Induction of alternative fate other than default neuronal fate of embryonic stem cells in a membrane-based two-chambered microbioreactor by cell-secreted BMP4

Cell-secreted soluble factor signaling in a diffusion dominant microenvironment plays an important role on early stage differentiation of pluripotent stem cells invivo. In this study, we utilized a membrane-based two-chambered microbioreactor (MB) to differentiate mouse embryonic stem cells (mESCs) in a diffusion dominant microenvironment of the top chamber while providing enough nutrient through the bottom chamber. Speculating that accumulated FGF4 in the small top chamber will augment neuronal differentiation in the MB culture, we first differentiated mESCs for 8 days by using a chemically optimized culture medium for neuronal induction. However, comparison of cellular morphology and expression of neuronal markers in the MB with that in the 6-well plate (6WP) indicated relatively lower neuronal differentiation in the MB culture. Therefore, to investigate whether microenvironment in the MB facilitates non-neuronal differentiation, we differentiated mESCs for 8 days by using chemically defined basal medium. In this case, differentiated cell morphology differed markedly between the MB and 6WP cultures: epithelial sheet-like morphology in the MB, whereas rosette morphology in the 6WP. Expression of markers from the three germ layers indicated lower neuronal but higher meso- and endo-dermal differentiation of mESCs in the MB than the 6WP culture. Moreover, among various cell-secreted soluble factors, BMP4 expression was remarkably upregulated in the MB culture. Inhibition of BMP4 signaling demonstrated that enhanced effect of upregulated BMP4 was responsible for the prominent meso- and endo-dermal differentiation in the MB. However, in the 6WP, downregulated BMP4 had a minimal influence on the differentiation behavior. Our study demonstrated utilization of a microbioreactor to modulate the effect of cell-secreted soluble factors by autoregulation and thereby inducing alternative self-capability of mESCs. Understanding and implementation of autoregulation of soluble factors similar to this study will lead to the development of robust culture systems to control ESC behavior.     

Microfluidic point-of-care blood panel based on a novel technique: Reversible electroosmotic flow

A wide range of diseases and conditions are monitored or diagnosed from blood plasma, but the ability to analyze a whole blood sample with the requirements for a point-of-care device, such as robustness, user-friendliness, and simple handling, remains unmet. Microfluidics technology offers the possibility not only to work fresh thumb-pricked whole blood but also to maximize the amount of the obtained plasma from the initial sample and therefore the possibility to implement multiple tests in a single cartridge. The microfluidic design presented in this paper is a combination of cross-flow filtration with a reversible electroosmotic flow that prevents clogging at the filter entrance and maximizes the amount of separated plasma. The main advantage of this design is its efficiency, since from a small amount of sample (a single droplet  ～ 10 μl) almost 10% of this (approx 1 μl) is extracted and collected with high purity (more than 99%) in a reasonable time (5–8 min). To validate the quality and quantity of the separated plasma and to show its potential as a clinical tool, the microfluidic chip has been combined with lateral flow immunochromatography technology to perform a qualitative detection of the thyroid-stimulating hormone and a blood panel for measuring cardiac Troponin and Creatine Kinase MB. The results from the microfluidic system are comparable to previous commercial lateral flow assays that required more sample for implementing fewer tests.     

以礼草属的地理分布

根据植物类群的地理分布与系统发育相统一的原理，本文讨论了以礼草属的分布中心、起源地、 起源时间和现代分布格局的形成。以礼草属全世界约26种、6变种，隶属于3个组，主要分布于中国，哈萨克斯坦、吉尔吉斯斯坦、塔吉克斯坦、阿富汗和伊朗也有分布。其中，中国的青藏高原汇聚了该属的大多数种类，且不同等级和演化水平的类群均集居于此，使其成为该属的现代分布中心；而该属的原始类群、以及与原始类群很近缘的鹅观草属却分布在这一中心之外的天山地区，加之天山地区自新生代的晚第三纪再次抬升以来，具备了以礼草属发生和繁衍的自然条件，因而天山地区很可能就是该属的起源地，起源时间也可能在晚第三纪或第四纪初。以礼草属自天山起源后，扩散的途径大概有3条，其中西南向途径和东南向途径从东、西两侧侵入青藏高原，在青藏高原得到极度发展，并随着高原的继续隆起，进一步衍生出最高级的类群短穗组，从而形成了以礼草属现今的分布格局。     

High genetic diversity and small genetic variation among populations of Magnolia wufengensis (Magnoliaceae), revealed by ISSR and SRAP markers

BackgroundGenetic diversity and genetic variation of 10 populations and subpopulations of Magnolia wufengensis, a new and endangered endemic species, were examined by inter simple sequence repeat (ISSR) and sequence-related amplified polymorphism (SRAP) molecular markers. Compared with other endangered endemic Magnolia taxa, M. wufengensis holds a relatively high level of genetic variation.ResultTotal genetic diversity was found to be 87.7% for ISSR and 88.0% for SRAP markers. For polymorphic loci (P), the effective mean number of alleles (Ae) was 1.414 for ISSR markers and 1.458 for SRAP markers, while the mean expected heterozygosity (H) was 0.256 using ISSR and 0.291 for SRAP markers. Within-population variation was estimated for P as 74.9% using ISSR and 74.6% with SRAP markers; the number of alleles Ae was 1.379 with ISSR and 1.397 for SRAP and H 0.235 with ISSR and 0.247 for SRAP markers.ConclusionThe analysis of molecular variation of both ISSR and SRAP marker systems indicated that most genetic variation is within populations, with values of 90.64% and 82.92% respectively. Mantel tests indicated a moderate association between the two marker systems and a low correlation between genetic and geographic distances. High levels of genetic diversity and low levels of population divergence suggest that genetic drift is not currently of great concern for this species. Severe habitat loss and fragmentation, predominantly ascribed to anthropogenic pressures, caused in-situ developing restriction of this species. Action for conserving this rare species for its long-term survival should be taken immediately.     

桦木科植物的系统发育和地理分布(待续)

本文对桦木种植物的研究历史作了详细的总结。在钻研文献的基础上，补充了部分系统学资料，使得花序、花，花粉、叶表皮等各类性状能够在属间进行比较。根据外类群比较、和谐性分析等原则确定了性状的演化极性，利用最大同步法和最小平行演化法对桦木科植物进行了分支分析。对各属的现代分布和地史分布作了描述，在此基础上，讨论了桦木科植物的分布中心、起源地、起源的时间和散布的途径。作者试图回到遥远的晚白垩纪和早第三纪，从描绘桦木科植物起源和早期分化的古地理和古气候背景人手，分析了在这种背景下桦木科植物所发生的空间辐射以及植物体本身所产生的形态进化，以求得对桦木科植物起源、散布和分化作出比较合理的解释。最后对桦木科组以上的等级作了分类处理。     

Detection of Bone Metastases in Breast Cancer (BC) Patients by Serum Tartrate-Resistant Acid Phosphatase 5b (TRACP 5b), a Bone Resorption Marker and Serum Alkaline Phosphatase (ALP), a Bone Formation Marker,in Lieu of Whole Body Skeletal Scintigraphy with Technetium99m MDP

Bone metastases are a serious problem in patients with advanced cancer disease and their presence usually signifies serious morbidity prior to the patient’s death. In breast cancer patients the incidence of bone metastasis is observed to be very high at 70 %, as seen during post-mortem examination. Bone metastasis is difficult to diagnose, treat or follow clinically without radiological tools. This study was designed to evaluate the utility of a novel bone resorption marker–serum tartrate-resistant acid phosphatase 5b (TRACP5b) and the bone formation marker such as serum total alkaline phosphatase (ALP), in comparison with whole body skeletal scintigraphy with Technetium99m MDP for the diagnosis of bone metastases (BM) in breast cancer (BC) patients. This study is intended to help the clinician to diagnose bone metastasis without resorting to radiological tools, as they are not cost effective and carry the risk of radiation. Experimental design: Four groups of samples were analysed. 1st group consists 52 normal female (cancer free women), 2nd group consists 38 BC patients without bone metastasis, 3rd group consists 27 breast cancer patients with limited bone metastasis (3 or less than 3 skeletal lesions) and 4th group consists 35 breast cancer patients with extensive bone metastasis (4 or more than 4 skeletal lesions), conformed by whole body skeletal scintigraphy with Technetium99m MDP. One way ANOVA was used to compare serum TRACP5b and serum ALP among these groups. Both serum TRACP5b and serum ALP are not markedly elevated in limited bone metastasis but are strongly elevated in extensive bone metastasis (p < 0.0001). As seen in this study the biochemical bone resorption marker, serum TRACP5b, abnormally increased in extensive bone metastasis of breast cancer patients and can be used as a specific marker for bone metastasis in lieu of radiological tools.     

The complex nature of regional knowledge production: Evidence on European regions

Knowledge creation is widely considered as the central driver for innovation, and accordingly, for creating competitive advantage. However, most measurement approaches have so far mainly focused on the quantitative dimension of knowledge creation, neglecting that not all knowledge has the same value (Balland and Rigby, 2017). The notion of knowledge complexity has come into use in this context just recently as an attempt to measure the quality of knowledge in terms of its uniqueness and its replicability. The central underlying assumption is that more complex knowledge is more difficult to be replicated, and therefore provides a higher competitive advantage for firms, or at an aggregated level, regions and countries. The objective of this study is to advance and apply measures for regional knowledge complexity to a set of European regions, and to highlight its potential in a regional policy context. This is done by, first, characterising the spatial distribution of complex knowledge in Europe and its dynamics in recent years, second, establishing that knowledge complexity is associated with future regional economic growth, and third, illustrating the usefulness of the measures by means of some policy relevant example applications. We proxy the production of complex knowledge with a regional knowledge complexity index (KCI) that is based on regional patent data of European metropolitan regions from current EU and EFTA member countries. The results are promising as the regional KCI unveils knowledge creation patterns not observed by conventional measures. Moreover, regional complexity measures can be easily combined with relatedness metrics to support policy makers in a smart specialisation context.     

A quantitative study of isobaric equilibrium and gravity anomalies in the hawaiian islands

The deformation of a strong elastic lithosphere supported by an underlying weak magma is calculated for a long mountainous load. The deformations, produce vertical superposed stresses in the lithosphere that contribute to the support of the mountain and distribute its weight over a large area.Employing the principle of isobaric equilibrium, the distribution of the vertical supporting stress and the associated gravity anomalies may be determined by analysis.The results of the analysis are applied to the Hawaiian chain and it is shown that the calculated physical properties and gravity anomalies are remarkably like those observed. It is inferred from the study that: (a) a strong lithosphere underlies the Hawaiians and this section is practically identical with those underlying other regions; (b) the lithosphere will support one-sided stresses approximating 10⁹ dynes/cm.² for long periods of time; (c) the distribution of gravity anomaly may be described quantitatively in terms of the calculated deformations; (d) the principle of isobaric equilibrium is obeyed throughout the region whereas the isostatic principle is generally violated; and (e) the distribution of compensating masses is not at all like that demanded by the principle of isostasy.It is concluded that isostasy leads to results that are clearly wrong when applied to mountains or other deformed regions. The principle of isobaric equilibrium appears, however, to be well established by the investigation.     

Query-focused multi-document summarization using hypergraph-based ranking

General graph random walk has been successfully applied in multi-document summarization, but it has some limitations to process documents by this way. In this paper, we propose a novel hypergraph based vertex-reinforced random walk framework for multi-document summarization. The framework first exploits the Hierarchical Dirichlet Process (HDP) topic model to learn a word-topic probability distribution in sentences. Then the hypergraph is used to capture both cluster relationship based on the word-topic probability distribution and pairwise similarity among sentences. Finally, a time-variant random walk algorithm for hypergraphs is developed to rank sentences which ensures sentence diversity by vertex-reinforcement in summaries. Experimental results on the public available dataset demonstrate the effectiveness of our framework.     

肋柱花属的系统研究

本文对肋柱花属的属下分类、系统发育和地理分布等方面进行了深入研究。文用分支系统学的方法和原理，用计算机PAUP程序处理，获得了几个最简约的支序图。  肋柱花属属于龙胆亚族辐状花冠群，在这群中，论亲缘关系它与辐花属最近，与獐牙菜属次之，而与黄秦艽属关系较远。  獐牙菜属在进化程度上较肋柱花属低，因此它被选为肋柱花属的外类群。 经过支序分析，肋柱花属的18个种根据Hennig的“共近裔性原则”可组合为三个组，其中肉质根茎组为较原始的组，肋柱花组为中级进化水平的组，合萼组是进化程度最高的组。 肋柱花属是北温带分布型的属，分布于亚洲、欧洲及北美洲，直达北极。从种的地理分布型分析，表明秦岭一横断山区是本属的起源与分化中心。 随文报道了一个新组、一个新种和一个新变种。  研究了全部种类的命名模式。     

獐牙菜属植物的起源, 散布和分布区形成

本文根据植物类群的系统发育和地理分布统一的原理，讨论了獐牙菜属植物的起源、散布和分 布区的形成。獐牙菜属包括11组16系154种，间断分布在亚洲、欧洲、北美洲和非洲。中国西南部- 喜马拉雅地区汇集了大多数种类、不同演化水平的类群以及形形色色的特有类群，成为该属的多样化 中心和多度中心。该属的原始类群和外类群也集中分布在中国西南山地，极有可能是该属的起源地。该 属的分布区类型中出现了各式的间断分布，根据有该属植物分布的大陆间及大陆与岛屿间分离和连接 的时间推测，该属的起源时间至少不会晚于晚白垩纪，也许更早，可追溯到中白垩纪。通过分类群间亲 缘关系和现代分布分析，显示出该属植物从起源地向周围和一定方向散布，形成了三个主要散布途径。在散布过程中植物本身也发生演化和就地特化，形成新的类群。     

Production rate and diameter analysis of spherical monodisperse microbubbles from two-dimensional,expanding-nozzle flow-focusing microfluidic devices

Flow-focusing microfluidic devices (FFMDs) can produce microbubbles (MBs) with precisely controlled diameters and a narrow size distribution. In this paper, poly-dimethyl-siloxane based, rectangular-nozzle, two-dimensional (2-D) planar, expanding-nozzle FFMDs were characterized using a high speed camera to determine the production rate and diameter of Tween 20 (2% v/v) stabilized MBs. The effect of gas pressure and liquid flow rate on MB production rate and diameter was analyzed in order to develop a relationship between FFMD input parameters and MB production. MB generation was observed to transition through five regimes at a constant gas pressure and increasing liquid flow rate. Each MB generation event (i.e., break-off to break-off) was further separated into two characteristic phases: bubbling and waiting. The duration of the bubbling phase was linearly related to the liquid flow rate, while the duration of the waiting phase was related to both liquid flow rate and gas pressure. The MB production rate was found to be inversely proportional to the sum of the bubbling and waiting times, while the diameter was found to be proportional to the product of the gas pressure and bubbling time.     

Comment on “The T-class of time-frequency distributions: Time-only kernels with amplitude estimation”

It is shown that the recently introduced T-class of time-frequency distributions is a subclass of the S-method distributions. From the generalization of the S-method distribution by rotating it in the time-frequency plane, a similar generalization of the T-class distribution follows readily. The generalized T-class distribution is then applicable to signals that behave chirp like, with their instantaneous frequency slowly varying around the slope of the chirp; this slope needs no longer be zero, as is the case for the original T-class distribution, but may take an arbitrary value.     

Early specializations for mimicry and defense in a Jurassic stick insect

Mimicry and secondary defense are staples among predator–prey interactions. Among insects, the stick and leaf insects are masters of camouflage. Nonetheless, a meager understanding of their origin and early mimetic evolution persists. Here, we report the earliest mimetic and defensive strategies of a stick insect from the Middle Jurassic of China, Aclistophasma echinulatum gen. et sp. nov., exquisitely preserving abdominal extensions and femoral spines. The distribution of these characteristics mapped onto the phylogeny of Phasmatodea reveals that abdominal extensions and femoral spines developed multiple times during the evolution of stick insects, and indicates that the origin of abdominal extensions predates other modifications, while tergal extensions predate other expansions of the body, such as those of the sterna and pleura, as well as defensive femoral spines. The new fossil provides clues into early antipredator defensive strategies, allows inferences as to the potential environment and predators, and reveals the mimetic and defensive mechanisms of stick insects from 165 million years ago.     

中药金芎原植物的研究

 A comparison of morphology, karyotype and the chemical compounds among “Jinxiong”, Ligasticum chuanxiong Hort. and L. chuanxiong cv. Fuxiong shows that “Jin- xiong”, like L. chuanxiong cv. Fuxiong, is a triploid and its karyotype is similar to that of L. chuanxiong with the formula K(2n)=33=24m+6sm+3st(SAT).   Thin-layer chromato- graphy of essential oils extracted from stem tubers confirms that the three taxa are extremely alike in chemical compounds. Using the features of leaves and the forms of stem tubers, they can be easily distinguished.  A new triploid cultivar of L. chuanxiong Hort. i.e.L. chuan-xiong cv. Jinxiong   is described for “Jinxiong” in the present paper.     

柑桔种质资源谷氨酸草酰乙酸转氨酶同工酶研究

本文分析了125份柑桔属、枳属、金柑属和指来檬属种质资源的谷氨酸草酰乙酸转氨酶同工 酶(GOT)。新发现了GOT-1的两个等位基因B和C。宽皮柑桔的GOT同工酶颇为一致(仅两个例 外)，表明可能有共同的起源。酸橙的GOT同工酶较复杂，可能有多种起源，其中朱栾和小红橙的起 源可能与宜昌橙或香橙有关。在单胚种柚中发现了6种GOT基因组合。宜昌橙存在着两种GOT同工酶类型。本文讨论了甜橙、酸橙、葡萄柚、香橙、柠檬等种类的可能起源。     

豆科黄华属的植物地理研究

首次全面论述了全世界黄华属(豆科)植物地理。黄华属是豆科少数几个东亚-北美间断分布属之一。对黄华属5组21种的分布进行了分析,发现本属4个频度分布中心依次是：东亚地区(8种／3组,其中特有种4种),伊朗-土兰地区(7种／3组,其中特有种3种),落基山地区(7种／2组,均为特有种)及大西洋北美地区(3种／1组,均为特有种)。基于以下事实：在东亚地区存在本属最多的组与种;在此区可以见到黄华属系统发育系列;该属最原始的组种及最进化的组种也在该区出现等,可以认为东亚地区是该属的现代分布中心及分化中心。伊朗-土兰地区(中亚东部至喜马拉雅)及落基山地区所含种、组数仅次于东亚地区,而且多倍体现象多发生于这两区,因此可认为是本属的次生分布中心及分化中心。在此二地区,物种分化较活跃且复杂,先后描述了很多新种和变种,也曾进行过较多的归并处理。最近的分子生物学证据不断揭示,在这地区曾被归并的一些分类群存在着较大不同,从而提醒分类学家对年轻区系中物种分化较活跃的类群进行分类处理时,无论是建新分类群还是对某些类群进行归并,应持谨慎态度。作者根据黄华属植物的现代地理分布、形态演化趋势、现有的化石及地质历史资料,推测黄华属植物在中新世之前早已形成,并且在晚第三纪欧亚大陆与北美大陆失去陆地连接之前在两大陆已经存在,很可能是于早第三纪或晚白垩纪在劳亚古陆上起源于一个含羽扇豆生物碱的古槐成员。两大陆分离后,在不同的成种因子的影响下,形成了各自的演化格局：在亚洲,晚第三纪的喜马拉雅造山运动、古地中海消失及第四纪冰川作用引起的旱化、寒化,促进了该属植物的强烈分化;而在北美,第四纪的冰川作用及局部的山体隆起,可能是促进该属植物演化的主要动力。根据黄华属植物的系统演化趋势及原始类群的分布式样分析,东亚地区的中国-日本亚区可能是本属植物的原始类型中心。     

中国角盘兰属植物的研究

Herminium is a genus of about 26 species, mainly distributed in the temperate and subtropical regions of Asia and Europe.  Yunnan, Sichuan and Xizang in China are the pre- sent distribution centre as well as differentiation centre of the genus. In the present paper, taxa of Herminium hitherto recorded in China are taxonomically and phytogeographically discussed and revised, and, as a result, 18 species are recongnized, including two newly recorded spe- cies, H. angustilabre King et Pantl. and H. quinquelobum King et Pantl., and 12 species en- demic to China.  A full list of synonyms is given, a key to the species is provided and the distribution areas of all taxa are mapped.     

Herpetological phylogeographic analyses support a Miocene focal point of Himalayan uplift and biological diversification

The Himalaya are among the youngest and highest mountains in the world, but the exact timing of their uplift and origins of their biodiversity are still in debate. The Himalayan region is a relatively small area but with exceptional diversity and endemism. One common hypothesis to explain the rich montane diversity is uplift-driven diversification—that orogeny creates conditions favoring rapid in situ speciation of resident lineages. We test this hypothesis in the Himalayan region using amphibians and reptiles, two environmentally sensitive vertebrate groups. In addition, analysis of diversification of the herpetofauna provides an independent source of information to test competing geological hypotheses of Himalayan orogenesis. We conclude that the origins of the Himalayan herpetofauna date to the early Paleocene, but that diversification of most groups was concentrated in the Miocene. There was an increase in both rates and modes of diversification during the early to middle Miocene, together with regional interchange (dispersal) between the Himalaya and adjacent regions. Our analyses support a recently proposed stepwise geological model of Himalayan uplift beginning in the Paleocene, with a subsequent rapid increase of uplifting during the Miocene, finally giving rise to the intensification of the modern South Asian Monsoon.     

The maximal value of a zipf size variable: Sampling properties and relationship to other parameters

Because the Zipf size-frequency distribution is used so often as a mathematical model for bibliometric variables, it is important that the relationships among its parameters and its sampling properties be understood by investigators in this field. This paper examines these relationships and properties. In addition, it provides tables for the sampling distribution of the maximal value of a finite Zipf distribution and an approximation formula for confidence intervals. Confidence limits for the maximal value in a number of previous studies are determined.