Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Tuberculosis of pancreas and peripancreatic lymph nodes in immunocompetent patients: Experience from China

Aim: To determine the clinical, radiographic and laboratory characteristics, diagnostic methods, and therapeutic variables in immunocompetent patients with tuberculosis (TB) of the pancreas and peripancreatic lymph nodes. Methods: The records of 16 patients (6 male, 10 female; mean age 37 years, range 18-56years) with tuberculosis of the pancreas and peripancreatic lymph nodes from 1983 to 2001 in the Southwest Hospital were analyzed retrospectively. In addition, 58 similar cases published in Chinese literature were reviewed and summarized. We reviewed the clinical, radiographic and laboratory findings, diagnostic methods, therapeutic approaches, and outcome in the patients. Criteria for the diagnosis of pancreatic tuberculosis were the presence of granuloma in histological sections or the presence of Mycobacterium tuberculosis DNA by polymerase chain reaction (PCR). Results: Predominant symptoms consisted of abdominal nodule and pain (75 %), anorexia/weight loss (69 %), malaise/weakness (64 %), fever and night sweats (50 %), back pain (38 %) and jaundice (31 %). Swelling of the head of the pancreas with heterogeneous attenuation echo was detected with ultrasound in 75 % (12/16). CT scan showed pancreatic mass with heterogeneous hypodensity focus in all patients, with calcification in 56 % (9/16) patients, and peripancreatic nodules in 38 % (6/16) patients. Anemia and lymphocytopenia were seen in 50 % (8/16) patients, and pancytopenia occurred in 13 % (2/ 16) patients. Hypertransaminasemia, elevated alkaline phosphatase (AP) and GGT were seen in 56 % (9/16) patients. The erythrocyte sedimentation rate (ESR) was elevated in 69 % (11/16) cases. Granulomas were found in 75 % (12/16) cases, and in 38 % (6/16) cases caseous necrosis tissue was found. Laparotomy was performed in 75 % (12/16) cases, and ultrasound-guided fine needle aspiration (FNA) was done in 63 % (10 of 16). The most commonly used combinations of medications were isoniazid/rifampin/streptomycin (63 %, n=10) and isoniazid/rifampin pyrazinamide/streptomycin or ethambutol (38 %, n=6). The duration of treatment lasted for half or one year and treatment was successful in all cases. The characteristics of 58 cases from Chinese literature were also summarized. Conclusion: Tuberculosis of the pancreas and peripancreatic lymph nodes should be considered as a diagnostic possibility in patients presenting with a pancreatic mass, and diagnosis without laparotomy is possible if only doctors are aware of its clinical features and investigate it with appropriate modalities. Pancreatic tuberculosis can be effectively cured by antituberculous drugs.published_or_final_versio

Compact Drawings of 1-Planar Graphs with Right-Angle Crossings and Few Bends

We study the following classes of beyond-planar graphs: 1-planar, IC-planar, and NIC-planar graphs. These are the graphs that admit a 1-planar, IC-planar, and NIC-planar drawing, respectively. A drawing of a graph is 1-planar if every edge is crossed at most once. A 1-planar drawing is IC-planar if no two pairs of crossing edges share a vertex. A 1-planar drawing is NIC-planar if no two pairs of crossing edges share two vertices. We study the relations of these beyond-planar graph classes (beyond-planar graphs is a collective term for the primary attempts to generalize the planar graphs) to right-angle crossing (RAC) graphs that admit compact drawings on the grid with few bends. We present four drawing algorithms that preserve the given embeddings. First, we show that every $n$-vertex NIC-planar graph admits a NIC-planar RAC drawing with at most one bend per edge on a grid of size $O(n) \times O(n)$. Then, we show that every $n$-vertex 1-planar graph admits a 1-planar RAC drawing with at most two bends per edge on a grid of size $O(n^3) \times O(n^3)$. Finally, we make two known algorithms embedding-preserving; for drawing 1-planar RAC graphs with at most one bend per edge and for drawing IC-planar RAC graphs straight-line

Inner retinal inhibition shapes the receptive field of retinal ganglion cells in primate

The centre-surround organisation of receptive fields is a feature of most retinal ganglion cells (RGCs) and is critical for spatial discrimination and contrast detection. Although lateral inhibitory processes are known to be important in generating the receptive field surround, the contribution of each of the two synaptic layers in the primate retina remains unclear. Here we studied the spatial organisation of excitatory and inhibitory synaptic inputs onto ON and OFF ganglion cells in the primate retina. All RGCs showed an increase in excitation in response to stimulus of preferred polarity. Inhibition onto RGCs comprised two types of responses to preferred polarity: some RGCs showed an increase in inhibition whilst others showed removal of tonic inhibition. Excitatory inputs were strongly spatially tuned but inhibitory inputs showed more variable organisation: in some neurons they were as strongly tuned as excitation, and in others inhibitory inputs showed no spatial tuning. We targeted one source of inner retinal inhibition by functionally ablating spiking amacrine cells with bath application of tetrodotoxin (TTX). TTX significantly reduced the spatial tuning of excitatory inputs. In addition, TTX reduced inhibition onto those RGCs where a stimulus of preferred polarity increased inhibition. Reconstruction of the spatial tuning properties by somatic injection of excitatory and inhibitory synaptic conductances verified that TTX-mediated inhibition onto bipolar cells increases the strength of the surround in RGC spiking output. These results indicate that in the primate retina inhibitory mechanisms in the inner plexiform layer sharpen the spatial tuning of ganglion cells. © 2013 The Physiological Society

The role of cardiac troponin T quantity and function in cardiac development and dilated cardiomyopathy

Background: Hypertrophic (HCM) and dilated (DCM) cardiomyopathies results from sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT function or quantity; whether the severity of DCM is related to the ratio of mutant to wildtype cTnT; whether Ca2+ desensitization occurs in DCM; and whether absence of cTnT impairs early embryonic cardiogenesis. Methods and Findings: We ablated Tnnt2 to produce heterozygous Tnnt2+/ mice, and crossbreeding produced homozygous null Tnnt2-/-embryos. We also generated transgenic mice overexpressing wildtype (TGWT) or DCM mutant (TGK210Δ) Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying wildtype (Tnnt2+/-/TGWT) or mutant (Tnnt2+/-/TGK210Δ) transgenes. Tnnt2+/-mice relative to wildtype had significantly reduced transcript (0.82 ± 0.06 [SD] vs. 1.00 ± 0.12 arbitrary units; p = 0.025), but not protein (1.01 ± 0.20 vs. 1.00 ± 0.13 arbitrary units; p = 0.44). Tnnt2+/-mice had normal hearts (histology, mass, left ventricular end diastolic diameter [LVEDD], fractional shortening [FS]). Moreover, whereas Tnnt2+/-/ TGK210Δ mice had severe DCM, TGK210Δ mice had only mild DCM (FS 18 ± 4 vs. 29 ± 7%; p < 0.01). The difference in severity of DCM may be attributable to a greater ratio of mutant to wildtype Tnnt2 transcript in Tnnt2+/-/TGK210Δ relative to TGK210Δ mice (2.42±0.08, p = 0.03). Tnnt2+/-/TGK210Δ muscle showed Ca2+ desensitization (pCa50 = 5.34 ± 0.08 vs. 5.58 ± 0.03 at sarcomere length 1.9 μm. p<0.01), but no difference in maximum force generation. Day 9.5 Tnnt2-/-embryos had normally looped hearts, but thin ventricular walls, large pericardial effusions, noncontractile hearts, and severely disorganized sarcomeres. Conclusions: Absence of one Tnnt2 allele leads to a mild deficit in transcript but not protein, leading to a normal cardiac phenotype. DCM results from abnormal function of a mutant protein, which is associated with myocyte Ca2+ desensitization. The severity of DCM depends on the ratio of mutant to wildtype Tnnt2 transcript. cTnT is essential for sarcomere formation, but normal embryonic heart looping occurs without contractile activity. © 2008 Ahmad et al

Aspects of structural health and condition monitoring of offshore wind turbines

Wind power has expanded significantly over the past years, although reliability of wind turbine systems, especially of offshore wind turbines, has been many times unsatisfactory in the past. Wind turbine failures are equivalent to crucial financial losses. Therefore, creating and applying strategies that improve the reliability of their components is important for a successful implementation of such systems. Structural health monitoring (SHM) addresses these problems through the monitoring of parameters indicative of the state of the structure examined. Condition monitoring (CM), on the other hand, can be seen as a specialized area of the SHM community that aims at damage detection of, particularly, rotating machinery. The paper is divided into two parts: in the first part, advanced signal processing and machine learning methods are discussed for SHM and CM on wind turbine gearbox and blade damage detection examples. In the second part, an initial exploration of supervisor control and data acquisition systems data of an offshore wind farm is presented, and data-driven approaches are proposed for detecting abnormal behaviour of wind turbines. It is shown that the advanced signal processing methods discussed are effective and that it is important to adopt these SHM strategies in the wind energy sector

Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure

Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.published_or_final_versio

Super-resolution far-field ghost imaging via compressive sampling

Much more image details can be resolved by improving the system's imaging resolution and enhancing the resolution beyond the system's Rayleigh diffraction limit is generally called super-resolution. By combining the sparse prior property of images with the ghost imaging method, we demonstrated experimentally that super-resolution imaging can be nonlocally achieved in the far field even without looking at the object. Physical explanation of super-resolution ghost imaging via compressive sampling and its potential applications are also discussed.Comment: 4pages,4figure

Visual Similarity Perception of Directed Acyclic Graphs: A Study on Influencing Factors

While visual comparison of directed acyclic graphs (DAGs) is commonly encountered in various disciplines (e.g., finance, biology), knowledge about humans' perception of graph similarity is currently quite limited. By graph similarity perception we mean how humans perceive commonalities and differences in graphs and herewith come to a similarity judgment. As a step toward filling this gap the study reported in this paper strives to identify factors which influence the similarity perception of DAGs. In particular, we conducted a card-sorting study employing a qualitative and quantitative analysis approach to identify 1) groups of DAGs that are perceived as similar by the participants and 2) the reasons behind their choice of groups. Our results suggest that similarity is mainly influenced by the number of levels, the number of nodes on a level, and the overall shape of the graph.Comment: Graph Drawing 2017 - arXiv Version; Keywords: Graphs, Perception, Similarity, Comparison, Visualizatio

One-loop SYM-supergravity relation for five-point amplitudes

We derive a linear relation between the one-loop five-point amplitude of N=8 supergravity and the one-loop five-point subleading-color amplitudes of N=4 supersymmetric Yang-Mills theory.Comment: 17 pages, 2 figures; v2: very minor correction