LLA/GA/ε-CL摩尔比对三元共聚物性能的影响

辛酸亚锡为催化剂,采用本体开环聚合方法,合成了一组不同摩尔比的L-丙交酯/乙交酯/ε-己内酯(LLA/GA/CL)三元共聚物。通过GPC、1H-NMR、DSC和XRD测试,研究了摩尔比对共聚物分子量及其分布、热性能和结晶性能的影响。结果表明共聚物组成摩尔比与投料摩尔比基本一致,共聚物玻璃化转变温度(Tg)随LLA和CL含量增加分别呈现升高和降低趋势,并且当LLA含量增加至77 mol%,即LLA/GA摩尔比85∶15时,共聚物表现出明显的部分结晶性。     

Bioceramic materials in endodontics

During the past two decades, a number of major advances have been made in the field of bioactive ceramics used for endodontic treatment. This article reviews the physico-chemical and biological properties of bioceramic materials and the application of bioceramic technology to endodontics. Bioceramic materials, with their biocompatible nature and excellent physico-chemical properties, are widely used in endodontic applications. They can function as cements, root repair materials, root canal sealers and filling materials, which have the advantages of enhanced biocompatibility, potential increased root strength following obturation, antibacterial properties and sealing ability. New bioceramic materials have demonstrated the ability to overcome some of the significant limitations of earlier generations of endodontic materials. Most bioceramic materials have been shown to be biocompatible and have good physico-chemical characteristics, therefore having a potential use in clinical endodontics. Although in vitro studies on the use of bioceramic materials in endodontics have given encouraging results, randomized and double-blind clinical studies of sufficient length with these materials are needed to confirm long-term success following their use.     

蛋白酶抑制剂茚地那韦的知识产权保护状况和风险分析

通过对蛋白酶抑制剂茚地那韦国内外知识产权保护状况的初步分析,以及茚地那韦国际和国内的申请量、申请地区、申请人、保护状况和期限等方面统计,可见国外原研企业对于茚地那韦专利申请已逐年下降,但目前专利仍对该药有一定的保护力度,该药在合成方法、衍生物、新剂型、新用途等方面尚有较大的研发和保护空间,相关医药企业仍可从这些方面对该药进行研究改进或创新.     

The CSD Drug Subset: The Changing Chemistry and Crystallography of Small Molecule Pharmaceuticals

We report the generation and statistical analysis of the CSD drug subset: a subset of the Cambridge Structural Database (CSD) consisting of every published small-molecule crystal structure containing an approved drug molecule. By making use of InChI matching, a CSD Python API workflow to link CSD entries to the online database Drugbank.ca has been produced. This has resulted in a subset of 8632 crystal structures, representing all published solid forms of 785 unique drug molecules. We hope that this new resource will lead to improvements in targeted cheminformatics and statistical model building in a pharmaceutical setting. In addition to this, as part of the Advanced Digital Design of Pharmaceutical Therapeutics collaboration between academia and industry, we have been given the unique opportunity to run comparative analysis on the internal crystal structure databases of AstraZeneca and Pfizer, alongside comparison to the CSD as a whole.     

Soft spots and their structural signature in a metallic glass

In a 3D model mimicking realistic Cu₆₄Zr₃₆ metallic glass, we uncovered a direct link between the quasi-localized low-frequency vibrational modes and the local atomic packing structure. We also demonstrate that quasi-localized soft modes correlate strongly with fertile sites for shear transformations: geometrically unfavored motifs constitute the most flexible local environments that encourage soft modes and high propensity for shear transformations, whereas local configurations preferred in this alloy, i.e., the full icosahedra (around Cu) and Z16 Kasper polyhedra (around Zr), contribute the least.Metallic glasses (MGs) have an inherently inhomogeneous internal structure, with a wide spectrum of atomic-packing heterogeneities (1–4). As a result, an a priori identification of structural defects that carry atomic rearrangements (strains) under imposed stimuli such as temperature and externally applied stresses has always been a major challenge (3–6). In several quasi-2D or 3D models of amorphous solids (such as jammed packings of soft spheres interacting via repulsive potentials or colloidal particles), low-frequency vibrational normal modes have been characterized, and it has recently been demonstrated that some of these modes are quasi-localized (7–14). A population of “soft spots” has been identified among them in terms of their low-energy barriers for local rearrangements (13, 14), correlating also with properties in supercooled liquids such as dynamic heterogeneity (15–17). However, it is not certain where the soft spots are in realistic MGs (18), in terms of an explicit correlation with local atomic packing and topological arrangements (18–20). In particular, there is a pressing need to determine whether it is possible to identify shear transformation zones, i.e., the local defects that carry inelastic deformation (21, 22). Accomplishing this would permit the characterization of MG microstructure in a way that directly ties atomic configuration with mechanical response beyond the elastic regime. We will show here that there is indeed a correlation between soft modes and atoms that undergo shear transformations, and both have their structural signature in specific atomic packing environments defined in terms of coordination polyhedra (3).Fig. 1 displays the vibrational density of states (V-DOS), D(ω), calculated from the eigen-frequencies obtained by normal mode analysis of the Cu₆₄Zr₃₆MG prepared with a cooling rate of 10⁹ K/s (Methods). The main peak stays around 14 meV and becomes only slightly narrower (or wider) when the cooling rate used to prepare the MG is slower (or faster), as seen in Fig. S1; the glasses cooled at slower rates exhibit fewer low-frequency (or low-energy) vibrational modes. The blue portion in Fig. 1 indicates the 1% lowest-frequency normal modes, which will be summed over in our calculations of the participation fraction, P_i, in soft modes (Methods). Those low-frequency vibrational modes are confirmed to be quasi-localized, similar to previous work on 2D models (15), as they involve a compact group of atoms on the basis of the amplitude distribution of their corresponding eigenvectors (also see the contour maps in Fig. 4).Open in a separate windowFig. 1.V-DOS of the inherent structure for Cu₆₄Zr₃₆ MG produced with the cooling rate of 10⁹ K/s. The blue portion indicates the 1% lowest frequency normal modes that were summed over to calculate the participation fraction (in soft modes) of atoms.Open in a separate windowFig. 4.Contoured maps showing the spatial distribution of participation fraction P_i (see sidebar) for Cu and Zr atoms in the Cu₆₄Zr₃₆ metallic glass with the cooling rate of 10⁹ K/s. The four sampled representative thin slabs (A–D) each has a thickness of 2.5 Å. White spots superimposed in the maps mark the locations of atoms that have experienced clear shear transformations (Methods) under AQS to a strain of 5%.We first demonstrate that certain types of coordination polyhedra, specifically those geometrically unfavored motifs (GUMs), contribute preferentially to the quasi-localized soft modes identified above, whereas the geometrically preferable clusters at this alloy composition represent the short-range order that participate the least. To establish the connection between the low-frequency modes and atomic packing structure, we analyze the latter first from the perspective of Cu-centered coordination polyhedra (23), in terms of the P_i of Cu atoms that are in the center of different types of polyhedra. In Fig. 2A, from left to right, each solid bar represents a bin that contains 10% of all of the Cu atoms, in ascending order from the lowest to the highest P_i. In addition, the 1% Cu atoms with the lowest P_i and the top 1% with the highest P_i are displayed on either end, each with a separate bar. The Cu atoms in full icosahedra (with Voronoi index <0, 0, 12, 0>) dominate the lowest P_i, which is consistent with the notion that full icosahedra are the short-range order most energetically and geometrically comfortable and hence least likely to participate in soft spots at this MG composition (23). Specifically, ∼98% of the Cu atoms with the 1% lowest participation fraction are enclosed in <0, 0, 12, 0>, which is much greater than the average value that ∼40% of Cu atoms center full icosahedra in this MG sample (23). In stark contrast, the local configurations on the other end of the coordination polyhedra spectrum, i.e., the GUMs (see examples below) that deviate considerably from the coordination number (CN) = 12 full icosahedra and their close cousins (Fig. 2), are not found at all among the atoms with the lowest 1% participation fraction. For the 1% of Cu atoms with the highest participation fraction, GUMs account for as high as 63%, whereas the share of full icosahedra is as low as only 1.1%. This observation clearly indicates that atoms involved with soft spots in low-frequency normal modes (i.e., soft modes) are those with the most unfavorable local coordination polyhedra.Open in a separate windowFig. 2.Atoms at the center of different types of (A) Cu-centered and (B) Zr-centered coordination polyhedra contribute differently to low-frequency normal modes. Each solid bar contains 10% of all of the Cu (or Zr) atoms; from left to right, the bins are ordered from the lowest to the highest participation fraction. Two additional bars describe the makeup of atoms contributing to the lowest 1% participation fraction and the highest 1% participation fraction, respectively. The latter is seen to be dominated by Cu (or Zr) atoms in GUMs.We also examined the dependence on local environments for Zr atoms. A plot analogous to Fig. 2A, this time for Zr-centered coordination polyhedra, is shown in Fig. 2B. From left to right, each solid bar represents a bin that contains 10% of all of the Zr atoms, in ascending order from the lowest to the highest P_i. In addition, the 1% Zr atoms with the lowest P_i and the top 1% with the highest P_i are displayed on either end, each with a separate bar. The most favorable Zr-centered Kasper polyhedra in this MG are of the Z16 type (<0, 0, 12, 4>) (23). Interestingly, for the Zr atoms with the 1% lowest participation fraction, ∼75% of them are enclosed in <0, 0, 12, 4>, which is much greater than the sample average of ∼17% in this MG (23). In contrast, GUMs that deviate considerably from the CN = 16 Kasper polyhedra and their close cousins (Fig. 2) only constitute ∼5%. Conversely, for the 1% of Zr atoms with the highest participation fraction, GUMs account for as high as 76%, whereas the share of Z16 clusters is as low as 1.6%.We now illustrate the GUMs, i.e., the typical types of coordination polyhedra that are strongly correlated with the soft modes. Fig. 3 A and B illustrates the local environments of the top five Cu atoms and Zr atoms, respectively, i.e., those with the highest participation fractions. For these five Cu-centered GUMs, the coordination polyhedra have Voronoi indices of <0, 0, 12, 2>, <0, 4, 4, 4>, <0, 6, 0, 6>, <0, 4, 4, 3>, and <0, 3, 6, 2>. For the five Zr GUMs, they are <1, 3, 4, 4>, <1, 2, 6, 5>, <0, 2, 9, 4>, <0, 3, 7, 4>, and <0, 4, 5, 6>. Clearly, they are among the polyhedra that deviate most significantly from the geometrically preferable Frank-Kasper polyhedra <0, 0, 12, 0> (for Cu) and <0, 0, 12, 4> (for Zr). Specifically, they are non-Kasper polyhedra and contain an increased density of extrinsic (e.g., fourfold) disclinations (3) at the favored CN, or clusters (including Kasper polyhedra) with unfavorable (too large or too small) CNs. In fact, those Zr-centered GUMs even contain sevenfold bonds, e.g., <1, 3, 4, 4> is actually <1, 3, 4, 4, 1> (except for these Zr-centered GUMs, the fifth digit is zero in the Voronoi indices for all the other coordination polyhedra in this work). From the perspective of either constituent element, Cu or Zr, these are the most geometrically unfavored clusters at the given alloy composition and atomic size ratio. According to ref. 24, transverse vibrational modes associated with defective (more disordered) soft structures could also be an origin of the boson peak [the excess rise in the D(ω) at low-frequency vibrational modes].Open in a separate windowFig. 3.Configurations of five different (A) Cu-centered and (B) Zr-centered polyhedra, in which the center atoms are the top five atoms with the highest participation fractions for each constituent species. These are representatives of GUMs in this MG. Orange spheres are for Cu atoms and silver ones for Zr atoms.The next task at hand is to correlate the relaxation events with vibrational modes. In a 2D sheared model glass, Manning et al. (14) recently associated low-frequency vibrational modes with soft spots where particle rearrangements are initiated. Here we use a similar analysis on our 3D realistic Cu₆₄Zr₃₆ glass. The contoured maps of participation fraction P_i for all of the (Cu and Zr) atoms inside four representative slabs, each with a thickness of 2.5 Å (roughly the average atomic spacing), are plotted in Fig. 4 A–D. We notice that the P_i distributions are heterogeneous: atoms that participated the most in soft modes tend to aggregate together, with a typical correlation length of ∼1 nm. For a direct comparison, the local atomic rearrangements in sheared Cu₆₄Zr₃₆ MG [under athermal quasi-static shear (AQS) to a global shear strain γ = 5%, well before global yielding/flow of the entire sample at γ ∼ 12%] are superimposed in Fig. 4 A–D, where white spheres represent the (Cu or Zr) atoms that have experienced the most obvious shear transformations (indicated by their large and simultaneous jumps of Dmin2 that are clearly above other atoms; Methods, Fig. S2, and SI Text). The distribution of these atoms is also inhomogeneous and, interestingly, almost always overlaps with the regions with high P_i. This observation is consistent with the correlation between quasi-localized low-frequency modes and low energy barriers (13). Fig. 5 displays the locations of all such Cu and Zr atoms in the simulation model, which are about 2% of the total number of atoms in the box. Two features are highly noteworthy. First, they cluster into patches (only 6 atoms are exceptions, being isolated in a group of <3 atoms), each comprising 10–40 atoms (Cu in orange and Zr in gray color). Second, the atoms in each cluster record a simultaneous jump in Dmin2. Taken together, the spatial and temporal correlations clearly indicate that these are the clusters of atoms that each has been through a well-defined shear transformation. The several representative cases in Fig. 4 (and Fig. S3) give a visual illustration of the correlation that, under imposed deformation, the most obvious shear transformations have a strong tendency to arise from the collection of atoms involved in soft modes. Each group (cluster) of the activated atoms in Fig. 5 centers a shear transformation zone.Open in a separate windowFig. 5.Cluster of atoms that have undergone obvious shear transformations (Methods) (24) in Cu₆₄Zr₃₆ MG sheared to γ = 5%. Atoms in each cluster are activated at the same time, as indicated by their simultaneous jump in ΔDmin2 at the same shear strain γ. Two such shear transformation zones are circled, with the Inset displaying the overlapping ΔDmin2 jumps of the atoms involved in each cluster.Note here that not all of the regions with the highest participation fraction P_i would undergo shear transformation for a particular loading condition, as seen in Fig. 4 and Fig. S3. One should keep in mind that such a local structure–property correlation in an amorphous system is expected to be statistical (better perceived in Fig. 6), rather than deterministic with a one-to-one correspondence (12, 14). The soft spots are only candidates for potential shear transformation zones. The ones actually activated are not necessarily the softest, and would be determined by the loading direction and local stress field interacting with the anisotropy of the soft spots. The statistical correlation is obvious for the entire range of imposed γ, from 2% to 10%. The contour maps similar to those in Fig. 4 for γ = 10% (before global yielding) are shown in Fig. S3. As another way to see this correlation, we present in Fig. 6 a plot correlating the average participation fraction with Dmin2 (with respect to the undeformed configuration) for γ from 2% to 10%. Each data point is an average for 5% of all of the atoms inside a bin (each bin contains atoms grouped in ascending participation fraction). Obviously, the atoms with higher participation in soft mode contribute more to the nonaffine deformation and therefore shear transformations. This trend persists throughout the entire range of strains we studied and is therefore statistically valid for all the atoms in the metallic glass.Open in a separate windowFig. 6.Correlation between the average Dmin2 (with reference to undeformed configuration) with participation fraction P_i for all of the (Cu and Zr) atoms in the Cu₆₄Zr₃₆ MG deformed to different γ levels (2–10%). Each data point is the average for 5% of all of the atoms, sorted in the order of increasing P_i.In conclusion, we identified soft spots in an MG. They are soft in the sense that the atoms (Cu and Zr in our case) in those local environments participate preferentially in soft vibrational modes and at the same time they have the highest propensity to undergo shear transformations. These two aspects are found to be strongly correlated: shear transformations in an MG preferentially occur at localized soft modes. In the language of the potential energy landscape, we established a correlation between the curvature at the bottom of the basin (stiffness) with the barrier for transitions between basins (energy barrier against reconfiguration). Importantly, we showed that both have a common signature in the local atomic packing environments: the GUMs are the local configurations most prone to instability. The GUMs, as the most disordered atomic arrangements, hence tend to constitute or center the “liquid-like regions” often hypothesized in the literature (4, 5, 25). They tend to be soft and fertile for shear transformations. Such a correlation, albeit statistical (not all soft modes or GUMs would be activated to undergo shear transformations for a given stress state/magnitude and loading duration), is very useful and important as a step forward in establishing a concrete structure–property relationship for MGs, i.e., a direct connection between short-range order and vibrational soft modes, as well as stress-induced atomic rearrangements. The spatial distribution of nanometer-scale patches observed in Fig. 4 and Fig. S3 (a 3D view from outside the MD box is in Fig. S4), in terms of property (soft spots) and corresponding structure (GUMs), may also help explain the origin of the heterogeneity in local elastic modulus and local viscoelasticity recently mapped out in experiments (26–28).     

Structural and functional characterization of a TGFβ molecule from amphioxus reveals an ancient origin of both immune-enhancing and -inhibitory functions

Transforming growth factor beta (TGFβ) is a pleiotropic cytokine with important roles in mediating inflammatory response. TGFβ has been shown to be widely present in invertebrates, but little is known about its functions in immune and inflammatory responses. Moreover, structural and functional insights into TGFβ molecules in invertebrates remain completely lacking. Here we demonstrate the presence of a single TGFβ-like gene in the amphioxus Branchiostoma japonicum, Bjtgfβ, which represents the archetype of vertebrate TGFβ proteins, and displays a higher expression in the hind-gut, hepatic caecum, ovary, and gill. We also show that amphioxus TGFβ exerts both enhancing and suppressing effects on the migration of macrophages like RAW264.7, and the motif WSTD is important for TGFβ in inducing or inhibiting the migration of macrophages. Altogether, these data suggest that amphioxus TGFβ is phylogenetically and functionally similar to vertebrate TGFβ, suggesting an ancient origin of bipolar function of TGFβ proteins.     

变压吸附制氧设备部分理化性能检测方法的研究

目的 变压吸附（pressure swing adsorption,PSA）设备制备的富氧空气主要用于临床治疗,必须通过质量控制以保证患者安全,但目前行业标准“YY 0298-1998”中对PSA制氧设备制备的氧气的部分理化指标的检测方法描述并不清楚.本文针对PSA设备制备的富氧空气的理化指标中,CO含量、CO2含量、固体物质含量和固体物质粒径4个项目的检测方法做了适当调整并进行验证.方法 通过优化气路解决了现行标准中无法同时检测CO和CO2的问题,提高了检测效率.采用注射器滤头替代粉尘捕集器进行固体物质含量的检测,并结合倒置显微镜对其粒径进行了考察.结果 CO最小检出限为0.1×10^-6（体积分数）,CO2最小检出限为0.08×10^-6（体积分数）,能够满足标准中对CO和CO2含量检测的规定,符合方法学验证的要求.样品中固体物质含量为小于0.1 mg/m^3、最大固体物质粒径为4.00 μm,均符合YY 0298-1998中的要求.结论 本文在现行标准的基础上优化试验方案并对PSA设备制备的富氧空气进行检测,得到了较为满意的结果,对评价PSA设备质量具有重要的实际意义.     

3种消毒剂浸泡消毒对甲基丙烯酸树脂基托机械性能的影响

目的:测量3种消毒剂浸泡过的甲基丙烯酸树脂的机械性能,了解消毒剂对树脂基托机械性能的影响,为临床应用提供依据.方法:制备80 mm×15 mm×4 mm丙烯酸树脂试样40个,随机分成A、B、C、D 4组,每组10个,分别浸泡于1：200"84"消毒液、体积分数为0.1%的过氧乙酸、体积分数为2%的戊二醛消毒液和蒸馏水中,30 min后从每组取出5个(共20个)试样为组1,分别测试每组树脂基托的弯曲强度和弯曲模量;取出每组中的另外5个(共20个)为组2,测试其冲击强度.结果:1：200"84"消毒液、体积分数为0.1%的过氧乙酸、体积分数为2%的戊二醛3种消毒液浸泡前后,反映材料机械性能的弯曲强度和弯曲模量及冲击强度3项指标差异均无统计学意义,且与蒸馏水浸泡组差异无统计学意义.结论:甲基丙烯酸树脂在1：200"84"消毒液、体积分数为0.1%的过氧乙酸、体积分数为2%的戊二醛中浸泡30 min,其机械性能均不受影响.