Role of Counterions in the Structural Stabilisation of Redox-Active Metal-Organic Frameworks.

The crystal structures of metal-organic frameworks (MOFs) are typically determined by the strong chemical bonds formed between the organic and inorganic building units. However, the latest generation of redox-active frameworks often rely on counterions in the pores to access specific charge states of the components. Here, we model the crystal structures of three layered MOFs based on the redox-active ligand 2,5-dihydroxybenzoquinone (dhbq): Ti2 (Cl2 dhbq)3 , V2 (Cl2 dhbq)3 and Fe2 (Cl2 dhbq)3 with implicit and explicit counterions. Our full-potential first-principles calculations indicate that while the reported hexagonal structure is readily obtained for Ti and V, the Fe framework is stabilised only by the presence of explicit counterions. For high counterion concentrations, we observe the formation of an electride-like pocket in the pore center. An outlook is provided on the implications of solvent and counterion control for engineering the structures and properties of porous solids.

Effect of intracranial bleeds on the neurocognitive, academic, behavioural and adaptive functioning of boys with haemophilia.

Brain insults are a risk factor for neuropsychological and academic deficits across several paediatric conditions. However, little is known about the specific effects of intracranial haemorrhage (ICH) in boys with haemophilia. The study compared neurocognitive, academic and socio-emotional/behavioural outcomes of boys with haemophilia with and without a history of ICH. Of 172 consecutive patients seen at a Pediatric Comprehensive Care Hemophila Centre, 18 had a history of ICH. Sixteen boys between the ages of 3 and 17 years were available for study and were matched to controls with haemophilia of the same age and disease severity and on the basis of maternal education. Groups were compared on neuropsychological and academic outcomes. Attention, socio-emotional function and executive skills were compared using data from parent questionnaires. Differences were found in intellectual function, visual-spatial skill, fine motor dexterity and particularly language-related skills, including vocabulary, word reading and applied math problem solving. Despite these group differences, outcomes were within the average range for most boys with ICH. No group differences were found in behavioural and socio-emotional functioning. Although ICH in haemophilia is not benign, it was not associated with significant cognitive and academic consequences for most boys. Early neuropsychological assessment may be indicated when there is a history of ICH. Investigation of age at ICH and quantitative measures of brain in relation to neurocognitive outcomes in larger groups of boys with ICH would be useful.

Aspirin reduces the prothrombotic activity of C-reactive protein.

AIM: C-reactive protein (CRP) is a risk marker and a potential modulator of vascular disease. Previous studies support a prothrombotic activity of CRP, with impaired thromboregulation. The present study examined the antithrombotic effect of aspirin in mice transgenic for human CRP (CRPtg mice). Mechanistic investigations further elucidated the effect of CRP on prostanoid metabolism in vivo and in vitro. METHODS AND RESULTS: Administration of aspirin (30 mg kg(-1) day(-1)) to CRPtg mice slowed the accelerated thrombosis after photochemical injury to the carotid (99 +/- 32 vs. 45 +/- 24 min and 75 +/- 23 vs. 82 +/- 26 min in wild-type mice vs. CRPtg mice, without and following aspirin treatment, respectively). Vascular injury modulated the expression of key pathways in prostanoid metabolism differently in CRPtg mice and wild-type mice. Suppression of cyclo-oxygenase 2 (COX-2)-derived metabolism with suppression of prostaglandin I2 (PGI2) synthase and PGI2 metabolism was recorded in the injured artery with increased thromboxane receptor expression. Aspirin therapy reduced the difference in PGI2 biosynthesis between CRPtg mice and wild-type mice. In vitro studies in human-derived cells further supported these findings. Incubation of human umbilical vein endothelial cells (HUVECs) with human recombinant CRP (5 microg mL(-1)) suppressed PGI2 synthase expression and significantly increased thromboxane receptor levels. Incubation of smooth muscle cells with CRP did not affect prostanoid expression. CONCLUSIONS: CRP modulates prostanoid metabolism to favor vascular occlusion. Elevated CRP levels might predispose to the cardiovascular hazard conferred by selective COX-2 inhibitors, and the risk mediated by CRP may be limited by aspirin.

Over 4000 nm bandwidth of mid-IR supercontinuum generation in sub-centimeter segments of highly nonlinear tellurite PCFs.

We report broad bandwidth, mid-IR supercontinuum generation using a sub-cm (8 mm) length of highly nonlinear tellurite microstructured photonic crystal fiber (PCF). We pump the fiber at telecommunication wavelengths by using 1550 nm, 100 fs pulses of energy E=1.9 nJ. When coupled in the PCF, these pulses result in a supercontinuum (SC) bandwidth of 4080 nm extending from 789 to 4870 nm measured at 20 dBm below the peak spectral power. This bandwidth is comparable or in excess of previously reported spectra for other nonlinear glass fiber formulations despite the significantly shorter fiber length. In addition, besides offering a convenient pump wavelength, short fiber lengths enable smoother SC spectra, lower dispersion, and reduced material absorption at longer wavelengths making the use of this PCF particularly interesting.

Innate immunity has a dual effect on vascular healing: suppression and aggravation of neointimal formation and remodeling post-endotoxin challenge.

BACKGROUND: Inflammation is important to vascular repair following injury, modulating neointimal proliferation and remodeling. Previously, we have shown that a low-intensity inflammatory response aggravates neointimal formation following balloon and stent injury. The present study examined whether modulation of the extent and timing of nonspecific inflammation mediates the local vascular response in an additive unidirectional or rather a bidirectional fashion. METHODS AND RESULTS: Rabbits subjected to denudation and balloon injury of the iliac artery were treated with low (1 microg/kg) or high (100 microg/kg) doses of bacterial endotoxin (LPS) immediately after injury, or with early high-dose LPS administered 3 days prior to injury (preconditioning). Neointimal formation at 28 days was significantly increased in the low-dose group (0.537+/-0.059 mm(2)) as compared with controls (0.3+/-0.03 mm(2)). High-dose LPS did not significantly affect neointimal formation while early high dose significantly reduced neointima (0.296+/-0.033 and 0.194+/-0.025 mm(2), respectively, n=12-14/group). Arterial wall and systemically circulating interleukin-1 beta levels, and monocyte CD14 activation correlated with neointimal formation. Vascular remodeling was accelerated in animals treated with low- or high-dose LPS while not affected in the preconditioned group. Remodeling index inversely correlated with arterial matrix metalloproteinase-2 levels 6 days after injury. CONCLUSIONS: The extent and timing of nonspecific inflammation that is concurrent with vascular injury can determine different and opposite vascular repair patterns.

Steroid-responsive neurologic relapses in a child with a proteolipid protein-1 mutation.

A 10-year-old boy developed corticosteroid-responsive relapsing neurologic signs, including nystagmus and ataxia. MRI revealed multifocal T2 white matter hyperintensities; several were gadolinium-enhancing. CSF contained oligoclonal bands. Although the patient met criteria for multiple sclerosis (MS), the proteolipid protein-1 gene (PLP1) contained a mutation in exon 3B (c.409C>T), predicting a tryptophan-for-arginine substitution. This case raises questions about the role of inflammation in PLP1-related disorders and, conversely, PLP1 mutations in MS.

Application of optical trapping to beam manipulation in optofluidics.

We introduce a novel method of attaining all-optical beam control in an optofluidic device by displacing an optically trapped microsphere through a light beam. The micro-sphere causes the beam to be refracted by various degrees as a function of the sphere position, providing tunable attenuation and beam-steering in the device. The device itself consists of the manipulated light beam extending between two buried waveguides which are on either side of a microfluidic channel. This channel contains the micro-spheres which are suspended in water. We simulate this geometry using the Finite Difference Time Domain method and find good agreement between simulation and experiment.

Surface organization and nanopatterning of collagen by dip-pen nanolithography.

Collagen is a key fibrous protein in biological systems, characterized by a complex structural hierarchy as well as the ability to self-assemble into liquid crystalline mesophases. The structural features of collagen influence cellular responses and material properties, with importance for a wide range of biomaterials and tissue architectures. The mechanism by which fibrillar collagen structures form from liquid crystalline mesophases is not well characterized. We report positive printing of collagen and a collagen-like peptide down to 30-50-nm line widths, using the atomic force microscopy technique of dip-pen nanolithography. The method preserved the triple-helical structure and biological activity of collagen and even fostered the formation of characteristic higher levels of structural organization. The "direct-write" capability of biologically relevant molecules, while preserving their structure and functionality, provides tremendous flexibility in future biological device applications and in proteomics arrays, as well as a new strategy to study the important hierarchical assembly processes of biological systems.

Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes.

A subgroup of children with arterial ischemic stroke in the pre- or perinatal period present with delayed diagnosis. We identified 22 children who met the following criteria: (1) normal neonatal neurological history, (2) hemiparesis and/or seizures first recognized after two months of age, and (3) computed tomography or magnetic resonance imaging showing remote cerebral infarct. Laboratory evaluations included protein C, protein S, antithrombin, activated protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin antibody (ACLA), and lupus anticoagulant. Not all children received all tests. Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve were boys. Fourteen had left hemisphere infarcts. Median age at presentation was 6 months. Eighteen had gestational complications. Fourteen children had at least transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with FVL + MTHFR = 1); six of these children had family histories suggestive of thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes included persistent hemiparesis in 22; speech, behavior, or learning problems in 12; and persistent seizures in five, with no evidence of further stroke in any patient. The persistence and importance of coagulation abnormalities in this group need further study.

Evolution of an autotransporter: domain shuffling and lateral transfer from pathogenic Haemophilus to Neisseria.

The genomes of pathogenic Haemophilus influenzae strains are larger than that of Rd KW20 (Rd), the nonpathogenic laboratory strain whose genome has been sequenced. To identify potential virulence genes, we examined genes possessed by Int1, an invasive nonencapsulated isolate from a meningitis patient, but absent from Rd. Int1 was found to have a novel gene termed lav, predicted to encode a member of the AIDA-I/VirG/PerT family of virulence-associated autotransporters (ATs). Associated with lav are multiple repeats of the tetranucleotide GCAA, implicated in translational phase variation of surface molecules. Laterally acquired by H. influenzae, lav is restricted in distribution to a few pathogenic strains, including H. influenzae biotype aegyptius and Brazilian purpuric fever isolates. The DNA sequence of lav is surprisingly similar to that of a gene previously described for Neisseria meningitidis. Sequence comparisons suggest that lav was transferred relatively recently from Haemophilus to Neisseria, shortly before the divergence of N. meningitidis and Neisseria gonorrhoeae. Segments of lav predicted to encode passenger and beta-domains differ sharply in G+C base content, supporting the idea that AT genes have evolved by fusing domains which originated in different genomes. Homology and base sequence comparisons suggest that a novel biotype aegyptius AT arose by swapping an unrelated sequence for the passenger domain of lav. The unusually mobile lav locus joins a growing list of genes transferred from H. influenzae to Neisseria. Frequent gene exchange suggests a common pool of hypervariable contingency genes and may help to explain the origin of invasiveness in certain respiratory pathogens.

Facial frequency manipulation normalizes face discrimination in AD.

People with AD have deficient contrast sensitivity and impaired face discrimination. The authors presented photographs of unfamiliar faces of three different sizes to enhance the low, middle, or high facial frequency information (cycles per face). Patients with AD demonstrated normal discrimination of small faces only, indicating that impaired contrast sensitivity at low facial frequencies contributes to their poor face discrimination.

Evolution of the major pilus gene cluster of Haemophilus influenzae.

Haemophilus influenzae is a ubiquitous colonizer of the human respiratory tract and causes diseases ranging from otitis media to meningitis. Many H. influenzae isolates express pili (fimbriae), which mediate adherence to epithelial cells and facilitate colonization. The pilus gene (hif) cluster of H. influenzae type b maps between purE and pepN and resembles a pathogenicity island: it is present in invasive strains, absent from the nonpathogenic Rd strain, and flanked by direct repeats of sequence at the insertion site. To investigate the evolution and role in pathogenesis of the hif cluster, we compared the purE-pepN regions of various H. influenzae laboratory strains and clinical isolates. Unlike Rd, most strains had an insert at this site, which usually was the only chromosomal locus of hif DNA. The inserts are diverse in length and organization: among 20 strains, nine different arrangements were found. Several nontypeable isolates lack hif genes but have two conserved open reading frames (hicA and hicB) upstream of purE; their inferred products are small proteins with no data bank homologs. Other isolates have hif genes but lack hic DNA or have combinations of hif and hic genes. By comparing these arrangements, we have reconstructed a hypothetical ancestral genotype, the extended hif cluster. The hif region of INT1, an invasive nontypeable isolate, resembles the hypothetical ancestor. We propose that a progenitor strain acquired the extended cluster by horizontal transfer and that other variants arose as deletions. The structure of the hif cluster may correlate with colonization site or pathogenicity.

The tryptophanase gene cluster of Haemophilus influenzae type b: evidence for horizontal gene transfer.

Among strains of Haemophilus influenzae, the ability to catabolize tryptophan (as detected by indole production) varies and is correlated with pathogenicity. Tryptophan catabolism is widespread (70 to 75%) among harmless respiratory isolates but is nearly universal (94 to 100%) among strains causing serious disease, including meningitis. As a first step in investigating the relationship between tryptophan catabolism and virulence, we have identified genes in pathogenic H. influenzae which are homologous to the tryptophanase (tna) operon of Escherichia coli. The tna genes are located on a 3.1-kb fragment between nlpD and mutS in the H. influenzae type b (Eagan) genome, are flanked by 43-bp direct repeats of an uptake signal sequence downstream from nlpD, and appear to have been inserted as a mobile unit within this sequence. The organization of this insertion is reminiscent of pathogenicity islands. The tna cluster is found at the same map location in all indole-positive strains of H. influenzae surveyed and is absent from reference type d and e genomes. In contrast to H. influenzae, most other Haemophilus species lack tna genes. Phylogenetic comparisons suggest that the tna cluster was acquired by intergeneric lateral transfer, either by H. influenzae or a recent ancestor, and that E. coli may have acquired its tnaA gene from a related source. Genomes of virulent H. influenzae resemble those of pathogenic enterics in having an island of laterally transferred DNA next to mutS.

Turbulence-aberration correction with high-speed high-gain optical phase conjugation in sodium vapor.

Optical aberrations that are due to high-speed turbulence in the aero-optical regime are corrected with optical phase conjugation based on coherent population trapping in sodium vapor. Experimental measurements of an unheated, forced helium jet in air have demonstrated aberration correction by a factor of 7.8 at a forcing frequency of 18kHz with an optical power gain of 32.

Distortion-free gain and noise correlation in sodium vapor with four-wave mixing and coherent population trapping.

We observed optical gain as great as 30 with nearly distortion-free beam propagation in optically dense sodium vapor, using four-wave mixing. Moreover, 15-dB classical noise correlations were seen in the amplified probe and conjugate beams. To achieve this performance in such a strongly absorbing medium, one must suppress unwanted absorption and self-focusing effects. This is accomplished with coherent population trapping.