Mechanical Distortion Research Articles

P-025: ABNORMAL MITOCHONDRIA RETENTION IN MATURE RED BLOOD CELLS OCCURS NOT ONLY IN SS BUT ALSO SC PATIENTS AND IS ASSOCIATED WITH HEMOLYTIC MARKERS

Purpose: Sickle cell disease (SCD), the most frequent genetic disease worldwide, results from a unique point mutation leading to the synthesis of the abnormal hemoglobin S (HbS). Under hypoxic condition, HbS polymerization causes a mechanical distortion of red blood cells (RBCs) called sickling, which is accompanied by a decrease of their deformability and their life span. SCD is characterized by a wide variability of clinical expression and a complex pathophysiology including vaso-occlusive processes, intravascular hemolysis as well as pro-inflammation, pro-coagulant and vaso-constrictive states. Recently, the abnormal mitochondria retention in mature RBCs has been documented in small series of SS patients but the biological consequences of this abnormality have not been fully documented and not been documented in other sickle cell syndromes. In the present study, we analyzed mature RBC mitochondria retention in both SS and SC patients, the second most frequent sickle cell syndrome, taking into account the biological/clinical features associated with these abnormal RBCs. Materials and methods: Eighty-nine adult SCD patients were included: 35 SS patients treated with hydroxyurea (HU), 15 SS patients not treated with HU and 39 SC patients. All of them were at steady-state and regularly followed by the sickle center of Guadeloupe. Twenty-one Guadeloupean adult controls (AA) were also included. Mature RBCs containing mitochondria were identified by flow cytometry using MitoTracker® probe as well as thiazole orange and anti-CD71 antibody to discriminate total and stress reticulocytes respectively. Correlations between the percentage of mature mitochondria+-RBCs and the following parameters were then analyzed: RBC deformability (Ektacytometry), reticulocytes (both total and CD71+) counts and levels of hemoglobin, total bilirubin, aminotransferase aspartate and lactate dehydrogenase levels using routine procedures. The impact of splenic function was evaluated using Howell-Jolly bodies, assessed by classic May-Grünwald Giemsa smears, as a marker of splenic dysfunction. We also analyzed the relationships between mitochondria+-RBCs and HU treatment as well as the rates of hyper vaso-occlusive (painful vaso-occlusion, acute chest syndrome, osteonecrosis) and hyper hemolytic (micro/macro-albuminuria, leg ulcer) complications. Results: Abnormal mitochondria+ RBCs were detected not only in SS but also in SC patients, although at a less extend. In both sickle cell syndromes, positive correlations with mitochondria+ RBCs were detected with hemolysis markers (percentage of total and stress reticulocytes). In addition, a negative relationship with hemoglobin level was detected in SS patients. A negative correlation was also detected between these abnormal mitochondria+ RBCs and RBC deformability. In contrast, no association between the presence of this RBC sub-population and clinical manifestations, hydroxyurea treatment or Howell-Jolly bodies was detected. Conclusion: In the present report, we demonstrated that abnormal retention of mitochondria in mature RBCs occurred not only in SS but also in SC patients. We also presented evidence that this phenotype could be related to hemolysis rate. Further studies are warranted to reveal the molecular mechanisms involved. E. BERNIT declares a conflict of interest: Consultancy, Expert: for NOVARTIS PHARMA SAS

Chronic Pain after Bone Fracture: Current Insights into Molecular Mechanisms and Therapeutic Strategies.

Bone fracture following traumatic injury or due to osteoporosis is characterized by severe pain and motor impairment and is a major cause of global mortality and disability. Fracture pain often originates from mechanical distortion of somatosensory nerve terminals innervating bones and muscles and is maintained by central sensitization. Chronic fracture pain (CFP) after orthopedic repairs is considered one of the most critical contributors to interference with the physical rehabilitation and musculoskeletal functional recovery. Analgesics available for CFP in clinics not only have poor curative potency but also have considerable side effects; therefore, it is important to further explore the pathogenesis of CFP and identify safe and effective therapies. The typical physiopathological characteristics of CFP are a neuroinflammatory response and excitatory synaptic plasticity, but the specific molecular mechanisms involved remain poorly elucidated. Recent progress has deepened our understanding of the emerging properties of chemokine production, proinflammatory mediator secretion, caspase activation, neurotransmitter release, and neuron-glia interaction in initiating and sustaining synaptogenesis, synaptic strength, and signal transduction in central pain sensitization, indicating the possibility of targeting neuroinflammation to prevent and treat CFP. This review summarizes current literature on the excitatory synaptic plasticity, microgliosis, and microglial activation-associated signaling molecules and discusses the unconventional modulation of caspases and stimulator of interferon genes (STING) in the pathophysiology of CFP. We also review the mechanisms of action of analgesics in the clinic and their side effects as well as promising therapeutic candidates (e.g., specialized pro-resolving mediators, a caspase-6 inhibitor, and a STING agonist) for pain relief by the attenuation of neuroinflammation with the aim of better managing patients undergoing CFP in the clinical setting.

Characterizing Streamwise Development of Surface Roughness Effects on a Supersonic Boundary Layer

Two-component particle image velocimetry was employed to measure the influence of surface roughness on a Mach 2 boundary layer. Three surface conditions were examined: a smooth wall, patterned diamond-shaped roughness, and an approximately random realistic roughness. The response of the boundary layer was characterized in ensemble-averaged measurements of the mean velocity and Reynolds stresses. The streamwise development of the mechanical distortions introduced by the diamond-shaped roughness was also explored through observation of roughness-generated shock waves and changes in the boundary-layer profile. Measurements acquired at three streamwise locations are consistent with the trends observed in other studies when scaled by the roughness friction velocity. Ensemble-averaged outer-scaled streamwise velocity profiles showed a velocity deficit in the near-wall region. Inner-scaled boundary-layer profiles showed a downward vertical shift in the scaled velocities of 4.5 and 3 for the diamond roughness and nonuniform/realistic roughness topologies, respectively. These values show similar responses to the results seen in the literature for similar test conditions. The roughness effects were shown to increase in magnitude along the streamwise distance.

Improvement of mechanical properties and heat distortion temperature of polylactic acid by highly aromatic hyperbranched polyamide

AbstractThe highly aromatic hyperbranched polyamide (HBPA) was synthesized and used as a modifier in order to enhance the physical performance of polylactic acid (PLA). The results showed that compared to the neat PLA, the tensile strength of the PLA/HBPA blends increased by 41.8%; fracture energy increased by 42.8% when the content of HBPA was 1.0 phr. The addition of HBPA can significantly improve the thermal deformation temperature of PLA. The polarized optical microscope images suggested that HBPA can act as a nucleating agent for PLA during the isothermal crystallization. This research indicated HBPA exhibits excellent reinforcing effect for PLA, due to the formation of hydrogen bonds and/or chemical crosslinking between HBPA and PLA.

The distortion of distributed metric social choice

We consider a social choice setting with agents that are partitioned into disjoint groups, and have metric preferences over a set of alternatives. Our goal is to choose a single alternative aiming to optimize various objectives that are functions of the distances between agents and alternatives in the metric space, under the constraint that this choice must be made in a distributed way: The preferences of the agents within each group are first aggregated into a representative alternative for the group, and then these group representatives are aggregated into the final winner. Deciding the winner in such a way naturally leads to loss of efficiency, even when complete information about the metric space is available. We provide a series of (mostly tight) bounds on the distortion of distributed mechanisms for variations of well-known objectives, such as the (average) total cost and the maximum cost, and also for new objectives that are particularly appropriate for this distributed setting and have not been studied before.

Cas12a target search and cleavage on force stretched DNA

Using optical tweezers, we investigate target search and cleavage by CRISPR-Cas12a on force-stretched λ-DNA. Cas12a uses fast, one-dimensional hopping to locate its target. Binding and cleavage occur rapidly and specifically at low forces (≤ 5 pN), with a 1.8nm rate-limiting conformational change. Mechanical distortion slows diffusion, increases off-target binding but hinders cleavage.

Mechanically enhanced magnetism in flexible semitransparent CuFe2O4/mica epitaxial heterostructures

Mechanical strain tuning of magnetic properties is crucial for developing flexible electronic and spintronic devices. Here, (111)-oriented CuFe2O4 (CuFO) thin films are epitaxially grown on flexible mica substrates, and the influence of the mechanical strain on magnetic properties is investigated by altering the curvature of the CuFO/mica structures. Both the in-plane and out-of-plane saturation magnetic moments increase monotonously with the decrease of bending radius, which can be ascribed to the mechanical strain-induced Jahn-Teller distortion and much easier neighboring ferromagnetic domain switching in the CuFO films. Particularly, the residual magnetization can be dramatically enhanced by mechanical strain with a large gauge factor of 321.25, demonstrating effective strain tuning of magnetism. Moreover, the CuFO/mica structures exhibit strain tunable parallel magnetic anisotropy and excellent mechanical antifatigue properties. This work implies a great potential for promissing applications in flexible spintronics and electronics.

COMPARATIVE STUDY OF RESONANCE FREQUENCY OF CIRCULAR PIEZO MICROPHONE BASED ON PHOTOACOUSTIC, LASER SPECKLE, AND PIEZOELECTRIC EFFECTS

Resonance frequency of a circular piezoelectric microphone was measured by two types of methods which were named as photoacoustic and speckle method. In the photoacoustic method; acoustic waves were obtained due to the optical excitation and resulting thermally induced mechanical distortion was measured by the piezoelectric layer of microphone. Photoacoustic effect is a type of optical excitation, which creates an acoustic wave due to the absorbed light energy which causes thermal expansion of material. In contrast to the photoacoustic method, speckle method was conducted by electrical excitation of the piezoelectric layer which results in mechanical distortion and this distortion was detected by using changes in laser speckle pattern. Measurements were taken from 6 different piezo microphones in 3 different diameters of 15 mm, 35 mm, and 50 mm and the same thickness of brass plate in the frequency range of 0-11 kHz. As a conclusion, it is found that the resonance frequencies of same diameter microphones determined by the photoacoustic method are close but different with the results of the speckle method. It is believed that the differences in the results are caused by differences of excitation/detection mechanism for same microphones and shape, material parameter differences between microphones for different microphones.

Mechanics of CRISPR-Cas12a and engineered variants on λ-DNA.

Cas12a is an RNA-guided endonuclease that is emerging as a powerful genome-editing tool. Here, we selected a target site on bacteriophage λ-DNA and used optical tweezers combined with fluorescence to provide mechanistic insight into wild type Cas12a and three engineered variants, where the specific dsDNA and the unspecific ssDNA cleavage are dissociated (M1 and M2) and a third one which nicks the target DNA (M3). At low forces wtCas12a and the variants display two main off-target binding sites, while on stretched dsDNA at higher forces numerous binding events appear driven by the mechanical distortion of the DNA and partial matches to the crRNA. The multiple binding events onto dsDNA at high tension do not lead to cleavage, which is observed on the target site at low forces when the DNA is flexible. In addition, activity assays also show that the preferential off-target sites for this crRNA are not cleaved by wtCas12a, indicating that λ-DNA is only severed at the target site. Our single molecule data indicate that the Cas12a scaffold presents singular mechanical properties, which could be used to generate new endonucleases with biomedical and biotechnological applications.

Mechanical Jurisprudence and Domain Distortion: How Predictive Algorithms Warp the Law

The value-ladenness of computer algorithms is typically framed around issues of epistemic risk. In this article, I examine a deeper sense of value-ladenness: algorithmic methods are not only themselves value-laden but also introduce value into how we reason about their domain of application. I call this domain distortion. In particular, using insights from jurisprudence, I show that the use of recidivism risk assessment algorithms (1) presupposes legal formalism and (2) blurs the distinction between liability assessment and sentencing, which distorts how the domain of criminal punishment is conceived and provides a distinctive avenue for values to enter the legal process.

Outer hair cell driven reticular lamina mechanical distortion in living cochleae

Cochlear distortions afford researchers and clinicians a glimpse into the conditions and properties of inner ear signal processing mechanisms. Until recently, our examination of these distortions has been limited to measuring the vibration of the basilar membrane or recording acoustic distortion output in the ear canal. Despite its importance, the generation mechanism of cochlear distortion remains a substantial task to understand. The ability to measure the vibration of the reticular lamina in rodent models is a recent experimental advance. Surprising mechanical properties have been revealed. These properties merit both discussion in context with our current understanding of distortion, and appraisal of the significance of new interpretations of cochlear mechanics. This review focusses on some of the recent data from our research groups and discusses the implications of these data on our understanding of vocalization processing in the periphery, and their influence upon future experimental directions.This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam

Mechanical and nonlinear optical properties of two-dimensional LiXY2 (X=Al, Ga, In; Y[dbnd]S, Se, Te) monolayers

Two-dimensional (2D) nonlinear optical (NLO) materials with large flexibility possess application advantages for phototransistors and flexible laser fields. In this work, we studied the electronic, mechanical and NLO properties of 2D LiXY2 (X = Al, Ga, In; YS, Se, Te) monolayers via first-principles calculations. Theoretical results suggest that their bandgaps, which determine laser damage threshold (LDT) and harmful two-photon absorption (TPA), are as wide as that of typical 2D NLO materials single-layer GaSe and MoS2. The large energy gap between In-5s and Y-pz states will help single-layer LiXY2 to avoid TPA in a wide range of optical energies. Their NLO coefficients are comparable to that of bulk AgGaS2 and single-layer GaSe. Moreover, 2D LiXY2 monolayers are stable under mechanical distortion, and even more flexible than single-layer GaSe and MoS2. Overall, this work supplies a group of 2D materials exhibiting superiority as flexible NLO devices in nanotechnology.

Investigation of the Seismic Performance of a Special Truss Moment Frame with SMAs Incorporated

AbstractThe present work deals with the improvement of the seismic performance of Special Truss Moment Frames (STMFs) by incorporating Shape Memory Alloys (SMAs) as dissipation devices in the special segment, which have the ability to recover their initial geometry after mechanical distortion by unloading through the phase transformation (martensitic‐austenitic phase). STMFs were initially designed with a special segment located in the middle of the truss to dissipate the input energy through the formation of plastic hinges at the four corners of the chord members. This mechanism is replaced with the input energy dissipation through the SMA deformation in a pin‐ended special segment. In what follows, a single‐story single‐bay frame is examined incorporating 1, 12 and 25 SMAs per diagonal, simulated via a 4‐DOF mechanical model consisting of two lumped masses, under selected ground motions. To further evaluate the performance of the frame with SMAs incorporated and at the same time verify the 4‐DOF model, a non‐linear dynamic time‐history analysis was conducted using SeismoStruct 2018 finite element software. The response of the proposed system is compared with the response of the conventional one. Results showed that the proposed system leads to decrease of the maximum displacement and would potentially allow a much lighter construction.

The origin of mechanical harmonic distortion within the organ of Corti in living gerbil cochleae

Although auditory harmonic distortion has been demonstrated psychophysically in humans and electrophysiologically in experimental animals, the cellular origin of the mechanical harmonic distortion remains unclear. To demonstrate the outer hair cell-generated harmonics within the organ of Corti, we measured sub-nanometer vibrations of the reticular lamina from the apical ends of the outer hair cells in living gerbil cochleae using a custom-built heterodyne low-coherence interferometer. The harmonics in the reticular lamina vibration are significantly larger and have broader spectra and shorter latencies than those in the basilar membrane vibration. The latency of the second harmonic is significantly greater than that of the fundamental at low stimulus frequencies. These data indicate that the mechanical harmonics are generated by the outer hair cells over a broad cochlear region and propagate from the generation sites to their own best-frequency locations.

First-principles study on the P-induced embrittlement and de-embrittling effect of B and C in ferritic steels

First-principles calculations of the Σ5(310) grain boundary in Fe with B, C and P were performed to reveal the mechanism of P-caused embrittlement and de-embrittling effect of B and C. Independent and/or joint effect of B, C and P on the grain boundary energetics and cohesion were determined as a function of concentration. It is found that interstitial segregation sites are more favorable than substitutional sites for all the three elements, and only substitutional P aggravates the grain boundary cohesion, which explains the experimental observation that P only embrittles the grain boundary beyond a critical content. The energetic preference of interstitial B and C makes interstitial P at a disadvantage during the site competition, whereas the de-embrittling cannot be simply explained by the intrinsic strengthening effect of B and C. The influence of these elements on the grain boundary cohesion is further interpreted as a net result of mechanical contribution and chemical contribution, which proved to play the dominant role in the embrittling/strengthening effect of substitutional P and interstitial segregants, respectively. It turns out that replacing part of P atoms by B and C can mitigate the strong mechanical distortion, and thus alleviate the P-caused embrittlement. In the spirit of the Rice-Wang model, we propose a possible method to quantify the variation in chemical bonding upon fracture based on the concept of integral of crystal orbital Hamilton populations (ICOHP). A close relationship was found between the change in total ICOHP of bonds across the grain boundary and the calculated chemical contribution.

The effect of sand quality on the bending strength and thermal distortion of chemically bonded sand cores

The quality of chemically bonded sand cores used during the manufacturing process of cast components is highly dependent on the properties of the sand, which constitutes the refractory base media of the core. One of the main advantages of the application of different types of sands as molding aggregates that after casting, they can be reclaimed and can be used again during core shooting. The properties of the sand, however, could be remarkably changed during the casting and reclamation processes. This study aims to investigate the effects of the properties of the base sand on the mechanical strength and thermal distortion properties of samples made from new and thermally reclaimed silica sand. For this purpose, particle size analysis, specific surface area, and loss on ignition measurements, as well as differential thermal analysis coupled with thermogravimetry, were executed on the base sands, and the sand grains were analyzed with scanning electron microscopy and X-ray diffraction. Test pieces were made with hot box and cold box technology for bending and hot distortion tests. It was found that by the utilization of reclaimed sand, cores with higher average bending strength and lower thermal deformation can be produced. These differences can be traced back to the more advantageous granulometric properties, lower impurity content, and lower thermal expansion of thermally reclaimed sand.

Investigation of the seismic performance of a single story – Single bay special truss moment frame with SMAs incorporated

The present work deals with the improvement of the seismic performance of a Single Story-Single Bay Special Truss Moment Frame (STMF) by incorporating Shape Memory Alloys (SMAs) as dissipation devices in the special segment, which can recover their initial geometry after mechanical distortion by unloading through the phase transformation (martensitic-austenitic phase). STMFs were initially designed with a special segment located in the middle of the truss to dissipate the input energy through the formation of plastic hinges at the four corners of the chord members. This mechanism is replaced with the input energy dissipation through the SMA deformation in a pin-ended special segment. In what follows, the frame at hand is examined incorporating SMA bars per diagonal of either 0.025 m or 0.035 m in diameter, restrained against buckling, simulated via a 4-DOF mechanical model consisting of two lumped masses, under selected ground motions. To further evaluate the performance of the frame with SMAs incorporated and at the same time verify the model, a non-linear dynamic time-history analysis is conducted using SeismoStruct Finite Element software. The response of the proposed system is compared with the one of the conventional one. Results show that the proposed system leads to a decrease of the maximum displacement and potentially allows a much lighter construction.

How does vertical fiscal imbalance affect the upgrading of industrial structure? Empirical evidence from China

The vertical fiscal imbalance (VFI) caused by fiscal decentralization may have important implications on the upgrading of industrial structure. Based on the provincial panel data from 1995 to 2017 in China, this paper empirically studies the impact of VFI on the upgrading of industrial structure from the perspectives of regional heterogeneity, influence channels, and marginal effect. The empirical results show that: (1) VFI is not conducive to the rationalization and advancement of industrial structure, but this effect has significant regional heterogeneity. (2) VFI affects the upgrading of industrial structure through three channels, including investment-driven effect, market mechanism distortion effect, and technological innovation crowding effect. (3) With the increasing rationalization and advancement of industrial structure, the marginal restraining effect of VFI is gradually strengthened. Therefore, it is very necessary to control VFI between the central government and the local governments as much as possible for the upgrading of industrial structure.

Selective killing of transformed cells by mechanical stretch

Cancer cells differ from normal cells in several important features like anchorage independence, Warburg effect and mechanosensing. Further, in recent studies, they respond aberrantly to external mechanical distortion. Consistent with altered mechano-responsiveness, we find that cyclic stretching of tumor cells from many different tissues reduces growth rate and causes apoptosis on soft surfaces. Surprisingly, normal cells behave similarly when transformed by depletion of the rigidity sensor protein (Tropomyosin 2.1). Restoration of rigidity sensing in tumor cells promotes rigidity dependent mechanical behavior, i.e. cyclic stretching enhances growth and reduces apoptosis on soft surfaces. The mechanism of mechanical apoptosis (mechanoptosis) of transformed cells involves calcium influx through the mechanosensitive channel, Piezo1 that activates calpain 2 dependent apoptosis through the BAX molecule and subsequent mitochondrial activation of caspase 3 on both fibronetin and collagen matrices. Thus, it is possible to selectively kill tumor cells by mechanical perturbations, while stimulating the growth of normal cells.

Carbonized Cellulose Nanofibril with Individualized Fibrous Morphology: toward Multifunctional Applications in Polycaprolactone Conductive Composites.

Drying cellulose nanofibril (CNF) from aqueous suspensions often leads to aggregated fibril morphology, negatively affecting its performance in ensuing applications. In this work, we introduced a new solvent drying approach to acquire dry CNF from aqueous suspensions and subsequently pyrolyzed the CNF precursor to obtain carbonized CNF (CCNF) without loss of its fibrous morphology. The fibrous CCNF was dispersed homogeneously in polycaprolactone (PCL) thermoplastic resin, greatly enhancing PCL composite tensile performance. After being further mixed with carbon black (CB), the CCNF helped to minimize CB aggregation due to formation of interconnected three-dimensional (3D) structures. The CCNF/CB/PCL composite exhibited superior electrical conductivity ascribed to electrons transporting more efficiently among CB aggregates. The composite is also suitable for applications such as 3D printed electromagnetic interference (EMI) shielding and deformation sensing. Specifically, the 3D printed EMI shielding composite efficiently absorbed EM radiation in the frequency range of 4-26 GHz, and the 3D printed deformation sensor exhibited excellent sensitivity, durability, and flexibility in monitoring mechanical distortions. Herein, this study sheds light on the development of multifunctional conductive composites embedded with fibrous CCNF from sustainable resources.