基于改进 abcd 模型的黄河源区径流变化与归因

为改进模型对高寒地区融雪径流模拟不足的缺陷，将融雪模块耦合到传统 abcd 模型。利用 1980—2018 年 逐月实测的径流数据和通过 AnuSpline 方法插值的格网气象要素，驱动改进后的abcd 模型，分析三江源生态保护 措施实施前后（1980—1999 年和 2000—2018 年）黄河源区径流的动态变化，并量化关键气象因素与人类活动对 径流变化的影响程度，即相对贡献。结果表明：耦合融雪模块的 abcd-snow 模型完善了高寒地区水文过程的模拟， 提高对径流的模拟性能，在黄河源区表现出较好的适用性；整个研究时段黄河源区的实测径流呈不显著减少趋势 （?0.80?mm/a，p>0.05），但 2000 年前径流则呈现显著下降趋势（?4.12?mm/a，p<0.05），2000 年后径流则呈显著增加 趋势（3.16?mm/a，p<0.05）；?归因分析表明气候变化是源区径流变化的主导因素。2000 年前，气候变化对径流减少 的相对贡献率为 62.8%，人类活动对径流的贡献为 37.2%；2000 年后，气候变化对径流增加的贡献率达到 120.0?%， 人类活动对径流的贡献为?20.0%。其中：降水的变化是决定径流变化主导因素；其他气候因素的相对贡献较小； 以人类活动为主的生态恢复可显著降低河川径流。本研究有助于理解气候变化和下垫面变化对黄河源区水资源 变化的系统驱动机理，并为流域水资源合理配置提供科学参考依据。     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

退火工艺对激光选区熔化成形Ti6Al4V合金组织及室温力学性能的影响

以Ti6Al4V球形粉末为原料,利用激光选区熔化成形方法制备了Ti6Al4V合金试样,采用光学显微镜、扫描电镜及力学性能测试等手段,研究了退火工艺对Ti6Al4V合金室温力学性能及组织的影响规律。结果表明: SLM成形沉积态Ti6Al4V合金室温抗拉强度超过1200 MPa,而平均断后伸长率仅为4.0%;在650 ℃下进行真空退火处理,合金的抗拉强度仍保持在1200 MPa左右,规定塑性延伸强度R_p0.2高于1150 MPa,但试样的断后伸长率<10%;而在750及800 ℃下进行真空退火处理,合金试样的抗拉强度降至1100 MPa左右,规定塑性延伸强度高于1050 MPa,伸长率达到甚至超过10%,材料的综合强韧性得到明显提升。随着真空退火加热温度和保温时间的增加,SLM成形Ti6Al4V合金原始β晶界逐渐变模糊,晶粒趋向于等轴化。与此同时,快速冷却转变的α′针状马氏体未出现明显地粗化。     

Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α₁-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.     

Unsupervised Segmentation of Stereoscopic Video Objects: Constrained Segmentation Fusion Versus Greedy Active Contours

In this paper, we present a novel memory access reduction scheme (MARS) for two-dimension fast cosine transform (2-D FCT). It targets programmable DSPs with high memory-access latency. It reduces the number of memory accesses by: 1) reducing the number of weighting factors and 2) combining butterflies in vector-radix 2-D FCT pruning diagram from two stages to one stage with an efficient structure. Hardware platform based on general purpose processor is used to verify the effectiveness of the proposed method for vector-radix 2-D FCT pruning implementation. Experimental results validate the benefits of the proposed method with reduced memory access, less clock cycle and fewer memory space compared with the conventional implementation.     

New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

The Amyloid Precursor Protein (APP) has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ) in Alzheimer’s disease (AD). However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y₆₈₂ mutation in the ₆₈₂YENPTY₆₈₇ domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS) on hippocampal tissue extracts of three month-old mice incubated with either the ₆₈₂YENPTY₆₈₇ peptide, its mutated form, ₆₈₂GENPTY₆₈₇ or its phosphorylated form, ₆₈₂pYENPTY₆₈₇. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc) and its Adaptor Protein 2 (AP-2). Overall our results consolidate and refine the importance of Y₆₈₂ in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Allyl Isothiocyanate Inhibits Actin-Dependent Intracellular Transport in Arabidopsis thaliana

Volatile allyl isothiocyanate (AITC) derives from the biodegradation of the glucosinolate sinigrin and has been associated with growth inhibition in several plants, including the model plant Arabidopsis thaliana. However, the underlying cellular mechanisms of this feature remain scarcely investigated in plants. In this study, we present evidence of an AITC-induced inhibition of actin-dependent intracellular transport in A. thaliana. A transgenic line of A. thaliana expressing yellow fluorescent protein (YFP)-tagged actin filaments was used to show attenuation of actin filament movement by AITC. This appeared gradually in a time- and dose-dependent manner and resulted in actin filaments appearing close to static. Further, we employed four transgenic lines with YFP-fusion proteins labeling the Golgi apparatus, endoplasmic reticulum (ER), vacuoles and peroxisomes to demonstrate an AITC-induced inhibition of actin-dependent intracellular transport of or, in these structures, consistent with the decline in actin filament movement. Furthermore, the morphologies of actin filaments, ER and vacuoles appeared aberrant following AITC-exposure. However, AITC-treated seedlings of all transgenic lines tested displayed morphologies and intracellular movements similar to that of the corresponding untreated and control-treated plants, following overnight incubation in an AITC-absent environment, indicating that AITC-induced decline in actin-related movements is a reversible process. These findings provide novel insights into the cellular events in plant cells following exposure to AITC, which may further expose clues to the physiological significance of the glucosinolate-myrosinase system.