The ferroelectric nematic phase: on the role of lateral alkyloxy chains.

The synthesis and characterisation of the 4-({[4’-nitro-(1,1'-biphenyl)−4-yl]oxy}carbonyl)phenyl 2-alkoxy-4-methoxybenzoates are reported: the 1O(m-On)PEPEBNO2 series. These materials include an additional phenyl ring compared to the extensively studied ferroelectric nematogen RM734, added to increase the liquid crystal transition temperatures. All members of the series exhibited both conventional nematic (N) phase and ferroelectric nematic (NF) phases; TNI and TNFN both decrease on increasing n, the length of the lateral alkoxy chain. The properties of this four-ring series are compared with analogous three-ring laterally substituted variants of RM734; the addition of the extra phenyl ring has a significantly more pronounced effect on the value of TNI than on TNFN. The increase in TNI may be attributed to the enhanced structural anisotropy and more favourable intermolecular interactions arising from the insertion of the phenyl ring, whereas the much weaker effect on TNFN may reflect a change in the shape of the molecule. We also report two materials with three-ring structures, the 4'-nitro-(1,1'-biphenyl)-4-yl 2-alkoxy-4-methoxybenzoates: 1O(m-On)PEBNO2 (n=1 and 2). The removal of the ester linkage between RM734 and 1O(m-O1)PEPNO2 extinguishes the NF phase and this appears to be consistent with a model in which the molecules are described in terms of a longitudinal surface charge density wave

The influence of molecular shape and electronic properties on the formation of the ferroelectric nematic phase.

The synthesis and characterisation of two series of ferroelectric nematogens based on RM734 having an additional methoxy group on the central phenyl ring are reported, the 3-methoxy-4-((4-nitrophenoxy)carbonyl)phenyl 2-alkoxy-4-alkoxybenzoates (7-m-n) and the 3-methoxy-4-((3-fluoro-4-nitro-phenoxy)carbonyl)phenyl 2-alkoxy-4-alkoxybenzoates (8-m-n). In order to compare the behaviour of these series to those of the corresponding materials that do not contain the methoxy group on the central phenyl ring, we also report the synthesis and characterisation of 4-[(4-nitrophenoxy)carbonyl] phenyl 4-methoxybenzoate (11-0-1), 4-[(3-fluoro-4-nitrophenoxy)carbonyl]phenyl 4-methoxybenzoate (12-0-1) and 4-[(3-fluoro-4-nitrophenoxy)carbonyl]phenyl 2,4-diethoxybenzoate (12-2-2). Two compounds in which a lateral ethoxy chain is attached to the central ring, 3-ethoxy-4-[(4-nitrophenoxy)carbonyl]phenyl 2,4-dimethoxybenzoate (18-2-1) and 3-ethoxy-4-[(3-fluoro-4-nitrophenoxy) carbonyl]phenyl 2,4-dimethoxybenzoate (19-2-1), are also described. The behaviour of these materials shows that the relative stabilities of the ferroelectric nematic, NF, and conventional nematic, N, phases are governed by a subtle interplay of steric and electronic factors. Furthermore, the electronic factors are better understood in terms of isolated regions of electron density rather than by a single large longitudinal dipole moment. In terms of molecular shape, to observe the NF phase it appears that the molecular structure must include one or more lateral substituents that enhance molecular biaxiality and destabilise the N phase

Multiple polar and non‐polar nematic phases.

Liquid-crystal materials exhibiting up to three nematic phases are reported. Dielectric response measurements show that while the lower temperature nematic phase has ferroelectric order and the highest temperature nematic phase is apolar, the intermediate phase has local antiferroelectric order. The modification of the molecular structure by increasing the number of lateral fluorine substituents leads to one of the materials showing a direct isotropic-ferronematic phase transition

Ferroelectric nematogens containing a methylthio group.

The synthesis and characterisation of eight nematogens containing a terminal methylthio group is reported. The compounds are based on RM734 and differ in the number and position of fluorine substituents, and in the position of the lateral methoxy substituent. Seven of these compounds exhibit a monotropic ferroelectric nematic phase, NF, including examples of NF-isotropic phase transitions. Two of the compounds show the anti-ferroelectric NX phase. Their transitional behaviour is discussed in terms of molecular shape and changes in electronic properties. Their phase behaviour is similar to that of the corresponding compounds containing a terminal methoxy group, but the methoxy terminated materials consistently show the higher transition temperatures. This is accounted for by the larger reduction in molecular shape anisotropy associated with the methylthio group, and the associated change in the electronic properties. The NX phase seen for the methylthio substituted compounds are thought to reflect the suppression of the NF phase by the methylthio group rather than any specific stabilising effect. Specific interactions between methylthio groups thought to stabilise nematic behaviour do not appear to stabilise the NF phase

Exotic and Emerging Diseases of Animals: An Internet Course for Veterinary Students

US agricultural and companion animals are very vulnerable to the introduction of exotic and emerging animal diseases (EEAD). These diseases could occur through unintentional introduction (the risk of outbreaks grows as free trade increases), could occur through the deliberate introduction of disease agents (bio-terrorism or agro-terrorism), or could emerge as new diseases. EEAD, for the purpose of this course, are defined as those animal diseases that are reportable in the US. This includes diseases on the Office international des épizooties (OIE) List A, selected diseases on List B that either are not found in the US or are reportable, and selected emerging diseases. Some of the exotic and emerging diseases are considered to be foreign animal diseases because they do not occur in the US. Others are found in the US but are under eradication programs. Some are zoonotic and must be monitored and controlled to protect human health. Many of these diseases are important causes of animal suffering and are economically very important. It is essential that veterinarians be familiar with these diseases and have access to accurate, concise information about their salient characteristics

Case report: Abomasal ulcer secondary to congenital pyloric and duodenal stenosis in a 3-day-old heifer

Abomasal ulcers, an economic concern for all calf-raising farms, are usually silent until perforation occurs, at which time management is complicated and often unrewarding. This case study describes perforating ulcer in a 3-day-old Brahman heifer, occurring secondary to a congenital narrowing of the pylorus and proximal duodenum and leading to marked abomasal distention, leakage, and eventual peritonitis and sepsis

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

A three-arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel in metastatic uveal melanoma

\ua9 2024 The AuthorsAims: The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy in metastatic UM. Pre-clinical studies support synergistic cytotoxic activity for MEK inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib and paclitaxel. Patients and methods: Seventy-seven patients with metastatic UM who had not received prior chemotherapy were randomised to selumetinib alone, or combined with paclitaxel with or without interruption in selumetinib two days before paclitaxel. The primary endpoint was progression free survival (PFS). After amendment, the combination arms were combined for analysis and the sample size adjusted to detect a hazard ratio (HR): 0.55, 80% power at 1-sided 5% significance level. Results: The median PFS in the combination arms was 4.8 months (95% CI: 3.8 - 5.6) compared with 3.4 months (2.0 - 3.9) in the selumetinib arm (HR 0.62 [90% CI 0.41 - 0.92], 1-sided p-value = 0.022). ORR was 14% and 4% in the combination and monotherapy arms respectively. Median OS was 9 months for the combination and was not significantly different from selumetinib alone (10 months) with HR of 0.98 [90% CI 0.58 - 1.66], 1-sided p-value = 0.469. Toxicity was in keeping with the known profiles of the agents involved. Conclusions: SelPac met its primary endpoint, demonstrating an improvement in PFS for combination selumetinib and paclitaxel. No improvement in OS was observed, and the modest improvement in PFS is not practice changing

Relationships of Risk Factors for Pre-Eclampsia with Patterns of Occurrence of Isolated Gestational Proteinuria during Normal Term Pregnancy

<p><b>Background:</b> Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.</p> <p><b>Methods:</b> Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.</p> <p><b>Results:</b> Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (<= 20 weeks gestation), and onset at 21-28 weeks, 29-32 weeks, 33-36 weeks and >= 37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.</p> <p><b>Conclusions:</b> Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of preeclampsia.</p&gt