Software Lock Mass by Two-Dimensional Minimization of Peptide Mass Errors

Mass accuracy is a key parameter in proteomic experiments, improving specificity, and success rates of peptide identification. Advances in instrumentation now make it possible to routinely obtain high resolution data in proteomic experiments. To compensate for drifts in instrument calibration, a compound of known mass is often employed. This ‘lock mass’ provides an internal mass standard in every spectrum. Here we take advantage of the complexity of typical peptide mixtures in proteomics to eliminate the requirement for a physical lock mass. We find that mass scale drift is primarily a function of the m/z and the elution time dimensions. Using a subset of high confidence peptide identifications from a first pass database search, which effectively substitute for the lock mass, we set up a global mathematical minimization problem. We perform a simultaneous fit in two dimensions using a function whose parameterization is automatically adjusted to the complexity of the analyzed peptide mixture. Mass deviation of the high confidence peptides from their calculated values is then minimized globally as a function of both m/z value and elution time. The resulting recalibration function performs equal or better than adding a lock mass from laboratory air to LTQ-Orbitrap spectra. This ‘software lock mass’ drastically improves mass accuracy compared with mass measurement without lock mass (up to 10-fold), with none of the experimental cost of a physical lock mass, and it integrated into the freely available MaxQuant analysis pipeline (www.maxquant.org)

A preliminary report of an educational intervention in practice management

BACKGROUND: Practice management education continues to evolve, and little information exists regarding its curriculum design and effectiveness for resident education. We report the results of an exploratory study of a practice management curriculum for primary care residents. METHODS: After performing a needs assessment with a group of primary care residents at Wright State University, we designed a monthly seminar series covering twelve practice management topics. The curriculum consisted of interactive lectures and practice-based application, whenever possible. We descriptively evaluated two cognitive components (practice management knowledge and skills) and the residents' evaluation of the curriculum. RESULTS: The mean correct on the knowledge test for this group of residents was 74% (n = 12) and 91% (n = 12) before and after the curriculum, respectively. The mean scores for the practice management skill assessments were 2.62 before (n = 12), and 3.65 after (n = 12) the curriculum (modified Likert, 1 = strongly disagree, 5 = strongly agree). The residents rated the curriculum consistently high. CONCLUSIONS: This exploratory study suggests that this curriculum may be useful in developing knowledge and skills in practice management for primary care residents. This study suggests further research into evaluation of this curriculum may be informative for practice-based education

Structural Basis of the Association of HIV-1 Matrix Protein with DNA

HIV-1 matrix (MA) is a multifunctional protein that is synthesized as a polyprotein that is cleaved by protease during viral maturation. MA contains a cluster of basic residues whose role is controversial. Proposed functions include membrane anchoring, facilitating viral assembly, and directing nuclear import of the viral DNA. Since MA has been reported to be a component of the preintegration complex (PIC), we have used NMR to probe its interaction with other PIC components. We show that MA interacts with DNA and this is likely sufficient to account for its association with the PIC

Melting of a 2D Quantum Electron Solid in High Magnetic Field

The melting temperature ($T_m$) of a solid is generally determined by the pressure applied to it, or indirectly by its density ($n$) through the equation of state. This remains true even for helium solids\cite{wilk:67}, where quantum effects often lead to unusual properties\cite{ekim:04}. In this letter we present experimental evidence to show that for a two dimensional (2D) solid formed by electrons in a semiconductor sample under a strong perpendicular magnetic field\cite{shay:97} ($B$), the $T_m$ is not controlled by $n$, but effectively by the \textit{quantum correlation} between the electrons through the Landau level filling factor $\nu$=$nh/eB$. Such melting behavior, different from that of all other known solids (including a classical 2D electron solid at zero magnetic field\cite{grim:79}), attests to the quantum nature of the magnetic field induced electron solid. Moreover, we found the $T_m$ to increase with the strength of the sample-dependent disorder that pins the electron solid.Comment: Some typos corrected and 2 references added. Final version with minor editoriol revisions published in Nature Physic

Observation of the Fractional Quantum Hall Effect in Graphene

When electrons are confined in two dimensions and subjected to strong magnetic fields, the Coulomb interactions between them become dominant and can lead to novel states of matter such as fractional quantum Hall liquids. In these liquids electrons linked to magnetic flux quanta form complex composite quasipartices, which are manifested in the quantization of the Hall conductivity as rational fractions of the conductance quantum. The recent experimental discovery of an anomalous integer quantum Hall effect in graphene has opened up a new avenue in the study of correlated 2D electronic systems, in which the interacting electron wavefunctions are those of massless chiral fermions. However, due to the prevailing disorder, graphene has thus far exhibited only weak signatures of correlated electron phenomena, despite concerted experimental efforts and intense theoretical interest. Here, we report the observation of the fractional quantum Hall effect in ultraclean suspended graphene, supporting the existence of strongly correlated electron states in the presence of a magnetic field. In addition, at low carrier density graphene becomes an insulator with an energy gap tunable by magnetic field. These newly discovered quantum states offer the opportunity to study a new state of matter of strongly correlated Dirac fermions in the presence of large magnetic fields

Lutzomyia adiketis sp. n. (Diptera: Phlebotomidae), a vector of Paleoleishmania neotropicum sp. n. (Kinetoplastida: Trypanosomatidae) in Dominican amber

<p>Abstract</p> <p>Background</p> <p>Amber fossils can be used to trace the history of disease-vector associations because microorganisms are preserved "in situ" inside the alimentary tract and body cavity of blood-sucking insects.</p> <p>Results</p> <p><it>Lutzomyia adiketis </it>sp. n. (Phlebotomidae: Diptera) is described from Dominican amber as a vector of <it>Paleoleishmania neotropicum </it>sp. n. (Kinetoplastida: Trypanosomatidae). The fossil sand fly differs from all previously described extinct and extant members of the genus by the following combination of characters: Sc forked with the branches meeting the costa and radius veins; wing L/W value of 4.1; a δ value of 18; a ratio β/α value of 0.86, and the shape and size of the spatulate rods on the ninth sternite. The trypanosomatid is characterized by the structure of its promastigotes, amastigotes and paramastigotes and its transmission by an extinct species of sand fly.</p> <p>Conclusion</p> <p>Morphological characters show that the fossil sand fly is a new extinct species and that it is host to a digenetic species of trypanosomatid. This study provides the first fossil evidence that Neotropical sand flies were vectors of trypanosomatids in the mid-Tertiary (20–30 mya).</p

Aviation turbulence: dynamics, forecasting, and response to climate change

Atmospheric turbulence is a major hazard in the aviation industry and can cause injuries to passengers and crew. Understanding the physical and dynamical generation mechanisms of turbulence aids with the development of new forecasting algorithms and, therefore, reduces the impact that it has on the aviation industry. The scope of this paper is to review the dynamics of aviation turbulence, its response to climate change, and current forecasting methods at the cruising altitude of aircraft. Aviation-affecting turbulence comes from three main sources: vertical wind shear instabilities, convection, and mountain waves. Understanding these features helps researchers to develop better turbulence diagnostics. Recent research suggests that turbulence will increase in frequency and strength with climate change, and therefore, turbulence forecasting may become more important in the future. The current methods of forecasting are unable to predict every turbulence event, and research is ongoing to find the best solution to this problem by combining turbulence predictors and using ensemble forecasts to increase skill. The skill of operational turbulence forecasts has increased steadily over recent decades, mirroring improvements in our understanding. However, more work is needed—ideally in collaboration with the aviation industry—to improve observations and increase forecast skill, to help maintain and enhance aviation safety standards in the future

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Randomised trials comparing different healthcare settings : an exploratory review of the impact of pre-trial preferences on participation, and discussion of other methodological challenges

BACKGROUND: We recently published a systematic review of different healthcare settings (such as outpatient, community or home) for administering intravenous chemotherapy, and concluded that performing conventionally designed randomised trials was difficult. The main problems were achieving adequate trial accrual rates and recruiting a study population which adequately represented the target population of interest. These issues stemmed from the fact that potential participants may have had pre-trial perceptions about the trial settings they may be allocated; such preferences will sometimes be strong enough for patients to decline an invitation to participate in a trial. A patient preference trial design (in which patients can choose, or be randomised to, an intervention) may have obviated these recruitment issues, although none of the trials used such a design. METHODS: In order to gain a better understanding of the broader prevalence and extent of these preference issues (and any other methodological challenges), we undertook an exploratory review of settings trials in any area of healthcare treatment research. We searched The Cochrane Library and Google Scholar and used snowballing methods to identify trials comparing different healthcare settings. RESULTS: Trial accrual was affected by patient preferences for a setting in 15 of the 16 identified studies; birth setting trials were the most markedly affected, with between 68 % and 85 % of eligible women declining to participate specifically because of preference for a particular healthcare setting. Recruitment into substance abuse and chemotherapy setting studies was also notably affected by preferences. Only four trials used a preference design: the proportion of eligible patients choosing to participate via a preference group ranged from between 33 % and 67 %. CONCLUSIONS: In trials of healthcare settings, accrual may be seriously affected by patient preferences. The use of trial designs which incorporate a preference component should therefore strongly be considered. When designing such trials, investigators should consider settings to be complex interventions, which are likely to have linked components which may be difficult to control for. Careful thought is also needed regarding the choice of comparator settings and the most appropriate outcome measures to be used