Yale University

About: Yale University is a education organization based out in New Haven, Connecticut, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 89824 authors who have published 220665 publications receiving 12834776 citations. The organization is also known as: Yale & Collegiate School.

Head and neck squamous cell carcinoma

Abstract: Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour–node–metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies. Head and neck squamous cell carcinomas (HNSCCs) originate from the mucosal epithelium in the oral cavity, pharynx and larynx and are commonly associated with viral infection and tobacco use. This Primer provides an overview of the epidemiology, pathogenesis and treatment of HNSCCs of different aetiologies and the effects of the cancer and its treatment on patient quality of life.

The size of the proton

Abstract: Considering that the proton is a basic subatomic component of all ordinary matter — as well as being ubiquitous in its solo role as the hydrogen ion H+ — there are some surprising gaps in our knowledge of its structure and behaviour. A collaborative project to determine the root-mean-square charge radius of the proton to better than the 1% accuracy of the current 'best' value suggests that those knowledge gaps may be greater than was thought. The new determination comes from a technically challenging spectroscopic experiment — the measurement of the Lamb shift (the energy difference between a specific pair of energy states) in 'muonic hydrogen', an exotic atom in which the electron is replaced by its heavier twin, the muon. The result is unexpected: a charge radius about 4% smaller than the previous value. The discrepancy remains unexplained. Possible implications are that the value of the most accurately determined fundamental constant, the Rydberg constant, will need to be revised — or that the validity of quantum electrodynamics theory is called into question. Here, a technically challenging spectroscopic experiment is described: the measurement of the muonic Lamb shift. The results lead to a new determination of the charge radius of the proton. The new value is 5.0 standard deviations smaller than the previous world average, a large discrepancy that remains unexplained. Possible implications of the new finding are that the value of the Rydberg constant will need to be revised, or that the validity of quantum electrodynamics theory is called into question. The proton is the primary building block of the visible Universe, but many of its properties—such as its charge radius and its anomalous magnetic moment—are not well understood. The root-mean-square charge radius, rp, has been determined with an accuracy of 2 per cent (at best) by electron–proton scattering experiments1,2. The present most accurate value of rp (with an uncertainty of 1 per cent) is given by the CODATA compilation of physical constants3. This value is based mainly on precision spectroscopy of atomic hydrogen4,5,6,7 and calculations of bound-state quantum electrodynamics (QED; refs 8, 9). The accuracy of rp as deduced from electron–proton scattering limits the testing of bound-state QED in atomic hydrogen as well as the determination of the Rydberg constant (currently the most accurately measured fundamental physical constant3). An attractive means to improve the accuracy in the measurement of rp is provided by muonic hydrogen (a proton orbited by a negative muon); its much smaller Bohr radius compared to ordinary atomic hydrogen causes enhancement of effects related to the finite size of the proton. In particular, the Lamb shift10 (the energy difference between the 2S1/2 and 2P1/2 states) is affected by as much as 2 per cent. Here we use pulsed laser spectroscopy to measure a muonic Lamb shift of 49,881.88(76) GHz. On the basis of present calculations11,12,13,14,15 of fine and hyperfine splittings and QED terms, we find rp = 0.84184(67) fm, which differs by 5.0 standard deviations from the CODATA value3 of 0.8768(69) fm. Our result implies that either the Rydberg constant has to be shifted by −110 kHz/c (4.9 standard deviations), or the calculations of the QED effects in atomic hydrogen or muonic hydrogen atoms are insufficient.

The renaissance of black phosphorus

Abstract: One hundred years after its first successful synthesis in the bulk form in 1914, black phosphorus (black P) was recently rediscovered from the perspective of a 2D layered material, attracting tremendous interest from condensed matter physicists, chemists, semiconductor device engineers, and material scientists. Similar to graphite and transition metal dichalcogenides (TMDs), black P has a layered structure but with a unique puckered single-layer geometry. Because the direct electronic band gap of thin film black P can be varied from 0.3 eV to around 2 eV, depending on its film thickness, and because of its high carrier mobility and anisotropic in-plane properties, black P is promising for novel applications in nanoelectronics and nanophotonics different from graphene and TMDs. Black P as a nanomaterial has already attracted much attention from researchers within the past year. Here, we offer our opinions on this emerging material with the goal of motivating and inspiring fellow researchers in the 2D materials community and the broad readership of PNAS to discuss and contribute to this exciting new field. We also give our perspectives on future 2D and thin film black P research directions, aiming to assist researchers coming from a variety of disciplines who are desirous of working in this exciting research field.

Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells.

Abstract: Vascular endothelial growth factor (VEGF) is a regulator of vasculogenesis and angiogenesis. To investigate the role of nitric oxide (NO) in VEGF-induced proliferation and in vitro angiogenesis, human umbilical vein endothelial cells (HUVEC) were used. VEGF stimulated the growth of HUVEC in an NO-dependent manner. In addition, VEGF promoted the NO-dependent formation of network-like structures in HUVEC cultured in three dimensional (3D) collagen gels. Exposure of cells to VEGF led to a concentration-dependent increase in cGMP levels, an indicator of NO production, that was inhibited by nitro-L-arginine methyl ester. VEGF-stimulated NO production required activation of tyrosine kinases and increases in intracellular calcium, since tyrosine kinase inhibitors and calcium chelators attenuated VEGF-induced NO release. Moreover, two chemically distinct phosphoinositide 3 kinase (PI-3K) inhibitors attenuated NO release after VEGF stimulation. In addition, HUVEC incubated with VEGF for 24 h showed an increase in the amount of endothelial NO synthase (eNOS) protein and the release of NO. In summary, both short- and long-term exposure of human EC to VEGF stimulates the release of biologically active NO. While long-term exposure increases eNOS protein levels, short-term stimulation with VEGF promotes NO release through mechanisms involving tyrosine and PI-3K kinases, suggesting that NO mediates aspects of VEGF signaling required for EC proliferation and organization in vitro.