Reproducible pharmacogenomic profiling of cancer cell line panels.

The use of large-scale genomic and drug response screening of cancer cell lines depends crucially on the reproducibility of results. Here we consider two previously published screens, plus a later critique of these studies. Using independent data, we show that consistency is achievable, and provide a systematic description of the best laboratory and analysis practices for future studies.

Spectrally resolved wedged reversal shearing interferometer.

In this Letter, we introduce a technique to fully determine the spatio-temporal electric field E(x,y,t) of an arbitrary ultrashort pulse. By passing the beam through a wedged reversal shearing interferometer followed by a scanning Michelson interferometer, the field autocorrelation of the shearing interferograms is measured. The spectrum of the shearing interferograms is obtained after a Fourier transform by the Whittaker-Shannon sampling theorem, yielding the amplitude and wavefront information at every wavelength. With the addition of the phase information of a single point, we are able to directly reconstruct the spatio-temporal electric field E(x,y,t) of an arbitrary ultrashort pulse.

Compact vectorial optical field generator using a single phase-only spatial light modulator.

In this study, we demonstrate a compact vectorial optical field generator for any coherent light, including femtosecond laser beams. The apparatus utilizes a single Köster prism for both beam splitting and recombining. A phase-only spatial light modulator is used as a diffractive optical element to encode the two complex fields that recombine after being converted to orthogonal polarizations, generating an arbitrary vectorial optical field. We apply this setup to shape focused femtosecond pulses in producing patterned structures.

High-efficiency non-diffractive generator of arbitrary vectorial optical fields with minimal optical elements.

Tailoring electromagnetic waves has a wide range of applications, such as optical trapping, focus engineering, imaging, laser cutting, and optical communication. To do so, the spatial distribution of at least one of the four degrees of freedom of electromagnetic waves, amplitude, phase, polarization ratio, and retardance, must be modified. Arbitrary vectorial optical fields (VOF) can be engineered by spatially modulating all four degrees of freedom simultaneously. However, existing dynamic vectorial optical field generators (VOF-Gens) require intensive alignment and many optical elements in order to achieve high efficiency. Here, we design a dynamic VOF-Gen that can generate arbitrary VOFs using only five optical elements. Experimentally, we demonstrated an efficiency of 72%, the highest ever demonstrated.

Real-time in situ study of femtosecond-laser-induced periodic structures on metals by linear and nonlinear optics.

Femtosecond-laser surface structuring on metals is investigated in real time by both fundamental and second harmonic generation (SHG) signals. The onset of surface modification and its progress can be monitored by both the fundamental and SHG probes. However, the dynamics of femtosecond-laser-induced periodic surface structures (FLIPSSs) formation can only be revealed by SHG but not fundamental because of the higher sensitivity of SHG to structural geometry on metal. Our technique provides a simple and effective way to monitor the surface modification and FLIPSS formation thresholds and allows us to obtain the optimal FLIPSS for SHG enhancement.

Generation of continuously rotating polarization by combining cross-polarizations and its application in surface structuring.

In this study, we develop a simple but highly effective technique that generates a continuously varying polarization within a laser beam. This is achieved by having orthogonal linear polarizations on each side of the beam. By simply focusing such a laser beam, we can attain a gradually and continuously changing polarization within the entire Rayleigh range due to diffraction. To demonstrate this polarization distribution, we apply this laser beam onto a metal surface and create a continuously rotating laser induced periodic surface structure pattern. This technique provides a very effective way to produce complex surface structures that may potentially find applications, such as polarization modulators and metasurfaces.

Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity.

BRAF(V600E) is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting "active" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf(V600E) kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf(V600E)-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. In B-Raf(V600E)-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf(V600E)-driven tumors.

Spatial Wavefunction Characterization of Femtosecond Pulses at Single-Photon Level.

Reading quantum information of single photons is commonly realized by quantum tomography or the direct (weak) measurement approach. However, these methods are time-consuming and face enormous challenges in characterizing single photons from an ultrafast light source due to the stringent temporal mode matching requirements. Here, we retrieve the spatial wavefunction of indistinguishable single photons from both a continuous wave source and a femtosecond light source using a self-referencing interferometer. Our method only requires nine ensemble-averaged measurements. This technique simplifies the measurement procedure of single-photon wavefunction and automatically mode matches each self-interfering single photon temporally, which enables the measurement of the spatial wavefunction of single photons from an ultrafast light source.

A new and standardized approach for trocar placement in laparoscopic Roux-en-Y gastric bypass.

INTRODUCTION: Super-morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) present unique technical challenges. In our experience the ease of the operation and the operative time seem to be more dependent on body habitus than body mass index (BMI). We hypothesized that the distance between the xyphoid process and the umbilicus (the XU distance) correlated with surgical difficulty and described an original modification of trocar placement based on this measurement to improve the ease of the operation. METHODS: Seven hundred and seventy-four patients underwent LRYGB, and the XU distance was measured in a subset of 38 patients midway through the experience. The need for additional trocars was assessed intraoperatively and the relationship between the XU distance and the need for extra trocars was subsequently analyzed. A standardized approach for trocar placement was implemented in the second half of our series. The operative time was compared between the standardized and nonstandardized groups. RESULTS: Fifty percent of the patients required a five-trocar technique. Median XU distance in this group was 21.4 cm (range 17-25 cm). In the remaining 19 patients additional trocars were added; median XU distance was 27.3 cm (range 24-33 cm). From the 774 patients included in the study period, the operative time for the first 322 patients who were completed with a nonstandardized trocar approach was significantly longer than the subsequent 452 cases in which the standardized trocar approach was used (210 versus 173 min, p < 0.001). CONCLUSIONS: We define XU distance as the key element in determining the choice of trocar placement. When XU distance is less then 25 cm, the basic approach should be used and if it is greater than 25 cm, the advanced trocar approach is recommended. This standardized technique leads to decreased operative time and improved ease of operation.

Plasmonic metasurfaces with 42.3% transmission efficiency in the visible.

Metasurfaces are two-dimensional nanoantenna arrays that can control the propagation of light at will. In particular, plasmonic metasurfaces feature ultrathin thicknesses, ease of fabrication, field confinement beyond the diffraction limit, superior nonlinear properties, and ultrafast performances. However, the technological relevance of plasmonic metasurfaces operating in the transmission mode at optical frequencies is questionable due to their limited efficiency. The state-of-the-art efficiency of geometric plasmonic metasurfaces at visible and near-infrared frequencies, for example, is ≤10%. Here, we report a multipole-interference-based transmission-type geometric plasmonic metasurface with a polarization conversion efficiency that reaches 42.3% at 744 nm, over 400% increase over the state of the art. The efficiency is augmented by breaking the scattering symmetry due to simultaneously approaching the generalized Kerker condition for two orthogonal polarizations. In addition, the design of the metasurface proposed in this study introduces an air gap between the antennas and the surrounding media that confines the field within the gap, which mitigates the crosstalk between meta-atoms and minimizes metallic absorption. The proposed metasurface is broadband, versatile, easy to fabricate, and highly tolerant to fabrication errors. We highlight the technological relevance of our plasmonic metasurface by demonstrating a transmission-type beam deflector and hologram with record efficiencies.

Laparoscopic intragastric approach for stromal tumours located at the posterior gastric wall.

Surgical resection is indicated for gastrointestinal stromal tumour (GIST). Laparoscopic resection with clear margins is effective in gastric GIST. However, GIST located in the posterior gastric wall with close proximity to the oesophagogastric junction poses special challenges. Laparoscopic intragastric resection offers a new approach to the management of these tumours. The surgical technique, our experience and a summary of the literature are presented.

Complete characterization of ultrashort optical pulses with a phase-shifting wedged reversal shearing interferometer.

The ability of an interferometer to characterize the spatial information of a light beam is often limited by the temporal profile of the beam, with femtosecond pulse characterization being particularly challenging. In this study, we developed a simple, stable, controllable shearing and vectorial phase-shifting wedged reversal shearing interferometer that is able to characterize all types of coherent and partially coherent light beams. The proposed interferometer consists of only a single beam splitter cube with one wedged entrance face and is insensitive to environmental vibration due to its common path configuration. A near zero-path length difference of the proposed interferometer ensures its operation for ultrashort pulses, providing, for the first time, a simple and stable interferometric tool to fully characterize sub-100 fs laser pulses. All common beam characterization can be carried out with the interferometer, such as the amplitude, phase, polarization, wavelength, and pulse duration. Furthermore, this technique is sensitive to the wavefront tilt and can be used for precise beam alignment. Therefore, this interferometer can be an essential tool for beam characterization, optical imaging, and the testing required for a wide range of applications, including astronomy, biomedicine, ophthalmology, optical testing and imaging systems, and adaptive optics.

Femtosecond laser­induced herringbone patterns.

Femtosecond laser-induced herringbone patterns are formed on copper (Cu). These novel periodic structures are created following s-polarized, large incident angle, femtosecond laser pulses. Forming as slanted and axially symmetric laser-induced periodic surface structures along the side walls of ablated channels, the result is a series of v-shaped structures that resemble a herringbone pattern. Fluence mapping, incident angle studies, as well as polarization studies have been conducted and provide a clear understanding of this new structure.

Randomized trial comparing pantoprazole infusion, bolus and no treatment on gastric pH and recurrent bleeding in peptic ulcers.

BACKGROUND: To study the effects of pantoprazole on gastric pH and recurrent bleeding after endoscopic treatment for bleeding peptic ulcers. METHODS: After endoscopic haemostasis, patients were randomly assigned to infusion group (pantoprazole 80 mg i.v. bolus followed by continuous infusion of 8 mg/h for 3 days), bolus group (pantoprazole 80 mg i.v. bolus followed by 40 mg i.v. bolus every 12 h for 3 days) and no-treatment group (no acid suppression in the first 3 days). Gastric pH was monitored. Rebleeding rate within 30 days, the need for surgery, transfusion requirement, total hospital stay, mortality rate and gastric pH were compared. RESULTS: One hundred and sixty-eight patients were included, with 15 patients excluded from the analysis. There were 54 patients in the infusion group, 49 in the bolus group and 50 in the no-treatment group. There was fewer rebleeding (3.7 vs 16.0%, P = 0.034), less operative intervention (0 vs 8.0%, P = 0.034) and shorter hospital stay (6.4 vs 8.2 days, P = 0.040) in the infusion group compared with that in no-treatment group. When the bolus group was compared with no-treatment group, there were fewer rebleed (4.1 vs 16.0%, P = 0.049) and less blood transfusion (1.5 vs 2.9 units, P = 0.007). There was no difference in mortality among the three groups. Patients who received either pantoprazole infusion or bolus had significantly higher mean pH and longer duration of pH above 6 compared with the no-treatment group. There was no difference in the rebleeding rate, transfusion requirement, need for operation and hospital stay between the infusion and bolus groups. The mean pH and the duration of pH above 6 were also similar. CONCLUSION: Pantoprazole either as infusion or bolus decreased rebleeding after endoscopic treatment for bleeding peptic ulcer.

APACHE system is better than Ranson system in the prediction of severity of acute pancreatitis.

BACKGROUND: It has been suggested that addition of obesity score to the APACHE-II system can lead to more accurate prediction of severity of acute pancreatitis. However there is scanty information on the usefulness of the combined APACHE-O scoring system in Asian patients. This study aimed to compare the accuracy of Ranson, APACHE-II and APACHE-O systems in assessing severity of acute pancreatitis in a local Chinese population. METHODS: One hundred and one consecutive patients with acute pancreatitis were prospectively studied. Body mass index (BMI) was measured on admission. Ranson score, APACHE-II and APACHE-O scores were recorded on admission and at 48 hours. By adopting the cut-off levels and definitions advocated in the Atlanta consensus for severe disease, the diagnostic accuracy of the three scoring systems was compared by the area under the curve (AUC) under the receiver operator characteristic curve. RESULTS: Of the 101 patients, 12 (11.9%) patients suffered from severe pancreatitis. Obesity was uncommon and only two patients (2.0%) had BMI>30. Eighty-two (81.2%) patients were normal weight (BMI< or =25) whereas 17 (16.8%) were overweight (BMI 25-30). Overweight or obesity (BMI>25) was not associated with severe pancreatitis (P=0.40). The AUC for admission scores of Ranson, APACHE-II, and APACHE-O systems was 0.549, 0.904 and 0.904, respectively. The AUC for 48-hour scores of Ranson, APACHE-II and APACHE-O systems was 0.808, 0.955 and 0.951, respectively. CONCLUSIONS: The APACHE-II scoring system is more accurate than the Ranson scoring system of the prediction of severity in acute pancreatitis. Addition of obesity score does not significantly improve the predictive accuracy of the APACHE-II system in our local population with a low prevalence of obesity.