Preferential Loading Research Articles

Selective laser melting of high strength and toughness stainless steel parts: The roles of laser hatch style and part placement strategy

Laser hatch style and part placement strategy are acknowledged to have a considerable effect on processing quality and mechanical performance of selective laser melting (SLM) products. In an effort to obtain 316L stainless steel products with favorable properties, hatch style integration and part placement optimization were adopted in this study. The tensile property of SLM parts at different placement angle ψ was identified and the corresponding deformation behavior and failure mechanism were investigated. Interestingly, the part prepared by double stagger melt (DSM) style presented a strong <001> texture along the transverse direction (TD) rather than the growth orientation of the columnar grains (building direction, BD). This crystallographic variation imposed an immense effect on yield strength of SLM-processed parts by modifying the orientation relationship between texture and growth direction of grains. As ψ was set to 60°, the DSM-fabricated parts exhibited a lower Schmid factor, hence achieving a higher average yield strength σs of 536.6 MPa. The static fracture toughness UT was closely associated with the normal component force Fn imposed on preferential loading plane. By means of hatch style integration and part placement optimization, the dangerous “opening or tensile” loading mode was effectively avoided and reasonable compromise between the strength and ductility was achieved elaborately, thus obtaining an ultrahigh UT (3.478 × 108 J/m3) of SLM-processed parts. This study scientifically showed the great potentials of the SLM process to prepare 316L stainless steel products demanding challenging high-strength and high-toughness performance.

Methionine 109 plays a key role in Cu(II) binding to His111 in the 92–115 fragment of the human prion protein

The cellular prion protein (PrPC) is a monomeric glycoprotein expressed mainly in the central nervous system. Although its function is not understood, it has been proposed to be involved in Cu transport. Human PrP (hPrP) can bind up to six Cu(II) ions at its unstructured N-terminal region; two of them at the non-octarepeat region, encompassing His96 and His111. The Cu(II) coordination features of these two sites are practically identical, yet Cu ions have a preference for binding at the His111 site, which is unique in that it contains two Met residues in a MKHM motif. Here, the hPrP(92–115) peptide fragment, containing both His binding sites, and its variants with Met to Ile substitutions have been studied, to evaluate the role of Met109 and Met112 in the relative Cu(II) loading into the His111 and His96 sites. The fact that Cu(II) bound to His96 and His111 display distinct circular dichroism spectra allowed to discern Cu binding to each site under different experimental conditions. Through a combination of spectroscopic and calorimetric studies, we demonstrate that His111 has a slightly higher affinity for Cu(II) than His96, and that Met109 plays an important role in the binding preference of Cu(II) for the His111 site. Met109 profiles as a highly important residue that, not only assures a preferential loading of Cu(II) ions into the His111 site, but it also serves as a Cu(I) anchoring residue and it might be a key player for Cu transport by hPrP.

Tunable Permeability of Cross-Linked Microcapsules from pH-Responsive Amphiphilic Diblock Copolymers: A Dissipative Particle Dynamics Study.

Using dissipative particle dynamics simulation, we probe the tunable permeability of cross-linked microcapsules made from pH-sensitive diblock copolymers poly(ethylene oxide)-b-poly(N,N-diethylamino-2-ethyl methacrylate) (PEO-b-PDEAEMA). We first examine the self-assembly of non-cross-linked microcapsules and their pH-responsive collapse and then explore the effects of cross-linking and block interaction on the swelling or deswelling of cross-linked microcapsules. Our results reveal a preferential loading of hydrophobic dicyclopentadiene (DCPD) molecules in PEO-b-PDEAEMA copolymers. Upon reduction of pH, non-cross-linked microcapsules fully decompose into small wormlike clusters as a result of large self-repulsions of protonated copolymers. With increasing degree of cross-linking, the morphology of the microcapsule becomes more stable to pH change. The highly cross-linked microcapsule shell undergoes significant local polymer rearrangement in acidic solution, which eliminates the amphiphilicility and therefore enlarges the permeability of the shell. The responsive cross-linked shell experiences a disperse-to-buckle configurational transition upon reduction of pH, which is effective for the steady or pulsatile regulation of shell permeability. The swelling rate of the cross-linked shell is dependent on both electrostatic and nonelectrostatic interactions between the pH-sensitive groups as well as the other groups. Our study highlights the combination of cross-linking structure and block interactions in stabilizing microcapsules and tuning their selective permeability.

Abstract 3042: MIR142 loss-of-function mutations promote leukemogenesis through derepression of ASH1L resulting in increased HOX gene expression

Abstract MIR142 mutations have been identified in acute myeloid leukemia (AML) and non-Hodgkins lymphoma. In AML, all MIR142 mutations localize to the miR-142-3p seed sequence. We show that mutated MIR142 is unable to suppress several well-known targets of miR-142-3p. Interestingly, the mutations of miR-142-3p result in their preferential loading into the RNA-induced silencing complex, leading to the degradation of miR-142-5p. Accordingly, miR-142-5p expression is decreased in MIR142 mutated AML. Hence, MIR142 mutations in AML disrupt both miR-142-3p/5p functions. Thus, we modeled the effect of MIR142 mutations on hematopoiesis using Mir142-/- mice. We show that loss of miR142 results in significant increases in myeloid hematopoietic stem/progenitor cells (HSPCs), including granulocyte-macrophage progenitors, myeloid-biased multipotent progenitors (CD150- CD48+ Flk2- Kit+ Sca+ lineage-) and CD229- myeloid-biased HSCs (CD150+ CD48- Kit+ Sca+ lineage-). In contrast, there are significant decreases of megakaryocyte-erythroid progenitors and erythroid precursors. Although the number of HSCs is normal in Mir142-/- mice, HSC transplantation suggest that they are myeloid-biased. In AML, MIR142 mutations are commonly found in conjunction with mutations of IDH1/2. To assess the importance of this association, we transduced wildtype or Mir142-/- HSPCs with retrovirus expressing IDH2 R172K and then transplanted into lethally irradiated recipients. Expression of IDH2 R172K alone was sufficient to induce a lethal myeloproliferative neoplasm (MPN). In contrast, Mir142-/- alone did not result in MPN. However, loss of Mir142 cooperates with IDH2 R172K to produce a more severe MPN, with increased CD34+ blasts and more severe anemia. Moreover, secondary transplantation shows that Mir142-/- x IDH2 R172K cells but not IDH2 R172K cells efficiently engraft and induce MPN, suggesting that loss of miR142 increases leukemia-initiating activity. We identify the histone methyltransferase ASH1L as a target gene of miR142 that contributes to altered hematopoiesis in Mir142-/- mice. The 3’-untranslated region of ASH1L has four miR-142-3p binding sites, and luciferase reporter assay shows that miR142 suppresses its translation by 80%. Consistent with this observation, Ashl1 protein expression is 3-fold higher in Mir142-/- bone marrow. ASH1L is a key positive regulator of HOX gene expression. Accordingly, we observed markedly (5-10 fold) increased HoxA9/A10 expression in myeloid progenitors in Mir142-/- mice. Likewise, HoxA9/A10 expression is increased in CD34+ blasts from Mir142-/- x IDH2 R172K transplanted mice. Of note, increased HoxA9 expression has been shown to cooperate with mutant IDH1 to induce AML in mice. Together, these findings support a model in which loss-of-function mutations of MIR142 contribute to hematopoietic malignancies by derepressing ASH1L and inducing HOXA9/10 gene expression. Citation Format: Juo-Chin Yao, Terrence N. Wong, Maria Trissal, Rahul Ramaswamy, Yaping Sun, Pavan R. Reddy, Daniel C. Link. MIR142 loss-of-function mutations promote leukemogenesis through derepression of ASH1L resulting in increased HOX gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3042. doi:10.1158/1538-7445.AM2017-3042

The expression of heterologous Fe (III) phytosiderophore transporter HvYS1 in rice increases Fe uptake, translocation and seed loading and excludes heavy metals by selective Fe transport.

SummaryMany metal transporters in plants are promiscuous, accommodating multiple divalent cations including some which are toxic to humans. Previous attempts to increase the iron (Fe) and zinc (Zn) content of rice endosperm by overexpressing different metal transporters have therefore led unintentionally to the accumulation of copper (Cu), manganese (Mn) and cadmium (Cd). Unlike other metal transporters, barley Yellow Stripe 1 (HvYS1) is specific for Fe. We investigated the mechanistic basis of this preference by constitutively expressing HvYS1 in rice under the control of the maize ubiquitin1 promoter and comparing the mobilization and loading of different metals. Plants expressing HvYS1 showed modest increases in Fe uptake, root‐to‐shoot translocation, seed accumulation and endosperm loading, but without any change in the uptake and root‐to‐shoot translocation of Zn, Mn or Cu, confirming the selective transport of Fe. The concentrations of Zn and Mn in the endosperm did not differ significantly between the wild‐type and HvYS1 lines, but the transgenic endosperm contained significantly lower concentrations of Cu. Furthermore, the transgenic lines showed a significantly reduced Cd uptake, root‐to‐shoot translocation and accumulation in the seeds. The underlying mechanism of metal uptake and translocation reflects the down‐regulation of promiscuous endogenous metal transporters revealing an internal feedback mechanism that limits seed loading with Fe. This promotes the preferential mobilization and loading of Fe, therefore displacing Cu and Cd in the seed.

Abstract 2068: Engineering of hairpin loop enhances the loading of endogenously expressed pre-miRNA into extracellular vesicles

Abstract Extracellular vesicles (EVs) hold tremendous potential as drug delivery carriers for therapeutic nucleic acids such as microRNA (miRNA) due to their natural composition and ability to be engineered to contain targeting peptides on their surface. We have engineered HEK293T cells to secrete EVs by overexpressing Lamp-2A protein containing liver cancer targeting peptide PC94 and therapeutic pre-miR-199. The novel feature of this system is that both the cargo and the microvesicles are synthesized by the same cells, thus abrogating the need for loading synthetic oligonucleotides into EVs. The pre-miR-199a loop region was modified such that it resembled the HIV-1 transactivation response (TAR) RNA which was engineered into the Lamp2A intron. Correct splicing of the intron portion and processing of the mature miRNA was evaluated after its transfection into HEK293T cells. Computational modeling was used to study the interaction between the modified pre-miR-199a loop (TAR RNA) and the TAT peptide. This study exhibited a stable interaction between the two and also showed that the peptide is not bound to the stem portion of the RNA loop, permitting the insertion of any pre-miRNA sequence. EMSA gel shift, rDICER processing and luciferase assays were performed to study the correct binding, processing and functionality of the modified sequence. These results show that the modified loop is actively involved in binding with the TAT peptide and it enables the modified miRNA to be loaded in the microvesicles. In an effort to assess the loading of the therapeutic miR-199a-3p relative to other endogenous miRNAs contained within the EVs, we performed small RNA sequencing on RNA isolated from both the producing cells and purified EVs. Triplicate samples of RNA isolated from 3 different HEK293T producing cells were sequenced: wild type HEK293T and those stably transfected with the empty vector (empty) or the TAT/TAR pre-miR-199a (full). The expression of the miRNAs were ranked from the RNA sequenced in both the cells and EVs. Producing cells engineered to express miR-199a-3p containing the TAT/TAR loading motif ranked third when comparing the ratio of miRNAs loaded in the EVs from the full to empty cells. Interestingly, certain mature miRNAs were preferentially loaded into the EVs, including miR-451a, miR-122 and miR-1246. As reported by Villarroya-Beltri, et al., (Nature Comm., 2013) in human peripheral blood mononuclear cells, all three mature miRNAs contained 4 nucleotide “exo motifs” in their 3’ end that likely caused preferential loading into HEK293T EVs. Our data demonstrate that stably transfecting HEK293T cells with vectors expressing therapeutic miRNAs dramatically increases their loading into EVs. These mature miRNAs may be further engineered to contain exo motifs that could conceivably enhance their loading into EV drug carrier systems. Citation Format: Dhruvitkumar S. Sutaria, Jinmai Jiang, Ola A. Elgamal, Ana-Clara P. Azevedo-Pouly, Ryan E. Pavlovicz, Chenglong Li, Mitch A. Phelps, Thomas D. Schmittgen. Engineering of hairpin loop enhances the loading of endogenously expressed pre-miRNA into extracellular vesicles. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2068.

Evaluation of the sonosensitizing properties of nano-graphene oxide in comparison with iron oxide and gold nanoparticles

In cancer hyperthermia, ultrasound is considered as an appropriate source of energy to achieve desired therapeutic levels of heating. It is assumed that such a heating is targeted to cancer cells by using nanoparticles as sonosensitization agents. Here, we report the sonosensitizing effects of Nano-Graphene Oxide (NGO) and compare them with gold nanoparticles (AuNPs), Iron Oxide nanoparticles (IONPs).Experiments were conducted to explore the effects of nanoparticle type and concentration, as well as ultrasound power, on transient heating up of the solutions exposed by 1MHz ultrasound. Nanoparticles concentration was selected from 0.25 to 2.5mg/ml and the solutions were exposed by ultrasound powers from 1 to 8W. Real time temperature monitoring was done by a thermocouple and obtained data was analyzed.Temperature profiles of various nanoparticle solutions showed the higher heating rates, in comparison to water. Heating rise was strongly depended on nanoparticles concentration and ultrasound power. AuNPs showed a superior efficiency in heat generation enhancement in comparison to IONPs and NGO.Our result supports the idea of sonosensitizing capabilities of AuNPs, IONPs, and NGO. Targeted hyperthermia may be achievable by preferential loading of tumor with nanoparticles and subsequent ultrasound irradiation.

Studying Isoform-Specific mRNA Recruitment to Polyribosomes with Frac-seq.

Gene expression profiling is widely used as a measure of the protein output of cells. However, it is becoming more evident that there are multiple layers of post-transcriptional gene regulation that greatly impact protein output (Battle et al., Science 347:664-667, 2014; Khan et al., Science 342:1100-1104, 2013; Vogel et al., Mol Syst Biol 6:400, 2010). Alternative splicing (AS) impacts the expression of protein coding genes in several ways. Firstly, AS increases exponentially the coding-capacity of genes generating multiple transcripts from the same genomic sequence. Secondly, alternatively spliced mRNAs are subjected differentially to RNA-degradation via pathways such as nonsense mediated decay (AS-NMD) or microRNAs (Shyu et al., EMBO J 27:471-481, 2008). And thirdly, cytoplasmic export from the nucleus and translation are regulated in an isoform-specific manner, adding an extra layer of regulation that impacts the protein output of the cell (Martin and Ephrussi, Cell 136:719-730, 2009; Sterne-Weiler et al., Genome Res 23:1615-1623, 2013). These data highlight the need of a method that allows analyzing both the nuclear events (AS) and the cytoplasmic fate (polyribosome-binding) of individual mRNA isoforms.In order to determine how alternative splicing determines the polyribosome association of mRNA isoforms we developed Frac-seq. Frac-seq combines subcellular fractionation and high throughput RNA sequencing (RNA-seq). Frac-seq gives a window onto the translational fate of specific alternatively spliced isoforms on a genome-wide scale. There is evidence of preferential translation of specific mRNA isoforms (Coldwell and Morley, Mol Cell Biol 26:8448-8460, 2006; Sanford et al., Genes Dev 18:755-768; Zhong et al., Mol Cell 35:1-10, 2009; Michlewski et al., Mol Cell 30:179-189, 2008); the advantage of Frac-seq is that it allows analyzing the binding of alternatively spliced isoforms to polyribosomes and comparing their relative abundance to the cytosolic fraction. Polyribosomes are resolved by sucrose gradient centrifugation of cytoplasmic extracts, subsequent reading and extraction. The total mRNA fraction is taken prior ultracentrifugation as a measure of all mRNAs present in the sample. Both populations of RNAs are then isolated using phenol-chloroform precipitation; polyadenylated RNAs are selected and converted into libraries and sequenced. Bioinformatics analysis is then performed to measure alternatively spliced isoforms; several tools can be used such as MISO, RSEM, or Cufflinks (Katz et al., Nat Methods 7:1009-1015, 2010; Li and Dewey, BMC Bioinformatics 12:323, 2011; Trapnell et al., Nat Protoc 7:562-578, 2012). Comparison of total mRNAs and polyribosome-bound mRNAs can be used as a measure of the polyribosome association of specific isoforms based on the presence/absence of specific alternative splicing events in each fraction. Frac-seq shows that not all isoforms from a gene are equally loaded into polyribosomes, that mRNA preferential loading does not always correlate to its expression in the cytoplasm and that the presence of specific events such as microRNA binding sites or Premature Termination Codons determine the loading of specific isoforms into polyribosomes.

Effect of relative humidity on mechanical properties of a woven thermoplastic composite for automotive application

The purpose of this work is to characterise the influence of moisture content in a woven glass fibre reinforced polyamide 6,6 composite. Two different stacking sequences are studied: [(0/90)3] and [(±45)3] as well as the neat PA6,6 matrix. Samples have been conditioned through three ways: either water immersed, left at ambient temperature and humidity or dried in 35 °C oven. A one dimensional Fick's law has been used to model the water uptake in immersed samples. The glass transition temperature is highly affected by the presence of water and has been measured using modulated DSC technique. Finally, the effects of water on these composite materials have been investigated through tensile tests instrumented with acoustic emission monitoring (AE). Mechanical properties are highly affected by the presence of water in the composite. This result is even more visible on [(±45)3] sample because of the preferential loading of the matrix.

Tissue Iron Distribution Assessed by MRI in Patients with Iron Loading Anemias.

Bone marrow, spleen, liver and kidney proton transverse relaxation rates (R2), together with cardiac R2* from patients with sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNH) and non-transfusion dependent thalassemia (NTDT) have been compared with a control group. Increased liver and bone marrow R2 values for the three groups of patients in comparison with the controls have been found. SCD and PNH patients also present an increased spleen R2 in comparison with the controls. The simultaneous measurement of R2 values for several tissue types by magnetic resonance imaging (MRI) has allowed the identification of iron distribution patterns in diseases associated with iron imbalance. Preferential liver iron loading is found in the highly transfused SCD patients, while the low transfused ones present a preferential iron loading of the spleen. Similar to the highly transfused SCD group, PNH patients preferentially accumulate iron in the liver. A reduced spleen iron accumulation in comparison with the liver and bone marrow loading has been found in NTDT patients, presumably related to the differential increased intestinal iron absorption. The correlation between serum ferritin and tissue R2 is moderate to good for the liver, spleen and bone marrow in SCD and PNH patients. However, serum ferritin does not correlate with NTDT liver R2, spleen R2 or heart R2*. As opposed to serum ferritin measurements, tissue R2 values are a more direct measurement of each tissue’s iron loading. This kind of determination will allow a better understanding of the different patterns of tissue iron biodistribution in diseases predisposed to tissue iron accumulation.

In‐Solution Structural Considerations by 1H NMR and Solid‐State Thermal Properties of Inulin‐d‐α‐Tocopherol Succinate (INVITE) Micelles as Drug Delivery Systems for Hydrophobic Drugs

1H NMR is a suitable method to clarify the kind of interactions leading to the self‐assembly of amphiphilic polymers. This work shows, from 1H NMR studies performed in solution, that the self‐assembly ability of the synthesized Inulin‐d‐α‐tocopherol succinate (INVITE) amphiphilic polymers, can be addressed to specific π–π interactions between the aromatic regions of d‐α‐tocopherol. This result suggests the use of INVITE systems for the preferential loading of aromatic group bearing drugs such as curcumin. The preparation conditions, effect of drug loading, and lyophilization on the INVITE systems are evaluated by DSC and thermogravimetric analysis (TGA) analysis to assess whether common pharmaceutical processes could influence the physical properties of the amphiphilic polymers, such as crystallinity, glass‐transition temperature or thermal degradation, to predict the physical stability of the systems upon administration. Furthermore, the size stability of the micelle systems up to 60 days is monitored to assess the feasibility of the INVITE micelles’ long‐term storage upon reconstitution with water. image

Asymmetrical hip loading correlates with metal ion levels in patients with metal-on-metal hip resurfacing during sit-to-stand

The occurrence of pseudotumours following metal-on-metal hip resurfacing arthroplasty (MoMHRA) has been associated with high serum metal ion levels and consequently higher than normal bearing wear. Measuring ground reaction force is a simple method of collecting information on joint loading during a sit-to-stand (STS). We investigated vertical ground reaction force (VGRF) asymmetry during sit-to-stand for 12 MoMHRA patients with known serum metal ion levels. Asymmetry was assessed using two methods: a ratio of VGRF for implanted/unimplanted side and an absolute symmetry index (ASI). It was found that subjects with high serum metal ion levels preferentially loaded their implanted sides. The difference between the two groups was most apparent during the first 22% of STS. VGRF ratio showed significant and strong correlation with serum metal ion levels (Spearman's rho = 0.8, p = 0.003). These results suggest that individual activity patterns play a role in the wear of MoMHRA and preferential loading of an implanted limb during the initiation of motion may increase the wear of metal-on-metal hip replacements.

Moving toward a precise nutrition: preferential loading of seeds with essential nutrients over non-essential toxic elements

Plants and seeds are the main source of essential nutrients for humans and livestock. Many advances have recently been made in understanding the molecular mechanisms by which plants take up and accumulate micronutrients such as iron, zinc, copper and manganese. Some of these mechanisms, however, also facilitate the accumulation of non-essential toxic elements such as cadmium (Cd) and arsenic (As). In humans, Cd and As intake has been associated with multiple disorders including kidney failure, diabetes, cancer and mental health issues. Recent studies have shown that some transporters can discriminate between essential metals and non-essential elements. Furthermore, sequestration of non-essential elements in roots has been described in several plant species as a key process limiting the translocation of non-essential elements to aboveground edible tissues, including seeds. Increasing the concentration of bioavailable micronutrients (biofortification) in grains while lowering the accumulation of non-essential elements will likely require the concerted action of several transporters. This review discusses the most recent advances on mineral nutrition that could be used to preferentially enrich seeds with micronutrients and also illustrates how precision breeding and transport engineering could be used to enhance the nutritional value of crops by re-routing essential and non-essential elements to separate sink tissues (roots and seeds).

Preferential Loading of the ACL Compared With the MCL During Landing

Background: Strong biomechanical and epidemiological evidence associates knee valgus collapse with isolated, noncontact anterior cruciate ligament (ACL) injuries. However, a concomitant injury to the medial collateral ligament (MCL) would be expected under valgus collapse, based on the MCL’s anatomic orientation and biomechanical role in knee stability. Purpose/Hypothesis: The purpose of this study was to investigate the relative ACL to MCL strain patterns during physiological simulations of a wide range of high-risk dynamic landing scenarios. We hypothesized that both knee abduction and internal tibial rotation moments would generate a disproportionate increase in the ACL strain relative to the MCL strain. However, the physiological range of knee abduction and internal tibial rotation moments that produce ACL injuries are not of sufficient magnitude to compromise the MCL’s integrity consistently. Study Design: Controlled laboratory study. Methods: A novel in sim approach was used to test our hypothesis. Seventeen cadaveric lower extremities (mean age, 45 ± 7 years; 9 female and 8 male) were tested to simulate a broad range of landings after a jump under anterior tibial shear force, knee abduction, and internal tibial rotation at 25° of knee flexion. The ACL and MCL strains were quantified using differential variable reluctance transducers. An extensively validated, detailed finite element model of the lower extremity was used to help better interpret experimental findings. Results: Anterior cruciate ligament failure occurred in 15 of 17 specimens (88%). Increased anterior tibial shear force and knee abduction and internal tibial rotation moments resulted in significantly higher ACL:MCL strain ratios (P < .05). Under all modes of single-planar and multiplanar loading, the ACL:MCL strain ratio remained greater than 1.7, while the relative ACL strain was significantly higher than the relative MCL strain (P < .01). Relative change in the ACL strain was demonstrated to be significantly greater under combined multiplanar loading compared with anterior tibial shear force (P = .016), knee abduction (P = .018), and internal tibial rotation (P < .0005) moments alone. Conclusion: While both the ACL and the MCL resist knee valgus during landing, physiological magnitudes of the applied loads leading to high ACL strain levels and injuries were not sufficient to compromise the MCL’s integrity. Clinical Relevance: A better understanding of injury mechanisms may provide insight that improves current risk screening and injury prevention strategies. Current findings support multiplanar knee valgus collapse as a primary factor contributing to a noncontact ACL injury.

Integrating arm movement into bridge exercise: Effect on EMG activity of selected trunk muscles

The purpose of this study was to determine whether incorporating arm movement into bridge exercise changes the electromyographic (EMG) activity of selected trunk muscles. Twenty healthy young men were recruited for this study. EMG data were collected for the rectus abdominis (RA), internal oblique (IO), erector spinae (ES), and multifidus (MF) muscles of the dominant side. During bridging, an experimental procedure was performed with two options: an intervention factor (with and without arm movement) and a bridging factor (on the floor and on a therapeutic ball). There were significant main effects for the intervention factor in the IO and ES and for the bridging factor in the IO. The RA and IO showed significant interaction between the intervention and bridge factors. Furthermore, IO/RA ratio during bridging on the floor (without arm movement, 2.05±2.61; with arm movement, 3.24±3.42) and bridging on the ball (without arm movement: 2.95±3.87; with arm movement: 5.77±4.85) showed significant main effects for, and significant interaction between the intervention and bridge factors. However, no significant main effects or interaction were found for the MF/ES ratio. These findings suggest that integrating arm movements during bridge exercises may be used to provide preferential loading to certain trunk muscle groups and that these effects may be better derived by performing bridge exercises on a therapeutic ball.

MicroRNAs

MicroRNAs (miRs) are small noncoding RNAs (≈23 nucleotides) that regulate gene expression at a posttranscriptional level by degradation or translational inhibition of target mRNAs. Initially discovered as regulators of development in plants, worms, and fruitflies, miRs are emerging as pivotal modulators of cardiovascular biology and disease in mice and men.1 Besides a cell-specific transcription factor profile, cell-specific miR-regulated gene expression is integral to cell fate and activation decisions. Thus, the cell types involved in atherosclerosis, vascular disease, and its myocardial sequelae may be differentially regulated by distinct miRs, thereby controlling highly complex processes, for example, smooth muscle cell phenotype and inflammatory responses of endothelial cells or macrophages.2 The generation of mature miR strands requires several steps of processing of the primary miR gene transcript, including cleavage of the terminal loop of miR-precursors by the RNase III enzyme, Dicer, to produce miR duplexes. Although either strand of the miR duplex can be stably associated with an Argonaute (Ago) family protein, preferential loading of a specific strand (ie, the guide strand) onto the miR-induced silencing complex (RISC) is common. The strand that is not loaded into the RISC (ie, the passenger strand or miR*) is typically degraded.3 Strand selection may be tissue-specific, and an accumulation observed for both strands implies that each strand can separately enter the silencing complex.4 Because of the often imperfect complementary binding of the miR seed sequence to the mRNA recognition element, an individual miR can affect the expression of hundreds of target mRNAs. However, the degree of repression seems to be …

Composite Sr2TiO4/SrTiO3(La,Cr) heterojunction based photocatalyst for hydrogen production under visible light irradiation

A composite Sr2TiO4/SrTiO3(La,Cr) heterojunction photocatalyst has been prepared by a simple in situ polymerized complex method. Upon Pt cocatalyst loading, this catalyst shows higher photocatalytic activity towards hydrogen production than individual SrTiO3(La,Cr) and Sr2TiO4(La,Cr) in the presence of methanol sacrificial reagent. Microscopic morphology studies show that well defined heterojunctions are formed by matching the lattice fringes of SrTiO3(La,Cr) and Sr2TiO4(La,Cr), and Pt was preferentially loaded on the surface of the Sr2TiO4(La,Cr) component in the composite Sr2TiO4/SrTiO3(La,Cr) photocatalyst. XPS and EPR analyses show that the composite photocatalyst also has the lowest amount of Cr6+ electron trapping sites. Band structure analysis by combining absorption spectroscopy and Mott–Schottky plots shows that, in the composite photocatalyst, the photogenerated electrons and holes tend to migrate from SrTiO3(La,Cr) to Sr2TiO4(La,Cr) and from Sr2TiO4(La,Cr) to SrTiO3(La,Cr), respectively. This kind of band structure can facilitate charge transfer and separation driven by the minor potential difference between the two components, which is further confirmed by the observation of long lived electrons in the time resolved FT-IR spectroscopic study. It is concluded that the superior photocatalytic activity of the composite heterojunction photocatalyst is due to efficient charge transfer and separation by well defined heterojunctions formed between SrTiO3(La,Cr) and Sr2TiO4(La,Cr), preferential loading of Pt nanoparticles on the Sr2TiO4(La,Cr) component, and the lowest amount of Cr6+ in the composite photocatalyst. The tailored design and synthesis of the composite heterojunction structure is a promising approach for the improvement of the photocatalytic activity of a photocatalyst.

Preferential Loading of the ACL Compared to the MCL during Landing: A Novel In Sim Approach Yields the Multi-Planar Mechanism of Dynamic Valgus during ACL Injury

Objectives:Strong biomechanical and epidemiologic evidence associates knee valgus collapse with isolated non-contact ACL injury. However, the predominance of isolated non-contact anterior cruciate ligament (ACL) injuries is challenging for clinicians and researchers to explain, as the medial collateral ligament (MCL) has been reported to be the primary restraint against knee valgus. The purpose of this study was to investigate the relative ACL to MCL strain patterns during physiologic simulations of a wide range of high-risk dynamic landing scenarios. We hypothesized that both knee abduction and internal tibial rotation moments would generate a disproportionate increase in ACL strain relative to MCL strain. However, the physiologic range of knee abduction and internal tibial rotation moments that produce ACL injuries would not be of sufficient magnitude to consistently compromise MCL integrity.Methods:A novel in sim approach was used to test our hypotheses. 17 cadaveric lower extremities (45 ± 7 years, 9 female & 8 male) were tested to simulate a broad range of landing conditions following a jump under anterior tibial shear, knee abduction and internal tibial rotation. Specimens were oriented to simulate lower extremity posture during ground strike while landing from a jump. Landing was simulated by applying an impulsive axial impact load (simulating ground reaction forces) under simulated muscle forces. ACL and MCL strains were quantified using DVRT displacement transducers arthroscopically placed across the ACL AM-bundle and sutured to the anterior/middle/posterior aspects of superficial MCL across the joint line. Specimens were tested until failure. Multiple paired and independent t-tests along with general linear models were used to investigate the changes in strain levels under each modes of loading. An extensively validated, detailed finite element model of the lower extremity was used to better interpret experimental findings.Results:ACL failure was generated in 15 of 17 specimens (88%). Increased anterior tibial shear force, and knee abduction and internal tibial rotation moments resulted in significantly higher ACL: MCL strain ratios (p<0.05) compared to landing under no applied external loads. Under all modes of single- and multi-planar loading, ACL: MCL strain ratio remained greater than 1.7, and relative ACL strain was significantly higher than relative MCL strain (p<0.003, Figure 1). Relative change in ACL strain was significantly greater under combined multi-planar loading compared to ACL strain under anterior tibial shear force (p=0.016), knee abduction (p=0.018) and internal tibial rotation (p<0.0005) moments alone.Conclusion:The tibiofemoral frontal plane loading mechanism has become a recent topic of debate as a contributing factor to non-contact ACL injuries. Both in vivo and video analyses studies indicate that increased knee abduction is associated with increased risk for ACL injury. The current findings demonstrates that while both the ACL and MCL resist knee valgus during landing, physiological magnitudes of the applied loads that lead to high ACL strain levels and injury were not sufficient to compromise MCL integrity. Further, these findings support multi-planar knee valgus collapse as a primary mechanism of non-contact ACL injury. This enhances our understanding of the non-contact ACL injury mechanism, and provides insight that can improve current risk screening and injury prevention strategies.

Characterization of Ca2 + signaling in the external yolk syncytial layer during the late blastula and early gastrula periods of zebrafish development

Preferential loading of the complementary bioluminescent (f-aequorin) and fluorescent (Calcium Green-1 dextran) Ca2+ reporters into the yolk syncytial layer (YSL) of zebrafish embryos, revealed the generation of stochastic patterns of fast, short-range, and slow, long-range Ca2+ waves that propagate exclusively through the external YSL (E-YSL). Starting abruptly just after doming (~4.5h post-fertilization: hpf), and ending at the shield stage (~6.0hpf) these distinct classes of waves propagated at mean velocities of ~50 and ~4μm/s, respectively. Although the number and pattern of these waves varied between embryos, their initiation site and arcs of propagation displayed a distinct dorsal bias, suggesting an association with the formation and maintenance of the nascent dorsal-ventral axis. Wave initiation coincided with a characteristic clustering of YSL nuclei (YSN), and their associated perinuclear ER, in the E-YSL. Furthermore, the inter-YSN distance (IND) appeared to be critical such that Ca2+ wave propagation occurred only when this was <~8μm; an IND >~8μm was coincidental with wave termination at shield stage. Treatment with the IP3R antagonist, 2-APB, the Ca2+ buffer, 5,5′-dibromo BAPTA, and the SERCA-pump inhibitor, thapsigargin, resulted in a significant disruption of the E-YSL Ca2+ waves, whereas exposure to the RyR antagonists, ryanodine and dantrolene, had no significant effect. These findings led us to propose that the E-YSL Ca2+ waves are generated mainly via Ca2+ release from IP3Rs located in the perinuclear ER, and that the clustering of the YSN is an essential step in providing a CICR pathway required for wave propagation. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.

On stress and strain in a continuous-discontinuous shear zone undergoing simple shear and volume loss

I summarise observations within a continuous-discontinuous shear zone to discuss the local stress and strain conditions experienced within a mixed rheology shear zone undergoing volume loss and deformation approximating simple shear. The Chrystalls Beach Complex, New Zealand, comprises phacoids formed from dismembered beds by layer-parallel extension, enclosed within a relatively incompetent matrix. Local extension is generally subparallel to the regional direction of shortening, and overall it appears that layer-parallel extension is a geometrical necessity in low angle shear zones where significant flattening occurs in response to simple shear accompanied by volume loss.Preferential stress loading of phacoids is predicted by fibre-loading theory, and the failure of phacoids by brittle fracture is thereby governed by fibre stresses transferred from the matrix. The principal stress orientations in a phacoid are likely rotated relative to the matrix, and either parallel or perpendicular to the phacoid-matrix interface. As preferential loading of phacoids decreases the stress level in the matrix, an increased volume fraction of phacoids increases the strength of the shear zone as a whole. However, only small matrix volume fractions are required for the composite to act nearly as weak as the matrix.