Sequencing proteins with transverse ionic transport in nanochannels

{\it De novo} protein sequencing is essential for understanding cellular processes that govern the function of living organisms and all post-translational events and other sequence modifications that occur after a protein has been constructed from its corresponding DNA code. By obtaining the order of the amino acids that composes a given protein one can then determine both its secondary and tertiary structures through structure prediction, which is used to create models for protein aggregation diseases such as Alzheimer's Disease. Mass spectrometry is the current technique of choice for {\it de novo} sequencing. However, because some amino acids have the same mass the sequence cannot be completely determined in many cases. Here, we propose a new technique for {\it de novo} protein sequencing that involves translocating a polypeptide through a synthetic nanochannel and measuring the ionic current of each amino acid through an intersecting {\it perpendicular} nanochannel. To calculate the transverse ionic current blockaded by a given amino acid we use a Monte Carlo method along with Ramachandran plots to determine the available flow area, modified by the local density of ions obtained from molecular dynamics and the local flow velocity ratio derived from the Stokes equation. We find that the distribution of ionic currents for each of the 20 proteinogenic amino acids encoded by eukaryotic genes is statistically distinct, showing this technique's potential for {\it de novo} protein sequencing.Comment: 12 pages (9 of main text, 3 of supporting information), 4 figures, 1 table in supporting informatio

Soft networks for bridging the gap between research and practice: illuminative evaluation of CHAIN

Objectives To explore the process of knowledge exchange in an informal email network for evidence based health care, to illuminate the value of the service and its critical success factors, and to identify areas for improvement.Design Illuminative evaluationSetting Targeted email and networking service for UK healthcare practitioners and researchers.Participants 2800 members of a networking service.Main outcome measures Tracking of email messages, interviews with core staff, and a qualitative analysis of messages, postings from focus groups, and invited and unsolicited feedback to the service.Results The informal email network helped to bridge the gap between research and practice by serving as a rich source of information, providing access to members' experiences, suggestions, and ideas, facilitating cross boundary collaboration, and enabling participation in networking at a variety of levels. Ad hoc groupings and communities of practice emerged spontaneously as members discovered common areas of interest.Conclusion This study illuminated how knowledge for evidence based health care can be targeted, personalised, and made meaningful through informal social processes. Critical success factors include a broad based membership from both the research and service communities; a loose and fluid network structure; fight targeting of messages based on members' interests; the presence of a strong network identity and culture of reciprocity; and the opportunity for new members to learn through passive participation

Optimal Estimation of Several Linear Parameters in the Presence of Lorentzian Thermal Noise

In a previous article we developed an approach to the optimal (minimum variance, unbiased) statistical estimation technique for the equilibrium displacement of a damped, harmonic oscillator in the presence of thermal noise. Here, we expand that work to include the optimal estimation of several linear parameters from a continuous time series. We show that working in the basis of the thermal driving force both simplifies the calculations and provides additional insight to why various approximate (not optimal) estimation techniques perform as they do. To illustrate this point, we compare the variance in the optimal estimator that we derive for thermal noise with those of two approximate methods which, like the optimal estimator, suppress the contribution to the variance that would come from the irrelevant, resonant motion of the oscillator. We discuss how these methods fare when the dominant noise process is either white displacement noise or noise with power spectral density that is inversely proportional to the frequency ($1/f$ noise). We also construct, in the basis of the driving force, an estimator that performs well for a mixture of white noise and thermal noise. To find the optimal multi-parameter estimators for thermal noise, we derive and illustrate a generalization of traditional matrix methods for parameter estimation that can accommodate continuous data. We discuss how this approach may help refine the design of experiments as they allow an exact, quantitative comparison of the precision of estimated parameters under various data acquisition and data analysis strategies.Comment: 16 pages, 10 figures. Accepted for publication in Classical and Quantum Gravit

LIENS - EXTENT TO WHICH COMMON-LAW ARTISAN\u27S LIEN HAS BEEN SUPPLANTED BY STATUTE

An artisan\u27s lien is the right of a bailee, who by his labor, skill, or material adds value to the chattel of another at the request of the owner, directly or impliedly, to retain possession of the chattel until the reasonable value of his services has been paid. The right to this lien, which is a specific lien, is of common-law origin, and in the absence of anything inconsistent in the contract has long been extended to all artisans. This common-law artisan\u27s lien, however, has been supplanted by statute in some respect in all but five states. In the other forty-three states and in the District of Columbia, statutes have in various ways extended the artisan\u27s lien beyond one or more of its common-law limitations. In an attempt to classify the numerous statutes into definite groupings, the best basis for any division seems to be the extent to which they have extended the common-law artisan\u27s lien

TAXATION - SOCIAL SECURITY - DISSOLUTION OF CORPORATION AND FORMATION OF PARTNERSHIP AS MEANS OF AVOIDING TAX

The O Company surrendered its corporate charter and began operating under an agreement purporting to establish a partnership relation between the former officers and employees whereby complete management including the power to employ, discharge and control the duties of its members was vested in a board of control elected by and subject to changes made by the majority in interest. Net profits and losses were shared in proportion to the respective interests. The firm could be dissolved only by a vote of the majority in interest and not by transfer of interest, death or resignation of a member. Advice was requested of the Internal Revenue Bureau whether this organization was a partnership for purposes of the social security taxes. Held, that the organization as such was not a partnership but an association taxable as a corporation for purposes of Titles VIII and IX of the Social Security Act, and individuals performing services for the organization were employees thereof for purposes of those titles. S. S. T. 337, INT. REV, BULL., No. 43, p. 6 (Oct. 24, 1938), 1 C. C. H. UNEMPLOYMENT INSURANCE SERVICE, U 8722 (1938)

TORTS - LIABILITY OF LANDLORD FOR INJURY TO PROPERTY OF TENANT\u27S CUSTOMER

A customer of the tenant sued the landlord for damage, to fur coats left with the tenant in the normal course of his business, from water, due to a leaky condition of the roof of the building which was in the control of landlord. Held, that it was the duty of the landlord to exercise reasonable care to keep the roof in reasonable repair not only as regards the safety of persons in the building but also as respects property lawfully there; that this duty was not performed and the damage resulted therefrom. Whelkin Coat Co. v. Long Beach Trust Co., 121 N. J. L. 106, 1 A. (2d) 394 (1938)

CARRIERS - DISCRIMINATION -ALLOWANCE IN LIEU OF SPOTTING SERVICE BY RAILROADS -VALIDITY OF CEASE AND DESIST ORDER

Nine industrial corporations sought to set aside an order of the Interstate Commerce Commission commanding the railroad or railroads serving industrial plants of the plaintiffs to cease and desist from the payment of allowance for the spotting of cars and switching services performed by plaintiffs on plant facilities. They contended the commission exceeded its powers in making the order and that its findings were not supported by substantial evidence. Held, that there was substantial evidence to support the findings and that the order was valid and should be sustained. United States v. Pan American Petroleum Corp., 304 U.S. 156, 58 S. Ct. 771 (1938)

BANKRUPTCY - CORPORATE REORGANIZATION - GOOD FAITH IN PRESENTING PETITIONS FOR REORGANIZATION PROCEEDINGS

Reorganization proceedings for corporations are now provided for in chapter ten of the recently enacted Chandler Act, which supersedes the provisions of 77B. This legislation, designed to aid corporations which are insolvent or unable to meet their debts as they mature, is available to all commercial corporations except municipal, insurance, and banking corporations and railroad corporations authorized to file a petition under section 77 upon the proper showing. Sections 130 and 131 enumerate the necessary requirements of any petition filed for the purpose of obtaining reorganization. However, the most important prerequisite to this relief, from the standpoint of difficulty in compliance, is found in sections 141 to 144 of the act, requiring the court to find that the petition was filed in good faith or dismiss it. This question lies at the threshold of the case and must be clearly shown before the court will interfere with the affairs of the corporation