Reducing current noise in cryogenic experiments by vacuum-insulated cables.

We measure the current noise of several cryogenic cables in a pulse tube based dilution refrigerator at frequencies between about 1 mHz and 50 kHz. We show that vibration-induced noise can be efficiently suppressed by using vacuum-insulated cables between room temperature and the 2nd pulse tube stage. A noise peak below 4 fA at the 1.4 Hz operation frequency of the pulse tube and a white noise density of 0.44 fA/Hz in the millihertz range are obtained.

Accurate Coulomb blockade thermometry up to 60 kelvin.

We demonstrate experimentally a precise realization of Coulomb blockade thermometry working at temperatures up to 60 K. Advances in nano-fabrication methods using electron beam lithography allow us to fabricate uniform arrays of sufficiently small tunnel junctions to guarantee an overall temperature reading precision of about 1%.

Exome sequencing in single cells from the cerebrospinal fluid in multiple sclerosis.

BACKGROUND: Genome-wide association studies (GWAS) have identified over 100 germline variants that influence susceptibility to multiple sclerosis, most of which map within or near to genes with immunological function. However, the role of somatic mutations in multiple sclerosis has not been investigated. OBJECTIVE: The objective of this paper is to explore the role that somatic mutations might play in the development of multiple sclerosis. METHODS: We exome-sequenced in total 21 individual CD4+ lymphocytes isolated from cerebrospinal fluid of two patients. In addition we sequenced DNA from the patients' peripheral blood to serve as germline reference. RESULTS: In comparison with the respective germline sequence, each cell differed at an average of 1784 positions, but as anticipated subsequent analysis confirms that most, if not all, of these potential mutations are likely to represent artefacts generated during the amplification of a single genome and/or by sequencing. Fifty-six of the potential mutations were predicted to have likely functional effects on genes that have previously been implicated by GWAS, including three in the CD6 gene. CONCLUSION: More robust methods applied to larger numbers of cells will be needed to define the role of somatic mutations.

Excitation of single quasiparticles in a small superconducting Al island connected to normal-metal leads by tunnel junctions.

We investigate the dynamics of individual quasiparticle excitations on a small superconducting aluminum island connected to normal metallic leads by tunnel junctions. We find the island to be free of excitations within the measurement resolution. This allows us to show that the residual heating, which typically limits experiments on superconductors, has an ultralow value of less than 0.1 aW. By injecting electrons with a periodic gate voltage, we probe electron-phonon interaction and relaxation down to a single quasiparticle excitation pair, with a measured recombination rate of 16 kHz. Our experiment yields a strong test of BCS theory in aluminum as the results are consistent with it without free parameters.

Systematic review of genome-wide expression studies in multiple sclerosis.

Background Although recent genome-wide association studies have identified several genetic variants contributing to the complex aetiology of multiple sclerosis (MS), expression and functional studies are required to further understand its molecular basis. Objectives To identify genes and pathways with differential expression in MS. Design The authors conducted a systematic review of seven microarray studies, in which expression in immune cells was compared between MS patients and controls. These studies include a previously unpublished study, which is described here in detail. Results and conclusion Although in general the overlap between studies was poor, 229 genes were found to be differentially expressed in MS in at least two studies, of which 11 were in three studies and HSPA1A in four studies. After excluding the authors' unpublished experiment which may have been affected by certain confounding factors and inclusion of treated subjects, 135 genes were identified in at least two studies. The differentially expressed genes were significantly associated with several immunological pathways, including interleukin (IL)-4, IL-6, IL-17 and glucocorticoid receptor signalling pathways. 15 of the 229 loci have shown some association with MS in published genome-wide association studies (p<0.0001), including three loci with confirmed MS risk variants.

Environment-assisted tunneling as an origin of the Dynes density of states.

We show that the effect of a high-temperature environment in current transport through a normal metal-insulator-superconductor tunnel junction can be described by an effective density of states in the superconductor. In the limit of a resistive low-Ohmic environment, this density of states reduces into the well-known Dynes form. Our theoretical result is supported by experiments in engineered environments. We apply our findings to improve the performance of a single-electron turnstile, a potential candidate for a metrological current source.

A non-synonymous SNP within membrane metalloendopeptidase-like 1 (MMEL1) is associated with multiple sclerosis.

Several single-nucleotide polymorphism (SNP) genome-wide association studies (GWASs) have been completed in multiple sclerosis (MS). Follow-up studies of the variants with the most promising rankings, especially when supplemented by informed candidate gene selection, have proven to be extremely successful. In this study we report the results of a multi-stage replication analysis of the putatively associated SNPs identified in the Wellcome Trust Case Control Consortium non-synonymous SNP (nsSNP) screen. In total, the replication sample consisted of 3444 patients and 2595 controls. A combined analysis of the nsSNP screen and replication data provides evidence implicating a novel additional locus, rs3748816 in membrane metalloendopeptidase-like 1 (MMEL1; odds ratio=1.16, P=3.54 × 10⁻6) in MS susceptibility.

Single-electronic radio-frequency refrigerator.

We demonstrate experimentally that a hybrid single-electron transistor with superconducting leads and a normal-metal island can be refrigerated by an alternating voltage applied to the gate electrode. The simultaneous measurement of the dc current induced by the rf gate through the device at a small bias voltage serves as an in situ thermometer.

Determination of triacylglycerols in butterfat by normal-phase HPLC and electrospray-tandem mass spectrometry.

Here, we report the identification and quantification of the molecular species of long-, medium-, and short-chain triacylglycerols (TAG) in butterfat (BF), including TAG with an odd number of acyl carbons (ACN) and TAG with unidentified molecular species. In the present study, in addition to auto-MS(2), a large number of methods, each recording MS(2) for 1-4 ions, were used for identification of TAG species. For the quantification of long-chain, odd ACN TAG, and TAG with unidentified molecular species, molar correction factors (MCF) were calculated from the uncorrected mol% (area mol%) of each ACN:DB (number of double bonds) class in randomized butterfat (RBF), and the respective mol% in the calculated random composition of RBF. The butyrate, caproate, and medium-chain (C(8), C(10)) TAG were quantified using regio- or acyl-chain-specific MCF calculated from their area mol% in RBF and mol% in the calculated random composition. These methods enabled us to identify ca. 450 TAG species in 184 quantified peaks of 88 ACN:DB classes. The proportions of saturated, monoene, diene, triene, tetraene, pentaene, and hexaene TAG were 40.0, 38.4, 16.2, 4.5, 0.6, 0.1, and 0.03 mol%, respectively. The proportions of TAG with not identified molecular species and odd ACN TAG were 11.8 and 5.7 mol%, respectively. The most abundant short-chain TAG species were butyroyldipalmitoylglycerol + butyroylmyristoylstearoylglycerol (5.25 mol%) and butyroylpalmitoyloleoylglycerol (4.08 mol%).

Regiospecific determination of short-chain triacylglycerols in butterfat by normal-phase HPLC with on-line electrospray-tandem mass spectrometry.

This study uses normal-phase HPLC with on-line positive ion electrospray mass spectrometry (ESI-MS) to obtain quantitative compositional data on both synthetic and butterfat short-chain TAG. The product ion tandem MS of standards averaged 11.1 times lower in abundance of the ion formed by cleavage of FA from the sn-2-position for the pairs of regioisomers in the TAG classes: L/L/S-L/S/L and L/S/S-S/L/S, where L denotes long and S short acyl chain (C2-C6). The molar correction factors, determined for 42 regioisomeric pairs of short-chain TAG of 20 randomized mixture of standards, differed by 1.4-80% as the ratios varied between 0.217 and 5.847. Butterfat TAG were resolved into four fractions on short flash chromatography grade silica gel columns. Pairs of regioisomers in the TAG classes L/S/S-S/L/S with predominance of L/S/S isomers and the sole regioisomers in the TAG classes L/L(M)/S were identified by tandem MS, where M denotes either 8:0 or 10:0 acyl chain. The total proportion of L/L(M)/S isomers was estimated at 34.7 and that of L/S/S-S/L/S at 1.0 mol%, including a small proportion of S/S/S. In contrast to previous work, the present data indicate the presence of a small proportion of butyric and caproic acids in the sn-1-position. The overall distribution of the FA in the short-chain TAG of butterfat, calculated from direct MS measurements, was consistent with the results of indirect determinations based on stereospecific analyses of total butterfat.

Determination of positional distribution of butyryl groups in milkfat triacylglycerols, triacylglycerol mixtures, and isolated positional isomers of triacylglycerols by gas chromatography and 1H nuclear magnetic resonance spectroscopy.

Positional isomers (1-butyryl-2X-3Y-rac-glycerol and 2-butyryl-1X-3Y-rac-glycerol; X,Y = long-chain acyls) of saturated triacylglycerols (TAG) within 34 and 40 acyl carbons were shown to separate in two chromatographic peaks on immobilized phenyl(65%)methylsilicone column by gas-liquid chromatography, and on reversed-phase ODS-1 column by high-performance liquid chromatography. The analysis of 500-MHz 1H nuclear magnetic resonance (NMR) spectra showed distinct differences between 2-butyryl-1X-3Y-rac-glycerol and 1-butyryl-2X-3Y-rac-glycerol isomers in the resonance signals of methylene and methine protons of glycerol backbone, and carbon-2 methylene of acyl groups, and methyl protons of butyryl group. The 1H NMR spectra of three interesterified mixtures of three monacid TAG containing saturated butyrate and caproate TAG and unsaturated butyrate TAG showed that triplets of methyl protons of butyryl groups at sn-1(3)- and sn-2-positions in saturated and unsaturated TAG had similar chemical shifts and that the chemical shift of caproyl methyl protons was different from those of butyryl methyl protons. The positional distribution of butyryl groups in isolated positional isomers of butyrate TAG, interesterified TAG mixtures, and natural and interesterified butteroil can be determined by integration of these signals.