One-pot thiol–amine bioconjugation to maleimides: simultaneous stabilisation and dual functionalisation

Maleimide chemistry is widely used in the site-selective modification of proteins. However, hydrolysis of the resultant thiosuccinimides is required to provide robust stability to the bioconjugates. Herein, we present an alternative approach that affords simultaneous stabilisation and dual functionalisation in a one pot fashion. By consecutive conjugation of a thiol and an amine to dibromomaleimides, we show that aminothiomaleimides can be generated extremely efficiently. Furthermore, the amine serves to deactivate the electrophilicity of the maleimide, precluding further reactivity and hence generating stable conjugates. We have applied this conjugation strategy to peptides and proteins to generate stabilised trifunctional conjugates. We propose that this stabilisation-dual modification strategy could have widespread use in the generation of diverse conjugates

A Clinical and Epidemiological Investigation of the First Reported Human Infection With the Zoonotic Parasite Trypanosoma evansi in Southeast Asia

Background. Trypanosoma is a genus of unicellular parasitic flagellate protozoa. Trypanosoma brucei species and Trypanosoma cruzi are the major agents of human trypanosomiasis; other Trypanosoma species can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma. Methods. Microscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source. Results. PCR amplification and serological testing identified the infecting species as Trypanosoma evansi. Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive for T. evansi. Conclusions. We report the first laboratory-confirmed case of T. evansi in a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden of T. evansi in local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases

Large-scale Bright Fronts in the Solar Corona: A Review of "EIT waves"

``EIT waves" are large-scale coronal bright fronts (CBFs) that were first observed in 195 \AA\ images obtained using the Extreme-ultraviolet Imaging Telescope (EIT) onboard the \emph{Solar and Heliospheric Observatory (SOHO)}. Commonly called ``EIT waves", CBFs typically appear as diffuse fronts that propagate pseudo-radially across the solar disk at velocities of 100--700 km s$^{-1}$ with front widths of 50-100 Mm. As their speed is greater than the quiet coronal sound speed ($c_s\leq$200 km s$^{-1}$) and comparable to the local Alfv\'{e}n speed ($v_A\leq$1000 km s$^{-1}$), they were initially interpreted as fast-mode magnetoacoustic waves ($v_{f}=(c_s^2 + v_A^2)^{1/2}$). Their propagation is now known to be modified by regions where the magnetosonic sound speed varies, such as active regions and coronal holes, but there is also evidence for stationary CBFs at coronal hole boundaries. The latter has led to the suggestion that they may be a manifestation of a processes such as Joule heating or magnetic reconnection, rather than a wave-related phenomena. While the general morphological and kinematic properties of CBFs and their association with coronal mass ejections have now been well described, there are many questions regarding their excitation and propagation. In particular, the theoretical interpretation of these enigmatic events as magnetohydrodynamic waves or due to changes in magnetic topology remains the topic of much debate.Comment: 34 pages, 19 figure

On the Nature and Genesis of EUV Waves: A Synthesis of Observations from SOHO, STEREO, SDO, and Hinode

A major, albeit serendipitous, discovery of the SOlar and Heliospheric Observatory mission was the observation by the Extreme Ultraviolet Telescope (EIT) of large-scale Extreme Ultraviolet (EUV) intensity fronts propagating over a significant fraction of the Sun's surface. These so-called EIT or EUV waves are associated with eruptive phenomena and have been studied intensely. However, their wave nature has been challenged by non-wave (or pseudo-wave) interpretations and the subject remains under debate. A string of recent solar missions has provided a wealth of detailed EUV observations of these waves bringing us closer to resolving their nature. With this review, we gather the current state-of-art knowledge in the field and synthesize it into a picture of an EUV wave driven by the lateral expansion of the CME. This picture can account for both wave and pseudo-wave interpretations of the observations, thus resolving the controversy over the nature of EUV waves to a large degree but not completely. We close with a discussion of several remaining open questions in the field of EUV waves research.Comment: Solar Physics, Special Issue "The Sun in 360",2012, accepted for publicatio

Melting of tantalum at high pressure determined by angle dispersive x-ray diffraction in a double-sided laser-heated diamond-anvil cell

The high pressure and high temperature phase diagram of Ta has been studied in a laser-heated diamond-anvil cell (DAC) using x-ray diffraction measurements up to 52 GPa and 3800 K. The melting was observed at nine different pressures, being the melting temperature in good agreement with previous laser-heated DAC experiments, but in contradiction with several theoretical calculations and previous piston-cylinder apparatus experiments. A small slope for the melting curve of Ta is estimated (dTm/dP = 24 K/GPa at 1 bar) and a possible explanation for this behaviour is given. Finally, a P-V-T equation of states is obtained, being the temperature dependence of the thermal expansion coefficient and the bulk modulus estimated.Comment: 31 pages, 8 figures, to appear in J.Phys.:Cond.Matte

An NLO QCD analysis of inclusive cross-section and jet-production data from the ZEUS experiment

The ZEUS inclusive differential cross-section data from HERA, for charged and neutral current processes taken with e+ and e- beams, together with differential cross-section data on inclusive jet production in e+ p scattering and dijet production in \gamma p scattering, have been used in a new NLO QCD analysis to extract the parton distribution functions of the proton. The input of jet data constrains the gluon and allows an accurate extraction of \alpha_s(M_Z) at NLO; \alpha_s(M_Z) = 0.1183 \pm 0.0028(exp.) \pm 0.0008(model) An additional uncertainty from the choice of scales is estimated as \pm 0.005. This is the first extraction of \alpha_s(M_Z) from HERA data alone.Comment: 37 pages, 14 figures, to be submitted to EPJC. PDFs available at http://durpdg.dur.ac.uk/hepdata in LHAPDFv