Mouse Strains Influence Clearance and Efficacy of Antibody and Antibody-Drug Conjugate Via Fc-FcγR Interaction.

To provide a better understanding of the pharmacokinetics-pharmacodynamics relationships of antibody-based drugs, we analyzed several chimeric and humanized monoclonal antibodies or antibody-drug conjugates (ADC) for PK and efficacy among four strains of mice. Notably, antibodies and ADCs displayed a dose-dependent drug disposition profile in the plasma of NSG mice. The increased clearance rate in NSG mice resulted in the reduction of antitumor activity of ADCs.

Fast gas chromatography-atmospheric pressure (photo)ionization mass spectrometry of polybrominated diphenylether flame retardants.

Gas chromatography (GC) and mass spectrometry (MS) are powerful, complementary techniques for the analysis of environmental toxicants. Currently, most GC-MS instruments employ electron ionization under vacuum, but the concept of coupling GC to atmospheric pressure ionization (API) is attracting revitalized interest. API conditions are inherently compatible with a wide range of ionization techniques as well high carrier gas flows that enable fast GC separations.

Genetic origin of a large family with a novel PSEN1 mutation (Ile416Thr).

Introduction: A small percentage of Alzheimer's disease (AD) cases are caused by genetic mutations with autosomal dominant inheritance. We report a family with a novel variant in PSEN1.

Methods: We performed clinical and genetic evaluation of 93 related individuals from a Colombian admixed population.

Hybrid time-domain and continuous-wave diffuse optical tomography instrument with concurrent, clinical magnetic resonance imaging for breast cancer imaging.

Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow.

"Blueprinting" thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.

Early assessment of thrombogenicity and antithrombotic drug effects may be important for therapeutic decision making in patients presenting with acute stroke. In this prospective, single center, pilot study, a bedside thrombelastography assay (TEG6s) was used to measure thrombogenicity and antithrombotic drug response in serial patients presenting emergently with symptoms of acute stroke (n = 90). TEG6s measures were compared against diagnosis obtained by NIH Stroke Scale/Score and imaging.

Cardiac Sarcoidosis as an Uncommon Etiology for Posterior Circulation Stroke Presenting with Alexia without Agraphia.

Sarcoidosis is a systemic disease with cardiac involvement occurring in 20-50% of cases. Cardiogenic stroke caused by cardiac sarcoidosis, especially PCA infarction, is a rare clinical presentation that necessitates timely diagnosis and may warrant treatment prophylaxis against CVA. In this case report, we describe a 54-year-old Caucasian male presenting with left PCA stroke in the setting of cardiac and pulmonary sarcoidosis, and hypertension.

First Evidence for cos2β>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity.

We present first evidence that the cosine of the CP-violating weak phase 2β is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector.

Can empathy close the racial divide and gender gap in death penalty support?

Public opinion data indicate that the majority of US respondents support the death penalty. Research has consistently indicated, however, that Blacks and females are significantly less likely to support capital punishment than their White and male counterparts. Past research efforts attempting to account for these differences have, at best, only partially accounted for them: the racial divide and gender gap in death penalty support, while narrowed, remained evident.

Aberrant Inclusion of a Poison Exon Causes Dravet Syndrome and Related SCN1A-Associated Genetic Epilepsies.

Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies characterized by refractory seizures and developmental impairment. Sequencing approaches have identified causal genetic variants in only about 50% of individuals with DEEs. This suggests that unknown genetic etiologies exist, potentially in the ∼98% of human genomes not covered by exome sequencing (ES).

Combination of the Searches for Pair-Produced Vectorlike Partners of the Third-Generation Quarks at sqrt[s]=13 TeV with the ATLAS Detector.

A combination of the searches for pair-produced vectorlike partners of the top and bottom quarks in various decay channels (T→Zt/Wb/Ht, B→Zb/Wt/Hb) is performed using 36.1  fb^{-1} of pp collision data at sqrt[s]=13  TeV with the ATLAS detector at the Large Hadron Collider. The observed data are found to be in good agreement with the standard model background prediction in all individual searches.

Observation of Centrality-Dependent Acoplanarity for Muon Pairs Produced via Two-Photon Scattering in Pb+Pb Collisions at sqrt[s_{NN}]=5.02 TeV with the ATLAS Detector.

This Letter presents a measurement of γγ→μ^{+}μ^{-} production in Pb+Pb collisions recorded by the ATLAS detector at the Large Hadron Collider at sqrt[s_{NN}]=5.02  TeV with an integrated luminosity of 0.49  nb^{-1}.

Search for Resonant and Nonresonant Higgs Boson Pair Production in the bb[over ¯]τ^{+}τ^{-} Decay Channel in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

A search for resonant and nonresonant pair production of Higgs bosons in the bb[over ¯]τ^{+}τ^{-} final state is presented. The search uses 36.1  fb^{-1} of pp collision data with sqrt[s]=13  TeV recorded by the ATLAS experiment at the LHC in 2015 and 2016.

Vacuum Ultraviolet Spectroscopy as a New Tool for GC Analysis of Terpenes in Flavors and Fragrances.

: Traditional detectors such as flame ionization detection and MS have issues with coeluting isomers like terpenes; however, unique vacuum UV (VUV) absorbance spectra can be used to deliberately compress chromatography. : Deconvolution capabilities under various run conditions of GC-MS and GC-VUV are compared. : A standard terpenes mix and tea tree essential oil were run on both GC-MS (63 and 14 min run times) and GC-VUV (22, 11, and 7 min run times).

Lab-simulated downhole leaching of formaldehyde from proppants by high performance liquid chromatography (HPLC), headspace gas chromatography-vacuum ultraviolet (HS-GC-VUV) spectroscopy, and headspace gas chromatography-mass spectrometry (HS-GC-MS).

The ability of different methods to analyze formaldehyde and other leachates from proppants was investigated under lab-simulated downhole conditions. These methods include high performance liquid chromatography (HPLC), headspace gas chromatography-vacuum ultraviolet spectroscopy (HS-GC-VUV), and headspace gas chromatography-mass spectrometry (HS-GC-MS). Two different types of resin-coated proppants, phenol-formaldehyde- and polyurethane-based, were examined.

Search for heavy particles decaying into top-quark pairs using lepton-plus-jets events in proton-proton collisions at with the ATLAS detector.

A search for new heavy particles that decay into top-quark pairs is performed using data collected from proton-proton collisions at a centre-of-mass energy of 13  by the ATLAS detector at the Large Hadron Collider. The integrated luminosity of the data sample is 36.1 fb .

Rare variants in the neuronal ceroid lipofuscinosis gene MFSD8 are candidate risk factors for frontotemporal dementia.

Pathogenic variation in MAPT, GRN, and C9ORF72 accounts for at most only half of frontotemporal lobar degeneration (FTLD) cases with a family history of neurological disease. This suggests additional variants and genes that remain to be identified as risk factors for FTLD. We conducted a case-control genetic association study comparing pathologically diagnosed FTLD patients (n = 94) to cognitively normal older adults (n = 3541), and found suggestive evidence that gene-wide aggregate rare variant burden in MFSD8 is associated with FTLD risk.

Probing the Quantum Interference between Singly and Doubly Resonant Top-Quark Production in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter presents a normalized differential cross-section measurement in a fiducial phase-space region where interference effects between top-quark pair production and associated production of a single top quark with a W boson and a b-quark are significant. Events with exactly two leptons (ee, μμ, or eμ) and two b-tagged jets that satisfy a multiparticle invariant mass requirement are selected from 36.1  fb^{-1} of proton-proton collision data taken at sqrt[s]=13  TeV with the ATLAS detector at the LHC in 2015 and 2016.

Tissue oxygen saturation predicts response to breast cancer neoadjuvant chemotherapy within 10 days of treatment.

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling.

Targeted Delivery of Cytotoxic NAMPT Inhibitors Using Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) are a therapeutic modality that enables the targeted delivery of cytotoxic drugs to cancer cells. Identification of active payloads with unique mechanisms of action is a key aim of research efforts in the field. Herein, we report the development of inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) as a novel payload for ADC technology.

Measurement of the Soft-Drop Jet Mass in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

Jet substructure observables have significantly extended the search program for physics beyond the standard model at the Large Hadron Collider. The state-of-the-art tools have been motivated by theoretical calculations, but there has never been a direct comparison between data and calculations of jet substructure observables that are accurate beyond leading-logarithm approximation. Such observables are significant not only for probing the collinear regime of QCD that is largely unexplored at a hadron collider, but also for improving the understanding of jet substructure properties that are used in many studies at the Large Hadron Collider.

Search for new phenomena using the invariant mass distribution of same-flavour opposite-sign dilepton pairs in events with missing transverse momentum in collisions with the ATLAS detector.

A search for new phenomena in final states containing an or pair, jets, and large missing transverse momentum is presented. This analysis makes use of proton-proton collision data with an integrated luminosity of , collected during 2015 and 2016 at a centre-of-mass energy with the ATLAS detector at the Large Hadron Collider. The search targets the pair production of supersymmetric coloured particles (squarks or gluinos) and their decays into final states containing an or pair and the lightest neutralino ( ) via one of two next-to-lightest neutralino ( ) decay mechanisms: , where the boson decays leptonically leading to a peak in the dilepton invariant mass distribution around the boson mass; and with no intermediate resonance, yielding a kinematic endpoint in the dilepton invariant mass spectrum.

A genotypic and spatial epidemiologic analysis of Massachusetts' Mycobacterium tuberculosis cases from 2012 to 2015.

Background: Massachusetts had a rate of 2.8 cases of tuberculosis (TB) per 100,000 individuals in 2015. Although TB in Massachusetts is on the decline, the case rate remains far above the 2020 National TB Target of 1.

Coal combustion residues and their effects on trace element accumulation and health indices of eastern mud turtles (Kinosternon subrubrum).

Coal combustion is a major energy source in the US. The solid waste product of coal combustion, coal combustion residue (CCR), contains potentially toxic trace elements. Before 1980, the US primarily disposed of CCR in aquatic settling basins.

Search for Low-Mass Dijet Resonances Using Trigger-Level Jets with the ATLAS Detector in pp Collisions at sqrt[s]=13 TeV.

Searches for dijet resonances with sub-TeV masses using the ATLAS detector at the Large Hadron Collider can be statistically limited by the bandwidth available to inclusive single-jet triggers, whose data-collection rates at low transverse momentum are much lower than the rate from standard model multijet production. This Letter describes a new search for dijet resonances where this limitation is overcome by recording only the event information calculated by the jet trigger algorithms, thereby allowing much higher event rates with reduced storage needs. The search targets low-mass dijet resonances in the range 450-1800 GeV.