Recently, microfluidic stretchable electronics has attracted great interest from academia since conductive liquids allow for larger cross-sections when stretched and hence low resistance at longer lengths. However, as a serial process it has suffered from low throughput, and a parallel processing technology is needed for more complex systems and production at low costs. In this work, we demonstrate such a technology to implement microfluidic electronics by stencil printing of a liquid alloy onto a semi-cured polydimethylsiloxane (PDMS) substrate, assembly of rigid active components, encapsulation by pouring uncured PDMS on-top and subsequent curing. The printing showed resolution of 200 μm and linear resistance increase of the liquid conductors when elongated up to 60%. No significant change of resistance was shown for a circuit with one LED after 1000 times of cycling between a 0% and an elongation of 60% every 2 s. A radio frequency identity (RFID) tag was demonstrated using the developed technology, showing that good performance could be maintained well into the radio frequency (RF) range.
We recently introduced a generic single nucleotide polymorphism (SNP) genotyping method, termed DASH (dynamic allele-specific hybridization), which entails dynamic tracking of probe (oligonucleotide) to target (PCR product) hybridization as reaction temperature is steadily increased. The reliability of DASH and optimal design rules have not been previously reported. We have now evaluated crudely designed DASH assays (sequences unmodified from genomic DNA) for 89 randomly selected and confirmed SNPs. Accurate genotype assignment was achieved for 89% of these worst-case-scenario assays. Failures were determined to be caused by secondary structures in the target molecule, which could be reliably predicted from thermodynamic theory. Improved design rules were thereby established, and these were tested by redesigning six of the failed DASH assays. This involved reengineering PCR primers to eliminate amplified target sequence secondary structures. This sophisticated design strategy led to complete functional recovery of all six assays, implying that SNPs in most if not all sequence contexts can be effectively scored by DASH. Subsequent empirical support for this inference has been evidenced by ∼30 failure-free DASH assay designs implemented across a range of ongoing genotyping programs. Structured follow-on studies employed standardized assay conditions, and revealed that assay reproducibility (733 duplicated genotypes, six different assays) was as high as 100%, with an assay accuracy (1200 genotypes, three different assays) that exceeded 99.9%. No post-PCR assay failures were encountered. These findings, along with intrinsic low cost and high flexibility, validate DASH as an effective procedure for SNP genotyping.The envisioned benefits of high-throughput single nucleotide polymorphism (SNP) analysis are numerous (Brookes 1999), and several large-scale SNP discovery programs are now underway or have been completed (Taillon-Miller et al. 1998;Wang et al. 1998;Cambien et al. 1999;Cargill et al. 1999;Emahazion et al. 1999;Marshall 1999;Picoult-Newberg et al. 1999). Additionally, a number of SNP databases have been built and are steadily growing in content, that is, HGBASE ; http://hgbase.cgr.ki.se), dbSNP (Smigielski et al. 2000; http://www.ncbi.nlm.nih.gov/ SNP) and the SNP Consortium (TSC) (Marshall 1999; http://snp.cshl.org). In order to fully realize the benefits of such developments, further improvements in SNP genotyping technologies will be required. Critical issues here will include ease of assay design, equipment complexity, assay cost, reliability, accuracy, flexibility, and compatibility with automation. Alternative methods under development in different laboratories possess various advantages and disadvantages, making each suitable for a different range of applications. Arguably, however, standardized and simple assay design in addition to accurate allele determination are perhaps the most important prerequisites for a broadly applicable method. Given these features, further development efforts would enable ...
OBJECTIVE -To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR.RESEARCH DESIGN AND METHODS -We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n ϭ 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years.RESULTS -Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69 -1.68]; P Ͻ 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n ϭ 443; P Ͻ 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR Ͻ50 ml/min per 1.73 m 2 ) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40 -0.84]; P Ͻ 0.004).CONCLUSIONS -Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.
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