Stochastic dynamics of model proteins on a directed graph

A method for reconstructing the energy landscape of simple polypeptidic chains is described. We show that we can construct an equivalent representation of the energy landscape by a suitable directed graph. Its topological and dynamical features are shown to yield an effective estimate of the time scales associated with the folding and with the equilibration processes. This conclusion is drawn by comparing molecular dynamics simulations at constant temperature with the dynamics on the graph, defined by a temperature dependent Markov process. The main advantage of the graph representation is that its dynamics can be naturally renormalized by collecting nodes into "hubs", while redefining their connectivity. We show that both topological and dynamical properties are preserved by the renormalization procedure. Moreover, we obtain clear indications that the heteropolymers exhibit common topological properties, at variance with the homopolymer, whose peculiar graph structure stems from its spatial homogeneity. In order to obtain a clear distinction between a "fast folder" and a "slow folder" in the heteropolymers one has to look at kinetic features of the directed graph. We find that the average time needed to the fast folder for reaching its native configuration is two orders of magnitude smaller than its equilibration time, while for the bad folder these time scales are comparable. Accordingly, we can conclude that the strategy described in this paper can be successfully applied also to more realistic models, by studying their renormalized dynamics on the directed graph, rather than performing lengthy molecular dynamics simulations.Comment: 15 pages, 12 figure

Seismic microzonation for Muscat region, Sultanate of Oman

Site characterization was carried out for Muscat region using the ambient noise measurements applying the horizontal-to-vertical spectral ratio (HVSR) technique and using active seismic survey utilizing the multichannel analysis of surface waves (MASW) of survey data. Microtremors measurements were carried out at 459 sites using short-period sensors. This extensive survey allowed the fundamental resonance frequency of the soft soil to be mapped and areas prone to site amplification to be identified. The results indicate a progressive decrease in the fundamental resonance frequencies from the southern and eastern parts, where the bedrock outcrops, toward the northern coast where a thickness of sedimentary cover is present. Shear wave velocity (Vs) was evaluated using the 2-D MASW at carefully selected 99 representative sites in Muscat. These 99 sites were investigated with survey lines of 52 m length. 1-D and interpolated 2-D profiles were generated up to a depth range 20–40 m. The vertical Vs soundings were used in the SHAKE91 software in combination with suitable seismic input strong motion records to obtain the soil effect. Most of the study area has amplification values less than 2.0 for all the considered spectral periods. The estimated fundamental frequencies obtained using the H/V spectral ratio method and using SHAKE91 are found to be in a relatively good agreement. Maps of spectral amplification, earthquake characteristics on the ground surface for peak ground and spectral accelerations at 0.1, 0.2, 0.3, 1.0, and 2.0 s, for 475 years return period are produced. The surface ground motion maps show that the hazard level is moderate with expected PGA in the range 0.059–0.145 g for 475 years return period.Oman Ministerial Cabinet (project # 22409017

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Editing of the urease gene by CRISPR-Cas in the diatom Thalassiosira pseudonana

Background: CRISPR-Cas is a recent and powerful addition to the molecular toolbox which allows programmable genome editing. It has been used to modify genes in a wide variety of organisms, but only two alga to date. Here we present a methodology to edit the genome of Thalassiosira pseudonana, a model centric diatom with both ecological significance and high biotechnological potential, using CRISPR-Cas. Results: A single construct was assembled using Golden Gate cloning. Two sgRNAs were used to introduce a precise 37 nt deletion early in the coding region of the urease gene. A high percentage of bi-allelic mutations (≤61.5%) were observed in clones with the CRISPR-Cas construct. Growth of bi-allelic mutants in urea led to a significant reduction in growth rate and cell size compared to growth in nitrate. Conclusions: CRISPR-Cas can precisely and efficiently edit the genome of T. pseudonana. The use of Golden Gate cloning to assemble CRISPR-Cas constructs gives additional flexibility to the CRISPR-Cas method and facilitates modifications to target alternative genes or species

Synthesis and Antibacterial Study of New Microporous Zinc Phosphate Bioceramics

In a ternary system composed of aluminum phosphate, zinc oxide, and orthophosphoric acid, we have prepared microporous ceramics for orthopedic and dental uses. Firstly, we have prepared the ceramics with uncontrollable porosity by sintering blocs of the zinc phosphate cement drawn from the ternary system. Then, based on a binary system consisted of aluminum phosphate, zinc oxide, and some porogenic additives, we have prepared ceramics with good and homogeneous porosity structure. In the second issue, the preparation is made by a simple mixture of powders. Thus, after homogenization, compaction and sintering at high temperatures, the resulted ceramics developed high mechanical resistances. Besides, antibacterial tests on the ceramics have been conducted and shown good biological performances. The mechanical behavior as well as the biological properties candidate the ceramics to be a good alternative to the hard tissue. Eventually, all preparations are controlled and investigated using several technics such as FTIR, XRD, SEM, TAG-TAD, mechanical test, and an antibacterial activity test

The Function of Bachelardian Epistemology in the Post-colonial Project of Mohammed ‘Abed al-Jabri

This paper explores the function of historical epistemology in the thought of Gaston Bachelard (1884–1962) and Mohammed ‘Abed al-Jabri (1935–2010). Attributing thought with a particular function challenges our tendency to explain the development of thought in other socio-historical contexts in terms of mere conceptual influence. Available English-language literature on al-Jabri commonly references Bachelard’s concept of epistemological rupture as a source of inspiration. Though the reference is astute, this term remains poorly understood and has long been overshadowed by Thomas Kuhn’s notion of ‘paradigm shift’. The broader function of Bachelard’s thought as a renegotiation of time, place, subject, and reason in the natural sciences has been largely neglected in historiographies of the philosophy of science outside of France. This paper emphasizes the level of insight and ingenuity with which al-Jabri employs the function of Bachelard’s epistemology by re-interpreting it within the framework of his own socio-historical context. Far from reducing al-Jabri’s thought to a mere programmatic reproduction of French thought, I suggest that al-Jabri was among the most astute interpreters of this long-misunderstood theorist

Deep Theorizing in International Relations

This paper starts from the observation that, at a time when the popularity of grand theory is in decline among IR scholars, they do not agree on what they mean by theory. In fact, the celebration of theoretical pluralism is accompanied by the relative absence of a serious conversation about what ‘theory’ is, could, or should be. Taking the view that we need such a conversation, this puts forward the notion of ‘deep theorizing’. Countering both the shallow theorizing of modern scholarship that conflates theory with scientific method, and the postmodern view that abstract narratives must be deconstructed and rejected, it offers a reading of the parameters along which substantial theorizing proceeds. Specifically, it suggests that ‘deep theorizing’ is the conceptual effort of explaining (inter)action by developing a reading of drives/basic motivations and the ontology of its carrier through an account of the human condition, that is, a particular account of how the subject (the political actor) is positioned in social space and time. The paper illustrates the plausibility of this meta-theoretical angle in a discussion of realist, liberal and postcolonial schools of thought

Military business and the business of the military

Contrary to dominant approaches that locate the causes for military entrepreneurialism in eastern Democratic Republic of the Congo predominantly in criminal military elites, this article highlights the importance of the Congolese military’s (FARDC) civilian context for understanding military revenue-generation. It analyses how the latter is shaped by structures of domination, signification and legitimisation that drive and are driven by the FARDC’s governance, private protection and security practices. It argues that these practices contribute to bestowing a degree of legitimacy on both the FARDC’s position of power and some of its revenue-generation activities. Furthermore, by emphasising that the FARDC’s regulatory and protection practices are partly the product of popular demands and the routine actions of civilians, the article contends that the causes of military revenue-generation are co-located in the military’s civilian environment. In this manner, it offers a more nuanced conceptualisation of military entrepreneurialism, thus opening up new perspectives on policy interventions in this area

Transglutaminase 6: a protein associated with central nervous system development and motor function.

Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons

Robust Adaptive Control of the Mold Level in the Continuous Casting Process Using Multiple Models

Abstract-In the continuous casting of steel, mold level control is fundamental for obtaining high productivity and high quality. Using conventional methods, it is difficult to achieve both stability and performance robustness because of different classes of disturbances and parameters uncertainties in the process. This paper presents a multi-model adaptive control architecture based on the so-called RMMAC methodology. With the help of precise definition of robust performance requirements, the number of models, estimators and controllers are merely derived. More importantly, the combination of robust non-adaptive mixed-µ synthesis and stochastic hypothesis testing concepts enables controller performances prediction as well as online monitoring process parameters which could be used by operators to take corrective actions. The generated signals are likewise useful for understanding the physical phenomena in the process