Modeling and control of nanoparticle bloodstream concentration for cancer therapies

Currently, the most commonly used treatments for cancerous tumors (chemotherapy, radiation, etc.) have almost no method of monitoring the administration of the treatment for adverse effects in real time. Without any real time feedback or control, treatment becomes a guess and check method with no way of predicting the effects of the drugs based on the actual bioavailability to the patient\u27s body. One particular drug may be effective for one patient, yet provide no benefit to another. Doctors and scientists do not routinely attempt to quantifiably explain this discrepancy. In this work, mathematical modeling and analysis techniques are joined together with experimentation to gain further insight into the challenges of nanoparticle uptake and retention in the bloodstream. Several models are presented here which predict both the uptake and retention phases of the experiment. There does exist a commonly accepted model of drug clearance in the pharmacokinetics community, and it is demonstrated here that this model provides an accurate reflection of reality, as observed in experiments, for delivery of gold-coated nanorods. This model is then utilized in a state space feedback control framework to regulate the nanoparticle concentration in the bloodstream. An equal time delay is also introduced in both the state and control input for the purpose of studying alternate dosing strategies. This study will aid in the prediction of the effects of the drugs in a patient\u27s body, thus leading to better models for drug regimen and administration

The charge and energy spectra of heavy cosmic ray nuclei

A charged particle detector array flown in a high altitude balloon detected and measured some 30,000 cosmic ray nuclei with Z greater than or equal to 12. The charge spectrum at the top of the atmosphere for nuclei with E greater than 650 MeV/n and the energy spectrum for 650 less than or equal to E less than 1800 MeV/n are reported and compared with previously published results. The charge spectrum at the source of cosmic rays is deduced from these data and compared with a recent compilation of galactic abundances

Survey of Aviation Technical Manuals, Phase 2 Report: User Evaluation of Maintenance Documents

This report contains the results from Phase 2 of a 3-phase research effort. Phase 1 (Human Factors Survey of Aviation Technical Manuals Phase 1 Report: Manual Development Procedures) of this research effort surveyed the procedures used by five manufacturers to develop maintenance documentation. Several potential human factors issues were identified in the development processes employed by these manufacturers. They included the reactive rather than proactive use of user evaluations, the limited use of user input and procedure validation, no systematic attempts to track error, and the lack of standards for measuring document quality. In Phase 2, a written survey was used to solicit information about user perception of errors in current manuals, manual usage rates, and general manual quality. On-site interviews of technicians were also conducted to gather feedback about the types of problems encountered with manuals, the associated impact, and suggestions for improving manuals. Feedback was obtained from technicians responsible for maintenance on a wide variety of Federal Aviation Regulations, Part 25 aircraft. Survey results revealed that, although user evaluations of the accuracy and quality of technical manuals are generally good, they rate manuals as having poor usability. Comparing the results of Phase 1 to the Phase 2 results supports the need for a higher level of user involvement during the document development process

Estrogenic activity, race/ethnicity, and Indigenous American ancestry among San Francisco Bay Area women.

Estrogens play a significant role in breast cancer development and are not only produced endogenously, but are also mimicked by estrogen-like compounds from environmental exposures. We evaluated associations between estrogenic (E) activity, demographic factors and breast cancer risk factors in Non-Latina Black (NLB), Non-Latina White (NLW), and Latina women. We examined the association between E activity and Indigenous American (IA) ancestry in Latina women. Total E activity was measured with a bioassay in plasma samples of 503 women who served as controls in the San Francisco Bay Area Breast Cancer Study. In the univariate model that included all women with race/ethnicity as the independent predictor, Latinas had 13% lower E activity (p = 0.239) and NLBs had 35% higher activity (p = 0.04) compared to NLWs. In the multivariable model that adjusted for demographic factors, Latinas continued to show lower E activity levels (26%, p = 0.026), but the difference between NLBs and NLWs was no longer statistically significant (p = 0.431). An inverse association was observed between E activity and IA ancestry among Latina women (50% lower in 0% vs. 100% European ancestry, p = 0.027) consistent with our previously reported association between IA ancestry and breast cancer risk. These findings suggest that endogenous estrogens and exogenous estrogen-like compounds that act on the estrogen receptor and modulate E activity may partially explain racial/ethnic differences in breast cancer risk

Development and application of rice starch based edible coating to improve the postharvest storage potential and quality of plum fruit (<i>Prunus salicina</i>)

The study investigated the possibility of enhancing the shelf life of plum fruit coated with rice starch-ι-carrageenan (RS-ι-car) composite coating blended with sucrose fatty acid esters (FAEs). Film solution (starch 3%, carrageenan 1.5% and FAEs 2%) was prepared by mixing the ingredients and properties of stand-alone films (physical, mechanical, barrier and surface morphology) were studied before applying the coating on fruit surface. Fruit were stored at 20 °C for 3 weeks and analyzed for weight loss, ethylene production, respiration rate, color change, firmness, and titratable acidity (TA) and soluble solid content (SSC). Surface morphology of stand-alone film and fruit surface (after applying on the plum fruit) was studied using scanning electron microscopy (SEM). Phytochemical analysis was performed during the storage period and total phenolic content (TPC), total antioxidant capacity (TAC), flavonoid content (FC) and free radical scavenging activity were determined. The rice starch composite coating was shown to be effective in reducing both weight loss (WL) and respiration rate and inhibiting the endogenous ethylene production when compared to the uncoated control fruit stored at room temperature (p &lt; 0.05). TPC, TAC, FC and free radical scavenging activity was unaffected in the coated fruit throughout the storage period (p &lt; 0.05). The findings reported in this study indicate that the RS-ι-car-FAEs coating prolongs the shelf life and maintains the overall quality of plum fruit during storage and could potentially be commercialized as a new edible coating for the plum fruit industry

Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase

PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid concentration (pUAc) was 11.3 ± 2.1 mg/dl (mean ± SD). By day seven after injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had normalized in 11 subjects, whose mean pUAc decreased to 2.8 ± 2.2 mg/dl. At doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no more than 6 mg/dl. In eight subjects, plasma uricase activity was still measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other five subjects, plasma uricase activity could not be detected beyond ten days after injection; this was associated with the appearance of relatively low-titer IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were directed against PEG itself rather than the uricase protein. Three PEG antibody-positive subjects had injection-site reactions at 8 to 9 days after injection. Gout flares in six subjects were the only other significant adverse reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating life and the ability to normalize plasma uric acid in markedly hyperuricemic subjects suggest that PEG-uricase could be effective in depleting expanded tissue stores of uric acid in subjects with chronic or tophaceous gout. The development of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves further investigation, because it has potential implications for other PEGylated therapeutic agents in clinical use

Regulation of Intracellular Calcium Concentration by Nanosecond Pulsed Electric Fields

Changes in [Ca2+]i response of individual Jurkat cells to nanosecond pulsed electric fields (nsPEFs) of 60 ns and field strengths of 25, 50, and 100 kV/cm were investigated. The magnitude of the nsPEF-induced rise in [Ca2+]i was dependent on the electric field strength. With 25 and 50 kV/cm, the [Ca2+]i response was due to the release of Ca2+ from intracellular stores and occurred in less than 18 ms. With 100 kV/cm, the increase in [Ca2+]i was due to both internal release and to influx across the plasma membrane. Spontaneous changes in [Ca2+]i exhibited a more gradual increase over several seconds. The initial, pulse-induced [Ca2+]i response initiates at the poles of the cell with respect to electrode placement and co-localizes with the endoplasmic reticulum. The results suggest that nsPEFs target both the plasma membrane and subcellular membranes and that one of the mechanisms for Ca2+ release may be due to nanopore formation in the endoplasmic reticulum