A phenotypic comparison of the Romanian and French ATTRv cohorts: Glu54Gln founder pathogenic variant vs the most common variants in Western Europe.

Aim And Methods: We conducted a retrospective observational study of the ATTRv heterozygous mutation frequency, phenotype, and all-cause mortality at two cardiac amyloidosis centers in Romania and France.

Results: 291 patients were included: 26 Glu54Gln (all Romanian), 200 Val122Ile, 47 Val30Met and 18 Ser77Tyr. On diagnosis, Gu54Gln patients were younger than Val122Ile or late-onset Val30Met (median age: 46 [42-50], 76 [71-80] and 70 [61-76], respectively; p < 0.

Microstructure and crystal order during freezing of supercooled water drops.

Supercooled water droplets are widely used to study supercooled water, ice nucleation and droplet freezing. Their freezing in the atmosphere affects the dynamics and climate feedback of clouds and can accelerate cloud freezing through secondary ice production. Droplet freezing occurs at several timescales and length scales and is sufficiently stochastic to make it unlikely that two frozen drops are identical.

Awareness of Nuclear Medicine Physicians in Romania Regarding the Diagnostic of Cardiac Amyloidosis-A Survey-Based Study.

Amyloidosis is a heterogeneous group of diseases caused by the extracellular deposition of amyloid insoluble fibrils in multiple organs, resulting in various clinical manifestations. Cardiac amyloidosis (CA) occurs mainly in primary light-chain (AL) amyloidosis, hereditary transthyretin (ATTRv) amyloidosis and senile or wild-type transthyretin (ATTRwt) amyloidosis. Knowing that myocardial uptake at bone scintigraphy is an essential step in the ATTR-CA diagnostic algorithm, the level of awareness among nuclear medicine physicians (NMPs) using bone tracer scintigraphy is of great importance.

Current Challenges of Cardiac Amyloidosis Awareness among Romanian Cardiologists.

Cardiac amyloidosis (CA) is a restrictive cardiomyopathy characterized by deposition of amyloid in the myocardium and recent studies revealed it is more frequently seen than we thought. Advances in diagnosis and treatment have been made over the last few years that make it desirable to diagnose CA without delay, and that may require extra education. An online survey was conducted among cardiologists from Romania, representing the first assessment of the knowledge of CA among them, with 195 cardiologists answering the questionnaire.

Effect of X-ray free-electron laser-induced shockwaves on haemoglobin microcrystals delivered in a liquid jet.

X-ray free-electron lasers (XFELs) enable obtaining novel insights in structural biology. The recently available MHz repetition rate XFELs allow full data sets to be collected in shorter time and can also decrease sample consumption. However, the microsecond spacing of MHz XFEL pulses raises new challenges, including possible sample damage induced by shock waves that are launched by preceding pulses in the sample-carrying jet.

Multimodality imaging in cardiac amyloidosis: a primer for cardiologists.

Amyloidosis is a systemic infiltrative disease, in which unstable proteins misfold, form aggregates and amyloid fibrils which can deposit in various organs: heart, kidneys, liver, gastrointestinal tract, nervous system structures, lungs, or soft tissue. Cardiac amyloidosis (CA) diagnosis requires awareness, high level of clinical suspicion and expertise in integrating clinical, electrocardiographic, and multimodality imaging data. The overall scenario is complex and no single test emerges over the others, but different techniques are useful at various stages of the diagnostic workup.

Clinical characteristics in patients with hereditary amyloidosis with Glu54Gln transthyretin identified in the Romanian population.

Background: In Romania, 23 patients have been diagnosed with hereditary transthyretin amyloidosis (ATTRh), 18 of whom have the Glu54Gln mutation. This retrospective cohort included all patients with Glu54Gln-mutated ATTRh who were diagnosed in Romania from 2005 to 2018.

Results: Of 18 patients, 10 were symptomatic, five were asymptomatic carriers and three died during the study.

MHz data collection of a microcrystalline mixture of different jack bean proteins.

We provide a detailed description of a serial femtosecond crystallography (SFX) dataset collected at the European X-ray free-electron laser facility (EuXFEL). The EuXFEL is the first high repetition rate XFEL delivering MHz X-ray pulse trains at 10 Hz. The short spacing (<1 µs) between pulses requires fast flowing microjets for sample injection and high frame rate detectors.

Rapid sample delivery for megahertz serial crystallography at X-ray FELs.

Liquid microjets are a common means of delivering protein crystals to the focus of X-ray free-electron lasers (FELs) for serial femtosecond crystallography measurements. The high X-ray intensity in the focus initiates an explosion of the microjet and sample. With the advent of X-ray FELs with megahertz rates, the typical velocities of these jets must be increased significantly in order to replenish the damaged material in time for the subsequent measurement with the next X-ray pulse.

Megahertz data collection from protein microcrystals at an X-ray free-electron laser.

X-ray free-electron lasers (XFELs) enable novel experiments because of their high peak brilliance and femtosecond pulse duration. However, non-superconducting XFELs offer repetition rates of only 10-120 Hz, placing significant demands on beam time and sample consumption. We describe serial femtosecond crystallography experiments performed at the European XFEL, the first MHz repetition rate XFEL, delivering 1.

How Cubic Can Ice Be?

Using an X-ray laser, we investigated the crystal structure of ice formed by homogeneous ice nucleation in deeply supercooled water nanodrops (r ≈ 10 nm) at ∼225 K. The nanodrops were formed by condensation of vapor in a supersonic nozzle, and the ice was probed within 100 μs of freezing using femtosecond wide-angle X-ray scattering at the Linac Coherent Light Source free-electron X-ray laser. The X-ray diffraction spectra indicate that this ice has a metastable, predominantly cubic structure; the shape of the first ice diffraction peak suggests stacking-disordered ice with a cubicity value, χ, in the range of 0.

Erratum: Sheathless hydrodynamic positioning of buoyant drops and bubbles inside microchannels [Phys. Rev. E 84, 036302 (2011)].

This corrects the article DOI: 10.1103/PhysRevE.84.

Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers.

X-ray crystallography at X-ray free-electron laser sources is a powerful method for studying macromolecules at biologically relevant temperatures. Moreover, when combined with complementary techniques like X-ray emission spectroscopy, both global structures and chemical properties of metalloenzymes can be obtained concurrently, providing insights into the interplay between the protein structure and dynamics and the chemistry at an active site. The implementation of such a multimodal approach can be compromised by conflicting requirements to optimize each individual method.

Correction: The magnitude of lift forces acting on drops and bubbles in liquids flowing inside microchannels.

Correction for 'The magnitude of lift forces acting on drops and bubbles in liquids flowing inside microchannels' by Claudiu A. Stan et al., Lab Chip, 2013, 13, 365-376.

Structure of photosystem II and substrate binding at room temperature.

Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the MnCaO cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S to S), in which S is the dark-stable state and S is the last semi-stable state before O-O bond formation and O evolution.

Negative Pressures and Spallation in Water Drops Subjected to Nanosecond Shock Waves.

Most experimental studies of cavitation in liquid water at negative pressures reported cavitation at tensions significantly smaller than those expected for homogeneous nucleation, suggesting that achievable tensions are limited by heterogeneous cavitation. We generated tension pulses with nanosecond rise times in water by reflecting cylindrical shock waves, produced by X-ray laser pulses, at the internal surface of drops of water. Depending on the X-ray pulse energy, a range of cavitation phenomena occurred, including the rupture and detachment, or spallation, of thin liquid layers at the surface of the drop.

Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II.

We describe a concentric-flow electrokinetic injector for efficiently delivering microcrystals for serial femtosecond X-ray crystallography analysis that enables studies of challenging biological systems in their unadulterated mother liquor. We used the injector to analyze microcrystals of Geobacillus stearothermophilus thermolysin (2.2-Å structure), Thermosynechococcus elongatus photosystem II (<3-Å diffraction) and Thermus thermophilus small ribosomal subunit bound to the antibiotic paromomycin at ambient temperature (3.

Taking snapshots of photosynthetic water oxidation using femtosecond X-ray diffraction and spectroscopy.

The dioxygen we breathe is formed by light-induced oxidation of water in photosystem II. O2 formation takes place at a catalytic manganese cluster within milliseconds after the photosystem II reaction centre is excited by three single-turnover flashes. Here we present combined X-ray emission spectra and diffraction data of 2-flash (2F) and 3-flash (3F) photosystem II samples, and of a transient 3F' state (250 μs after the third flash), collected under functional conditions using an X-ray free electron laser.

The magnitude of lift forces acting on drops and bubbles in liquids flowing inside microchannels.

Hydrodynamic lift forces offer a convenient way to manipulate particles in microfluidic applications, but there is little quantitative information on how non-inertial lift mechanisms act and compete with each other in the confined space of microfluidic channels. This paper reports measurements of lift forces on nearly spherical drops and bubbles, with diameters from one quarter to one half of the width of the channel, flowing in microfluidic channels, under flow conditions characterized by particle capillary numbers Ca(P) = 0.0003-0.

Sheathless hydrodynamic positioning of buoyant drops and bubbles inside microchannels.

Particles, bubbles, and drops carried by a fluid in a confined environment such as a pipe can be subjected to hydrodynamic lift forces, i.e., forces that are perpendicular to the direction of the flow.

Externally applied electric fields up to 1.6 × 10(5) V/m do not affect the homogeneous nucleation of ice in supercooled water.

The freezing of water can initiate at electrically conducting electrodes kept at a high electric potential or at charged electrically insulating surfaces. The microscopic mechanisms of these phenomena are unknown, but they must involve interactions between water molecules and electric fields. This paper investigates the effect of uniform electric fields on the homogeneous nucleation of ice in supercooled water.

A microfluidic apparatus for the study of ice nucleation in supercooled water drops.

This paper describes a microfluidic instrument that produces drops of supercooled water suspended in a moving stream of liquid fluorocarbon, and measures the temperatures at which ice nucleates in the drops. A microfluidic chip containing a monodisperse drop generator and a straight channel with 38 embedded resistance thermometers was placed in contact with a seven-zone temperature-control plate and imaged under a microscope with a high-speed camera. This instrument can record the freezing temperatures of tens of thousands of drops within minutes, with an accuracy of 0.

Independent control of drop size and velocity in microfluidic flow-focusing generators using variable temperature and flow rate.

This paper describes a method to control the volume and the velocity of drops generated in a flow-focusing device dynamically and independently. This method involves simultaneous tuning of the temperature of the nozzle of the device and of the flow rate of the continuous phase; the method requires a continuous phase liquid that has a viscosity that varies steeply with temperature. Increasing the temperature of the flow-focusing nozzle from 0 to 80 degrees C increased the volume of the drops by almost 2 orders of magnitude.