Statistical data analysis of x-ray spectroscopy data enabled by neural network accelerated Bayesian inference.

Bayesian inference applied to x-ray spectroscopy data analysis enables uncertainty quantification necessary to rigorously test theoretical models. However, when comparing to data, detailed atomic physics and radiation transfer calculations of x-ray emission from non-uniform plasma conditions are typically too slow to be performed in line with statistical sampling methods, such as Markov Chain Monte Carlo sampling. Furthermore, differences in transition energies and x-ray opacities often make direct comparisons between simulated and measured spectra unreliable.

Extended X-ray absorption fine structure of dynamically-compressed copper up to 1 terapascal.

Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal.

Pertuzumab as second‑ or later‑line therapy for human epidermal growth factor receptor 2‑positive metastatic breast cancer: A clinical experience.

Trastuzumab and pertuzumab with taxane-based chemotherapy are considered the first-line standard therapy for human epidermal growth factor receptor 2 ()-positive metastatic breast cancer (mBC). Pertuzumab is also a later-line therapy for mBC in Switzerland, although limited safety and efficacy data are available. The present study assessed the therapeutic regimens, toxicities and clinical outcomes after second- or later-line pertuzumab therapy in patients with mBC who did not receive pertuzumab as a first-line therapy.

Amyloid fibril formation, structure and domain swapping of acyl-coenzyme A thioesterase-7.

Acyl-coenzyme A thioesterase (Acot) enzymes are involved in a broad range of essential intracellular roles including cell signalling, lipid metabolism, inflammation and the opening of ion channels. Dysregulation in lipid metabolism has been linked to neuroinflammatory and neurological disorders such as Alzheimer's and Parkinson's diseases. Structurally, Acot enzymes adopt a circularised trimeric arrangement with each monomer containing an N- and a C-terminal hotdog domain.

Role of Oxidative Stress in Ocular Diseases: A Balancing Act.

Redox homeostasis is a delicate balancing act of maintaining appropriate levels of antioxidant defense mechanisms and reactive oxidizing oxygen and nitrogen species. Any disruption of this balance leads to oxidative stress, which is a key pathogenic factor in several ocular diseases. In this review, we present the current evidence for oxidative stress and mitochondrial dysfunction in conditions affecting both the anterior segment (e.

Amyloid fibril formation by α- and β-casein implies that fibril formation is a general property of casein proteins.

Caseins are a diverse family of intrinsically disordered proteins present in the milks of all mammals. A property common to two cow paralogues, α- and κ-casein, is their propensity in vitro to form amyloid fibrils, the highly ordered protein aggregates associated with many age-related, including neurological, diseases. In this study, we explored whether amyloid fibril-forming propensity is a general feature of casein proteins by examining the other cow caseins (α and β) as well as β-caseins from camel and goat.

A native chemical chaperone in the human eye lens.

Cataract is one of the most prevalent protein aggregation disorders and still the most common cause of vision loss worldwide. The metabolically quiescent core region of the human lens lacks cellular or protein turnover; it has therefore evolved remarkable mechanisms to resist light-scattering protein aggregation for a lifetime. We now report that one such mechanism involves an unusually abundant lens metabolite, inositol, suppressing aggregation of lens crystallins.

Hot Spot Evolution Measured by High-Resolution X-Ray Spectroscopy at the National Ignition Facility.

Evolution of the hot spot plasma conditions was measured using high-resolution x-ray spectroscopy at the National Ignition Facility. The capsules were filled with DD gas with trace levels of Kr and had either a high-density-carbon (HDC) ablator or a tungsten (W)-doped HDC ablator. Time-resolved measurement of the Kr Heβ spectra, absolutely calibrated by a simultaneous time-integrated measurement, allows inference of the electron density and temperature through observing Stark broadening and the relative intensities of dielectronic satellites.

Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer's Disease Patients.

Alzheimer's disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls.

The Amyloid Fibril-Forming β-Sheet Regions of Amyloid β and α-Synuclein Preferentially Interact with the Molecular Chaperone 14-3-3ζ.

14-3-3 proteins are abundant, intramolecular proteins that play a pivotal role in cellular signal transduction by interacting with phosphorylated ligands. In addition, they are molecular chaperones that prevent protein unfolding and aggregation under cellular stress conditions in a similar manner to the unrelated small heat-shock proteins. In vivo, amyloid β (Aβ) and α-synuclein (α-syn) form amyloid fibrils in Alzheimer's and Parkinson's diseases, respectively, a process that is intimately linked to the diseases' progression.

MALDI imaging mass spectrometry: an emerging tool in neurology.

Neurological disease and disorders remain a large public health threat. Thus, research to improve early detection and/or develop more effective treatment approaches are necessary. Although there are many common techniques and imaging modalities utilized to study these diseases, existing approaches often require a label which can be costly and time consuming.

Redox chemistry of lens crystallins: A system of cysteines.

The nuclear region of the lens is metabolically quiescent, but it is far from inert chemically. Without cellular renewal and with decades of environmental exposures, the lens proteome, lipidome, and metabolome change. The lens crystallins have evolved exquisite mechanisms for resisting, slowing, adapting to, and perhaps even harnessing the effects of these cumulative chemical modifications to minimize the amount of light-scattering aggregation in the lens over a lifetime.

A new class of focusing crystal shapes for Bragg spectroscopy of small, point-like, x-ray sources in laser produced plasmas.

This paper describes a new class of focusing crystal forms for the x-ray Bragg crystal spectroscopy of small, point-like, x-ray sources. These new crystal forms are designed with the aid of sinusoidal spirals, a family of curves, whose shapes are defined by only one parameter, which can assume any real value. The potential of the sinusoidal spirals for the design x-ray crystal spectrometers is demonstrated with the design of a toroidally bent crystal of varying major and minor radii for measurements of the extended x-ray absorption fine structure near the Ta-L3 absorption edge at the National Ignition Facility.

The multi-optics high-resolution absorption x-ray spectrometer (HiRAXS) for studies of materials under extreme conditions.

We report the development of a high-resolution spectrometer for extended x-ray absorption fine structure (EXAFS) studies of materials under extreme conditions. A curved crystal and detector in the spectrometer are replaceable such that a single body is employed to perform EXAFS measurements at different x-ray energy intervals of interest. Two configurations have been implemented using toroidal crystals with Ge 311 reflection set to provide EXAFS at the Cu K-edge (energy range 8.

A Novel Approach to Augmenting Allograft Hamstring Anterior Cruciate Ligament Reconstructions Utilizing a Resorbable Type I Collagen Matrix with Platelet Rich Plasma.

Background: Anterior cruciate ligament reconstruction (ACLR) is one of the most common lower extremity orthopedic surgeries performed in the United States. Annually, between 100,000 and 200,000 ACL tears affect 1 in 3,000 people. The selection of autograft versus allograft for ACLR has been widely discussed in terms of risk of graft failure.

[Outpatient breast cancer treatment after the hospital: what's next? - Adjuvant medical therapies, management of side effects and common fears, planing and coordination of optimal follow-up care in view of current guidelines].

Outpatient breast cancer treatment after the hospital: what's next? - Adjuvant medical therapies, management of side effects and common fears, planing and coordination of optimal follow-up care in view of current guidelines Following successful breast cancer surgery patients will generally be facing a certain prolonged period of medical treatment accompanied by several years of follow-up care, usually in the setting of a private practice or outpatient clinic. These medical treatments, which have proven by evidence to substantially reduce the risk of breast cancer recurrence and thereby significantly added to the boost in overall prognosis of this disease, are discussed in the light of current international treatment guidelines in this article. The standard approach to modern medical therapies is outlined on the basis of clinical pathological risk factors and tumor biology for different breast cancer subtypes (e.

Native disulphide-linked dimers facilitate amyloid fibril formation by bovine milk α-casein.

Bovine milk α-casein, an intrinsically disordered protein, readily forms amyloid fibrils in vitro and is implicated in the formation of amyloid fibril deposits in mammary tissue. Its two cysteine residues participate in the formation of either intra- or intermolecular disulphide bonds, generating monomer and dimer species. X-ray solution scattering measurements indicated that both forms of the protein adopt large, spherical oligomers at 20 °C.

The Aggregation of αB-Crystallin under Crowding Conditions Is Prevented by αA-Crystallin: Implications for α-Crystallin Stability and Lens Transparency.

One of the most crowded biological environments is the eye lens which contains a high concentration of crystallin proteins. The molecular chaperones αB-crystallin (αBc) with its lens partner αA-crystallin (αAc) prevent deleterious crystallin aggregation and cataract formation. However, some forms of cataract are associated with structural alteration and dysfunction of αBc.

Cumulative deamidations of the major lens protein γS-crystallin increase its aggregation during unfolding and oxidation.

Age-related lens cataract is the major cause of blindness worldwide. The mechanisms whereby crystallins, the predominant lens proteins, assemble into large aggregates that scatter light within the lens, and cause cataract, are poorly understood. Due to the lack of protein turnover in the lens, crystallins are long-lived.

Optimized x-ray sources for x-ray diffraction measurements at the Omega Laser Facility.

The use of x-ray diffraction (XRD) measurements in laser-driven dynamic compression experiments at high-power laser facilities is becoming increasingly common. Diffraction allows one to probe in situ the transformations occurring at the atomic level at extreme conditions of pressure, temperature, and time scale. In these measurements, the x-ray source is generated by irradiation of a solid foil.

Image-plate sensitivity to x rays at 2 to 60 keV.

The sensitivity of Fuji SR and MS image plates (IPs) used in x-ray spectrometers on OMEGA and the National Ignition Facility has been measured using two techniques. A set of radioisotopes has been used to constrain image-plate sensitivity between 6 and 60 keV, while a Manson source has been used to expose image plates to x rays at energies between 1.5 and 8 keV.

The Structure and Stability of the Disulfide-Linked γS-Crystallin Dimer Provide Insight into Oxidation Products Associated with Lens Cataract Formation.

The reducing environment in the eye lens diminishes with age, leading to significant oxidative stress. Oxidation of lens crystallin proteins is the major contributor to their destabilization and deleterious aggregation that scatters visible light, obscures vision, and ultimately leads to cataract. However, the molecular basis for oxidation-induced aggregation is unknown.