Clicking Well-Defined Biodegradable Nanoparticles and Nanocapsules by UV-Induced Thiol-Ene Cross-Linking in Transparent Miniemulsions

A novel approach for the preparation of nanomaterials is developed by tuning miniemulsion reaction systems to be transparent in order to enable highly efficient photoreactions. Biodegradable nanoparticles and nanocapsules are obtained by UV-induced thiol-ene cross-linking of polylactide (PLA)-based precursor polymers preassembled in transparent miniemulsions. These well-defined nanomaterials may potentially serve as ideal scaffolds for drug delivery.

The mend of the bend-flexor pollicis longus tendon has an additional pulley distal to its point of angulation

The tendon of flexor pollicis longus angulates at the trapezio-metacarpal joint level. The degree of angulation varies with extent of radial/ulnar deviation (Rack and Ross [1984] J. Physiol. 351:99–110). We report a fibrous pulley at this level that helps stabilize the tendon and facilitates its action. The morphology of the pulley is described. We believe that it has an important role to play in the unique function of the tendon facilitating the movement of the thumb perpendicular to the plane of the thumbnail. Clin. Anat. 21:427–432, 2008. © 2008 Wiley-Liss, Inc

Comportamento flessionale di nodi esterni in calcestruzzo fibrorinforzato

SOMMARIO – Si presenta un macro modello di tipo reticolare in grado di riprodurre il comportamento in presenza di taglio e momento di nodi esterni trave-colonna di telai in calcestruzzo fibrorinforzato con fibre di acciaio
uncinato ed ordinario. Il caricamento del sistema è di tipo monotono come nel caso dell’analisi di pushover. Il modello considera la presenza di armature orizzontali e verticali della regione nodale e tiene in conto delle modalità
di rottura legate allo snervamento delle barre e allo schiacciamento delle regioni compresse in regime di sforzi pluriassiali. Il modello include le deformazioni flessionali della trave e della colonna in presenza di sforzo normale costante e restituisce la risposta del sistema colonna-nodo-trave (sub-assembralggio) tramite le curve carico-freccia all’estremità della semitrave. Per i singoli costituenti (trave, colonna e nodo) si è considerata la prima fessurazione, lo snervamento e lo schiacciamento delle regioni compresse e si sono fornite precise indicazioni sulla sequenza degli eventi che come è noto sono di fondamentale importanza per lo sviluppo di un progetto plastico che rispetti la gerarchia delle resistenze. Con l’uso del modello il controllo della gerarchia delle resistenze avviene a livello sezionale (lo snervamento delle barre deve avvenire prima dello schiacciamento delle regioni compresse) o di macro elemento (nella regione nodale lo snervamento delle staffe precede la crisi dei puntoni) e dell’intero elemento
sub-assemblaggio trave debole, colonna forte e nodo sovraresistente.
La risposta ottenuta con i modello proposto è in buon accordo con le risposte sperimentali disponibili in letteratura (almeno in termini di resistenza del sub-assemblaggio). Il modello è stato ulteriormente validato con analisi
numeriche agli elementi finiti condotte con il codice ATENA-2D. Le analisi numeriche sono state condotte utilizzando per il calcestruzzo fibroso adeguate leggi costitutive proposte dagli autori ed in grado di cogliere gli effetti
di softening e di resistenza residua a trazione legati alla presenza di fibre. Ulteriori sviluppi del modello saranno indirizzati a includere gli effetti di sfilamento delle barre d’armatura della trave e del conseguente degrado delle
tensioni d’aderenza per effetto di carichi monotonici e ciclici.

SUMMARY – A softened strut-and-tie macro model able to reproduce the flexural behavior of external beam-tocolumn joints with the presence of horizontal and vertical steel bars, including softening of compressed struts and yielding of main and secondary steel bars, is presented, to be used for the pushover analysis. The model proposed is able to calculate also the flexural response of fibrous reinforced concrete (FRC) beam-to-column sub-assemblages in term of a multilinear load-deflection curves. The model is able to take into account of the tensile behavior of main bars embedded in the surrounding concrete and of the softening of the compressed strut, the arrangement and percentage of the steel bars, the percentage and the geometry of steel fibers. First cracking, yielding of main steel and crushing of concrete were identified to determine the corresponding loads and displacement and to plot the simplified monotonic load-deflection curves of the sub-assemblages subjected in the column to constant vertical
load and at the tip of the beam to monotonically increasing lateral force. Through these load-delfection curves the component (beam, joint and column) that first collapse can be recognized and the capacity design can be verified.
The experimental results available in the literature are compared with the results obtained through the proposed model. Further, a validation of the proposed model is numerically made by using a non linear finite element program (ATENA-2D) able to analyze the flexural behavior of sub-assemblages.

Mechanical properties of polyamide 6 reinforced microfibrilar composites

The mechanical behavior of microfibrilar composites (MFC), consisting of a matrix of high-density polyethylene (HDPE) and reinforcement of polyamide 6 (PA6) fibrils, with and without compatibilization, was studied. The composites were produced by conventional processing techniques with various shape and arrangement of the PA6 reinforcing entities: long, unidirectional, or crossed bundles of fibrils (UDP and CPC, respectively), middle-length, randomly oriented bristles (MRB), or non-oriented micrometric PA6 spheres (NOM). The tensile, flexural, and impact properties of the MFC materials (UDP, CPC, and MRB) were determined as a function of the PA6 reinforcement shape, alignment and content, and compared with those of NOM, the non-fibrous composite. It was concluded that the in-situ MFC materials based on HDPE/PA6 blends display improvements in the mechanical behavior when compared with the neat HDPE matrix, e.g., up to 33% for the Young modulus, up to 119% for the ultimate tensile strength, and up to 80% for the flexural stiffness. Copyright © 2011 Society of Plastics Engineers.

Porous organic-inorganic hybrid aerogels based on Cr3+/Fe3+ and rigid bridging carboxylates

A general method to prepare organic-inorganic hybrid aerogels has been presented. A series of organic-inorganic hybrid aerogels were successfully produced from 3d trivalent transition metals (Cr3+, Fe3+) and bridging carboxylic acids. Gelation of the Cr(III) gels was achieved by heating the precursor solution to temperatures above 80 degrees C, which is in sharp contrast to usual supramolecular gels. Among a range of ligands used, highly porous aerogels could be prepared from rigid carboxylate, e.g. 1,4-benzenedicarboxylate and 1,3,5-benzenetricarboxylate. The porous aerogels can be described as a coherent, rigid spongy network of continuous nanometre-sized particles, which is significantly different from the usual fibrous network of supramolecular gels. The aerogels have tunable porous structures with micro-and mesoporosity depending on their reactant concentrations. Their surface areas, pore volumes, and average pore sizes were analysed by using nitrogen sorption, and the accessibility of the pores to bulky molecules was also evaluated. It represents a strategy to prepare hybrid materials with large porosity utilising structurally simple building blocks as precursors.

Composite materials based on silk proteins

A number of animals have evolved to produce silk-based composite materials for a variety of task-specific applications. The review initially focuses on the composite structure of silk fibers produced naturally by silkworms and spiders, followed by the preparation and applications of man-made composite materials (including fibers, films, foams, gels and particulates) incorporating silk proteins in combination with other polymers (both natural and synthetic) and/or inorganic particles. 

The lip:A histologic and analytical approach of relevance to esthetic plastic surgery

This is a study done for the first time to understand the histologic features of the lip deeply, quantitatively, and analytically and identify the differences between the outer, intermediate, and inner parts of the lips. Previous researchers did not tackle the histologic features of the lip from this point of view. Half lip was obtained from different well-preserved cadavers where the upper lip, lower lip, and lip angle were evaluated by coronal histologic sections. A total of 43 slides were studied and photographed using light and digital microscopes (Nikon COOLSCOPE, Nikon Corporation, Tokyo, Japan), respectively. The cadavers (26 men and 17 women) were in the age group of 45 to 65 years old, and older than 65 years. Data were entered on a study pro forma and statistically analyzed. Normal histologic features of the upper lip, intermediate, and the inner lip sections were observed. Fibrous septations that sometimes had muscular components inserting into them could be identified. In between these septations, there were loose areas (chambers). The mean numbers of chambers identified in the upper and lower lips were higher in the red areas, and more septations and chambers were identified in the lower lip. New histologic observations were classified into types 1 to 7. Significant relations were identified between the total number of septations and chambers in relation to age group and sex. Higher means of septations and chambers were detected in the age group older than 65 years, and in women as a whole. In conclusion, the findings detected in this work could explain the congenital lip pits that are familial or syndromic and many post-lip augmentation complications. © 2009 Lippincott Williams & Wilkins, Inc.

Reactions of nitrogen nucleophiles with enantiopure cyclohexenyl electrophiles:a stereo- and regio- selective study

The reactions of enantiopure cyclohexene epoxides and trans-1,2-bromoacetates, derived from the corresponding substituted benzene cis-dihydrodiol metabolites, with nitrogen nucleophiles, were examined and possible mechanisms proposed. An initial objective was the synthesis of new 1,2-aminoalcohol enantiomers as potential chiral ligands and synthetic scaffolds for library generation. These apparently simple substitution reactions proved to be more complex than initially anticipated and were found to involve a combination of different reaction mechanisms. Allylic trans-1,2-azidohydrins were prepared by Lewis acid-catalysed ring-opening of cyclic vinyl epoxides with sodium azide via an S(N)2 mechanism. On heating, these trans-1,2-azidohydrins isomerized to the corresponding trans-1,4-azidohydrins via a suprafacial allyl azide [3,3]-sigmatropic rearrangement mechanism. Conversion of a 1,2-azidohydrin to a 1,2-azidoacetate moved the equilibrium position in favour of the 1,4-substitution product. Allylic trans-1,2-bromoacetates reacted with sodium azide at room temperature to give C-2 and C-4 substituted products. A clean inversion of configuration at C-2 was found, as expected, from a concerted S(N)2-pathway. However, substitution at C-4 was not stereoselective and resulted in mixtures of 1,4-cis and 1,4-trans products. This observation can be rationalized in terms of competitive S(N)2 and S(N)2 reactions allied to a [3,3]-sigmatropic rearrangement. cis-1,2-Azidohydrins and cis-1,2-azidoacetates were much more prone to rearrange than the corresponding trans-isomers. Reaction of the softer tosamide nucleophile with trans-1,2-bromoacetates resulted, predominantly, in C-4 substitution via a syn-S(N)2 mechanism. One application of the reaction of secondary amines with allylic cyclohexene epoxides, to give trans-1,2-aminoalcohols, is in the synthesis of the anticholinergic drug vesamicol, via an S(N)2 mechanism. Copyright (c) 2013 John Wiley & Sons, Ltd.

Composite hunting technologies from the Terminal Pleistocene and Early Holocene, Niah Cave, Borneo

Renewed archaeological investigation of the West Mouth of Niah Cave, Borneo has demonstrated that even within lowland equatorial environments depositional conditions do exist where organic remains of late glacial and early post-glacial age can be preserved. Excavations by the Niah Cave Research Project (NCP) (2000-2003) towards the rear of the archaeological reserve produced several bone points and worked stingray spines, which exhibit evidence of hafting mastic and fibrous binding still adhering to their shafts. The position of both gives strong indication of how these cartilaginous points were hafted and gives insight into their potential function. These artefacts were recovered from secure and (14)C dated stratigraphic horizons. The results of this study have implications for our understanding the function of the Terminal Pleistocene and Early Holocene bone tools recovered from other regions of Island Southeast Asia. They demonstrate that by the end the Pleistocene rainforest foragers in Borneo were producing composite technologies that probably included fishing leisters and potentially the bow and arrow. (C) 2009 Elsevier Ltd. All rights reserved.

Accessory minerals and potentially toxic elements in Tanzanian vermiculites with respect to agricultural applications

The study assessed accessory minerals and metals in Tanzanian vermiculites with respect to their potential suitability for agricultural applications. Mineral and chemical analyses were involved. Pot experiments were also conducted to assess plant uptake of metals from soil with vermiculites. Fibrous sepiolite and amphiboles were minerals of health concern found in some samples. The sepiolite fibers had aspect ratios similar to those of asbestos minerals, which cause respiratory disorders and lung cancer when inhaled and thus pose a potential health risk to animals and humans. The amphibole fibers were thicker than 10 μm and are unlikely to be inhaled. Chromium (Cr) and nickel (Ni) concentrations in some samples were greater than the limits permitted in agricultural soils, but the elements are not highly plant available and do not inhibit the uptake of essential macronutrients. Heating vermiculites at 400-600° C enhanced extractability of Cr and Ni and should preferably be avoided. © Taylor & Francis Group, LLC.

Mineralogical and chemical characterization of some vermiculites from the mozambique belt of tanzania for agricultural use

Vermiculite minerals are locally available in the Mozambique Belt of Tanzania but are not currently commercially exploited. In part this may be due to lack of any precise characterization. This study was carried out as a first step to assess the suitability of these vermiculites for crop production by characterization of their mineralogical and chemical compositions. X-ray diffraction and scanning electron microscopy combined with an energydispersive X-ray system were used to establish the mineralogy. Electron microprobe analysis and inductively coupled plasma-mass spectrometry were used to study the chemical compositions and to identify any possible issues related to chemical composition that might affect their use if applied as soil conditioners. The samples were characterized as vermiculites and hydrobiotites with a wide variety of accessory minerals. Accessory minerals that might be of some concern are galena, fibrous amphiboles and sepiolite. The total levels of Ni in all vermiculites, and Cr in some, were also found to be high relative to common European standards and this might limit their potential as soil conditioners. It is clear that a field assessment of the bioavailability of various elements would be necessary before decisions relating to potential agricultural use could be made. © 2009 The Mineralogical Society.

Activation of the c-Jun N-terminal kinase (JNK) signaling pathway is essential during PBOX-6-induced apoptosis in chronic myelogenous leukemia (CML) cells

The mitogen-activated protein (MAP) kinase family is activated in response to a wide variety of external stress signals such as UV irradiation, heat shock, and many chemotherapeutic drugs and leads to the induction of apoptosis. A novel series of pyrrolo-1,5-benzoxazepines have been shown to potently induce apoptosis in chronic myelogenous leukemia (CML) cells, which are resistant to many chemotherapeutic agents. In this study we have delineated part of the mechanism by which a representative compound known as PBOX-6 induces apoptosis. We have investigated whether PBOX-6 induces activation of MAP kinase signaling pathways in CML cells. Treatment of K562 cells with PBOX-6 resulted in the transient activation of two JNK isoforms, JNK1 and JNK2. In contrast, PBOX-6 did not activate the extracellular signal-regulated kinase (ERK) or p38. Apoptosis was found to occur independently of the small GTPases Ras, Rac, and Cdc42 but involved phosphorylation of the JNK substrates, c-Jun and ATF-2. Pretreatment of K562 cells with the JNK inhibitor, dicoumarol, abolished PBOX-6-induced phosphorylation of c-Jun and ATF-2 and inhibited the induced apoptosis, suggesting that JNK activation is an essential component of the apoptotic pathway induced by PBOX-6. Consistent with this finding, transfection of K562 cells with the JNK scaffold protein, JIP-1, inhibited JNK activity and apoptosis induced by PBOX-6. JIP-1 specifically scaffolds JNK, MKK7, and members of the mixed-lineage kinase (MLK) family, implicating these kinases upstream of JNK in the apoptotic pathway induced by PBOX-6 in K562 cells.

Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains

Shallow hydrophobic insertions and crescent-shaped BAR scaffolds promote membrane curvature. Here, we investigate membrane fission by shallow hydrophobic insertions quantitatively and mechanistically. We provide evidence that membrane insertion of the ENTH domain of epsin leads to liposome vesiculation, and that epsin is required for clathrin-coated vesicle budding in cells. We also show that BAR-domain scaffolds from endophilin, amphiphysin, GRAF, and β2-centaurin limit membrane fission driven by hydrophobic insertions. A quantitative assay for vesiculation reveals an antagonistic relationship between amphipathic helices and scaffolds of N-BAR domains in fission. The extent of vesiculation by these proteins and vesicle size depend on the number and length of amphipathic helices per BAR domain, in accord with theoretical considerations. This fission mechanism gives a new framework for understanding membrane scission in the absence of mechanoenzymes such as dynamin and suggests how Arf and Sar proteins work in vesicle scission.

c-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway

The development of decellularised scaffolds for small diameter vascular grafts is hampered by their limited patency, due to the lack of luminal cell coverage by endothelial cells (EC) and to the low tone of the vessel due to absence of a contractile smooth muscle cells (SMC). In this study, we identify a population of vascular progenitor c-Kit+/Sca-1- cells available in large numbers and derived from immuno-privileged embryonic stem cells (ESCs). We also define an efficient and controlled differentiation protocol yielding fully to differentiated ECs and SMCs in sufficient numbers to allow the repopulation of a tissue engineered vascular graft. When seeded ex vivo on a decellularised vessel, c-Kit+/Sca-1-derived cells recapitulated the native vessel structure and upon in vivo implantation in the mouse, markedly reduced neointima formation and mortality, restoring functional vascularisation. We showed that Krüppel-like transcription factor 4 (Klf4) regulates the choice of differentiation pathway of these cells through β-catenin activation and was itself regulated by the canonical Wnt pathway activator lithium chloride. Our data show that ESC-derived c-Kit+/Sca-1-cells can be differentiated through a Klf4/β-catenin dependent pathway and are a suitable source of vascular progenitors for the creation of superior tissue-engineered vessels from decellularised scaffolds.

Biofabricação de enxertos porosos de PCL/FastOs™: aplicação óssea

A Engenharia de Tecidos é um domínio multidisciplinar que combina especialistas de múltiplos domínios, no sentido de se desenvolverem substitutos biológicos para a regeneração, reparação ou restauração de funções de órgãos ou tecidos. A estratégia mais comum em engenharia de tecidos consiste na utilização de matrizes de suporte (scaffolds) tridimensionais, biocompatíveis, biodegradáveis e altamente porosos, os quais servem de substrato físico ao processo de adesão, proliferação e diferenciação celular. O objectivo deste trabalho de investigação centrou-se na produção e caracterização de scaffolds de PCL e de PCL com partículas de biovidro, abordando um processo de biofabricação, que teve por base o princípio da extrusão. Utilizou-se para tal um equipamento patenteado pelo Centro para o Desenvolvimento Rápido e Sustentado do Produto (CDRsp) designado Bioextruder. Trata-se de um sistema concebido para a produção de matrizes com ou sem encapsulamento de células, de uma forma automática, flexível e integrada. As estruturas obtidas caracterizaram-se quanto às propriedades térmicas, químicas, morfológicas e mecânicas. Realizaram-se ainda, testes de bioactividade e testes de degradação in vitro. Os resultados obtidos mostram que as condições de processamento não induzem qualquer alteração no que diz respeito às propriedades térmicas e químicas dos materiais, que o aumento do teor de biovidro conduz a uma fragmentação da matriz polimérica num período de tempo mais curto, que os scaffolds obtidos apresentam uma geometria bem definida e uma distribuição de poros uniforme. Demonstra-se assim, que a combinação da matriz polimérica (PCL) com o biovidro, sob a forma de scaffolds é promissora para aplicações em Engenharia de Tecidos e Medicina Regenerativa.