Concepts contain rich structures that support flexible semantic cognition. These structures can be characterized by patterns of feature covariation: Certain features tend to cluster in the same items (e.g.
View Article and Find Full Text PDFMedical students who underperform or find they are not a "good fit" for medicine have limited options. A terminal master's degree represents an exit alternative that recognizes students' completed coursework and acknowledges their commitment to the medical sciences. Although medical educators have called for the creation of such programs, termed "compassionate off-ramps," the prevalence of degree offerings in US programs is unknown.
View Article and Find Full Text PDFConceptual combination is the act of building complex concepts from simpler ones. Although research has examined how inferences about compound objects (e.g.
View Article and Find Full Text PDFCOVID-19, caused by SARS-CoV-2, is a systemic illness due to its multiorgan effects in patients. The disease has a detrimental impact on respiratory and cardiovascular systems. One early symptom of infection is anosmia or lack of smell; this implicates the involvement of the olfactory bulb in COVID-19 disease and provides a route into the central nervous system.
View Article and Find Full Text PDFThe cognitive and neural structure of conceptual knowledge affects how concepts combine in language and thought. Examining the principles by which individual concepts (e.g.
View Article and Find Full Text PDFWhat role does the hippocampus play in semantic memory? In a recent paper, Cutler et al. use a vector space model of semantics to characterize semantic search deficits in hippocampal amnesia. We relate their findings to properties of the hippocampal neural code and to controversies regarding hippocampal contributions to cognition.
View Article and Find Full Text PDFThe same concept can mean different things or be instantiated in different forms, depending on context, suggesting a degree of flexibility within the conceptual system. We propose that a feature-based network model can be used to capture and predict this flexibility. We modeled individual concepts (e.
View Article and Find Full Text PDFCytotoxic function and cytokine profile of NK cells are compromised in patients with systemic lupus erythematosus (SLE). CD3ζ, an important molecule for NK cell activation, is downregulated in SLE T cells and contributes to their altered function. However, little is known about the role of CD3ζ in SLE NK cells.
View Article and Find Full Text PDFObject concepts refer to unique clusters of properties that can be selectively activated or inhibited depending on what information is currently relevant. This conceptual "stretching" enables limitless new meanings to be generated, and figurative language provides a useful framework in which to study this conceptual flexibility. Here we probe the cognitive and neural mechanisms underlying the comprehension of novel metaphors as a means of understanding the conceptual flexibility inherent to language processing more generally.
View Article and Find Full Text PDFBackground: Immunotherapy has changed the therapeutic landscape in oncology. Advanced uterine leiomyosarcoma (ULMS) remains an incurable disease in most cases, and despite new drug approvals, improvements in overall survival have been modest at best. The goal of this study was to evaluate programmed-death 1 (PD-1) inhibition with nivolumab in this patient population.
View Article and Find Full Text PDFCyclic peptides (CPs) are promising modulators of protein-protein interactions (PPIs), but their application remains challenging. It is currently difficult to predict the structures and bioavailability of CPs. The ability to design CPs using computer modeling would greatly facilitate the development of CPs as potent PPI modulators for fundamental studies and as potential therapeutics.
View Article and Find Full Text PDFInformation in the human visual system is encoded in the activity of distributed populations of neurons, which in turn is reflected in functional magnetic resonance imaging (fMRI) data. Over the last fifteen years, activity patterns underlying a variety of perceptual features and objects have been decoded from the brains of participants in fMRI scans. Through a novel multi-study meta-analysis, we have analyzed and modeled relations between decoding strength in the visual ventral stream, and stimulus and methodological variables that differ across studies.
View Article and Find Full Text PDFUnderstanding events often requires recognizing unique stimuli as alternative, mutually exclusive states of the same persisting object. Using fMRI, we examined the neural mechanisms underlying the representation of object states and object-state changes. We found that subjective ratings of visual dissimilarity between a depicted object and an unseen alternative state of that object predicted the corresponding multivoxel pattern dissimilarity in early visual cortex during an imagery task, while late visual cortex patterns tracked dissimilarity among distinct objects.
View Article and Find Full Text PDFPurpose: Metastatic GI stromal tumor (GIST) is a life-threatening disease with no therapy of proven efficacy after failure of imatinib and sunitinib. Regorafenib is a structurally unique inhibitor of multiple cancer-associated kinases, including KIT and platelet-derived growth factor receptor (PDGFR), with broad-spectrum anticancer activity in preclinical and early-phase trials. Because KIT and PDGFR-α remain drivers of GIST after resistance to imatinib and sunitinib, we performed a multicenter single-stage phase II trial of regorafenib in patients with advanced GIST after failure of at least imatinib and sunitinib.
View Article and Find Full Text PDFWe recently reported that HIV-1 resistant to 3'-azido-3'-deoxythymidine (AZT) is not cross-resistant to 3'-azido-2',3'-dideoxypurines. This finding suggested that the nucleoside base is a major determinant of HIV-1 resistance to nucleoside analogs. To further explore this hypothesis, we conducted in vitro selection experiments by serial passage of HIV-1(LAI) in MT-2 cells in increasing concentrations of 3'-azido-2',3'-dideoxyguanosine (3'-azido-ddG), 3'-azido-2',3'-dideoxycytidine (3'-azido-ddC), or 3'-azido-2',3'-dideoxyadenosine (3'-azido-ddA).
View Article and Find Full Text PDFBased on the promising drug resistance profile and potent anti-HIV activity of beta-d-3'-azido-2',3'-dideoxyguanosine, a series of purine modified nucleosides were synthesized by a chemical transglycosylation reaction and evaluated for their antiviral activity, cytotoxicity, and intracellular metabolism. Among the synthesized compounds, several show potent and selective anti-HIV activity in primary lymphocytes.
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