太渊穴自发红外辐射光谱研究

为研究穴位自发红外辐射特性，采用自制高灵敏度PHE201体裹红外光谱仪检测47名健康成年人和50名冠心病患者太渊穴1．5-16μm波段自发红外辐射光谱。结果：冠心病患者与正常人太渊穴自发红外辐射光谱形态基本相似，其峰值相位不存在统计学差异；在某些波段，冠心病患者的红外辐射强度与正常人的相比有显着差异。结论：冠心病患者心脏病理信息在太渊穴红外辐射特性上的反映主要是某些特定波段红外辐射强度的变化。     

人血清中环境雌激素的柱前荧光衍生-高效液相色谱测定法

目的建立对硝基苯甲酰氯柱前荧光衍生-高效液相色谱法同时测定人血清中环境雌激素双酚A、壬基酚、17α-乙炔基雌二醇以及内源性雌激素雌三醇、17α-雌二醇和17β-雌二醇的方法。方法血清样品经乙腈沉淀蛋白后,用乙醚萃取游离态雌激素,N2气流挥干、在无水条件下,雌激素与对硝基苯甲酰氯反应生成荧光产物,用高效液相色谱法定量。结果该法线性范围上限可达1.0×104μg/L,检测限为2.7~8.3μg/L,加标回收率范围为72.6%~98.6%。方法精密度为1.29%~4.52%。结论应用该法对10份血清样进行了测定,结果满意,该方法有应用推广价值。     

Algorithm for Determining Time Series of Phase Transformations in the Solid State Using Long-Short-Term Memory Neural Network

In the numerical analysis of manufacturing processes of metal parts, many material properties depending on, for example, the temperature or stress state, must be taken into account. Often these data are dependent on the temperature changes over time. Strongly non-linear material property relationships are usually represented using diagrams. In numerical calculations, these diagrams are analyzed in order to take into account the coupling between the properties. An example of these types of material properties is the dependence of the kinetics of phase transformations in the solid state on the rate and history of temperature change. In literature, these data are visualized Continuous Heating Transformation (CHT) and Continuous Cooling Transformation (CCT) diagrams. Therefore, it can be concluded that time series analysis is important in numerical modeling. This analysis can also be performed using neural networks. This work presents a new approach to storing and analyzing the data contained in the discussed CCT diagrams. The application of Long-Short-Term Memory (LSTM) neural networks and their architecture to determine the correct values of phase fractions depending on the history of temperature change was analyzed. Moreover, an area of research was elements that determine what type of information should be stored by LSTM network coefficients, e.g., whether the network should store information about changes of single phase transformations, or whether it would be better to extract data from differences between several networks with similar architecture. The purpose of the studied network is strongly different from typical applications of artificial neural networks. The main goal of the network was to store information (even by overfitting the network) rather than some form of generalization that allows computation for unknown cases. Therefore, the authors primarily investigated in the ability of the layer-based LSTM network to store nonlinear time series data. The analyses presented in this paper are an extension of the issues presented in the paper entitled “Model of the Austenite Decomposition during Cooling of the Medium Carbon Steel Using LSTM Recurrent Neural Network”.     

Formation and Thermal Stability of the ω-Phase in Ti–Nb and Ti–Mo Alloys Subjected to HPT

This paper discusses the features of ω-phase formation and its thermal stability depending on the phase composition, alloying element and the grain size of the initial microstructure of Ti–Nb and Ti–Mo alloys subjected to high-pressure torsion (HPT) deformation. In the case of two-phase Ti–3wt.% Nb and Ti–20wt.% Nb alloys with different volume fractions of α- and β-phases, a complete β→ω phase transformation and partial α→ω transformation were found. The dependence of the α→ω transformation on the concentration of the alloying element was determined: the greater content of Nb in the α-phase, the lower the amount of ω-phase that was formed from it. In the case of single-phase Ti–Mo alloys, it was found that the amount of ω-phase formed from the coarse-grained β-phase of the Ti–18wt.% Mo alloy was less than the amount of the ω-phase formed from the fine α′-martensite of the Ti–2wt.% Mo alloy. This was despite the fact that the ω-phase is easier to form from the β-phase than from the α- or α′-phase. It is possible that the grain size of the microstructure also affected the phase transformation, namely, the fine martensitic plates more easily gain deformation and overcome the critical shear stresses necessary for the phase transformation. It was also found that the thermal stability of the ω-phase in the Ti–Nb and Ti–Mo alloys increased with the increasing concentration of Nb or Mo.     

Tomonaga–Luttinger Spin Liquid and Kosterlitz–Thouless Transition in the Spin-1/2 Branched Chains: The Study of Topological Phase Transition

In the present work, we provide a comprehensive numerical investigation of the magnetic properties and phase spectra of three types of spin-1/2 branched chains consisting of one, two and three side spins per unit block with intra-chain interaction and a uniform inter-chain interaction in the presence of an external magnetic field. In a specific magnetic field interval, the low-temperature magnetization of these chains shows a step-like behavior with a pronounced plateau depending on the strength and the type of intra-chain interaction being ferromagnetic or antiferromagnetic. We demonstrate that when inter-chain interaction J1 is antiferromagnetic and intra-chain interaction J2 is ferromagnetic, the magnetization of the models manifests a smooth increase without a plateau, which is evidence of the existence of a Luttinger-like spin liquid phase before reaching its saturation value. On the other hand, when J1 is ferromagnetic and J2 is antiferromagnetic, the low-temperature magnetization of the chain with two branches shows an intermediate plateau at one-half of the saturation magnetization that breaks a quantum spin liquid phase into two regions. The magnetization of the chain with three branches exhibits two intermediate plateaus and two regions of a quantum spin liquid. We demonstrate that the chains with more than one side spin illustrate in their ground-state phase diagram a Kosterlitz–Thouless transition from a gapful phase to a gapless spin liquid phase.     

A two-component protein condensate of the EGFR cytoplasmic tail and Grb2 regulates Ras activation by SOS at the membrane

We reconstitute a phosphotyrosine-mediated protein condensation phase transition of the ∼200 residue cytoplasmic tail of the epidermal growth factor receptor (EGFR) and the adaptor protein, Grb2, on a membrane surface. The phase transition depends on phosphorylation of the EGFR tail, which recruits Grb2, and crosslinking through a Grb2-Grb2 binding interface. The Grb2 Y160 residue plays a structurally critical role in the Grb2-Grb2 interaction, and phosphorylation or mutation of Y160 prevents EGFR:Grb2 condensation. By extending the reconstitution experiment to include the guanine nucleotide exchange factor, SOS, and its substrate Ras, we further find that the condensation state of the EGFR tail controls the ability of SOS, recruited via Grb2, to activate Ras. These results identify an EGFR:Grb2 protein condensation phase transition as a regulator of signal propagation from EGFR to the MAPK pathway.

Recently, a class of phenomena known as protein condensation phase transitions has begun to emerge in biology. Originally identified in the context of nuclear organization (1) and gene expression (2), a distinct two-dimensional protein condensation on the cell membrane has now been discovered in the T cell receptor (TCR) signaling system involving the scaffold protein LAT (3–5). TCR activation results in phosphorylation of LAT on at least four distinct tyrosine sites, which subsequently recruit the adaptor protein Grb2 and the signaling molecule PLCγ via selective binding interactions with their SH2 domains. Additional scaffold and signaling molecules, including SOS, GADS, and SLP76, are recruited to Grb2 and PLCγ through further specific protein–protein interactions (6, 7). Multivalency among some of these binding interactions can crosslink LAT molecules in a two-dimensional bond percolation network on the membrane surface. The resulting LAT protein condensate resembles the nephrin:NCK:N-WASP condensate (8) in that both form on the membrane surface under control of tyrosine phosphorylation and exert at least one aspect of functional control over signaling output via a distinct type of kinetic regulatory mechanism (9–11). The basic molecular features controlling the LAT and nephrin protein condensates are common among biological signaling machinery, and other similar condensates continue to be discovered (12, 13). The LAT condensation shares downstream signaling molecules with the EGF-receptor (EGFR) signaling system, raising the question if EGFR may participate in a signaling-mediated protein condensation itself.EGFR signals to the mitogen-activated protein kinase (MAPK) pathway and controls key cellular functions, including growth and proliferation (14–16). EGFR is a paradigmatic model system in studies of signal transduction, and immense, collective scientific effort has revealed the inner workings of its signaling mechanism down to the atomic level (17). EGFR is autoinhibited in its monomeric form. Ligand-driven activation is achieved through formation of an asymmetric receptor dimer in which one kinase activates the other to phosphorylate the nine tyrosine sites in the C-terminal tails (17, 18). There is an obvious conceptual connection between EGFR and the LAT signaling system in T cells. The ∼200-residue–long cytoplasmic tail of EGFR resembles LAT in that both are intrinsically disordered and contain multiple sites of tyrosine phosphorylation that recruit adaptor proteins, including Grb2, upon receptor activation (19). Phosphorylation at tyrosine residues Y1068, Y1086, Y1148, and Y1173 in the EGFR tail creates sites to which Grb2 can bind via its SH2 domain. EGFR-associated Grb2 subsequently recruits SOS, through binding of its SH3 domains to the proline-rich domain of SOS. Once at the membrane, SOS undergoes a multistep autoinhibition-release process and begins to catalyze nucleotide exchange of RasGDP to RasGTP, activating Ras and the MAPK pathway (20).While these most basic elements of the EGFR activation mechanism are widely accepted, larger-scale features of the signaling complex remain enigmatic. A number of studies have reported higher-ordered multimers of EGFR during activation, including early observations by Förster Resonance Energy Transfer and fluorescence lifetime studies (21–23), as have more recent studies using single molecule (24, 25) and computational methods (26). Structural analyses and point mutation studies on EGFR have identified a binding interface enabling EGFR asymmetric dimers to associate (27), but the role of these higher-order assemblies remains unclear. At the same time, many functional properties of the signaling system remain unexplained as well. For example, EGFR is a frequently altered oncogene in human cancers, and drugs (including tyrosine kinase inhibitors) targeting EGFR signaling have produced impressive initial patient responses (28). All too often, however, these drugs fail to offer sustained patient benefits, in large part because of poorly understood resistance mechanisms (29). Physical aspects of the cellular microenvironment have been implicated as possible contributors to resistance development (30), and there is a growing realization that EGFR possesses kinase-independent (e.g., signaling independent) prosurvival functions in cancer cells (31). These points fuel speculation that additional layers of regulation over the EGFR signaling mechanism exist, including at the level of the receptor signaling complex itself.Here we report that EGFR undergoes a protein condensation-phase transition upon activation. We reconstituted the cytoplasmic tails of EGFR on supported bilayers and characterized the system behavior upon interaction with Grb2 and SOS, using total internal reflection fluorescence (TIRF) imaging. This experimental platform has been highly effective for revealing both phase-transition characteristics and functional signaling aspects of LAT protein condensates (4, 5, 10, 32–34). Published reports on the LAT system to date have emphasized SOS (or the SOS proline-rich [PR] domain) as a critical crosslinking element. Titrating the SOS PR domain into an initially homogeneous mixture of phosphorylated LAT and Grb2 revealed a sharp transition to the condensed phase, which we have also observed with the EGFR:Grb2:SOS system. Under slightly different conditions, however, we report observations of an EGFR:Grb2 condensation-phase transition without any SOS or other crosslinking molecule. We show that crosslinking is achieved through a Grb2–Grb2 binding interface. Phosphorylation on Grb2 at Y160 as well as a Y160E mutation [both reported to disrupt Grb2–Grb2 binding (35, 36)] were observed to prevent formation of EGFR condensates. We note that the evidence of Grb2–Grb2 binding we observed occurred in the context of EGFR-associated Grb2, which is localized to the membrane surface; free Grb2 dimers are not necessary.The consequence of EGFR condensation on downstream signaling is characterized by mapping the catalytic efficiency of SOS to activate Ras as a function of the EGFR condensation state. SOS is the primary Ras guanine nucleotide exchange factor (GEF) responsible for activating Ras in the EGFR-to-MAPK signaling pathway (37–40). At the membrane, SOS undergoes a multistep process of autoinhibition release before beginning to activate Ras. Once fully activated, SOS is highly processive, and a single SOS molecule can activate hundreds of Ras molecules before disengaging from the membrane (41–43). Autoinhibition release in SOS is a slow process, which necessitates that SOS be retained at the membrane for an extended time in order for Ras activation to begin (5, 10). This delay between initial recruitment of SOS and subsequent initiation of its Ras GEF activity provides a kinetic proofreading mechanism that essentially requires SOS to achieve multivalent engagement with the membrane (e.g., through multiple Grb2 or other interactions) in order for it to activate any Ras molecules.Experimental results described here reveal that Ras activation by SOS is strongly enhanced by EGFR condensation. Calibrated measurements of both SOS recruitment and Ras activation confirmed enhanced SOS catalytic activity on a per-molecule basis, in addition to enhanced recruitment to the condensates. These results suggest that a Grb2-mediated EGFR protein condensation-phase transition is a functional element controlling signal propagation from EGFR downstream to the MAPK signaling pathway.     

运动员心动时相及左室顺应性观察

作者认为,对运动员左室功能的全面评价,应包括收缩和舒张功能两个方面,而不应该只是前者。文章提出XJY-6型心脏机能诊断仪可一机多用,尤以对LVEdp和ΔV/ΔP的测试,能为医务监督提供有价值的参据。     

Establishing a baseline phase behavior in magnetic resonance imaging to determine normal vs. abnormal iron content in the brain

PURPOSE: To establish a baseline of phase differences between tissues in a number of regions of the human brain as a means of detecting iron abnormalities using magnetic resonance imaging (MRI). MATERIALS AND METHODS: A fully flow-compensated, three-dimensional (3D), high-resolution, gradient-echo (GRE) susceptibility-weighted imaging (SWI) sequence was used to collect magnitude and phase data at 1.5 T. The phase images were high-pass-filtered and processed region by region with hand-drawn areas. The regions evaluated included the motor cortex (MC), putamen (PUT), globus pallidus (GP), caudate nucleus (CN), substantia nigra (SN), and red nucleus (RN). A total of 75 subjects, ranging in age from 55 to 89 years, were analyzed. RESULTS: The phase was found to have a Gaussian-like distribution with a standard deviation (SD) of 0.046 radians on a pixel-by-pixel basis. Most regions of interest (ROIs) contained at least 100 pixels, giving a standard error of the mean (SEM) of 0.0046 radians or less. In the MC, phase differences were found to be roughly 0.273 radians between CSF and gray matter (GM), and 0.083 radians between CSF and white matter (WM). The difference between CSF and the GP was 0.201 radians, and between CSF and the CN (head) it was 0.213 radians. For CSF and the PUT (the lower outer part) the difference was 0.449 radians, and between CSF and the RN (third slice vascularized region) it was 0.353 radians. Finally, the phase difference between CSF and SN was 0.345 radians. CONCLUSION: The Gaussian-like distributions in phase make it possible to predict deviations from normal phase behavior for tissues in the brain. Using phase as an iron marker may be useful for studying absorption of iron in diseases such as Parkinson's, Huntington's, neurodegeneration with brain iron accumulation (NBIA), Alzheimer's, and multiple sclerosis (MS), and other iron-related diseases. The phases quoted here will serve as a baseline for future studies that look for changes in iron content.     

Evaluation of in-stent stenosis by magnetic resonance phase-velocity mapping in nickel-titanium stents

PURPOSE: To evaluate different grades of in-stent stenosis in a nickel-titanium stent with MRI. MATERIALS AND METHODS: Magnetic resonance phase velocity mapping (MR-PVM) was used to measure flow velocity through a 9-mm NiTi stent with three different degrees of stenosis in a phantom study. The tested stenotic geometries were 1) axisymmetric 75%, 2) axisymmetric 90%, and 3) asymmetric 50%. The MR-PVM data were subsequently compared with the velocities from computational fluid dynamic (CFD) simulations of identical conditions. RESULTS: Good quantitative agreement in velocity distribution for the 50% and 75% stenoses was observed. The agreement was poor for the 90% stenosis, most likely due to turbulence and the high-velocity gradients found in the small luminal area relative to the pixel resolution in our imaging settings. CONCLUSION: The accuracy of the MRI velocities inside the stented area renders MRI a modality that may be used to assess moderate to severe in-stent restenosis (ISR) in medium-sized vascular stents in peripheral vessels, such as the iliac, carotid, and femoral arteries. Advances in MR instrumentation may provide sufficient resolution to obtain adequate velocity information from smaller vessels, such as the coronary arteries, and allow MRI to substitute for invasive and expensive catheterization procedures currently in clinical use.     

Efficacy,safety, and tolerability of mirabegron in patients aged ≥65 yr with overactive bladder wet: a phase IV,double-blind,randomised, placebo-controlled study (PILLAR)

BackgroundThe majority of patients with overactive bladder (OAB) are aged >65 yr. There has been no prospectively designed study assessing treatment efficacy with the β3-adrenoreceptor agonist, mirabegron, specifically in this age group.ObjectiveA phase IV study comparing flexibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence.Design, setting, and participantsCommunity-dwelling patients aged ≥65 yr with OAB for ≥3 mo.InterventionFollowing a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/24 h were randomised 1:1 to double-blind 25 mg/d mirabegron or matched placebo, for 12 wk. After week 4 or 8, the dose could be increased to 50 mg/d mirabegron/matched placebo based on patient and investigator discretion.Outcome measurements and statistical analysisCoprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24 h and incontinence episodes/24 h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24 h, mean volume voided/micturition, and mean number of urgency episodes/24 h. Stratified rank ANCOVA was used for the mean numbers of incontinence episodes/24 h and urgency incontinence episodes/24 h.Results and limitationsStatistically significant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Safety and tolerability were consistent with the known mirabegron safety profile.ConclusionsMirabegron efficacy, safety, and tolerability over 12 wk were confirmed in patients aged ≥65 yr with OAB and incontinence.Patient summaryWe examined the effect of mirabegron compared with placebo in people aged 65 yr or older with overactive bladder and incontinence. Mirabegron improved the symptoms of overactive bladder compared with placebo. Side effects were similar to those already known for mirabegron.