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A straightforward, two step method for the self-assembly of single-walled carbon nanotubes (SWNTs) between gold electrodes is presented. The technique utilizes the hybridization between short complementary DNA sequences located on metal contacts and SWNTs. The new technique enables simple production of hundreds of devices with high yields. The electrical characteristics are shown to depend strongly on the existence of the chemical binding group, and are controlled by the transport through these groups. The current measured is larger by two orders of magnitude than the values reported for direct metal-SWNT contacts.

OBJECTIVE Endogenous insulin secretion, measured by C-peptide area under the curve (AUC), can be tested using both the glucagon stimulation test (GST) and the mixed-meal tolerance test (MMTT). This study compares these two stimulation methods using long-term data from patients newly diagnosed with type 1 diabetes or with latent autoimmune diabetes. RESEARCH DESIGN AND METHODS A recently completed phase 3 intervention study with DiaPep277 demonstrated improved glycemic control and a significant treatment effect of glucagon-stimulated C-peptide secretion. Unexpectedly, MMTT failed to detect differences between the treated and control groups. Data from 343 patients in two balanced-randomized, double-blind, placebo-controlled, parallel-group trials of DiaPep277 were used to compare and correlate between GST- and MMTT-derived C-peptide AUC. Pearson’s correlations were calculated for absolute C-peptide AUC at baseline and 12 and 24 months and for long-term changes in AUC (∆AUC). RESULTS The absolute AUC values obtained at any single time point by the two tests were well correlated in both data sets (r = 0.74–0.9). However, the correlations between the ∆AUC were much weaker (r = 0.39–0.58). GST-stimulated C-peptide secretion was stable over the fasting glucose range permitted for the test (4–11.1 mmol/L), but MMTT-stimulated C-peptide secretion decreased over the same range, implying differences in sensitivity to glucose. CONCLUSIONS Measurement of long-term changes in stimulated C-peptide, reflecting endogenous insulin secretion, during the course of intervention trials may be affected by the method of stimulation, possibly reflecting different sensitivities to the physiological status of the tested subject.

OBJECTIVE To evaluate safety and efficacy of DiaPep277 in preserving β-cell function in type 1 diabetic patients. RESEARCH DESIGN AND METHODS DIA-AID 1 is a multinational, phase 3, balanced-randomized, double-blind, placebo-controlled, parallel-group clinical study. Newly diagnosed patients (N = 457, aged 16–45 years) were randomized to subcutaneous injections of DiaPep277 or placebo quarterly for 2 years. The primary efficacy end point was the change from baseline in the area under the glucagon-stimulated C-peptide curve. Secondary end points were the change from baseline in mixed-meal stimulated C-peptide secretion and in fasting C-peptide and achieving target HbA1c ≤7% (≤53 mmol/mol). Partial remission (target HbA1c on insulin ≤0.5 units/kg/day) and hypoglycemic event rate were exploratory end points. RESULTS DiaPep277 was safe and well tolerated. Significant preservation of C-peptide secretion was observed in the DiaPep277-treated group compared with the placebo (relative treatment effects of 23.4%, P = 0.037, and 29.2%, P = 0.011, in the modified intent-to-treat [mITT] and per-protocol [PP] populations, respectively). The mixed-meal stimulation failed to distinguish between the groups. There was a trend toward efficacy in fasting C-peptide levels, though not statistically significant. Significantly more DiaPep277-treated than placebo-treated patients maintained target HbA1c (mITT 56% versus 44%, P = 0.03; PP 60% versus 45%, P = 0.0082) and entered partial remission (mITT 38% versus 29%, P = 0.08; PP 42% versus 30%, P = 0.035). DiaPep277 treatment reduced the relative hypoglycemic event risk (mITT by 20%; PP by 28%). CONCLUSIONS DiaPep277 safely contributes to preservation of β-cell function and to improved glycemic control in patients with type 1 diabetes.

Self-assembled carbon-nanotube-based field-effect transistors (CNTFETs) were produced with high yield using the natural process of DNA hybridization. In principle, the devices made by this method behave like those made using direct metal-carbon nanotube contacts. The inverse subthreshold slope of the CNTFETs depends on the source-drain voltage applied to the device, confirming that the conductance of CNTFETs is determined by the Schottky barriers at the interfaces between the CNTs and the gold electrodes.

Self-assembled patterned multilayers may be fabricated using DNA monolayers and the orchestrated reactions of DNA-modifying enzymes. To demonstrate this approach, DNA monolayers were formed on silicon and cleaved quantitatively with a restriction enzyme. Subsequently, fluorescently labeled nucleotides were covalently incorporated to the cleaved DNA. Nucleotide addition was shown to be highly selective according to the sequence at the cleavage site, and no nonspecific adsorption to the surface was observed. The dual action of the DNA-modifying enzymes was quantitative and could be utilized in the fabrication of multilayered structures. Other DNA-modifying enzymes can be exploited in this manner to enrich the repertoire of self-assembly supramolecular structure fabrication.

The adsorption of DNA on surfaces is a widespread procedure and is a common way for fabrication of biosensors, DNA chips, and nanoelectronic devices. Although the biologically relevant and prevailing in vivo structure of DNA is its double-stranded (dsDNA) conformation, the characterization of DNA on surfaces has mainly focused on single-stranded DNA (ssDNA). Studying the structure of dsDNA on surfaces is of invaluable importance to microarray performance since their effectiveness relies on the ability of two DNA molecules to hybridize and remain stable. In addition, many of the enzymatic transactions performed on DNA require dsDNA, rather than ssDNA, as a substrate. However, it is not established that adsorbed dsDNA remains in its structure and does not denature. Here, two methodologies have been developed for distinguishing between surface-adsorbed single- and double-stranded DNA. We demonstrate that, upon formation of a dense monolayer, the nonthiolated strand comprising the dsDNA is released and the monolayer consists of mostly ssDNA. The fraction of dsDNA within the ssDNA monolayer depends on the length of the oligomers. A likely mechanism leading to this rearrangement is discussed.

International audience; We present results from high-resolution electron energy loss spectroscopy (HREELS) and XPS studies of self-assembled monolayers of DNA. The monolayers are well-organized and display sharp vibrational peaks in the HREEL spectra. The electrons interact mainly with the backbone of the DNA. The XPS results indicate that, in most of the samples studied, the phosphates on the DNA are not charged.

A straightforward method for the self assembly of single walled carbon nanotubes (SWNTs) between gold electrodes was developed. The technique utilizes the hybridization between short complementary DNA sequences located on metal contacts and SWNTs. The new technique enables simple production of hundreds of devices with high yields. The electrical characteristics are shown to depend strongly on the existence of the chemical binding groups at the contacts as well as along the tubes. This technique was used to drive the self assembly of SWNT-based field effect transistors (CNTFETs). In principle, the devices made by this method behave like those made using direct metal–carbon nanotube contacts. The inverse subthreshold slope of the CNTFETs depends on the source–drain voltage applied to the device, confirming that the conductance of CNTFETs is determined by the Schottky barriers at the interfaces between the CNTs and the gold electrodes.

On behalf of the authors identified below, the corresponding author has formally requested to retract the above-cited article. An accompanying article (1) has also been retracted. The article reports on the DIA-AID 1 trial, which examined the safety and efficacy of DiaPep277 to treat type 1 diabetes. The DIA-AID 1 trial, as noted in the Duality of Interest section, was funded by Andromeda Biotech, Ltd. On 8 September 2014, Hyperion Therapeutics, Inc., which acquired Andromeda Biotech in June 2014, announced that it had chosen to terminate the DiaPep277 program. As stated in the press release …

On behalf of the authors identified below, the corresponding author has formally requested to retract the above-cited article. An accompanying article (1) has also been retracted. The study described in this article uses data from the DIA-AID 1 trial on DiaPep277 to compare treatment effects in patients with type 1 diabetes. The DIA-AID 1 trial, as noted in the Duality of Interest section, was funded by Andromeda Biotech, Ltd. On 8 September 2014, Hyperion Therapeutics, Inc., which acquired Andromeda Biotech in June 2014, announced that it had chosen to terminate the …