Peptide-Based, Two-Fluorophore, Ratiometric Probe for Quantifying Mobile Zinc in Biological Solutions

Small-molecule fluorescent sensors are versatile agents for detecting mobile zinc in biology. Capitalizing on the abundance of validated mobile zinc probes, we devised a strategy for repurposing existing intensity-based sensors for quantitative applications. Using solid-phase peptide synthesis, we conjugated a zinc-sensitive Zinpyr-1 derivative and a zinc-insensitive 7-hydroxycoumarin derivative onto opposite ends of a rigid P₉K peptide scaffold to create HcZ9, a ratiometric fluorescent probe for mobile zinc. A plate reader-based assay using HcZ9 was developed, the accuracy of which is comparable to that of atomic absorption spectroscopy. We investigated zinc accumulation in prostatic cells and zinc levels in human seminal fluid. When normal and tumorigenic cells are bathed in zinc-enriched media, cellular mobile zinc is buffered and changes slightly, but total zinc levels increase significantly. Quantification of mobile and total zinc levels in human seminal plasma revealed that the two are positively correlated with a Pearson’s coefficient of 0.73.National Institute of General Medical Sciences (U.S.) (GM065519

Collaborative Musical Expression and Creativity Among Academics: When Intellectualism Meets Twelve Bar Blues

The Professors are a blues, rock, and sometime heavy metal band made up of communication professors from a number of New Jersey schools. Formed in 1995, the band has played in clubs in New York City as well as a number of academic venues, including the annual conference of the International Communication Association in Chicago in 1996 and the annual conference of the National Communication Association in New York City in 1998. The Professors have been featured in both local and national press, including the Chronicle of Higher Education. When we learned of the call for papers for this special issue of the American Communication Journal addressing the creative endeavors of Communication scholars beyond their regular research agendas, we were delighted to have the opportunity to reflect upon the place of musical creativity within our lives as working academics. What follows in this paper are the thoughts of a number of band members, past and present, who trace the relationship of the musical, the creative, and the intellectual in terms of their own personal histories and academic interests

Reaction-Based Probes for Imaging Mobile Zinc in Live Cells and Tissues

Chelatable, or mobile, forms of zinc play critical signaling roles in numerous biological processes. Elucidating the action of mobile Zn(II) in complex biological environments requires sensitive tools for visualizing, tracking, and manipulating Zn(II) ions. A large toolbox of synthetic photoinduced electron transfer (PET)-based fluorescent Zn(II) sensors are available, but the applicability of many of these probes is limited by poor zinc sensitivity and low dynamic ranges owing to proton interference. We present here a general approach for acetylating PET-based probes containing a variety of fluorophores and zinc-binding units. The new sensors provide substantially improved zinc sensitivity and allow for incubation of live cells and tissue slices with nM probe concentrations, a significant improvement compared to the μM concentrations that are typically required for a measurable fluorescence signal. Acetylation effectively reduces or completely quenches background fluorescence in the metal-free sensor. Binding of Zn(II) selectively and quickly mediates hydrolytic cleavage of the acetyl groups, providing a large fluorescence response. An acetylated blue coumarin-based sensor was used to carry out detailed analyses of metal binding and metal-promoted acetyl hydrolysis. Acetylated benzoresorufin-based red-emitting probes with different zinc-binding sites are effective for sensing Zn(II) ions in live cells when applied at low concentrations (∼50–100 nM). We used green diacetylated Zinpyr1 (DA-ZP1) to image endogenous mobile Zn(II) in the molecular layer of mouse dorsal cochlear nucleus (DCN), confirming that acetylation is a suitable approach for preparing sensors that are highly specific and sensitive to mobile zinc in biological systems.National Institutes of Health (U.S.) (NIH grant GM065519)National Institutes of Health (U.S.) (NIH grant R01-DC007905)National Institutes of Health (U.S.) (NIH Fellowship (F32- EB019243))National Institutes of Health (U.S.) (NIH Fellowship (T32-DC011499))National Institutes of Health (U.S.) (NIH Fellowship (F32-DC013734)

CASIMIR: a high resolution far-IR/submm spectrometer for airborne astronomy

CASIMIR, the Caltech Airborne Submillimeter Interstellar Medium Investigations Receiver, is a far-infrared and submillimeter heterodyne spectrometer, being developed for the Stratospheric Observatory For Infrared Astronomy, SOFIA. CASIMIR will use newly developed superconducting-insulating-superconducting (SIS) mixers. Combined with the 2.5 m mirror of SOFIA, these detectors will allow observations with high sensitivity to be made in the frequency range from 500 GHz up to 1.4 THz. Initially, at least 5 frequency bands in this range are planned, each with a 4-8 GHz IF passband. Up to 4 frequency bands will be available on each flight and bands may be swapped readily between flights. The local oscillators for all bands are synthesized and tuner-less, using solid state multipliers. CASIMIR also uses a novel, commercial, field-programmable gate array (FPGA) based, fast Fourier transform spectrometer, with extremely high resolution, 22000 (268 kHz at 6 GHz), yielding a system resolution > 10^6. CASIMIR is extremely well suited to observe the warm, ≈ 100K, interstellar medium, particularly hydrides and water lines, in both galactic and extragalactic sources. We present an overview of the instrument, its capabilities and systems. We also describe recent progress in development of the local oscillators and present our first astronomical observations obtained with the new type of spectrometer

Unit 4-Dairy Calf Housing and Environment

This archival publication may not reflect current scientific knowledge or recommendations. Current information available from the University of Minnesota Extension: https://www.extension.umn.edu

Immunochemotherapy With Obinutuzumab or Rituximab for Previously Untreated Follicular Lymphoma in the GALLIUM Study: Influence of Chemotherapy on Efficacy and Safety

PurposeThe GALLIUM study (ClinicalTrials.gov identifier: NCT01332968) showed that obinutuzumab (GA101;G) significantly prolonged progression-free survival (PFS) in previously untreated patients with follicular lymphoma relative to rituximab (R) when combined with cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P;CHOP);CVP;or bendamustine. This report focuses on the impact of chemotherapy backbone on efficacy and safety.Patients and Methods: A total of 1,202 patients with previously untreated follicular lymphoma (grades 1 to 3a), advanced disease (stage III or IV, or stage II with tumor diameter 7 cm), Eastern Cooperative Oncology Group performance status 0 to 2, and requiring treatment were randomly assigned 1:1 to G 1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles or R 375 mg/m(2) on day 1 of each cycle, for six to eight cycles, depending on chemotherapy (allocated nonrandomly by center). Responding patients received G or R for 2 years or until disease progression.Results: Baseline Follicular Lymphoma International Prognostic Index risk, bulky disease, and comorbidities differed by chemotherapy. After 41.1 months median follow-up, PFS (primary end point) was superior for G plus chemotherapy (overall hazard ratio [HR], 0.68;95% CI, 0.54 to 0.87;P = .0016), with consistent results across chemotherapy backbones (bendamustine: HR, 0.63;95% CI, 0.46 to 0.88;CHOP: HR, 0.72;95% CI, 0.48 to 1.10;CVP: HR, 0.79;95% CI, 0.42 to 1.47). Grade 3 to 5 adverse events, notably cytopenias, were most frequent with CHOP. Grade 3 to 5 infections and second neoplasms were most frequent with bendamustine, which was associated with marked and prolonged reductions in T-cell counts. Fatal events were more frequent in patients treated with bendamustine, possibly reflecting differences in patient risk profiles.Conclusion: Improved PFS was observed for G plus chemotherapy for all three chemotherapy backbones. Safety profiles differed, although comparisons are confounded by nonrandom chemotherapy allocation

Mainstreaming domestic and gender-based violence into sociology and the criminology of violence

Sociological and criminological views of domestic and gender-based violencegenerally either dismiss it as not worthy of consideration, or focus on specificgroups of offenders and victims (male youth gangs, partner violence victims). Inthis paper, we take a holistic approach to violence, extending the definition fromthat commonly in use to encompass domestic violence and sexual violence. Weoperationalize that definition by using data from the latest sweep of the CrimeSurvey for England and Wales. By so doing, we identify that violence is currentlyunder-measured and ubiquitous; that it is gendered, and that other forms of violence (family violence, acquaintance violence against women) are equally ofconcern. We argue that violence studies are an important form of activity forsociologists

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma

Hodgkin, 9p24Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response 65 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker