Magnetically aligned single wall carbon nanotube films: preferred orientation and anisotropic transport properties

Thick films of single wall carbon nanotubes (SWNT) exhibiting in-plane preferred orientation have been produced by filter deposition from suspension in strong magnetic fields. We characterize the field-induced alignment with x-ray fiber diagrams and polarized Raman scattering, using a model which includes a completely unaligned fraction. We correlate the texture parameters with resistivity and thermal conductivity measured parallel and perpendicular to the alignment direction. Results obtained with 7 and 26 Tesla fields are compared. We find no significant field dependence of the distribution width, while the aligned fraction is slightly greater at the higher field. Anisotropy in both transport properties is modest, with ratios in the range 5–9, consistent with the measured texture parameters assuming a simple model of rigid rod conductors. We suggest that further enhancements in anisotropic properties will require optimizing the filter deposition process rather than larger magnetic fields. We show that both x-ray and Raman data are required for a complete texture analysis of oriented SWNT materials

Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

<p>Abstract</p> <p>Background</p> <p>The JAK2^V617Fmutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1.</p> <p>Methods</p> <p>Pharmacological inhibition of JAK2/STAT5 signaling in JAK2^V617Fmutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins.</p> <p>Results</p> <p>Treatment of JAK2^V617Fmutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2^V617Fmutant cell viability and sensitized the cells to JAK2 inhibition.</p> <p>Conclusions</p> <p>We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2^V617Fcell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential for the treatment of chronic myeloproliferative neoplasms.</p

Study of the temperature distribution in Si nanowires under microscopic laser beam excitation

The use of laser beams as excitation sources for the characterization of semiconductor nanowires (NWs) is largely extended. Raman spectroscopy and photoluminescence (PL) are currently applied to the study of NWs. However, NWs are systems with poor thermal conductivity and poor heat dissipation, which result in unintentional heating under the excitation with a focused laser beam with microscopic size, as those usually used in microRaman and microPL experiments. On the other hand, the NWs have subwavelength diameter, which changes the optical absorption with respect to the absorption in bulk materials. Furthermore, the NW diameter is smaller than the laser beam spot, which means that the optical power absorbed by the NW depends on its position inside the laser beam spot. A detailed analysis of the interaction between a microscopic focused laser beam and semiconductor NWs is necessary for the understanding of the experiments involving laser beam excitation of NWs. We present in this work a numerical analysis of the thermal transport in Si NWs, where the heat source is the laser energy locally absorbed by the NW. This analysis takes account of the optical absorption, the thermal conductivity, the dimensions, diameter and length of the NWs, and the immersion medium. Both free standing and heat-sunk NWs are considered. Also, the temperature distribution in ensembles of NWs is discussed. This analysis intends to constitute a tool for the understanding of the thermal phenomena induced by laser beams in semiconductor NWs

Specific detection of proteins using nanomechanical resonators

Rapid, sensitive and inexpensive analysis of biological molecules is vital to many fundamental problems in molecular biology. Nanomechanical resonators are of great interest for such applications. The use of these devices for the analysis of protein mixtures would however require the immobilization of probes onto their surfaces in order to enable the specificity of the detection. Such nanoresonator-based specific detection of proteins is here reported using streptavidin as target system, and immobilized biotin as probe. Nanomechanical resonators resistant to stiction were first realized from silicon carbonitride using a novel fabrication method. Vapor-phase deposition of mercaptopropyl trimethoxysilane was performed, and an added mass of 2.22 \ub1 0.07 fg/\u3bcm2 was measured. This linker molecule was used to attach biotin onto the devices, enabling the specific detection of streptavidin. A mass of 3.6 fg/\u3bcm2 was attributed to the added streptavidin, corresponding to one molecule per 27 nm2. The specificity of this recognition was confirmed by exposing the devices to a solution of streptavidin that was already saturated with biotin. An additional negative control was also performed by also exposing bare devices to streptavidin in absence of the attached biotin. No resonance frequency shift was observed in either case, confirming the specificity of the detection.Peer reviewed: YesNRC publication: Ye

Large-scale arrays of nanomechanical sensors for biomolecular fingerprinting

A review of activities involving the development of large arrays of nanomechanical resonators is presented. This review includes demonstration of the use of these arrays for the detection of biological targets. Both top-down and bottom-up approaches to the realization of such arrays were developed. Using a top-down approach, a nanomachining method for the fabrication of large arrays of doubly-clamped silicon carbonitride (SiCN) resonators with width as narrow as 16 nm and a yield approaching 100% was developed. The specific detection of protein-A using such resonator arrays functionalized with single domain antibody fragments (sdAb) was also demonstrated with femtogram-level mass sensitivity. A nano-imprinting based fabrication of these resonator arrays was also realized, opening up their potential for cost-effective manufacturing. On a bottom-up approach, resonant silicon nanowires were also produced using directed chemical vapor deposition methods. These bottom-up resonant nanowires were in turn successfully employed for the specific detection of streptavidin with attogram-level mass sensitivity.Peer reviewed: YesNRC publication: Ye

Modulation of drug resistance by artificial transcription factors

The efficiency of chemotherapeutic treatments in cancer patients is often impaired by the acquisition of drug resistance. Cancer cells develop drug resistance through dysregulation of one or more genes or cellular pathways. To isolate efficient regulators of drug resistance in tumor cells, we have adopted a genome-wide scanning approach based on the screening of large libraries of artificial transcription factors (ATFs) made of three and six randomly assembled zinc finger domains. Zinc finger libraries were linked to a VP64 activation domain and delivered into a paclitaxel-sensitive tumor cell line. Following drug treatment, several ATFs were isolated that promoted drug resistance. One of these ATFs, 3ZF-1-VP, promoted paclitaxel resistance in cell lines having mutated or inactivated p53, such as MDA-MB-435 and Kaposi's sarcoma cell lines. 3ZF-1-VP also induced strong resistance to etoposide, vincristine, and cisplatinum. Linkage of a repression domain to the selected ATF resulted in enhanced sensitivity to multiple drugs, particularly vincristine, cisplatinum, and 5-fluorouracil. Small interfering RNA-mediated inhibition of p53 revealed that 3ZF-1-VP activated both p53-dependent and p53-independent mechanisms to promote survival, whereas other ATF required intact p53. Real-time expression analysis and DNA microarrays showed that several ATFs up-regulated targets of p53, such as the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), and genes participating in the p14(ARF)-MDM2-p53 tumor suppressor pathway, such as hDMP1. Thus, ATF can be used to map genes and pathways involved in drug resistance phenotypes and have potential as novel therapeutic agents to inhibit drug resistance