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BackgroundSpinal muscular atrophy (SMA) is a motor neuron disease caused by mutations of survival of motor neuron 1 (SMN1) gene, which encodes the SMN protein. SMN2, a nearly identical copy of SMN1, with several single-nucleotide substitutions leading to predominant skipping of its exon 7, is insufficient to compensate for loss of SMN1. Heterogeneous nuclear ribonucleoprotein R (hnRNPR) has been previously shown to interact with SMN in the 7SK complex in motoneuron axons and is implicated in the pathogenesis of SMA. Here, we show that hnRNPR also interacts with SMN1/2pre-mRNAs and potently inhibits exon 7 inclusion.MethodsIn this study, to examine the mechanism that hnRNPR regulates SMN1/2splicing, deletion analysis in an SMN2minigene system, RNA-affinity chromatography, co-overexpression analysis and tethering assay were performed. We screened antisense oligonucleotides (ASOs) in a minigene system and identified a few that markedly promoted SMN2exon 7 splicing.ResultsWe pinpointed an AU-rich element located towards the 3′ end of the exon that mediates splicing repression by hnRNPR. We uncovered that both hnRNPR and Sam68 bind to the element in a competitive manner, and the inhibitory effect of hnRNPR is much stronger than Sam68. Moreover, we found that, among the four hnRNPR splicing isoforms, the exon 5-skipped one has the minimal inhibitory effect, and ASOs inducing hnRNPRexon 5 skipping also promote SMN2exon 7 inclusion.ConclusionWe identified a novel mechanism that contributes to mis-splicing of SMN2exon 7.

It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripheral adenosine A1receptor (pADORA1) signaling; however, it remains unclear whether systemic and adipose tissue metabolism would also be under the control of central (c) ADORA1signaling. Here, we use tissue-specific pharmacology and metabolic tools to clarify the roles of cADORA1signaling in energy and adipocyte physiology. We found that cADORA1signaling reduces body weight while also inducing adipose tissue lipolysis. cADORA1signaling also increases adipose tissue sympathetic norepinephrine content. In contrast, pADORA1signaling facilitates a high-fat diet-induced obesity (DIO). We propose here a novel mechanism in which cADORA1and pADORA1signaling hinder and aggravate DIO, respectively.

Breast cancer represents a heterogeneous group of human cancer at both histological and molecular levels. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are the most commonly used biomarkers in clinical practice for making treatment plans for breast cancer patients by oncologists. Recently, PD-L1 testing plays an important role for immunotherapy for triple-negative breast cancer. With the increased understanding of the molecular characterization of breast cancer and the emergence of novel targeted therapies, more potential biomarkers are needed for the development of more personalized treatments. In this review, we summarized several main prognostic and predictive biomarkers in breast cancer at genomic, transcriptomic and proteomic levels, including hormone receptors, HER2, Ki67, multiple gene expression assays, PD-L1 testing, mismatch repair deficiency/microsatellite instability, tumor mutational burden, PIK3CA, ESR1 andNTRKand briefly introduced the roles of digital imaging analysis in breast biomarker evaluation.

A comparative study was carried out on the wear of 38CrSi high-alloy steel using TiCrAlN- and TiAlN-coated tools. The presence of elemental Cr in the TiCrAlN coating resulted in formation of a Cr–O film on the tool, which provided a lower friction coefficient. This also mitigated transfer of cutting heat to the tool substrate and inhibited elemental diffusion between the tool and the workpiece. Simultaneously, the hard Cr–O film, which formed outside the Al–O film, provided excellent wear resistance and protected the Al–O film. Thus, elemental Cr played an active role in enhancing the wear resistance of the tool, prolonging its life. A workpiece cut using a TiCrAlN-coated tool had a surface roughness of 0.79 µm, which was about 62% lower than that obtained using a TiAlN-coated tool. Although wear of the TiCrAlN-coated tool was reduced, reaching 0.2 mm over the standard test time of 8 min, this time was 300% longer than that observed with the TiAlN-coated tool. Furthermore, the cutting force components were smaller, at up to 8 N, and the cutting force was 50% lower than with the TiAlN-coated tool. The wear and failure mechanisms of micro-milling 38CrSi alloy were the product of a combination of forms of wear and followed the wear law in terms of tool tip breakage, coating damage, abrasive wear, and adhesive wear; coating damage had the most important effect on tool life.

Papanicolaou testing is effective in identifying squamous intraepithelial lesions of the cervix. Endocervical adenocarcinoma (EAC) and adenocarcinoma in situ (AIS) are far less commonly identified. Endocervical curettings (ECCs) are usually obtained after colposcopic biopsy, sample the endocervical canal, and aid in the detection of endocervical glandular lesions. Here, we examine the utility of Papanicolaou testing and endocervical curetting for detecting AIS and EAC.

Abdominopelvic washing cytology is a common specimen evaluated for ovarian, fallopian tubal, and peritoneal cancer staging or other nongynecologic malignancies presented as metastases. We reviewed our experience in diagnosing abdominopelvic washing specimens and assessing the primary tumor types and origins of the positive abdominopelvic washings.

Functional polymers show great potential in information storage applications. However, most of these polymer-based memory devices demonstrate limited capacity because of binary memory characteristic. Herein, three novel donor–acceptor-type bipolar conjugated copolymers containing the naphthalene benzimidazole unit as the acceptor and fluorene/carbazol as the donor were synthesized by Suzuki cross-coupling reaction. When applied in memory devices, these as-prepared polymers exhibit unique ternary resistance switch memory behaviors with high switching current ratios of 1:101.5:104, 1:101.7:105.5, and 1:102.3:103.2, respectively, low threshold voltage of −1.00 V/–1.60 V, −1.00 V/–1.45 V, and −1.45 V/–2.00 V, respectively. The retention time exceeds 104s and excellent stability over 103cycles. The resistance switching mechanism is well explained by the charge trap model. This work provides a new direction for the rational design and fabrication of high-performance electrical storage devices with multistage transition states.

In this paper, the Taguchi method has been used to optimize cutting parameters in the turning of Ti6Al4V/Al7050 laminates under elliptical vibration cutting. The turning tests were conducted based on L16 orthogonal array, which was designed by the Taguchi method. The analysis of variance was used to calculate impacts of cutting parameters on cutting forces and temperature. The analysis of results showed that the vibration frequency is the dominant factor on the cutting force and the vibration amplitude is a dominant factor affecting the temperature. The analysis of variance was also used to predict the cutting force and temperature in the turning of Ti6Al4V/Al7050 laminate. A good agreement between the predicted and the actual value can be found in the results.

Endometrial polyps embedded in the fetal membranes have only rarely been described. A review of the English literature showed only one abstract describing this occurrence and to the best of our knowledge, there have been no other publications of this entity. Herein we present a case of a 37-yr-old woman with a history prior abortion and complicated pregnancy (type 2 diabetes mellitus and preeclampsia) who delivered by cesarean section. Although the placenta did not show hypertensive vasculopathic changes or other pathologic findings, an endometrial polyp embedded within the fetal membranes was present. Recognition of this rarely reported entity is important in order to avoid confusion with a significant neoplastic process.

Metastases that present as pancreatic masses are rare. Understanding and recognizing this uncommon occurrence during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) will help in making an accurate diagnosis and planning for clinical management. In this study, we reviewed our experience in diagnosing pancreatic secondary tumors.

In the conceptual design stage of new product development, one of the major challenges is how to effectively determine the single best scheme from multiple alternatives. Based on the Axiomatic Design Theory, this paper proposes a new method to analyze and compare alternative schemes, and the Markov function is then used to calculate cost and determine the optimization direction of the chosen scheme. The cost of the optimal solution is estimated through calculations with utility functions. To add more details to the final design, it is necessary to consider both the working environment and user preferences, then to further analyze the schemes via fuzzy intuitions in order to determine the best prototyping and optimization strategy. This paper employs the design process of a library robot, which is designed in the context of university campus environment, as an illustrate example to showcase how to use the proposed method.

C50H38F18O16Ce2, monoclinic, C2/c(no. 15), a= 15.589(3)Å, b= 13.118(2) Å, c= 29.118(5) Å, β= 92.285(2)°, V= 5949.8(18) Å3, Z= 4, Rgt(F) = 0.0452, wRref(F2) = 0.1321, T = 273 K.

AbstractA series of tensile tests for pure copper sheets containing drilled holes of multi-configurations are carried out on a tensile split Hopkinson bar (TSHB) at a range of tensile velocities. The dynamic growth and coalescence of drilled voids were recorded by a high-speed camera. The results of scanning electron microscopical (SEM) investigation of microvoid evolution at edges of ruptured zones between drilled voids in recovered sheets show void coalescence mechanisms, which are similar to evolution of visualized drilled voids. The experimentally recovered and high-speed camera recorded evolution of drilled voids in pure copper sheets are compared with the numerical simulations involving different models for void coalescence in order to overcome the difficulty of assessing the validity of available models for void coalescence. The possible application of Thomason model and Brown–Embury model for void coalescence to thermoviscoplastic material was explored under impact tension, and the rapid local straining of intervoid ligament was revealed.

In order to make effective measure for the stress, strain and strain rate in the specimen, a tensile split Hopkinson bar (TSHB) was optimized in the first loading duration and the thermoviscoplastic models for a pure copper were determined. The deformation of the pure copper bar during the multi-tensile loading including the necking process in the optimized TSHB testing was recorded by a high speed camera and was used in providing an extensional check of the determined thermoviscoplastic models of the pure copper. The thermoviscoplastic models determined in a certain range of strain were employed in numerically simulating the large deformation of the pure copper bar to adjust the thermoviscoplastic model to describing large strain range. The instability strain of thermoviscoplastic materials in simple tension given by Batra et al was compared with the experimental strain at diffuse necking of the pure copper bar and the computed instability strain based on the load-average strain of the pure copper bar. The local necking of the pure copper bar in the optimized TSHB testing was numerically simulated using the micro-mechanical data given by Ragab and was compared with the recorded necking.

In order to make effective measure for the stress, strain and strain rate in the specimen, a tensile split Hopkinson bar (TSHB) was optimized in the first loading duration and the thermoviscoplastic models for a pure copper were determined. The deformation of the pure copper bar during the multi-tensile loading including the necking process in the optimized TSHB testing was recorded by a high speed camera and was used in providing an extensional check of the determined thermoviscoplastic models of the pure copper. The thermoviscoplastic models determined in a certain range of strain were employed in numerically simulating the large deformation of the pure copper bar to adjust the thermoviscoplastic model to describing large strain range. The instability strain of thermoviscoplastic materials in simple tension given by Batra et al was compared with the experimental strain at diffuse necking of the pure copper bar and the computed instability strain based on the load-average strain of the pure copper bar. The local necking of the pure copper bar in the optimized TSHB testing was numerically simulated using the micro-mechanical data given by Ragab and was compared with the recorded necking.

AbstractIn order to make effective measure for the stress, strain and strain rate in the specimen, a tensile split Hopkinson bar (TSHB) was optimized in the first loading duration and the thermoviscoplastic models for a pure copper were determined. The deformation of the pure copper bar during the multi-tensile loading including the necking process in the optimized TSHB testing was recorded by a high speed camera and was used in providing an extensional check of the determined thermoviscoplastic models of the pure copper. The thermoviscoplastic models determined in a certain range of strain were employed in numerically simulating the large deformation of the pure copper bar to adjust the thermoviscoplastic model to describing large strain range. The instability strain of thermoviscoplastic materials in simple tension given by Batra et al was compared with the experimental strain at diffuse necking of the pure copper bar and the computed instability strain based on the load-average strain of the pure copper bar. The local necking of the pure copper bar in the optimized TSHB testing was numerically simulated using the micro-mechanical data given by Ragab and was compared with the recorded necking.

C50H38F18Lu2O16, monoclinic, C2/c(no. 15), a= 15.7024(12) Å, b= 12.6169(10) Å, c= 29.715(2) Å, β= 91.919(10)°, V= 5883.7(8) Å3, Z= 4, Rgt(F) = 0.0273, wRref(F2) = 0.066, T= 273 K.

C24H16CuF6O4, triclinic, P1̄ (no. 2), a= 6.5651(7) Å, b= 9.4145(10) Å, c= 9.5014(11) Å, α= 68.668(10)°, β= 77.063(9)°, γ= 86.847(9)°, V= 532.91(11) Å3, Z= 1, Rgt(F) = 0.0596, wRref(F2) = 0.1477, T= 293 K.

C13H10BF5O3, triclinic, P1̄ (no. 2), a= 7.737(2) Å, b= 7.8600(19) Å, c= 11.803(3) Å, α= 82.03(2)°, β= 76.91(2)°, γ= 69.69(2)°, V= 654.2(3) Å3, Z= 2, Rgt(F) = 0.0471, wRref(F2) = 0.1203, T= 293 K.

C11H6BF5O3, orthorhombic, P21212 (no. 18), a= 13.236(4) Å, b= 18.566(5) Å, c= 4.7869(13) Å, V= 1176.3(6) Å3, Z= 4, Rgt(F) = 0.0442, wRref(F2) = 0.1307, T= 296 K.

C12H6F6O3, monoclinic, P21/c(no. 14), a= 9.433(1) Å, b= 15.567(2) Å, c= 7.682(1) Å, β= 102.83(1)°, V=1099.95(3) Å3, Z= 4, Rgt(F) = 0.0433, wRref(F2) = 0.1264, T= 293 K.

C10H11ClO2, triclinic, P1̅ (No. 2), a= 7.8485(8) Å, b= 8.0420(8) Å, c= 8.8701(9) Å, α= 107.4340(10)°, β= 106.307(10)°, γ= 101.9710(10)°, V= 485.97(8) Å3, Z= 2, Rgt(F)= 0.0513, wRref(F2)= 0.1405, T= 296 K.

C10H11ClO2triclinic, P1̅ (No. 2), a= 7.8470(3) Å, b= 8.0375(3) Å, c= 9.2261(4) Å, α= 77.052(4)°, β= 86.981(5)°, γ= 61.011(4)°, V= 494.98(3) Å3, Z= 4, Rgt(F)= 0.0441, wRref(F2)= 0.1388, T= 296 K.