52,138 results match your criteria: "HARVARD UNIVERSITY.[Affiliation]"

Strong, affiliative bonds often function to facilitate social competition through cooperative defence of resources, but the benefits of social bonds may be low when direct competition is less intense or less beneficial. In such cases, one possible outcome is that relationships are weak and undifferentiated. Alternatively, negotiating stable, selectively tolerant relationships may be a strategy to mitigate the costs and risks of sharing space when direct competition is undesirable.

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The HIV-1 Rev-RRE regulatory axis plays a crucial role in viral replication by facilitating the nucleo-cytoplasmic export and expression of viral mRNAs with retained introns. In this study, we investigated the impact of variation in Rev-RRE functional activity on HIV-1 replication kinetics and reactivation from latency. Using a novel HIV-1 clone with an interchangeable Rev cassette, we engineered viruses with different Rev functional activities and demonstrated that higher Rev-RRE activity confers greater viral replication capacity while maintaining a constant level of Nef expression.

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CRISPR-Cas enzymes must recognize a protospacer-adjacent motif (PAM) to edit a genomic site, significantly limiting the range of targetable sequences in a genome. Machine learning-based protein engineering provides a powerful solution to efficiently generate Cas protein variants tailored to recognize specific PAMs. Here, we present Protein2PAM, an evolution-informed deep learning model trained on a dataset of over 45,000 CRISPR-Cas PAMs.

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Enhanced Stability and Sensitivity for CA-125 Detection Under Microfluidic Shear Flow Using Polyethylene Glycol-Coated Biosensor.

ACS Omega

January 2025

Advanced Energy Systems and Microdevices Laboratory, Department of Mechanical and Industrial Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102, United States.

The microfluidic-based point-of-care (POC) diagnostic tool has garnered significant interest in recent years, offering rapid and cost-effective disease detection. There is a growing trend toward integrating microfluidic platforms with biosensors, aligning lab-on-a-chip technologies with POC diagnostic devices. Despite numerous efforts to incorporate biosensors into microfluidic systems, researchers have performed very limited investigations on the stability of biomarker detection when biosensors operate under microfluidic shear flow conditions.

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An Open-Shell Fe Nitrido.

J Am Chem Soc

January 2025

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.

We report the photogeneration and characterization of an open-shell, terminal iron nitrido (L)Fe(N) using a sterically encumbered dipyrrin ligand environment. The Fe-N distance in the solid-state, zero-field Fe Mössbauer spectrum, and computational analysis are consistent with a triplet electronic ground state of the iron nitrido. Notably, the attenuation of Fe-N multiple bond character through occupying π* enables (i) primary C(sp)-H amination, (ii) H cleavage, (iii) aromatic C-C cleavage, and (iv) photocatalytic -atom transfer reactivity.

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Narrative accounts have documented the potential for suffering to degrade a person's well-being by undermining their sense of meaning in life, but few studies have investigated this among nonclinical samples living in non-Western contexts of the Global South. Leveraging data from a set of three-wave longitudinal studies with younger Indonesian (Study 1: Wave 1 [December 2020], Wave 2 [January 2021], Wave 3 [February 2021]; N = 620) and Colombian adults (Study 2: Wave 1 [August/September 2021], Wave 2 [October/November 2021], Wave 3 [February 2022]; N = 2626), the present research used causal mediation methods within a counterfactual framework to examine whether the associations between suffering (Wave 1) and subsequent anxiety symptoms, depression symptoms, and general mental health (Wave 3) are mediated by meaning in life (Wave 2). Mediation analyses in both studies provided some evidence indicating that overall suffering (Wave 1) is indirectly associated with worse subsequent mental well-being on all three outcomes (Wave 3) via lower meaning in life (Wave 2).

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Purpose: There is evidence of the role of dark adaptation (DA) as a functional biomarker in age-related macular degeneration (AMD) where foveal cones are impacted during the initial stages of AMD. In this study we determine the repeatability of smartphone application (MOBILE DA) to evaluate the cone-mediated dark adaptation (DA) in healthy young adults.

Methods: Testing was done by placing a smartphone in front of the subject in a dark room.

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Advancing Mental Health Economics: Insights from the Themed Section.

Value Health

January 2025

Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Center for Health Decision Science, Harvard University, Boston, MA, United States.

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Recent theoretical work has argued that moral psychology can be understood through the lens of "resource rational contractualism." The view posits that the best way of making a decision that affects other people is to get everyone together to negotiate under idealized conditions. The outcome of that negotiation is an arrangement (or "contract") that would lead to mutual benefit.

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The regular workshops held by the Center for Alternatives to Animal Testing (CAAT) on biology-inspired microphysiological systems (MPS) taking place every four years, have become a reliable measure to assess fundamental scientific, industrial and regulatory trends for translational science in the MPS-field from a bird's eye view. The 2023 workshop participants at that time concluded that the technology as used within academia has matured significantly, underlined by the broad use of MPS and the steadily increasing number of high quality research publications - yet, broad industry adoption of MPS has been slow, despite strong interest. Academic research using MPS primarily aims to accurately recapitulate human biology in MPS-based organ models in areas where traditional models have been lacking key elements of human physiology, thereby enabling breakthrough discoveries for life sciences.

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Background: Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations.

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Characterisation of the ocular inflammatory response to AAV reveals divergence by sex and age.

Mol Ther

January 2025

Academic Unit of Ophthalmology, Translational Health Sciences, University of Bristol, Bristol, BS8 1TD, UK; NIHR Biomedical Research Centre of Ophthalmology, Moorfields Eye Hospital, London, EC1V 2PD, UK. Electronic address:

Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes.

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The genus Streptococcus is highly diverse and a core member of the primate oral microbiome. Streptococcus species are grouped into at least eight phylogenetically-supported clades, five of which are found almost exclusively in the oral cavity. We explored the dominant Streptococcus phylogenetic clades in samples from multiple oral sites and from ancient and modern-day humans and non-human primates and found that clade dominance is conserved across human oral sites, with most Streptococcus reads assigned to species falling in the Sanguinis or Mitis clades.

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Purpose: Clonal hematopoiesis (CH) has been associated with a variety of adverse outcomes, most notably hematologic malignancy and ischemic cardiovascular disease. A series of recent studies also suggest that CH may play a role in the outcomes of patients with solid tumors, including breast cancer. Here, we review the clinical and biological data that underlie potential connections between CH, inflammation, and breast cancer, with a focus on the prevalence and impact of clonal hematopoiesis of indeterminate potential in patients with breast cancer.

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Riparian spiders are used in ecotoxicology as sentinels of bioavailable contaminants that are transferred from aquatic to terrestrial habitats via emergent aquatic insects. Spiders in the family Tetragnathidae are particularly of interest because a high proportion of their diet consists of emergent aquatic insects and their contaminant loads reflect the amount transferred through the food web to riparian predators. The transfer of contaminants can be determined through food web tracers such as stable isotopes and polyunsaturated fatty acids; however, it is unclear how contaminants and tracers vary over the course of a year.

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Purpose: Adavosertib is an oral small molecular inhibitor of Wee1. The Adult Brain Tumor Consortium performed a phase I study of adavosertib, radiation (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) as well as a surgical window of opportunity study in recurrent GBM.

Patients And Methods: The maximum tolerated dose (MTD) of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in 2 separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ.

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Children are often instructed to "use their words" to communicate their emotions, which requires them to quickly access words that best describe their feelings. Adults vary in their ability to bring both nonemotion and emotion words to mind (two capacities called and ). However, no studies have examined how emotion fluency emerges across development, despite the fact that mastering emotion language is an important developmental task.

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A case for broadening our view of mechanism in developmental biology.

Development

January 2025

Department of Organismic and Evolutionary Biology, Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138, USA.

Developmental biologists can perform studies that describe a phenomenon (descriptive work) and/or explain how the phenomenon works (mechanistic work). There is a prevalent perception that molecular/genetic explanations achieved via perturbations of gene function are the primary means of advancing mechanistic knowledge. We believe this to be a limited perspective, one that does not effectively represent the breadth of work in our field.

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Cementless fixation in total joint arthroplasty: Factors impacting osseointegration.

J Clin Orthop Trauma

February 2025

Orthopedic Surgery, Brigham & Women's Hospital, Harvard University, Boston, MA, USA.

•The success of cementless fixation in TJA depends on a multitude of factors including biological, mechanical, implant, surgical, and material properties.•Biologic fixation has become the primary mode of fixation for the majority of primary total hip arthroplasty (THA) surgeries done today in the United States (US) due to its low complication rate and superior longevity compared to cemented fixation.•Cementless fixation has yet to gain wider acceptance in total knee arthroplasty (TKA) and hip hemiarthroplasty due to several factors including host bone quality, implant design, and surgical technique.

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Sulfur Vacancies Limit the Open-Circuit Voltage of SbS Solar Cells.

ACS Energy Lett

January 2025

Department of Materials, Imperial College London, Exhibition Road, London SW7 2AZ, U.K.

Antimony sulfide (SbS) is a promising candidate as an absorber layer for single-junction solar cells and the top subcell in tandem solar cells. However, the power conversion efficiency of SbS-based solar cells has remained stagnant over the past decade, largely due to trap-assisted nonradiative recombination. Here we assess the trap-limited conversion efficiency of SbS by investigating nonradiative carrier capture rates for intrinsic point defects using first-principles calculations and Sah-Shockley statistics.

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Many human diseases result from a complex interplay of behavioral, clinical, and molecular factors. Integrating low-dimensional behavioral and clinical features with high-dimensional molecular profiles can significantly improve disease outcome prediction and diagnosis. However, while some biomarkers are crucial, many lack informative value.

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Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo.

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