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Hardcover, Kindle, Audiobook – March 3, 2020

Arden helped usher computers into widespread use and played a key role in establishing Princeton's Department of Computer Science.

Early Music Princeton presents a melange of Italian and English masterpieces. The EMP Singers will present pieces representing the “Cult of Melancholy”- mournful pieces by Dowland, Tallis, and Campion that celebrate the beauty and artistry of romantic despair. The EMP Treble quintet will be performing pieces by Strozzi, Monteverdi and Morley: love songs of passion and torment! To complete the program, the EMP Chamber Players and Viol Consort will present spirited Italian works by Frescobaldi and Corelli alongside the rich textures of English composers Tomkins and Coperario.

A working group analyzing Nahuatl-language documents of the sixteenth to nineteenth centuries with a concentration on deciphering paleography and considering issues of translation. The workshop will commence with Mesoamerican Manuscripts held in the special collections of the Princeton University Library in support of the Translating Mesoamerica project that will provide increased accessibility and analysis of these archival treasures.

A UN agency verified victims from a six-month period and said it found international law violations.

One man tells BBC London not enough is being done to keep prisoners released early off the streets.

The best early Black Friday MacBook deals include all-time low prices on the latest MacBook Air models.

A tech recruiting firm left a database unsecured that exposed emails, passport numbers and partial SSNs of job seekers, a security researcher says.

The “Reading Peaceniks” The authors of this article are a group of researchers and practitioners who are looking to end the divisiveness of the “reading wars” — and help children learn to read and write with competence and pleasure. See the list of contributing editors as well as the 25 nationally recognized colleagues who support this effort.

Joris J. Benschop
Jul 1, 2007; 6:1198-1214
Research

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

Visual Abstract

Juntuo Zhou
Nov 30, 2020; 0:RA120.002384v1-mcp.RA120.002384
Research

The glucagon receptor (GCGR) activated by the peptide hormone glucagon is a seven-transmembrane G protein–coupled receptor (GPCR) that regulates blood glucose levels. Ubiquitination influences trafficking and signaling of many GPCRs, but its characterization for the GCGR is lacking. Using endocytic colocalization and ubiquitination assays, we have identified a correlation between the ubiquitination profile and recycling of the GCGR. Our experiments revealed that GCGRs are constitutively ubiquitinated at the cell surface. Glucagon stimulation not only promoted GCGR endocytic trafficking through Rab5a early endosomes and Rab4a recycling endosomes, but also induced rapid deubiquitination of GCGRs. Inhibiting GCGR internalization or disrupting endocytic trafficking prevented agonist-induced deubiquitination of the GCGR. Furthermore, a Rab4a dominant negative (DN) that blocks trafficking at recycling endosomes enabled GCGR deubiquitination, whereas a Rab5a DN that blocks trafficking at early endosomes eliminated agonist-induced GCGR deubiquitination. By down-regulating candidate deubiquitinases that are either linked with GPCR trafficking or localized on endosomes, we identified signal-transducing adaptor molecule–binding protein (STAMBP) and ubiquitin-specific protease 33 (USP33) as cognate deubiquitinases for the GCGR. Our data suggest that USP33 constitutively deubiquitinates the GCGR, whereas both STAMBP and USP33 deubiquitinate agonist-activated GCGRs at early endosomes. A mutant GCGR with all five intracellular lysines altered to arginines remains deubiquitinated and shows augmented trafficking to Rab4a recycling endosomes compared with the WT, thus affirming the role of deubiquitination in GCGR recycling. We conclude that the GCGRs are rapidly deubiquitinated after agonist-activation to facilitate Rab4a-dependent recycling and that USP33 and STAMBP activities are critical for the endocytic recycling of the GCGR.

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

The histopathological subtype of lung adenocarcinoma (LUAD) is closely associated with prognosis. Micropapillary or solid predominant LUAD tends to relapse after surgery at an early stage, whereas lepidic pattern shows a favorable outcome. However, the molecular mechanism underlying this phenomenon remains unknown. Here, we recruited 31 lepidic predominant LUADs (LR: low-risk subtype group) and 28 micropapillary or solid predominant LUADs (HR: high-risk subtype group). Tissues of these cases were obtained and label-free quantitative proteomic and bioinformatic analyses were performed. Additionally, prognostic impact of targeted proteins was validated using The Cancer Genome Atlas databases (n=492) and tissue microarrays composed of early-stage LUADs (n=228). A total of 192 differentially expressed proteins were identified between tumor tissues of LR and HR and three clusters were identified via hierarchical clustering excluding eight proteins. Cluster 1 (65 proteins) showed a sequential decrease in expression from normal tissues to tumor tissues of LR and then to HR and was predominantly enriched in pathways such as tyrosine metabolism and ECM-receptor interaction, and increased matched mRNA expression of 18 proteins from this cluster predicted favorable prognosis. Cluster 2 (70 proteins) demonstrated a sequential increase in expression from normal tissues to tumor tissues of LR and then to HR and was mainly enriched in pathways such as extracellular organization, DNA replication and cell cycle, and high matched mRNA expression of 25 proteins indicated poor prognosis. Cluster 3 (49 proteins) showed high expression only in LR, with high matched mRNA expression of 20 proteins in this cluster indicating favorable prognosis. Furthermore, high expression of ERO1A and FEN1 at protein level predicted poor prognosis in early-stage LUAD, supporting the mRNA results. In conclusion, we discovered key differentially expressed proteins and pathways between low-risk and high-risk subtypes of early-stage LUAD. Some of these proteins could serve as potential biomarkers in prognostic evaluation.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [¹⁷⁷Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [¹⁷⁷Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (TBS) and changes in normalized peak count (nPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in TBS_second-first, TBS_third-first, and TBS_fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [¹⁷⁷Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. –0.049, 0.08 vs. –0.116, and 0.109 vs. –0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). nPC_second-first showed significant group differences (mean, –0.107 vs. –0.282; P = 0.033); nPC_third-first and nPC_fourth-first did not reach statistical significance (mean, –0.122 vs. –0.312 and –0.183 vs. –0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, TBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. TBS_second-first and TBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. nPC_second-first, nPC_third-first, and nPC_fourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: TBS and nPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.

How to Explain Turkey's Early Elections 14 June 2018 — 12:30PM TO 1:30PM Anonymous (not verified) 29 May 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

On 24 June 2018 Turkey will go to the polls to vote in early presidential and parliamentary elections. Following a constitutional referendum last spring and against the backdrop of Turkey’s continued intervention in Syria and rising economic problems, President Erdogan has argued that an early election would help reduce uncertainty and set the country on a course to greater prosperity. The elections, likely to be held under the state of emergency in place since the attempted coup in July 2016, will also mark the country’s transformation from a parliamentary democracy to one with a powerful executive presidency.

In this session, the speaker will discuss what other factors led President Erdogan to call for an early election, what the state of the opposition is and what we can expect from Turkey should Erdogan win another term.

The Dow Jones Industrial Average and the S&P 500 hit new highs in early trading on Wednesday as former President Donald Trump claimed victory in Tuesday's presidential election over Kamala Harris.

Costco voluntarily recalled 79,200 pounds of two types of its store-brand butter over the past month because their labels may not have said the products contain milk.

Zapata Computing, which was founded in 2017 as a Harvard spinout specializing in quantum software and later pivoted to an AI focus, is ceasing operations, according to an SEC filing […]

The post Zapata Computing, Early Quantum-AI Software Specialist, Ceases Operations appeared first on HPCwire.

Oct. 16, 2024 — The ISC High Performance Jack Dongarra Early Career Award and Lecture Series is an annual event that honors the remarkable contributions of Professor Jack Dongarra to […]

The post ISC Opens Nominations for 2025 Jack Dongarra Early Career Award in HPC appeared first on HPCwire.

Costco voluntarily recalled 79,200 pounds of two types of its store-brand butter over the past month because their labels may not have said the products contain milk.

A simple 8-minute exercise can free up your brain and make you more efficient under stress.

Wayne Sanstead, who has been North Dakota's state schools superintendent for nearly three decades, has decided not to run for an eighth term this fall.

Democrat Gavin Newsom, who takes office Jan. 7, plans to expand full-day kindergarten and child-care offerings in the state, according to media reports.

A new study says that problems surrounding child-care hurt Georgia parents economically in many ways including in turned down promotions and having to cut back on work and school hours.

Charter schools are playing a notable role in remarks about education from candidates like Joe Biden and Bernie Sanders. Yet it's not clear what if any role they'll have in important states like Iowa and New Hampshire.

Research from REL Midwest examines the student characteristics associated with early college success in Indiana, with a focus on financial aid.

An audit of the early-childhood education offerings in Minnesota finds complexity and fragmentation as well as a lack of data about program effectiveness.

In Kodiak, Alaska, a school district with deep ties to the U.S. Coast Guard has been walloped by the government shutdown with hundreds of families going without paychecks. And news of a deal to temporarily reopen the government was doing little to allay the community's anxieties.

5 December 2014, Rome – At the closure of the FAO Council held today, the [...]

A shipwreck discovered off New Zealand dates to a time before Cook's arrival

The Canadian Post-Impressionist artist was famous for her evocative landscapes and paintings incorporating motifs from First Nations groups

"Transforming Energy," the artist's first museum show in China, focuses on "artworks and objects that actively engage the audience"

Scientists aren't sure how the circular indentations some 450 feet below the surface formed, but they hope to investigate further

The giant salmon carp was formally identified in 1991, and since then, fewer than 30 individuals had been documented

Using high-res scans, a researcher uncovered scribbled etchings likely made by the British poet and artist while working as a teenage apprentice engraver in the 1770s

The one-minute composition, which dates to the 1830s, was found on a piece of paper about the size of an index card at a museum in New York City

A new study has shattered historians' long-held assumptions about some of the people who died in Mount Vesuvius' eruption in 79 C.E.

A man from Queens County has been sentenced to five years and nine months in federal prison for charges including making and transmitting child pornography, voyeurism and intercepting private communications.