Quantification of probe-sample interactions of a scanning thermal microscope using a nanofabricated calibration sample having programmable size.

We report a method for quantifying scanning thermal microscopy (SThM) probe-sample thermal interactions in air using a novel temperature calibration device. This new device has been designed, fabricated and characterised using SThM to provide an accurate and spatially variable temperature distribution that can be used as a temperature reference due to its unique design. The device was characterised by means of a microfabricated SThM probe operating in passive mode. This data was interpreted using a heat transfer model, built to describe the thermal interactions during a SThM thermal scan. This permitted the thermal contact resistance between the SThM tip and the device to be determined as 8.33 × 10(5) K W(-1). It also permitted the probe-sample contact radius to be clarified as being the same size as the probe's tip radius of curvature. Finally, the data were used in the construction of a lumped-system steady state model for the SThM probe and its potential applications were addressed.

Cultural Adaptation of Interventions in Real Practice Settings.

This article provides an overview of some common challenges and opportunities related to cultural adaptation of behavioral interventions. Cultural adaptation is presented as a necessary action to ponder when considering the adoption of an evidence-based intervention with ethnic and other minority groups. It proposes a roadmap to choose existing interventions and a specific approach to evaluate prevention and treatment interventions for cultural relevancy. An approach to conducting cultural adaptations is proposed, followed by an outline of a cultural adaptation protocol. A case study is presented, and lessons learned are shared as well as recommendations for culturally grounded social work practice.

Interactions of Anopheles gambiae odorant-binding proteins with a human-derived repellent: implications for the mode of action of n,n-diethyl-3-methylbenzamide (DEET).

The Anopheles gambiae mosquito, which is the vector for Plasmodium falciparum malaria, uses a series of olfactory cues emanating from human sweat to select humans as their source for a blood meal. Perception of these odors within the mosquito olfactory system involves the interplay of odorant-binding proteins (OBPs) and odorant receptors and disrupting the normal responses to those odorants that guide mosquito-human interactions represents an attractive approach to prevent the transmission of malaria. Previously, it has been shown that DEET targets multiple components of the olfactory system, including OBPs and odorant receptors. Here, we present the crystal structure of A. gambiae OBP1 (OBP1) in the complex it forms with a natural repellent 6-methyl-5-heptene-2-one (6-MH). We find that 6-MH binds to OBP1 at exactly the same site as DEET. However, key interactions with a highly conserved water molecule that are proposed to be important for DEET binding are not involved in binding of 6-MH. We show that 6-MH and DEET can compete for the binding of attractive odorants and in doing so disrupt the interaction that OBP1 makes with OBP4. We further show that 6-MH and DEET can bind simultaneously to OBPs with other ligands. These results suggest that the successful discovery of novel reagents targeting OBP function requires knowledge about the specific mechanism of binding to the OBP rather than their binding affinity.

Quantitative multiplex immunohistochemistry reveals inter-patient lymphovascular and immune heterogeneity in primary cutaneous melanoma.

Introduction: Quantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms and tissue structures that determine leukocyte distribution within and around tumor nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates that blood and lymphatic vessels (lymphovasculature) also dictate leukocyte trafficking within tumor microenvironments and thereby impact anti-tumor immunity. Here we interrogate these relationships in primary human cutaneous melanoma. Methods: We established a quantitative, multiplexed imaging platform to simultaneously detect immune infiltrates and tumor-associated vessels in formalin-fixed paraffin embedded patient samples. We performed a discovery, retrospective analysis of 28 treatment-naïve, primary cutaneous melanomas. Results: Here we find that the lymphvasculature and immune infiltrate is heterogenous across patients in treatment naïve, primary melanoma. We categorized five lymphovascular subtypes that differ by functionality and morphology and mapped their localization in and around primary tumors. Interestingly, the localization of specific vessel subtypes, but not overall vessel density, significantly associated with the presence of lymphoid aggregates, regional progression, and intratumoral T cell infiltrates. Discussion: We describe a quantitative platform to enable simultaneous lymphovascular and immune infiltrate analysis and map their spatial relationships in primary melanoma. Our data indicate that tumor-associated vessels exist in different states and that their localization may determine potential for metastasis or immune infiltration. This platform will support future efforts to map tumor-associated lymphovascular evolution across stage, assess its prognostic value, and stratify patients for adjuvant therapy.

Discrimination and Rejection: The Effects of Ethnic and Sexuality-Based Discrimination Against Latino Gay and Bisexual Men.

Latino gay and bisexual men (GBM) may experience discrimination attributed to their sexual orientation and ethnicity, necessitating an examination of their experiences from an intersectional lens. While relationships between discrimination and the internalization of those messages have been previously researched, less is known about experiencing discrimination attributed to different identities and its relationships with discrete attributions of internalized stigma. Understanding how different attributes of identity-based discrimination are related to different attributes of identity-based internalization of stigma among gay and bisexual men of color may be important in the design of interventions to help Latino GBM cope with discrimination and prevent negative mental health outcomes. In order to achieve this aim, the current study utilized data from the Latino MSM Community Involvement: HIV Protective Effects Study, which included 571 self-identified Latino GBM. Results demonstrate that experiences of external anti-Latino discrimination were significantly linked to both internalized ethnicity- and sexuality-based stigma, whereas experiences of external sexuality-based discrimination were not significantly linked with internalized ethnicity- or sexuality-based stigma. Results suggest a need for future research to further examine effects of external ethnic discrimination on the psychosocial health of Latino GBM.

Self-Assembled Asperities for Pressure-Tunable Adhesion.

Control of adhesion is important in a host of applications including soft robotics, pick-and-place manufacturing, wearable devices, and transfer printing. While there are adhesive systems with discrete switchability between states of high and low adhesion, achieving continuously variable adhesion strength remains a challenge. In this work, a pressure-tunable adhesive (PTA) that is based on the self-assembly of stiff microscale asperities on an elastomeric substrate is presented. It is demonstrated that the adhesion strength of the PTA increases with the applied compressive preload due to the unique contact formation mechanism caused by the asperities. Additionally, a contact mechanics model is developed to explain the resulting trends. For a specific PTA design, the critical pull-off force can be increased from 0.4 to 30 mN by increasing the applied preload from 1 to 30 mN. Finally, the applicability of precision control of adhesion strength is demonstrated by utilizing the PTA for pick-and-place material handling. The approach in pressure-tunable adhesive design based on self-assembly of asperities presents a scalable and versatile approach that is applicable to a variety of material systems having different mechanical or surface properties.

Preventing Catastrophic Failure of Microfibrillar Adhesives in Compliant Systems Based on Statistical Analysis of Adhesive Strength.

Adhesives based on fibrillar surface microstructures have shown great potential for handling applications requiring strong, reversible, and switchable adhesion. Recently, the importance of the statistical distribution of adhesive strength of individual fibrils in controlling the overall performance was revealed. Strength variations physically correspond to different interfacial defect sizes, which, among other factors, are related to surface roughness. For analysis of the strength distribution, Weibull's statistical theory of fracture was introduced. In this study, the importance of the statistical properties in controlling the stability of attachment is explored. Considering the compliance of the loading system, we develop a stability criterion based on the Weibull statistical parameters. It is shown that when the distribution in fibril adhesive strength is narrow, the global strength is higher but unstable detachment is more likely. Experimental variation of the loading system compliance for a specimen of differing statistical properties shows a transition to unstable detachment at low system stiffness, in good agreement with the theoretical stability map. This map serves to inform the design of gripper compliance, when coupled with statistical analysis of strength on the target surface of interest. Such a treatment could prevent catastrophic failure by spontaneous detachment of an object from an adhesive gripper.

Yang-Mills structure for electron-phonon interactions in vanadium dioxide.

This work presents a method of grouping the electron spinors and the phonon modes of metal oxide crystals such as vanadium dioxide into an SU(2) gauge theory. The gauge "charge" is the electron spin, which is assumed to couple to the transverse acoustic phonons on the basis of spin ordering phenomena in [Formula: see text]- and [Formula: see text]-[Formula: see text], while the longitudinal mode is neutral. A generalization of the Peierls Mechanism is presented based on the discrete gauge invariance of crystals and the corresponding Ward-Takahashi identity. The introduction of a band index results in violation of this discrete Ward-Takahashi identity for interband transitions, resulting in scattering from the longitudinal component. Thus both the spinors and the bosons acquire mass and an electronic band gap and optical phonon modes result: a symmetry-breaking metal-insulator transition, which can manifest concurrent spin-ordering.

Statistical properties of defect-dependent detachment strength in bioinspired dry adhesives.

Dry adhesives using surface microstructures inspired by climbing animals have been recognized for their potentially novel capabilities, with relevance to a range of applications including pick-and-place handling. Past work has suggested that performance may be strongly dependent on variability in the critical defect size among fibrillar sub-contacts. However, it has not been directly verified that the resulting adhesive strength distribution is well described by the statistical theory of fracture used. Using in situ contact visualization, we characterize adhesive strength on a fibril-by-fibril basis for a synthetic fibrillar adhesive. Two distinct detachment mechanisms are observed. The fundamental, design-dependent mechanism involves defect propagation from within the contact. The secondary mechanism involves defect propagation from fabrication imperfections at the perimeter. The existence of two defect populations complicates characterization of the statistical properties. This is addressed by using the mean order ranking method to isolate the fundamental mechanism. The statistical properties obtained are subsequently used within a bimodal framework, allowing description of the secondary mechanism. Implications for performance are discussed, including the improvement of strength associated with elimination of fabrication imperfections. This statistical analysis of defect-dependent detachment represents a more complete approach to the characterization of fibrillar adhesives, offering new insight for design and fabrication.

Diversifying the solid state and lyotropic phase behavior of nonionic urea-based surfactants.

The solid state and lyotropic phase behavior of 10 new nonionic urea-based surfactants has been characterized. The strong homo-urea interaction, which can prevent urea surfactants from forming lyotropic liquid crystalline phases, has been ameliorated through the use of isoprenoid hydrocarbon tails such as phytanyl (3,7,11,15-tetramethyl-hexadecyl) and hexahydrofarnesyl (3,7,11-trimethyl-dodecyl) or the oleyl chain (cis-octadec-9-enyl). Additionally, the urea head group was modified by attaching either a hydroxy alkyl (short chain alcohol) moiety to one of the nitrogens of the urea or by effectively "doubling" the urea head group by replacing it with a biuret head group. The solid state phase behavior, including the liquid crystal-isotropic liquid, polymorphic, and glass transitions, is interpreted in terms of molecular geometries and probable hydrogen-bonding interactions. Four of the modified urea surfactants displayed ordered lyotropic liquid crystalline phases that were stable in excess water at both room and physiological temperatures, namely, 1-(2-hydroxyethyl)-1-oleyl urea (oleyl 1,1-HEU) with a 1D lamellar phase (Lalpha), 1-(2-hydroxyethyl)-3-phytanyl urea (Phyt 1,3-HEU) with a 2D inverse hexagonal phase (HII), and 1-(2-hydroxyethyl)-1-phytanyl urea (Phyt 1,1-HEU) and 1-(2-hydroxyethyl)-3-hexahydrofarnesyl urea (Hfarn 1,3-HEU) with a 3D bicontinuous cubic phase (QII). Phyt 1,1-HEU exhibited rich mesomorphism (QII1, QII2, Lalpha, LU, and HII), as did one other surfactant, oleyl 1,3-HEU (QII1, QII2, Lalpha, LU, and HII), in the study group. LU is an unusual phase which is mobile and isotropic but possesses shear birefringence, and has been very tentatively assigned as an inverse sponge phase. Three other surfactants exhibited a single lyotropic liquid crystalline phase, either Lalpha or HII, at temperatures >50 degrees C. The 10 new surfactants are compared with other recently reported nonionic urea surfactants. Structure-property correlations are examined for this novel group of self-assembling amphiphiles.

Influence of Humidity on Grip and Release Adhesion Mechanisms for Gecko-Inspired Microfibrillar Surfaces.

Geckos have developed foot pads that allow them to maintain their unique climbing ability despite vast differences of surfaces and environments, from dry desert to humid rainforest. Likewise, successful gecko-inspired mimics should exhibit adhesive and frictional performance across a similarly diverse range of climates. In this work, we focus on the effect of relative humidity (RH) on the "frictional-adhesion" behavior of gecko-inspired adhesive pads. A surface forces apparatus was used to quantitatively measure adhesion and friction forces of a microfibrillar cross-linked polydimethylsiloxane surface against a smooth hemispherical glass disk at varying relative humidity, from 0 to 100% (including fully submerged under water). Geometrically anisotropic tilted half-cylinder microfibers yield a "grip state" (high adhesion and friction forces after shearing along the tilt of the fibers, Fad+ and F∥+) and a "release state" (low adhesion and friction after shearing against the tilt of the fibers, Fad- and F∥-). By appropriate control of the loading path, this allows for transition between strong attachment and easy detachment. Changing the preload and shear direction gives rise to differences in the effective contact area at each fiber and the microscale and nanoscale structure of the contact while changing the relative humidity results in differences in the relative contributions of van der Waals and capillary forces. In combination, both effects lead to interesting trends in the adhesion and friction forces. At up to 75% RH, the grip state adhesion force remains constant and the ratio of grip to release adhesion force does not drop below 4.0. In addition, the friction forces F∥+ and F∥- and the release state adhesion force Fad- exhibit a maximum at intermediate relative humidity between 40% and 75%.

Lymphatic Vessels Balance Viral Dissemination and Immune Activation following Cutaneous Viral Infection.

Lymphatic vessels lie at the interface between peripheral sites of pathogen entry, adaptive immunity, and the systemic host. Though the paradigm is that their open structure allows for passive flow of infectious particles from peripheral tissues to lymphoid organs, virus applied to skin by scarification does not spread to draining lymph nodes. Using cutaneous infection by scarification, we analyzed the effect of viral infection on lymphatic transport and evaluated its role at the host-pathogen interface. We found that, in the absence of lymphatic vessels, canonical lymph-node-dependent immune induction was impaired, resulting in exacerbated pathology and compensatory, systemic priming. Furthermore, lymphatic vessels decouple fluid and cellular transport in an interferon-dependent manner, leading to viral sequestration while maintaining dendritic cell transport for immune induction. In conclusion, we found that lymphatic vessels balance immune activation and viral dissemination and act as an "innate-like" component of tissue host viral defense.

Correlating the Energetics and Atomic Motions of the Metal-Insulator Transition of M1 Vanadium Dioxide.

Materials that undergo reversible metal-insulator transitions are obvious candidates for new generations of devices. For such potential to be realised, the underlying microscopic mechanisms of such transitions must be fully determined. In this work we probe the correlation between the energy landscape and electronic structure of the metal-insulator transition of vanadium dioxide and the atomic motions occurring using first principles calculations and high resolution X-ray diffraction. Calculations find an energy barrier between the high and low temperature phases corresponding to contraction followed by expansion of the distances between vanadium atoms on neighbouring sub-lattices. X-ray diffraction reveals anisotropic strain broadening in the low temperature structure's crystal planes, however only for those with spacings affected by this compression/expansion. GW calculations reveal that traversing this barrier destabilises the bonding/anti-bonding splitting of the low temperature phase. This precise atomic description of the origin of the energy barrier separating the two structures will facilitate more precise control over the transition characteristics for new applications and devices.

1H, 13C and 15N NMR assignments of the C1A and C1B subdomains of PKC-delta.

The Protein Kinase C family of enzymes is a group of serine/threonine kinases that play central roles in cell-cycle regulation, development and cancer. A key step in the activation of PKC is translocation to membranes and binding of membrane-associated activators including diacylglycerol (DAG). Interaction of novel and conventional isotypes of PKC with DAG and phorbol esters occurs through the two C1 regulatory domains (C1A and C1B), which exhibit distinct ligand binding selectivity that likely controls enzyme activation by different co-activators. PKC has also been implicated in physiological responses to alcohol consumption and it has been proposed that PKCα (Slater et al. J Biol Chem 272(10):6167-6173, 1997; Slater et al. Biochemistry 43(23):7601-7609, 2004), PKCε (Das et al. Biochem J 421(3):405-413, 2009) and PKCδ (Das et al. J Biol Chem 279(36):37964-37972, 2004; Das et al. Protein Sci 15(9):2107-2119, 2006) contain specific alcohol-binding sites in their C1 domains. We are interested in understanding how ethanol affects signal transduction processes through its affects on the structure and function of the C1 domains of PKC. Here we present the (1)H, (15)N and (13)C NMR chemical shift assignments for the Rattus norvegicus PKCδ C1A and C1B proteins.

Periodic mesoporous Li(x)(Mn(1/3)Ni(1/3)Co(1/3))O2 spinel.

A monoclinic periodic mesoporous Li(x)(Mn(1/3)Ni(1/3)Co(1/3))O(2) spinel has been successfully prepared for the first time using a 'two solvents' pore infiltration methodology on hard silica templates. More commonly used synthetic techniques are not applicable to this complex material. This important battery cathode has a surface area of over 180 m(2)g(-1) and a pore size of 5.5 nm.

Anisotropic structure deformation in the VO2 metal-insulator transition.

X-ray absorption fine structure data of tungsten (VI)-doped vanadium dioxide in the insulating phase, and during the metal-insulator transition, are presented for the first time. Tungsten L(III)- and vanadium K-edge data suggest that significant expansion in the [110] and [110] directions occurs across the phase transition from low to high temperature. This distortion breaks the bonds between Peierls-paired vanadium ions, opening a band gap, and reveals the nature of the mechanism by which tungsten doping lowers the transition temperature and enthalpy.

Production of VO2 M1 and M2 nanoparticles and composites and the influence of the substrate on the structural phase transition.

A two-step, high-purity, high-yield synthesis of nanoparticulate vanadium dioxide, which has a greater than 10-fold potential cost reduction is reported. This consists of a short reflux of V2O5 with aspartic acid, followed by calcination at 600 degrees C or above. The particles produced have a mean diameter of approximately 90 nm with phase change characteristics of transition temperature and enthalpy that compare favorably with a commercial standard. In cases where the reduction reaction has progressed too far and a mixture of vanadium(III) and -(IV) is formed, redispersion and aging of the particulate product in water preferentially oxidizes the vanadium(III) component to vanadium(IV), thus allowing a versatile route to achieving a high-purity material. The synthesis was also used to deposit high-purity phases of VO2 onto the surfaces of other particles, and significant differences in the structural phase transition behavior and even the crystal structure were found for deposited samples. The data suggest that substrate properties may affect the characteristics of the structural phase transition, and this has significant implications for measurements on, and applications of, deposited VO2 layers and films.

Gold nanoparticle formation during bromoaurate reduction by amino acids.

The synthesis and characterization of water-soluble dispersions of gold nanoparticles by the reduction of a potassium tetrabromoaurate precursor solution using the amino acids L-tyrosine, glycyl-L-tyrosine, and L-arginine using alkaline synthesis conditions are reported. The particle sizes determined by small-angle X-ray scattering (SAXS) and high-resolution transmission electron microscopy (HRTEM) measurements are found to be inversely proportional to the rate of particle formation, which was determined by time-resolved UV-visible spectrophotometry measurements, and vary very slowly at intermediate gold concentrations and rapidly at the extremes. Dispersions produced with a mixture of the two amino acids glycyl-L-tyrosine and L-tyrosine showed particle sizes and particle size distributions which were directly proportional to the ratio of the two L-amino acids, thus offering the possibility for control over the properties of the gold nanoparticle dispersions.