Primary and secondary dissociation pathways in the ultraviolet photolysis of Cl_2O

The photodissociation of dichlorine monoxide (Cl_2O) at 308, 248, and 193 nm was studied by photofragment translational energy spectroscopy. The primary channel upon excitation at 308 and 248 nm was Cl–O bond fission with production of ClO+Cl. A fraction of the ClO photoproducts also underwent spontaneous secondary dissociation at 248 nm. The center-of-mass translational energy distribution for the ClO+Cl channel at 248 nm appeared to be bimodal with a high energy component that was similar in shape to the 308 nm distribution and a second, low energy component with a maximum close to the threshold for the 2Cl+O(3P) channel. Observation of a bimodal distribution suggests that two pathways with different dissociation dynamics lead to ClO+Cl products. The high product internal energy of the second component raises the possibility that ClO is formed in a previously unobserved spin-excited state a 4∑−. Following excitation at 193 nm, a concerted dissociation pathway leading to Cl_2+O was observed in addition to primary Cl–O bond breakage. In both processes, most of the diatomic photofragments were formed with sufficient internal energy that they spontaneously dissociated. The time-of-flight distributions of the Cl_2+O products suggest that these fragments are formed in two different channels Cl_2(3II)+O(3P) and Cl_2(X1∑)+O(1D)

Computational Design of the β-Sheet Surface of a Red Fluorescent Protein Allows Control of Protein Oligomerization

Computational design has been used with mixed success for the design of protein surfaces, with directed evolution heretofore providing better practical solutions than explicit design. Directed evolution, however, requires a tractable high-throughput screen because the random nature of mutation does not enrich for desired traits. Here we demonstrate the successful design of the β-sheet surface of a red fluorescent protein (RFP), enabling control over its oligomerization. To isolate the problem of surface design, we created a hybrid RFP from DsRed and mCherry with a stabilized protein core that allows for monomerization without loss of fluorescence. We designed an explicit library for which 93 of 96 (97%) of the protein variants are soluble, stably fluorescent, and monomeric. RFPs are heavily used in biology, but are natively tetrameric, and creating RFP monomers has proven extremely difficult. We show that surface design and core engineering are separate problems in RFP development and that the next generation of RFP markers will depend on improved methods for core design

A SYSTEMATIC REVIEW OF METHODOLOGIES USED TO ASSESS “UNANTICIPATED” CUTTING MECHANICS

Biomechanical analysis of cutting mechanics is a popular approach to assessing risk factors for injuries such as anterior cruciate ligament ruptures. The purpose of this study was to systematically review the methodological approaches to assessing unanticipated cutting mechanics and provide a review of such approaches. A total of 93 articles where identified that had assessed unanticipated cutting. The most common methodological design was a 45° cutting task following a run-up where the direction of the cut was determined by a light-based stimulus. External light stimuli create a worst-case scenario by providing information about the task at the last moment meaning opportunity for preparatory mechanics is limited. However, light stimuli do not allow for perception-action to take place and may therefore not truly reflect an athlete’s cutting mechanics

Reliability of the Myotonometer for Assessment of Posterior Shoulder Tightness

BACKGROUND/PURPOSE: The Myotonometer® is an electronic tissue compliance meter that has been used to quantify the compliance of soft tissues. The Myotonometer® may be a valuable tool to measure the effectiveness of interventions commonly used to increase tissue compliance in individuals with posterior shoulder tightness (PST). Limited data exist on reliability and responsiveness of the Myotonometer® for assessment of soft tissues about the shoulder; therefore, the purpose of this study is to determine the intra- and inter-session reliability and responsiveness of the Myotonometer® in measuring tissue compliance of the posterior shoulder musculature in asymptomatic subjects with PST. METHODS: Fifteen asymptomatic subjects with unilateral shoulder range of motion deficits attended two measurement sessions to assess the compliance of the tissues overlying the posterior deltoid, infraspinatus, and teres musculature. Analyses of reliability and responsiveness were conducted using intra-class correlation coefficients (ICCs) and the determination of minimal detectible change (MDC). RESULTS: Intra-session ICC values ranged from 0.69 to 0.91 for all muscles with MDC never exceeding 1.0 mm. Inter-session ICC values were best for the posterior deltoid, which averaged 0.82, compared to the infraspinatus and the teres complex, which averaged 0.42 and 0.5 respectively. Inter-session MDC ranged from 0.55 to 1.20 mm across all muscles. CONCLUSIONS: Clinicians can reliably detect relatively small changes in tissue compliance within a single treatment session utilizing the Myotonometer®. The Myotonometer® can reliably detect changes between sessions for tissues overlying the posterior deltoid; however, observed change in the infraspinatus and teres musculature must be above 1 mm to achieve meaningful change and account for decreased inter-session reliability. LEVEL OF EVIDENCE: 3

Gas Rich Dwarf Spheroidals

We present evidence that nearly half of the dwarf spheroidal galaxies (dSph and dSph/dIrr) in the Local Group are associated with large reservoirs of atomic gas, in some cases larger than the stellar mass. The gas is sometimes found at large distance (~10 kpc) from the center of a galaxy and is not necessarily centered on it. Similarly large quantities of ionized gas could be hidden in these systems as well. The properties of some of the gas reservoirs are similar to the median properties of the High-Velocity Clouds (HVCs); two of the HI reservoirs are catalogued HVCs. The association of the HI with the dwarf spheroidals might thus provide a link between the HVCs and stars. We show that the HI content of the Local Group dSphs and dIrrs exhibits a sharp decline if the galaxy is within 250 kpc of either the Milky Way or M31. This can be explained if both galaxies have a sufficiently massive x-ray emitting halo that produces ram-pressure stripping if a dwarf ventures too close to either giant spiral. We also investigate tidal stripping of the dwarf galaxies and find that although it may play a role, it cannot explain the apparent total absence of neutral gas in most dSph galaxies at distances less than 250 kpc. For the derived mean density of the hot gas, n_0 = 2.5e-5 cm^-2, ram-pressure stripping is found to be more than an order of magnitude more effective in removing the gas from the dSph galaxies. The hot halo, with an inferred mass of 1e10 solar masses, may represent a reservoir of ~1000 destroyed dwarf systems, either HVCs or true dwarf galaxies similar to those we observe now.Comment: AASTex preprint style, 27 pages including 12 figures. Submitted to ApJ. See also http://astro.berkeley.edu/~robisha

Higher Education Instructional Change in a U.S. Context: Investigating the Scholarship of Teaching and Learning (SoTL) Innovations at Niagara University

A metà Settembre 2013, due degli autori di questo articolo sono stati a Lecce (Italia) realizzando una presentazionein una conferenza sull’istruzione superiore. In quella sede, è stato possibile condividere con i partecipanti i dieci cambiamenti più potenti e significativi che hanno avuto luogo nel vasto panoramadell’accademia americana. L’elenco si componeva di sviluppi di tipo teorico; così come da diversi livelli di implementazione e pratica presso l’Università di Niagara, nell’angolo Nord Est degli Stati Uniti. Tra le iniziative messe in evidenza è stata prima e soprattutto menzionato il lavoro di Ernest Boyer sulla Scholarshipof Teaching and Learning (SoTL), ovvero la sua visione su strade alternative comunque accademiche, basate sulla didattica, per il successo della formazione universitaria. Il percorso tracciato dal movimento SoTL cambia la cultura universitaria, collocando l’insegnamento come priorità; e la “scholarship” (ricerca didattica) emergente dagli studi sull’innovazione didattica come una disciplina di ricerca che può alinearse ad altre nell’ambito accademico. Le esperienze all’Università Niagara forniscono sia un caso di studio dell’implementazione dei suddetti concetti in una moderna istituzione americana; sia un’opportunità per la comparazione con i vari casi delle istituzioni italiane. Inoltre, il lavoro portato avanti dall’università di Niagara risulta competitivo con riguardo ad alcune delle più riconosciute università americane, potendo essere considerato all’avanguardia dell’emergente movimentoSoTL. Questo articolo fornisce un breve resoconto e definizione del modello di Boyer su SoTL, suggerendo come le istituzioni potrebbero adottare tale paradigma sia come strategia per lo sviluppo professionale accademico, sia come adeguata base per la valutazione del lavoro del docente universitario

Cooperation across Organizational Boundaries: Experimental Evidence from a Major Sustainability Science Project

Engaged research emphasizes researcher–stakeholder collaborations as means of improving the relevance of research outcomes and the chances for science-based decision-making. Sustainability science, as a form of engaged research, depends on the collaborative abilities and cooperative tendencies of researchers. We use an economic experiment to measure cooperation between university faculty, local citizens, and faculty engaged in a large sustainability science project to test a set of hypotheses: (1) faculty on the sustainability project will cooperate more with local residents than non-affiliated faculty, (2) sustainability faculty will have the highest level of internal cooperation of any group, and (3) that cooperation may vary due to academic training and culture in different departments amongst sustainability faculty. Our results demonstrate that affiliation with the sustainability project is not associated with differences in cooperation with local citizens or with in-group peers, but that disciplinary differences amongst sustainability faculty do correlate with cooperative tendencies within our sample. We also find that non-affiliated faculty cooperated less with each other than with faculty affiliated with the sustainability project. We conclude that economic experiments can be useful in discovering patterns of prosociality within institutional settings, and list challenges for further applications

Level of Patient-Physician Agreement in Assessment of Change Following Conservative Rehabilitation for Shoulder Pain

Background Assessment of health-related status has been shown to vary between patients and physicians, although the degree of patient–physician discordance in the assessment of the change in status is unknown. Methods Ninety-nine patients with shoulder dysfunction underwent a standardized physician examination and completed several self-reported questionnaires. All patients were prescribed the same physical therapy intervention. Six weeks later, the patients returned to the physician, when self-report questionnaires were re-assessed and the Global Rating of Change (GROC) was completed by the patient. The physician completed the GROC retrospectively. To determine agreement between patient and physician, intra-class correlation (ICC) coefficient and Pearson’s r using the 15-point GROC and weighted kappa using a consolidated three-point GROC were calculated. Results Utilizing the 15-point GROC, complete agreement was observed in 37 of 99 patients (37%). ICC and Pearson’s r between patient and physician were 0.62 and 0.63, respectively. Utilizing a consolidated three-point GROC, complete agreement was observed in 76 of 99 patients (77%). Weighted kappa was 0.62. Conclusions Assessment of change reported by the patient demonstrates moderate to good agreement with physician assessment. These findings indicate that the GROC does reflect and represent similar assessment of change in health status by patients and physicians. This can aid discussion of both past treatment results and future treatment plans

Predicting and harnessing protein flexibility in the design of species-specific inhibitors of thymidylate synthase1,21Escherichia coli thymidylate synthase numbering is used unless otherwise noted.2PDB coordinates have been deposited with the RCSB with accession ID: 1JG0.

AbstractBackground: Protein plasticity in response to ligand binding abrogates the notion of a rigid receptor site. Thus, computational docking alone misses important prospective drug design leads. Bacterial-specific inhibitors of an essential enzyme, thymidylate synthase (TS), were developed using a combination of computer-based screening followed by in-parallel synthetic elaboration and enzyme assay [Tondi et al. (1999) Chem. Biol. 6, 319–331]. Specificity was achieved through protein plasticity and despite the very high sequence conservation of the enzyme between species.Results: The most potent of the inhibitors synthesized, N,O-didansyl-L-tyrosine (DDT), binds to Lactobacillus casei TS (LcTS) with 35-fold higher affinity and to Escherichia coli TS (EcTS) with 24-fold higher affinity than to human TS (hTS). To reveal the molecular basis for this specificity, we have determined the crystal structure of EcTS complexed with DDT and 2′-deoxyuridine-5′-monophosphate (dUMP). The 2.0 Å structure shows that DDT binds to EcTS in a conformation not predicted by molecular docking studies and substantially differently than other TS inhibitors. Binding of DDT is accompanied by large rearrangements of the protein both near and distal to the enzyme’s active site with movement of Cα carbons up to 6 Å relative to other ternary complexes. This protein plasticity results in novel interactions with DDT including the formation of hydrogen bonds and van der Waals interactions to residues conserved in bacterial TS but not hTS and which are hypothesized to account for DDT’s specificity. The conformation DDT adopts when bound to EcTS explains the activity of several other LcTS inhibitors synthesized in-parallel with DDT suggesting that DDT binds to the two enzymes in similar orientations.Conclusions: Dramatic protein rearrangements involving both main and side chain atoms play an important role in the recognition of DDT by EcTS and highlight the importance of incorporating protein plasticity in drug design. The crystal structure of the EcTS/dUMP/DDT complex is a model system to develop more selective TS inhibitors aimed at pathogenic bacterial species. The crystal structure also suggests a general formula for identifying regions of TS and other enzymes that may be treated as flexible to aid in computational methods of drug discovery