Development of an integrated chromatographic system for ω-transaminase-IMER characterization useful for flow-chemistry applications.

An integrated chromatographic system was developed to rapidly investigate the biocatalytic properties of ω-transaminases useful for the synthesis of chiral amines. ATA-117, an (R)-selective ω-transaminase was selected as a proof of concept. The enzyme was purified and covalently immobilized on an epoxy monolithic silica support to create an immobilized enzyme reactor (IMER). Reactor efficiency was evaluated in the conversion of a model substrate. The IMER was coupled through a switching valve to an achiral analytical column for separation and quantitation of the transamination products. The best conditions of the transaminase-catalyzed bioconversion were optimized by a design of experiments (DoE) approach. The production of (R)-1-(4-methoxyphenyl)propan-2-amine and (R)-1-methyl-3-phenylpropylamine, intermediates for the synthesis of the bronchodilator formoterol and the antihypertensive dilevalol respectively, was achieved in the presence of different amino donors. The enantiomeric excess (ee) was determined off-line by developing a derivatization procedure using Nα-(2,4-dinitro-5-fluorophenyl)-L-alaninamide reagent. The most satisfactory conversion yields were 60% for (R)-1-(4-methoxyphenyl)propan-2-amine and 29% for (R)-1-methyl-3-phenylpropylamine, using isopropylamine as amino donor. The enantiomeric excess of the reactions were 84%R and 99%R, respectively.

SIFTING FOR SAPPHIRES: SYSTEMATIC SELECTION OF TIDAL DISRUPTION EVENTS IN iPTF.

We present results from a systematic selection of tidal disruption events (TDEs) in a wide-area (4800 deg2), g + R band, Intermediate Palomar Transient Factory (iPTF) experiment. Our selection targets typical optically-selected TDEs: bright (>60% flux increase) and blue transients residing in the center of red galaxies. Using photometric selection criteria to down-select from a total of 493 nuclear transients to a sample of 26 sources, we then use follow-up UV imaging with the Neil Gehrels Swift Telescope, ground-based optical spectroscopy, and light curve fitting to classify them as 14 Type Ia supernovae (SNe Ia), 9 highly variable active galactic nuclei (AGNs), 2 confirmed TDEs, and 1 potential core-collapse supernova. We find it possible to filter AGNs by employing a more stringent transient color cut (g - r < -0.2 mag); further, UV imaging is the best discriminator for filtering SNe, since SNe Ia can appear as blue, optically, as TDEs in their early phases. However, when UV-optical color is unavailable, higher precision astrometry can also effectively reduce SNe contamination in the optical. Our most stringent optical photometric selection criteria yields a 4.5:1 contamination rate, allowing for a manageable number of TDE candidates for complete spectroscopic follow-up and real-time classification in the ZTF era. We measure a TDE per galaxy rate of 1.7 - 1.3 + 2.9 × 10 - 4 gal - 1 yr - 1 (90% CL in Poisson statistics). This does not account for TDEs outside our selection criteria, thus may not reflect the total TDE population, which is yet to be fully mapped.

iPTF16geu: A multiply imaged, gravitationally lensed type Ia supernova.

We report the discovery of a multiply imaged, gravitationally lensed type Ia supernova, iPTF16geu (SN 2016geu), at redshift z = 0.409. This phenomenon was identified because the light from the stellar explosion was magnified more than 50 times by the curvature of space around matter in an intervening galaxy. We used high-spatial-resolution observations to resolve four images of the lensed supernova, approximately 0.3 arc seconds from the center of the foreground galaxy. The observations probe a physical scale of ~1 kiloparsec, smaller than is typical in other studies of extragalactic gravitational lensing. The large magnification and symmetric image configuration imply close alignment between the lines of sight to the supernova and to the lens. The relative magnifications of the four images provide evidence for substructures in the lensing galaxy.

A radio-pulsing white dwarf binary star.

White dwarfs are compact stars, similar in size to Earth but approximately 200,000 times more massive. Isolated white dwarfs emit most of their power from ultraviolet to near-infrared wavelengths, but when in close orbits with less dense stars, white dwarfs can strip material from their companions and the resulting mass transfer can generate atomic line and X-ray emission, as well as near- and mid-infrared radiation if the white dwarf is magnetic. However, even in binaries, white dwarfs are rarely detected at far-infrared or radio frequencies. Here we report the discovery of a white dwarf/cool star binary that emits from X-ray to radio wavelengths. The star, AR Scorpii (henceforth AR Sco), was classified in the early 1970s as a δ-Scuti star, a common variety of periodic variable star. Our observations reveal instead a 3.56-hour period close binary, pulsing in brightness on a period of 1.97 minutes. The pulses are so intense that AR Sco's optical flux can increase by a factor of four within 30 seconds, and they are also detectable at radio frequencies. They reflect the spin of a magnetic white dwarf, which we find to be slowing down on a 107-year timescale. The spin-down power is an order of magnitude larger than that seen in electromagnetic radiation, which, together with an absence of obvious signs of accretion, suggests that AR Sco is primarily spin-powered. Although the pulsations are driven by the white dwarf's spin, they mainly originate from the cool star. AR Sco's broadband spectrum is characteristic of synchrotron radiation, requiring relativistic electrons. These must either originate from near the white dwarf or be generated in situ at the M star through direct interaction with the white dwarf's magnetosphere.

Uranium Hydridoborates: Synthesis, Magnetism, and X-ray/Neutron Diffraction Structures.

While uranium hydridoborate complexes containing the [BH4](-) moiety have been well-known in the literature for many years, species with functionalized borate centers remained considerably rare. We were now able to prepare several uranium hydridoborates (1-4) with amino-substituted borate moieties with high selectivity by smooth reaction of [Cp*2UMe2] (Cp* = C5Me5) and [Cp'2UMe2] (Cp' = 1,2,4-tBu3C5H2) with the aminoborane H2BN(SiMe3)2. A combination of nuclear magnetic resonance spectroscopy, deuteration experiments, magnetic SQUID measurements, and X-ray/neutron diffraction studies was used to verify the anticipated molecular structures and oxidation states of 1-4 and helped to establish a linear tridentate coordination mode of the borate anions.

Stellar dynamics. The fastest unbound star in our Galaxy ejected by a thermonuclear supernova.

Hypervelocity stars (HVSs) travel with velocities so high that they exceed the escape velocity of the Galaxy. Several acceleration mechanisms have been discussed. Only one HVS (US 708, HVS 2) is a compact helium star. Here we present a spectroscopic and kinematic analysis of US 708. Traveling with a velocity of ~1200 kilometers per second, it is the fastest unbound star in our Galaxy. In reconstructing its trajectory, the Galactic center becomes very unlikely as an origin, which is hardly consistent with the most favored ejection mechanism for the other HVSs. Furthermore, we detected that US 708 is a fast rotator. According to our binary evolution model, it was spun-up by tidal interaction in a close binary and is likely to be the ejected donor remnant of a thermonuclear supernova.

Generation of 1,2-azaboretidines via reduction of ADC borane adducts.

Reaction of the acyclic (diamino)carbene (ADC) :C(NiPr2)2 (1) with different dihaloboranes of the type RBX2 (R = Mes, Dur; X = Cl, Br) smoothly afforded a novel class of ADC-stabilized borane adducts. For MesBBr2 however, the reaction did not stop at the adduct level, but an uncommon rearrangement process occurred, which eventually resulted in the formation of a 5-membered boracycle after elimination of mesitylene. Chemical reduction of the ADC borane adducts by KC8 selectively yielded air stable 1,2-azaboretidines. Detailed DFT studies suggest a reduction mechanism involving a highly reactive borylene intermediate, which is converted into the boracycles via a rearrangement/C-H activation sequence.

[Peripheral facial palsy after embolization of a dural arteriovenous fistula with Onyx®]. / Periphere Fazialisparese nach Onyx®-Embolisation einer duralen arteriovenösen Fistel.

Dural arteriovenous fistulas (DAVF) are intracranial vascular malformations which can cause severe complications, such as intracranial bleeding and neurological deficits. We report the case of a patient presenting with pulsatile tinnitus caused by a DAVF. The DAVF was endovascularly treated including transarterial embolization with the liquid embolic agent Onyx®. The fistula and tinnitus were cured successfully, however, the rare complication of facial nerve palsy due to reflux of Onyx® into the vasa nervorum occurred. This could be confirmed directly during surgery and by histological analysis.

[Persistent extramedullary plasmacytoma of the nose after radiotherapy]. / Persistierendes extramedulläres Plasmozytom der Nase nach Radiatio.

Solitary extramedullary plasmacytomas of the head and neck are rare tumors. These tumors are known to be very radiosensitive and therefore radiotherapy is often considered as the treatment of choice. We present the case of a solitary extramedullary plasmacytoma of the nose which did not respond sufficiently to radiotherapy, i.e. persistence of the tumor led to surgical treatment. After a discussion of the recent literature we primarily recommend the excision of this type of tumor whenever possible.

"Indirect" acute islet allograft destruction in nonobese diabetic mice is independent of donor major histocompatibility complex and requires host B lymphocytes.

Islet allografts are destroyed rapidly in spontaneously diabetic nonobese diabetic (NOD) mice. However, whether this process is more similar to conventional allograft immunity, islet-specific autoimmune pathogenesis, or both remains controversial. In particular, we sought to determine whether C57BI/6 donor islet major histocompatibility complex (MHC) class I or class II expression was required for islet allograft destruction in autoimmune prone NOD mice versus non-autoimmune-prone BALB/c mice. Results show that islet allografts deficient in both MHC I and II are uniformly accepted in BALB/c mice. In sharp contrast, such MHC-deficient allografts were destroyed acutely in spontaneously diabetic NOD mice. Such donor MHC-independent rejection implicates "indirect" (host MHC-restricted) immunity as a pathway responsible for islet injury. To determine whether host NOD B lymphocytes could contribute to indirect graft recognition, wild-type and MHC I/II-deficient allografts were grafted into B-lymphocyte-deficient (microMT) NOD mice. Whereas wild-type NOD mice could reject MHC-I/II-deficient islet allografts, such grafts were all accepted in B-lymphocyte-deficient NOD mice. Taken together, these results indicate that NOD mice are capable of vigorous donor MHC-independent islet allograft rejection not found in non-autoimmune-prone recipients. Importantly, B lymphocytes may play a key role as antigen-presenting cells in this exuberant host 'indirect' response found in NOD mice.