Laudan vs. Lakatos: kilka uwag na temat ostatecznej oceny demarkacjonizmu

The paper reconstructs and examines the meta-criterion of demarcation between science and pseudo-science as proposed by Laudan (1983). The analysis shows that Laudan’s meta-criterion overlooks a crucial demand that any reliable criterion should satisfy. This, in turn, opens up a possibility of a non-ad hoc modification of Laudan’s proposal. When the meta-criterion finally meets the requirement which states that any reliable criterion of demarcation has to enable a comparison of any two scientific theories with regard to the degree of their progressiveness, it is possible to point out at least one advanced theory which gives an acceptable definition of science, i.e. Lakatos’s methodology of scientific research programs – strangely enough, not attended to by Laudan. Therefore, the skeptical conclusions of his paper can be refuted; furthermore, after such a modification the meta-criterion of demarcation acquires a homogenous form what makes it stable in a way originally intended by Laudan.El artículo reconstruye y examina el metacriterio de demarcación entre ciencia y pseudociencia como fue propuesto por Laudan (1983). Este análisis demuestra que el metacriterio de Laudan pasa por alto requisitos cruciales que cualquier criterio aceptable debería cumplir. Lo que a su vez posibilita una modificación no ad hoc de la propuesta de Laudan. Cuando el metacriterio finalmente se enfrenta al requisito que establece que cualquier criterio de demarcación aceptable tiene que posibilitar la comparación de dos teorías científicas cualesquiera con respecto a su grado de progresividad, es posible señalar al menos una teoría avanzada que dé una definición aceptable de ciencia, es decir, la metodología de los programas de investigación científica de Lakatos, omitidos en el artículo de Laudan, por extraño que parezca. Por esto pueden refutarse las conclusiones dudosas de su artículo; y lo que es más, tras la modificación, el metracriterio de demarcación adquiere una forma homogénea que lo hace estable, tal y como Laudan pretendía originariamente.Celem artykułu jest rekonstrukcja i analiza przedstawionego przez Laudana (1983) metakryterium demarkacji między nauką a pseudonauką. Okazuje się, że Laudan przeoczył kluczowy warunek, który powinno uwzględniać każde godne uwagi metakryterium. Otwiera to z kolei możliwość wprowadzenia do jego propozycji poprawek, które nie będą miały charakteru ad hoc. Kiedy tym sposobem metakryterium obejmuje również wymóg, by kryterium demarkacji umożliwiało porównanie teorii naukowych co do stopnia ich postępowości czy naukowości, można wskazać przynajmniej jedną teorię podającą akceptowalne kryterium demarkacji, mianowicie Lakatosową metodologię naukowych programów badawczych, którą w swej pracy Laudan pominął jednak milczeniem. Wtedy też można odrzucić sceptyczne wnioski jego artykułu. Dzięki tej modyfikacji metakryterium demarkacji otrzymuje dodatkowo jednolitą postać, za sprawą której staje się ono stabilne, tak jak tego pierwotnie chciał Laudan

Quine’s Two Dogmas as a Criticism of Logical Empiricism

Dans les « Deux dogmes», Quine voulait démontrer que le positivisme logique n’était possible qu’en raison d’hypothèses injustifiées. L’intention de Quine était de montrer qu’il n’est possible de sauver l’empirisme que si l’on accepte une autre approche, holistique. Toutefois, l’article de Quine était anachronique dès le moment de sa publication. Le but de cet article est double. Tout d’abord, on esquissera l’argument de Quine et on le confrontera aux positions de Carnap et Dubislav. On montrera que la critique de Quine était en retard d’au moins 15 ans. En deuxième lieu, on examinera le postulat de Quine de l’empirisme sans dogmes et on comparera brièvement à la théorie de Poznański et Wundheiler. On soutiendra que ce postulat avait été réalisé déjà dans les années 1930.“Two Dogmas” was to demonstrate that logical positivism was possible solely due to unjustified assumptions. Quine aimed to point out that the rescuing of empiricism was possible only if another, holistic approach was accepted. However, Quine’s article was anachronistic already at the time of its publication. The aim of this paper is twofold. Firstly, it will sketch Quine’s argument and contrast it with the views held by Carnap and Dubislav. It will be claimed that Quine’s criticism was late by more than fifteen years. Secondly, it is to examine Quine’s postulate of empiricism without the dogmas and compare it briefly with a theory of Poznański and Wundheiler. It will be claimed that Quine postulate was realized already in the 1930s

Blood genomic profiles of exposures to Venezuelan equine encephalitis in Cynomolgus macaques (Macaca fascicularis)

<p>Abstract</p> <p>Background</p> <p>Lymphocytes provide invaluable whistle blowers of changes due to infections. We use the information registered by these cells using their mRNAs as they encounter the pathogen to develop patterns of expression that correspond to that specific pathogen.</p> <p>Venezuelan equine encephalitis (VEE) is a mosquito-borne viral disease characterized by fever and one or more of the following: severe headache, back pain, myalgias, prostration, chills, nausea, vomiting, weakness and other flu-like symptoms.</p> <p>Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment.</p> <p>Results</p> <p>We have been carrying out gene expression analysis of PBMC exposed to VEEV to extract signatures and diagnostic markers of early exposure to be used in non invasive blood analysis methods.</p> <p>In this study, we used high throughput gene expression analysis to identify markers of early and late exposures to VEEV in vivo in Cynomolgus macaques (<it>Macaca fascicularis</it>). We carried out cDNA microarrays and real time PCR on blood samples obtained from the NHP model resulting in a panel of host genes that are altered in response to VEEV.</p> <p>Conclusion</p> <p>Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment.</p

Gadd45α activity is the principal effector of Shigella mitochondria-dependent epithelial cell death in vitro and ex vivo

Modulation of death is a pathogen strategy to establish residence and promote survival in host cells and tissues. Shigella spp. are human pathogens that invade colonic mucosa, where they provoke lesions caused by their ability to manipulate the host cell responses. Shigella spp. induce various types of cell death in different cell populations. However, they are equally able to protect host cells from death. Here, we have investigated on the molecular mechanisms and cell effectors governing the balance between survival and death in epithelial cells infected with Shigella. To explore these aspects, we have exploited both, the HeLa cell invasion assay and a novel ex vivo human colon organ culture model of infection that mimics natural conditions of shigellosis. Our results definitely show that Shigella induces a rapid intrinsic apoptosis of infected cells, via mitochondrial depolarization and the ensuing caspase-9 activation. Moreover, for the first time we identify the eukaryotic stress-response factor growth arrest and DNA damage 45α as a key player in the induction of the apoptotic process elicited by Shigella in epithelial cells, revealing an unexplored role of this molecule in the course of infections sustained by invasive pathogens

Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis

Background: In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55–75 % mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated. Methods and Findings: Efficacy of synthetic short interfering RNA (siRNA) or short hairpin RNA (shRNA) in protecting mice from CHPV infection was assessed. The target genes were P and M genes primarily because important role of the former in viral replication and lethal nature of the latter. Real time one step RT-PCR and plaque assay were used for the assessment of gene silencing. Using pAcGFP1N1-CHPV-P, we showed that P-2 siRNA was most efficient in reducing the expression of P gene in-vitro. Both quantitative assays documented 2logs reduction in the virus titer when P-2, M-5 or M-6 siRNAs were transfected 2hr post infection (PI). Use of these siRNAs in combination did not result in enhanced efficiency. P-2 siRNA was found to tolerate four mismatches in the center. As compared to five different shRNAs, P-2 siRNA was most effective in inhibiting CHPV replication. An extended survival was noted when mice infected intracranially with 100 LD 50 CHPV were treated with cationic lipid complexed 5 mg P-2 siRNA simultaneously. Infection with 10LD 50 and treatment with two doses of siRNA first, simultaneously and second 24 hr PI, resulted in 70 % survival. Surviving mice showed 4logs less CHPV titers in brain without histopathological changes or antibody response. Gene expression profiles of P-2 siRNA treated mice showed no interferon response. First dose of siRNA at 2h

Septins restrict inflammation and protect zebrafish larvae from Shigella infection

Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood. Here, we use S. flexneri infection of zebrafish (Danio rerio) larvae to study in vivo the role of septins in inflammation and infection control. We found that depletion of Sept15 or Sept7b, zebrafish orthologs of human SEPT7, significantly increased host susceptibility to bacterial infection. Live-cell imaging of Sept15-depleted larvae revealed increasing bacterial burdens and a failure of neutrophils to control infection. Strikingly, Sept15-depleted larvae present significantly increased activity of Caspase-1 and more cell death upon S. flexneri infection. Dampening of the inflammatory response with anakinra, an antagonist of interleukin-1 receptor (IL-1R), counteracts Sept15 deficiency in vivo by protecting zebrafish from hyper-inflammation and S. flexneri infection. These findings highlight a new role for septins in host defence against bacterial infection, and suggest that septin dysfunction may be an underlying factor in cases of hyper-inflammation

The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity

Although the murine immune response to Venezuelan equine encephalitis virus (VEEV) is well-characterized, little is known about the human antibody response to VEEV. In this study we used phage display technology to isolate a panel of 11 VEEV-specfic Fabs from two human donors. Seven E2-specific and four E1-specific Fabs were identified and mapped to five E2 epitopes and three E1 epitopes. Two neutralizing Fabs were isolated, E2-specific F5 and E1-specific L1A7, although the neutralizing capacity of L1A7 was 300-fold lower than F5. F5 Fab was expressed as a complete IgG1 molecule, F5 native (n) IgG. Neutralization-escape VEEV variants for F5 nIgG were isolated and their structural genes were sequenced to determine the theoretical binding site of F5. Based on this sequence analysis as well as the ability of F5 to neutralize four neutralization-escape variants of anti-VEEV murine monoclonal antibodies (mapped to E2 amino acids 182–207), a unique neutralization domain on E2 was identified and mapped to E2 amino acids 115–119