505 research outputs found
The Function of Bachelardian Epistemology in the Post-colonial Project of Mohammed âAbed al-Jabri
This paper explores the function of historical epistemology in the thought of Gaston Bachelard (1884â1962) and Mohammed âAbed al-Jabri (1935â2010). 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 Bachelardâs 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 Kuhnâs notion of âparadigm shiftâ. The broader function of Bachelardâs 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 Bachelardâs epistemology by re-interpreting it within the framework of his own socio-historical context. Far from reducing al-Jabriâs 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
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
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-” 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
An efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease
Celiac disease (CeD) is an autoimmune disorder induced by consuming gluten proteins from wheat, barley, and rye. Glutens resist gastrointestinal proteolysis, resulting in peptides that elicit inflammation in patients with CeD. Despite well-established connections between glutens and CeD, chemically defined, bioavailable peptides produced from dietary proteins have never been identified from humans in an unbiased manner. This is largely attributable to technical challenges, impeding our knowledge of potentially diverse peptide species that encounter the immune system. Here, we develop a liquid chromatographic-mass spectrometric workflow for untargeted sequence analysis of the urinary peptidome. We detect over 600 distinct dietary peptides, of which ~35% have a CeD-relevant T cell epitope and ~5% are known to stimulate innate immune responses. Remarkably, gluten peptides from patients with CeD qualitatively and quantitatively differ from controls. Our results provide a new foundation for understanding gluten immunogenicity, improving CeD management, and characterizing the dietary and urinary peptidomes.Ministerio de Ciencia e InnovaciĂłn SAF2017-83700-
Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A
Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses
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 20â40 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 0.059â0.145 g for 475 years return period.Oman Ministerial Cabinet (project # 22409017
Reprogramming of CTLs into natural killerâlike cells in celiac disease
Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon Îłâproducing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases
Analysis of Blood Cultures in Major Burns in Tertiary Care Burn Unit in Oman
Objectives: In this study we review blood stream infections of major burns in a tertiary care burn unit to determine the most prevalent organisms in order to have a better empirical therapy protocol. Methods: This is a retrospective study where blood stream infection of major burns (>20% Total Body Surface Area) were analysed. Results:155 patients fulfilled the criteria. Median age was 33 years. Median TBSA was 38%. 57.42% were males and 42.58% were females. Mortality was 25.16%. 50.9% of patients had positive blood culture. Expired patients had higher TBSA, Abbreviated Burns Severity Index score and earlier first positive blood culture. The most prevalent organisms grown from all blood cultures were Acinetobacter, staphylococci, Klebsiella, Enterococcus and pseudomonas. Candida is also commonly grown in blood cultures. All Acinetobacter species are always multidrug resistant. 8 of 14 patients had multidrug resistant Klebsiella. There were only 4 patients who had Methicilin resistant Staphylococcus Aureus (MRSA) grown. The number of blood cultures samples taken ranged from 1 to 28 (median 6). First positive blood culture showed that Staphylococcus epidermidis and Acinetobacter are the most common organisms. Conclusion: In conclusion multidrug resistant Acinetobcater has become the most predominant microorganism grown in blood cultures of major burns in our unit. Empirical therapy should include antibiotics that are effective against it to reduce the mortality.
Keywords: Infection; Blood; Burn; Resistance; Antibiotics; Culture
Molecular modelling of the GIR1 branching ribozyme gives new insight into evolution of structurally related ribozymes
Twin-ribozyme introns contain a branching ribozyme (GIR1) followed by a homing endonuclease (HE) encoding sequence embedded in a peripheral domain of a group I splicing ribozyme (GIR2). GIR1 catalyses the formation of a lariat with 3 nt in the loop, which caps the HE mRNA. GIR1 is structurally related to group I ribozymes raising the question about how two closely related ribozymes can carry out very different reactions. Modelling of GIR1 based on new biochemical and mutational data shows an extended substrate domain containing a GoU pair distinct from the nucleophilic residue that dock onto a catalytic core showing a different topology from that of group I ribozymes. The differences include a core J8/7 region that has been reduced and is complemented by residues from the pre-lariat fold. These findings provide the basis for an evolutionary mechanism that accounts for the change from group I splicing ribozyme to the branching GIR1 architecture. Such an evolutionary mechanism can be applied to other large RNAs such as the ribonuclease P
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