PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons.

Type I MET inhibitors cooperate with PD-1 blockade to promote rejection of hepatocellular carcinoma.

Blockade of the immune checkpoints programmed death-1 (PD-1) and cytotoxic lymphocyte antigen 4 has improved outcomes for patients with hepatocellular carcinoma (HCC), yet most still fail to achieve objective clinical benefit. MET plays key roles in both HCC tumorigenesis and immunosuppressive conditioning; however, inhibition of MET causes upregulation of PD-ligand 1 (PD-L1) suggesting the use of these inhibitors in the context of PD-1 blockade. We sought to investigate across the Hepa1-6, HCA-1 and diethylnitrosamine (DEN) models of HCC whether the combination of more specific type I versus more pleiotropic type II MET inhibitors would confer superior outcomes in combination with PD-1 blockade.

ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.

Ataxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy.

Representations and consequences of race in AI systems.

Race is directly or indirectly incorporated into many AI systems. These systems, which automate typically human tasks, are used across various domains such as predictive policing, disease detection, government resource allocation, and loan approvals. However, these tools have been criticized for handling race insensitively or inaccurately.

School choice increases racial segregation even when parents do not care about race.

This research examines how school choice impacts school segregation. Specifically, this work demonstrates that even if parents do not take the racial demographics of schools into account, preference differences between Black and White parents for other school attributes can still result in segregation. These preference differences stem from motivational differences in pursuit of social status.

Targeted Inhibition of DNA-PKcs, ATM, ATR, PARP, and Rad51 Modulate Response to X Rays and Protons.

Small molecule inhibitors are currently in preclinical and clinical development for the treatment of selected cancers, particularly those with existing genetic alterations in DNA repair and DNA damage response (DDR) pathways. Keen interest has also been expressed in combining such agents with other targeted antitumor strategies such as radiotherapy. Radiotherapy exerts its cytotoxic effects primarily through DNA damage-induced cell death; therefore, inhibiting DNA repair and the DDR should lead to additive and/or synergistic radiosensitizing effects.

An empirical model of proton RBE based on the linear correlation between x-ray and proton radiosensitivity.

Background: Proton relative biological effectiveness (RBE) is known to depend on physical factors of the proton beam, such as its linear energy transfer (LET), as well as on cell-line specific biological factors, such as their ability to repair DNA damage. However, in a clinical setting, proton RBE is still considered to have a fixed value of 1.1 despite the existence of several empirical models that can predict proton RBE based on how a cell's survival curve (linear-quadratic model [LQM]) parameters α and β vary with the LET of the proton beam.

Cell lines of the same anatomic site and histologic type show large variability in intrinsic radiosensitivity and relative biological effectiveness to protons and carbon ions.

Purpose: To show that intrinsic radiosensitivity varies greatly for protons and carbon (C) ions in addition to photons, and that DNA repair capacity remains important in governing this variability.

Methods: We measured or obtained from the literature clonogenic survival data for a number of human cancer cell lines exposed to photons, protons (9.9 keV/μm), and C-ions (13.

A Novel Resistance Pathway for Calcineurin Inhibitors in the Human-Pathogenic Mucorales Mucor circinelloides.

Mucormycosis is an emerging lethal fungal infection in immunocompromised patients. is a causal agent of mucormycosis and serves as a model system to understand genetics in Mucorales. Calcineurin is a conserved virulence factor in many pathogenic fungi, and calcineurin inhibition or deletion of the calcineurin regulatory subunit (CnbR) in results in a shift from hyphal to yeast growth.

Body camera footage leads to lower judgments of intent than dash camera footage.

Police departments use body-worn cameras (body cams) and dashboard cameras (dash cams) to monitor the activity of police officers in the field. Video from these cameras informs review of police conduct in disputed circumstances, often with the goal of determining an officer's intent. Eight experiments ( = 2,119) reveal that body cam video of an incident results in lower observer judgments of intentionality than dash cam video of the same incident, an effect documented with both scripted videos and real police videos.