Proof by analogy in mural

One of the most important advantages of using a formal method of developing software is that one can prove that development steps are correct with respect to their specification. Conducting proofs by hand, however,can be time consuming to the extent that designers have to judge whether a proof of a particular obligation is worth conducting. Even if hand proofs are worth conducting, how do we know that they are correct? One approach to overcoming this problem is to use an automatic theorem proving system to develop and check our proofs. However, in order to enable present day theorem provers to check proofs, one has to conduct them in much more detail than hand proofs. Carrying out more detailed proofs is of course more time consuming. This paper describes the use of proof by analogy in an attempt to reduce the time spent on proofs. We develop and implement a proof follower based on analogy and present two examples to illustrate its characteristics. One example illustrates the successful use of the proof follower. The other example illustrates that the follower's failure can provide a hint that enables the user to complete a proof

Glioblastoma Multiforme: Novel Therapeutic Approaches

The current therapy for glioblastoma multiforme involves total surgical resection followed by combination of radiation therapy and temozolomide. Unfortunately, the efficacy for such current therapy is limited, and newer approaches are sorely needed to treat this deadly disease. We have recently described the isolation of bacterial proteins and peptides with anticancer activity. In phase I human clinical trials, one such peptide, p28, derived from a bacterial protein azurin, showed partial and complete regression of tumors in several patients among 15 advanced-stage cancer patients with refractory metastatic tumors where the tumors were no longer responsive to current conventional drugs. An azurin-like protein called Laz derived from Neisseria meningitides demonstrates efficient entry and high cytotoxicity towards glioblastoma cells. Laz differs from azurin in having an additional 39-amino-acid peptide called an H.8 epitope, which allows entry and high cytotoxicity towards glioblastoma cells. Since p28 has been shown to have very little toxicity and high anti-tumor activity in advanced-stage cancer patients, it will be worthwhile to explore the use of H.8-p28, H.8-azurin, and Laz in toxicity studies and glioblastoma therapy in preclinical and human clinical trials

A Machine Checked Model of Idempotent MGU Axioms For Lists of Equational Constraints

We present formalized proofs verifying that the first-order unification algorithm defined over lists of satisfiable constraints generates a most general unifier (MGU), which also happens to be idempotent. All of our proofs have been formalized in the Coq theorem prover. Our proofs show that finite maps produced by the unification algorithm provide a model of the axioms characterizing idempotent MGUs of lists of constraints. The axioms that serve as the basis for our verification are derived from a standard set by extending them to lists of constraints. For us, constraints are equalities between terms in the language of simple types. Substitutions are formally modeled as finite maps using the Coq library Coq.FSets.FMapInterface. Coq's method of functional induction is the main proof technique used in proving many of the axioms.Comment: In Proceedings UNIF 2010, arXiv:1012.455

An unusual iminoacylation of 2-amino pyridyl thiazole: Synthesis, X-ray crystallography and DFT study of copper(II) amidine complexes and their cytotoxicity, DNA binding and cleavage study

Insertion of acetonitrile in the exocyclic NH2 group of the thiazole unit of 2-amino-4-(2-pyridyl)thiazole (HL) in the presence of copper chloride results in the formation of the monomeric amidine complex [Cu{LC(Me)double bondNH)}Cl2] (1). The same reaction of HL and copper(II) perchlorate yields the complex [Cu(HL)2](ClO4)2 (2), without acetonitrile insertion. However, the presence of a spacer donor, e.g. pyrazine, in the reaction medium results in the formation of a dinuclear amidine derivative, [(ClO4){LC(Me)double bondNH}Cu(μ-pyrazine)Cu{LC(Me)double bondNH}(ClO4)] (ClO4)2 (3). Complexes 1 and 3 are the first examples of copper assisted iminoacylation of 2-amino pyridylthiazole derivatives, confirming a nitrile to amidine transformation. The new complexes were characterized by single crystal X-ray crystallography, cyclic voltammetry and a DFT study. The complexes have a potential cytotoxic effect in human monocytic cells (U937) with IC50 values ranging from 0.84 to 4.5 μM. Significant necrotic activities are ascertained by a lactate dehydrogenase (LDH) enzyme release assay. The interaction with calf thymus (CT) DNA shows the binding constant (Kb) values are ∼104 M−1. The chemical nuclease activity of 1, 2 and 3 result in 65, 99 and 80% relaxation of supercoiled DNA at 10 μM in the presence of glutathione (GSH, 1 mM), respectively. The study with radical scavengers proved that a hydroxyl or singlet oxygen-like species is responsible for the DNA degradation.publishe

Synthesis, characterization, cytotoxicity effect and DNA cleavage study of symmetric dinuclear chloro and azido bridged copper(II) complexes of napthyl-pyrazole based ligand

Symmetric dinuclear chloro copper(II) complex [Cu(L)(Cl)(µ-Cl)]2 (1) and azo dinuclear azido copper(II) complex [Cu2(L)2(N3)3(µ2-N3)]n (2) [where L represents (5-methyl-pyrazol-1-ylmethyl)-napthalen-1-ylmethyl-amine] have been synthesized to examine the effect of napthyl group in the structure of pyrazole based dinuclear copper(II) complexes in DNA nuclease activity. The structure of 1 and 2 are characterized by X-ray crystallography, electrochemistry and various spectroscopic techniques. Coordinating ligand L is generated in situ from bis(3,5-dimethyl-pyrazol-1-ylmethyl)-napthalen-1-ylmethyl-amine (A) during complexation. Cytotoxic potential of free ligand (A), synthesized complexes 1, 2 and one cobalt(II) complex derived from ligand A, CoII(A)Cl2 (3) are analyzed using MTT cytotoxicity assay in U937 human monocytic cell line. Complexes 1 and 2 show very potent cytotoxicity (IC50 = 13–17 μM); the best IC50 value is found for 1. LDH assay revealed that A and 3 has greater necrotic activity than the copper complexes. However, the results of DNA cleavage study clearly demonstrated that symmetric bridged dinuclear complexes with napthyl group lead to high level of nuclease activity 72–75% in the presence of glutathione. The bridged dinuclear copper(II) complexes undergo facile transformation to Cu(I) centre through inner sphere electron transfer mechanism (ISET) in presence of glutathione which facilitate the formation of free radicals/ions for DNA cleavage. Lacking of any reducible metal center in mononuclear cobalt(II) complex make it inactive towards free radicals generation in DNA cleavage activity.publishe

A Study of Nuclear Transcription Factor-Kappa B in Childhood Autism

BACKGROUND: Several children with autism show regression in language and social development while maintaining normal motor milestones. A clear period of normal development followed by regression and subsequent improvement with treatment, suggests a multifactorial etiology. The role of inflammation in autism is now a major area of study. Viral and bacterial infections, hypoxia, or medication could affect both foetus and infant. These stressors could upregulate transcription factors like nuclear factor kappa B (NF-κB), a master switch for many genes including some implicated in autism like tumor necrosis factor (TNF). On this hypothesis, it was proposed to determine NF-κB in children with autism. METHODS: Peripheral blood samples of 67 children with autism and 29 control children were evaluated for NF-κB using electrophoretic mobility shift assay (EMSA). A phosphor imaging technique was used to quantify values. The fold increase over the control sample was calculated and statistical analysis was carried out using SPSS 15. RESULTS: We have noted significant increase in NF-κB DNA binding activity in peripheral blood samples of children with autism. When the fold increase of NF-κB in cases (n = 67) was compared with that of controls (n = 29), there was a significant difference (3.14 vs. 1.40, respectively; p<0.02). CONCLUSION: This finding has immense value in understanding many of the known biochemical changes reported in autism. As NF-κB is a response to stressors of several kinds and a master switch for many genes, autism may then arise at least in part from an NF-κB pathway gone awry

Ethnobotany genomics - discovery and innovation in a new era of exploratory research

We present here the first use of DNA barcoding in a new approach to ethnobotany we coined "ethnobotany genomics". This new approach is founded on the concept of 'assemblage' of biodiversity knowledge, which includes a coming together of different ways of knowing and valorizing species variation in a novel approach seeking to add value to both traditional knowledge (TK) and scientific knowledge (SK). We employed contemporary genomic technology, DNA barcoding, as an important tool for identifying cryptic species, which were already recognized ethnotaxa using the TK classification systems of local cultures in the Velliangiri Hills of India. This research is based on several case studies in our lab, which define an approach to that is poised to evolve quickly with the advent of new ideas and technology. Our results show that DNA barcoding validated several new cryptic plant species to science that were previously recognized by TK classifications of the Irulas and Malasars, and were lumped using SK classification. The contribution of the local aboriginal knowledge concerning plant diversity and utility in India is considerable; our study presents new ethnomedicine to science. Ethnobotany genomics can also be used to determine the distribution of rare species and their ecological requirements, including traditional ecological knowledge so that conservation strategies can be implemented. This is aligned with the Convention on Biological Diversity that was signed by over 150 nations, and thus the world's complex array of human-natural-technological relationships has effectively been re-organized

From the periphery to the brain: Lipocalin-2, a friend or foe?

Lipocalin-2 (LCN2) is an acute-phase protein that, by binding to iron-loaded siderophores, acts as a potent bacteriostatic agent in the iron-depletion strategy of the immune system to control pathogens. The recent identification of a mammalian siderophore also suggests a physiological role for LCN2 in iron homeostasis, specifically in iron delivery to cells via a transferrin-independent mechanism. LCN2 participates, as well, in a variety of cellular processes, including cell proliferation, cell differentiation and apoptosis, and has been mostly found up-regulated in various tissues and under inflammatory states, being its expression regulated by several inducers. In the central nervous system less is known about the processes involving LCN2, namely by which cells it is produced/secreted, and its impact on cell proliferation and death, or in neuronal plasticity and behaviour. Importantly, LCN2 recently emerged as a potential clinical biomarker in multiple sclerosis and in ageing-related cognitive decline. Still, there are conflicting views on the role of LCN2 in pathophysiological processes, with some studies pointing to its neurodeleterious effects, while others indicate neuroprotection. Herein, these various perspectives are reviewed and a comprehensive and cohesive view of the general function of LCN2, particularly in the brain, is provided.Ana Catarina Ferreira and Sandro Da Mesquita are recipients of PhD fellowships by the Fundação para a Ciência e Tecnologia (FCT, Portugal)/FEDER. Fernanda Marques is an assistant researcher IF/ 00231/2013 of the Fundação para a Ciência e Tecnologia (FCT, Portugal). This work was supported by Fundação para a Ciência e Tecnologia (FCT) and COMPETE through the project: EXPL/NEUOSD/2196/2013 (to Marques F). The authors thank Nadine Santos for the helpful comments on the manuscript

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació