Electric-field-directed growth of single-walled carbon nanotubes by chemical-vapor deposition is demonstrated. The field-alignment effect originates from the high polarizability of single-walled nanotubes. Large induced dipole moments lead to large aligning torques and forces on the nanotube, and prevent randomization of nanotube orientation by thermal fluctuations and gas flows. The results shall open up possibilities in directed growth of ordered molecular-wire architectures and networks on surfaces.

Heparin‐binding epidermal growth factor (HB‐EGF) and betacellulin (BTC) are activating ligands for EGF receptor (EGFR/ErbB1) and ErbB4. To identify their physiological functions, we disrupted mouse HB‐EGF and BTC alleles by homologous recombination. Most HB‐EGF−/− mice died before weaning, and survivors had enlarged, dysfunctional hearts and reduced lifespans. Although BTC−/− mice were viable and fertile and displayed no overt defects, the lifespan of double null HB‐EGF−/−/BTC−/− mice was further reduced, apparently due to accelerated heart failure. HB‐EGF−/− newborns had enlarged and malformed semilunar and atrioventricular heart valves, and hypoplastic, poorly differentiated lungs. Defective cardiac valvulogenesis was the result of abnormal mesenchymal cell proliferation during remodeling, and was associated with dramatic increases in activated Smad1/5/8. Consistent with the phenotype, HB‐EGF transcripts were localized to endocardial cells lining the margins of wild‐type valves. Similarly defective valvulogenesis was observed in newborn mice lacking EGFR and tumor necrosis factor‐α converting enzyme (TACE). These results suggest that cardiac valvulogenesis is dependent on EGFR activation by TACE‐derived soluble HB‐EGF, and that EGFR signaling is required to regulate bone morphogenetic protein signaling in this context.

Summary Background Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. Objectives To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. Methods Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence‐based definitions and diagnostic methods. Results The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence‐based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. Conclusions The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.

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Understanding the specificity of cell-surface carbohydrates interaction with antibodies and receptors is important for the development of new therapeutics and high-sensitivity diagnostics. This approach is, however, limited to the availability of natural and truncated sequences of the oligosaccharides and the sensitivity of the assay system. Reported here is the synthesis of the cancer antigen Globo H hexasaccharide, an epitope found on the cell surface of breast, prostate, and ovarian cancers, and its truncated sequences by using the programmable one-pot synthesis strategy. The saccharides were then arrayed covalently on glass slides with different density and used for the fluorencense-based binding analysis of two monoclonal antibodies against Globo H and the serum from breast cancer patients, to define the specificity of these antibodies. It was shown that the terminal tetrasaccharide binds the monoclonal antibodies equally well as does the hexasaccharide and the fucose residue is required for effective binding. The serum binds both the defucosylated pentasaccharide and the fucosylated hexasaccharide without a significant difference, perhaps because of the polyclonal nature of the serum or the presence of diverse immune responses to different sugar epitopes at various stages. This method requires very small amounts of materials and is more effective and sensitive than the traditional ELISA method, and thus provides another platform to monitor the immune response to carbohydrate epitopes at different stages during differentiation, metastasis, or treatment.programmable one-pot synthesis ͉ glycoarray ͉ glycan epitope ͉ Globo H-truncated sequences T he cell-surface glycosphingolipid Globo H is a member of a family of antigenic carbohydrates that are highly expressed on a range of cancer cell lines, especially breast cancer cells (1-4). Furthermore, it has been established that the serum of breast cancer patients contains high levels of antibodies against the Globo H epitope, and this epitope is also targeted by the monoclonal antibodies MBr1 (5-7) and VK-9 (8). As a result, this hexasaccharide has been the focus of studies aimed at anticancer vaccine development (9-15). Many elegant syntheses of Globo H have been reported (11,(16)(17)(18)(19)(20)(21)(22)(23)(24), including one approach that uses the one-pot programmable oligosaccharide synthesis developed in our laboratory (25). Previously, it has been reported that certain truncated Globo H derivatives can still be effective in binding MBr1 and VK-9 antibodies, which could increase the efficiency of immunogen development for vaccine therapy (8,(26)(27)(28)(29)(30). We set out to further characterize the binding specificities of these and cancer patient antibodies by using carbohydrate microarray analysis.Carbohydrate microarrays allow for the direct characterization of carbohydrate-protein interactions. In addition, the attachment of sugars to surfaces can effectively mimic the presentation of these compounds on the cell membrane. A large factor which is present...

Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. Scabies causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Recent scientific advances suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases (NTDs) in 2017. In order to develop a global control program, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring and evaluation of control strategies are also necessary.

EGF family growth factors, including transforming growth factor-alpha (TGFalpha), amphiregulin (AR), and heparin-binding EGF (HB-EGF), are invariably expressed as transmembrane precursors that are cleaved at one or more sites in the extracellular domain to release soluble growth factor. Considerable attention has focused on the identification of proteases responsible for these processing events. We previously implicated tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) in the generation of soluble TGFalpha from its transmembrane precursor, proTGFalpha. Here, we review our findings that primary keratinocytes from Tace(deltaZn/deltaZn) mice, which express a nonfunctional TACE, released dramatically lower levels of soluble TGFalpha compared to their normal counterparts, even though TGFalpha mRNA and cell-associated protein levels were similar in the two cell populations. Restoration of TACE activity in Tace(deltaZn/deltaZn) cells increased shedding of TGFalpha species, including the mature, 6-kDa protein. Further, exogenous TACE enzyme accurately cleaved the N-terminal processing site of proTGFalpha in cell lysates, as well as both physiologic sites of a soluble proTGFalpha ectodomain. TACE also accurately cleaved peptide substrates corresponding to the processing sites of several additional EGF family members, and restoration of TACE activity enhanced the shedding of soluble AR and HB-EGF proteins from Tace(deltaZn/deltaZn) cells. Finally, reduction of functional TACE gene dosage greatly exacerbated the open-eye defect of Egfr(wa-2/wa-2) newborns, which is regulated by redundant actions of several EGF family ligands. The implications of these results for the biology of the EGF family and TACE are discussed.

A covalent array for the display of complex oligosaccharides in microtiter plates has been developed. This strategy is conducive to the display of carbohydrates to proteins of interest such as lectins and antibodies, including the broadly neutralizing antibody 2G12 against HIV envelope oligomannose and can be cleaved from the surface for further characterization by mass spectrometry. The system was used to probe the multivalent interaction of 2G12 with an optimal epitope (Kd 0.1 muM).