Graphene overcoats for ultra-high storage density magnetic media.

Hard disk drives (HDDs) are used as secondary storage in digital electronic devices owing to low cost and large data storage capacity. Due to the exponentially increasing amount of data, there is a need to increase areal storage densities beyond ~1 Tb/in2. This requires the thickness of carbon overcoats (COCs) to be <2 nm. However, friction, wear, corrosion, and thermal stability are critical concerns below 2 nm, limiting current technology, and restricting COC integration with heat assisted magnetic recording technology (HAMR). Here we show that graphene-based overcoats can overcome all these limitations, and achieve two-fold reduction in friction and provide better corrosion and wear resistance than state-of-the-art COCs, while withstanding HAMR conditions. Thus, we expect that graphene overcoats may enable the development of 4-10 Tb/in2 areal density HDDs when employing suitable recording technologies, such as HAMR and HAMR+bit patterned media.

Preparation of an Antibacterial Poly(ionic liquid) Graft Copolymer of Hydroxyethyl Cellulose.

Poly(ionic liquid)s (P(IL)s) of different degrees of polymerization (10, 50, and 100) were prepared via RAFT polymerization using an alkyne-terminated xanthate as transfer agent, with a monomer conversion of up to ∼80% and a DM of 1.5 for P(IL)100. Subsequently, P(IL) chains were coupled to (15)N-labeled azido-functionalized hydroxyethyl cellulose (HEC), forming graft copolymers of HEC with different chain length and graft densities, which were characterized using ((13)C and (15)N) CP-MAS NMR and FT-IR spectroscopies. The antibacterial activities of HEC-g-P(IL)s were tested against Escherichia coli and Staphylococcus aureus and were comparable to ampicillin, a well-known antibiotic, demonstrating efficient activity of the graft copolymers against bacteria. Moreover, HEC-g-P(IL)s were slightly more effective against E. coli than S. aureus. A decrease in graft density of P(IL)10 on the HEC backbone decreased the activity of the graft copolymers against both bacteria. These findings suggest that HEC-g-P(IL) could find applications as an antiseptic compound, for example, in paint formulation.

Validation of a nomogram in the prediction of local recurrence risks after conserving surgery for Asian women with ductal carcinoma in situ of the breast.

AIMS: At our centre, ductal carcinoma in situ (DCIS) was commonly treated with breast-conservation therapy (BCT). Local recurrence after BCT is a major concern. The aims of our study were to review the outcomes of DCIS treatment in our patients and to evaluate a nomogram from Memorial Sloan Kettering Cancer Centre (MSKCC) for predicting ipsilateral breast tumour recurrence (IBTR) in our Asian population. MATERIALS AND METHODS: Chart reviews of 716 patients with pure DCIS treated from 1992 to 2011 were carried out. Univariable Cox regression analyses were used to evaluate the effects of the 10 prognostic factors of the MSKCC nomogram on IBTR. We constructed a separate National Cancer Centre Singapore (NCCS) nomogram based on multivariable Cox regression via reduced model selection by applying the stopping rule of Akaike's information criterion to predict IBTR-free survival. The abilities of the NCCS nomogram and the MSKCC nomogram to predict IBTR of individual patients were evaluated with bootstrapping of 200 sets of resamples and the NCCS dataset, respectively. Harrell's c-index was calculated for each nomogram to evaluate the concordance between predicted and observed responses of individual subjects. RESULTS: Study patients were followed up for a median of 70 months. Over 95% of patients received adjuvant radiotherapy. The 5 and 10 year actuarial IBTR-free survival rates for the cohort were 95.5 and 92.6%, respectively. In the multivariate analysis, independent prognostic factors for IBTR included use of adjuvant endocrine therapy, presence of comedonecrosis and younger age at diagnosis. These factors formed the basis of the NCCS nomogram, which had a similar c-index (NCCS: 0.696; MSKCC: 0.673) compared with the MSKCC nomogram. CONCLUSION: The MSKCC nomogram was validated in an Asian population. A simpler NCCS nomogram using a different combination of fewer prognostic factors may be sufficient for the prediction of IBTR in Asians, but requires external validation to compare for relative performance.

The impact of parent socio-economic status on executive functioning and cortical morphology in individuals with schizophrenia and healthy controls.

BACKGROUND: Relatively lower executive functioning is characteristic of individuals with schizophrenia. As low socio-economic status (SES) early in life (i.e. parent SES) has been linked with lower executive skills in healthy children, we hypothesized that parental SES (pSES) would be more strongly related to executive functioning in individuals with schizophrenia than in controls and have a greater impact on prefrontal cortical morphology. METHOD: Healthy controls (n = 125) and individuals with schizophrenia (n = 102) completed tests assessing executive functioning and intelligence. The groups were matched on pSES, which was evaluated with the Hollingshead-Redlich scale. A principal components analysis (PCA) was conducted on 10 variables from six executive tests, yielding three specific components (fluency, planning and response inhibition). Voxel-based morphometry (VBM) was used to evaluate effects of pSES on gray matter (GM) concentration. RESULTS: Lower pSES was associated with lower scores across the three executive functioning components, and a significant group by pSES interaction was observed such that low pSES, in particular, affected individuals with schizophrenia. These effects remained significant when intellectual ability, education and self-SES (sSES) were added as covariates. VBM revealed that lower pSES was associated with reduced GM volume in several anterior brain regions, especially the superior frontal gyrus, in patients but not in controls. CONCLUSIONS: These findings suggest that individuals with schizophrenia may be particularly vulnerable to the adverse impact of low pSES, in terms of both lower executive skills and reduced anterior GM volumes.

Why are East Asians more susceptible to several infection-associated cancers (carcinomas of the nasopharynx, stomach, liver, adenocarcinoma of the lung, nasal NK/T-cell lymphomas)?

There are at least five cancers with uniquely high incidence amongst East and Southeast Asian ethnic groups - namely nasopharyngeal carcinoma (NPC); gastric carcinoma; hepatocellular carcinoma (HCC); adeno-carcinoma of the lung in female non-smokers and nasal NK/T-cell lymphomas. They all appear to be related to an infective cause (Epstein Barr Virus, Helicobacter pylori, hepatitis B virus). We hypothesize that a genetic bottleneck 30,000years ago at the Last Glacial Maximum could have resulted in unique genetic polymorphisms in Toll-like receptor 8, making East Asians more vulnerable to these infective associated cancers. This bottleneck could have been caused by the presence of malaria in the southern Himalayan conduit between central and East Asia; and only those with an attenuated innate immune response to the malarial parasite (perhaps reflected by the TLR8 polymorphism) were spared the ravages of cerebral malaria; allowing these people to cross into east Asia, but then rendering them susceptible to later endemic infections and their associated cancers.

Alzheimer's disease and intelligence.

A significant body of evidence has accumulated suggesting that individual variation in intellectual ability, whether assessed directly by intelligence tests or indirectly through proxy measures, is related to risk of developing Alzheimer's disease (AD) in later life. Important questions remain unanswered, however, such as the specificity of risk for AD vs. other forms of dementia, and the specific links between premorbid intelligence and development of the neuropathology characteristic of AD. Lower premorbid intelligence has also emerged as a risk factor for greater mortality across myriad health and mental health diagnoses. Genetic covariance contributes importantly to these associations, and pleiotropic genetic effects may impact diverse organ systems through similar processes, including inefficient design and oxidative stress. Through such processes, the genetic underpinnings of intelligence, specifically, mutation load, may also increase the risk of developing AD. We discuss how specific neurobiologic features of relatively lower premorbid intelligence, including reduced metabolic efficiency, may facilitate the development of AD neuropathology. The cognitive reserve hypothesis, the most widely accepted account of the intelligence-AD association, is reviewed in the context of this larger literature.

Influence of lipids on the interfacial disposition of respiratory syncytical virus matrix protein.

The propensity of a matrix protein from an enveloped virus of the Mononegavirales family to associate with lipids representative of the viral envelope has been determined using label-free methods, including tensiometry and Brewster angle microscopy on lipid films at the air-water interface and atomic force microscopy on monolayers transferred to OTS-treated silicon wafers. This has enabled factors that influence the disposition of the protein with respect to the lipid interface to be characterized. In the absence of sphingomyelin, respiratory syncytial virus matrix protein penetrates monolayers composed of mixtures of phosphocholines with phosphoethanolamines or cholesterol at the air-water interface. In ternary mixtures composed of sphingomyelin, 1,2-dioleoyl-sn-glycero-3-phosphocholine, and cholesterol, the protein exhibits two separate behaviors: (1) peripheral association with the surface of sphingomyelin-rich domains and (2) penetration of sphingomyelin-poor domains. Prolonged incubation of the protein with mixtures of phosphocholines and phosphoethanolamines leads to the formation of helical protein assemblies of uniform diameter that demonstrate an inherent propensity of the protein to assemble into a filamentous form.

A prospective diffusion tensor imaging study in mild traumatic brain injury.

OBJECTIVES: Only a handful of studies have investigated the nature, functional significance, and course of white matter abnormalities associated with mild traumatic brain injury (mTBI) during the semi-acute stage of injury. The present study used diffusion tensor imaging (DTI) to investigate white matter integrity and compared the accuracy of traditional anatomic scans, neuropsychological testing, and DTI for objectively classifying mTBI patients from controls. METHODS: Twenty-two patients with semi-acute mTBI (mean = 12 days postinjury), 21 matched healthy controls, and a larger sample (n = 32) of healthy controls were studied with an extensive imaging and clinical battery. A subset of participants was examined longitudinally 3-5 months after their initial visit. RESULTS: mTBI patients did not differ from controls on clinical imaging scans or neuropsychological performance, although effect sizes were consistent with literature values. In contrast, mTBI patients demonstrated significantly greater fractional anisotropy as a result of reduced radial diffusivity in the corpus callosum and several left hemisphere tracts. DTI measures were more accurate than traditional clinical measures in classifying patients from controls. Longitudinal data provided preliminary evidence of partial normalization of DTI values in several white matter tracts. CONCLUSIONS: Current findings of white matter abnormalities suggest that cytotoxic edema may be present during the semi-acute phase of mild traumatic brain injury (mTBI). Initial mechanical damage to axons disrupts ionic homeostasis and the ratio of intracellular and extracellular water, primarily affecting diffusion perpendicular to axons. Diffusion tensor imaging measurement may have utility for objectively classifying mTBI, and may serve as a potential biomarker of recovery.

The 24-angstrom structure of respiratory syncytial virus nucleocapsid protein-RNA decameric rings.

Respiratory syncytial virus (RSV), a nonsegmented, negative-sense RNA-containing virus, is a common cause of lower respiratory tract disease. Expression of RSV nucleocapsid protein (N) in insect cells using the baculovirus expression system leads to the formation of N-RNA complexes that are morphologically indistinguishable from viral nucleocapsids. When imaged in an electron microscope, three distinct types of structures were observed: tightly wound short-pitch helices, highly extended helices, and rings. Negative stain images of N-RNA rings were used to calculate a three-dimensional reconstruction at 24 A resolution, revealing features similar to those observed in nucleocapsids from other viruses of the order Mononegavirales. The reconstructed N-RNA rings comprise 10 N monomers and have an external radius of 83 A and an internal radius of 40 A. Comparison of this structure with crystallographic data from rabies virus and vesicular stomatitis virus N-RNA rings reveals striking morphological similarities.

FIGO stage 1B2 cervical carcinoma--the KK Women's and Children's Hospital experience.

INTRODUCTION: The objectives of this review were to document the surgico-pathological characteristics of surgically resected FIGO stage 1B2 cervical carcinoma and to review our overall experience with this disease. MATERIALS AND METHODS: This is a retrospective review of 35 patients diagnosed and treated from September 1990 to November 2001. RESULTS: The median age was 42 years and the mean tumour diameter was 5.1 cm. Majority were squamous cell carcinomas (65.7%), 28.6% were adenocarcinomas and 5.7% were adeno-squamous carcinomas. The primary treatment comprised radical surgery in 77.1%, radiotherapy in 20% and neoadjuvant chemotherapy followed by radical surgery and adjuvant radiotherapy in 2.9%. Significant surgico-pathological features noted were deep stromal invasion (66.7%), lympho-vascular space invasion (55.6%), parametrial involvement (22.2%), positive margins (3.7%) and pelvic node metastases (33.3%). Postoperative radiation was given to 92.6% of the patients who underwent primary surgery, of whom 29% received concurrent chemotherapy. Radiation toxicity was mild with no grade 3 or 4 toxicity documented. For the patients who had surgery, the recurRence rate was 14.8% (11.1% pelvic and 3.7% distant) and the survival rate was 88.9%. For those who had primary radiation, the rate of persistent disease was 28.6%, the distant recurrence rate was 28.6% and the survival rate was 57.1%. CONCLUSION: FIGO stage 1B2 cervical carcinomas are associated with significant rates of adverse surgico-pathological features. The ideal primary treatment is yet to be established and should be determined by prospective randomised trials.

Characterization of monoclonal antibodies raised against recombinant respiratory syncytial virus nucleocapsid (N) protein: identification of a region in the carboxy terminus of N involved in the interaction with P protein.

To investigate structure and biological properties of the nucleocapsid (N) protein of respiratory syncytial virus (RSV), we have generated a panel of 16 monoclonal antibodies, raised against recombinant N protein, and epitope mapped seven of these to three antigenic sites (Site I aa 16-30; Site II aa 341-350; Site III aa 351-365). Characterization by immunofluorescence and by immunoprecipitation assay demonstrated that a monoclonal antibody to antigenic site I can detect N protein complexed with phospho (P) protein. Antibodies to antigenic sites II and III, which are adjacent to each other near the carboxyl terminus of the N protein, have distinct properties. A site III monoclonal antibody detected N protein in cytoplasmic inclusion bodies and in the cytosol, but not when N was complexed to P protein, while the site II antibody reacted with N protein in the nucleocapsid fraction but did not detect cytosolic N protein. Further investigation into the reactivities of the antibodies after binding of P to N in vitro demonstrated that antigenic sites II and III were blocked by the interaction, indicating an involvement for the carboxy domain of N in the N-P interaction. This was confirmed by the ability of peptides from the carboxy terminus of N to inhibit the N-P interaction in vitro.

Gerstmann syndrome in systemic lupus erythematosus: neuropsychological, neuroimaging and spectroscopic findings.

Gerstmann syndrome (GS) comprises four interlaced neuropsychological symptoms including finger agnosia, right-left confusion, agraphia, and acalculia. While GS is commonly associated with focal lesions to the region of the left angular gyrus, it has also been associated with numerous diffuse etiologies including atrophy, alcoholism, carbon monoxide poisoning, lead intoxication and anaphylactic shock. Thus, a vigorous debate has emerged as to whether GS represents a syndrome arising from general brain decline or a distinct and localizing lesion. We report a right-handed patient who developed neuropsychological dysfunction secondary to systemic lupus erythematosus (SLE). Neuropsychological evaluation found the patient to exhibit symptoms consistent with the GS tetrad, as well as general cognitive decline. Magnetic resonance imaging revealed a distinct focal lesion of the left parieto-occipital white matter underlying the angular gyrus as well as diffuse atrophy. (1)H-magnetic resonance spectroscopy revealed substantial metabolic derangement in a voxel placed within the visible lesion, although substantial metabolic derangement was observed in regions remote from the focal pathology. Thus, GS in this first case in SLE would appear to comprise a focal neurological tetrad of disorders within a more general pattern of cognitive decline and metabolic derangement.

Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study.

Proton magnetic resonance spectroscopy (1H-MRS) offers a unique insight into brain cellular metabolism following traumatic brain injury (TBI). The aim of the present study was to assess change in neurometabolite markers of brain injury during the recovery period following TBI. We studied 19 TBI patients at 1.5, 3, and 6 months postinjury and 28 controls. We used 1H-MRS to quantify N-acetylaspartate (NAA), creatine (Cre), choline (Cho), and myoinositol (mIns) in occipitoparietal gray matter (GM) and white matter (WM) remote from the primary injury focus. Neuropsychological testing quantified cognitive impairment and recovery. At 1.5 months, we found cognitive impairment (mean z score = -1.36 vs. 0.18,p < 0.01), lower NAA (GM: 12.42 mM vs. 13.03, p = 0.01; WM: 11.75 vs. 12.81, p < 0.01), and elevated Cho (GM: 1.51 vs. 1.25, p < 0.01; WM: 1.98 vs. 1.79, p < 0.01) in TBI patients compared with controls. GM NAA at 1.5 months predicted cognitive function at outcome (6 months postinjury; r = 0.63, p = 0.04). GM NAA continued to fall by 0.46 mM between 1.5 and 3 months (p = 0.02) indicating continuing neuronal loss, metabolic dysfunction, or both. Between 3 and 6 months, WM NAA increased by 0.55 mM (p = 0.06) suggesting metabolic recovery. Patients with poorer outcomes had elevated mean GM Cho at 3 months postinjury, suggesting active inflammation, as compared to patients with better outcomes (p = 0.002). 1H-MRS offers a noninvasive approach to assessing neuronal injury and inflammation following TBI, and may provide unique data for patient management and assessment of therapeutic efficacy.

Developmental instability and working memory ability in children: a magnetic resonance spectroscopy investigation.

This study of children (ages 7 through 12) wishes to determine (a) whether variation in frontal lobe brain chemistry, determined from proton magnetic resonance spectroscopy (1H-MRS), is related to performance on a working memory task in children, and (b) whether developmental instability (DI; the imprecise expression of the genetic plan for development due to several known genetic and environmental effects) underlies phenotypic variation in brain chemistry. 1H-MRS assessed neurometabolites in a right frontal white matter voxel. The Visual Two-Back test assessed working memory. A composite measure of DI was created from measures of minor physical anomalies, fluctuating asymmetry of body characteristics, and fluctuating asymmetry of dermatoglyphic features. Greater DI strongly predicted lower concentrations of creatine-phosphocreatine (Cre) and choline-containing compounds, whereas Cre and N-acetyl-aspartate positively correlated with working memory skills. Working memory skills thus seem related to frontal lobe energy metabolism, which in turn is related to DI.

Developmental instability predicts individual variation in verbal memory skill after caffeine ingestion.

OBJECTIVE: To determine the mediating effects of developmental instability on individual differences in response to caffeine. BACKGROUND: Individual variation of drug effects might reflect broad genomic factors as well as the direct effects of specific alleles. The current study tested the hypothesis that individual differences in developmental instability, in part determined by genomic characteristics, would predict individual variation in the magnitude of caffeine-induced verbal memory deficits. Minor physical anomalies and fluctuating asymmetry were used as measures of developmental instability. METHOD: One hundred participants were (1) administered one version of the Rey Auditory Verbal Learning Test; (2) given a dose of caffeine determined by body weight (3 mg/kg); (3) assessed for minor physical anomalies and fluctuating asymmetry; and (4) given an alternate randomized version of the Rey Auditory Verbal Learning Test. RESULTS: Consistent with predictions, a composite measure of developmental instability predicted the magnitude of caffeine-induced memory decrements. CONCLUSIONS: These results may have important implications for the genetic underpinnings of individual differences in drug effects.

Myths of neuropsychology: intelligence, neurometabolism, and cognitive ability.

Recently, Dodrill (1999) revised a previously described "Myth of neuropsychology" (1997) to state: "Just as below average performances on neuropsychological tests are found when intelligence is below average, to that same degree above average performances on neuropsychological tests are expected when intellectual abilities are above average." This study addresses the relationship between intellectual and neuropsychological performance in the context of Magnetic Resonance Spectroscopy (MRS) measurements of the neurometabolite N-acetylaspartate (NAA). When subjects were stratified by Full Scale IQ (Average, High Average, Superior) they differed significantly in terms of total neuropsychological performance [F(2,47) = 17.63; p <.001] and the neuronal marker NAA [F(2,47) = 3.25; p <.05]. Regression analysis across groups demonstrated that FSIQ and NAA were independently related to Total z-score [F(1,47) = 29.43; p <.0001] and accounted for over half the variance (r(2) of model =.56). The concurrent relationship of FSIQ and NAA to total neuropsychological performance suggests that the relationship between measures sensitive to intellectual ability and neuropsychological performance is real, and does not reflect arbitrary psychometric or scaling properties of the WAIS-III.

Biochemical markers of cognition: a proton MR spectroscopy study of normal human brain.

In the current study we explored the relationship between neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) and cognitive ability assessed with a battery of neuropsychological tests. Forty-five participants were recruited from the local college community, and examined utilizing neuropsychological testing and 1H-MRS. Our central finding was that N-acetylaspartate (NAA) was associated with overall neuropsychological performance (F(1,42) = 23.16, p < 0.0001], r2 = 0.35. We found an even stronger association between timed neuropsychological measures and NAA (F(1,42) = 31.15, p < 0.0001], r = 0.43. These results reveal the specific relationship of NAA to neuropsychological functioning in normal human brain. The current observations in healthy individuals are consistent with the hypothesis that variability in NAA levels and neuropsychological performance may be related to mitochondrial function.

The evolutionary genetic underpinnings of schizophrenia: the developmental instability model.

The importance of genes in the etiology of schizophrenia is well known, but the manner in which the relevant genomic factors influence neural development and the nature of selection forces operating on these factors are poorly understood. In several prominent papers, Crow has provided a unique and comprehensive theory that attempts to deal with these issues. A central aspect of his theory is that a single gene leads to reduced cerebral lateralization, increased ventricular size, and risk for developing schizophrenia. He relies greatly on Annett's right shift theory of individual variation in handedness. An alternative approach, based on the construct of developmental instability, provides a different way to conceptualize genetic influences, selection forces, and atypical lateralization in schizophrenia. We suggest that the developmental instability model has stronger empirical support and is better grounded in contemporary evolutionary genetics.