Final-state kinematic imbalances are measured in mesonless production of νμ+A→μ-+p+X in the MINERvA tracker. Initial- and final-state nuclear effects are probed using the direction of the μ- - p ...transverse momentum imbalance and the initial-state momentum of the struck neutron. Differential cross sections are compared to predictions based on current approaches to medium modeling. These models underpredict the cross section at intermediate intranuclear momentum transfers that generally exceed the Fermi momenta. As neutrino interaction models need to correctly incorporate the effect of the nucleus in order to predict neutrino energy resolution in oscillation experiments, this result points to a region of phase space where additional cross section strength is needed in current models, and demonstrates a new technique that would be suitable for use in fine-grained liquid argon detectors where the effect of the nucleus may be even larger.
Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by the protocol-defined guidelines. This phase 2 study ...evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer (ED-SCLC).
Patients (n=130) with chemotherapy-naïve ED-SCLC were randomized 1: 1: 1 to receive paclitaxel (175mg/m2)/carboplatin (area under the curve=6) with either placebo (control) or ipilimumab 10mg/kg in two alternative regimens, concurrent ipilimumab (ipilimumab+paclitaxel/carboplatin followed by placebo+paclitaxel/carboplatin) or phased ipilimumab (placebo+paclitaxel/carboplatin followed by ipilimumab+paclitaxel/carboplatin). Treatment was administered every 3 weeks for a maximum of 18 weeks (induction), followed by maintenance ipilimumab or placebo every 12 weeks. End points included progression-free survival (PFS), irPFS, best overall response rate (BORR); irBORR, overall survival (OS), and safety.
Phased ipilimumab, but not concurrent ipilimumab, improved irPFS versus control HR (hazard ratio)=0.64; P=0.03. No improvement in PFS (HR=0.93; P=0.37) or OS (HR=0.75; P=0.13) occurred. Phased ipilimumab, concurrent ipilimumab and control, respectively, were associated with median irPFS of 6.4, 5.7 and 5.3 months; median PFS of 5.2, 3.9 and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade 3/4 irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and control, respectively.
These results suggest further investigation of ipilimumab in ED-SCLC.
We report the discovery of multiferroic behavior in double perovskite Y2NiMnO6. X-ray diffraction shows that the material has a centrosymmetric crystal structure of space group P2 1/n with Ni2+/Mn4+ ...ordering. This result is further confirmed by aberration-corrected scanning transmission electron microscopy combined with atomic resolution electron energy loss spectroscopy. The appearance of ferroelectric polarization coincides with the magnetic phase transition (∼67 K), which indicates that the ferroelectricity is driven by magnetism, and this is further confirmed by its strong magnetoelectric (ME) effect. We proposed the origin of the ferroelectricity is associated with the combination of Ni2+/Mn4+ charge ordering and the ↑↑↓↓ spin ordering. When compared with other known magnetic multiferroics, Y2NiMnO6 displays several attractive multiferroic properties, including high polarization (∼145 μC/m2), a high multiferroic transition temperature (∼67 K), and strong ME coupling (∼21%).
Transmembrane channels and pores have key roles in fundamental biological processes
and in biotechnological applications such as DNA nanopore sequencing
, resulting in considerable interest in the ...design of pore-containing proteins. Synthetic amphiphilic peptides have been found to form ion channels
, and there have been recent advances in de novo membrane protein design
and in redesigning naturally occurring channel-containing proteins
. However, the de novo design of stable, well-defined transmembrane protein pores that are capable of conducting ions selectively or are large enough to enable the passage of small-molecule fluorophores remains an outstanding challenge
. Here we report the computational design of protein pores formed by two concentric rings of α-helices that are stable and monodisperse in both their water-soluble and their transmembrane forms. Crystal structures of the water-soluble forms of a 12-helical pore and a 16-helical pore closely match the computational design models. Patch-clamp electrophysiology experiments show that, when expressed in insect cells, the transmembrane form of the 12-helix pore enables the passage of ions across the membrane with high selectivity for potassium over sodium; ion passage is blocked by specific chemical modification at the pore entrance. When incorporated into liposomes using in vitro protein synthesis, the transmembrane form of the 16-helix pore-but not the 12-helix pore-enables the passage of biotinylated Alexa Fluor 488. A cryo-electron microscopy structure of the 16-helix transmembrane pore closely matches the design model. The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer channels and pores for a wide variety of applications.
A silicon-based micro direct methanol fuel cell (μDMFC) for portable applications has been developed and its electrochemical characterization carried out in this study. Anode and cathode flowfields ...with channel and rib width of 750
μm and channel depth of 400
μm were fabricated on Si wafers using the microelectromechanical system (MEMS) technology. A membrane-electrode assembly (MEA) was specially fabricated to mitigate methanol crossover. This MEA features a modified anode backing structure in which a compact microporous layer is added to create an additional barrier to methanol transport thereby reducing the rate of methanol crossing over the polymer membrane. The cell with the active area of 1.625
cm
2 was assembled by sandwiching the MEA between two micro-fabricated Si wafers. Extensive cell polarization testing demonstrated a maximum power density of 50
mW/cm
2 using 2
M methanol feed at 60
°C. When the cell was operated at room temperature, the maximum power density was shown to be about 16
mW/cm
2 with both 2 and 4
M methanol feed. It was further found that the present μDMFC still produced reasonable performance under 8
M methanol solution at room temperature.
We review the thermal characteristics of all-metallic sandwich structures with two dimensional prismatic and truss cores. Results are presented based on measurements in conjunction with analytical ...modeling and numerical simulation. The periodic nature of these core structures allows derivation of the macroscopic quantities of interest—namely, the overall Nusselt number and friction factor—by means of correlations derived at the unit cell level. A fin analogy model is used to bridge length scales. Various measurements and simulations are used to examine the robustness of this approach and the limitations discussed. Topological preferences are addressed in terms scaling relations obtained with three dimensionless parameters—friction factor, Nusselt number and Reynolds number—expressed both at the panel and the cell levels. Countervailing influences of topology on the Nusselt number and friction factor are found. Case studies are presented to illustrate that the topology preference is highly application dependent.
Specificity of interactions between two DNA strands, or between protein and DNA, is often achieved by varying bases or side chains coming off the DNA or protein backbone-for example, the bases ...participating in Watson-Crick pairing in the double helix, or the side chains contacting DNA in TALEN-DNA complexes. By contrast, specificity of protein-protein interactions usually involves backbone shape complementarity
, which is less modular and hence harder to generalize. Coiled-coil heterodimers are an exception, but the restricted geometry of interactions across the heterodimer interface (primarily at the heptad a and d positions
) limits the number of orthogonal pairs that can be created simply by varying side-chain interactions
. Here we show that protein-protein interaction specificity can be achieved using extensive and modular side-chain hydrogen-bond networks. We used the Crick generating equations
to produce millions of four-helix backbones with varying degrees of supercoiling around a central axis, identified those accommodating extensive hydrogen-bond networks, and used Rosetta to connect pairs of helices with short loops and to optimize the remainder of the sequence. Of 97 such designs expressed in Escherichia coli, 65 formed constitutive heterodimers, and the crystal structures of four designs were in close agreement with the computational models and confirmed the designed hydrogen-bond networks. In cells, six heterodimers were fully orthogonal, and in vitro-following mixing of 32 chains from 16 heterodimer designs, denaturation in 5 M guanidine hydrochloride and reannealing-almost all of the interactions observed by native mass spectrometry were between the designed cognate pairs. The ability to design orthogonal protein heterodimers should enable sophisticated protein-based control logic for synthetic biology, and illustrates that nature has not fully explored the possibilities for programmable biomolecular interaction modalities.
In response to insect attack, plants release complex blends of volatile compounds. These volatiles serve as foraging cues for herbivores, predators and parasitoids, leading to plant‐mediated ...interactions within and between trophic levels. Hence, plant volatiles may be important determinants of insect community composition. To test this, we created rice lines that are impaired in the emission of two major signals, S‐linalool and (E)‐β‐caryophyllene. We found that inducible S‐linalool attracted predators and parasitoids as well as chewing herbivores, but repelled the rice brown planthopper Nilaparvata lugens, a major pest. The constitutively produced (E)‐β‐caryophyllene on the other hand attracted both parasitoids and planthoppers, resulting in an increased herbivore load. Thus, silencing either signal resulted in specific insect assemblages in the field, highlighting the importance of plant volatiles in determining insect community structures. Moreover, the results imply that the manipulation of volatile emissions in crops has great potential for the control of pest populations.
PDF
