Highlights • Multifunctional PM for the co-delivery of survivin siRNA and PXL were developed. • The developed PM were able to significantly silence survivin in cancer cells. • The survivin silencing ...by using PM sensitized cancer cells to PXL activity.
Density profiles of 4 ash-flow deposits in Oregon and Idaho are simulated using the model of Riehle et al. (1995) to calculate heat flow, degassing, and compaction. The deposits are all <
45
m thick ...and most have well defined density reversals and lack substantial alteration or vapor-phase deposition. Model results are made to closely match the measured profiles of 3 simpler deposits by making the assumptions that density reversals represent cooling breaks between ash flows or that subtle density inflections at the base of the profiles are cooler surge deposits. The first assumption is supported by a fossil fumarole pipe truncated at a density inflection, and the second by foreset bedding at the base of the deposit. Deposit temperatures within each unit of thermally stratified deposits are assumed to be homogeneous.
The Rattlesnake Tuff—a more complex ignimbrite sheet—was sampled at 3 distal sites near to one another, a medial site, and 4 proximal sites. Model results of distal profiles are similar despite more than twofold variation in thickness and comprise 3 early deposits having emplacement temperatures of 724–732
°C, followed by two hotter deposits (785–790
°C), and a cooler capping deposit of about 735
°C. One distal site has an inferred surge deposit at its base. Density reversals simulated as cooling intervals all range from 3 to 10
days. Correlated cooling intervals agree to within a factor of two, however, the duration of a cooling interval cannot be precisely hindcast owing to potential complications by rainfall or accumulation of chilled airfall ash. Thus, the seemingly wide range of model results for the cooling intervals is perhaps not surprising.
Proximal profiles have more density reversals implying more deposits than the distal profiles. They also have greater overall compaction and consequential loss of detail in the density profiles. Some earlier deposits have model temperatures of 736–757
°C and may correlate with the lower distal deposits; at one site these are overlain by two hotter deposits (790–796
°C) and a cooler capping deposit (745
°C) that are almost surely correlatives of the upper distal deposits. Some sites have additional, early hotter deposits and one site has an uppermost deposit that is the coolest of all model deposits. Thus a picture emerges of thermally stratified, near-source flows during early eruptive activity and more far-travelled flows during later eruptions. Shards analyzed by Streck and Grunder (1997) show a compositional range and corresponding magma temperatures of 795–880
°C, which is permissive of thermally layered deposits and implies cooling during fallback and travel of 50–100
°C.
Rare textural evidence for internal flow boundaries, as well as our consistent model results among multiple sites despite variation in deposit thickness, support the assumption that density reversals represent partial cooling breaks. If so, then modeling of density profiles can provide important evidence for how large ignimbrites are constructed. Sheridan and Wang (2004) also report stratigraphically consistent results by modeling density reversals in distal Bishop Tuff as cooling breaks. Our results contrast with those of Wilson and Hildreth (2003), who concluded that density reversals in the proximal Bishop Tuff do not represent cooling breaks but instead are evidence for thermally heterogeneous deposits. It may be that the proximal Bishop Tuff is not amenable to modeling due to its great thickness (100–200
m) and deposition on steeply dipping, rugged terrain, factors which would likely cause turbulent flow, obscure subtle stratigraphic details of flow boundaries, and complicate resulting compaction zonation.
Dengue virus, primarily transmitted by the Aedes aegypti (L.) mosquito, has rapidly expanded in geographic extent over the past several decades. In some areas, however, dengue fever has not emerged ...despite established Ae. aegypti populations. The reasons for this are unclear and have sometimes been attributed to socioeconomic differences. In 2013 we compared Ae. aegypti adult density and population age structure between two cities in Sonora, Mexico: Hermosillo, which has regular seasonal dengue virus transmission, and Nogales, which has minimal transmission. Larval and pupal abundance was greater in Nogales, and adult density was only higher in Hermosillo during September. Population age structure, however, was consistently older in Hermosillo. This difference in longevity may have been one factor that limited dengue virus transmission in Nogales in 2013, as a smaller proportion of Ae. aegypti females survived past the extrinsic incubation period.
Dengue virus, primarily transmitted by the Aedes aegypti (L.) mosquito, has rapidly expanded in geographic extent over the past several decades. In some areas, however, dengue fever has not emerged ...despite established Ae. aegypti populations. The reasons for this are unclear and have sometimes been attributed to socio-economic differences. In 2013 we compared Ae. aegypti adult density and population age structure between two cities in Sonora, Mexico: Hermosillo, which has regular seasonal dengue virus transmission, and Nogales, which has minimal transmission. Larval and pupal abundance was greater in Nogales, and adult density was only higher in Hermosillo during September. Population age structure, however, was consistently older in Hermosillo. This difference in longevity may have been one factor that limited dengue virus transmission in Nogales in 2013, as a smaller proportion of Ae. aegypti females survived past the extrinsic incubation period.
We reviewed 53 patients with infection stones treated by extracorporeal shock wave lithotripsy (ESWL*) monotherapy to determine the long-term rate free of stones and the stone recurrence rate as ...correlated with the pre-treatment stone burden and the radiological presence of sand or fragments after the procedure. Long-term followup (mean 26.6 months) was available on 33 patients representing 38 kidneys. Although only 3 kidneys were free of stones immediately after ESWL, 20 were without stones at 3 months and 18 (47%) were stone-free at followup. Of 9 kidneys with fragments of more than 5 mm. after the final treatment 7 (78%) had residual fragments at 3 months and experienced stone progression. Of 9 kidneys with sand remaining 6 (66%) and all 3 kidneys that appeared to be free of stones after ESWL were without stones at followup. The 3-month plain film of the kidneys, ureters and bladder was a reliable indicator of eventual outcome. Of 20 kidneys that were free of stones at 3 months 16 remained without stones. Of 18 kidneys with residual stone particles at 3 months 14 showed disease progression, 2 had stable disease and 2 passed residual sand. Only 1 of 17 patients who were free of stones or had stable stone disease had a positive urine culture at followup. Patients with infection stone fragments 3 months after ESWL monotherapy have a high rate of stone progression (78%) and should undergo further treatment. ESWL monotherapy of infection stones requires close patient followup to assure that all residual fragments have passed and urine remains sterile.
Placement of internal ureteral stents before extracorporeal shock wave lithotripsy of large stone burdens has decreased the incidence of post-extracorporeal shock wave lithotripsy colic, secondary ...endoscopic procedures and prolonged hospital stays. However, indwelling stents have an associated patient morbidity and intolerance. A telephone survey of 50 patients (average stone burden 28 mm.) who were discharged from the hospital after treatment with an indwelling internal polymer stent was performed with a standard questionnaire. Symptoms reported with in situ internal ureteral stents included gross hematuria (42 per cent), fever or chills (20 per cent), and persistent discomfort or pain in the bladder and/or flank (26 to 38 per cent). Of the patients 44 per cent reported moderate to intolerable discomfort that was relieved by removal of the stent. The degree of symptoms was not associated with stent composition, style or length, or the presence of a transurethral string. Five patients had premature migration or dislodgment of the internal stent and 4 reported episodes of obstructive pyelonephritis requiring removal of an impacted stent or endourological intervention. Internal ureteral stents placed before extracorporeal shock wave lithotripsy have an identifiable patient morbidity while indwelling and, therefore, they should be used judiciously according to the stone burden, renal anatomy and body habitus.
The discovery that survivin, a small anti-apoptotic protein, is involved in chemoresistance, opens a new scenario to overcome the drug resistance in cancer. It was shown that siRNA can efficiently ...inhibit the expression of survivin in cancer cells. However, the clinical use of siRNA is still hampered by an unfavorable pharmacokinetic profile. To address this problem, earlier we developed a novel system to deliver siR-NA into cancer cells. Namely, we reversibly modified the survivin siRNA with a phosphothioethanol (PE) portion via a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE conjugate into nano-sized polyethyelene glycol 2000-phosphatidyl ethanolamine (PEG 2000-PE)-based polymeric micelles (PM), obtaining survivin siRNA PM. The activity of these nanopreparations was evaluated by survivin protein down-regulation, tumor cell growth inhibition, and chemosensitization of the treated tumor cells to paclitaxel (PXL). We found a significant decrease of cell viability and down-regulation of survivin protein levels after treatment with survivin siRNA PM in several cancer cell lines. In addition, the down-regulation of survivin by treating cells with survivin siRNA PM, elicited a significant sensitization of the cells to PXL, in both sensitive and resistant cancer cell lines. Finally, we demonstrated successful co-delivery of PXL and survivin siRNA in the same PM leading to superior therapeutic activity compared to their sequential administration. Our results support the use of this new platform for the treatment of the most aggressive tumors.
The documented long-term health of the living related renal donor is a tribute to careful preoperative selection and surgical technique. At our medical center 187 prospective donors were evaluated ...during a 6-year period and 91 underwent donor nephrectomy. Hypertension, renal artery anomalies and donor indecision were the most common reasons for donor rejection. Recipient health and/or death, or a positive crossmatch after pre-transplant donor specific transfusion were other post-arteriogram reasons not to proceed with transplantation. Women were more likely to undergo nephrectomy than men, and older or heavier donors were more likely to be rejected. Using the transcostal, extrapleural surgical approach for nephrectomy there were no deaths or major complications, and the mean postoperative length of stay was 6.4 days. The average postoperative increase in serum creatinine was 0.33 mg./dl. with an average creatinine at discharge of the patient from the hospital of 1.2 mg./dl. The latter creatinine values varied concordantly with donor age. Only 56% of fully evaluated donors (91 of 159) actually underwent donor nephrectomy. The minimal morbidity sustained by these patients re-emphasizes the importance of careful donor selection.
We have searched for correlations between the pointing directions of ultrahigh energy cosmic rays observed by the High Resolution Fly’s Eye experiment and active galactic nuclei (AGN) visible from ...its northern hemisphere location. No correlations, other than random correlations, have been found. We report our results using search parameters prescribed by the Pierre Auger collaboration. Using these parameters, the Auger collaboration concludes that a positive correlation exists for sources visible to their southern hemisphere location. We also describe results using two methods for determining the chance probability of correlations: one in which a hypothesis is formed from scanning one half of the data and tested on the second half, and another which involves a scan over the entire data set. The most significant correlation found occurred with a chance probability of 24%.
The object of this study was to determine if a strong association between soft drink (soda) consumption and recurrence of urinary stone disease, found in an earlier case-control study of adult males, ...had a causal component. The study sample consisted of 1009 male subjects, who completed an episode of urinary stone disease, who were aged 18-75 at that time, and who reported consuming at least 160 ml per day of soft drinks. Half of the subjects were randomized to refrain from consuming soft drinks, while the remaining subjects served as controls. The intervention group had an observed 6.4% advantage in actuarial 3 yr freedom from recurrence (p = 0.023 one-sided) over the control group. One important secondary finding was that for those who reported at the time of the index stone that their most consumed drink was acidified by phosphoric acid but not citric acid, the experimental group had a 15% higher 3 yr recurrence-free rate than the controls, p = 0.002, while for those who reported at the time of the index stone that their most consumed drink was acidified by citric acid with or without phosphoric acid, the experimental group had a similar 3 yr recurrence-free rate to the controls, p = 0.55. This interaction was significant, p = 0.019.
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