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Search Results: 1 - 10 of 100578 matches for " Mark W. Geraci "
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Genomic approaches to research in pulmonary hypertension
Mark W Geraci, Bifeng Gao, Yasushi Hoshikawa, Michael E Yeager, Rubin M Tuder, Norbert F Voelkel
Respiratory Research , 2001, DOI: 10.1186/rr59
Abstract: Pulmonary hypertension (PH) refers to a spectrum of diseases where the pulmonary artery pressure is elevated. A new classification of PH has recently been proposed [1]. No cause can be elucidated in primary (or sporadic, idiopathic) pulmonary hypertension (PPH). Secondary forms of PH can occur in association with congenital heart disease, thromboembolic disease, HIV, anorexigen usage, and a variety of connective tissue disorders. Familial primary pulmonary hypertension (FPPH) has been associated with heterozygous germline mutations in the bone morphogenetic protein type II receptor gene (BMPR2) [2,3]. While this recent discovery has generated extreme interest, the pathobiology of severe PH remains enigmatic. Recent genomic approaches to investigate PH are reviewed. Early studies investigated the alterations of vasoactive and growth factor related genes. Animal models, using either pharmaceutical approaches, transgenics, or targeted disruption of genes, have allowed for whole animal modeling of specific pathways in the development of PH. Progress in medical genetic investigations has lead to the discovery of a gene (BMPR2) associated with FPPH. Finally, microarray expression analysis has been utilized to investigate animal models, and has shown to be a useful tool providing novel information and better characterization of the molecular pathobiology of distinct clinical phenotypes of PH.Most investigations of the role of specific genes in the pathobiology of PH have focused either on the balance of vasoconstriction and vasodilation or on specific growth factors, inflammatory mediators, or ion channels. Another approach has been to compartmentalize the vasculature, and focus the investigations on the endothelium, smooth muscle cells, and the adventitia/extracellular matrix. Christman et al initially reported an imbalance of prostacyclin (PGI2) and thromboxane metabolites in the urine of patients with both primary and secondary forms of PH, with more vasoconstrictor thr
Platelet Gene Expression as a Biomarker Risk Stratification Tool in Acute Myocardial Infarction: A Pilot Investigation
David C. Calverley, Ivan P. Casserly, Qamrul G. Choudhury, Tzu L. Phang, Bifeng Gao, John C. Messenger and Mark W. Geraci
Clinical Medicine Insights: Blood Disorders , 2012, DOI: 10.4137/CMBD.S5005
Abstract: Platelets play a major role in the pathophysiology of acute myocardial infarction (AMI). Recent evidence reveals megakaryocyte-derived platelet pre-mRNA is spliced to mRNA and then translated into functional proteins in response to external stimulation. An exon microarray analyzes pre-mRNA alternative splicing and is thus applicable for studying gene expression in the anucleate platelet. We hypothesized a subset of megakaryocyte/platelet genes exists that are significantly over or underexpressed in AMI compared with stable coronary artery disease (CAD), yielding a gene expression profile for further study. Microarray analysis employing platelet mRNA was used to generate gene expression data in the above two patient groups. Unsupervised hierarchical clustering has revealed an expression profile that includes 95 over- or under-expressed genes depicted in a heat map where separation of both sets takes place. This preliminary study reveals a platelet-based gene expression signature that differentiates between AMI and stable CAD, and further study may yield a prognostic tool for a future AMI event in atherosclerosis risk factor-based subsets of CAD patients.
MODMatcher: Multi-Omics Data Matcher for Integrative Genomic Analysis
Seungyeul Yoo,Tao Huang,Joshua D. Campbell,Eunjee Lee,Zhidong Tu,Mark W. Geraci,Charles A. Powell,Eric E. Schadt,Avrum Spira,Jun Zhu
PLOS Computational Biology , 2014, DOI: doi/10.1371/journal.pcbi.1003790
Abstract: Errors in sample annotation or labeling often occur in large-scale genetic or genomic studies and are difficult to avoid completely during data generation and management. For integrative genomic studies, it is critical to identify and correct these errors. Different types of genetic and genomic data are inter-connected by cis-regulations. On that basis, we developed a computational approach, Multi-Omics Data Matcher (MODMatcher), to identify and correct sample labeling errors in multiple types of molecular data, which can be used in further integrative analysis. Our results indicate that inspection of sample annotation and labeling error is an indispensable data quality assurance step. Applied to a large lung genomic study, MODMatcher increased statistically significant genetic associations and genomic correlations by more than two-fold. In a simulation study, MODMatcher provided more robust results by using three types of omics data than two types of omics data. We further demonstrate that MODMatcher can be broadly applied to large genomic data sets containing multiple types of omics data, such as The Cancer Genome Atlas (TCGA) data sets.
Frequency and Energy Difference Detection of Dolphin Biosonar Signals Using a Decomposition Algorithm  [PDF]
Mark W. Muller
Open Journal of Acoustics (OJA) , 2016, DOI: 10.4236/oja.2016.61001
Abstract: A set of dolphin echolocation signals previously collected from an Atlantic bottlenose dolphin in Kaneohe Bay, Hawai’i are decomposed using a matching pursuit algorithm to further investigate the role of four types of echolocation signals outlined elsewhere [1]. The method decomposes the echolocation signals into optimal linear expansions of waveforms, which are Gabor functions defined in a dictionary. The method allows for study of the changes in frequency content within a dolphin’s functional bandwidth during discrimination tasks. We investigate the role of the functional bandwidth in terms of the signal energy levels and echolocations task performance. Furthermore, ROC analysis is applied to the relative energies of the matched waveforms to determine probability of discrimination. The results suggest that dolphins may discriminate by inspection of the relevant frequency differences between targets. In addition, the results from the ROC analysis provides insight into the role of the different classes of dolphin signals and of the importance of modification of the outgoing echolocation clicks, which may be fundamental to a dolphin’s ability to identify and discriminate targets.
Resolution of Amenorrhea and Chronic Constipation in an Adult Patient with Idiopathic Scoliosis Wearing a Scoliosis Activity Suit for 6 Months: A Case Report  [PDF]
Mark W. Morningstar
Open Journal of Therapy and Rehabilitation (OJTR) , 2018, DOI: 10.4236/ojtr.2018.62007
Abstract: Objective: To report the symptomatic and radiographic changes in an adult scoliosis patient with a history of amenorrhea and chronic constipation. Clinical Features: Patient presented for treatment with an 8-year history of amenorrhea and chronic constipation. Radiographic study showed a right thoracic/left lumbar double major scoliosis. Intervention and Outcome: Patient was fitted for a scoliosis activity suit and given instructions for continued home use, building up to 3 - 4 hours total daily. After 6 months of use, her amenorrhea and chronic constipation had resolved, and both scoliosis Cobb angles also improved. Scores on before and after SRS-22r questionnaires, as well as a quadruple numerical pain rating scale, also improved. Conclusion: A patient wearing a scoliosis activity suit for 6 months reported symptomatic changes as well as radiographic, pain, and quality of life improvements. The results of this case cannot be generalized. More investigation into the association of scoliosis and other organic symptoms is warranted.
Iron Overdose during Pregnancy: Case and Treatment Review  [PDF]
Matthew J. Geraci, Haesuk Heagney
International Journal of Clinical Medicine (IJCM) , 2012, DOI: 10.4236/ijcm.2012.37A126

A 22-year-old pregnant female was transferred to the emergency department having ingested a bottle of iron-containing prenatal vitamins, ondansetron (Zofran?) tablets and alcohol. The patient was hemodynamically stable but suffered from intense bouts of brown, sandy emesis for the first few hours. Investigation revealed the patient ingested 13.57 mg/kg of elemental iron. Due to the initial iron level, history and presentation time whole bowel irrigation was initiated with polyethylene glycol solution. Acute iron toxicity in pregnancy is a medical emergency that can result in multisystem organ failure leading to maternal death and potential fetal demise. High maternal serum iron loads do not affect the developing fetus and are not associated with fetal malformations; however advanced poisoning can lead to maternal death, spontaneous abortions or preterm emergency deliveries. Initial treatment strategies may include whole bowel irrigation using polyethylene glycol electrolyte lavage solution and deferoxamine treatment along with necessary supportive care management. Despite concerns of teratogenicity deferoxamine does not cross the placenta and is regarded as safe for use during pregnancy. Maternal resuscitation must always be the primary objective in acute iron overdoses and, therefore such concern should not delay clinically indicated maternal treatment.

Testing Atom and Neutron Neutrality with Atom Interferometry
Arvanitaki, Asimina;Dimopoulos, Savas;Geraci, Andrew A.;Hogan, Jason;Kasevich, Mark
High Energy Physics - Phenomenology , 2007, DOI: 10.1103/PhysRevLett.100.120407
Abstract: We propose an atom-interferometry experiment based on the scalar Aharonov-Bohm effect which detects an atom charge at the 10^{-28}e level, and improves the current laboratory limits by 8 orders of magnitude. This setup independently probes neutron charges down to 10^{-28}e, 7 orders of magnitude below current bounds.
Testing Atom and Neutron Neutrality with Atom Interferometry
Asimina Arvanitaki,Savas Dimopoulos,Andrew A. Geraci,Jason Hogan,Mark Kasevich
Physics , 2007, DOI: 10.1103/PhysRevLett.100.120407
Abstract: We propose an atom-interferometry experiment based on the scalar Aharonov-Bohm effect which detects an atom charge at the 10^{-28}e level, and improves the current laboratory limits by 8 orders of magnitude. This setup independently probes neutron charges down to 10^{-28}e, 7 orders of magnitude below current bounds.
Attonewton force detection using microspheres in a dual-beam optical trap in high vacuum
Gambhir Ranjit,David P. Atherton,Jordan H. Stutz,Mark Cunningham,Andrew A. Geraci
Physics , 2015, DOI: 10.1103/PhysRevA.91.051805
Abstract: We describe the implementation of laser-cooled silica microspheres as force sensors in a dual-beam optical dipole trap in high vacuum. Using this system we have demonstrated trap lifetimes exceeding several days, attonewton force detection capability, and wide tunability in trapping and cooling parameters. Measurements have been performed with charged and neutral beads to calibrate the sensitivity of the detector. This work establishes the suitability of dual beam optical dipole traps for precision force measurement in high vacuum with long averaging times, and enables future applications including the study of gravitational inverse square law violations at short range, Casimir forces, acceleration sensing, and quantum opto-mechanics.
Cyclosporine and Hepatitis C  [PDF]
Ryan Caballes, Mark W. Russo
Open Journal of Organ Transplant Surgery (OJOTS) , 2012, DOI: 10.4236/ojots.2012.24009
Abstract: End stage liver disease from hepatitis C is a leading indication for liver transplantation. Recurrent hepatitis C after liver transplant may lead to cirrhosis and graft failure in up to 25% of recipients five years after liver transplantation. Anti-viral therapy is challenging after liver transplantation due to increased side effects including cytopenias and decreased efficacy compared to the nontransplant population. Tacrolimus and cyclosporine are the most common immunosuppressants used to prevent graft rejection. Tacrolimus is more potent than cyclosporine and may be preferred to cyclosporine. However, cyclosporine may have activity against hepatitis C and may have a theoretical advantage to tacrolimus in hepatitis liver transplant recipients. Cyclosporine may inhibit NS5B and NS5A protein complexes and increase endogenous interferon activity. Cyclophilin inhibitors without immunosuppressive properties are under development and represent a novel mechanisms for inhibiting HCV replication.
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