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Search Results: 1 - 10 of 403428 matches for " Colin M. Stack "
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The Importance of pH in Regulating the Function of the Fasciola hepatica Cathepsin L1 Cysteine Protease
Jonathan Lowther,Mark W. Robinson,Sheila M. Donnelly,Weibo Xu,Colin M. Stack,Jacqueline M. Matthews,John P. Dalton
PLOS Neglected Tropical Diseases , 2009, DOI: 10.1371/journal.pntd.0000369
Abstract: The helminth parasite Fasciola hepatica secretes cathepsin L cysteine proteases to invade its host, migrate through tissues and digest haemoglobin, its main source of amino acids. Here we investigated the importance of pH in regulating the activity and functions of the major cathepsin L protease FheCL1. The slightly acidic pH of the parasite gut facilitates the auto-catalytic activation of FheCL1 from its inactive proFheCL1 zymogen; this process was ~40-fold faster at pH 4.5 than at pH 7.0. Active mature FheCL1 is very stable at acidic and neutral conditions (the enzyme retained ~45% activity when incubated at 37°C and pH 4.5 for 10 days) and displayed a broad pH range for activity peptide substrates and the protein ovalbumin, peaking between pH 5.5 and pH 7.0. This pH profile likely reflects the need for FheCL1 to function both in the parasite gut and in the host tissues. FheCL1, however, could not cleave its natural substrate Hb in the pH range pH 5.5 and pH 7.0; digestion occurred only at pH≤4.5, which coincided with pH-induced dissociation of the Hb tetramer. Our studies indicate that the acidic pH of the parasite relaxes the Hb structure, making it susceptible to proteolysis by FheCL1. This process is enhanced by glutathione (GSH), the main reducing agent contained in red blood cells. Using mass spectrometry, we show that FheCL1 can degrade Hb to small peptides, predominantly of 4–14 residues, but cannot release free amino acids. Therefore, we suggest that Hb degradation is not completed in the gut lumen but that the resulting peptides are absorbed by the gut epithelial cells for further processing by intracellular di- and amino-peptidases to free amino acids that are distributed through the parasite tissue for protein anabolism.
The string tension in the maximally Abelian gauge after smoothing
A. Hart,J. D. Stack,M. Teper
Physics , 1998, DOI: 10.1016/S0920-5632(99)85129-9
Abstract: We apply smoothing to SU(2) lattice field configurations in 3+1 dimensions before fixing to the maximally Abelian gauge. The Abelian projected string tension is shown to be stable under this, whilst the monopole string tension declines by O(30%). Blocking of the SU(2) fields reduces this effect, but the use of extended monopole definitions does not. We discuss these results in the context of additional confining excitations in the U(1) vacuum.
Fluorescence In Situ Hybridization for MicroRNA Detection in Archived Oral Cancer Tissues
Zonggao Shi,Jeffrey J. Johnson,M. Sharon Stack
Journal of Oncology , 2012, DOI: 10.1155/2012/903581
Abstract: The noncoding RNA designated as microRNA (miRNA) is a large group of small single-stranded regulatory RNA and has generated wide-spread interest in human disease studies. To facilitate delineating the role of microRNAs in cancer pathology, we sought to explore the feasibility of detecting microRNA expression in formalin-fixed paraffin-embedded (FFPE) tissues. Using FFPE materials, we have compared fluorescent in situ hybridization (FISH) procedures to detect miR-146a with (a) different synthetic probes: regular custom DNA oligonucleotides versus locked nucleic acid (LNA) incorporated DNA oligonucleotides; (b) different reporters for the probes: biotin versus digoxigenin (DIG); (c) different visualization: traditional versus tyramide signal amplification (TSA) system; (d) different blocking reagents for endogenous peroxidase. Finally, we performed miR-146a FISH on a commercially available oral cancer tissue microarray, which contains 40 cases of oral squamous cell carcinoma (OSCC) and 10 cases of normal epithelia from the human oral cavity. A sample FISH protocol for detecting miR-146a is provided. In summary, we have established reliable in situ hybridization procedures for detecting the expression of microRNA in FFPE oral cancer tissues. This method is an important tool for studies on the involvement of microRNA in oral cancer pathology and may have potential prognostic or diagnostic value. 1. Introduction MicroRNA refers to the category of single-stranded small noncoding RNAs that are approximately 22 nucleotides in length. More than 1500 human microRNA have been identified and registered via various approaches including high throughput screenings (http://www.mirbase.org/). As more than 30% of human of mRNAs are regulated by microRNAs, the functional impact of microRNA in physiology and pathology has yet to be fully elucidated [1]. Generally speaking, microRNA imposes its regulatory role by sequence-specific but incomplete complementary binding to its target mRNA sequences, which are usually located at the 3′ untranslated region [1, 2]. This binding may mediate the degradation of target mRNA or the inhibition of protein translation efficiency of target mRNA. However, due to the loose stringency of this kind of targeting, the exact mechanism of specific microRNA function remains undefined and is an actively addressed research topic. The function and target mRNAs of individual microRNAs cannot be reliably predicted via current bioinformatic approaches, thereby warranting continued experimental interrogation. The investigation of microRNA expression and
On the Phase Diagram of the SU(2) Adjoint Higgs Model in 2+1 Dimensions
A. Hart,O. Philipsen,J. D. Stack,M. Teper
Physics , 1996, DOI: 10.1016/S0370-2693(97)00104-4
Abstract: The phase diagram is investigated for SU(2) lattice gauge theory in d=3, coupled to adjoint scalars. For small values of the quartic scalar coupling, lambda, the transition separating Higgs and confinement phases is found to be first-order, in agreement with earlier work by Nadkarni. The surface of second-order transitions conjectured by Nadkarni, however, is shown instead to correspond to crossover behaviour. This conclusion is based on a finite size analysis of the scalar mass and susceptibility. The nature of the phase transition at the termination of first-order behaviour is investigated and we find evidence for a critical point at which the scalar mass vanishes. The photon mass and confining string tension are measured and are found to be negligibly small in the Higgs phase. This is correlated with the very small density of magnetic monopoles in the Higgs phase. The string tension and photon mass rise rapidly as the crossover is traversed towards the symmetric phase.
Adatom Fe(III) on the hematite surface: Observation of a key reactive surface species
Carrick M Eggleston, Andrew G Stack, Kevin M Rosso, Angela M Bice
Geochemical Transactions , 2004, DOI: 10.1186/1467-4866-5-33
Abstract: Mineral surfaces are the medium upon which the Earth's solids and fluids interact. Their reactivity in the fundamental processes of adsorption, dissolution/growth, and electron transfer is directly tied to their atomic structure.[1] In addition to two-dimensionally periodic surface structures, there are one-dimensional periodic and zero-dimensional structures such as steps and kink sites that play important roles in mineral reactivity. These include adsorbed or adatom sites. There are long-standing models of surface chemistry that appeal to the existence of populations of adatom species having properties distinct from both the solid and aqueous solutes. In crystal growth theories,[2] for example, dissolved nutrient is postulated to pass through the "adsorbed nutrient" state before incorporation into the crystal structure. Despite the theoretical importance of a pool of adsorbed nutrient in mineral dissolution and growth, there is little work confirming its existence or properties on mineral oxides. Surface adatom species (or sites) are difficult to study because of their small size, restriction to surfaces and interfaces, and nonperiodic nature. Indirectly, it has been shown that transient spikes in dissolution rate occur in response to pH changes in a way consistent with the formation and dissolution of adsorbed Fe at the hematite surface, [3-6] and an isotopic exchange and M?ssbauer study by Rea et al[7] concluded that a population of kinetically labile sites characterizes the ferrihydrite surface.Nonperiodic adatom sites at mineral surfaces can behave quite differently from other surface sites, and thus are crucial to understanding the overall chemical reactivity of mineral surfaces. Adatom sites are more sterically accessible than other sites and thus may be more easily complexed by organic molecules that are prone to formation of multidentate surface complexes. There is evidence that organic molecule adsorption can be enhanced by formation of organic-Fe ternary
Processing single-use medical devices for use in surgery – importance, status quo and potential
Krüger, Colin M.
GMS Krankenhaushygiene Interdisziplin?r , 2008,
Abstract: In summary, it is possible with the technology and scientific knowledge currently available to allow products intended for single use to be reprocessed using validated and certified processing procedures, while maintaining the full function and without any loss in quality. How many times a product can be re-processed must be determined separately for each individual medical technology device; it is not possible to make any kind of blanket statement as to the permissible number of cycles. This is due to the differing construction, the various combinations of materials and the diverse demands made of each device during clinical use. The exigency of the reprocessing issue is evident both to the user and the primary manufacturer. For the user, where there is a correspondingly high-quality primary product with suitably costed, technically-sound and certified reprocessing procedures, repeat usage can mean real savings while maintaining full functionality in each use. For the primary manufacturers of highly specialised instruments, only part of which can be represented by the medical facility in terms of a corresponding DRG (Diagnosis-Related Group), it is reprocessing that opens the door to widespread routine clinical use. The patient, in turn, benefits greatly from this, since his demand for medical treatment using the most up-to-date technology is taken into account. If processing complies in full with medical technology and hygiene directives, from the medical point of view (without being able to definitively evaluate each individual case using this criterion) the specific advantages of the reprocessing procedure are obvious. In order to establish broad acceptance for the purposes of good marketing, corresponding controlling and quality instruments have to be developed to allow the decision-making process regarding the permissibility of the reprocessing of a certain device and the number of times it can be reprocessed using this procedure to be made transparent. Taking this a step further, possibilities arise for the establishment of corresponding quality-assurance instruments on the part of the clinical establishments involved, within which reprocessed products, in the interest of quality assurance, can be referred back to the processor in the event of defective function and can also be removed from clinical use prior to completing the intended number of processing cycles. Furthermore, it can be assumed that the widespread use of reprocessing procedures in today’s high-cost single-use medical device sector will have a long-term cost/price-regulating effect
Deterministically driven random walks on a finite state space
Colin M. W. Little
Mathematics , 2013,
Abstract: We introduce the concept of a deterministic walk. Confining our attention to the finite state case, we establish hypotheses that ensure that the deterministic walk is transitive, and show that this property is in some sense robust. We also establish conditions that ensure the existence of asymptotic occupation times.
Deterministically driven random walks in a random environment on Z
Colin M. W. Little
Mathematics , 2013,
Abstract: We introduce the concept of a deterministic walk in a deterministic environment on a countable state space (DWDE). For the deterministic walk in a fixed environment we establish properties analogous to those found in Markov chain theory, but for systems that do not in general have the Markov property. In particular, we establish hypotheses ensuring that a DWDE on $\Z$ is either recurrent or transient. An immediate consequence of this result is that a symmetric DWDE on $\Z$ is recurrent. Moreover, in the transient case, we show that the probability that the DWDE diverges to $+ \infty$ is either 0 or 1. In certain cases we compute the direction of divergence in the transient case.
Development of a model of focal pneumococcal pneumonia in young rats
Malley Richard,Stack Anne M,Husson Robert N,Thompson Claudette M
Journal of Immune Based Therapies and Vaccines , 2004, DOI: 10.1186/1476-8518-2-2
Abstract: Background A recently licensed pneumococcal conjugate vaccine has been shown to be highly effective in the prevention of bacteremia in immunized children but the degree of protection against pneumonia has been difficult to determine. Methods We sought to develop a model of Streptococcus pneumoniae pneumonia in Sprague-Dawley rats. We challenged three-week old Sprague-Dawley pups via intrapulmonary injection of S. pneumoniae serotypes 3 and 6B. Outcomes included bacteremia, mortality as well histologic sections of the lungs. Results Pneumonia was reliably produced in animals receiving either 10 or 100 cfu of type 3 pneumococci, with 30% and 50% mortality respectively. Similarly, with type 6B, the likelihood of pneumonia increased with the inoculum, as did the mortality rate. Prophylactic administration of a preparation of high-titered anticapsular antibody prevented the development of type 3 pneumonia and death. Conclusion We propose that this model may be useful for the evaluation of vaccines for the prevention of pneumococcal pneumonia.
Targeting the EGF Receptor for Ovarian Cancer Therapy
Reema Zeineldin,Carolyn Y. Muller,M. Sharon Stack,Laurie G. Hudson
Journal of Oncology , 2010, DOI: 10.1155/2010/414676
Abstract: Ovarian carcinoma is the leading cause of death from gynecologic malignancy in the US. Factors such as the molecular heterogeneity of ovarian tumors and frequent diagnosis at advanced stages hamper effective disease treatment. There is growing emphasis on the identification and development of targeted therapies to disrupt molecular pathways in cancer. The epidermal growth factor (EGF) receptor is one such protein target with potential utility in the management of ovarian cancer. This paper will discuss contributions of EGF receptor activation to ovarian cancer pathogenesis and the status of EGF receptor inhibitors and EGF receptor targeted therapies in ovarian cancer treatment.
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