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1.
J Forensic Leg Med ; 18(7): 295-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21907930

ABSTRACT

As forensic DNA technology has become a common tool in criminal investigations, scientists have attempted to obtain DNA evidence from what were once considered unlikely sources. "Touch DNA" refers to the DNA that is left behind from skin cells when a person touches or comes into contact with an item. This present study shows, DNA profiling of touched evidence materials is reported employing a combination of LCN typing and miniSTRs. The technology is highly valuable for increasing the scope of DNA profiling to large number touched evidence materials.


Subject(s)
DNA Fingerprinting/methods , DNA/analysis , Minisatellite Repeats , Touch , Electrophoresis , Humans , Real-Time Polymerase Chain Reaction , Skin/cytology
2.
J Comput Biol ; 11(6): 1073-89, 2004.
Article in English | MEDLINE | ID: mdl-15662199

ABSTRACT

Molecular profiling studies can generate abundance measurements for thousands of transcripts, proteins, metabolites, or other species in, for example, normal and tumor tissue samples. Treating such measurements as features and the samples as labeled data points, sparse hyperplanes provide a statistical methodology for classifying data points into one of two categories (classification and prediction) and defining a small subset of discriminatory features (relevant feature identification). However, this and other extant classification methods address only implicitly the issue of observed data being a combination of underlying signals and noise. Recently, robust optimization has emerged as a powerful framework for handling uncertain data explicitly. Here, ideas from this field are exploited to develop robust sparse hyperplanes, i.e., classification and relevant feature identification algorithms that are resilient to variation in the data. Specifically, each data point is associated with an explicit data uncertainty model in the form of an ellipsoid parameterized by a center and covariance matrix. The task of learning a robust sparse hyperplane from such data is formulated as a second order cone program (SOCP). Gaussian and distribution-free data uncertainty models are shown to yield SOCPs that are equivalent to the SCOP based on ellipsoidal uncertainty. The real-world utility of robust sparse hyperplanes is demonstrated via retrospective analysis of breast cancer related transcript profiles. Data-dependent heuristics are used to compute the parameters of each ellipsoidal data uncertainty model. The generalization performance of a specific implementation, designated "robust LIKNON," is better than its nominal counterpart. Finally, the strengths and limitations of robust sparse hyperplanes are discussed.


Subject(s)
Computational Biology , Sequence Analysis, DNA/statistics & numerical data , Sequence Analysis, Protein/statistics & numerical data , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Data Interpretation, Statistical , Female , Genes, BRCA1 , Genes, BRCA2 , Humans
3.
Mech Ageing Dev ; 124(1): 109-14, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12618013

ABSTRACT

Transcript profiling can be used to elucidate the molecular and cellular mechanisms involved in ageing and cancer. A recent study of human gastrointestinal stromal tumours (GISTs) with mutations in the KIT gene, Cancer Res. 61 (2001) 8624 exemplifies a common type of investigation. cDNA microarrays were used to generate measurements for 1987 clones in two types of tissues: 13 KIT mutation-positive GISTs and 6 spindle cell tumours from locations outside the gastrointestinal tract. Statistical problems associated with such two-class, high-dimensional profiling data include simultaneous classification and relevant feature identification, probabilistic clustering and protein sequence family modelling. Here, the GIST data were reexamined using specific solutions to these problems, namely sparse hyperplanes, nai;ve Bayes models and profile hidden Markov models respectively. The integrated analysis of molecular profiling and sequence data highlighted 6 clones that may be of clinical and experimental interest. The protein encoded by one of these putative biomarkers defined a novel protein family present in diverse eucarya. The family may be involved in chromosome segregation and/or stability. One family member is a potential biomarker identified recently from a retrospective analysis of transcript profiles for sporadic breast cancer samples from patients with poor and good prognosis, Signal Process. (in press).


Subject(s)
Gene Expression Profiling/statistics & numerical data , Sequence Analysis, Protein/statistics & numerical data , Amino Acid Sequence , Animals , Bayes Theorem , Carcinoma/genetics , Cluster Analysis , Data Interpretation, Statistical , Gastrointestinal Neoplasms/genetics , Humans , Markov Chains , Models, Statistical , Molecular Sequence Data , Mutation , Oligonucleotide Array Sequence Analysis/statistics & numerical data , Proto-Oncogene Proteins c-kit/genetics , Sequence Homology, Amino Acid , Transcription, Genetic
4.
Biochem Biophys Res Commun ; 286(5): 1082-6, 2001 Sep 07.
Article in English | MEDLINE | ID: mdl-11527411

ABSTRACT

Alcohol dehydrogenase (ADH) is the primary enzyme responsible for metabolism of ethanol to acetaldehyde. One class of ADH has been described in fish, and has been found to be structurally similar to mammalian class III ADH (glutathione-dependent formaldehyde dehydrogenase) but functionally similar to class I ADH (primarily responsible for ethanol metabolism). We have cloned a cDNA by RT-PCR from zebrafish (Danio rerio) liver representing the zebrafish ADH3 gene product, with a coding region of 1131 nucleotides. The deduced amino acid sequences share 90% identity to ADH3 from the marine fish Sparus aurata, and 82 and 81% identity to the mouse and human sequences, respectively. Using a quantitative competitive RT-PCR assay, ADH3 mRNA was detected at all timepoints analyzed and was lowest between 8 and 24 h postfertilization. Thus, differential ADH3 expression may be at least partly responsible for temporal variations in the sensitivity of zebrafish embryos to developmental alcohol exposure.


Subject(s)
Alcohol Dehydrogenase/biosynthesis , Alcohol Dehydrogenase/chemistry , Amino Acid Sequence , Animals , Binding, Competitive , Cytosol , DNA, Complementary/metabolism , Embryo, Nonmammalian/metabolism , Glutathione/metabolism , Humans , Kinetics , Larva/metabolism , Liver/metabolism , Molecular Sequence Data , Phylogeny , Protein Isoforms , RNA/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Zebrafish
5.
J Glaucoma ; 9(6): 453-7, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11131751

ABSTRACT

PURPOSE: To determine the effect of cataract surgery on glaucomatous eyes with functioning tube shunts. METHODS: Retrospective analysis of 11 eyes of 11 patients with functioning tube shunts who underwent cataract extraction. RESULTS: The mean follow-up after cataract extraction was 21 +/- 27 months (range, 4-97 months). There was no statistically significant difference between the mean preoperative intraocular pressure and mean postoperative intraocular pressure (17.4 +/- 3.7 mm Hg vs 17.8 +/- 5.9 mmHg; P = 0.85, paired t test). Most patients exhibited a statistically significant rise or drop in pressure, but in none was there a clinically significant change. The mean number of preoperative and postoperative antiglaucoma medications was also not significantly different (1.5 +/- 1.1 vs 1.7 +/- 1.2; P = 0.44, paired t test). Snellen visual acuity improved at least 2 lines in 6 eyes (55%). Complications after cataract extraction included corneal edema in three eyes, one of which had subsequent loss of control of intraocular pressure. CONCLUSIONS: Eyes with a functioning tube shunt undergoing cataract extraction can maintain control of intraocular pressure while achieving visual improvement.


Subject(s)
Cataract Extraction , Glaucoma Drainage Implants , Glaucoma/surgery , Adult , Aged , Cataract/physiopathology , Female , Follow-Up Studies , Glaucoma/physiopathology , Humans , Intraocular Pressure , Lens Implantation, Intraocular , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Visual Acuity
6.
IEEE Trans Neural Netw ; 11(1): 124-36, 2000.
Article in English | MEDLINE | ID: mdl-18249745

ABSTRACT

In this paper we give a new fast iterative algorithm for support vector machine (SVM) classifier design. The basic problem treated is one that does not allow classification violations. The problem is converted to a problem of computing the nearest point between two convex polytopes. The suitability of two classical nearest point algorithms, due to Gilbert, and Mitchell et al., is studied. Ideas from both these algorithms are combined and modified to derive our fast algorithm. For problems which require classification violations to be allowed, the violations are quadratically penalized and an idea due to Cortes and Vapnik and Friess is used to convert it to a problem in which there are no classification violations. Comparative computational evaluation of our algorithm against powerful SVM methods such as Platt's sequential minimal optimization shows that our algorithm is very competitive.

7.
IEEE Trans Neural Netw ; 11(5): 1188-93, 2000.
Article in English | MEDLINE | ID: mdl-18249845

ABSTRACT

This paper points out an important source of inefficiency in Smola and Schölkopf's sequential minimal optimization (SMO) algorithm for support vector machine (SVM) regression that is caused by the use of a single threshold value. Using clues from the KKT conditions for the dual problem, two threshold parameters are employed to derive modifications of SMO for regression. These modified algorithms perform significantly faster than the original SMO on the datasets tried.

8.
J Infect Dis ; 172(3): 785-93, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7544820

ABSTRACT

The integrin CD11b/CD18 promotes leukocyte extravasation during inflammation. Filamentous hemagglutinin (FHA) of Bordetella pertussis binds to CD11b/CD18, raising the possibility that peptides derived from FHA might inhibit leukocyte migration. The Arg-Gly-Asp (RGD) sequence of FHA has been suggested to modulate binding of ligands to CD11b/CD18. Peptides derived from this region inhibited adherence and transendothelial migration of neutrophils in vitro and prevented recruitment of leukocytes into the cerebrospinal fluid in an experimental model of meningitis in rabbits. The mechanism of the antiinflammatory effect may involve modulation of the activity of CD11b/CD18 through peptide interaction with the leukocyte response integrin/integrin-associated protein complex.


Subject(s)
Adhesins, Bacterial/pharmacology , CD18 Antigens/physiology , Cell Adhesion Molecules/biosynthesis , Chemotaxis, Leukocyte/drug effects , Hemagglutinins/pharmacology , Macrophage-1 Antigen/physiology , Neutrophils/physiology , Peptide Fragments/pharmacology , Virulence Factors, Bordetella , Amino Acid Sequence , Animals , Bordetella pertussis/immunology , Cells, Cultured , Dose-Response Relationship, Drug , Endothelium, Vascular , Humans , L-Selectin , Meningitis/blood , Meningitis/cerebrospinal fluid , Meningitis/immunology , Molecular Sequence Data , Neutrophils/drug effects , Oligopeptides , Rabbits , Respiratory Burst , Umbilical Veins
9.
J Clin Invest ; 95(3): 1078-85, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7883955

ABSTRACT

Factor X (factor ten) of the coagulation cascade binds to the integrin CD11b/CD18 during inflammation, initiating procoagulant activity on the surface of leukocytes (Altieri, D.C., O.R. Etingin, D.S. Fair, T.K. Brunk, J.E. Geltosky, D.P. Hajjar, and T. S. Edgington. 1991. Science [Wash.DC]. 254:1200-1202). Filamentous hemagglutinin (FHA), an adhesin of Bordetella pertussis also binds to the CD11b/CD18 integrin (Relman D., E. Tuomanen, S. Falkow, D.T. Golenbock, K. Saukkonen, and S.D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 binding loops of Factor X share amino acid sequence similarity. FHA peptides similar to Factor X binding loops inhibited 125I-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leukocytes in vitro and reduced leukocytosis and blood brain barrier disruption in vivo. Interference with leukocyte migration by a coagulation-based peptide suggests a novel strategy for antiinflammatory therapy.


Subject(s)
Adhesins, Bacterial , Endothelium, Vascular/drug effects , Factor X/pharmacology , Hemagglutinins/pharmacology , Inflammation/metabolism , Leukocytes/drug effects , Peptide Fragments/pharmacology , Virulence Factors, Bordetella , Amino Acid Sequence , Anti-Inflammatory Agents/pharmacology , Blood Coagulation/drug effects , Blood-Brain Barrier/drug effects , Bordetella pertussis , CD18 Antigens/physiology , Cell Adhesion/drug effects , Cell Adhesion Molecules/pharmacology , Cell Communication/drug effects , Chemotaxis, Leukocyte/drug effects , Factor Xa/drug effects , Humans , Macrophage-1 Antigen/physiology , Molecular Mimicry , Molecular Sequence Data , Monocytes/drug effects , Protein Binding/drug effects , Sequence Homology, Amino Acid
10.
Infect Immun ; 61(4): 1538-43, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8454360

ABSTRACT

Streptococcus pneumoniae interacts with vascular endothelial cells during the course of bacteremia. In this study, we characterized the initial attachment of pneumococci to human endothelial cells (EC) and the response of the endothelium to this interaction. Pneumococci adhered to EC in a dose-dependent fashion. Attachment was rapid, with the majority of bacteria attached by 30 min. No difference was found between the attachment of unencapsulated (R6) and encapsulated (SIII) strains. Purified pneumococcal cell wall components competitively inhibited attachment of R6 by a maximum of 60% in a dose-dependent manner. Following attachment of pneumococci or exposure of EC to pneumococcal cell wall, pronounced changes in EC morphology ensued, resulting in striking separation of the cells of the monolayer and, eventually, destruction of the cells. The cytopathic effects of the cell wall were inhibited by antibodies to interleukin-1 but not to tumor necrosis factor. Both antibodies were required to neutralize the cytopathology caused by intact pneumococci. We conclude that pneumococci attach rapidly to human EC and that the cell wall is important in this interaction. Intact pneumococci and pneumococcal cell wall induce profound morphologic changes in human EC, leading to loss of barrier integrity. These cytopathic effects are likely to be cytokine mediated.


Subject(s)
Bacterial Adhesion , Cell Wall/immunology , Endothelium, Vascular/microbiology , Streptococcus pneumoniae/pathogenicity , Actins/metabolism , Cell Survival , Cells, Cultured , Cytokines/physiology , Fluorescent Antibody Technique , Humans , In Vitro Techniques , Microscopy, Electron , Streptococcus pneumoniae/cytology
11.
Infect Immun ; 60(10): 4179-83, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1398928

ABSTRACT

The inflammatory response in infection caused by gram-negative organisms involves induction of procoagulant activity (PCA) on human endothelial cells. Although infections caused by gram-positive organisms are also associated with fibrin formation and thrombosis, the bacterial determinants inducing PCA are unknown. This study shows that intact pneumococci and the pneumococcal cell wall efficiently induce PCA on human endothelial cells. Upon exposure of endothelial cells to pneumococci, PCA was first detectable at 30 min, peaked at 2 h, and disappeared by 6 h. The specific activities of encapsulated and unencapsulated strains for induction of PCA were equivalent. Purified pneumococcal cell walls were as potent as endotoxin in induction of PCA. The ability to induce a procoagulant state on endothelial cells is a new biological activity of gram-positive cell walls which promotes the participation of the coagulation cascade in the inflammatory response to disease caused by gram-positive organisms.


Subject(s)
Blood Coagulation Factors/biosynthesis , Endothelium, Vascular/metabolism , Streptococcus pneumoniae/physiology , Cell Wall/physiology , Cells, Cultured , Humans
12.
Med Sci Law ; 29(3): 249-50, 1989 Jul.
Article in English | MEDLINE | ID: mdl-2770476

ABSTRACT

The possibility of identifying tandem bullets, causing separate entry holes on one or two victims, or found separately at the scene of a crime, is investigated. The phenomenon of tandem bullets has been studied to evaluate the physical evidence. The presence of deep indentations of propellant particles on the exposed lead base cavity, along with patches of striations on the inner periphery of the cavity, have been found to be useful physical evidence to conclude that the bullet had moved in tandem and was a lodged bullet. An outward protrusion of the base acts as corroborative physical evidence that the bullet was the striking bullet.


Subject(s)
Firearms , Forensic Medicine/methods
13.
Phys Rev C Nucl Phys ; 38(1): 558-560, 1988 Jul.
Article in English | MEDLINE | ID: mdl-9954838
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