Genomic aberrations in normal tissue adjacent to HER2-amplified breast cancers: field cancerization or contaminating tumor cells?

Field cancerization effects as well as isolated tumor cell foci extending well beyond the invasive tumor margin have been described previously to account for local recurrence rates following breast conserving surgery despite adequate surgical margins and breast radiotherapy. To look for evidence of possible tumor cell contamination or field cancerization by genetic effects, a pilot study (Study 1: 12 sample pairs) followed by a verification study (Study 2: 20 sample pairs) were performed on DNA extracted from HER2-positive breast tumors and matching normal adjacent mammary tissue samples excised 1-3 cm beyond the invasive tumor margin. High-resolution molecular inversion probe (MIP) arrays were used to compare genomic copy number variations, including increased HER2 gene copies, between the paired samples; as well, a detailed histologic and immunohistochemical (IHC) re-evaluation of all Study 2 samples was performed blinded to the genomic results to characterize the adjacent normal tissue composition bracketing the DNA-extracted samples. Overall, 14/32 (44 %) sample pairs from both studies produced genome-wide evidence of genetic aberrations including HER2 copy number gains within the adjacent normal tissue samples. The observed single-parental origin of monoallelic HER2 amplicon haplotypes shared by informative tumor-normal pairs, as well as commonly gained loci elsewhere on 17q, suggested the presence of contaminating tumor cells in the genomically aberrant normal samples. Histologic and IHC analyses identified occult 25-200 μm tumor cell clusters overexpressing HER2 scattered in more than half, but not all, of the genomically aberrant normal samples re-evaluated, but in none of the genomically normal samples. These genomic and microscopic findings support the conclusion that tumor cell contamination rather than genetic field cancerization represents the likeliest cause of local clinical recurrence rates following breast conserving surgery, and mandate caution in assuming the genomic normalcy of histologically benign appearing peritumor breast tissue

Information sciences experiment system

The rapid expansion of remote sensing capability over the last two decades will take another major leap forward with the advent of the Earth Observing System (Eos). An approach is presented that will permit experiments and demonstrations in onboard information extraction. The approach is a non-intrusive, eavesdropping mode in which a small amount of spacecraft real estate is allocated to an onboard computation resource. How such an approach allows the evaluation of advanced technology in the space environment, advanced techniques in information extraction for both Earth science and information science studies, direct to user data products, and real-time response to events, all without affecting other on-board instrumentation is discussed

\u3ci\u3eLevisunguis subaequalis\u3c/i\u3e n. g., n. sp., a Tongue Worm (Pentastomida: Porocephalida: Sebekidae) Infecting Softshell Turtles, \u3ci\u3eApalone\u3c/i\u3e spp. (Testudines: Trionychidae), in the Southeastern United States

A new tongue worm (Pentastomida) belonging to the Sebekidae Sambon, 1922 (Porocephaloidea Sambon, 1922) is described based on exemplars collected from softshell terrapins Apalone spinifera aspera (Agassiz) and Apalone ferox (Schneider) in the southeastern United States; a new genus is erected to accommodate the new species. The new species belongs in the Sebekidae because adults possess four simple hooks arranged in a trapezoid pattern on the ventral surface of the cephalothorax, a mouth opening between the anterior and posterior pairs of hooks, a terminal anus, an elongated uterus with preanal uterine pore, and a Y-shaped seminal vesicle. Nymphs possess geminate hooks, and the new species has an aquatic life cycle in which nymphs become encapsulated in the body cavity of a freshwater fish and mature in the lungs of a terrapin. The new genus is distinct from other genera in the Sebekidae primarily by differences in hook morphology and the fact that representatives use a terrapin as a definitive host. Nymphs infecting fish and presumed to be the new species matured as postlarval juveniles conspecific with the new species when they were fed to the eastern mud turtle, Kinosternon subrubrum (Lacépède). Nymphs of the new species are anatomically similar to but larger than nymphs of Sebekia mississippiensis Overstreet, Self & Vliet, 1985 found in the mesentery of fishes captured in Florida, USA. Adults of the new species differ from those of S. mississippiensis based on hook features, chloride cell pore pattern on annuli, body size, and use of a turtle rather than crocodilian definitive host. The new species is the third North American member of the Sebekidae

Resonanzanalyse und Resonanzidentifikation mittels Eigenmoden

Für die Störaussendung und Störfestigkeit eines elektronischen Systems ist oftmals dessen Resonanzverhalten ausschlaggebend [1]. Es ist bekannt, dass sich Eigenmoden zum Auffinden von Resonanzkreisen eignen [2], [3]. In komplexen Elektroniken (die durch Netzwerke mit zahlreichen funktionalen und parasitären Schaltungselementen beschrieben werden können) ist es jedoch meist sehr aufwändig, den Anteil der verschiedenen Elemente an einer Resonanz zu bestimmen. Die vorgestellte Methodik zeigt, dass sich über eine modale Energie- und Leistungsberechnung der Beitrag dieser Elemente zu Resonanzen und den zugehörigen Gütefaktoren direkt berechnen lässt. In Kombination mit der Stromverteilung der Eigenmoden kann zwischen Elementen unterschieden werden, welche nur den Strom der Resonanz übertragen, und solchen, die ursächlich für die Resonanz sind, bzw. diese bedämpfen. Wird die Energie/Leistung anteilig bzgl. der Gesamtenergie/-leistung angegeben, lässt sich der Einfluss jedes Elements auf die Resonanzfrequenz und den Gütefaktor angeben. Die wesentlich an einer Resonanz beteiligten Elemente lassen sich direkt identifizieren und ermöglichen ein besseres Verständnis und das Entwickeln von Maßnahmen gegen diese Resonanz

Massive star formation: Nurture, not nature

We investigate the physical processes which lead to the formation of massive stars. Using a numerical simulation of the formation of a stellar cluster from a turbulent molecular cloud, we evaluate the relevant contributions of fragmentation and competitive accretion in determining the masses of the more massive stars. We find no correlation between the final mass of a massive star, and the mass of the clump from which it forms. Instead, we find that the bulk of the mass of massive stars comes from subsequent competitive accretion in a clustered environment. In fact, the majority of this mass infalls onto a pre-existing stellar cluster. Furthermore, the mass of the most massive star in a system increases as the system grows in numbers of stars and in total mass. This arises as the infalling gas is accompanied by newly formed stars, resulting in a larger cluster around a more massive star. High-mass stars gain mass as they gain companions, implying a direct causal relationship between the cluster formation process, and the formation of higher-mass stars therein.Comment: 8 pages, accepted for publication in MNRAS. Version including hi-res colour postscript figure available at http://star-www.st-and.ac.uk/~sgv/ps/massnurt.ps.g

Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes.

Background: vitreomacular adhesion can lead to pathologic traction and macular hole. The standard treatment for severe, symptomatic vitreomacular adhesion is vitrectomy. Ocriplasmin is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface. Methods: we conducted two multicenter, randomized, double-blind, phase 3 clinical trials to compare a single intravitreal injection of ocriplasmin (125 μg) with a placebo injection in patients with symptomatic vitreomacular adhesion. The primary end point was resolution of vitreomacular adhesion at day 28. Secondary end points were total posterior vitreous detachment and nonsurgical closure of a macular hole at 28 days, avoidance of vitrectomy, and change in best-corrected visual acuity. Results: overall, 652 eyes were treated: 464 with ocriplasmin and 188 with placebo. Vitreomacular adhesion resolved in 26.5% of ocriplasmin-injected eyes and in 10.1% of placebo-injected eyes (P<0.001). Total posterior vitreous detachment was more prevalent among the eyes treated with ocriplasmin than among those injected with placebo (13.4% vs. 3.7%, P<0.001). Nonsurgical closure of macular holes was achieved in 40.6% of ocriplasmin-injected eyes, as compared with 10.6% of placebo-injected eyes (P<0.001). The best-corrected visual acuity was more likely to improve by a gain of at least three lines on the eye chart with ocriplasmin than with placebo. Ocular adverse events (e.g., vitreous floaters, photopsia, or injection-related eye pain--all self-reported--or conjunctival hemorrhage) occurred in 68.4% of ocriplasmin-injected eyes and in 53.5% of placebo-injected eyes (P<0.001), and the incidence of serious ocular adverse events was similar in the two groups (P=0.26). Conclusions: intravitreal injection of the vitreolytic agent ocriplasmin resolved vitreomacular traction and closed macular holes in significantly more patients than did injection of placebo and was associated with a higher incidence of ocular adverse events, which were mainly transient. (Funded by ThromboGenics; ClinicalTrials.gov numbers, NCT00781859 and NCT00798317.)

Watching individual molecules flex within lipid membranes using SERS.

Interrogating individual molecules within bio-membranes is key to deepening our understanding of biological processes essential for life. Using Raman spectroscopy to map molecular vibrations is ideal to non-destructively 'fingerprint' biomolecules for dynamic information on their molecular structure, composition and conformation. Such tag-free tracking of molecules within lipid bio-membranes can directly connect structure and function. In this paper, stable co-assembly with gold nano-components in a 'nanoparticle-on-mirror' geometry strongly enhances the local optical field and reduces the volume probed to a few nm(3), enabling repeated measurements for many tens of minutes on the same molecules. The intense gap plasmons are assembled around model bio-membranes providing molecular identification of the diffusing lipids. Our experiments clearly evidence measurement of individual lipids flexing through telltale rapid correlated vibrational shifts and intensity fluctuations in the Raman spectrum. These track molecules that undergo bending and conformational changes within the probe volume, through their interactions with the environment. This technique allows for in situ high-speed single-molecule investigations of the molecules embedded within lipid bio-membranes. It thus offers a new way to investigate the hidden dynamics of cell membranes important to a myriad of life processes.We acknowledge financial support from EPSRC grant EP/G060649/1, EP/I012060/1, ERC grant LINASS 320503. FB acknowledges support from the Winton Programme for the Physics of Sustainability.This is the final published version. It's also available from Nature Publishing at http://www.nature.com/srep/2014/140812/srep05940/full/srep05940.html