A Shotgun Proteomic Method for the Identification of Membrane-Embedded Proteins and Peptides

Integral membrane proteins perform crucial cellular functions and are the targets for the majority of pharmaceutical agents. However, the hydrophobic nature of their membrane-embedded domains makes them difficult to work with. Here, we describe a shotgun proteomic method for the high-throughput analysis of the membrane-embedded transmembrane domains of integral membrane proteins which extends the depth of coverage of the membrane proteome

The benefit of context for facial composite construction.

Purpose - The aim of this study was to investigate whether the presence of a whole-face context during facial composite production facilitates construction of facial composite images.Design/Methodology - In Experiment 1, constructors viewed a celebrity face and then developed a facial composite using PRO-fit in one of two conditions: either the full-face was visible while facial features were selected, or only the feature currently being selected was visible. The composites were named by different participants. We then replicated the study using a more forensically-valid procedure: In Experiment 2 non-football fans viewed an image of a premiership footballer and 24 hours later constructed a composite of the face with a trained software operator. The resulting composites were named by football fans.Findings - In both studies we found that presence of the facial context promoted more identifiable facial composite images.Research limitations/implications – Though this study uses current software in an unconventional way, this was necessary to avoid error arising from between-system differences.Practical implications - Results confirm that composite software should have the whole-face context visible to witnesses throughout construction. Though some software systems do this, there remain others that present features in isolation and these findings show that these systems are unlikely to be optimal. Originality/value - This is the first study to demonstrate the importance of a full-face context for the construction of facial composite images. Results are valuable to police forces and developers of composite software

The Pine Needle, February 1947

Libraries and archives collect materials from different cultures and time periods to preserve and make available the historical record. As a result, materials such as those presented here may reflect sexist, misogynistic, abusive, racist, or discriminatory attitudes or actions that some may find disturbing, harmful, or difficult to view. Both a humor and literary magazine, The Pine Needle was a University of Maine student-produced periodical that began publication in the fall of 1946, the first post-World War II semester that saw GIs returning to campus. The Needle reflected an edginess and rebellion not found in previous UMaine student publications. While past student publications relied on euphemisms for alcohol and dating on campus, The Needle overtly sexualized co-eds and discussed the use of drugs, tobacco, and alcohol by students. Cover art for this issue is an unsigned pen-and-ink illustration produced by a member of The Needle\u27s art staff. It depicts the five members of the editorial staff gathered around a wood coffin labeled, The Needle. Included in this issue is a piece about former History Professor C. Dewitt Hardy II\u27s (1911-1992), term paper assignment entitled, Social Problems in My Home Town. The work mentions the birth of Hardy\u27s son and future artist, Clarion Dewitt Hardy III (1940-2017)

The Grizzly, November 14, 1980

Campus Life Committee Discusses Greek Societies • McDonald\u27s Opening Soon • Field Hockey Heading For Nationals • Frats Get Together for Clean-up • Ursinus News In Brief: Honors for Ursinus faculty member; College presents Rafferty art exhibit • Policy Unveiled for Gym • Elephant Man Seen As Statement On Human Behavior • Talented Student Performances • ProTheatre Opens • Aging Is Topic At College Forum • Coffeehouse Sings The Right Tune • En Garde, Ursinus! • Delta Pi Defeats Marines In Football • Disappointing Weekend For Volleyball • Harriers Take MAC Title • Demas, Rho To Meet In Hockey Finals • Grizzlies Win Behind Solid Offense Efforthttps://digitalcommons.ursinus.edu/grizzlynews/1047/thumbnail.jp

Inhalation of Ultrafine Particles Alters Blood Leukocyte Expression of Adhesion Molecules in Humans

Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter ~ 25 nm, geometric standard deviation ~ 1.6), for 2 hr, in three separate protocols: 10 μg/m(3) at rest, 10 and 25 μg/m(3) with exercise, and 50 μg/m(3) with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 μg/m(3) UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 μg/m(3) UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4(+) T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed

Acceptability of OP/Na swabbing for SARS-CoV-2: a prospective observational cohort surveillance study in Western Australian schools

Objectives: When the COVID-19 pandemic was declared, Governments responded with lockdown and isolation measures to combat viral spread, including the closure of many schools. More than a year later, widespread screening for SARS-CoV-2 is critical to allow schools and other institutions to remain open. Here, we describe the acceptability of a minimally invasive COVID-19 screening protocol trialled by the Western Australian Government to mitigate the risks of and boost public confidence in schools remaining open. To minimise discomfort, and optimise recruitment and tolerability in unaccompanied children, a combined throat and nasal (OP/Na) swab was chosen over the nasopharyngeal swab commonly used, despite slightly reduced test performance. Design, setting and participants: Trialling of OP/Na swabbing took place as part of a prospective observational cohort surveillance study in 79 schools across Western Australia. Swabs were collected from 5903 asymptomatic students and 1036 asymptomatic staff in 40 schools monthly between June and September 2020. Outcome measures: PCR testing was performed with a two-step diagnostic and independent confirmatory PCR for any diagnostic PCR positives. Concurrent surveys, collected online through the REDCap platform, evaluated participant experiences of in-school swabbing. Results: 13 988 swabs were collected from students and staff. There were zero positive test results for SARS-CoV-2, including no false positives. Participants reported high acceptability: 71% of students reported no or minimal discomfort and most were willing to be reswabbed (4% refusal rate). Conclusions: OP/Na swabbing is acceptable and repeatable in schoolchildren as young as 4 years old and may combat noncompliance rates by significantly increasing the acceptability of testing. This kind of minimally-invasive testing will be key to the success of ongoing, voluntary mass screening as society adjusts to a new ‘normal’ in the face of COVID-19. Trial registration number: Australian New Zealand Clinical Trials Registry—ACTRN12620000922976

Razvoj i biofarmaceutsko vrednovanje pripravka za povećano oslobađanje tramadol hidroklorida na principu osmotske tehnologije

Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve the same. Formulation variables like level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect the drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC0-24, MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with performance of two commercial tablets of TRH. The developed formulation provided more prolonged and controlled TRH release as compared to marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable during 6 months of accelerated stability testing.U radu je opisana priprava i evaluacija pripravaka tramadol hidroklorida (TRH) na principu osmotske tehnologije. Da bi se postigao željeni profil oslobađanja mijenjane su različite varijable. Pokazalo se da najveći utjacaj na oslobađanje ljekovite tvari imaju udjeli polimera koji bubri, plastifikatora i debljina ovojnice polupropusne membrane (SPM). TRH oslobađanje bilo je proporcionalno udjelu plastifikatora, a obrnuto proporcionalno udjelu polimera i vrijednosti SPM. Oslobađanje ljekovite tvari bilo je neovisno o pH i intenzitetu miješanja, a ovisno o osmotskom talku medija. U in vivo studiji provedenoj na šest zdravih volontera određeni su farmakokinetički parametri (cmax, tmax, AUC0-24, MRT) i izračunata relativna bioraspoloživost. Rezultati dobiveni u pokusima in vitro i in vivo uspoređeni su s dvije vrste komercijalno dostupnih tableta TRH: oslobađanje ljekovite tvari iz pripravka razvijenog u ovom radu bilo je dulje i više kontrolirano. In vitro-in vivo korelacija (IVIVC) je analizirana prema Wagner-Nelsonovoj metodi. Optimizirani pripravak (IVB) pokazao je dobru IVIV korelaciju (R = 0,9750). Proizvodni proces je bio reproducibilan i pripravci su bili stabilni tijekom 6 mjeseci u uvjetima ubrzanog starenja

Rapid Detection of the H275Y Oseltamivir Resistance Mutation in Influenza A/H1N1 2009 by Single Base Pair RT-PCR and High-Resolution Melting

Introduction: We aimed to design a real-time reverse-transcriptase-PCR (rRT-PCR), high-resolution melting (HRM) assay to detect the H275Y mutation that confers oseltamivir resistance in influenza A/H1N1 2009 viruses.Findings: A novel strategy of amplifying a single base pair, the relevant SNP at position 823 of the neuraminidase gene, was chosen to maintain specificity of the assay. Wildtype and mutant virus were differentiated when using known reference samples of cell-cultured virus. However, when dilutions of these reference samples were assayed, amplification of nonspecific primer-dimer was evident and affected the overall melting temperature (Tm) of the amplified products. Due to primer-dimer appearance at .30 cycles we found that if the cycle threshold (CT) for a dilution was .30, the HRM assay did not consistently discriminate mutant from wildtype. Where the CT was ,30 we noted an inverse relationship between CT and Tm and fitted quadratic curves allowed the discrimination of wildtype, mutant and 30:70 mutant:wildtype virus mixtures. We compared the CT values for a TaqMan H1N1 09 detection assay with those for the HRM assay using 59 clinical samples and demonstrated that samples with a TaqMan detection assay CT.32.98 would have an H275Y assay CT.30. Analysis of the TaqMan CT values for 609 consecutive clinical samples predicted that 207 (34%) of the samples would result in an HRM assay CT.30 and therefore not be amenable to the HRM assay.Conclusions: The use of single base pair PCR and HRM can be useful for specifically interrogating SNPs. When applied to H1N1 09, the constraints this placed on primer design resulted in amplification of primer-dimer products. The impact primer-dimer had on HRM curves was adjusted for by plotting Tm against CT. Although less sensitive than TaqMan assays, the HRM assay can rapidly, and at low cost, screen samples with moderate viral concentrations