497 research outputs found
Mid-infrared frequency comb spanning an octave based on an Er fiber laser and difference-frequency generation
We describe a coherent mid-infrared continuum source with 700 cm-1 usable
bandwidth, readily tuned within 600 - 2500 cm-1 (4 - 17 \mum) and thus covering
much of the infrared "fingerprint" molecular vibration region. It is based on
nonlinear frequency conversion in GaSe using a compact commercial 100-fs-pulsed
Er fiber laser system providing two amplified near-infrared beams, one of them
broadened by a nonlinear optical fiber. The resulting collimated mid-infrared
continuum beam of 1 mW quasi-cw power represents a coherent infrared frequency
comb with zero carrier-envelope phase, containing about 500,000 modes that are
exact multiples of the pulse repetition rate of 40 MHz. The beam's
diffraction-limited performance enables long-distance spectroscopic probing as
well as maximal focusability for classical and ultraresolving near-field
microscopies. Applications are foreseen also in studies of transient chemical
phenomena even at ultrafast pump-probe scale, and in high-resolution gas
spectroscopy for e.g. breath analysis.Comment: 8 pages, 2 figures revised version, added reference
Robust Fuzzy Clustering via Trimming and Constraints
ProducciĂłn CientĂficaA methodology for robust fuzzy clustering is proposed. This
methodology can be widely applied in very different statistical problems given
that it is based on probability likelihoods. Robustness is achieved by trimming
a fixed proportion of âmost outlyingâ observations which are indeed
self-determined by the data set at hand. Constraints on the clustersâ scatters
are also needed to get mathematically well-defined problems and to avoid the
detection of non-interesting spurious clusters. The main lines for computationally
feasible algorithms are provided and some simple guidelines about
how to choose tuning parameters are briefly outlined. The proposed methodology
is illustrated through two applications. The first one is aimed at heterogeneously
clustering under multivariate normal assumptions and the second
one migh be useful in fuzzy clusterwise linear regression problems.Ministerio de EconomĂa, Industria y Competitividad (MTM2014-56235-C2-1-P)Junta de Castilla y LeĂłn (programa de apoyo a proyectos de investigaciĂłn â Ref. VA212U13
High Natality Rates of Endangered Steller Sea Lions in Kenai Fjords, Alaska and Perceptions of Population Status in the Gulf of Alaska
Steller sea lions experienced a dramatic population collapse of more than 80% in the late 1970s through the 1990s across their western range in Alaska. One of several competing hypotheses about the cause holds that reduced female reproductive rates (natality) substantively contributed to the decline and continue to limit recovery in the Gulf of Alaska despite the fact that there have been very few attempts to directly measure natality in this species. We conducted a longitudinal study of natality among individual Steller sea lions (nâ=â151) at a rookery and nearby haulouts in Kenai Fjords, Gulf of Alaska during 2003â2009. Multi-state models were built and tested in Program MARK to estimate survival, resighting, and state transition probabilities dependent on whether or not a female gave birth in the previous year. The models that most closely fit the data suggested that females which gave birth had a higher probability of surviving and giving birth in the following year compared to females that did not give birth, indicating some females are more fit than others. Natality, estimated at 69%, was similar to natality for Steller sea lions in the Gulf of Alaska prior to their decline (67%) and much greater than the published estimate for the 2000s (43%) which was hypothesized from an inferential population dynamic model. Reasons for the disparity are discussed, and could be resolved by additional longitudinal estimates of natality at this and other rookeries over changing ocean climate regimes. Such estimates would provide an appropriate assessment of a key parameter of population dynamics in this endangered species which has heretofore been lacking. Without support for depressed natality as the explanation for a lack of recovery of Steller sea lions in the Gulf of Alaska, alternative hypotheses must be more seriously considered
Inter-rater reliability of three standardized functional tests in patients with low back pain
<p>Abstract</p> <p>Background</p> <p>Of all patients with low back pain, 85% are diagnosed as "non-specific lumbar pain". Lumbar instability has been described as one specific diagnosis which several authors have described as delayed muscular responses, impaired postural control as well as impaired muscular coordination among these patients. This has mostly been measured and evaluated in a laboratory setting. There are few standardized and evaluated functional tests, examining functional muscular coordination which are also applicable in the non-laboratory setting. In ordinary clinical work, tests of functional muscular coordination should be easy to apply. The aim of this present study was to therefore standardize and examine the inter-rater reliability of three functional tests of muscular functional coordination of the lumbar spine in patients with low back pain.</p> <p>Methods</p> <p>Nineteen consecutive individuals, ten men and nine women were included. (Mean age 42 years, SD ± 12 yrs). Two independent examiners assessed three tests: "single limb stance", "sitting on a Bobath ball with one leg lifted" and "unilateral pelvic lift" on the same occasion. The standardization procedure took altered positions of the spine or pelvis and compensatory movements of the free extremities into account. The inter-rater reliability was analyzed by Cohen's kappa coefficient (Îș) and by percentage agreement.</p> <p>Results</p> <p>The inter-rater reliability for the right and the left leg respectively was: for the single limb stance very good (Îș: 0.88â1.0), for sitting on a Bobath ball good (Îș: 0.79) and very good (Îș: 0.88) and for the unilateral pelvic lift: good (Îș: 0.61) and moderate (Îș: 0.47).</p> <p>Conclusion</p> <p>The present study showed good to very good inter-rater reliability for two standardized tests, that is, the single-limb stance and sitting on a Bobath-ball with one leg lifted. Inter-rater reliability for the unilateral pelvic lift test was moderate to good. Validation of the tests in their ability to evaluate lumbar stability is required.</p
Haploinsufficiency for p190B RhoGAP inhibits MMTV-Neu tumor progression
Introduction: Rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. P190B Rho GTPase activating protein (RhoGAP) functions as a major inhibitor of the Rho GTPases. P190B is required for mammary gland morphogenesis, and overexpression of p190B in the mammary gland induces hyperplastic lesions. Hence, we hypothesized that p190B may play a pivotal role in mammary tumorigenesis. Methods: To investigate the effects of loss of p190B function on mammary tumor progression, p190B heterozygous mice were crossed with an MMTV-Neu breast cancer model. Effects of p190B deficiency on tumor latency, multiplicity, growth, preneoplastic progression and metastasis were evaluated. To investigate potential differences in tumor angiogenesis between the two groups, immunohistochemistry to detect von Willebrand factor was performed and quantified. To examine gene expression of potential mediators of the angiogenic switch, an angiogenesis PCR array was utilized and results were confirmed using immunohistochemistry. Finally, reciprocal transplantation of tumor fragments was performed to determine the impact of stromal deficiency of p190B on tumor angiogenesis. Results: P190B deficiency reduced tumor penetrance (53% of mice vs. 100% of mice formed tumors) and markedly delayed tumor onset by an average of 46 weeks. Tumor multiplicity was also decreased, but an increase in the number of preneoplastic lesions was detected indicating that p190B deficiency inhibited preneoplastic progression. Angiogenesis was decreased in the p190B heterozygous tumors, and expression of a potent angiogenic inhibitor, thrombospondin-1, was elevated in mammary glands. Transplantation of tumor fragments into wild-type recipients restored tumor angiogenesis. Strikingly, tumor fragments were unable to grow when transplanted into recipients. Conclusions: These data suggest that p190B haploinsufficiency in the epithelium inhibits MMTV-Neu tumor initiation. Furthermore, p190B deficiency in the vasculature is responsible, in part, for the inhibition of MMTV-Neu tumor progression
Designing sequential transcription logic: a simple genetic circuit for conditional memory
The ability to learn and respond to recurrent events depends on the capacity
to remember transient biological signals received in the past. Moreover, it may
be desirable to remember or ignore these transient signals conditioned upon
other signals that are active at specific points in time or in unique
environments. Here, we propose a simple genetic circuit in bacteria that is
capable of conditionally memorizing a signal in the form of a transcription
factor concentration. The circuit behaves similarly to a "data latch" in an
electronic circuit, i.e. it reads and stores an input signal only when
conditioned to do so by a "read command". Our circuit is of the same size as
the well-known genetic toggle switch (an unconditional latch) which consists of
two mutually repressing genes, but is complemented with a "regulatory front
end" involving protein heterodimerization as a simple way to implement
conditional control. Deterministic and stochastic analysis of the circuit
dynamics indicate that an experimental implementation is feasible based on
well-characterized genes and proteins. It is not known, to which extent
molecular networks are able to conditionally store information in natural
contexts for bacteria. However, our results suggest that such sequential logic
elements may be readily implemented by cells through the combination of
existing protein-protein interactions and simple transcriptional regulation.Comment: 20 pages, 5 figures; supplementary material available upon request
from the author
Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance
The alarming growth of the antibiotic-resistant superbugs
methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
Enterococcus (VRE) is driving the development of new technologies to
investigate antibiotics and their modes of action. We report the label-free
detection of vancomycin binding to bacterial cell wall precursor analogues
(mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically
relevant concentrations in blood serum. Differential measurements quantified
binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide
analogues. Moreover, by systematically modifying the mucopeptide density we
gain new insights into the origin of surface stress. We propose that stress is
a product of a local chemical binding factor and a geometrical factor
describing the mechanical connectivity of regions affected by local binding in
terms of a percolation process. Our findings place BioMEMS devices in a new
class of percolative systems. The percolation concept will underpin the design
of devices and coatings to significantly lower the drug detection limit and may
also impact on our understanding of antibiotic drug action in bacteria.Comment: Comments: This paper consists of the main article (6 pages, 5
figures) plus Supplemental Material (6 pages, 3 figures). More details are
available at http://www.london-nano.co
Prevalence of non Helicobacter pylori species in patients presenting with dyspepsia
<p>Abstract</p> <p>Background</p> <p>Helicobacter species associated with human infection include <it>Helicobacter pylori, Helicobacter heilmannii </it>and <it>Helicobacter felis </it>among others. In this study we determined the prevalence of <it>H. pylori </it>and non-<it>Helicobacter pylori </it>organisms <it>H. felis and H. heilmannii </it>and analyzed the association between coinfection with these organisms and gastric pathology in patients presenting with dyspepsia. Biopsy specimens were obtained from patients with dyspepsia on esophagogastroduodenoscopy (EGD) for rapid urease test, histology and PCR examination for Helicobacter genus specific 16S rDNA, <it>H. pylori </it>phosphoglucosamine mutase (<it>glmM</it>) and urease B (<it>ureB</it>) gene of <it>H. heilmannii </it>and <it>H. felis</it>. Sequencing of PCR products of <it>H. heilmannii </it>and <it>H. felis </it>was done.</p> <p>Results</p> <p>Two hundred-fifty patients with dyspepsia were enrolled in the study. The mean age was 39 ± 12 years with males 162(65%). Twenty-six percent (66 out of 250) were exposed to cats or dogs. PCR for Helicobacter genus specific 16S rDNA was positive in 167/250 (67%), <it>H. pylori glmM </it>in 142/250 (57%), <it>H. heilmannii </it>in 17/250 (6%) and <it>H. felis </it>in 10/250 (4%), respectively. All the <it>H. heilmannii </it>and <it>H. felis </it>PCR positive patients were also positive for <it>H. pylori </it>PCR amplification. The occurrence of coinfection of <it>H. pylori </it>and <it>H. heilmannii </it>was 17(6%) and with <it>H. felis </it>was 10(4%), respectively. Only one out of 66 exposed to pets were positive for <it>H. heilmannii </it>and two for <it>H. felis</it>. Histopathology was carried out in 160(64%) of 250 cases. Chronic active inflammation was observed in 53(56%) (p = 0.001) of the patients with <it>H. pylori </it>infection alone as compared to 3(37%) (p = 0.73) coinfected with <it>H. heilmannii </it>and <it>H. pylori </it>and 3(60%) coinfected with <it>H. felis </it>and <it>H. pylori </it>(p = 0.66). Intestinal metaplasia was observed in 3(3%)(p = 1.0) of the patients with <it>H. pylori </it>infection alone as compared to 2(25%) (p = 0.02) coinfected with <it>H. heilmannii </it>and <it>H. pylori </it>and 1(20%) coinfected with <it>H. felis </it>and <it>H. pylori </it>(p = 0.15).</p> <p>Conclusion</p> <p>The prevalence of <it>H. heilmannii </it>and <it>H. felis </it>was low in our patients with dyspepsia. Exposure to pets did not increase the risk of <it>H. heilmannii </it>or <it>H. felis </it>infection. The coinfection of <it>H. pylori </it>with <it>H. heilmannii </it>was seen associated with intestinal metaplasia, however this need further confirmation.</p
Short term culture of breast cancer tissues to study the activity of the anticancer drug taxol in an intact tumor environment
BACKGROUND: Sensitivity of breast tumors to anticancer drugs depends upon dynamic interactions between epithelial tumor cells and their microenvironment including stromal cells and extracellular matrix. To study drug-sensitivity within different compartments of an individual tumor ex vivo, culture models directly established from fresh tumor tissues are absolutely essential. METHODS: We prepared 0.2 mm thick tissue slices from freshly excised tumor samples and cultivated them individually in the presence or absence of taxol for 4 days. To visualize viability, cell death, and expression of surface molecules in different compartments of non-fixed primary breast cancer tissues we established a method based on confocal imaging using mitochondria- and DNA-selective dyes and fluorescent-conjugated antibodies. Proliferation and apoptosis was assessed by immunohistochemistry in sections from paraffin-embedded slices. Overall viability was also analyzed in homogenized tissue slices by a combined ATP/DNA quantification assay. RESULTS: We obtained a mean of 49 tissue slices from 22 breast cancer specimens allowing a wide range of experiments in each individual tumor. In our culture system, cells remained viable and proliferated for at least 4 days within their tissue environment. Viability of tissue slices decreased significantly in the presence of taxol in a dose-dependent manner. A three-color fluorescence viability assay enabled a rapid and authentic estimation of cell viability in the different tumor compartments within non-fixed tissue slices. CONCLUSION: We describe a tissue culture method combined with a novel read out system for both tissue cultivation and rapid assessment of drug efficacy together with the simultaneous identification of different cell types within non-fixed breast cancer tissues. This method has potential significance for studying tumor responses to anticancer drugs in the complex environment of a primary cancer tissue
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