502 research outputs found
Synthesis and biological evaluation of benzodiazepines containing a pentafluorosulfanyl group
The widely used pentafluorosulfanyl group (SF5) was deployed as a bioisosteric replacement for a chloro-group in the benzodiazepine diazepam (Valiumâą). Reaction of 2-amino-5-pentafluorosulfanyl-benzophenone with chloroacetyl chloride followed by hexamethylenetetramine, in the presence of ammonia, led to 7-sulfurpentafluoro-5-phenyl-1H-benzo[1,4]diazepin-2(3H)-one (2c). The latter was able to undergo a Pd-catalysed ortho-arylation, demonstrating that these highly fluorinated benzodiazepines can be further modified to form more complicated scaffolds. The replacement of Cl by the SF5 group, led to a loss of potency for potentiating GABAA receptor activation, most likely because of a lost ligand interaction with His102 in the GABAA receptor α subunit.
Dedicated to Professor Jonathan Williams, an inspirational and humble pioneer, a colleague and mentor in chemistry
Proof of concept of faecal egg nematode counting as a practical means of veterinary engagement with planned livestock health management in a lower income country
Abstract Background The wellbeing and livelihood of farmers in impoverished regions of the world is intrinsically linked to the health and welfare of their livestock; hence improved animal health is a pragmatic component of poverty alleviation. Prerequisite knowledge and understanding of the animal health challenges facing cattle keepers in Malawi is constrained by the lack of veterinary infrastructure, which inevitably accompanies under-resourced rural development in a poor country. Methods We collaborated with public and private paraveterinary services to locate 62 village Zebu calves and 60 dairy co-operative calves dispersed over a wide geographical area. All calves were visited twice about 2 to 3Â weeks apart, when they were clinically examined and faecal samples were collected. The calves were treated with 7.5Â mg/kg of a locally-available albendazole drench on the first visit, and pre- and post- treatment trichostrongyle and Toxocara faecal egg counts were performed using a modified McMaster method. Results Our clinical findings point towards a generally poor level of animal health, implying a role of ticks and tick-transmitted diseases in village calves and need for improvement in neonatal calf husbandry in the dairy co-operative holdings. High faecal trichostrongyle egg counts were not intuitive, based on our interpretation of the animal management information that was provided. This shows the need for better understanding of nematode parasite epidemiology within the context of local husbandry and environmental conditions. The albendazole anthelmintic was effective against Toxocara, while efficacy against trichostrongyle nematodes was poor in both village and dairy co-operative calves, demonstrating the need for further research to inform sustainable drug use. Conclusions Here we describe the potential value of faecal nematode egg counting as a platform for communicating with and gaining access to cattle keepers and their animals, respectively, in southern Malawi, with the aim of providing informative background knowledge and understanding that may aid in the establishment of effective veterinary services in an under-resourced community
Spin-photon interface and spin-controlled photon switching in a nanobeam waveguide
Access to the electron spin is at the heart of many protocols for integrated
and distributed quantum-information processing [1-4]. For instance, interfacing
the spin-state of an electron and a photon can be utilized to perform quantum
gates between photons [2,5] or to entangle remote spin states [6-9].
Ultimately, a quantum network of entangled spins constitutes a new paradigm in
quantum optics [1]. Towards this goal, an integrated spin-photon interface
would be a major leap forward. Here we demonstrate an efficient and optically
programmable interface between the spin of an electron in a quantum dot and
photons in a nanophotonic waveguide. The spin can be deterministically prepared
with a fidelity of 96\%. Subsequently the system is used to implement a
"single-spin photonic switch", where the spin state of the electron directs the
flow of photons through the waveguide. The spin-photon interface may enable
on-chip photon-photon gates [2], single-photon transistors [10], and efficient
photonic cluster state generation [11]
The formation of professional identity in medical students: considerations for educators
<b>Context</b> Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity â ways of being and relating in professional contexts.<p></p>
<b>Objectives</b> This article conceptualises the processes underlying the formation and maintenance of medical studentsâ professional identity drawing on concepts from social psychology.<p></p>
<b>Implications</b> A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.<p></p>
<b>Conclusions</b> Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education
The VIMOS VLT Deep Survey: Evolution of the non-linear galaxy bias up to z=1.5
We present the first measurements of the Probability Distribution Function
(PDF) of galaxy fluctuations in the VIMOS-VLT Deep Survey (VVDS) cone, covering
0.4x0.4 deg between 0.4<z<1.5. The second moment of the PDF, i.e. the rms
fluctuations of the galaxy density field, is with good approximation constant
over the full redshift baseline investigated: we find that, in redshift space,
sigma_8 for galaxies brighter than M=-20+5log h has a mean value of 0.94\pm0.07
in the redshift interval 0.7<z<1.5. The third moment, i.e. the skewness,
increases with cosmic time: we find that the probability of having underdense
regions is greater at z~0.7 than it was at z~1.5. By comparing the PDF of
galaxy density contrasts with the theoretically predicted PDF of mass
fluctuations we infer the redshift-, density-, and scale-dependence of the
biasing function b(z, \delta, R) between galaxy and matter overdensities up to
redshift z=1.5. Our results can be summarized as follows: i) the galaxy bias is
an increasing function of redshift: evolution is marginal up to z~0.8 and more
pronounced for z>0.8; ii) the formation of bright galaxies is inhibited below a
characteristic mass-overdensity threshold whose amplitude increases with
redshift and luminosity; iii) the biasing function is non linear in all the
redshift bins investigated with non-linear effects of the order of a few to 10%
on scales >5Mpc.Comment: 30 pages, 17 figs, Accepted by A&
Synthesis and solid-state characterisation of 4-substituted methylidene oxindoles
Background
4-substituted methylidene oxindoles are pharmacologically important. Detailed analysis and comparison of all the interactions present in crystal structures is necessary to understand how these structures arise. The XPac procedure allows comparison of complete crystal structures of related families of compounds to identify assemblies that are mainly the result of close-packing as well as networks of directed interactions.
Results
Five 4-substituted methylidene oxindoles have been synthesized by the Knoevenagel condensation of oxindole with para-substituted aromatic aldehydes and were characterized in the solid state by x-ray crystallography. Hence, the structures of (3E)-3-(4-Bromobenzylidene)-1,3-dihydro-2H-indol-2-one, 3a, (3E)-3-(4-Chlorobenzylidene)-1,3-dihydro-2H-indol-2-one, 3b, (3E)-3-(4-Methoxybenzylidene)-1,3-dihydro-2H-indol-2-one, 3c, (3E)-3-(4-Methylbenzylidene)-1,3-dihydro-2H-indol-2-one, 3d and (3E)-3-(4-Nitrobenzylidene)-1,3-dihydro-2H-indol-2-one, 3e, were elucidated using single crystal X-ray crystallography.
Conclusions
A hydrogen bonded dimer molecular assembly or supramolecular construct was identified in all the crystal structures examined along with a further four 1D supramolecular constructs which were common to at least two of the family of structures studied. The 1D supramolecular constructs indicate that once the obvious strong interaction is satisfied to form hydrogen bonded dimer it is the conventionally weaker interactions, such as steric bulk and edge-to-face interactions which compete to influence the final structure formation
Bayesian analysis of cosmic structures
We revise the Bayesian inference steps required to analyse the cosmological
large-scale structure. Here we make special emphasis in the complications which
arise due to the non-Gaussian character of the galaxy and matter distribution.
In particular we investigate the advantages and limitations of the
Poisson-lognormal model and discuss how to extend this work. With the lognormal
prior using the Hamiltonian sampling technique and on scales of about 4 h^{-1}
Mpc we find that the over-dense regions are excellent reconstructed, however,
under-dense regions (void statistics) are quantitatively poorly recovered.
Contrary to the maximum a posteriori (MAP) solution which was shown to
over-estimate the density in the under-dense regions we obtain lower densities
than in N-body simulations. This is due to the fact that the MAP solution is
conservative whereas the full posterior yields samples which are consistent
with the prior statistics. The lognormal prior is not able to capture the full
non-linear regime at scales below ~ 10 h^{-1} Mpc for which higher order
correlations would be required to describe the matter statistics. However, we
confirm as it was recently shown in the context of Ly-alpha forest tomography
that the Poisson-lognormal model provides the correct two-point statistics (or
power-spectrum).Comment: 11 pages, 1 figure, report for the Astrostatistics and Data Mining
workshop, La Palma, Spain, 30 May - 3 June 2011, to appear in Springer Series
on Astrostatistic
COVID-19 and cancer registries: Learning from the first peak of the SARS-CoV-2 pandemic
The SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT-chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care
Perspectives on the chemical etiology of breast cancer.
Multiple factors, known and unknown, contribute to human breast cancer. Hereditary, hormonal, and reproductive factors are associated with risk of breast cancer. Environmental agents, including chemical carcinogens, are modifiable risk factors to which over 70% of breast cancers have been attributed. Polymorphisms of drug-metabolizing enzymes may influence risk of breast cancer from environmental chemicals, dietary agents, and endogenous steroids. The environmental factors discussed in this review include pollutants, occupational exposures, tobacco smoke, alcohol, and diet. Aromatic amines are discussed as potential mammary carcinogens, with a focus on heterocyclic amine food pyrolysis products. These compounds are excreted into the urine after consumption of meals containing cooked meats and have recently been detected in the breast milk of lactating women
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