The genetic legacy of the expansion of Turkic-speaking nomads across Eurasia.

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghanistan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language's expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. In agreement with the elite dominance model of language expansion most of the Turkic peoples studied genetically resemble their geographic neighbors. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area where historians center a series of early Turkic and non-Turkic steppe polities. While SSM matching IBD tracts (> 1cM) are also observed in non-Turkic populations, Turkic peoples demonstrate a higher percentage of such tracts (p-values ≤ 0.01) compared to their non-Turkic neighbors. Finally, we used the ALDER method and inferred admixture dates (~9th-17th centuries) that overlap with the Turkic migrations of the 5th-16th centuries. Thus, our results indicate historical admixture among Turkic peoples, and the recent shared ancestry with modern populations in SSM supports one of the hypothesized homelands for their nomadic Turkic and related Mongolic ancestors.

Microstructure Evolution during High-Pressure Torsion in a 7xxx AlZnMgZr Alloy.

A homogenized, supersaturated AlZnMgZr alloy was processed via severe plastic deformation (SPD) using a high-pressure torsion (HPT) technique for different revolutions at room temperature to obtain an ultrafine-grained (UFG) microstructure. The microstructure and mechanical properties of the UFG samples were then studied using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and tensile and hardness measurements. The main purpose was to study the effect of shear strain on the evolution of the microstructure of the investigated alloy. We found a very interesting evolution of the decomposed microstructure in a wide range of shear strains imposed by HPT. While the global properties, such as the average grain size (~200 nm) and hardness (~2200 MPa) appeared unchanged, the local microstructure was continuously transformed. After 1 turn of HPT, the decomposed UFG structure contained relatively large precipitates inside grains. In the sample processed by five turns in HPT, the segregation of Zn atoms into grain boundaries (GBs) was also observed. After 10 turns, more Zn atoms were segregated into GBs and only smaller-sized precipitates were observed inside grains. The intensive solute segregations into GBs may significantly affect the ductility of the material, leading to its ultralow-temperature superplasticity. Our findings pave the way for achieving advanced microstructural and mechanical properties in nanostructured metals and alloys by engineering their precipitation and segregation by means of applying different HPT regimes.

Low-Temperature Superplasticity and High Strength in the Al 2024 Alloy with Ultrafine Grains.

This study aims to achieve an ultrafine-grained (UFG) Al 2024 alloy superplasticity at temperatures lower than the traditional ones for commercial Al alloys (400-500 °C). The UFG structure with a mean grain size of 100 nm produced in the alloy by high-pressure torsion at room temperature provided a very high strength-microhardness (HV0.1) of 286 ± 4, offset yield strength (σ0.2) of 828 ± 9 MPa, and ultimate tensile strength (σUTS) of 871 ± 6 MPa at elongation to failure (δ) of 7 ± 0.2%. Complex tensile tests were performed at temperatures from 190 to 270 °C and strain rates from 10-2 to 5 × 10-5 s-1, and the values of flow stress, total elongation and strain rate-sensitivity coefficient were determined. The UFG alloy was shown to exhibit superplastic behavior at test temperatures of 240 and 270 °C. For the first time, 400% elongation was achieved in the alloy at an unusually low temperature of 270 °C (0.56 Tm) and strain rate of 10-3 s-1. The UFG 2024 alloy after superplastic deformation was found to have higher strength (150-160 HV) than that after the standard strengthening heat treatment T6.

Effect of the Equal Channel Angular Pressing on the Microstructure and Phase Composition of a 7xxx Series Al-Zn-Mg-Zr Alloy.

A supersaturated Al-4.8%Zn-1.2%Mg-0.14%Zr (wt%) alloy was processed by the equal-channel angular pressing (ECAP) technique at room temperature in order to obtain an ultrafine-grained (UFG) microstructure having an average grain size of about 260 nm. The hardness and microstructural characteristics, such as the phase composition and precipitations of this UFG microstructure were studied using depth-sensing indentation (DSI), transmission electron microscopy (TEM), as well as non-isothermal scanning of differential scanning calorimetry (DSC), and compared to the properties of the un-deformed sample. Emphasis was placed on the effect of the UFG microstructure on the subsequent thermal processes in DSC measurements. It has been shown that the ECAP process resulted in not only an ultrafine-grained but also a strongly precipitated microstructure, leading to a hardness (2115 MPa) two and a half times higher than the initial hardness of the freshly quenched sample. Because of the significant changes in microstructure, ECAP has also a strong effect on the dissolution (endothermic) and precipitation (exothermic) processes during DSC measurements, where the dissolution and precipitation processes were quantitatively characterized by using experimentally determined specific enthalpies, ΔH and activation energies, Q.

Whole Exome Sequencing Study Suggests an Impact of FANCA, CDH1 and VEGFA Genes on Diffuse Gastric Cancer Development.

Gastric cancer (GC) is one of the most common cancer types in the world with a high mortality rate. Hereditary predisposition for GC is not fully elucidated so far. The aim of this study was identification of possible new candidate genes, associated with the increased risk of gastric cancer development. Whole exome sequencing (WES) was performed on 18 DNA samples from adenocarcinoma specimens and non-tumor-bearing healthy stomach tissue from the same patient. Three pathogenic variants were identified: c.1320+1G>A in the CDH1 gene and c.27_28insCCCAGCCCCAGCTACCA (p.Ala9fs) of the VEGFA gene were found only in the tumor tissue, whereas c.G1874C (p.Cys625Ser) in the FANCA gene was found in both the tumor and normal tissue. These changes were found only in patients with diffuse gastric cancer and were absent in the DNA of healthy donors.

In Vivo Studies of Medical Implants for Maxillofacial Surgery Produced from Nanostructured Titanium.

This paper presents the results of comprehensive in vivo studies into the osseointegration behavior of medical implants for maxillofacial surgery produced from nanostructured grade 4 titanium. Special attention is given to the phenomenology of bone tissue formation with consideration of its surface relief features and to evaluating the quantitative parameters of the morphological indicators of osteoblast and endothelial cells in the osseointegration zone. These parameters were compared with their measurement data for standard factory-made implants, and considerable acceleration in the fixation of nanotitanium implants due to osseointegation was found. The obtained results indicate a better osseointegration of implants made of nanotitanium in comparison to similar standard products.

Finite Element Modeling for Virtual Design to Miniaturize Medical Implants Manufactured of Nanostructured Titanium with Enhanced Mechanical Performance.

The study is aimed to virtually miniaturize medical implants produced of the biocompatible Ti with improved mechanical performance. The results on the simulation-driven design of medical implants fabricated of nanostructured commercially pure Ti with significantly enhanced mechanical properties are presented. The microstructure of initially coarse-grained Ti has been refined to ultrafine grain size by severe plastic deformation. The ultrafine-grained (UFG) Ti exhibits remarkably high static and cyclic strength, allowing to design new dental and surgical implants with miniaturized geometry. The possibilities to reduce the implant dimensions via virtual fatigue tests for the digital twins of two particular medical devices (a dental implant and a maxillofacial surgery plate) are explored with the help of finite element modeling. Additionally, the effect of variation in loading direction and the fixation methods for the tested implants are studied in order to investigate the sensitivity of the fatigue test results to the testing conditions. It is shown that the UFG materials are promising for the design of a new generation of medical products.

Effect of Microstructure Refinement on the Corrosion Behavior of the Bioresorbable Mg-1Zn-0.2Ca and Mg-1Ca Alloys.

This paper presents a comprehensive study of the effect of the processing by high-pressure torsion (HPT) on the corrosion behavior in Ringer's solution for two popular bioresorbable magnesium alloys-Mg-1Ca and Mg-1Zn-0.2Ca. Three states were studied for each alloy-the initial homogenized state, the as-HPT-processed state and the state after subsequent annealing at 250 and 300 °C. It is shown that HPT processing results in a very strong grain refinement in both alloys down to a mean grain size of about 210 nm for the Mg-1Ca alloy and 90 nm for the Mg-1Zn-0.2Ca alloy, but their corrosion resistance values differ significantly (by an order of magnitude). The conducted precision scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction studies demonstrate that such a difference in the corrosion behavior is conditioned by a difference in the morphology and origin of the nano-sized particles of second phases, as well as by a change in the electrochemical properties of the "particle-α-Mg" pair. The obtained results are discussed from the perspective of the innovative applications of biodegradable Mg alloys for the manufacture of advanced medical implants and products.

The Microstructure and Strength of UFG 6060 Alloy after Superplastic Deformation at a Lower Homologous Temperature.

The paper reports on the features of low-temperature superplasticity of the heat-treatable aluminum Al-Mg-Si alloy in the ultrafine-grained state at temperatures below 0.5 times the melting point as well as on its post-deformation microstructure and tensile strength. We show that the refined microstructure is retained after superplastic deformation in the range of deformation temperatures of 120-180 °C and strain rates of 5 × 10-3 s-1-10-4 s-1. In the absence of noticeable grain growth, the ultrafine-grained alloy maintains the strength up to 380 MPa after SP deformation, which considerably exceeds the value (250 MPa) for the alloy in the peak-aged coarse-grain state. This finding opens pathways to form high-strength articles of Al-Mg-Si alloys after superplastic forming.

Strength of Products Made of Ultrafine-Grained Titanium for Bone Osteosynthesis.

This paper evaluates the fatigue strength of ultrafine-grained (UFG) Grade 4 Ti in the low-cycle fatigue region, as well as the strength of medical implants (plates and screws) made of UFG Ti under various types of loading in comparison with the strength of products made of coarse-grained (CG) Ti. To produce a UFG state, titanium billets after annealing were processed by the ECAP-Conform technique. The fatigue of the prismatic specimens with a thickness of 10 mm from CG and UFG Ti was tested by the three-point bending method using an Instron 8802 facility. The modeling and evaluation of the stress-strain state in the ANSYS software package for finite-element analysis revealed, in particular, the localization of equivalent stresses in the area of hole edges and at fillets during the tension of the plates. The performed research has demonstrated that medical implants (plates and screws) from UFG Grade 4 Ti have a higher strength under different types of loading (tension, fatigue strength, torsion) in comparison with products from CG Ti. This opens up a possibility for the miniaturization of medical products from UFG Ti while preserving their main performance properties at an acceptable level.

Modeling of Biological Activity of PEO-Coated Titanium Implants with Conjugates of Cyclic RGD Peptide with Amino Acid Bisphosphonates.

Titanium is considered to be the most essential metal in the field of implantology. The main factors determining metal biocompatibility, among others, include the morphology and chemical composition of the titanium surface. Therefore, the aim of this work was to develop approaches to control the biological activity of the titanium surface by creating coatings that combine both an inorganic phase with a given morphology and organic molecules containing an integrin-selective peptide that regulate cell adhesion and proliferation. As such, we synthesized new c(RGDfC) derivatives of amino acid bisphosphonates (four examples) with different bisphosphonate anchors and maleimide linkers. These molecules were deposited on a highly developed porous surface obtained via the plasma electrolytic oxidation (PEO) of coarse-grained and nanostructured titanium. In vitro studies demonstrated the increase in the viability degree of mesenchymal stem cells and fibroblasts on the surface of coarse-grained or nanostructured titanium modified with PEO and a c(RGDfC) derivative of ε-aminocaproic acid bisphophonate with an SMCC linker. As a result, the use of conjugates of amino acid bisphosphonates with a cyclic RGD peptide for the modification of PEO-coated titanium opens the ways for the effective control of the biological activity of the metal implant surface.

Unveiling the Local Atomic Arrangements in the Shear Band Regions of Metallic Glass.

The prospective applications of metallic glasses are limited by their lack of ductility, attributed to shear banding inducing catastrophic failure. A concise depiction of the local atomic arrangement (local atomic packing and chemical short-range order), induced by shear banding, is quintessential to understand the deformation mechanism, however still not clear. An explicit view of the complex interplay of local atomic structure and chemical environment is presented by mapping the atomic arrangements in shear bands (SBs) and in their vicinity in a deformed Vitreloy 105 metallic glass, using the scanning electron diffraction pair distribution function and atom probe tomography. The results experimentally prove that plastic deformation causes a reduction of geometrically favored polyhedral motifs. Localized motifs variations and antisymmetric (bond and chemical) segregation extend for several hundred nanometers from the SB, forming the shear band affected zones. Moreover, the variations within the SB are found both perpendicular and parallel to the SB plane, also observable in the oxidation activity. The knowledge of the structural-chemical changes provides a deeper understanding of the plastic deformation of metallic glasses especially for their functional applications and future improvements.

Strength and Fracture Mechanism of an Ultrafine-Grained Austenitic Steel for Medical Applications.

In this paper, we study the corrosion-resistant austenitic steel Fe-0.02C-18Cr-8Ni for medical applications. The microstructure and mechanical properties (tensile mechanical properties, torsional strength, impact toughness, and static and cyclic crack resistance) under different types of loading of the steel are investigated. The results are compared for the two states of the steel: the initial (coarse-grained) state and the ultrafine-grained state produced by severe plastic deformation processing via equal-channel angular pressing. It is demonstrated that the ultrafine-grained steel 0.08C-18Cr-9Ni has essentially better properties and is very promising for the manufacture of medical products for various applications that experience various static and cyclic loads during operation.

Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices.

Recent years have witnessed much progress in medical device manufacturing and the needs of the medical industry urges modern nanomaterials science to develop novel approaches for improving the properties of existing biomaterials. One of the ways to enhance the material properties is their nanostructuring by using severe plastic deformation (SPD) techniques. For medical devices, such properties include increased strength and fatigue life, and this determines nanostructured Ti and Ti alloys to be an excellent choice for the engineering of implants with improved design for orthopedics and dentistry. Various reported studies conducted in this field enable the fabrication of medical devices with enhanced functionality. This paper reviews recent development in the field of nanostructured Ti-based materials and provides examples of the use of ultra-fine grained Ti alloys in medicine.

Biological response of chemically treated surface of the ultrafine-grained Ti-6Al-7Nb alloy for biomedical applications.

BACKGROUND: Nanophase surface properties of titanium alloys must be obtained for a suitable biological performance, particularly to facilitate cell adhesion and bone tissue formation. Obtaining a bulk nanostructured material using severe plastic deformation is an ideal processing route to improve the mechanical performance of titanium alloys. By decreasing the grain size of a metallic material, a superior strength improvement can be obtained, while surface modification of a nanostructured surface can produce an attractive topography able to induce biological responses in osteoblastic cells. METHODS: Aiming to achieve such an excellent synergetic performance, a processing route, which included equal channel angular pressing (ECAP), hot and cold extrusion, and heat treatments, was used to produce a nanometric and ultrafine-grained (UFG) microstructure in the Ti-6Al-7Nb alloy (around of 200 nm). Additionally, UFG samples were surface-modified with acid etching (UFG-A) to produce a uniform micron and submicron porosity on the surface. Subsequently, alkaline treatment (UFG-AA) produced a sponge-like nanotopographic substrate able to modulate cellular interactions. RESULTS: After several kinds of biological tests for both treatment conditions (UFG-A and UFG-AA), the main results have shown that there was no cytotoxicity, expressed alkaline phosphatase activity and total protein amounts without statistical differences compared to control. However, the UFG-AA samples presented an attractive effect on the cell membranes, and cell adhesions were preferentially induced as compared with UFG-A. Both conditions demonstrated cell projections, but for UFG-AA, cells were more widely dispersed, and more quantities of filopodia formation could be observed. CONCLUSION: Herein, the reasons for such behaviors are discussed, and further results are presented in addition to those mentioned above.

Transition from poor ductility to room-temperature superplasticity in a nanostructured aluminum alloy.

Recent developments of nanostructured materials with grain sizes in the nanometer to submicrometer range have provided ground for numerous functional properties and new applications. However, in terms of mechanical properties, bulk nanostructured materials typically show poor ductility despite their high strength, which limits their use for structural applications. The present article shows that the poor ductility of nanostructured alloys can be changed to room-temperature superplastisity by a transition in the deformation mechanism from dislocation activity to grain-boundary sliding. We report the first observation of room-temperature superplasticity (over 400% tensile elongations) in a nanostructured Al alloy by enhanced grain-boundary sliding. The room-temperature grain-boundary sliding and superplasticity was realized by engineering the Zn segregation along the Al/Al boundaries through severe plastic deformation. This work introduces a new boundary-based strategy to improve the mechanical properties of nanostructured materials for structural applications, where high deformability is a requirement.

Psoriasis patients demonstrate HLA-Cw*06:02 allele dosage-dependent T cell proliferation when treated with hair follicle-derived keratin 17 protein.

It is broadly accepted that psoriasis is an immune-mediated disease with a heritable component, but it is not clear what causes inflammation in the skin. Previous research suggests that fragments of the keratin 17 (K17) protein, which are constitutively expressed in hair follicles, could act as autoantigens. In this study, we synthesized the K17 protein from mRNA derived from hair follicles and tested whether it elicited T cell responses depending on the patient genotype at the major susceptibility locus HLA-Cw*06:02. We treated peripheral blood-derived cells with the K17 protein and its short fragments to assess the T cell proliferation response using flow cytometry. Our analyses show a significantly stronger increase in cell proliferation among patients but not in healthy controls. We then examined whether the variation in T cell proliferation correlated with the patient HLA-Cw*06:02 risk genotype. Considering the affected status and patient genotype as two independent predictors, we fitted a linear model and showed that the HLA-Cw*06:02 allele dosage strongly predicted the T cell response. Our study findings suggest that the K17 protein likely acts as an autoantigen in psoriasis and that patients' risk genotype is strongly correlated with the magnitude of the response to this putative autoantigen.

Enhanced Osseointegrative Properties of Ultra-Fine-Grained Titanium Implants Modified by Chemical Etching and Atomic Layer Deposition.

An integrated approach combining severe plastic deformation (SPD), chemical etching (CE), and atomic layer deposition (ALD) was used to produce titanium implants with enhanced osseointegration. The relationship between morphology, topography, surface composition, and bioactivity of ultra-fine-grained (UFG) titanium modified by CE and ALD was studied in detail. The topography and morphology have been studied by means of atomic force microscopy, scanning electron microscopy, and the spectral ellipsometry. The composition and structure have been determined by X-ray fluorescence analysis, X-ray diffraction, and X-ray photoelectron spectroscopy. The wettability of the surfaces was examined by the contact angle measurement. The bioactivity and biocompatibility of the samples were studied in vitro and in vivo. CE of UFG titanium in basic (NH4OH/H2O2) or acidic (H2SO4/H2O2) piranha solution significantly enhances the surface roughness and leads to microstructures, nanostructures, and hierarchical micro-/nanostructures on the surfaces. In vitro results demonstrate deterioration of adhesion, proliferation, and differentiation of MC3T3-E1 osteoblasts cell for CE samples as compared to the non-treated ones. Atomic layer deposition of crystalline titanium oxide onto the CE samples increased hydrophilicity, changed the surface composition, and enhanced significantly in vitro characteristics. In vivo experiments demonstrated non-toxicity of the implants. Etching in basic piranha solution with subsequent ALD significantly improved implant osseointegration as compared with the non-modified samples.

Improved osseointegration properties of hierarchical microtopographic/nanotopographic coatings fabricated on titanium implants.

BACKGROUND: Titanium (Ti) implants are extensively used in reconstructive surgery and orthopedics. However, the intrinsic inertness of untreated Ti implants usually results in insufficient osseointegration. In order to improve the osteoconductivity properties of the implants, they are coated with hierarchical microtopographic/nanotopographic coatings employing the method of molecular layering of atomic layer deposition (ML-ALD). RESULTS: The analysis of the fabricated nanostructured relief employing scanning electron microscopy, atomic force microscopy, and electron spectroscopy for chemical analysis clearly demonstrated the formation of the nanotopographic (<100 nm) and microtopographic (0.1-0.5 µm) titano-organic structures on the surface of the nanograined Ti implants. Subsequent coincubation of the MC3T3-E1 mouse osteoblasts on the microtopographic/nanotopographic surface of the implants resulted in enhanced osteogenic cell differentiation (the production of alkaline phosphatase, osteopontin, and osteocalcin). In vivo assessment of the osseointegrative properties of the microtopographically/nanotopographically coated implants in a model of below-knee amputation in New Zealand rabbits demonstrated enhanced new bone formation in the zone of the bone-implant contact (as measured by X-ray study) and increased osseointegration strength (removal torque measurements). CONCLUSION: The fabrication of the hierarchical microtopographic/nanotopographic coatings on the nanograined Ti implants significantly improves the osseointegrative properties of the intraosseous Ti implants. This effect could be employed in both translational and clinical studies in orthopedic and reconstructive surgery.