Cancer Stem Cells: Biological Functions and Therapeutically Targeting

Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be important in treatment of malignant diseases both as targets and drug carriers. The efforts to understand the role of different signalling in cancer stem cells requires in depth knowledge about the mechanisms that control their self-renewal, differentiation and malignant potential. The aim of this paper is to discuss insights into cancer stem cells historical background and to provide a brief review of the new therapeutic strategies for targeting cancer stem cells.     

Chemical Bonding by the Chemical Orthogonal Space of Reactivity

The fashionable Parr–Pearson (PP) atoms-in-molecule/bonding (AIM/AIB) approach for determining the exchanged charge necessary for acquiring an equalized electronegativity within a chemical bond is refined and generalized here by introducing the concepts of chemical power within the chemical orthogonal space (COS) in terms of electronegativity and chemical hardness. Electronegativity and chemical hardness are conceptually orthogonal, since there are opposite tendencies in bonding, i.e., reactivity vs. stability or the HOMO-LUMO middy level vs. the HOMO-LUMO interval (gap). Thus, atoms-in-molecule/bond electronegativity and chemical hardness are provided for in orthogonal space (COS), along with a generalized analytical expression of the exchanged electrons in bonding. Moreover, the present formalism surpasses the earlier Parr–Pearson limitation to the context of hetero-bonding molecules so as to also include the important case of covalent homo-bonding. The connections of the present COS analysis with PP formalism is analytically revealed, while a numerical illustration regarding the patterning and fragmentation of chemical benchmarking bondings is also presented and fundamental open questions are critically discussed.     

Double Variational Binding—(SMILES) Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands

Variational quantitative binding–conformational analysis for a series of anti-HIV pyrimidine-based ligands is advanced at the individual molecular level. This was achieved by employing ligand-receptor docking algorithms for each molecule in the 1,3-disubstituted uracil derivative series that was studied. Such computational algorithms were employed for analyzing both genuine molecular cases and their simplified molecular input line entry system (SMILES) transformations, which were created via the controlled breaking of chemical bonds, so as to generate the longest SMILES molecular chain (LoSMoC) and Branching SMILES (BraS) conformations. The study identified the most active anti-HIV molecules, and analyzed their special and relevant bonding fragments (chemical alerts), and the recorded energetic and geometric docking results (i.e., binding and affinity energies, and the surface area and volume of bonding, respectively). Clear computational evidence was also produced concerning the ligand-receptor pocket binding efficacies of the LoSMoc and BraS conformation types, thus confirming their earlier presence (as suggested by variational quantitative structure-activity relationship, variational-QSAR) as active intermediates for the molecule-to-cell transduction process.     

Multiplicity results for some elliptic problems with nonlinear boundary conditions involving variable exponents

In this paper we analyze an elliptic partial differential equation involving variable exponent growth conditions coupled with a nonlinear boundary condition. We show the existence of infinitely many bounded weak solutions provided there is a suitable oscillatory behavior of the nonlinearity either at infinity or at zero. Our proofs rely on a method due to Saint Raymond.     

Sensitivity of SAR data to post-fire forest regrowth in Mediterranean and boreal forests

Disturbed forests may need decades to reach a mature stage and optically-based vegetation indices are usually poorly suited for monitoring purposes due to the rapid saturation of the signal with increasing canopy cover. Spaceborne synthetic aperture radar (SAR) data provide an alternate monitoring approach since the backscattered microwave energy is sensitive to the vegetation structure. Images from two regions in Spain and Alaska were used to analyze SAR metrics (cross-polarized backscatter and co-polarized interferometric coherence) from regrowing forests previously affected by fire. TerraSAR-X X-band backscatter showed the lowest sensitivity to forest regrowth, with the average backscatter increasing by 1-2 dB between the most recent fire scar and the unburned forest. Increased sensitivity (around 3-4 dB) was observed for C-band Envisat Advanced Synthetic Aperture (ASAR) backscatter. The Advanced Land Observing Satellite (ALOS) Phased Array-type L-band Synthetic Aperture Radar (PALSAR) L-band backscatter presented the highest dynamic range from unburned to recently burned forests (approximately 8 dB). The interferometric coherence showed low sensitivity to forest regrowth at all SAR frequencies. For Mediterranean forests, five phases of forest regrowth were discerned whereas for boreal forest, up to four different regrowth phases could be discerned with L-band SAR data. In comparison, the Normalized Difference Vegetation Index (NDVI) provided reliable differentiation only for the most recent development stages. The results obtained were consistent in both environments.     

Characterization of microdevices for ferrous chloride separation for biosensing applications

Ferrous chloride has a variety of applications such as a reducing flocculation agent in waste-water treatment, especially for wastes containing chromate, in the laboratory synthesis of iron complexes and it is employed as a reducing agent in many organic syntheses. The device used for experiment was fabricated on the silicon wafer as support for two electrodes in a SU8 polymer microchannel with an inlet, for the injection of aqueous solution of ferrous chloride, and two outlets, for the two by-products of separated solutions. The various parameters of the device were measured by White Light Interferometer (WLI) and Scanning Electron Microscopy (SEM). The magnetic field created by applying different types of potential between two electrodes determined ferrous chloride to separate in ferrous oxide and chlorine (in gaseous form). If a protein is added in this solution we have the possibility to immobilize the protein on the iron particles and on the channel area. The electrical results were collected using a semiconductor system analyzer Keithley and were examined subsequently. The Fe complexes deposited on the electrodes were characterized by XRD analyses.     

A new approach to predict ulcerative colitis activity through standard clinical–biological parameters using a robust neural network model

Neural Computing and Applications - Colonoscopy is the “gold” standard for evaluating disease activity in ulcerative colitis (UC). An important area of research is finding a...     

Subquadratic Algorithms for 3SUM

We obtain subquadratic algorithms for 3SUM on integers and rationals in several models. On a standard word RAM with w-bit words, we obtain a running time of . In the circuit RAM with one nonstandard AC ⁰ operation, we obtain . In external memory, we achieve O(n ²/(MB)), even under the standard assumption of data indivisibility. Cache-obliviously, we obtain a running time of . In all cases, our speedup is almost quadratic in the “parallelism” the model can afford, which may be the best possible. Our algorithms are Las Vegas randomized; time bounds hold in expectation, and in most cases, with high probability.     

Scheduling for electricity cost in a smart grid

We study an offline scheduling problem arising in demand response management in a smart grid. Consumers send in power requests with a flexible set of timeslots during which their requests can be served. For example, a consumer may request the dishwasher to operate for 1 h during the periods 8am to 11am or 2pm to 4pm. The grid controller, upon receiving power requests, schedules each request within the specified duration. The electricity cost is measured by a convex function of the load in each timeslot. The objective of the problem is to schedule all requests with the minimum total electricity cost. As a first attempt, we consider a special case in which the power requirement and the duration a for which a request needs service are both unit-size. For this problem, we present a polynomial time offline algorithm that gives an optimal solution and shows that the time complexity can be further improved if the given set of timeslots forms a contiguous interval.