Purcell-enhanced x-ray scintillation.

Scintillation materials convert high-energy radiation to optical light through a complex multistage process. The last stage of the process is spontaneous light emission, which usually governs and limits the scintillator emission rate and light yield. For decades, scintillator research focused on developing faster-emitting materials or external photonic coatings for improving light yields.

CNVoyant a machine learning framework for accurate and explainable copy number variant classification.

The precise classification of copy number variants (CNVs) presents a significant challenge in genomic medicine, primarily due to the complex nature of CNVs and their diverse impact on rare genetic diseases (RGDs). This complexity is compounded by the limitations of existing methods in accurately distinguishing between benign, uncertain, and pathogenic CNVs. Addressing this gap, we introduce CNVoyant, a machine learning-based multi-class framework designed to enhance the clinical significance classification of CNVs.

CNVoyant: A Highly Performant and Explainable Multi-Classifier Machine Learning Approach for Determining the Clinical Significance of Copy Number Variants.

The precise classification of copy number variants () presents a significant challenge in genomic medicine, primarily due to the complex nature of CNVs and their diverse impact on genetic disorders. This complexity is compounded by the limitations of existing methods in accurately distinguishing between benign, uncertain, and pathogenic CNVs. Addressing this gap, we introduce CNVoyant, a machine learning-based multi-class framework designed to enhance the clinical significance classification of CNVs.

Sub-PPB Detection with Gas-Phase Multiphoton Electron Extraction Spectroscopy under Ambient Conditions.

Multiphoton electron extraction spectroscopy (MEES) is an advanced analytical technique that has demonstrated exceptional sensitivity and specificity for detecting molecular traces on solid and liquid surfaces. Building upon the solid-state MEES foundations, this study introduces the first application of MEES in the gas phase (gas-phase MEES), specifically designed for quantitative detection of gas traces at sub-part per billion (sub-PPB) concentrations under ambient atmospheric conditions. Our experimental setup utilizes resonant multiphoton ionization processes using ns laser pulses under a high electrical field.

Sunscreens can preserve human skin microbiome upon erythemal UV exposure.

Objective: Ultraviolet radiation (UVR) is a known environmental key factor for premature skin ageing. Only few scientific evidence is available to support the effects of UVR on the skin microbiome. This in vivo pilot study aimed to evaluate the impact on the skin microbiome upon erythemal UV exposure and the protection of UV-exposed skin microbiome by UV filters.

Preliminary clinical pharmacokinetic evaluation of bemotrizinol - A new sunscreen active ingredient being considered for inclusion under FDA's over-the-counter (OTC) sunscreen monograph.

Protection against sunburn, skin damage and the carcinogenic effects of ultraviolet light are the primary health benefits associated with UV filters used in topical sunscreen drug products. Countries such as Europe have 30+ UV filters approved for sunscreen products while the US has about 10, greatly reducing the options to provide diverse, effective sun protection products. Bemotrizinol (BEMT) is the first new sunscreen active ingredient to be evaluated for inclusion in the Over-The-Counter (OTC) sunscreen monograph using FDA's new Generally Recognized as Safe and Effective (GRASE) testing guidelines.

A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores.

Purpose: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.

Methods: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included.

Defining early recurrence in patients with resected primary colorectal carcinoma and its respective risk factors.

Purpose: There is no evidence-based definition of early recurrence following resection of colorectal cancer. The purpose of this study is to define a point that discriminates between early and late recurrence in patients who have undergone colorectal cancer resection with curative intent and to analyze associated risk factors.

Methods: A retrospective single-center cohort study was performed at a university hospital recognized as a comprehensive cancer center, specializing in colorectal cancer surgery.

Pigmentation effects of blue light irradiation on skin and how to protect against them.

Background: Visible light, in particular blue light, has been identified as an additional contributor to cutaneous photoageing. However, clinical studies demonstrating the clear effect of blue light on photoageing are still scarce, and so far, most studies have focused on broad-spectrum visible light. Although there is evidence for increased skin pigmentation, the underlying mechanisms of photoageing in vivo are still unclear.

Discovery of a Highly Selective MC1R Agonists Pentapeptide to Be Used as a Skin Pigmentation Enhancer and with Potential Anti-Aging Properties.

One of the first lines of cutaneous defense against photoaging is a) the synthesis of melanin and b) the initiation of an oxidative stress response to protect skin against the harmful effects of solar radiation. Safe and selective means to stimulate epidermal pigmentation associated with oxidative stress defense are; however, scarce. Activation of the melanocortin-1 receptor (MC1R) on epidermal melanocytes represents a key step in cutaneous pigmentation initiation and, additionally, it regulates cellular defense mechanisms like oxidative stress and DNA-repair.

The Temple Scroll: Reconstructing an ancient manufacturing practice.

The miraculously preserved 2000-year-old Dead Sea Scrolls, ancient texts of invaluable historical significance, were discovered in the mid-20th century in the caves of the Judean desert. The texts were mainly written on parchment and exhibit vast diversity in their states of preservation. One particular scroll, the 8-m-long Temple Scroll is especially notable because of its exceptional thinness and bright ivory color.

Hypermineralization in the femoral neck of the elderly.

Hip fragility depends on the decline in bone mass as well as changes in bone microstructure and the properties of bone mineral and organic matrix. Although it is well-established that low bone mass or osteoporosis is a key factor in hip fracture risk, it is striking to observe that 92% of 24 patients who have sustained an intracapsular hip fracture showed hypermineralization at the superior-anterior quadrant, a critical region associated with increased hip fracture risk. In-depth material studies on a total of 12 human cadaver femurs revealed increased degree of mineralization in the hypermineralized tissue: calcium weight percentage as measured by quantitative backscattered electron imaging increased by approximately 15% compared with lamellar bone; mineral-to-matrix ratio obtained by Raman microspectroscopy imaging also increased.

The importance of plasmonic heating for the plasmon-driven photodimerization of 4-nitrothiophenol.

Metal nanoparticles form potent nanoreactors, driven by the optical generation of energetic electrons and nanoscale heat. The relative influence of these two factors on nanoscale chemistry is strongly debated. This article discusses the temperature dependence of the dimerization of 4-nitrothiophenol (4-NTP) into 4,4'-dimercaptoazobenzene (DMAB) adsorbed on gold nanoflowers by Surface-Enhanced Raman Scattering (SERS).

Protective effects of an extract of the freshwater microalga Scenedesmus rubescens on UV-irradiated skin cells.

Background: Skin ageing results from intrinsic but also extrinsic factors of which UV irradiation is a main cause. It is hence of interest to have means to protect skin from UV irradiation-induced damage. We selected an extract of the freshwater microalga Scenedesmus rubescens and assessed its potential to protect skin from photoageing caused by UV irradiation.

Multiscale Analysis of Mineralized Collagen Combining X-ray Scattering and Fluorescence with Raman Spectroscopy under Controlled Mechanical, Thermal, and Humidity Environments.

Biological materials, such as mineralized collagen, are structured over many length scales. This represents a challenge for quantitative characterization, in particular when complex specimen environments are required. This paper describes an approach based on synchrotron X-ray scattering and Raman spectroscopy to analyze the structure of biological materials from the molecular to the macroscopic range in controlled environments including humidity, temperature, and mechanical load.

Unraveling the Molecular Requirements for Macroscopic Silk Supercontraction.

Spider dragline silk is a protein material that has evolved over millions of years to achieve finely tuned mechanical properties. A less known feature of some dragline silk fibers is that they shrink along the main axis by up to 50% when exposed to high humidity, a phenomenon called supercontraction. This contrasts the typical behavior of many other materials that swell when exposed to humidity.

Deposition of Gold Nanotriangles in Large Scale Close-Packed Monolayers for X-ray-Based Temperature Calibration and SERS Monitoring of Plasmon-Driven Catalytic Reactions.

Anisotropic plasmonic particles such as gold nanotriangles have extraordinary structural, optical, and physicochemical properties. For many applications in different fields, it is essential to prepare them in a chemically and physically stable, structurally well-defined manner, e.g.

The role of water on the structure and mechanical properties of a thermoplastic natural block co-polymer from squid sucker ring teeth.

Hard biological polymers exhibiting a truly thermoplastic behavior that can maintain their structural properties after processing are extremely rare and highly desirable for use in advanced technological applications such as 3D-printing, biodegradable plastics and robust composites. One exception are the thermoplastic proteins that comprise the sucker ring teeth (SRT) of the Humboldt jumbo squid (Dosidicus gigas). In this work, we explore the mechanical properties of reconstituted SRT proteins and demonstrate that the material can be re-shaped by simple processing in water and at relatively low temperature (below 100 °C).

Osmotically driven tensile stress in collagen-based mineralized tissues.

Collagen is the most abundant protein in mammals and its primary role is to serve as mechanical support in many extracellular matrices such as those of bones, tendons, skin or blood vessels. Water is an integral part of the collagen structure, but its role is still poorly understood, though it is well-known that the mechanical properties of collagen depend on hydration. Recently, it was shown that the conformation of the collagen triple helix changes upon water removal, leading to a contraction of the molecule with considerable forces.

Anisotropy in bone demineralization revealed by polarized far-IR spectroscopy.

Bone material is composed of an organic matrix of collagen fibers and apatite nanoparticles. Previously, vibrational spectroscopy techniques such as infrared (IR) and Raman spectroscopy have proved to be particularly useful for characterizing the two constituent organic and inorganic phases of bone. In this work, we tested the potential use of high intensity synchrotron-based far-IR radiation (50-500 cm(-1)) to gain new insights into structure and chemical composition of bovine fibrolamellar bone.

Osmotic pressure induced tensile forces in tendon collagen.

Water is an important component of collagen in tendons, but its role for the function of this load-carrying protein structure is poorly understood. Here we use a combination of multi-scale experimentation and computation to show that water is an integral part of the collagen molecule, which changes conformation upon water removal. The consequence is a shortening of the molecule that translates into tensile stresses in the range of several to almost 100 MPa, largely surpassing those of about 0.

Chemical imaging of live fibroblasts by SERS effective nanofilm.

Reliable and strong surface enhanced Raman scattering (SERS) signatures of intracellular compartments in live NIH3T3 fibroblasts are collected in real time by means of SERS active thin nanofilm (30 nm) on colloidal silica (1.5 μm). Nanofilm is composed of preformed silver nanoparticles in the matrix of polyacrylic acid, protecting against heating (37 °C) in water, or culture medium or phosphate buffered saline aqueous solution.

Multidimensional optimality of microbial metabolism.

Although the network topology of metabolism is well known, understanding the principles that govern the distribution of fluxes through metabolism lags behind. Experimentally, these fluxes can be measured by (13)C-flux analysis, and there has been a long-standing interest in understanding this functional network operation from an evolutionary perspective. On the basis of (13)C-determined fluxes from nine bacteria and multi-objective optimization theory, we show that metabolism operates close to the Pareto-optimal surface of a three-dimensional space defined by competing objectives.

Observations of multiscale, stress-induced changes of collagen orientation in tendon by polarized Raman spectroscopy.

Collagen is a versatile structural molecule in nature and is used as a building block in many highly organized tissues, such as bone, skin, and cornea. The functionality and performance of these tissues are controlled by their hierarchical organization ranging from the molecular up to macroscopic length scales. In the present study, polarized Raman microspectroscopic and imaging analyses were used to elucidate collagen fibril orientation at various levels of structure in native rat tail tendon under mechanical load.

Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli.

To which extent can optimality principles describe the operation of metabolic networks? By explicitly considering experimental errors and in silico alternate optima in flux balance analysis, we systematically evaluate the capacity of 11 objective functions combined with eight adjustable constraints to predict (13)C-determined in vivo fluxes in Escherichia coli under six environmental conditions. While no single objective describes the flux states under all conditions, we identified two sets of objectives for biologically meaningful predictions without the need for further, potentially artificial constraints. Unlimited growth on glucose in oxygen or nitrate respiring batch cultures is best described by nonlinear maximization of the ATP yield per flux unit.