Optical Gain from InAs Nanocrystal Quantum Dots in a Polymer Matrix

We report on the first observation of optical gain from InAs nanocrystal quantum dots emitting at 1.55 microns based on a three-beam, time resolved pump-probe technique. The nanocrystals were embedded into a transparent polymer matrix platform suitable for the fabrication of integrated photonic devices.Comment: 8 pages, 3 figures. This second version is excactly the same as the first. It is resubmitted to correct some format errors appeared in the pdf file of the first versio

A Sensitive High Performance Liquid Chromatography (HPLC) Assay for the Quantification of Doxorubicin Bound to DNA

Doxorubicin, a widely used anticancer agent, exhibits antitumor activity against a wide variety of malignancies. The drug exerts its cytotoxic effects by binding to and intercalating within the DNA of tumor and tissue cells. However, current assays are unable to accurately determine the concentration of intracellular active form of doxorubicin. Thus, we have developed a high performance liquid chromatography (HPLC) methodology in order to quantify the concentrations of doxorubicin that are bound to DNA in tumors and tissues as an intracellular cytotoxic measure of doxorubicin exposure after administration of small molecule and nanoparticle formulations of doxorubicin. The assay uses daunorubicin as an internal standard; liquid-liquid phase extraction to isolate bound drug; a Shimadzu HPLC with fluorescence detection equipped with a Phenomenex Luna C18 (2 um, 2.0 x 100 mm) analytical column; and a gradient mobile phase of 0.1% formic acid in water and acetonitrile. The assay has a lower limit of quantification (LLOQ) of 10 ng/mL and is shown to be linear up to 3,000 ng/mL. We demonstrated the suitability of this assay for doxorubicin bound to DNA in vivo by using it to quantify the doxorubicin concentration within tumor samples from SKOV3 and HEC1A mice obtained 72 hours after administering PEGylated liposomal doxorubicin (Doxil®; PLD) IV at 6 mg/kg. This HPLC assay allows for a sensitive and simple intracellular quantification of doxorubicin as compared to other methods and will be an important tool for future studies evaluating intracellular pharmacokinetics of doxorubicin and various nanoparticle carriers.Doctor of Philosoph

History of the Innovation of Damage Control for Management of Trauma Patients: 1902-2016

Objective: To review the history of the innovation of damage control (DC) for management of trauma patients. Background: DC is an important development in trauma care that provides a valuable case study in surgical innovation. Methods: We searched bibliographic databases (1950-2015), conference abstracts (2009-2013), Web sites, textbooks, and bibliographies for articles relating to trauma DC. The innovation of DC was then classified according to the Innovation, Development, Exploration, Assessment, and Long-term study model of surgical innovation. Results: The innovation\u27\u27 of DC originated from the use of therapeutic liver packing, a practice that had previously been abandoned after World War II because of adverse events. It then developed\u27\u27 into abbreviated laparotomy using rapid conservative operative techniques.\u27\u27 Subsequent exploration\u27\u27 resulted in the application of DC to increasingly complex abdominal injuries and thoracic, peripheral vascular, and orthopedic injuries. Increasing use of DC laparotomy was followed by growing reports of postinjury abdominal compartment syndrome and prophylactic use of the open abdomen to prevent intra-abdominal hypertension after DC laparotomy. By the year 2000, DC surgery had been widely adopted and was recommended for use in surgical journals, textbooks, and teaching courses ( assessment\u27\u27 stage of innovation). Long-term study\u27\u27 of DC is raising questions about whether the procedure should be used more selectively in the context of improving resuscitation practices. Conclusions: The history of the innovation of DC illustrates how a previously abandoned surgical technique was adapted and readopted in response to an increased understanding of trauma patient physiology and changing injury patterns and trauma resuscitation practices

A sensitive high performance liquid chromatography assay for the quantification of doxorubicin associated with DNA in tumor and tissues

A HPLC method was validated to quantify doxorubicin associated to DNA from tissue.Successfully applied to an in vivo mouse-based pharmacokinetic study.Important tool for future studies evaluating intracellular pharmacokinetics.Doxorubicin, a widely used anticancer agent, exhibits antitumor activity against a wide variety of malignancies. The drug exerts its cytotoxic effects by binding to and intercalating within the DNA of tumor and tissue cells. However, current assays are unable to accurately determine the concentration of the intracellular active form of doxorubicin. Thus, the development of a sample processing method and a high-performance liquid chromatography (HPLC) methodology was performed in order to quantify doxorubicin that is associated with DNA in tumors and tissues, which provided an intracellular cytotoxic measure of doxorubicin exposure after administration of small molecule and nanoparticle formulations of doxorubicin. The assay uses daunorubicin as an internal standard; liquid–liquid phase extraction to isolate drug associated with DNA; a Shimadzu HPLC with fluorescence detection equipped with a Phenomenex Luna C18 (2 μm, 2.0 × 100 mm) analytical column and a gradient mobile phase of 0.1% formic acid in water or acetonitrile for separation and quantification. The assay has a lower limit of detection (LLOQ) of 10 ng/mL and is shown to be linear up to 3000 ng/mL. The intra- and inter-day precision of the assay expressed as a coefficient of variation (CV%) ranged from 4.01 to 8.81%. Furthermore, the suitability of this assay for measuring doxorubicin associated with DNA in vivo was demonstrated by using it to quantify the doxorubicin concentration within tumor samples from SKOV3 and HEC1A mice obtained 72 h after administration of PEGylated liposomal doxorubicin (Doxil®; PLD) at 6 mg/kg IV x 1. This HPLC assay allows for sensitive intracellular quantification of doxorubicin and will be an important tool for future studies evaluating intracellular pharmacokinetics of doxorubicin and various nanoparticle formulations of doxorubicin

Exploring Anatomic Variants to Enhance Anatomy Teaching: Musculus Sternalis

The opportunity to encounter and appreciate the range of human variation in anatomic structures—and its potential impact on related structures, function, and treatment—is one of the chief benefits of cadaveric dissection for students in clinical preprofessional programs. The dissection lab is also where students can examine unusual anatomic variants that may not be included in their textbooks, lab manuals, or other course materials. For students specializing in physical medicine, awareness and understanding of muscle variants has a practical relevance to their preparations for clinical practice. In a routine dissection of the superficial chest muscles, graduate students in a human gross anatomy class exposed a large, well-developed sternalis muscle. The exposure of this muscle generated many student questions about M sternalis: its prevalence and appearance, its function, its development, and its evolutionary roots. Students used an inquiry protocol to guide their searches through relevant literature to gather this information. Instructors developed a decision tree to assist students in their inquiries, both by helping them to make analytic inferences and by highlighting areas of interest needing further investigation. Answering these questions enriches the understanding and promotes “habits of mind” for exploring musculoskeletal anatomy beyond simple descriptions of function and structure

WFPC2 Observations of the Hubble Deep Field-South

The Hubble Deep Field-South observations targeted a high-galactic-latitude field near QSO J2233-606. We present WFPC2 observations of the field in four wide bandpasses centered at roughly 300, 450, 606, and 814 nm. Observations, data reduction procedures, and noise properties of the final images are discussed in detail. A catalog of sources is presented, and the number counts and color distributions of the galaxies are compared to a new catalog of the HDF-N that has been constructed in an identical manner. The two fields are qualitatively similar, with the galaxy number counts for the two fields agreeing to within 20%. The HDF-S has more candidate Lyman-break galaxies at z > 2 than the HDF-N. The star-formation rate per unit volume computed from the HDF-S, based on the UV luminosity of high-redshift candidates, is a factor of 1.9 higher than from the HDF-N at z ~ 2.7, and a factor of 1.3 higher at z ~ 4.Comment: 93 pages, 25 figures; contains very long table

Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments

Immune profiles and DNA methylation alterations related with non-muscle-invasive bladder cancer outcomes

Background: Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC. Methods and results: We used the Illumina HumanMethylationEPIC array to measure peripheral blood DNA methylation profiles of NMIBC patients (N = 603) enrolled in a population-based cohort study in New Hampshire and applied cell type deconvolution to estimate immune cell-type proportions. Using Cox proportional hazard models, we identified that increasing CD4T and CD8T cell proportions were associated with a statistically significant decreased hazard of tumor recurrence or death (CD4T: HR = 0.98, 95% CI = 0.97–1.00; CD8T: HR = 0.97, 95% CI = 0.95–1.00), whereas increasing monocyte proportion and methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) were associated with the increased hazard of tumor recurrence or death (monocyte: HR = 1.04, 95% CI = 1.00–1.07; mdNLR: HR = 1.12, 95% CI = 1.04–1.20). Then, using an epigenome-wide association study (EWAS) approach adjusting for age, sex, smoking status, BCG treatment status, and immune cell profiles, we identified 2528 CpGs associated with the hazard of tumor recurrence or death (P \u3c 0.005). Among these CpGs, the 1572 were associated with an increased hazard and were significantly enriched in open sea regions; the 956 remaining CpGs were associated with a decreased hazard and were significantly enriched in enhancer regions and DNase hypersensitive sites. Conclusions: Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence