Experimental linear-optics simulation of multipartite non-locality in the ground state of a quantum Ising ring

Critical phenomena involve structural changes in the correlations of its constituents. Such changes can be reproduced and characterized in quantum simulators able to tackle medium-to-large-size systems. We demonstrate these concepts by engineering the ground state of a three-spin Ising ring by using a pair of entangled photons. The effect of a simulated magnetic field, leading to a critical modification of the correlations within the ring, is analysed by studying two- and three-spin entanglement. In particular, we connect the violation of a multipartite Bell inequality with the amount of tripartite entanglement in our ring.

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside re- verse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities consid- ered sufficient to maintain vaginal fluid concentrations at levels 82–860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal trans- mission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median con- centrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo–in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mecha- nism rather than the expected diffusion-controlled mechanism.

THE SYNTHESIS OF BRIDGED-RING CARBOCYCLES AND HETEROCYCLES VIA PALLADIUM CATALYZED REGIOSPECIFIC CYCLIZATION REACTIONS

A catalyst system comprising 10 mol % (Pd(OAc) and 20 mol % PPh3 effects the cyclisation of aryl halides onto proximate alkenes via 5-, 6-, and 7-exo-trig, and 7-endo-trig processes giving a variety of bridged-ring carbo- and hetero-cycles in excellent yield. Double bond isomerisation in the product is rarely encountered and may be suppressed by the addition of Tl(1) salts. One example of diastereospecific bis-cyclisation is given and the crystal structure of 1-aza-2-sulphonyl-3,4-benzobicyclo[3.2.1]nona-6-ene is reported.

A Temperature-Monitoring Vaginal Ring for Measuring Adherence

Background

Product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.

Methods

A silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger has been developed and tested in vitro and in cynomolgus macaques for its potential to continuously monitor environmental temperature and accurately determine episodes of ring insertion and removal.

Results

In vitro studies demonstrated that DST nano-T temperature loggers encapsulated in medical grade silicone elastomer were able to accurately and continuously measure environmental temperature. The devices responded quickly to temperature changes despite being embedded in different thickness of silicone elastomer. Prototype vaginal rings measured higher temperatures compared with a subcutaneously implanted device, showed high sensitivity to diurnal fluctuations in vaginal temperature, and accurately detected periods of ring removal when tested in macaques.

Conclusions

Vaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials.

On the halogenation of N(1),N(2)-di-t-Boc-5-hydroxy-piperazic acid esters and the conformational preferences of their 5-halo-piperazic acid products. The importance of A1,3 rotameric-strain in determining N(2)-acyl piperazic acid ring conformation

In this Letter, an unambiguous synthetic strategy is reported for the preparation of enantiomerically purecis-5-halo-piperazic acid derivatives in single diastereoisomer form. Contrary to the recent report by Shin and co-workers (Chem. Lett. 2001, 1172), in which it is claimed that the Ph₃P and N-chlorosuccinimide (NCS)-mediated chlorination of (3R,5S)-trans-N(1),N(2)-di-t-Boc-5-hydroxy-piperazic acid derivative 1proceeds with retention of configuration at C(5) to give 2, we now show that this and related Ph₃P-mediated halogenations all occur with S_N2 inversion at the alcohol center, as is customary for such reactions. Specifically, we demonstrate that the (3R,5S)-trans-5-Cl-piperazic acid derivative 2 claimed by Shin and co-workers (Chem. Lett. 2001, 1172) is in actual fact the chlorinated (3S,5R)-enantiomer 6, which must have been prepared from the cis-(3S,5S)-alcohol 3, a molecule whose synthesis is not formally described in the Shin paper. We further show here that the cis-(3R,5R)-5-Cl-Piz 13 claimed by Shin and co-workers inChem. Lett. 2001, 1172, is also (3S,5R)-trans-5-Cl-Piz 6. Authentic 13 has now been synthesized by us, for the very first time, here. Since Lindsley and Kennedy have recently utilized the now invalid Shin and co-workers’ retentive Ph₃P/NCS chlorination procedure on 1 in their synthetic approach to piperazimycin A (Tetrahedron Lett. 2010, 51, 2493), it follows that their claimed 5-Cl-Piz-containing dipeptide 25 probably has the alternate structure 26, where the 5-Cl-Piz residue has a 3,5-cis-configuration. The aforementioned stereochemical misassignments appear to have come from a mix-up of starting materials by Shin and co-workers (Chem. Lett. 2001, 1172), and an under-appreciation of the various steric and conformational effects that operate in N(2)-acylated piperazic acid systems, most especially rotameric A^1,3-strain. The latter has now been unambiguously delineated and defined here under the banner of the A^1,3-rotamer effect.

Deregulation of genes related to iron and mitochondrial metabolism in refractory anemia with ring sideroblasts

The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified.

Split Ring FSS Reflectarray with Spiral Phase Distribution

The paper reports of a flat spiral phase plate structure based on reflectarray frequency selective surface, FSS, technology for the generation of helical far-field radiation patterns with circular polarization (CP) properties. Double split ring slot FSS is used as a means for adjusting the phase across the reflectarray. Simulations presented demonstrate generation of reflected helical beams at 10 GHz for CP wave incident on the structure. The far-field measurements are in a good agreement with the simulations and demonstrate a null of -11dB in the centre of the radiation pattern attributed to the helical wavefront.

Sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP from a rod insert vaginal ring

Administration of biomacromolecular drugs in effective quantities from conventional vaginal rings is hampered by poor drug permeability in the polymers from which rings are commonly constructed. Here, we report the formulation development and testing of rod insert rings for sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP (JNJ peptide), both of which have potential as HIV microbicides. Rod inserts were prepared comprising antiviral peptides T-1249 or JNJ peptide in combination with a hydrophilic excipient (sodium chloride, sodium glutamate, lactose or zinc acetate) dispersed at different loadings within a medical grade silicone elastomer. The inserts were tested for weight change and swelling when immersed in simulated vaginal fluid (SVF). Dye migration into the inserts was also assessed visually over 28 days. In vitro release of T-1249 and JNJ peptide from rings containing various insert types was tested. Weight change and degree of swelling of rods immersed in SVF was dependent on the type and concentration of excipient present. The rods displayed the following rank order in terms of weight change: sodium glutamate > zinc acetate ≈ sodium chloride > lactose. The weight change and degree of swelling of the inserts did not correlate with the level of dye uptake observed. In vitro release of T-1249 was improved through addition of lactose, sodium chloride and sodium glutamate, while release of JNJ peptide was improved through addition of sodium chloride or sodium glutamate. Sustained release of hydrophobic peptides can be achieved using a rod insert ring design formulated to include a hydrophilic excipient. Release rates were dependent upon the type of excipient used. The degree of release improvement with different inserts partially reflects their ability to imbibe surrounding fluid and swell in aqueous environments.

ALMA Observations of a Gap and a Ring in the Protoplanetary Disk around TW Hya

We report the first detection of a gap and a ring in dust continuum emission from the protoplanetary disk around TW Hya, using the Atacama Large Millimeter/Submillimeter Array. The gap and ring are located at 25 and 41 AU from the central star, respectively, and are associated with the CO snowline at ~ 30AU. The gap width and depth are 15AU at the maximum and 23% at the minimum, respectively, regarding that the observations are limited to an angular resolution of ~ 15AU. In addition, we detect a decrement in CO line emission down to ~ 10AU, indicating freeze-out of gas-phase CO onto grain surfaces and possible subsequent surface reactions to form larger molecules. According to theoretical studies, the gap could be caused by gravitational interaction between the disk gas and a planet with a mass less than super-Neptune (2 Neptune mass), or result from destruction of large dust aggregates due to the sintering of CO ice.

Equivalent Circuit Model of Twisted Split Ring Frequency Selective Surfaces

This paper proposes a wideband equivalent circuit model for a twisted split ring frequency selective surface (FSS). Such surfaces can be used for modelling and design of polarisation sensitive surfaces such as circularly polarized selective surfaces as well as structures with asymmetric transmission. The proposed model is based extraction of equivalent circuit parameters from a single split ring (SRR) FSS and magnetic coupling from periodic eigenmode analysis of the coupled SRR. The resulting equivalent circuit model demonstrates excellent agreement with full-wave simulations.