Thermal Imaging of Block Copolymers with Sub-10 nm Resolution.

Thermal silicon probes have demonstrated their potential to investigate the thermal properties of various materials at high resolution. However, a thorough assessment of the achievable resolution is missing. Here, we present a probe-based thermal-imaging technique capable of providing sub-10 nm lateral resolution at a sub-10 ms pixel rate. We demonstrate the resolution by resolving microphase-separated PS-b-PMMA block copolymers that self-assemble in 11 to 19 nm half-period lamellar structures. We resolve an asymmetry in the heat flux signal at submolecular dimensions and assess the ratio of heat flux into both polymers in various geometries. These observations are quantitatively compared with coarse-grained molecular simulations of energy transport that reveal an enhancement of transport along the macromolecular backbone and a Kapitza resistance at the internal interfaces of the self-assembled structure. This comparison discloses a tip-sample contact radius of a ≈ 4 nm and identifies combinations of enhanced intramolecular transport and Kapitza resistance.

Self-assembly of block copolymers under non-isothermal annealing conditions as revealed by grazing-incidence small-angle X-ray scattering.

An accurate knowledge of the parameters governing the kinetics of block copolymer self-assembly is crucial to model the time- and temperature-dependent evolution of pattern formation during annealing as well as to predict the most efficient conditions for the formation of defect-free patterns. Here, the self-assembly kinetics of a lamellar PS-b-PMMA block copolymer under both isothermal and non-isothermal annealing conditions are investigated by combining grazing-incidence small-angle X-ray scattering (GISAXS) experiments with a novel modelling methodology that accounts for the annealing history of the block copolymer film before it reaches the isothermal regime. Such a model allows conventional studies in isothermal annealing conditions to be extended to the more realistic case of non-isothermal annealing and prediction of the accuracy in the determination of the relevant parameters, namely the correlation length and the growth exponent, which define the kinetics of the self-assembly.

Grain-Boundary-Induced Alignment of Block Copolymer Thin Films.

We present and discuss the capability of grain boundaries to induce order in block copolymer thin films between horizontally and vertically assembled block copolymer grains. The system we use as a proof of principle is a thermally annealed 23.4 nm full-pitch lamellar Polystyrene-block-polymethylmetacrylate (PS-b-PMMA) di-block copolymer. In this paper, grain-boundary-induced alignment is achieved by the mechanical removal of the neutral brush layer via atomic force microscopy (AFM). The concept is also confirmed by a mask-less e-beam direct writing process. An elongated grain of vertically aligned lamellae is trapped between two grains of horizontally aligned lamellae. This configuration leads to the formation of 90° twist grain boundaries. The features maintain their orientation on a characteristic length scale, which is described by the material's correlation length ξ. As a result of an energy minimization process, the block copolymer domains in the vertically aligned grain orient perpendicularly to the grain boundary. The energy-minimizing feature is the grain boundary itself. The width of the manipulated area (e.g., the horizontally aligned grain) does not represent a critical process parameter.

Recessive GM3 synthase deficiency: Natural history, biochemistry, and therapeutic frontier.

GM3 synthase, encoded by ST3GAL5, initiates synthesis of all downstream cerebral gangliosides. Here, we present biochemical, functional, and natural history data from 50 individuals homozygous for a pathogenic ST3GAL5 c.862C>T founder allele (median age 8.1, range 0.7-30.5 years). GM3 and its derivatives were undetectable in plasma. Weight and head circumference were normal at birth and mean Apgar scores were 7.7 ±â€¯2.0 (1 min) and 8.9 ±â€¯0.5 (5 min). Somatic growth failure, progressive microcephaly, global developmental delay, visual inattentiveness, and dyskinetic movements developed within a few months of life. Infantile-onset epileptic encephalopathy was characterized by a slow, disorganized, high-voltage background, poor state transitions, absent posterior rhythm, and spike trains from multiple independent cortical foci; >90% of electrographic seizures were clinically silent. Hearing loss affected cochlea and central auditory pathways and 76% of children tested failed the newborn hearing screen. Development stagnated early in life; only 13 (26%) patients sat independently (median age 30 months), three (6%) learned to crawl, and none achieved reciprocal communication. Incessant irritability, often accompanied by insomnia, began during infancy and contributed to high parental stress. Despite catastrophic neurological dysfunction, neuroimaging showed only subtle or no destructive changes into late childhood and hospitalizations were surprisingly rare (0.2 per patient per year). Median survival was 23.5 years. Our observations corroborate findings from transgenic mice which indicate that gangliosides might have a limited role in embryonic neurodevelopment but become vital for postnatal brain growth and function. These results have critical implications for the design and implementation of ganglioside restitution therapies.

Nano-confinement of block copolymers in high accuracy topographical guiding patterns: modelling the emergence of defectivity due to incommensurability.

Extreme ultraviolet interference lithography (EUV-IL) is used to manufacture topographical guiding patterns to direct the self-assembly of block copolymers. High-accuracy silicon oxide-like patterns with trenches ranging from 68 nm to 117 nm width are fabricated by exposing a hydrogen silsesquioxane (HSQ) resist layer using EUV-IL. We investigate how the accuracy, the low line width roughness and the low line edge roughness of the resulting patterns allow achieving DSA line/space patterns of a PS-b-PMMA (polystyrene-block-poly methyl methacrylate) block copolymer of 11 nm half-pitch with low defectivity. We conduct an in-depth study of the dependence of the DSA pattern morphology on the trench width and on how the neutral brush covers the guiding pattern. We identify the relation between trench width and the emergence of defects with nanometer precision. Based on these studies, we develop a model that extends available free energy models, which allows us to predict the patterning process window.

Strong-Isospin-Breaking Correction to the Muon Anomalous Magnetic Moment from Lattice QCD at the Physical Point.

All lattice-QCD calculations of the hadronic-vacuum-polarization contribution to the muon's anomalous magnetic moment to date have been performed with degenerate up- and down-quark masses. Here we calculate directly the strong-isospin-breaking correction to a_{µ}^{HVP} for the first time with physical values of m_{u} and m_{d} and dynamical u, d, s, and c quarks, thereby removing this important source of systematic uncertainty. We obtain a relative shift to be applied to lattice-QCD results obtained with degenerate light-quark masses of δa_{µ}^{HVP,m_{u}≠m_{d}}=+1.5(7)%, in agreement with estimates from phenomenology.

Review of lattice results concerning low-energy particle physics: Flavour Lattice Averaging Group (FLAG).

We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the determination of the light-quark masses, the form factor [Formula: see text], arising in the semileptonic [Formula: see text] transition at zero momentum transfer, as well as the decay constant ratio [Formula: see text] and its consequences for the CKM matrix elements [Formula: see text] and [Formula: see text]. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of [Formula: see text] and [Formula: see text] Chiral Perturbation Theory. We review the determination of the [Formula: see text] parameter of neutral kaon mixing as well as the additional four B parameters that arise in theories of physics beyond the Standard Model. The latter quantities are an addition compared to the previous review. For the heavy-quark sector, we provide results for [Formula: see text] and [Formula: see text] (also new compared to the previous review), as well as those for D- and B-meson-decay constants, form factors, and mixing parameters. These are the heavy-quark quantities most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. Finally, we review the status of lattice determinations of the strong coupling constant [Formula: see text].

Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant.

Lissencephaly is a malformation of cortical development typically caused by deficient neuronal migration resulting in cortical thickening and reduced gyration. Here we describe a "thin" lissencephaly (TLIS) variant characterized by megalencephaly, frontal predominant pachygyria, intellectual disability, and seizures. Trio-based whole-exome sequencing and targeted re-sequencing identified recessive mutations of CRADD in six individuals with TLIS from four unrelated families of diverse ethnic backgrounds. CRADD (also known as RAIDD) is a death-domain-containing adaptor protein that oligomerizes with PIDD and caspase-2 to initiate apoptosis. TLIS variants cluster in the CRADD death domain, a platform for interaction with other death-domain-containing proteins including PIDD. Although caspase-2 is expressed in the developing mammalian brain, little is known about its role in cortical development. CRADD/caspase-2 signaling is implicated in neurotrophic factor withdrawal- and amyloid-ß-induced dendritic spine collapse and neuronal apoptosis, suggesting a role in cortical sculpting and plasticity. TLIS-associated CRADD variants do not disrupt interactions with caspase-2 or PIDD in co-immunoprecipitation assays, but still abolish CRADD's ability to activate caspase-2, resulting in reduced neuronal apoptosis in vitro. Homozygous Cradd knockout mice display megalencephaly and seizures without obvious defects in cortical lamination, supporting a role for CRADD/caspase-2 signaling in mammalian brain development. Megalencephaly and lissencephaly associated with defective programmed cell death from loss of CRADD function in humans implicate reduced apoptosis as an important pathophysiological mechanism of cortical malformation. Our data suggest that CRADD/caspase-2 signaling is critical for normal gyration of the developing human neocortex and for normal cognitive ability.

Simultaneous synthesis of nanodiamonds and graphene via plasma enhanced chemical vapor deposition (MW PE-CVD) on copper.

The simultaneous growth of both nanodiamonds and graphene on copper samples is described for the first time. A PE-CVD process is used to synthesize graphene layers and nanodiamond clusters from a hydrogen/methane gas mixture as it is typically done successfully in thermal CVD processes for graphene synthesis. However, the standard thermal CVD process is not without problems since the deposition of graphene is affected by the evaporation of a notable amount of copper caused by the slow temperature increase typical for thermal CVD resulting in a long process time. In sharp contrast, the synthesis of graphene by PE-CVD can circumvent this problem by substantially shortening the process time at holding out the prospect of a lower substrate temperature. The reduced thermal load and the possibility to industrially scale-up the PE-CVD process makes it a very attractive alternative to the thermal CVD process with respect to the graphene production in the future. Nanodiamonds are synthesized in PE-CVD reactors for a long time because these processes offer a high degree of control over the film's nanostructure and simultaneously providing a significant high deposition rate. To model the co-deposition process, the three relevant macroscopic parameters (pressure, gas mixture and microwave power) are correlated with three relevant process properties (plasma ball size, substrate temperature and C2/Hα-ratio) and the influence on the quality of the deposited carbon allotropes is investigated. For the evaluation of the graphene as well as the nanodiamond quality, Raman spectroscopy used whereas the plasma properties are measured by optical methods. It is found that the diamond nucleation can be influenced by the C2/Hα-ratio in the plasma, while the graphene quality remains mostly unchanged by this parameter. Moreover it is derived from the experimental data that the direct plasma contact with the copper surface is beneficial for the nucleation of the diamond while the growth and quality of the graphene benefits from a larger distance to the plasma. Therefore, this work presents a basis for a method to tailor the deposition of graphene-diamond hybrid films using a MW PE-CVD process or to suppress the diamond deposition entirely if desired.

B→πll Form Factors for New Physics Searches from Lattice QCD.

The rare decay B→πℓ^{+}ℓ^{-} arises from b→d flavor-changing neutral currents and could be sensitive to physics beyond the standard model. Here, we present the first ab initio QCD calculation of the B→π tensor form factor f_{T}. Together with the vector and scalar form factors f_{+} and f_{0} from our companion work [J. A. Bailey et al., Phys. Rev. D 92, 014024 (2015)], these parametrize the hadronic contribution to B→π semileptonic decays in any extension of the standard model. We obtain the total branching ratio BR(B^{+}→π^{+}µ^{+}µ^{-})=20.4(2.1)×10^{-9} in the standard model, which is the most precise theoretical determination to date, and agrees with the recent measurement from the LHCb experiment [R. Aaij et al., J. High Energy Phys. 12 (2012) 125].

Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells.

GM3 synthase (ST3GAL5) is the first biosynthetic enzyme of a- and b-series gangliosides. Patients with GM3 synthase deficiency suffer severe neurological disability and deafness. Eight children (ages 4.1 ± 2.3 years) homozygous for ST3GAL5 c.694C>T had no detectable GM3 (a-series) or GD3 (b-series) in plasma. Their auditory function was characterized by the absence of middle ear muscle reflexes, distortion product otoacoustic emissions and cochlear microphonics, as well as abnormal auditory brainstem responses and cortical auditory-evoked potentials. In St3gal5(-/-) mice, stereocilia of outer hair cells showed signs of degeneration as early as postnatal Day 3 (P3); thereafter, blebs devoid of actin or tubulin appeared at the region of vestigial kinocilia, suggesting impaired vesicular trafficking. Stereocilia of St3gal5(-/-) inner hair cells were fused by P17, and protein tyrosine phosphatase receptor Q, normally linked to myosin VI at the tapered base of stereocilia, was maldistributed along the cell membrane. B4galnt1(-/-) (GM2 synthase-deficient) mice expressing only GM3 and GD3 gangliosides had normal auditory structure and function. Thus, GM3-dependent membrane microdomains might be essential for the proper organization and maintenance of stereocilia in auditory hair cells.

Determination of |V(us)|| from a lattice QCD calculation of the K → πℓν semileptonic form factor with physical quark masses.

We calculate the kaon semileptonic form factor f+(0) from lattice QCD, working, for the first time, at the physical light-quark masses. We use gauge configurations generated by the MILC Collaboration with Nf = 2 + 1 + 1 flavors of sea quarks, which incorporate the effects of dynamical charm quarks as well as those of up, down, and strange. We employ data at three lattice spacings to extrapolate to the continuum limit. Our result, f+(0) = 0.9704(32), where the error is the total statistical plus systematic uncertainty added in quadrature, is the most precise determination to date. Combining our result with the latest experimental measurements of K semileptonic decays, one obtains the Cabibbo-Kobayashi-Maskawa matrix element |V(us)| = 0.22290(74)(52), where the first error is from f+(0) and the second one is from experiment. In the first-row test of Cabibbo-Kobayashi-Maskawa unitarity, the error stemming from |V(us)| is now comparable to that from |V(ud)|.

Leptonic-decay-constant ratio f(K+)/f(π+) from lattice QCD with physical light quarks.

A calculation of the ratio of leptonic decay constants f(K+)/f(π+) makes possible a precise determination of the ratio of Cabibbo-Kobayashi-Maskawa (CKM) matrix elements |V(us)|/|V(ud)| in the standard model, and places a stringent constraint on the scale of new physics that would lead to deviations from unitarity in the first row of the CKM matrix. We compute f(K+)/f(π+) numerically in unquenched lattice QCD using gauge-field ensembles recently generated that include four flavors of dynamical quarks: up, down, strange, and charm. We analyze data at four lattice spacings a ≈ 0.06, 0.09, 0.12, and 0.15 fm with simulated pion masses down to the physical value 135 MeV. We obtain f(K+)/f(π+) = 1.1947(26)(37), where the errors are statistical and total systematic, respectively. This is our first physics result from our N(f) = 2+1+1 ensembles, and the first calculation of f(K+)/f(π+) from lattice-QCD simulations at the physical point. Our result is the most precise lattice-QCD determination of f(K+)/f(π+), with an error comparable to the current world average. When combined with experimental measurements of the leptonic branching fractions, it leads to a precise determination of |V(us)|/|V(ud)| = 0.2309(9)(4) where the errors are theoretical and experimental, respectively.

Refining new-physics searches in B→Dτν with lattice QCD.

The semileptonic decay channel B→Dτν is sensitive to the presence of a scalar current, such as that mediated by a charged-Higgs boson. Recently, the BABAR experiment reported the first observation of the exclusive semileptonic decay B→Dτ(-)ν, finding an approximately 2σ disagreement with the standard-model prediction for the ratio R(D)=BR(B→Dτν)/BR(B→Dℓν), where ℓ = e,µ. We compute this ratio of branching fractions using hadronic form factors computed in unquenched lattice QCD and obtain R(D)=0.316(12)(7), where the errors are statistical and total systematic, respectively. This result is the first standard-model calculation of R(D) from ab initio full QCD. Its error is smaller than that of previous estimates, primarily due to the reduced uncertainty in the scalar form factor f(0)(q(2)). Our determination of R(D) is approximately 1σ higher than previous estimates and, thus, reduces the tension with experiment. We also compute R(D) in models with electrically charged scalar exchange, such as the type-II two-Higgs-doublet model. Once again, our result is consistent with, but approximately 1σ higher than, previous estimates for phenomenologically relevant values of the scalar coupling in the type-II model. As a by-product of our calculation, we also present the standard-model prediction for the longitudinal-polarization ratio P(L)(D)=0.325(4)(3).

Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5.

We used single nucleotide polymorphism (SNP) microarrays to investigate the cause of a symptomatic epilepsy syndrome in a group of seven distantly related Old Order Mennonite children. Autozygosity mapping was inconclusive, but closer inspection of the data followed by formal SNP copy number analyses showed that all affected patients had homozygous deletions of a single SNP (rs721575) and their parents were hemizygous for this marker. The deleted SNP marked a larger deletion encompassing exons 9-13 of LYK5, which encodes STE20-related adaptor protein, a pseudokinase necessary for proper localization and function of serine/threonine kinase 11 (a.k.a. LKB1). Homozygous LYK5 deletions were associated with polyhydramnios, preterm labour and distinctive craniofacial features. Affected children had large heads, infantile-onset intractable multifocal seizures and severe psychomotor retardation. We designated this condition PMSE syndrome (polyhydramnios, megalencephaly and symptomatic epilepsy). Thirty-eight percent (N = 16) of affected children died during childhood (ages 7 months to 6 years) from medical complications of the disorder, which included status epilepticus, congestive heart failure due to atrial septal defect and hypernatremic dehydration due to diabetes insipidus. A single post-mortem neuropathological study revealed megalencephaly, ventriculomegaly, cytomegaly and extensive vacuolization and astrocytosis of white matter. There was abundant anti-phospho-ribosomal S6 labelling of large cells within the frontal cortex, basal ganglia, hippocampus and spinal cord, consistent with constitutive activation of the mammalian target of rapamycin (mTOR) signalling pathway in brain.

Quality of life and psychological status of patients with implantable cardioverter defibrillators.

BACKGROUND: Implantable cardioverter defibrillators reduce mortality in patients at high risk for sudden cardiac death and in patients with heart failure. Patients with defibrillators often experience psychological distress and poor quality of life, which can potentiate pathological processes that increase the risk for sudden cardiac death. To achieve the full benefits of the defibrillators, patients must maintain their psychological status and quality of life. OBJECTIVES: To review the research on psychological status and quality of life of patients with implantable cardioverter defibrillators and suggest nursing interventions to improve the patients' health. METHOD: Searches of PubMed were used to find articles on depression, anxiety, and quality of life in patients with implantable cardioverter defibrillators. RESULTS: Poor quality of life is associated with anxiety and depression in patients with implantable cardioverter defibrillators. Discharges of the devices have adverse consequences for patients' psychological status and quality of life. Younger patients are at highest risk for psychological distress and poor quality of life after implantation. Longitudinal research would facilitate determining the course of the changes in psychological status and quality of life during the time patients have the defibrillators. More intensive intervention may be necessary for the most vulnerable recipients: patients who are young, have experienced shocks, and are in psychological distress. CONCLUSIONS: Poor quality of life and depression are common in patients with implantable cardioverter defibrillators. Nursing interventions to reduce psychological distress and improve quality of life may reduce morbidity and mortality in these patients. Additional research is needed to determine effective interventions.

Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.

Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2 and clusters voltage-gated potassium channels (K(v)1.1) at the nodes of Ranvier. We report a homozygous mutation of CNTNAP2 in Old Order Amish children with cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures began in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and mental retardation developed in all children. Resective surgery did not prevent the recurrence of seizures. Temporal-lobe specimens showed evidence of abnormalities of neuronal migration and structure, widespread astrogliosis, and reduced expression of CASPR2.

Charmed-meson decay constants in three-flavor lattice QCD.

We present the first lattice QCD calculation with realistic sea quark content of the D+-meson decay constant f(D+). We use the MILC Collaboration's publicly available ensembles of lattice gauge fields, which have a quark sea with two flavors (up and down) much lighter than a third (strange). We obtain f(D+)=201+/-3+/-17 MeV, where the errors are statistical and a combination of systematic errors. We also obtain f(Ds)=249+/-3+/-16 MeV for the Ds meson.