Macroscopic transport by synthetic molecular machines

Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with—and perform physical tasks in—the macroscopic world represents a significant hurdle for molecular nanotechnology. Here we describe a wholly synthetic molecular system that converts an external energy source (light) into biased brownian motion to transport a macroscopic cargo and do measurable work. The millimetre-scale directional transport of a liquid on a surface is achieved by using the biased brownian motion of stimuli-responsive rotaxanes (‘molecular shuttles’) to expose or conceal fluoroalkane residues and thereby modify surface tension. The collective operation of a monolayer of the molecular shuttles is sufficient to power the movement of a microlitre droplet of diiodomethane up a twelve-degree incline.

Measurement of the Transverse-Longitudinal Cross Sections in the p (e,e'p)pi0 Reaction in the Delta Region

Accurate measurements of the p(e,e?p)pi0 reaction were performed at Q^2=0.127(GeV/c)^2 in the Delta resonance energy region. The experiments at the MIT-Bates Linear Accelerator used an 820 MeV polarized electron beam with the out of plane magnetic spectrometer system (OOPS). In this paper we report the first simultaneous determination of both the TL and TL? (``fifth" or polarized) cross sections at low Q^{2} where the pion cloud contribution dominates the quadrupole amplitudes (E2 and C2). The real and imaginary parts of the transverse-longitudinal cross section provide both a sensitive determination of the Coulomb quadrupole amplitude and a test of reaction calculations. Comparisons with model calculations are presented. The empirical MAID calculation gives the best overall agreement with this accurate data. The parameters of this model for the values of the resonant multipoles are |M_{1+}(I=3/2)|= (40.9 \pm 0.3)10^{-3}/m_pi, CMR= C2/M1= -6.5 \pm 0.3%, EMR=E2/M1=-2.2 \pm 0.9%, where the errors are due to the experimental uncertainties.Comment: 10 pages, 3 figures, minor corrections and addition

Single-molecule experiments in biological physics: methods and applications

I review single-molecule experiments (SME) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SME it is possible to: manipulate molecules one at a time and measure distributions describing molecular properties; characterize the kinetics of biomolecular reactions and; detect molecular intermediates. SME provide the additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SME it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level emphasizing the importance of SME to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SME from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOT), magnetic tweezers (MT), biomembrane force probe (BFP) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation), proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SME to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.Comment: Latex, 60 pages, 12 figures, Topical Review for J. Phys. C (Cond. Matt

Relativistic effects and two-body currents in 2H(e⃗,e′p)n^{2}H(\vec{e},e^{\prime}p)n using out-of-plane detection

Measurements of the ${^2}H(\vec{e},e^{\prime}p)n$ reaction were performed using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator and with the out-of-plane magnetic spectrometers (OOPS). The longitudinal-transverse, $f_{LT}$ and $f_{LT}^{\prime}$, and the transverse-transverse, $f_{TT}$, interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q$^2$=0.15 (GeV/c)$^2$. On comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions, and the importance of the two-body meson-exchange currents and isobar configurations. We demonstrate that these effects can be disentangled and studied by extracting the interference response functions using the novel out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio

Identification of prognostic factors and risk groups in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix

In a retrospective study conducted at the University of Alabama at Birmingham, the University of Michigan, and the Mayo Clinic, 185 patients with previously untreated FIGO stage IB and IIA squamous cell carcinoma of the cervix were found to have nodal metastasis at the time of radical hysterectomy and pelvic lymphadenectomy. Of these patients, 103 received adjuvant pelvic irradiation. Cancer recurred in 76 patients; the median time to recurrence was 3.1 years. The prognostic significance of patient age, clinical stage, lesion diameter, number and location of nodal metastases, and use of adjuvant radiation therapy was determined by multivariate analysis. Only patient age (P = 0.0006), lesion diameter (P P = 0.0004) were noted to be significant factors in determining overall survival. Rates of recurrence were also related to these factors. Employment of these significant variables led to identification of four risk groups. In general, patients with small cervical lesions (diameter 4 cm) and more than two involved nodes fell into the high-risk category. All other patients were categorized into intermediate-risk groups. Ten-year survival was 92% in the low-risk group (n = 13), 70% in the low-intermediate-risk group (n = 66), 56% in the high-intermediate-risk group (n = 66), and 13% in the high-risk group (n = 20). This risk group classification identifies subgroups of early-stage cervical carcinoma patients found to have nodal metastasis at the time of radical hysterectomy that warrant appropriately selected adjuvant therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27695/1/0000081.pd

Evaluating intelligent interfaces for post-editing automatic transcriptions of online video lectures

Video lectures are fast becoming an everyday educational resource in higher education. They are being incorporated into existing university curricula around the world, while also emerging as a key component of the open education movement. In 2007, the Universitat Politècnica de València (UPV) implemented its poliMedia lecture capture system for the creation and publication of quality educational video content and now has a collection of over 10,000 video objects. In 2011, it embarked on the EU-subsidised transLectures project to add automatic subtitles to these videos in both Spanish and other languages. By doing so, it allows access to their educational content by non-native speakers and the deaf and hard-of-hearing, as well as enabling advanced repository management functions. In this paper, following a short introduction to poliMedia, transLectures and Docència en Xarxa (Teaching Online), the UPV s action plan to boost the use of digital resources at the university, we will discuss the three-stage evaluation process carried out with the collaboration of UPV lecturers to find the best interaction protocol for the task of post-editing automatic subtitles.Valor Miró, JD.; Spencer, RN.; Pérez González De Martos, AM.; Garcés Díaz-Munío, GV.; Turró Ribalta, C.; Civera Saiz, J.; Juan Císcar, A. (2014). Evaluating intelligent interfaces for post-editing automatic transcriptions of online video lectures. Open Learning: The Journal of Open and Distance Learning. 29(1):72-85. doi:10.1080/02680513.2014.909722S7285291Fujii, A., Itou, K., & Ishikawa, T. (2006). LODEM: A system for on-demand video lectures. Speech Communication, 48(5), 516-531. doi:10.1016/j.specom.2005.08.006Gilbert, M., Knight, K., & Young, S. (2008). Spoken Language Technology [From the Guest Editors]. IEEE Signal Processing Magazine, 25(3), 15-16. doi:10.1109/msp.2008.918412Leggetter, C. J., & Woodland, P. C. (1995). Maximum likelihood linear regression for speaker adaptation of continuous density hidden Markov models. Computer Speech & Language, 9(2), 171-185. doi:10.1006/csla.1995.0010Proceedings of the 9th ACM SIGCHI New Zealand Chapter’s International Conference on Human-Computer Interaction Design Centered HCI - CHINZ ’08. (2008). doi:10.1145/1496976Martinez-Villaronga, A., del Agua, M. A., Andres-Ferrer, J., & Juan, A. (2013). Language model adaptation for video lectures transcription. 2013 IEEE International Conference on Acoustics, Speech and Signal Processing. doi:10.1109/icassp.2013.6639314Munteanu, C., Baecker, R., & Penn, G. (2008). Collaborative editing for improved usefulness and usability of transcript-enhanced webcasts. Proceeding of the twenty-sixth annual CHI conference on Human factors in computing systems - CHI ’08. doi:10.1145/1357054.1357117Repp, S., Gross, A., & Meinel, C. (2008). Browsing within Lecture Videos Based on the Chain Index of Speech Transcription. IEEE Transactions on Learning Technologies, 1(3), 145-156. doi:10.1109/tlt.2008.22Proceedings of the 2012 ACM international conference on Intelligent User Interfaces - IUI ’12. (2012). doi:10.1145/2166966Serrano, N., Giménez, A., Civera, J., Sanchis, A., & Juan, A. (2013). Interactive handwriting recognition with limited user effort. International Journal on Document Analysis and Recognition (IJDAR), 17(1), 47-59. doi:10.1007/s10032-013-0204-5Torre Toledano, D., Ortega Giménez, A., Teixeira, A., González Rodríguez, J., Hernández Gómez, L., San Segundo Hernández, R., & Ramos Castro, D. (Eds.). (2012). Advances in Speech and Language Technologies for Iberian Languages. Communications in Computer and Information Science. doi:10.1007/978-3-642-35292-8Wald, M. (2006). Creating accessible educational multimedia through editing automatic speech recognition captioning in real time. Interactive Technology and Smart Education, 3(2), 131-141. doi:10.1108/1741565068000005

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Managing peatland vegetation for drinking water treatment

Peatland ecosystem services include drinking water provision, flood mitigation, habitat provision and carbon sequestration. Dissolved organic carbon (DOC) removal is a key treatment process for the supply of potable water downstream from peat-dominated catchments. A transition from peat-forming Sphagnum moss to vascular plants has been observed in peatlands degraded by (a) land management, (b) atmospheric deposition and (c) climate change. Here within we show that the presence of vascular plants with higher annual above-ground biomass production leads to a seasonal addition of labile plant material into the peatland ecosystem as litter recalcitrance is lower. The net effect will be a smaller litter carbon pool due to higher rates of decomposition, and a greater seasonal pattern of DOC flux. Conventional water treatment involving coagulation-flocculation-sedimentation may be impeded by vascular plant-derived DOC. It has been shown that vascular plant-derived DOC is more difficult to remove via these methods than DOC derived from Sphagnum, whilst also being less susceptible to microbial mineralisation before reaching the treatment works. These results provide evidence that practices aimed at re-establishing Sphagnum moss on degraded peatlands could reduce costs and improve efficacy at water treatment works, offering an alternative to ‘end-of-pipe’ solutions through management of ecosystem service provision