Novel Semisynthetic Derivatives of Bile Acids as Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.

An Important task in the treatment of oncological and neurodegenerative diseases is the search for new inhibitors of DNA repair system enzymes. Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the DNA repair system enzymes involved in the removal of DNA damages caused by topoisomerase I inhibitors. Thus, reducing the activity of Tdp1 can increase the effectiveness of currently used anticancer drugs. We describe here a new class of semisynthetic small molecule Tdp1 inhibitors based on the bile acid scaffold that were originally identified by virtual screening. The influence of functional groups of bile acids (hydroxy and acetoxy groups in the steroid framework and amide fragment in the side chain) on inhibitory activity was investigated. In vitro studies demonstrate the ability of the semisynthetic derivatives to effectively inhibit Tdp1 with IC50 up to 0.29 µM. Furthermore, an excellent fit is realized for the ligands when docked into the active site of the Tdp1 enzyme

Controlling the quantum stereodynamics of ultracold bimolecular reactions

Chemical reaction rates often depend strongly on stereodynamics, namely the orientation and movement of molecules in three-dimensional space. An ultracold molecular gas, with a temperature below 1 uK, provides a highly unusual regime for chemistry, where polar molecules can easily be oriented using an external electric field and where, moreover, the motion of two colliding molecules is strictly quantized. Recently, atom-exchange reactions were observed in a trapped ultracold gas of KRb molecules. In an external electric field, these exothermic and barrierless bimolecular reactions, KRb+KRb -> K2+Rb2, occur at a rate that rises steeply with increasing dipole moment. Here we show that the quantum stereodynamics of the ultracold collisions can be exploited to suppress the bimolecular chemical reaction rate by nearly two orders of magnitude. We use an optical lattice trap to confine the fermionic polar molecules in a quasi-two-dimensional, pancake-like geometry, with the dipoles oriented along the tight confinement direction. With the combination of sufficiently tight confinement and Fermi statistics of the molecules, two polar molecules can approach each other only in a "side-by-side" collision, where the chemical reaction rate is suppressed by the repulsive dipole-dipole interaction. We show that the suppression of the bimolecular reaction rate requires quantum-state control of both the internal and external degrees of freedom of the molecules. The suppression of chemical reactions for polar molecules in a quasi-two-dimensional trap opens the way for investigation of a dipolar molecular quantum gas. Because of the strong, long-range character of the dipole-dipole interactions, such a gas brings fundamentally new abilities to quantum-gas-based studies of strongly correlated many-body physics, where quantum phase transitions and new states of matter can emerge.Comment: 19 pages, 4 figure

KAJIAN PENGARUH JENIS IKAN DAN SUHU PENGERINGAN TERHADAP KARAKTERISTIK KEMPLANG IKAN

Abstrak : Pengaruh jenis ikan dan suhu pengeringan terhadap karakteristik kemplang, sehingga dapat bermanfaat untuk meningkatkan nilai gizi,nilai ekonomisdan Teknologi Pengolahan dari p[roduk tradisiona. Rancangan percobaan yang digunakan adalah pola faktorial 3 x 3 dalam Rancangan Acak Kelompok, dengan 3 kali ulangan.Faktor pertama adalah jenis ikan (bandeng, kakap , dan nila), Faktor kedua adalah suhu p engeringan (55oC, 60oC, 65oC). Hasil penelitian menunjukkan faktor jenis dan suhu pengeringan secara mandiri hanya berpengaruh terhadap respon warna,rasa, dan kerenyahan. Sedangkan interaksi faktor jenis ikan dan suhu pengeringan berpengaruh terhadap respon kadar air, kadar protein dan volume pengembangan. Kata kunci: jenis ikan,suhu pengeringan, kemplan

Effect of Dietary Components on Larval Life History Characteristics in the Medfly (Ceratitis capitata: Diptera, Tephritidae)

Background: The ability to respond to heterogenous nutritional resources is an important factor in the adaptive radiation of insects such as the highly polyphagous Medfly. Here we examined the breadth of the Medfly’s capacity to respond to different developmental conditions, by experimentally altering diet components as a proxy for host quality and novelty. Methodology/Principal Findings: We tested responses of larval life history to diets containing protein and carbohydrate components found in and outside the natural host range of this species. A 40% reduction in the quantity of protein caused a significant increase in egg to adult mortality by 26.5%±6% in comparison to the standard baseline diet. Proteins and carbohydrates had differential effects on larval versus pupal development and survival. Addition of a novel protein source, casein (i.e. milk protein), to the diet increased larval mortality by 19.4%±3% and also lengthened the duration of larval development by 1.93±0.5 days in comparison to the standard diet. Alteration of dietary carbohydrate, by replacing the baseline starch with simple sugars, increased mortality specifically within the pupal stage (by 28.2%±8% and 26.2%±9% for glucose and maltose diets, respectively). Development in the presence of the novel carbohydrate lactose (milk sugar) was successful, though on this diet there was a decrease of 29.8±1.6 µg in mean pupal weight in comparison to pupae reared on the baseline diet. Conclusions: The results confirm that laboratory reared Medfly retain the ability to survive development through a wide range of fluctuations in the nutritional environment. We highlight new facets of the responses of different stages of holometabolous life histories to key dietary components. The results are relevant to colonisation scenarios and key to the biology of this highly invasive species

Non-equilibrium coherence dynamics in one-dimensional Bose gases

Low-dimensional systems are beautiful examples of many-body quantum physics. For one-dimensional systems the Luttinger liquid approach provides insight into universal properties. Much is known of the equilibrium state, both in the weakly and strongly interacting regime. However, it remains a challenge to probe the dynamics by which this equilibrium state is reached. Here we present a direct experimental study of the coherence dynamics in both isolated and coupled degenerate 1d Bose gases. Dynamic splitting is used to create two 1d systems in a phase coherent state. The time evolution of the coherence is revealed in local phase shifts of the subsequently observed interference patterns. Completely isolated 1d Bose gases are observed to exhibit a universal sub-exponential coherence decay in excellent agreement with recent predictions by Burkov et al. [Phys. Rev. Lett. 98, 200404 (2007)]. For two coupled 1d Bose gases the coherence factor is observed to approach a non-zero equilibrium value as predicted by a Bogoliubov approach. This coupled-system decay to finite coherence is the matter wave equivalent of phase locking two lasers by injection. The non-equilibrium dynamics of superfluids plays an important role in a wide range of physical systems, such as superconductors, quantum-Hall systems, superfluid Helium, and spin systems. Our experiments studying coherence dynamics show that 1d Bose gases are ideally suited for investigating this class of phenomena.Comment: to appear in natur

Simulations of events for the LUX-ZEPLIN (LZ) dark matter experiment

The LUX-ZEPLIN dark matter search aims to achieve a sensitivity to the WIMP-nucleon spin-independent cross-section down to (1–2)×10−12 pb at a WIMP mass of 40 GeV/c2. This paper describes the simulations framework that, along with radioactivity measurements, was used to support this projection, and also to provide mock data for validating reconstruction and analysis software. Of particular note are the event generators, which allow us to model the background radiation, and the detector response physics used in the production of raw signals, which can be converted into digitized waveforms similar to data from the operational detector. Inclusion of the detector response allows us to process simulated data using the same analysis routines as developed to process the experimental data

Seismic reflection images of a near-axis melt sill within the lower crust at the Juan de Fuca ridge

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 460 (2009): 89-93, doi:10.1038/nature08095.The oceanic crust extends over two thirds of the Earth’s solid surface and is generated along mid-ocean ridges from melts derived from the upwelling mantle. The upper and mid crust are constructed by dyking and seafloor eruptions originating from magma accumulated in mid-crustal lenses at the spreading axis, but the style of accretion of the lower oceanic crust is actively debated. Models based on geological and petrological data from ophiolites propose that the lower oceanic crust is accreted from melt sills intruded at multiple levels between the Moho transition zone (MTZ) and the mid-crustal lens, consistent with geophysical studies that suggest the presence of melt within the lower crust. However, seismic images of molten sills within the lower crust have been elusive. To date only seismic reflections from mid-crustal melt lenses and sills within the MTZ have been described, suggesting that melt is efficiently transported through the lower crust. Here we report deep crustal seismic reflections off the southern Juan de Fuca Ridge that we interpret as originating from a molten sill presently accreting the lower oceanic crust. The sill sits 5-6 km beneath the seafloor and 850-900 m above the MTZ, and it is located 1.4-3.2 km off thespreading axis. Our results provide evidence for the existence of low permeability barriers to melt migration within the lower section of modern oceanic crust forming at intermediate-to-fast spreading rates, as inferred from ophiolite studies.This research was supported by grants form the US NSF

Projected sensitivity of the LUX-ZEPLIN experiment to the 0νββ decay of Xe 136

The LUX-ZEPLIN (LZ) experiment will enable a neutrinoless double β decay search in parallel to the main science goal of discovering dark matter particle interactions. We report the expected LZ sensitivity to Xe136 neutrinoless double β decay, taking advantage of the significant (>600 kg) Xe136 mass contained within the active volume of LZ without isotopic enrichment. After 1000 live-days, the median exclusion sensitivity to the half-life of Xe136 is projected to be 1.06×1026 years (90% confidence level), similar to existing constraints. We also report the expected sensitivity of a possible subsequent dedicated exposure using 90% enrichment with Xe136 at 1.06×1027 years

Flexible Indium-Tin Oxide Crystal on Plastic Substrates Supported by Graphene Monolayer

Flexible and crystallized indium-tin oxide (ITO) thin films were successfully obtained on plastic polyethylene terephthalate (PET) films with monolayered graphene as a platform. The highly crystalline ITO (c-ITO) was first fabricated on a rigid substrate of graphene on copper foil and it was subsequently transferred onto a PET substrate by a well-established technique. Despite the plasma damage during ITO deposition, the graphene layer effectively acted as a Cu-diffusion barrier. The c-ITO/graphene/ PET electrode with the 60-nm-thick ITO exhibited a reasonable sheet resistance of similar to 45 Omega sq(-1) and a transmittance of similar to 92% at a wavelength of 550 nm. The c-ITO on the monolayered graphene support showed significant enhancement in flexibility compared with the ITO/PET film without graphene because the atomically controlled monolayered graphene acted as a mechanically robust support. The prepared flexible transparent c-ITO/graphene/PET electrode was applied as the anode in a bulk heterojunction polymer solar cell (PSC) to evaluate its performance, which was comparable with that of the commonly used c-ITO/glass electrode. These results represent important progress in the fabrication of flexible transparent electrodes for future optoelectronics applications

Magnetism and its microscopic origin in iron-based high-temperature superconductors

High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and N$\rm \acute{e}$el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic