Fractal capacitors

A linear capacitor structure using fractal geometries is described. This capacitor exploits both lateral and vertical electric fields to increase the capacitance per unit area. Compared to standard parallel-plate capacitors, the parasitic bottom-plate capacitance is reduced. Unlike conventional metal-to-metal capacitors, the capacitance density increases with technology scaling. A classic fractal structure is implemented with 0.6-μm metal spacing, and a factor of 2.3 increase in the capacitance per unit area is observed. It is shown that capacitance boost factors in excess of ten may be possible as technology continues to scale. A computer-aided-design tool to automatically generate and analyze custom fractal layouts has been developed

Tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of Alzheimer's disease-relevant tau constructs in organotypic hippocampal slices

Alzheimer's disease (AD) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid beta, and intracellular fibrils containing hyperphosphorylated tau. Tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in AD remain elusive. Using Sindbis virus-mediated expression of AD-relevant tau constructs in hippocampal slices, we show that disease-like tau modifications affect tau phosphorylation at selected sites, induce Alz50/MC1-reactive pathological tau conformation, cause accumulation of insoluble tau, and induce region-specific neurodegeneration. Live imaging demonstrates that tau-dependent degeneration is associated with the development of a "ballooned" phenotype, a distinct feature of cell death. Spine density and morphology is not altered as judged from algorithm-based evaluation of dendritic spines, suggesting that synaptic integrity is remarkably stable against tau-dependent degeneration. The data provide evidence that tau-induced cell death involves apoptotic as well as nonapoptotic mechanisms. Furthermore, they demonstrate that targeted expression of tau in hippocampal slices provides a novel model to analyze tau modification and spatiotemporal dynamics of tau-dependent neurodegeneration in an authentic CNS environment

The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior.

The mammalian target of rapamycin (mTOR) is a ubiquitously expressed serine/threonine kinase protein complex (mTORC1 or mTORC2) that orchestrates diverse functions ranging from embryonic development to aging. However, its brain tissue-specific roles remain less explored. Here, we have identified that the depletion of the mTOR gene in the mice striatum completely prevented the extrapyramidal motor side effects (catalepsy) induced by the dopamine 2 receptor (D2R) antagonist haloperidol, which is the most widely used typical antipsychotic drug. Conversely, a lack of striatal mTOR in mice did not affect catalepsy triggered by the dopamine 1 receptor (D1R) antagonist SCH23390. Along with the lack of cataleptic effects, the administration of haloperidol in mTOR mutants failed to increase striatal phosphorylation levels of ribosomal protein pS6 (S235/236) as seen in control animals. To confirm the observations of the genetic approach, we used a pharmacological method and determined that the mTORC1 inhibitor rapamycin has a profound influence upon post-synaptic D2R-dependent functions. We consistently found that pretreatment with rapamycin entirely prevented (in a time-dependent manner) the haloperidol-induced catalepsy, and pS6K (T389) and pS6 (S235/236) signaling upregulation, in wild-type mice. Collectively, our data indicate that striatal mTORC1 blockade may offer therapeutic benefits with regard to the prevention of D2R-dependent extrapyramidal motor side effects of haloperidol in psychiatric illness

N-(5-Bromo­pyridin-2-yl)acetamide

The asymmetric unit of the title compound, C7H7BrN2O, contains two mol­ecules, in one of which the methyl H atoms are disorderd over two orientations in a 0.57 (3):0.43 (3) ratio. The dihedral angles between the pyridine rings and the acetamide groups are 7.27 (11) and 8.46 (11)°. In the crystal, mol­ecules are linked by N—H⋯O and C—H⋯O hydrogen bonds generating bifurcated R 2 1(5) ring motifs, which in turn lead to [110] chains

2-(4-Chloro­phen­yl)-2-oxoethyl 4-hy­droxy­benzoate

The title compound, C15H11ClO4, consists of a chloro­benzene ring and a phenol ring which are linked together by a 1,4-dioxo-2-oxabutane-1,4-diyl group. The dihedral angle between the chloro­benzene and phenol rings is 65.70 (11)°. In the crystal, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into chains along [010]

2-(4-Bromo­phen­yl)-2-oxoethyl 4-methyl­benzoate

The title compound, C16H13BrO3, consists of a toluene ring and a bromo­benzene ring which are linked together by a 2-oxopropyl acetate group. The dihedral angle formed between the toluene and bromo­benzene rings is 80.70 (7)°. In the crystal, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into a three-dimensional network

Severe dengue epidemics in Sri Lanka, 2003-2006

Recent emergence of dengue hemorrhagic fever in the Indian subcontinent has been well documented in Sri Lanka. We compare recent (2003-2006) and past (1980-1997) dengue surveillance data for Sri Lanka. The 4 dengue virus (DENV) serotypes have been cocirculating in Sri Lanka for >30 years. Over this period, a new genotype of DENV-1 has replaced an old genotype. Moreover, new clades of DENV-3 genotype III viruses have replaced older clades. Emergence of new clades of DENV-3 in 1989 and 2000 coincided with abrupt increases in the number of reported dengue cases, implicating this serotype in severe epidemics. In 1980-1997, most reported dengue cases were in children. Recent epidemics have been characterized by many cases in children and adults. Changes in local transmission dynamics and genetic changes in DENV-3 are likely increasing emergence of severe dengue epidemics in Sri Lanka

RasGRP1 is a causal factor in the development of l-DOPA-induced dyskinesia in Parkinson's disease.

The therapeutic effects of l-3,4-dihydroxyphenylalanine (l-DOPA) in patients with Parkinson's disease (PD) severely diminishes with the onset of abnormal involuntary movement, l-DOPA-induced dyskinesia (LID). However, the molecular mechanisms that promote LID remain unclear. Here, we demonstrated that RasGRP1 [(guanine nucleotide exchange factor (GEF)] controls the development of LID. l-DOPA treatment rapidly up-regulated RasGRP1 in the striatum of mouse and macaque model of PD. The lack of RasGRP1 in mice (RasGRP1-/- ) dramatically diminished LID without interfering with the therapeutic effects of l-DOPA. Besides acting as a GEF for Ras homolog enriched in the brain (Rheb), the activator of the mammalian target of rapamycin kinase (mTOR), RasGRP1 promotes l-DOPA-induced extracellular signal-regulated kinase (ERK) and the mTOR signaling in the striatum. High-resolution tandem mass spectrometry analysis revealed multiple RasGRP1 downstream targets linked to LID vulnerability. Collectively, the study demonstrated that RasGRP1 is a critical striatal regulator of LID