Continuous oral chloroquine as a novel route for Plasmodium prophylaxis and cure in experimental murine models

<p>Abstract</p> <p>Background</p> <p>Chloroquine (CQ) is utilized as both cure and prophylaxis to <it>Plasmodium </it>infection. In animal studies, CQ administration to experimental animals is via intraperitoneal (i.p.) injection of a single dose that varies from daily to several times per week. Such daily administration can be distressing to the animals and provoke aggressive behaviors that may affect the immune responses of the animal and interfere with data read-outs.</p> <p>Findings</p> <p>We describe a novel, viable and efficacious prophylactic and curative administration route whereby chloroquine is continuously supplied in the drinking water to experimental animals. The prophylactic effect is robust and the curative effect against patent blood stage infection comparable to the traditional route of i.p. administration. Continuous drinking water administration may decrease animal stress responses and thus improve the reliability of experimental data.</p

Climate Change and Global Food Systems: Potential Impacts on Food Security and Undernutrition.

Great progress has been made in addressing global undernutrition over the past several decades, in part because of large increases in food production from agricultural expansion and intensification. Food systems, however, face continued increases in demand and growing environmental pressures. Most prominently, human-caused climate change will influence the quality and quantity of food we produce and our ability to distribute it equitably. Our capacity to ensure food security and nutritional adequacy in the face of rapidly changing biophysical conditions will be a major determinant of the next century's global burden of disease. In this article, we review the main pathways by which climate change may affect our food production systems-agriculture, fisheries, and livestock-as well as the socioeconomic forces that may influence equitable distribution

Time-walk and jitter correction in SNSPDs at high count rates

Superconducting nanowire single-photon detectors (SNSPDs) are a leading detector type for time correlated single photon counting, especially in the near-infrared. When operated at high count rates, SNSPDs exhibit increased timing jitter caused by internal device properties and features of the RF amplification chain. Variations in RF pulse height and shape lead to variations in the latency of timing measurements. To compensate for this, we demonstrate a calibration method that correlates delays in detection events with the time elapsed between pulses. The increase in jitter at high rates can be largely canceled in software by applying corrections derived from the calibration process. We demonstrate our method with a single-pixel tungsten silicide SNSPD and show it decreases high count rate jitter. The technique is especially effective at removing a long tail that appears in the instrument response function at high count rates. At a count rate of 11.4 MCounts/s we reduce the full width at one percent maximum level (FW1%M) by 45%. The method therefore enables certain quantum communication protocols that are rate-limited by the (FW1%M) metric to operate almost twice as fast. \c{opyright} 2022. All rights reserved.Comment: 5 pages, 3 figure

Experimental high-dimensional entanglement certification and quantum steering with time-energy measurements

High-dimensional entanglement provides unique ways of transcending the limitations of current approaches in quantum information processing, quantum communications based on qubits. The generation of time-frequency qudit states offer significantly increased quantum capacities while keeping the number of photons constant, but pose significant challenges regarding the possible measurements for certification of entanglement. Here, we develop a new scheme and experimentally demonstrate the certification of 24-dimensional entanglement and a 9-dimensional quantum steering. We then subject our photon-pairs to dispersion conditions equivalent to the transmission through 600-km of fiber and still certify 21-dimensional entanglement. Furthermore, we use a steering inequality to prove 7-dimensional entanglement in a semi-device independent manner, proving that large chromatic dispersion is not an obstacle in distributing and certifying high-dimensional entanglement and quantum steering. Our highly scalable scheme is based on commercial telecommunication optical fiber components and recently developed low-jitter high-efficiency single-photon detectors, thus opening new pathways towards advanced large-scale quantum information processing and high-performance, noise-tolerant quantum communications with time-energy measurementsComment: 30 pages, 4 figure

A review of the anti-tumor potential of current therapeutics targeting the mitochondrial protease ClpP in H3K27-altered, diffuse midline glioma

Diffuse midline gliomas (DMGs) are devastating pediatric brain tumors recognized as the leading cause of cancer-related death in children. DMGs are high-grade gliomas (HGGs) diagnosed along the brain's midline. Euchromatin is the hallmark feature of DMG, caused by global hypomethylation of H3K27 either through point mutations in histone H3 genes (H3K27M), or by overexpression of the enhancer of zeste homolog inhibitory protein (EZHIP). In a clinical trial for adults with progressive HGGs, a 22-year-old patient with a thalamic H3K27-altered DMG, showed remarkable clinical and radiological responses to dordaviprone (ONC201). This response in a H3K27-altered HGG patient, coupled with the lack of response of patients harboring wildtype-H3 tumors, has increased the clinical interest in dordaviprone for the treatment of DMG. Additional reports of clinical benefit have emerged, but research defining mechanisms of action (MOA) fall behind dordaviprone's clinical use, with biomarkers of response unresolved. Here, we summarize dordaviprone's safety, interrogate its preclinical MOA- identifying the mitochondrial protease 'ClpP' as a biomarker of response, and discuss other ClpP-agonists, expanding the arsenal of potential weapons in the fight against DMG. Finally, we discuss combination strategies including ClpP-agonists, and its immunomodulatory effects suggestive of a role for the tumor microenvironment in DMG patients' response

Evolution and implementation of radiographic response criteria in neuro-oncology

Radiographic response assessment in neuro-oncology is critical in clinical practice and trials. Conventional criteria, such as the MacDonald and response assessment in neuro-oncology (RANO) criteria, rely on bidimensional (2D) measurements of a single tumor cross-section. Although RANO criteria are established for response assessment in clinical trials, there is a critical need to address the complexity of brain tumor treatment response with multiple new approaches being proposed. These include volumetric analysis of tumor compartments, structured MRI reporting systems like the Brain Tumor Reporting and Data System, and standardized approaches to advanced imaging techniques to distinguish tumor response from treatment effects. In this review, we discuss the strengths and limitations of different neuro-oncology response criteria and summarize current research findings on the role of novel response methods in neuro-oncology clinical trials and practice