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Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (P13K) pathway is frequently activated in solid tumors; however, currently, no reliable test for P13K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of P13K, results in robust activation of this pathway, we developed and

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucosidase, beta, acid (GBA) gene that encodes the lysosomal enzyme glucosylceramidase (GCase). GCase deficiency leads to characteristic visceral pathology and, in some patients, lethal neurological manifestations. Here, we report the generation of mouse models with the severe neuronopathic form o

Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) alpha-chain (c.719G>A;

Using a novel experimental approach based on near-infrared femtosecond absorption spectroscopy, we have determined the energy of the S-1 state of the carotenoid spheroidene. The energy of this state is 13 400 +/- 90 cm(-1) at both 293 and 186 K, showing that there is no temperature-induced shift of the S-1 level. A discrepancy of about 800 cm(-1) between the S-1 energy determined here and that obt

In this chapter various thermal, electronic and chemical devices are described, as well as well as the construction and calibration of a spectroradiometer. A separate section is devoted to the measurement of very weak light, such as the ultraweak luminescence from living cells.

Popular Abstract in Swedish Den engelska medeltidsdikten Pearl studeras främst mot bakgrund av Pseudo-Dionysius tankar samt den samtida kontemplativa litteraturen (d v s Julian of Norwich, Margery Kempe, Walter Hilton, Richard Rolle och den okände författaren av The Cloud of Unknowing). Det är framförallt med avseende på medeltida teologiska frågor om människans möjlighet och begränsing att förståThis dissertation places Pearl in the context of works by the English fourteenth-century contemplative writers (‘mystics’), as well as of patristic and other theological treatises, focusing on the theme of comprehending and speaking about a transcendent divine dimension. The purpose is to show that Pearl and the works of Julian of Norwich, Margery Kempe, Walter Hilton, Richard Rolle and the author

Artificial neural networks is one of the most commonly used machine learning algorithms in medical applications. However, they are still not used in practice in the clinics partly due to their lack of explanatory capacity. We compare two case-based explanation methods to two trained physicians on analysis of electrocardiogram (ECG) data from patients with a suspected acute coronary syndrome (ACS).

Approaches to determining the factuality of diagnoses and findings in clinical text tend to rely on dictionaries of marker words for uncertainty and negation. Here, a method for semi-automatically expanding a dictionary of marker words using distributional semantics is presented and evaluated. It is shown that ranking candidates for inclusion according to their proximity to cluster centroids of se

A combustion system was developed to burn a low value gas in the VT4400 IGT engine demonstrator. The combustor was designed in an engine configuration consisting of a single LCV combustor operating in combination with six LP combustors.

Little is known about pediatric surgical disease in resource-poor countries. This study documents the surgical care of children in central Haiti and demonstrates the influence of the 2010 earthquake on pediatric surgical delivery. METHODS: We conducted a retrospective review of operations performed at Partners in Health/Zanmi Lasante hospitals in central Haiti. RESULTS: Of 2,057 operations perfor

The aim of the thesis The Court Service in Sweden. Regulation and Development 1684-1989 is to investigate the special church service which was decreed by Swedish law in connection with trials in law courts between 1684 and 1989. The service was initiated by King Karl XI of Sweden in 1684 by a letter to the Bishop of Västerås Diocese. Initially, the service was held only within parts of the Dioces

Mucins are high-molecular-weight glycoproteins and major constituents of the mucus layer which covers the airway surface. We have studied the interactions between bacteria, mucins, and epithelial cells from the human respiratory tract. Nontypeable strains of Haemophilus influenzae were found to bind to purified airway mucins in suspension and on solid phase. Mucins in suspension inhibited the atta

We have previously shown that protein kinase Cepsilon (PKCepsilon) induces neurite outgrowth via its regulatory domain and independently of its kinase activity. This study aimed at identifying mechanisms regulating PKCepsilon-mediated neurite induction. We show an increased association of PKCepsilon to the cytoskeleton during neuronal differentiation. Furthermore, neurite induction by overexpressi

High hypoxia-inducible factor-2 alpha (HIF-2 alpha) protein levels predict poor outcome in neuroblastoma, and hypoxia dedifferentiates cultured neuroblastoma cells toward a neural crest-like phenotype. Here, we identify HIF-2 alpha as a marker of normoxic neural crest-like neuroblastoma tumor-initiating/stem cells (TICs) isolated from patient bone marrows. Knockdown of HIF-2 alpha reduced VEGF exp

A series of analogs with nitro or serinamide substituents at the C-2'-, C-5'-, or C-C-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization. The synthesis of these analogs typically featured a Wittig reaction between a suitably fun

This is the first attempt to budget average current annual carbon (C) and associated greenhouse gas (GHG) exchanges and transfers in a subarctic landscape, the Lake Torneträsk catchment in northern Sweden. This is a heterogeneous area consisting of almost 4000 km2 of mixed heath, birch and pine forest, and mires, lakes and alpine ecosystems. The magnitudes of atmospheric exchange of carbon in the

Here we unravel the structural features of human IgM and IgA that govern their interaction with the human Fc alpha/mu receptor (hFc alpha/mu R). Ligand polymerization status was crucial for the interaction, because hFc alpha/mu R binding did not occur with monomeric Ab of either class. hFc alpha/mu R bound IgM with an affinity in the nanomolar range, whereas the affinity for dimeric IgA (dIgA) was

Aims/hypothesis. We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT). Methods. We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor-1 alpha (HNF-1alpha) gene mutations. Results. BMI and age were si

How much is "anti" in the "anti-globalization" movement? And how much is "pro", and for what? In this paper I will analyze some common features, and divisions between organizations in the so called anti-globalization movement, with focus on the political articulations and different ways of political struggle. How is a common identity and a common adversary of the disparate movements constructed wi