Passively Targeted Curcumin‐Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half‐life and poor water solubility. Nanotechnology‐based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic‐co‐glycolic acid) (PLGA)‐based polymeric oil‐cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico‐chemical properties, and shelf‐life stability. The results indicate that castor oil‐cored PLGA‐based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin‐loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non‐PEGylated NC, and accumulates in the subcutaneous CT26‐tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer.     

Shotgun MS proteomic analysis of bronchoalveolar lavage fluid in normal subjects

We provide a review of proteomic techniques used to characterize the bronchoalveolar lavage fluid (BALF) proteome of normal healthy subjects. Bronchoalveolar lavage (BAL) is the most common technique for sampling the components of the alveolar space. The proteomic techniques used to study normal BALF include protein separation by 2DE, whereby proteins were identified by comparison to a reference gel as well as high pressure liquid chromatography (HPLC)-MS/MS, also known as shotgun proteomics. We summarize recent progress using shotgun MS technologies to define the normal BALF proteome. Surprisingly, we find that despite advances in shotgun proteomic technologies over the course of the last 10 years, which have resulted in greater numbers of proteins being identified, the functional landscape of normal BALF proteome was similarly described by all methods examined.     

Second order collision for the 42-step reduced DHA-256 hash function

At the Cryptographic Hash Workshop hosted by NIST in 2005, Lee et al. proposed the DHA-256 (Double Hash Algorithm-256) hash function. The design of DHA-256 builds upon the design of SHA-256, but introduces additional strengthening features such as optimizing the message expansion and step function against local collision attacks. Previously, DHA-256 was analyzed by J. Zhong and X. Lai, who presented a preimage attack on 35 steps of the compression function with complexity 2^239.6. In addition, the IAIK Krypto Group provided evidence that there exists a 9-step local collision for the DHA-256 compression function with probability higher than previously predicted. In this paper, we analyze DHA-256 in the context of higher order differential attacks. In particular, we provide a practical distinguisher for 42 out of 64 steps and give an example of a colliding quartet to validate our results.     

Exploration of the normal human bronchoalveolar lavage fluid proteome

We obtained insight into normal lung function by proteome analysis of bronchoalveolar lavage fluid (BALF) from six normal human subjects using a "Lyse-N-Go' shotgun proteomic protocol. Intra-sample variation was calculated using three different label-free methods, (i) protein sequence coverage; (ii) peptide spectral counts and (iii) peptide single-ion current areas (PICA), which generates protein expression data by summation of the area under the curve for a given peptide single-ion current trace and then adding values for all peptides from that same parent protein. PICA gave the least intra-subject variability and was used to calculate differences in protein expression between the six subjects. We observed an average threefold inter-sample variability, which affects analysis of changes in protein expression that occur in different diseases. We detected 167 unique proteins with >100 proteins detected in each of the six individual BAL samples, 42 of which were common to all six subjects. Gene ontology analysis demonstrated enrichment of several biological processes in the lung, reflecting its expected role in gas exchange and host defense as an immune organ. The same biological processes were enriched compared to either plasma or total genome proteome, suggesting an active enrichment of plasma proteins in the lung rather than passive capillary leak.     

White coat effect and reactivity to stress: cardiovascular and autonomic nervous system responses

The aim of this study was to elucidate further the precise nature of the so-called "white coat" (WC) effect. We enrolled 88 hypertensive (46 men, 42 women) and 18 normotensive (4 men, 14 women) subjects in whom beat-to-beat blood pressure (BP) and heart rate (HR) were measured with a Finapres device at rest (R period) and during conventional BP measurement (WC period). The WC effect was defined as WC period minus R period values of Finapres systolic BP. Using the same method, we also measured the BP and HR variations induced by mental stress (MS period) and by assuming the standing position (S period). Variability was estimated in the frequency domain for BP (BPV) and HR (HRV) and gave indices of the autonomic nervous system. Pulse wave velocity was taken as an index of arterial distensibility. In hypertensive subjects, the WC effect was significantly and positively correlated with the BP response to stress (0.51, P<.0001) and standing (0.63, P<.0001). An increased BPV was observed in the low-frequency band (0 to 0.150 Hz) during WC, MS, and S periods. In normotensive subjects, the WC effect was very slight and not correlated with the responses to stress and standing. In this group, the WC period was not accompanied with an increased BPV, unlike the stress and standing periods. HRV was similar in normotensives and in hypertensives: decreased, unchanged, and increased during MS, S, and WC periods, respectively. The PWV was significantly increased in the hypertensives relative to the normotensives, even in the quartile of those with the lowest BP (on average similar to that of the normotensives). This work shows that the WC effect is associated with an enhanced BP response to standing and mental stress; these three situations are characterized by an increased BPV in the low frequencies, suggesting a similar modification of the sympathovagal balance. The WC effect may entail an increased risk because it is associated with impaired arterial distensibility.     

Preparation and characterization of carvedilol-loaded poly(d,l) lactide nanoparticles/microparticles as a sustained-release system

Carvedilol poly(d,l)-lactide nanoparticles/microparticles were prepared. The size and morphology of the developed particles were optimized to study the carvedilol release profile by studying the effect of organic solvents and polymer amount through atomic force microscopy analysis. Spherical particles were obtained with a minimum size of 125?nm in the case of acetone and a maximum size of 970?nm in the case of dichloromethane affording microparticles formation. The interaction was confirmed by differential scanning calorimeter and Fourier transform infrared. The in vitro release profile of the multicompartment system (pure carvedilol, loaded nanoparticles and microparticles) has shown a sustained release with Korsmeyer–Peppas with T lag model.     

N‐phenyl‐3‐substituted 5‐pyrazolone derivatives as organic stabilizers for rigid poly(vinyl chloride) against photodegradation

N‐Phenyl‐3‐substituted 5‐pyrazolone derivatives were investigated as organic photostabilizers for rigid poly(vinyl chloride) (PVC). Their stabilizing efficiency was evaluated by the determination of the weight loss of the polymer after irradiation for different periods and by the determination of the amount of gel formation as well as the intrinsic viscosity of the soluble fraction of the degraded polymer. Moreover, the efficiency was evaluated from the extent of the discoloration of the degraded polymer. This was attributed not only to the radical trapping potency of the pyrazolone derivatives, which intervened with the radical degradation species in the degradation process of PVC, but also to the blocking of the newly formed radical sites on the polymeric chains. Their stabilizing efficiencies were compared with those of phenyl salicylate and 2‐hydroxy‐4‐(octyloxy)phenyl benzophenone, industrially known UV absorbers. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1543–1555, 2006     

Cost model development using virtual manufacturing and data mining: part II—comparison of data mining algorithms

Cost models of manufacturing processes are an important tool enabling enterprises to make reasonable predictions and forecasts in relation to the production costs for existing and new products. Accurate and robust cost models can help to provide significant competitive advantage for manufacturing organisations. Advanced computational methods such as virtual manufacturing and data mining have been identified as potentially powerful techniques for generating cost models that bypass the problems associated with traditional cost modelling processes. Part I, of this two-part paper, described the development of a cost model development methodology that makes use of virtual manufacturing models and data mining techniques and used case study data to validate this methodology. A critical part of this methodology is the selection and use of effective data analysis techniques that can identify accurate and robust cost estimating relationships. Part II now examines in detail the effectiveness of alternative data mining algorithms in terms of their ability to develop relationships that are (1) representative of the real causal relationships that exist and (2) able to provide a high level of estimating accuracy. More specifically, it focuses on the data generated by virtual manufacturing models and how the size and complexity of the generated data sets impact the accuracy of the cost estimating relationships.     

Integration of sketch-based conceptual design and commercial CAD systems for manufacturing

Sketch-based modeling is a very important step towards a complete design process digitalization. For a complete digitalization, integration of sketch-based design modeling and commercial CAD systems is being a necessity. This is because of the need of detailed modification and refinement for the 3D models created by sketching. The integration can speed up the design process and affect competition between companies. In this paper, we present a new method to achieve the integration between sketch-based interfaces and commercial CAD systems by using gesture-based sketch modeling techniques for producing 3D conceptual design models and then translating the 3D models into CAD systems with feature recognition through IGES exchange files. Gesture-based modeling method was used because it works in a similar way to feature-based design approach and it is easy to extract features from its 3D models. IGES file format was used for exchanging 3D geometric model information because it is widely available within commercial CAD systems for data exchange and it also can express features and hierarchy information. 3D models were created with a gesture-based sketch interface for modeling and then information was extracted from it. After that, information was translated into IGES entities which were organized in a specific order in an IGES file. This information can be inputted into commercial CAD systems and recognized as a feature-based model with feature recognition embedded within CAD systems. To evaluate the proposed method, we conducted four case studies. In these case studies, we created 3D models and then transferred them into Autodesk Inventor as a commercial CAD system. After the CAD system recognized the 3D models successfully, we applied some modifications on the 3D models such as changing dimensions, positions and drafting to demonstrate the effective integration.