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Phage Display: Selecting Straws Instead of a Needle from a Haystack  [PDF]
Miha Vodnik,Urska Zager,Borut Strukelj,Mojca Lunder
Molecules , 2011, DOI: 10.3390/molecules16010790
Abstract: An increasing number of peptides with specific binding affinity to various protein and even non-protein targets are being discovered from phage display libraries. The power of this method lies in its ability to efficiently and rapidly identify ligands with a desired target property from a large population of phage clones displaying diverse surface peptides. However, the search for the needle in the haystack does not always end successfully. False positive results may appear. Thus instead of specific binders phage with no actual affinity toward the target are recovered due to their propagation advantages or binding to other components of the screening system, such as the solid phase, capturing reagents, contaminants in the target sample or blocking agents, rather than the target. Biopanning experiments on different targets performed in our laboratory revealed some previously identified and many new target-unrelated peptide sequences, which have already been frequently described and published, but not yet recognized as target-unrelated. Distinguishing true binders from false positives is an important step toward phage display selections of greater integrity. This article thoroughly reviews and discusses already identified and new target-unrelated peptides and suggests strategies to avoid their isolation.
The diagnosis of colorectal cancer in patients with symptoms: finding a needle in a haystack
Robert H Fletcher
BMC Medicine , 2009, DOI: 10.1186/1741-7015-7-18
Abstract: Patients often see primary care physicians for symptoms that might signal colorectal cancer, raising difficult questions. Which patients should be evaluated? How aggressively should they be worked up? If another cause for the symptom is found, such as hemorrhoids for rectal bleeding, should that set the matter to rest or should a cancer diagnosis still be pursued?Table 1 lists 15 symptoms of colorectal cancer that have been suggested in textbooks and supported by research evidence [1]. Unfortunately, many of these same symptoms, especially constipation and fatigue, are common in patients who do not have colorectal cancer. True, some clinical presentations, such as bowel obstruction or severe abdominal or rectal pain, are sufficiently unusual and dramatic events that they would prompt quick evaluation in any case. However, most symptoms of colorectal cancer are not so compelling. As a result, first-contact physicians are in the familiar position of looking for a needle in a haystack.The stakes are high on either side of the decision. If the diagnosis is missed the patient will undergo unnecessary testing, prolonged uncertainty, and continuing symptoms until the diagnosis is finally made. The clinician will suffer chagrin [2] and in some settings he or she might also worry about malpractice claims. On the other hand, proper evaluation, which involves complete visualization of the large bowel by colonoscopy, is a big undertaking, with the inconvenience of a day off work, the discomfort of bowel cleansing if not the procedure itself, financial costs to the patients or society, and a small risk of perforation, bleeding, or other complications [3].Does diagnostic delay allow colorectal cancer to progress from a local to advanced stage, diminishing the possibility of cure? One might think so but the evidence is mixed and for the most part against this possibility [1,4-6]. The relationship between diagnostic delay and cancer stage or survival is at the very least complex. F
Finding a Needle in the Virus Metagenome Haystack - Micro-Metagenome Analysis Captures a Snapshot of the Diversity of a Bacteriophage Armoire  [PDF]
Jessica Ray, Michael Dondrup, Sejal Modha, Ida Helene Steen, Ruth-Anne Sandaa, Martha Clokie
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034238
Abstract: Viruses are ubiquitous in the oceans and critical components of marine microbial communities, regulating nutrient transfer to higher trophic levels or to the dissolved organic pool through lysis of host cells. Hydrothermal vent systems are oases of biological activity in the deep oceans, for which knowledge of biodiversity and its impact on global ocean biogeochemical cycling is still in its infancy. In order to gain biological insight into viral communities present in hydrothermal vent systems, we developed a method based on deep-sequencing of pulsed field gel electrophoretic bands representing key viral fractions present in seawater within and surrounding a hydrothermal plume derived from Loki's Castle vent field at the Arctic Mid-Ocean Ridge. The reduction in virus community complexity afforded by this novel approach enabled the near-complete reconstruction of a lambda-like phage genome from the virus fraction of the plume. Phylogenetic examination of distinct gene regions in this lambdoid phage genome unveiled diversity at loci encoding superinfection exclusion- and integrase-like proteins. This suggests the importance of fine-tuning lyosgenic conversion as a viral survival strategy, and provides insights into the nature of host-virus and virus-virus interactions, within hydrothermal plumes. By reducing the complexity of the viral community through targeted sequencing of prominent dsDNA viral fractions, this method has selectively mimicked virus dominance approaching that hitherto achieved only through culturing, thus enabling bioinformatic analysis to locate a lambdoid viral “needle" within the greater viral community “haystack". Such targeted analyses have great potential for accelerating the extraction of biological knowledge from diverse and poorly understood environmental viral communities.
Polimorfismos del ADN mitocondrial y mortalidad en la sepsis: Hemos hallado la aguja en el pajar? Polymorphisms of mitochondrial DNA and mortality in sepsis: Have we found the needle in the haystack?  [cached]
J. Garnacho Montero,C. Garnacho Montero
Medicina Intensiva , 2007,
Finding the needle in the haystack  [cached]
Alessandro Guffanti
Genome Biology , 2002, DOI: 10.1186/gb-2002-3-2-reports2008
Abstract: Expression Profiler has strictly functional navigation, so a certain sequence of operations must be followed in a given order: load a set of expression values, calculate the distance matrix, perform clustering, link with an external site, and so on. The first phase in the clustering procedure consists of the data upload. The data must be in a standard tabular format, with columns corresponding to different experiments and rows to different genes. Uploaded data can be selected and then stored in a folder on the server for subsequent use or directly carried on to cluster analysis. The clustering procedures can be based on hierarchical (producing a dendogram with the expression data) or K-means (partitioning the expression data set into k clusters) clustering methods with a wide choice of distance-measurement methods and parameters. Standard options are well-tuned, however, to ensure a good preliminary calculation. The output of hierarchical clustering is a nice GIF image containing the classic red and green graph, as used by Michael Eisen (Lawrence Orlando Berkeley National Laboratories, Berkeley, USA), side by side with the tree. By clicking on the various branches it is possible to jump to the various sub-trees (clusters), and it is also possibile to cut the tree according to a given threshold. When requesting K-means clustering, the output corresponds directly to the clusters.The software is in continuous development and the latest available version at the time of writing was 1 December 2001.EPCLUST (the clustering and analysis part of the Expression Profiler) is very fast, rich in options and produces nice GIF images that can be downloaded and used for presentation. The author gives prompt answers to any question; a mailing list (ep-users) is available for discussions.The lack of an extensive, centralized tutorial sometimes makes it hard to follow all the possible paths and to understand all the possibilities of the software. Some options allow one to make a wrong
Note on Needle in a Haystack  [PDF]
John Robert Burger
Computer Science , 2003,
Abstract: Introduced below is a quantum database method, not only for retrieval but also for creation. It uses a particular structure of true's and false's in a state vector of n qubits, permitting up to 2**2**n words, vastly more than for classical bits. Several copies are produced so that later they can be destructively observed and a word determined with high probability. Grover's algorithm is proposed below to read out, nondestructively the unknown contents of a given stored state vector using only one state vector.
Visualizing the Needle in the Haystack: In Situ Hybridization With Fluorescent Dendrimers
Gerhart Jacquelyn,Baytion Michael,Perlman Jordanna,Neely Christine
Biological Procedures Online , 2004, DOI: 10.1251/bpo84
Abstract: In situ hybridization with 3DNA dendrimers is a novel tool for detecting low levels of mRNA in tissue sections and whole embryos. Fluorescently labeled dendrimers were used to identify cells that express mRNA for the skeletal muscle transcription factor MyoD in the early chick embryo. A small population of MyoD mRNA positive cells was found in the epiblast prior to the initiation of gastrulation, two days earlier than previously detected using enzymatic or radiolabeled probes for mRNA. When isolated from the epiblast and placed in culture, the MyoD mRNA positive cells were able to differentiate into skeletal muscle cells. These results demonstrate that DNA dendrimers are sensitive and precise tools for identifying low levels of mRNA in single cells and tissues.
Primary gastric chorioadenocarcinoma: a needle in a haystack  [cached]
Aditi Shastri,Naval G. Daver,Teresa G. Hayes
Rare Tumors , 2011, DOI: 10.4081/rt.2011.e19
Abstract: Primary gastric chorioadenocarcinoma (PGC) is an exceedingly rare neoplasm which is often misdiagnosed as gastric adenocarcinoma at presentation. A markedly elevated serum beta human chorionic gonadotrophin (Beta HCG) level is a characteristic feature of this tumor. A 44 year old white male presented with generalized abdominal pain and fullness, tarry black stools and weight loss of 3 months duration. Medical work-up including imaging with CT scans revealed the presence of a gastric mass and multiple liver metastases. Tumor markers were significant for a Beta HCG of 23717.5 MIU/ML. Scrotal ultrasound did not show the presence of a testicular mass. Upper GI endoscopy with biopsy was positive for a poorly differentiated adenocarcinoma with Beta HCG staining on immunohistochemistry. The patient was diagnosed with metastatic PGC. He received four cycles of chemotherapy with Bleomycin, Etoposide and Cisplatinum. At the end of the fourth cycle, Beta HCG was 23 MIU/ML. CT scan for restaging, however showed an increase in the size of the metastatic lesions. The patient subsequently became profoundly pancytopenic, developed disseminated intravascular coagulation (DIC) and expired 12 months after initial presentation. PGC genetically and morphologically represents an adenocarcinoma and a choriocarcinoma. The significance of an elevated serum Beta HCG is controversial and it may have a role in evaluating response to treatment and tumor recurrence. Curative resection, appropriate chemotherapy and the absence of metastatic lesions is associated with improved survival. Hence, a high index of suspicion must be maintained to diagnose this tumor correctly at presentation and tailor therapy accordingly.
Needle in a haystack? Finding health information on the Web
Barbara F. Schloman
Online Journal of Issues in Nursing , 1999,
Gravitational Wave Astronomy: Needle in a Haystack  [PDF]
Neil J. Cornish
Physics , 2012, DOI: 10.1098/rsta.2011.0540
Abstract: A world-wide array of highly sensitive interferometers stands poised to usher in a new era in astronomy with the first direct detection of gravitational waves. The data from these instruments will provide a unique perspective on extreme astrophysical phenomena such as neutron stars and black holes, and will allow us to test Einstein's theory of gravity in the strong field, dynamical regime. To fully realize these goals we need to solve some challenging problems in signal processing and inference, such as finding rare and weak signals that are buried in non-stationary and non-Gaussian instrument noise, dealing with high-dimensional model spaces, and locating what are often extremely tight concentrations of posterior mass within the prior volume. Gravitational wave detection using space based detectors and Pulsar Timing Arrays bring with them the additional challenge of having to isolate individual signals that overlap one another in both time and frequency. Promising solutions to these problems will be discussed, along with some of the challenges that remain.
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