Generalized Fuzzy Password-Authenticated Key Exchange from Error Correcting Codes

Fuzzy Password-Authenticated Key Exchange (fuzzy PAKE) allows cryptographic keys to be generated from authentication data that is both fuzzy and of low entropy. The strong protection against offline attacks offered by fuzzy PAKE opens an interesting avenue towards secure biometric authentication, typo-tolerant password authentication, and automated IoT device pairing. Previous constructions of fuzzy PAKE are either based on Error Correcting Codes (ECC) or generic multi-party computation techniques such as Garbled Circuits. While ECC-based constructions are significantly more efficient, they rely on multiple special properties of error correcting codes such as maximum distance separability and smoothness. We contribute to the line of research on fuzzy PAKE in two ways. First, we identify a subtle but devastating gap in the security analysis of the currently most efficient fuzzy PAKE construction (Dupont et al., Eurocrypt 2018), allowing a man-in-the-middle attacker to test individual password characters. Second, we provide a new fuzzy PAKE scheme based on ECC and PAKE that provides a built-in protection against individual password character guesses and requires fewer, more standard properties of the underlying ECC. Additionally, our construction offers better error correction capabilities than previous ECC-based fuzzy PAKEs

Berries and leukemia: a systematic review of experimental studies and the in vitro effect of ellagic acid on chronic myeloid leukemia cells / Frutas vermelhas e leucemia: uma revisão sistemática de estudos experimentais e o efeito in vitro do ácido elágico sobre células de leucemia mieloide crônica

Diet is directly involved in cancer etiology, influencing positively or negatively. The aim of this study was to conduct a systematic review on the effect of berries on leukemia, identifying the main bioactive compounds involved in biochemical and molecular mechanisms through which they act and also to test the in vitro effect of ellagic acid, one of the phytochemicals found in berries, on leukemia cells. The work was subdivided into two parts: the first consisted of analysis of abstracts in Pubmed / Medline databases using MeSH (Medical Subject Headings) terms, synonyms, related and free terms, such as: leukemia, berries, anthocyanins, ellagic acid and flavonoids resulting in 274 articles. After abstract analysis, based on the eligibility criteria, this number was reduced to 21 articles. The second part was the in vitro investigation of the effect of ellagic acid by the MTT reduction in chronic myeloid leukemia cell lines (CML) resistant or not to chemotherapeutic agents. In vitro, in vivo and ex vivo studies associated the bioactive compounds present in berries with anticancer effect, acting mainly by induction of metabolic enzymes, modulation of gene expression and cell proliferation, chemotherapic resistance, free radical scavenging and induction of apoptosis. The present work also highlights the induction of collateral sensitivity by ellagic acid, since this compound was able to preferentially act on chemotherapeutic resistant cells. However, it is emphasized that animal models and clinical trials are for establishing the main mechanisms of action and possible dosages of berries intake daily or by dietary supplementation that could contribute to leukemia's treatment. 

mTORC1-mediated translational elongation limits intestinal tumour initiation and growth.

Inactivation of APC is a strongly predisposing event in the development of colorectal cancer, prompting the search for vulnerabilities specific to cells that have lost APC function. Signalling through the mTOR pathway is known to be required for epithelial cell proliferation and tumour growth, and the current paradigm suggests that a critical function of mTOR activity is to upregulate translational initiation through phosphorylation of 4EBP1 (refs 6, 7). This model predicts that the mTOR inhibitor rapamycin, which does not efficiently inhibit 4EBP1 (ref. 8), would be ineffective in limiting cancer progression in APC-deficient lesions. Here we show in mice that mTOR complex 1 (mTORC1) activity is absolutely required for the proliferation of Apc-deficient (but not wild-type) enterocytes, revealing an unexpected opportunity for therapeutic intervention. Although APC-deficient cells show the expected increases in protein synthesis, our study reveals that it is translation elongation, and not initiation, which is the rate-limiting component. Mechanistically, mTORC1-mediated inhibition of eEF2 kinase is required for the proliferation of APC-deficient cells. Importantly, treatment of established APC-deficient adenomas with rapamycin (which can target eEF2 through the mTORC1-S6K-eEF2K axis) causes tumour cells to undergo growth arrest and differentiation. Taken together, our data suggest that inhibition of translation elongation using existing, clinically approved drugs, such as the rapalogs, would provide clear therapeutic benefit for patients at high risk of developing colorectal cancer

Protection order and child endangerment in the context of a child protection service in Saxony

Die Masterarbeit beschäftigt sich mit der verantwortungsvollen Aufgabe der Erfüllung des Schutzauftrages bei Kindeswohlgefährdung, welche insbesondere die staatlichen sowie freien Träger zu erfüllen haben. Am Beispiel des Leipziger Allgemeinen Sozialen Dienstes wird die Bewältigung des Aufgabenspektrums hinsichtlich der zunehmend komplexen Problemlagen in den Familien sowie den beständigen in- und externen komplexen Erwartungshaltungen, untersucht. In Anlehnung an die grundlegende Darstellung der geltenden Rahmenbedingungen sowie strukturellen Voraussetzungen, wird sich explizit der Frage gewidmet, was für die Kooperation zwischen Allgemeinem Sozialen Dienst und den Netzwerkpartnern notwendig ist, um ein Gelingen der Hilfeleistung hinsichtlich des Kinderschutzes gewährleisten zu können

Management of malignancy-induced, life-threatening hypoxemic respiratory failure using a self-expanding Y stent

We present the case of a young woman transferred to our center with acute hypoxic respiratory failure due to an obstructing subcarinal mass. We review the management and rationale of this respiratory failure at different stages of her hospital course. We describe the approach and rationale in both the intensive care unit as well as the bronchoscopy suite. Finally, we discuss how the use of a novel hybrid Y stent effectively palliated her symptoms

Validation and Application of an HPLC-UV Method for Routine Therapeutic Drug Monitoring of Cefiderocol

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy

Activation of sickle red blood cell adhesion via integrin-associated protein/CD47–induced signal transduction

Peripheral human red blood cells (RBCs) are not generally known to become activated and adhesive in response to cell signaling. We show, however, that soluble thrombospondin via integrin-associated protein (IAP; CD47) increases the adhesiveness of sickle RBCs (SS RBCs) by activating signal transduction in the SS RBC. This stimulated adhesion requires occupancy of IAP and shear stress and is mediated by the activation of large G proteins and tyrosine kinases. Reticulocyte-enriched RBCs derived from sickle-cell disease (SCD) patients are most responsive to IAP-induced activation. These studies therefore establish peripheral SS RBCs as signaling cells that respond to a novel synergy between IAP-induced signal transduction and shear stress, suggesting new therapeutic targets in SCD

The Identification of Indacaterol as an Ultra-Long-Acting Inhaled Beta-2-Adrenoceptor Agonist

Following a lipophilicity-based hypothesis, a series of 2-aminoindan and 8-hydroxyquinolinone derived 2-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultra-long-acting bronchodilators. Determination of their activities at the human 2-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference 2-adrenoceptor agonists. Further assessment with an in vitro super-fused electrically-stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses which could be rationalised by considering the lipophilicity, potency and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung which led to the compound being selected as a development candidate