somatosensory stimulation increased rCBF by about 20% of baseline. in the cuse of both norm-and hyperoxia ils well us both normo-and hyperglycemi;c. The blood-flow response to CSD consisted of u temporary sharp Increase in rCBF to more than 4tM~%. At the same timo. the concentr&ttion of oxyhemoglobin !HbO,] increased, whtlr dcoxyheeioglobia [Hh] decreased, indicating cxccssivc oxyycuution. Hyperglycemiu altered neither the KTBF nor the rCB0 response. Preexisting hypcrcapnia. howcvcr. produced reductions in both hyperperfusion (rCBF) und hyperoxygenution MX30) during CSD. We found thut. for cxperimcntnl hyperglycemia. i.v. may bc hupcrior to i.p. application of glucose because of the luttcr's side effects in connection wide blood flow. Our finding\ cannot 'rupp~ ~hc hypothc\i\ of u substrate sensing mechanism in coupling. (~7 1997 El\evier Scicnrc I3.V. 1, lntraduction Since the phenomenon was described for the first time in a seminal paper by Roy and Sherrington [44], coupling of cercbrdl blood flow and metabolism under resting and under stimulated conditions has been int,enseiy studied. The high temporal und spatial resolution of stimulation induced coupling bus been demonstrated with various techniques [23.53,12], and modem brain imaging techniques like positron emission tomography (PET) or functional nuclear magnetic resonance imaging rely on coupling to localize activated brain ureas [S2]. Various tncdintors which Gbbraviutions: ICBF, regional cerebral blood flow: rCB0. regional cerebral bltwd oxygenation changes; CSD. cortical spreading deprcbsion; NIRS near infrared specrmscopy; LDF, laser Doppler tlowmctry: 00:.

Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the hypothesis that their common denominator might be suppression of CSD we studied in rats the effect of three drugs used in migraine prevention: lamotrigine which is selectively effective on the aura but not on the headache, valproate and riboflavin which have a non-selective effect. Rats received for 4 weeks daily intraperitoneal injections of one of the three drugs. For valproate and riboflavin we used saline as control, for lamotrigine its vehicle dimethyl sulfoxide. After treatment, cortical spreading depressions were elicited for 2 h by occipital KCl application. We measured CSD frequency, its propagation between a posterior (parieto-occipital) and an anterior (frontal) electrode, and number of Fos-immunoreactive nuclei in frontal cortex. Lamotrigine suppressed CSDs by 37% and 60% at posterior and anterior electrodes. Valproate had no effect on posterior CSDs, but reduced anterior ones by 32% and slowed propagation velocity. Riboflavin had no significant effect at neither recording site. Frontal Fos expression was decreased after lamotrigine and valproate, but not after riboflavin. Serum levels of administered drugs were within the range of those usually effective in patients. Our study shows that preventive anti-migraine drugs have differential effects on CSD. Lamotrigine has a marked suppressive effect which correlates with its rather selective action on the migraine aura. Valproate and riboflavin have no effect on the triggering of CSD, although they are effective in migraine without aura. Taken together, these results are compatible with a causal role of CSD in migraine with aura, but not in migraine without aura.

Primary sensory cortex integrates sensory information from afferent feedforward thalamocortical projection systems and convergent intracortical microcircuits. Both input systems have been demonstrated to provide different aspects of sensory information. Here we have used high-density recordings of laminar current source density (CSD) distributions in primary auditory cortex of Mongolian gerbils in combination with pharmacological silencing of cortical activity and analysis of the residual CSD, to dissociate the feedforward thalamocortical contribution and the intracortical contribution to spectral integration. We found a temporally highly precise integration of both types of inputs when the stimulation frequency was in close spectral neighborhood of the best frequency of the measurement site, in which the overlap between both inputs is maximal. Local intracortical connections provide both directly feedforward excitatory and modulatory input from adjacent cortical sites, which determ...

The pre-surgical planning of brain neoplasms is strongly contributing to change the
prognosis of neoplastic patients. Indeed, it supplies more and more detailed and reliable functional
and morphological information before as well as during surgery. Both invasive and noninvasive
approaches are available to achieve this goal. A powerful technique for the pre-surgical
planning of brain neoplasms is Diffusion Weighted Imaging (DWI) based tractography.
Differently from other approaches, tractography is able to provide, non-invasively, morphological
information regarding brain pathways relationship with the neoplasm, by analyzing
water diffusion within white matter.

Optic Radiations (ORs) are two white matter fiber bundles allowing direct connection
between homolateral Lateral Geniculate Nucleus (LGN) and visual cortex. From the
anatomical point of view, ORs are conventionally divided in three different portions, namely
anterior, middle and posterior; the Meyer’s loop represents the anterior portion, and it has
been shown to be a bundle with a very high variability in human brain.1-3 The latter aspect has
to be taken into account when studying ORs in clinical and surgical contexts. Indeed, ORs
represent eloquent white matter bundles often reconstructed by means of Magnetic Resonance
Imaging (MRI) based approaches in order to assess their involvement by pathological
conditions as well as to prevent post-surgical damages. Both these conditions can compromise
visual function by causing, for instance, visual field deficits.4,5 Schematic representation

During the last 30 years the scope of biocatalysis has been expanding due to the advances in several technological fields. Diverse techniques as structural enzyme improvement (e.g. protein engineering, direct evolution), engineering approaches (e.g. ionic liquids, supercritical fluids) and physical stabilization (e.g. immobilization, CLEAS) have been developed, which in combination are powerful tools to improve biotransformation and to synthesize new products. In the present work, recent advances in biocatalysis are reviewed.

To better characterize neurophysiologic processes underlying olfactory dysfunction in schizophrenia, nose-referenced 30-channel electroencephalogram was recorded from 32 patients and 35 healthy adults (18 and 18 male) during detection of hydrogen sulfide (constant-flow olfactometer, 200 ms unirhinal exposure). Event-related potentials (ERPs) were transformed to reference-free current source density (CSD) waveforms and analyzed by unrestricted Varimax-PCA. Participants indicated when they perceived a high (10 ppm) or low (50% dilution) odor concentration. Patients and controls did not differ in detection of high (23% misses) and low (43%) intensities and also had similar olfactory ERP waveforms. CSDs showed a greater bilateral frontotemporal N1 sink (305 ms) and mid-parietal P2 source (630 ms) for high than low intensities. N1 sink and P2 source were markedly reduced in patients for high intensity stimuli, providing further neurophysiological evidence of olfactory dysfunction in schizophrenia.

CSD ϭ clinically significant disease DCE-MRI ϭ dynamic contrast enhanced MRI DR ϭ detection rate GS ϭ Gleason score M-M ϭ multimodal MR ϭ magnetic resonance MR-GB ϭ MRI guided biopsy MRI ϭ MR imaging PSA ϭ prostate specific antigen PSAD ϭ PSA density PZ ϭ peripheral zone T2-w ϭ T2-weighted TRUS ϭ transrectal ultrasound TRUS-GB ϭ TRUS guided biopsy TSR ϭ tumor suspicious region TZ ϭ transition zone ).

Ascorbic acid (AA) is an antioxidant molecule that is highly concentrated in the brain and can exert both anticonvulsant and proconvulsant effects in distinct models of experimental seizures. Herein, we investigated whether chronic AA administration alters cortical excitability as indexed by the cortical spreading depression (CSD). Well-nourished (W) and malnourished (M) rats were treated, by gavage, with 60 mg/kg/day of l-AA from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to the W groups, M rats presented higher (p < 0.05) CSD amplitudes and velocities of propagation. In both nutritional conditions, AA-treatment significantly increased CSD amplitudes and propagation velocities (p < 0.05), as compared to non-treated ('naïve'; Nv) and saline-treated (Sal) controls. The mean ± standard deviation CSD velocities of propagation (in mm/min) for the Sal, AA and Nv groups were respectively 3.75 ± 0.03, 4.26 ± 0.08 and 3.81 ± 0.04 for the W condition and 4.29 ± 0.08, 4.51 ± 0.04 and 4.30 ± 0.04 for the M groups. The results demonstrate a CSD-facilitation by AA regardless of nutritional status. They also suggest that, at the dose of 60 mg/kg/day chronically administered during brain development, AA may act as a prooxidant in brain, in view of the contrasting effect as compared with other antioxidants, which reduce CSD.

Heterochromatin protein 1 Hsa (HP1 Hsa ) is one of three human proteins that share sequence similarity with Drosophila HP1. HP1 proteins are enriched at centric heterochromatin and play a role in chromatin packaging and gene regulation. In humans, HP1 Hsa is downregulated in highly invasive/metastatic breast cancer cells, compared to poorly invasive/non-metastatic breast cancer cells. To gain insight into this differential regulation, we have cloned the HP1 Hsa gene and characterized its genomic region. HP1 Hsa is located on human chromosome 12q13.13, 589 bp upstream of the divergently transcribed hnRNPA1 gene. Analysis of the promoter region revealed that differential regulation of HP1 Hsa between the two types of breast cancer cells is lost upon mutation of an USF/c-myc transcription factor binding site located 172 bp upstream of the predicted HP1 Hsa transcription start site. These findings provide insights into the down-regulation of HP1 Hsa in highly invasive/metastatic breast cancer cells. To examine the functional properties of HP1 Hsa , experiments were performed using Drosophila melanogaster as a genetic system. When human HP1 Hsa was expressed in transgenic Drosophila, silencing of reporter genes inserted at centric and telomeric locations was enhanced. Furthermore, expression of HP1 Hsa rescued the lethality of homozygous Su(var)2-5 mutants lacking HP1. Taken together, these results demonstrate the participation of HP1 Hsa in silent chromatin formation and that HP1 Hsa is a functional homologue of Drosophila HP1. D

The anteroventral temporal lobe integrates visual, lexical, semantic and mnestic aspects of wordprocessing, through its reciprocal connections with the ventral visual stream, language areas, and the hippocampal formation. We used linear microelectrode arrays to probe population synaptic currents and neuronal firing in different cortical layers of the anteroventral temporal lobe, during semantic judgments with implicit priming, and overt word recognition. Since different extrinsic and associative inputs preferentially target different cortical layers, this method can help reveal the sequence and nature of local processing stages at a higher resolution than was previously possible. entorhinal cortex. Word processing involves a systematic sequence of fast feedforward information transfer from visual areas to anteroventral temporal cortex, followed by prolonged interactions of this feedforward information with local associations, and feedback mnestic information from the medial temporal lobe.

Ascorbic acid (AA) is an antioxidant molecule that is highly concentrated in the brain and can exert both anticonvulsant and proconvulsant effects in distinct models of experimental seizures. Herein, we investigated whether chronic AA administration alters cortical excitability as indexed by the cortical spreading depression (CSD). Well-nourished (W) and malnourished (M) rats were treated, by gavage, with 60 mg/kg/day of l-AA from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to the W groups, M rats presented higher (p < 0.05) CSD amplitudes and velocities of propagation. In both nutritional conditions, AA-treatment significantly increased CSD amplitudes and propagation velocities (p < 0.05), as compared to non-treated ('naïve'; Nv) and saline-treated (Sal) controls. The mean ± standard deviation CSD velocities of propagation (in mm/min) for the Sal, AA and Nv groups were respectively 3.75 ± 0.03, 4.26 ± 0.08 and 3.81 ± 0.04 for the W condition and 4.29 ± 0.08, 4.51 ± 0.04 and 4.30 ± 0.04 for the M groups. The results demonstrate a CSD-facilitation by AA regardless of nutritional status. They also suggest that, at the dose of 60 mg/kg/day chronically administered during brain development, AA may act as a prooxidant in brain, in view of the contrasting effect as compared with other antioxidants, which reduce CSD.