Quantum spatial superresolution by optical centroid measurements

Quantum lithography (QL) has been suggested as a means of achieving enhanced spatial resolution for optical imaging, but its realization has been held back by the low multi-photon detection rates of recording materials. Recently, an optical centroid measurement (OCM) procedure was proposed as a way to obtain spatial resolution enhancement identical to that of QL but with higher detection efficiency (M. Tsang, Phys. Rev. Lett. 102, 253601, 2009). Here we describe a variation of the OCM method with still higher detection efficiency based on the use of photon-number-resolving detection. We also report laboratory results for two-photon interference. We compare these results with those of the standard QL method based on multi-photon detection and show that the new method leads to superresolution but with higher detection efficiency.Comment: 4 pages, 2 figure

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

The Chemical Compositions of Very Metal-Poor Stars HD 122563 and HD 140283; A View From the Infrared

From high resolution (R = 45,000), high signal-to-noise (S/N > 400) spectra gathered with the Immersion Grating Infrared Spectrograph (IGRINS) in the H and K photometric bands, we have derived elemental abundances of two bright, well-known metal-poor halo stars: the red giant HD 122563 and the subgiant HD 140283. Since these stars have metallicities approaching [Fe/H] = -3, their absorption features are generally very weak. Neutral-species lines of Mg, Si, S and Ca are detectable, as well as those of the light odd-Z elements Na and Al. The derived IR-based abundances agree with those obtained from optical-wavelength spectra. For Mg and Si the abundances from the infrared transitions are improvements to those derived from shorter wavelength data. Many useful OH and CO lines can be detected in the IGRINS HD 122563 spectrum, from which derived O and C abundances are consistent to those obtained from the traditional [O I] and CH features. IGRINS high resolutions H- and K-band spectroscopy offers promising ways to determine more reliable abundances for additional metal-poor stars whose optical features are either not detectable, or too weak, or are based on lines with analytical difficulties.Comment: Accepted for publication in ApJ (28 pages, 4 tables, 6 figures

Locally-applied 5-fluorouracil-loaded slow-release patch prevents pancreatic cancer growth in an orthotopic mouse model

To obtain improved efficacy against pancreatic cancer, we investigated the efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing polymeric patch was produced by 3D printing. After application of the patch, it released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was performed longitudinally. The drug patch delivered a 30.2 times higher level of 5-FU than an intra-peritoneal (i.p.) bolus injection on day-1. High 5-FU levels were accumulated within one week by the patch. Four groups were compared for efficacy of 5-FU. Drug-free patch as a negative control (Group I); 30% 5-FU-loaded patch (4.8 mg) (Group II); 5-FU i.p. once (4.8 mg) (Group III); 5-FU i.p. once a week (1.2 mg), three times (Group IV). The tumor growth rate was significantly faster in Group I than Group II, III, IV (p=0.047 at day-8, p=0.022 at day-12, p=0.002 at day-18 and p=0.034 at day-21). All mice in Group III died of drug toxicity within two weeks after injection. Group II showed more effective suppression of tumor growth than Group IV (p=0.018 at day-12 and p=0.017 at day-21). Histological analysis showed extensive apoptosis in the TUNEL assay and by Ki -67 staining. Western blotting confirmed strong expression of cleaved caspase-3 in Group II. No significant changes were found hematologically and histologically in the liver, kidney and spleen in Groups I, II, IV but were found in Group III.113Ysciescopu

A Physical Basis for the Probabilistic Prediction of the Accumulated Tropical Cyclone Kinetic Energy in the Western North Pacific

The relationship between El Nino-Southern Oscillation (ENSO) andtropical storm (TS) activity over the western North Pacific Ocean is examined for the period from 1981 to 2010. In El Nino years, TS genesis locations are generally shifted to the southeast relative to normal years and the passages of TSs tend to recurve to the northeast. TSs of greater duration and more intensity during an El Nino summer induce an increase of the accumulated tropical cyclone kinetic energy (ACE). Based on the strong relationship between the TS properties and ENSO, a probabilistic predictionfor seasonal ACE is investigated using a hybrid dynamical-statistical model. A statistical relationship is developed between the observed ACE and largescale variables taken from the ECMWF seasonal forecast system 4 hindcasts.The ACE correlates positively with the SST anomaly over the central to eastern Pacific and negatively with the vertical wind shear near the date line.The vertical wind shear anomalies over the central and western Pacific are selected aspredictors based on sensitivity tests of ACE predictive skill. The hybrid model performs quite well in forecasting seasonal ACE with a correlation coefficient between the observed and predicted ACE at 0.80 over the30-yr period. A relative operating characteristic analysis also indicates that the ensembles have significant probabilistic skill for both the above-normal and below-normal categories. By comparing the ACE prediction over theperiod from 2003 to 2011, the hybrid model appears more skillful than the forecast from the Tropical Storm Risk consortium.open1

A girl with sternal malformation/vascular dysplasia association

Sternal malformation/vascular dysplasia association is a rare congenital dysmorphology, which has not yet been reported in Korea. Its typical clinical features include a sternal cleft covered with atrophic skin, a median abdominal raphe extending from the sternal defect to the umbilicus, and cutaneous craniofacial hemangiomata. We report a case of a full-term newborn who presented with no anomalies at birth, except for a skin defect over the sternum and a supraumbilical raphe. Multiple hemangiomas appeared subsequently on her chin and upper chest wall, and respiratory distress due to subglottic hemangioma developed during the first 2 months of life. Her symptoms were controlled with oral prednisolone administration. No respiratory distress have recurred during the 3-year follow-up period

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

BACKGROUND: Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. METHODS: A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. RESULTS: Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. CONCLUSION: The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. TRIAL REGISTRATION: ClinicalTrials.gov: http://NCT0163425