2,5-Bis(4-meth­oxy­phen­yl)-1,3,4-oxadiazole

In the title compound, C16H14N2O3, the essentially planar 1,3,4-oxadiazole ring [maximum deviation = 0.0021 (11) Å] is inclined at dihedral angles of 8.06 (6) and 11.21 (6)° with respect to the two benzene rings; the dihedral angle between the latter rings is 11.66 (5)°. In the crystal, short inter­molecular C⋯O inter­actions [2.9968 (15) Å] connect adjacent mol­ecules into chains propagating in [203]. The crystal structure is further stabilized by weak inter­molecular C—H⋯π inter­actions

Who Sold During the Crash of 2008-9? Evidence from Tax-Return Data on Daily Sales of Stock

We examine individual stock sales from 2008 to 2009 using population tax return data. The share of sales by the top 0.1 percent of income recipients and other top income groups rose sharply following the Lehman Brothers bankruptcy and remained elevated throughout the financial crisis. Sales by top income and older age groups were relatively more responsive to increased stock market volatility. Volatility-driven sales were not concentrated in any one sector, but mutual fund sales responded more strongly to increased volatility than stock sales. Additional analysis suggests that gross sales in tax return data are informative about unobserved net sales.http://deepblue.lib.umich.edu/bitstream/2027.42/118067/1/1316_Nagel.pd

Bounds on the Probability of Success of Postselected Non-linear Sign Shifts Implemented with Linear Optics

The fundamental gates of linear optics quantum computation are realized by using single photons sources, linear optics and photon counters. Success of these gates is conditioned on the pattern of photons detected without using feedback. Here it is shown that the maximum probability of success of these gates is typically strictly less than 1. For the one-mode non-linear sign shift, the probability of success is bounded by 1/2. For the conditional sign shift of two modes, this probability is bounded by 3/4. These bounds are still substantially larger than the highest probabilities shown to be achievable so far, which are 1/4 and 2/27, respectively.Comment: 6 page

Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C.

The unidirectional and opposite-polarity microtubule-based motors, dynein and kinesin, drive long-distance intracellular cargo transport. Cellular observations suggest that opposite-polarity motors may be coupled. We recently identified an interaction between the cytoplasmic dynein-1 activating adaptor Hook3 and the kinesin-3 KIF1C. Here, using in vitro reconstitutions with purified components, we show that KIF1C and dynein/dynactin can exist in a complex scaffolded by Hook3. Full-length Hook3 binds to and activates dynein/dynactin motility. Hook3 also binds to a short region in the "tail" of KIF1C, but unlike dynein/dynactin, this interaction does not activate KIF1C. Hook3 scaffolding allows dynein to transport KIF1C toward the microtubule minus end, and KIF1C to transport dynein toward the microtubule plus end. In cells, KIF1C can recruit Hook3 to the cell periphery, although the cellular role of the complex containing both motors remains unknown. We propose that Hook3's ability to scaffold dynein/dynactin and KIF1C may regulate bidirectional motility, promote motor recycling, or sequester the pool of available dynein/dynactin activating adaptors

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator

Background: Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. Methods: We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO2), creating a "therapeutic pneumoperitoneum.” A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesionmodulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. Results: The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO2 pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no systemrelated complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. Conclusions: As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesion

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update

Inmunoterapia dual; Ipilimumab; NivolumabImmunoteràpia dual; Ipilimumab; NivolumabDual immunotherapy; Ipilimumab; NivolumabBackground To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. Patients and methods Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. Results With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. Conclusions With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.This work was supported by Bristol Myers Squibb (Princeton, New Jersey) (no grant number). Authors received no financial support or compensation for publication of this manuscript

Characterization of the Mutagenic Spectrum of 4-Nitroquinoline 1-Oxide (4-NQO) in Aspergillus nidulans by Whole Genome Sequencing

4-Nitroquinoline 1-oxide (4-NQO) is a highly carcinogenic chemical that induces mutations in bacteria, fungi, and animals through the formation of bulky purine adducts. 4-NQO has been used as a mutagen for genetic screens and in both the study of DNA damage and DNA repair. In the model eukaryote Aspergillus nidulans, 4-NQO−based genetic screens have been used to study diverse processes, including gene regulation, mitosis, metabolism, organelle transport, and septation. Early work during the 1970s using bacterial and yeast mutation tester strains concluded that 4-NQO was a guanine-specific mutagen. However, these strains were limited in their ability to determine full mutagenic potential, as they could not identify mutations at multiple sites, unlinked suppressor mutations, or G:C to C:G transversions. We have now used a whole genome resequencing approach with mutant strains generated from two independent genetic screens to determine the full mutagenic spectrum of 4-NQO in A. nidulans. Analysis of 3994 mutations from 38 mutant strains reveals that 4-NQO induces substitutions in both guanine and adenine residues, although with a 19-fold preference for guanine. We found no association between mutation load and mutagen dose and observed no sequence bias in the residues flanking the mutated purine base. The mutations were distributed randomly throughout most of the genome. Our data provide new evidence that 4-NQO can potentially target all base pairs. Furthermore, we predict that current practices for 4-NQO−induced mutagenesis are sufficient to reach gene saturation for genetic screens with feasible identification of causative mutations via whole genome resequencing

Quantum synthesis of arbitrary unitary operators

Nature provides us with a restricted set of microscopic interactions. The question is whether we can synthesize out of these fundamental interactions an arbitrary unitary operator. In this paper we present a constructive algorithm for realization of any unitary operator which acts on a (truncated) Hilbert space of a single bosonic mode. In particular, we consider a physical implementation of unitary transformations acting on 1-dimensional vibrational states of a trapped ion. As an example we present an algorithm which realizes the discrete Fourier transform.Comment: 6 RevTeX pages with 3 figures, submitted to Phys.Rev.A, see also http://nic.savba.sk/sav/inst/fyzi/qo

No-hidden-variables proof for two spin-1/2 particles preselected and postselected in unentangled states

It is a well-known fact that all the statistical predictions of quantum mechanics on the state of any physical system represented by a two-dimensional Hilbert space can always be duplicated by a noncontextual hidden-variables model. In this paper, I show that, in some cases, when we consider an additional independent (unentangled) two-dimensional system, the quantum description of the resulting composite system cannot be reproduced using noncontextual hidden variables. In particular, a no-hidden-variables proof is presented for two individual spin-1/2 particles preselected in an uncorrelated state AB and postselected in another uncorrelated state aB, B being the same state for the second particle in both preselection and postselection.Comment: LaTeX, 8 page