Kinases are important therapeutic targets in oncology due to their frequent deregulation in cancer. Typical ATP-competitive kinase inhibitors, however, also inhibit off-target kinases that could lead to drug toxicity. Allosteric inhibitors represent an alternative approach to achieve greater kinase selectivity, although examples of such compounds are few. Here, we elucidate the mechanism of act...

Two ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates eIF2α. We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization,...

Background We evaluated the utility of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) in nonneutropenic patients. Methods A total of 183 patients were included in the final analysis. Bronchoscopies and the detection of GM in BALF were all performed on them. Results Ten cases of IPA were diagnosed. ROC data demonstrated t...

A 12-year retrospective analysis was done to identify and evaluate in detail cases of invasive pulmonary aspergillosis (IPA) caused by Aspergillus terreus. We identified 13 A. terreus infections among 133 total cases of confirmed invasive aspergillosis; 11 were IPA and 2 were primary peritoneal infections. Of the 11 patients with IPA, 7 developed neutropenia during hospitalization, and the rema...

The Intelligent Parking Assistant (IPA) system helps the user chose, find and pay for parking. IPA automatically fetches parking lot information from a relevant service, automatically assesses if the vehicle is stopped, evaluates if stopped inside a payed parking lot, and automatically initiates payment for the parking. IPA is published via the MOBiNET platform: A European-wide ITS platform off...

We examine motivations for, and costs/benefits of, participation in three interviews across a one-year period among women recently exposed to intimate partner abuse (IPA). Recruited from publicly accessible police reports, women were not informed that the study focused on IPA in recruiting materials or when they scheduled the first interview. Women's ratings on the Response to Research Particip...

The main advantage of tetramethyl ammnium hydroxide (TMAH)-based solutions is their full compatibility with IC technologies. In this work a new etching system of TMAH/IPA (isopropyl alcohol) is suggested. The influence of the addition of IPA to TMAH solutions on their etching characteristics is presented. The etch rates of (100) oriented silicon crystal planes decreases linearly with decreasing...

Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in immunosuppressed patients. Timely diagnosis of IPA improves survival but is difficult to make. We examined the analytical and clinical validity of galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in diagnosing IPA in a mixed population by retrospectively reviewing records of 251 consecutive at-risk patients fo...

BACKGROUND AND PURPOSE The aim of this study was to determine the face and criterion validity, stability reliability, and internal consistency of the Persian version of the Impact on Participation and Autonomy (IPA-p) scale among Iranian people with multiple sclerosis (MS). METHODS Trained experts interviewed 364 MS patients and their relatives to assess the criterion validity, stability reli...

BACKGROUND Ticagrelor is the first reversibly binding oral P2Y(12) receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. METHODS AND RESULTS In a multicenter, randomized, double-blind study,...