The form of the empirical law relating acquired drive strength to UCS intensity and number of CS-UCS pairings was investigated in two experiments using 120 and 30 male albino rats, respectively. Strength of UCS was varied at a broad range of intensities. Controls were introduced to prevent the intrusion of competing crouching responses (R1) on the measurement of response strength (R2). Acquired drive strength was found to be curvilinearly related to UCS intensity and number of CS-UCS pairings during conditioning. The relationship was monotonic and negatively accelerated. Habit strength, or sHr, was found to be jointly determined by UCS intensity (D) and number of CS-UCS pairings during aversive conditioning. These results were contrasted with findings for the instrumental appetitive learning case of Hull's system, where it has been shown that sHr and D are independent and interact in a multiplicative fashion in their effect on performance. An historical review of acquired drive experiments was also presented.
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http://dx.doi.org/10.1080/00221309.1977.9920798 | DOI Listing |
J Med Chem
January 2025
Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.
Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.
View Article and Find Full Text PDFPf bacteriophages, lysogenic viruses that infect are implicated in the pathogenesis of chronic infections; phage-infected (Pf+) strains are known to predominate in people with cystic fibrosis (pwCF) who are older and have more severe disease. However, the transmission patterns of Pf underlying the progressive dominance of Pf+ strains are unclear. In particular, it is unknown whether phage transmission commonly occurs horizontally between bacteria within the airway via viral particles or if Pf+ bacteria are mostly acquired via new infections.
View Article and Find Full Text PDFBackground: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g.
View Article and Find Full Text PDFGenome Biol Evol
January 2025
Department of Biological Sciences, University of Alberta, BS CW405 Edmonton, AB, T6G 2R3, Canada.
Fungi are well known for their ability to both produce and catabolize complex carbohydrates to acquire carbon, often in the most extreme of environments. Glucuronoxylomannan (GXM)-based gel matrices are widely produced by fungi in nature and though they are of key interest in medicine and pharmaceuticals, their biodegradation is poorly understood. Though some organisms, including other fungi, are adapted to life in and on GXM-like matrices in nature, they are almost entirely unstudied, and it is unknown if they are involved in matrix degradation.
View Article and Find Full Text PDFOtolaryngol Head Neck Surg
January 2025
Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.
Objective: Cystic fibrosis (CF) is a clinical entity defined by aberrant chloride (Cl) ion transport causing downstream effects on mucociliary clearance (MCC) in sinonasal epithelia. Inducible deficiencies in transepithelial Cl transport via CF transmembrane conductance regulator (CFTR) has been theorized to be a driving process in recalcitrant chronic rhinosinusitis (CRS) in patients without CF. We have previously identified that brief exposures to bacterial lipopolysaccharide (LPS) in mammalian cells induces an acquired dysfunction of CFTR in vitro and in vivo.
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