Damage coefficients in low resistivity silicon

Electron and proton damage coefficients are determined for low resistivity silicon based on minority-carrier lifetime measurements on bulk material and diffusion length measurements on solar cells. Irradiations were performed on bulk samples and cells fabricated from four types of boron-doped 0.1 ohm-cm silicon ingots, including the four possible combinations of high and low oxygen content and high and low dislocation density. Measurements were also made on higher resistivity boron-doped bulk samples and solar cells. Major observations and conclusions from the investigation are discussed

Rare Aggressive Form of Multiple Myeloma with Diffuse Osteosclerosis and Elevated CA 15-3 Levels

Abstract We report the case of a 56-year-old female who had recently been examined for back and epigastric pain, and was diagnosed in the internal medicine ward as having an aggressive rare form of multiple myeloma with diffuse osteoblastic bone lesions. She also had high levels of breast tumor marker (CA 15-3), severe tumor lysis syndrome, and pleural and central nervous system involvement. A few cases of multiple myeloma with diffuse osteosclerosis that are not part of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changeshave) have been described. None of these cases were as aggressive as our case. To our knowledge it is the first report describing an elevation in CA 15-3 in conjunction with multiple myeloma

Jejunal Perforation following Screening Colonoscopy

Colonoscopy is rarely associated with complications such as colonic perforation. Perforation of the small bowel is extremely rare, especially if the procedure is done without therapeutic interventions. Several factors are associated with this entity. Perforation of the ileum has been reported, but proximal jejunal perforation secondary to rupture of jejunal diverticulum during colonoscopy has not been reported. We present the case of an 88-year-old patient who developed abdominal pain after undergoing colonoscopy without any additional interventions. Urgent exploration revealed perforation of the proximal jejunum secondary to rupture of a jejunal diverticulum. No therapy or biopsies were undertaken during the colonoscopy, which are known predisposing factors

Detection of Neptune-size planetary candidates with CoRoT data. Comparison with the planet occurrence rate derived from Kepler

[Abridged] Context. The CoRoT space mission has been searching for transiting planets since the end of December 2006. Aims. We aim to investigate the capability of CoRoT to detect small-size transiting planets in short-period orbits, and to compare the number of CoRoT planets with 2 \leq R_p \leq 4 Rearth with the occurrence rate of small-size planets provided by the distribution of Kepler planetary candidates (Howard et al. 2012). Methods. We performed a test that simulates transits of super-Earths and Neptunes in real CoRoT light curves and searches for them blindly by using the LAM transit detection pipeline. Results. The CoRoT detection rate of planets with radius between 2 and 4 Rearth and orbital period P \leq 20 days is 59% (31%) around stars brighter than r'=14.0 (15.5). By properly taking the CoRoT detection rate for Neptune-size planets and the transit probability into account, we found that according to the Kepler planet occurrence rate, CoRoT should have discovered 12 \pm 2 Neptunes orbiting G and K dwarfs with P \leq 17 days in six observational runs. This estimate must be compared with the validated Neptune CoRoT-24b and five CoRoT planetary candidates in the considered range of planetary radii. We thus found a disagreement with expectations from Kepler at 3 \sigma or 5 \sigma, assuming a blend fraction of 0% (six Neptunes) and 100% (one Neptune) for these candidates. Conclusions. This underabundance of CoRoT Neptunes with respect to Kepler may be due to several reasons. Regardless of the origin of the disagreement, which needs to be investigated in more detail, the noticeable deficiency of CoRoT Neptunes at short orbital periods seems to indirectly support the general trend found in Kepler data, i.e. that the frequency of small-size planets increases with increasing orbital periods and decreasing planet radii.Comment: 10 pages, 7 figures. Accepted for publication in A&

Estradiol-regulated MicroRNAs Control Estradiol Response in Breast Cancer Cells

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). E2-inducible proteins c-Myc and E2Fs are required for optimal ERα activity and secondary estrogen responses, respectively. We show that E2 induces 21 microRNAs and represses seven microRNAs in MCF-7 breast cancer cells; these microRNAs have the potential to control 420 E2-regulated and 757 non-E2-regulated mRNAs at the post-transcriptional level. The serine/threonine kinase, AKT, alters E2-regulated expression of microRNAs. E2 induced the expression of eight Let-7 family members, miR-98 and miR-21 microRNAs; these microRNAs reduced the levels of c-Myc and E2F2 proteins. Dicer, a ribonuclease III enzyme required for microRNA processing, is also an E2-inducible gene. Several E2-regulated microRNA genes are associated with ERα-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ERα-positive breast cancers is dependent on the balance between E2-regulated tumor-suppressor microRNAs and oncogenic microRNAs. Additionally, our studies reveal a negative-regulatory loop controlling E2 response through microRNAs as well as differences in E2-induced transcriptome and proteome

Cell adhesion molecule CD166 drives malignant progression and osteolytic disease in multiple myeloma

Multiple myeloma (MM) is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in MM cell lines and primary bone marrow (BM) cells from patients. CD166+ MM cells homed more efficiently than CD166− cells to the BM of engrafted immunodeficient NSG mice. CD166 silencing in MM cells enabled longer survival, a smaller tumor burden and less osteolytic lesions, as compared to mice bearing control cells. CD166 deficiency in MM cell lines or CD138+ BM cells from MM patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Further, CD166 deficiency in MM cells also reduced formation of osteolytic disease in vivo after intra-tibial engraftment. Mechanistic investigation revealed that CD166 expression in MM cells inhibited osteoblastogenesis of BM-derived osteoblast progenitors by suppressing RUNX2 gene expression. Conversely, CD166 expression in MM cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in MM cell homing to the BM and MM progression, rationalizing its further study as a candidate therapeutic target for MM treatment

Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2

SUMMARY To maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSC (LT-HSC) reside in several, perhaps overlapping, niches that produce regulatory molecules/signals necessary for homeostasis and increased output following stress/injury 1–5. Despite significant advances in specific cellular or molecular mechanisms governing HSC/niche interactions, little is understood about regulatory function within the intact mammalian hematopoietic niche. Recently, we and others described a positive regulatory role for Prostaglandin E2 (PGE2) on HSC function ex vivo 6,7. While exploring the role of endogenous PGE2 we unexpectedly observed hematopoietic egress after nonsteroidal anti-inflammatory drug (NSAID) treatment. Surprisingly, this was independent of the SDF-1/CXCR4 axis. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin (OPN). Hematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in higher species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced EP4 receptor signaling. These results not only uncover unique regulatory roles for EP4 signaling in HSC retention in the niche but also define a rapidly translatable strategy to therapeutically enhance transplantation

Conjugation with L, L-diphenylalanine Self-Assemblies Enhances In Vitro Antitumor Activity of Phthalocyanine Photosensitizer

We present the synthesis and characterization of new peptide conjugates obtained by hierarchical co-assembly of L,L-diphenylalanine (FF) and zinc phthalocyanine complexes (ZnPc) in water. Self-assembly capabilities under defined conditions were investigated by scanning electron microscopy, and photophysical properties were evaluated using UV-Vis and fluorescence spectroscopy. AFM observations demonstrated that these ZnPcs form different highly ordered arrays on the crystalline faces of the FF microplates and that surface roughness significantly changes with the presence of differently substituted phthalocyanine units. XRD assays showed that the overall molecular packing of the conjugates is organized according to a hexagonal symmetry, with ZnPcs hosted in the interstices of the peptide phase. In vitro photodynamic studies were conducted on human breast cancer MCF-7 cells to investigate both cellular uptake and cytotoxicity. It was shown that FF self-assemblies are not toxicity and enhance accumulation of ZnPc in MCF-7 cells, improving apoptotic cell death upon irradiation. Our findings demonstrate enhancement of ZnPc antitumor efficiency by FF conjugates and a proof-of-concept for new photosensitizer carriers based on peptide conjugates