Edible: By grafting natural peptide antagonists onto the cyclotide kalata B1, orally active peptides were engineered, which are potentially useful therapeutics for the treatment of inflammatory pain. For example, the entire loop 6 of kalata B1 was replaced with the peptidic bradykinin B1 receptor antagonist DALK (red in scheme) to obtain the cyclic bradykinin antagonist ckb‐kal.

A finite element formulation for a digital image correlation method is presented that will determine directly the complete, two-dimensional displacement field during the image correlation process on digital images. The entire interested image area is discretized into finite elements that are involved in the common image correlation process by use of our algorithms. This image correlation method with finite element formulation has an advantage over subset-based image correlation methods because it satisfies the requirements of displacement continuity and derivative continuity among elements on images. Numerical studies and a real experiment are used to verify the proposed formulation. Results have shown that the image correlation with the finite element formulation is computationally efficient, accurate, and robust.

Essbar: Durch Aufpropfen von natürlichen Peptid‐Antagonisten auf das Cyclotid Kalata B1 wurden Peptide hergestellt, die nützliche oral verabreichbare Schmerzmittel sein könnten. Zum Beispiel wurde die gesamte Schleife 6 von Kalata B1 durch den peptidischen Bradykinin‐B1‐Rezeptor‐Antagonisten DALK (rot im Schema) ersetzt, um den cyclischen Bradykinin‐Antagonisten ckb‐kal zu erhalten.

In this paper, anodic bonding between silicon wafer and glass wafer (Pyrex 7740) has been achieved at low temperature. The bond strength is measured using a tensile testing machine. The interfaces are examined and analyzed by scanning acoustic microscopy (SAM), scanning electron microscopy (SEM) and secondary ion mass spectrometry (SIMS). The effects of the bonding parameters on bond quality are investigated using the Taguchi method. The bonding temperature used ranges from 200 °C to 300 °C. Almost bubble-free interfaces have been obtained. The bonded area increases with increasing bonding temperature. The unbonded area is less than 1.5% within the whole wafer for bonding temperature between 200 °C and 300 °C. The bond strength is higher than 10 MPa and increases with the bonding temperature. Fracture mainly occurs inside the glass wafer other than in the interface when the bonding temperature is higher than 225 °C. Higher bonding temperature results in more oxygen migration to the interface and more Si–O bonds. The bonding mechanisms consist of hydrogen bonding and Si–O chemical reaction.

SummaryPluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP) cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.

No abstract

Chromosomal instability (CIN), a high rate of chromosome loss or gain, is often associated with poor prognosis and drug resistance in cancers. Aneuploid, including near-polyploid, cells contain an abnormal number of chromosomes and exhibit CIN. The post-mitotic cell fates following generation of different degrees of chromosome mis-segregation and aneuploidy are unclear. Here we used aneuploidy inducers, nocodazole and reversine, to create different levels of aneuploidy. A higher extent of aneuploid and near-polyploid cells in a given population led to senescence. This was in contrast to cells with relatively lower levels of abnormal ploidy that continued to proliferate. Our findings revealed that senescence was accompanied by DNA damage and robust p53 activation. These senescent cells acquired the senescence-associated secretory phenotype (SASP). Depletion of p53 reduced the number of senescent cells with concomitant increase in cells undergoing DNA replication. Characterisation of these SASP factors demonstrated that they conferred paracrine pro-tumourigenic effects such as invasion, migration and angiogenesis both in vitro and in vivo. Finally, a correlation between increased aneuploidy and senescence was observed at the invasive front in breast carcinomas. Our findings demonstrate functional non-equivalence of discernable aneuploidies on tumourigenesis and suggest a cell non-autonomous mechanism by which aneuploidy-induced senescent cells and SASP can affect the tumour microenvironment to promote tumour progression.

Recently, a lane-based optimization method was developed for the design of isolated signal-controlled junctions. The lane markings are relaxed as binary-type control variables and are integrated into the design framework, in which the lane markings and signal settings can be optimized simultaneously to maximize the overall junction performance. To take into account the time-varying effects of traffic demand, the lane-based optimization method has been enhanced to cater for multi-period demand patterns. To eliminate ambiguity, only a single set of lane markings (also referred to as the permitted movements) can be established on the ground for operation throughout all of the design periods, which implies that during various design periods road users that approach a junction will be guided by the same set of lane markings. In accordance with the specific traffic conditions in different design periods, road users can make their own choice of traffic lane for turning, provided that they do not violate the permitted movement patterns. In the present formulation, the actual lane utilization patterns are referred to as the effective movements. A set of linear constraints is developed to relate all of the lane-based control variables and to prescribe the feasible solution region. The optimization for the usual objective function is formulated as a mathematical program. Standard and heuristic solution methods are derived, and numerical examples are also given for demonstration.