Nanoscale optical writing through upconversion resonance energy transfer.

Nanoscale optical writing using far-field super-resolution methods provides an unprecedented approach for high-capacity data storage. However, current nanoscale optical writing methods typically rely on photoinitiation and photoinhibition with high beam intensity, high energy consumption, and short device life span. We demonstrate a simple and broadly applicable method based on resonance energy transfer from lanthanide-doped upconversion nanoparticles to graphene oxide for nanoscale optical writing. The transfer of high-energy quanta from upconversion nanoparticles induces a localized chemical reduction in graphene oxide flakes for optical writing, with a lateral feature size of ~50 nm (1/20th of the wavelength) under an inhibition intensity of 11.25 MW cm-2 Upconversion resonance energy transfer may enable next-generation optical data storage with high capacity and low energy consumption, while offering a powerful tool for energy-efficient nanofabrication of flexible electronic devices.

Testing commercial biopreservative against spoilage microorganisms in MAP packed Ricotta fresca cheese.

Ricotta fresca cheese is susceptible to secondary contamination and is able to support the growth of pathogens or spoilage psychotrophic bacteria during storage. The aim of the present study was to evaluate which among three commercial biopreservatives was suitable to be used to control the growth of spoilage microorganisms in sheep's milk MAP ricotta fresca cheese. 144 Ricotta fresca cheese samples were inoculated either with the bioprotective culture Lyofast FPR 2 (including Enterococcus faecium, Lactobacillus plantarum e Lactobacillus rhamnosus) or Lyofast CNBAL (Carnobacterium spp) or the fermentate MicroGARD 430. Not inoculated control and experimental ricotta were MAP packed (30% CO2 and 70% N2) and stored at 4 °C. Triplicate samples were analyzed after 5 h and 7, 14 and 21 days after inoculation for total bacterial count, mesophilic lactic acid bacteria, Enterobacteriaceae, Pseudomonas spp, Listeria monocytogenes, moulds and yeasts. Among the tested biopreservatives only Carnobacterium spp was able to control Pseudomonas spp and Enterobacteriaceae. The maximum reduction in the concentration of Pseudomonas spp and Enterobacteriaceae was respectively 1.93 and 2.66 log10 cfu/g, observed 14 days after production. Therefore, Carnobacterium spp was selected as the culture of choice to conduct a challenge study against Pseudomonas spp.

Striated muscle activator of Rho signalling (STARS) is reduced in ageing human skeletal muscle and targeted by miR-628-5p.

AIM: The striated muscle activator of Rho signalling (STARS) is a muscle-specific actin-binding protein. The STARS signalling pathway is activated by resistance exercise and is anticipated to play a role in signal mechanotransduction. Animal studies have reported a negative regulation of STARS signalling with age, but such regulation has not been investigated in humans. METHODS: Ten young (18-30 years) and 10 older (60-75 years) subjects completed an acute bout of resistance exercise. Gene and protein expression of members of the STARS signalling pathway and miRNA expression of a subset of miRNAs, predicted or known to target members of STARS signalling pathway, were measured in muscle biopsies collected pre-exercise and 2 h post-exercise. RESULTS: For the first time, we report a significant downregulation of the STARS protein in older subjects. However, there was no effect of age on the magnitude of STARS activation in response to an acute bout of exercise. Finally, we established that miR-628-5p, a miRNA regulated by age and exercise, binds to the STARS 3'UTR to directly downregulate its transcription. CONCLUSION: This study describes for the first time the resistance exercise-induced regulation of STARS signalling in skeletal muscle from older humans and identifies a new miRNA involved in the transcriptional control of STARS.

Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice.

PURPOSE: The molecular factors targeted by androgens and estrogens on muscle mass are not fully understood. The current study aimed to explore gene and protein expression of Atrogin-1, MuRF1, and myostatin in an androgen deprivation-induced muscle atrophy model. METHODS: We examined the effects of Orx either with or without testosterone (T) or estradiol (E2) administration on Atrogin-1 gene expression, and MuRF1 and myostatin gene and protein expression. Measurements were made in soleus (SOL), extensor digitorum longus (EDL) and levator ani/bulbocavernosus (LA/BC) of male C57BL/6 mice. RESULTS: Thirty days of Orx resulted in a reduction in weight gain and muscle mass. These effects were prevented by T. In LA/BC, Atrogin-1 and MuRF1 mRNA was increased throughout 30 days of Orx, which was fully reversed by T and partially by E2 administration. In EDL and SOL, a less pronounced upregulation of both genes was only detectable at the early stages of Orx. Myostatin mRNA levels were downregulated in LA/BC and upregulated in EDL following Orx. T, but not E2, reversed these effects. No changes in protein levels of MuRF1 and myostatin were found in EDL at any time point following Orx. CONCLUSIONS: The atrophy in SOL and EDL in response to androgen deprivation, and its restoration by T, is accompanied by only minimal changes in atrogenes and myostatin gene expression. The marked differences in muscle atrophy and atrogene and myostatin mRNA between LA/BC and the locomotor muscles suggest that the murine LA/BC is not an optimal model to study Orx-induced muscle atrophy.

Definition and measurement of affective variables: theoretical and methodological considerations.

Research in the affective domain is handicapped by the absence of a theory to guide empirical work. Without a theoretical framework to guide the selection of variables, to design appropriate measures, and to interpret results, research consists of a set of discrete studies that have no collective impact.

Mitomycin C and vinorelbine in pretreated breast cancer.

AIMS AND BACKGROUND: Vinorelbine, a new semi-synthetic vinca alkaloid, has demonstrated high activity as a single agent in pretreated metastatic breast cancer. PATIENTS AND METHODS: To evaluate the activity of the combination vinorelbine-mitomycin C and to reduce the incidence of side effects, in particular myelotoxicity, patients with metastatic breast cancer pretreated with 1 or more chemotherapy regimens for metastatic disease were treated according to the following schedule: mitomycin C, 10 mg/m2 day 1, and vinorelbine, 25 mg/m2, days 1, 8 and 15, every 28 days. RESULTS: Twenty-seven patients were enrolled and were evaluable for activity and side effects. A total of 157 cycles were delivered (median 5 cycles per patient). There were 10 partial remissions (37%; 95% confidence interval 20-59%), 5 instances of stable disease and 12 of disease progression. Grade III-IV toxicity was mostly hematological and included thrombocytopenia (4%) and neutropenia (42%). CONCLUSION: Our results indicate that the combination of mitomycin C and vinorelbine has moderate activity in pretreated breast cancer.

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers. A single-institution study.

BACKGROUND: Patients with advanced, inoperable head and neck cancers have cure rates of approximately 10-15%. In these patients, concomitant chemoradiotherapy seems to improve local control and survival. 5-Fluorouracil (5-FU) administered by continuous infusion and cisplatin plus concomitant conventional radiation therapy may be promising in treating advanced, inoperable head and neck cancers. METHODS: Forty-five evaluable patients with primary nonmetastatic, inoperable head and neck cancers were treated. From January 1987 to April 1988, the patients were treated with cisplatin plus radiation therapy (Group 1) and from May 1988 to November 1990, they were treated with the same combination plus 5-FU, given in continuous infusion (Group 2). Clinical and pathologic responses were assessed after radiation therapy was completed. Patients who relapsed underwent salvage surgery, if possible. The disease free and overall survival rates of the patients were evaluated. RESULTS: The overall response rate (complete and partial response) was 93%, 60% of which comprised complete remissions. Despite the high response rates obtained in the two groups, the time to progression for complete responses and the median survival time were unsatisfactory (13 [Group 1] and 10 months [Group 2] and 17 [Group 1] and 16 months [Group 2], respectively). The toxicity rate from the two treatments was not relevant. A Grade II mucositis, according to the World Health Organization, was found in 25 patients, and the treatment was interrupted for 7-10 days in 5. CONCLUSIONS: In this study, despite an improvement in the number of complete responses, the chemotherapeutic regimen with or without 5-FU did not prolong the overall patient survival significantly.

Gender differences in mathematics performance: a meta-analysis.

Reviewers have consistently concluded that males perform better on mathematics tests than females do. To make a refined assessment of the magnitude of gender differences in mathematics performance, we performed a meta-analysis of 100 studies. They yielded 254 independent effect sizes, representing the testing of 3,175,188 Ss. Averaged over all effect sizes based on samples of the general population, d was -0.05, indicating that females outperformed males by only a negligible amount. For computation, d was -0.14 (the negative value indicating superior performance by females). For understanding of mathematical concepts, d was -0.03; for complex problem solving, d was 0.08. An examination of age trends indicated that girls showed a slight superiority in computation in elementary school and middle school. There were no gender differences in problem solving in elementary or middle school; differences favoring men emerged in high school (d = 0.29) and in college (d = 0.32). Gender differences were smallest and actually favored females in samples of the general population, grew larger with increasingly selective samples, and were largest for highly selected samples and samples of highly precocious persons. The magnitude of the gender difference has declined over the years; for studies published in 1973 or earlier d was 0.31, whereas it was 0.14 for studies published in 1974 or later. We conclude that gender differences in mathematics performance are small. Nonetheless, the lower performance of women in problem solving that is evident in high school requires attention.

A phase II study of mitoxantrone.

Thirty pretreated patients with progressive and measurable solid tumors (24/30 patients) or myeloproliferative diseases (6/30 patients) were given mitoxantrone at the dose of 5 mg/m2/day in 250 ml normal saline over 30 minutes infusion for 3 consecutive days every 3 weeks. A total of 104 cycles were administered, median 3 for each patient. 39/104 cycles were delayed for a median of 9 days (from 2 to 59 days) because of myelodepression grade I to III (median I); no infection or bleeding was observed. Grade I to II alopecia was recorded in 16 patients. Chronic cardiac toxicity was observed in one patient previously treated with adriamycin. Mitoxantrone at the studied dose schedule in heavily pretreated subjects was well tolerated every 3 to 4 weeks. In 25/30 patients evaluable for response, one patient had a PR, another had 25% reduction (both patients previously treated) and eleven patients obtained disease stability. This effectiveness, 1 PR, 1 MR, 11 disease stability, is not negligible when it is considered that mitoxantrone was the seventh median line of therapy and the fifth median antiblastic drug.

Effect of probucol treatment on lipoprotein cholesterol and drug levels in blood and lipoproteins in familial hypercholesterolemia.

Twelve patients with mild and 3 with severe hypercholesterolemia were stabilized with an isocaloric diet containing less than 300 mg cholesterol daily with a P/S ratio of 1.8, and placebo period of 4 weeks. They were administered 1000 mg probucol daily for 12 weeks, followed by placebo for 6 weeks. In patients with mild disease, a significant cholesterol reduction was achieved in serum, LDL, and HDL (maximum decrease, 17%, 13%, and 31%, respectively). While HDL3 cholesterol was reduced significantly throughout the period (P less than 0.001), HDL2 cholesterol showed a significant decrease only at the 4th week of treatment (P less than 0.001), and returned to basal levels at the 8th and 12th treatment weeks. Serum apo B levels decreased only slightly, but the HDL-apo A-I fall was significant with a reduction in the HDL-CH/HDL-apo A-I ratio throughout the treatment period. In 3 patients with severe disease, cholesterol decrease in serum and in VLDL, LDL and HDL fractions varied, but on the whole was lower than in patients with mild disease. A decrease in VLDL-CH and HDL-CH was present in all 3, but LDL-CH levels were only slightly lowered in 2 patients, and unchanged in the third. Serum probucol levels fell 66% from the 4th to the 12th treatment week, and in parallel, the percentage of lipoprotein-bound drug increased about 2-fold. It is suggested that these changes in pharmacokinetics as well as the cholesterol-lowering effect of the drug may be due to a change in lipoprotein composition or structure.

Effects of high CaCO3 supplements on serum calcium and phosphorus in patients on regular hemodialysis treatment.

The effect of high doses of CaCO3 on serum phosphorus and calcium (sPi,sCa) and the changes in serum aluminum (sAl) induced by Al(OH)3 interruption were investigated in patients on regular hemodialysis treatment. Some patients were administered Al(OH)3 and CaCO3, others only the former or the latter and others nothing. Al(OH)3 was stopped in all but one in whom it was only reduced, and CaCO3 was started or increased in all patients. A better control of sPi and serum Ca-Pi product was observed during high Ca supplementation, despite Al(OH)3 discontinuation, and was associated with a significant decrease of sAl. As expected, taking into account the dialysate Ca level of 4 mEq/l, a significant hypercalcemia occurred in some patients, especially in those who had a normal predialytic sPi without Al(OH)3 supplementation. Therefore, lowering the dialysate Ca concentration according to individual need and increasing interdialytic oral Ca supplements can be recommended with the dual purpose of keeping a positive Ca balance and correcting hyperphosphatemia.

Urinary cobalt as a measure of exposure in the hard metal industry.

Twenty-six workers in a hard metal manufacturing plant were monitored by cobalt urinary and ambient air measurements during the first month after summer holidays. Cobalt determinations were performed utilizing AAS, with a preliminary chelation and extraction procedure for urinary samples. Almost all personal ambient air samples turned out to be under the cobalt dust TLV of 0.1 mg/m3. When restarting work after the holidays, urinary values did not differ from the control group. At the end of the first working week, urinary cobalt had increased four fold, then decreased to the original values on the following Monday before restarting work. Thereafter, the weekend was no longer sufficient to reduce the levels to normal urinary cobalt values. The values rose to the same level observed before the holidays, and dit not substantially decrease even after the weekend. End-shift urinary cobalt values showed a good relationship with present as well as with mean past exposure on the first and the fifth weekday, but the third day did not. The correlation was better with present exposure on Monday and with mean past exposure on Friday. The observed differences may be explained by the minor influence of recent exposure on present exposure on Monday. The highest values were found on Wednesday. We suggest the utilization of end-shift urinary cobalt determination as a measure of the present exposure on Monday, and of mean recent or preceding exposure on Friday.

Oxazepam induced mouse killing by rats.

Oxazepam (2.5-80 mg/kg) induced significant mouse killing among large samples (N = 100/dose) of Holtzman strain albino rats. Meprobamate (2.5-80 mg/kg) and Chlorpromazine (0.5-4 mg/kg) did not induce killing. Despite its lesser tendency to induce aggression in humans, Oxazepam is as potent as Chlordiazepoxide for inducing killing by rats. Induction of mouse killing by rats appears to the predict clinical potency rather than the aggressive side-effects of anxiolytic benzodiazepines.

Despite various drugs, cats continue to kill mice.

Amphetamines (d- at 0.5--4 mg/kg; 1- at 2--4 mg/kg) inhibited spontaneous mouse killing by some, but not all cats. Various other drugs (drugs and maximum tested doses were: imipramine, 64 mg/kg; amitriptyline, 32 mg/kg; tranylcypromine, 2 mg/kg; tripelennamine, 4 mg/kg; scopolamine, 1 mg/kg; methyl scopolamine 1 mg/kg; chlordiazepoxide 16 mg/kg; diazepam 4 mg/kg; meprobamate, 80 mg/kg; pentobarbital, 16 mg/kg; chlorpromazine, 8 mg/kg; and haloperidol, 0.5 mg/kg) did not reliably inhibit such killing. In contrast with rats, mouse killing by cats was not consistently blocked by antidepressants or amphetamines. When individual cats were inhibited, their reduction of killing seemed related to anorexia rather than to affective arousal.