Characteristic features of the temperature dependence of the surface impedance in polycrystalline MgB2_2 samples

The real $R_s(T)$ and imaginary $X_s(T)$ parts of the surface impedance $Z_s(T)=R_s(T)+iX_s(T)$ in polycrystalline MgB$_2$ samples of different density with the critical temperature $T_c\approx 38$ K are measured at the frequency of 9.4 GHz and in the temperature range $5\le T<200$ K. The normal skin-effect condition $R_s(T)=X_s(T)$ at $T\ge T_c$ holds only for the samples of the highest density with roughness sizes not more than 0.1 $\mu$m. For such samples extrapolation $T\to 0$ of the linear at $T<T_c/2$ temperature dependences $\lambda_L(T)=X_s(T)/\omega\mu_0$ and $R_s(T)$ results in values of the London penetration depth $\lambda_L(0)\approx 600$ \AA and residual surface resistance $R_{res}\approx 0.8$ m$\Omega$. In the entire temperature range the dependences $R_s(T)$ and $X_s(T)$ are well described by the modified two-fluid model.Comment: 7 pages, 3 figures. Europhysics Letters, accepted for publicatio

Global Transcriptomic Profiling Using Small Volumes of Whole Blood: A Cost-Effective Method for Translational Genomic Biomarker Identification in Small Animals

Blood is an ideal tissue for the identification of novel genomic biomarkers for toxicity or efficacy. However, using blood for transcriptomic profiling presents significant technical challenges due to the transcriptomic changes induced by ex vivo handling and the interference of highly abundant globin mRNA. Most whole blood RNA stabilization and isolation methods also require significant volumes of blood, limiting their effective use in small animal species, such as rodents. To overcome these challenges, a QIAzol-based RNA stabilization and isolation method (QSI) was developed to isolate sufficient amounts of high quality total RNA from 25 to 500 μL of rat whole blood. The method was compared to the standard PAXgene Blood RNA System using blood collected from rats exposed to saline or lipopolysaccharide (LPS). The QSI method yielded an average of 54 ng total RNA per μL of rat whole blood with an average RNA Integrity Number (RIN) of 9, a performance comparable with the standard PAXgene method. Total RNA samples were further processed using the NuGEN Ovation Whole Blood Solution system and cDNA was hybridized to Affymetrix Rat Genome 230 2.0 Arrays. The microarray QC parameters using RNA isolated with the QSI method were within the acceptable range for microarray analysis. The transcriptomic profiles were highly correlated with those using RNA isolated with the PAXgene method and were consistent with expected LPS-induced inflammatory responses. The present study demonstrated that the QSI method coupled with NuGEN Ovation Whole Blood Solution system is cost-effective and particularly suitable for transcriptomic profiling of minimal volumes of whole blood, typical of those obtained with small animal species

Secretory breast carcinoma with metastatic sentinel lymph node

BACKGROUND: Secretory mammary carcinoma is a rare breast neoplasia originally described in children but sometimes also found in adults. It presents a more favourable outcome than more common histological types of breast carcinoma; published literature in fact reports only a few cases with axillary lymph node metastases and only four cases with distant metastases. CLINICAL PRESENTATION: In this paper we report a rare case of secretory breast carcinoma with axillary lymph node metastases in a 33-year-old woman. To our knowledge, this is the first case of secretory carcinoma involving biopsy of the sentinel lymph node and investigation of the e-cadherin expression. We found positivity for e-cadherin, which would support the hypothesis that this type of tumour is a variant of the infiltrating ductal carcinoma. CONCLUSION: After a careful analysis of reported data, we have come to the conclusion that the treatment of choice for patients with secretory breast carcinoma should be conservative surgery with sentinel lymph node biopsy, followed by accurate follow-up. We are of the opinion that while post-operative radiotherapy is indicated in adult patients who have undergone quadrantectomy, it should not be used in children. Although several cases of secretory carcinoma have been treated with adjuvant chemotherapy, there are still no reliable data regarding the real value of such a choice

Lipoprotein Lipase Links Dietary Fat to Solid Tumor Cell Proliferation

Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain pre-formed, diet-derived fatty acids by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further demonstrate that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or fatty acid uptake will be necessary to target the requirement of cancer cells for FA

Physical Mapping of Bread Wheat Chromosome 5A: An Integrated Approach

The huge size, redundancy, and highly repetitive nature of the bread wheat [Triticum aestivum (L.)] genome, makes it among the most difficult species to be sequenced. To overcome these limitations, a strategy based on the separation of individual chromosomes or chromosome arms and the subsequent production of physical maps was established within the frame of the International Wheat Genome Sequence Consortium (IWGSC). A total of 95,812 bacterial artificial chromosome (BAC) clones of short-arm chromosome 5A (5AS) and long-arm chromosome 5A (5AL) arm-specific BAC libraries were fingerprinted and assembled into contigs by complementary analytical approaches based on the FingerPrinted Contig (FPC) and Linear Topological Contig (LTC) tools. Combined anchoring approaches based on polymerase chain reaction (PCR) marker screening, microarray, and sequence homology searches applied to several genomic tools (i. e., genetic maps, deletion bin map, neighbor maps, BAC end sequences (BESs), genome zipper, and chromosome survey sequences) allowed the development of a high-quality physical map with an anchored physical coverage of 75% for 5AS and 53% for 5AL with high portions (64 and 48%, respectively) of contigs ordered along the chromosome. In the genome of grasses, Brachypodium [Brachypodium distachyon (L.) Beauv.], rice (Oryza sativa L.), and sorghum [Sorghum bicolor (L.) Moench] homologs of genes on wheat chromosome 5A were separated into syntenic blocks on different chromosomes as a result of translocations and inversions during evolution. The physical map presented represents an essential resource for fine genetic mapping and map-based cloning of agronomically relevant traits and a reference for the 5A sequencing projects

Substituted Indazoles as Na_v1.7 Blockers for the Treatment of Pain

The genetic validation for the role of the Na_v1.7 voltage-gated ion channel in pain signaling pathways makes it an appealing target for the potential development of new pain drugs. The utility of nonselective Na_v blockers is often limited due to adverse cardiovascular and CNS side effects. We sought more selective Na_v1.7 blockers with oral activity, improved selectivity, and good druglike properties. The work described herein focused on a series of 3- and 4-substituted indazoles. SAR studies of 3-substituted indazoles yielded analog <b>7</b> which demonstrated good in vitro and in vivo activity but poor rat pharmacokinetics. Optimization of 4-substituted indazoles yielded two compounds, <b>27</b> and <b>48</b>, that exhibited good in vitro and in vivo activity with improved rat pharmacokinetic profiles. Both <b>27</b> and <b>48</b> demonstrated robust activity in the acute rat monoiodoacetate-induced osteoarthritis model of pain, and subchronic dosing of <b>48</b> showed a shift to a lower EC₅₀ over 7 days

Substituted Indazoles as Na_v1.7 Blockers for the Treatment of Pain

The genetic validation for the role of the Na_v1.7 voltage-gated ion channel in pain signaling pathways makes it an appealing target for the potential development of new pain drugs. The utility of nonselective Na_v blockers is often limited due to adverse cardiovascular and CNS side effects. We sought more selective Na_v1.7 blockers with oral activity, improved selectivity, and good druglike properties. The work described herein focused on a series of 3- and 4-substituted indazoles. SAR studies of 3-substituted indazoles yielded analog <b>7</b> which demonstrated good in vitro and in vivo activity but poor rat pharmacokinetics. Optimization of 4-substituted indazoles yielded two compounds, <b>27</b> and <b>48</b>, that exhibited good in vitro and in vivo activity with improved rat pharmacokinetic profiles. Both <b>27</b> and <b>48</b> demonstrated robust activity in the acute rat monoiodoacetate-induced osteoarthritis model of pain, and subchronic dosing of <b>48</b> showed a shift to a lower EC₅₀ over 7 days