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Abstract Background Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV) and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE) virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol. Results The heterologous prime-boost vaccination protocol, using a VV recombinant and bacterial plasmid, both containing the NS1 TBE virus protein gene under the control of different promoters, achieved a high level of protection in mice against lethal challenge with a highly pathogenic TBE virus strain. No signs of pronounced TBE infection were detected in the surviving animals. Conclusion Heterologous prime-boost vaccination protocols using recombinant VV and bacterial plasmids could be used for the development of flavivirus vaccines.

This study employed a phronetic (practical wisdom) analytic framework to explore the Tehran, Iran, City Council's Article 5 Commission's land use decisions from 1999 to 2024. We argue that, during that period, the Commission nominally embraced practical wisdom in lieu of episteme or techne as the arbiter of its choice making. Nonetheless, during those years, its members disproportionately granted land use change permits to the Tehran Comprehensive Plan that principally benefited members of the city's upper class. Our central finding underscores the Commission's role in advancing elite rather than broader public interest needs. We conclude that even a nominally phronetic planning process can fall prey to willfully undemocratic choice making. In this case, this occurred when the discretionary powers delegated to the Commission to serve the broader public interest were instead employed routinely to serve the interests of an elite. Our analysis highlights the urgent need for more ethical, popularly accountable, and equitable planning practices to serve the general population of Tehran. [ABSTRACT FROM AUTHOR]

The article discusses two books reviewed in the Journal of Supreme Court History. The first book, "Vaulting Ambition" by Michael Nelson, focuses on FDR's attempt to pack the Supreme Court in 1937. The second book, "Justice and Faith" by Greg Zipes, explores the life of Frank Murphy, a Supreme Court justice with a diverse background. Both books provide valuable insights into significant historical events and individuals, offering readers a deeper understanding of the Supreme Court's history and the impact of key decisions. [Extracted from the article]

Introduction: Antibiotic-resistant Gram-negative bacteria are of a growing concern globally, especially those producing enzymes conferring resistance. OXA-48-like carbapenemases hydrolyze most β-lactam antibiotics, with typically low-level hydrolysis of carbapenems, but have limited effect on broad-spectrum cephalosporins. These are frequently co-expressed with extended spectrum β-lactamases, especially CTX-M-15, which typically shows high level resistance to broad-spectrum cephalosporins, yet is carbapenem susceptible. The combined resistance profile makes the need for successful detection of these specific resistance determinants imperative for effective antibiotic therapy. Objectives: The objective of this study is to detect and identify OXA-48-like and CTX-M-15 enzymes using mass spectrometry, and to subsequently develop a method for detection of both enzyme types in combination with liquid chromatography. Methods: Cells grown in either broth or on agar were harvested, lysed, and, in some cases buffer-exchanged. Lysates produced from bacterial cells were separated and analyzed via liquid chromatography with mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS). Results: The intact proteins of OXA-48, OXA-181, and OXA-232 (collectively OXA-48-like herein) and CTX-M-15 were characterized and detected. Acceptance criteria based on sequence-informative fragments from each protein group were established as confirmatory markers for the presence of the protein(s). A total of 25 isolates were successfully tested for OXA-48 like (2), CTX-M-15 (3), or expression of both (7) enzymes. Thirteen isolates served as negative controls. Conclusions: Here we present a method for the direct and independent detection of both OXA-48-like carbapenemases and CTX-M-15 β-lactamases using LC-MS/MS. The added sensitivity of MS/MS allows for simultaneous detection of at least two co-eluting, co-isolated and co-fragmented proteins from a single mass spectrum.

Brazil's favela residents have long challenged the dominant media and social narrative that has described them by employing discourses of criminality. That prevailing, and discriminatory, view obscures the complex and multifaceted character, dynamism, and individual and collective agency of these communities' populations. This article examines the work of Redes da Maré, a civil society organization that offers cultural spaces for community-based creation and diffusion of the arts in its namesake favela. We employ the concepts of the social imaginary as well as individual and collective agency to investigate whether and in what ways this nongovernmental organization (NGO), which has adopted a cultural development approach, encourages participants' democratic attitudes and behaviors at the organizational and community level by fostering participation in the development process and offering a platform for the expression of the voices of those it engages. Our analysis is based on interviews with organizers and participants of Redes' arts program and its Free Dance School of Maré and on a review of relevant events in Maré's Arts Center. This inquiry contributes to a more nuanced view of the roles the arts can play in encouraging democratic agency and possibility among favela citizens despite adverse political and social conditions. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Critical praxis and the social imaginary for sustainable food systems," discusses the need for a fundamental reimagining of how individuals and social collectives understand their roles in contemporary food systems. The dominant neoliberal and technical-rational perspectives that govern globalized food systems are intertwined with systemic inequities and extractive practices. The article emphasizes the importance of shifting away from these perspectives and highlights the concept of critical praxis as a way to navigate and reimagine practices in food systems. The article also explores various themes and perspectives that challenge the dominant thinking in food systems and call for more just and sustainable approaches. [Extracted from the article]

Introduction: The visibility of rurality contributes to optimizing the planning and administrative management processes of the territories by providing contextualized information about the relationship of the inhabitants with the area under study. The objective of this research is to identify the mechanisms of visibility of rurality in Usme, a locality in Bogotá, Colombia. Methods: A case study was carried out using a mixed methodology. Based on a literature review, conceptual categories that support the visibility of rurality were formulated, and based on them, a perception survey addressed to the peasant leaders of Usme was designed. The survey contained 22 questions that inquired about socio-demographic data, citizen participation, roles of the inhabitants, participation scenarios, conditions, institutions, opportunities for improvement, and the needs and processes of the locality; the questions were multiple-choice with a single answer and open-ended. The survey was sent to 50 peasant leaders, of whom 36 responded (13 men, 21 women, and 2 LGBTIQ), who were residents of low (25), medium(3), and high (8) localities in the rural zone of Usme. Using the ATLAS.ti program, a frequency analysis was carried out for the multiple-choice questions and the textual data, as well as a content analysis of deductive and emergent categories; then, a nomological network on the mechanisms of visibility was constructed. Results: Findings show that participants understand rurality visibility mechanisms in terms of five dimensions: spaces of visibility, dimensions of rurality, forms of participation, places of participation, and types of impact. Discussion: The delimitation and definition of the dimensions that constitute the mechanisms of rurality visibility in the borders contribute to the designing of effective strategies to improve the conditions of the inhabitants of this area, as well as their participation in increasing the impact and coverage of the institutions of the territory, aiming to improve the quality of life of the inhabitants of the area. We concluded that, in order for this to happen, it is necessary to have community empowerment and social co-responsibility among the community, civil institutions, and government. [ABSTRACT FROM AUTHOR]

The governance of community public space is one of the most concerned issue of people's livelihood, and its effectiveness determines the residents' living experience and even the stability of the grassroots political authority. In order to explore the factors of the effectiveness of community public space governance and the path to enhance the effectiveness of community public space governance, this analysis combines the influencing factors with the three stages of identification, management and confirmation in public value management theory, and constructs an indicator system for measuring and analyzing the effectiveness of community public space governance. The fsQCA3.0 is used to analyze the data of 300 residents in Tianjin, China, after which several aims that affect the effectiveness of community public space governance are obtained. The results show that the paths of "resident trust, property management is authoritative" and "customer oriented, democratic consultation" that bring higher governance efficiency have a consistency of 0.874761 and a coverage of 0.480994, which explains well what combination of antecedent factors should be present in communities with high public space governance effectiveness. Based on this, in order to improve the governance efficiency of community public space, improving residents' living experience and promote the modernization of China's urban construction, the government, property management company, owners' committee and neighborhood committee should increase investment in enhancing policy support, establishing service concepts, introducing technology and equipment, enhancing residents' trust and establishing dispute coordination agencies. [ABSTRACT FROM AUTHOR]

Brazil's favela residents have long challenged the dominant media and social narrative that has, for decades, described them via discourses of criminality. This article examines the work of Redes da Maré, a civil society organization that offers cultural spaces and services for community-based creation and diffusion of the arts in its namesake favela. We employ the concepts of the social imaginary as well as individual and collective agency to investigate whether and in what ways a service-providing civil society organization that has adopted a cultural development approach encourages participants' democratic attitudes and behaviors at the organizational and community level to challenge existing systemic social oppression by fostering participation in the development process and offering a platform for the expression of the voices of those it engages. Our analysis is based in part on interviews with 4 lead organizers and participants in Redes' Free Dance School of Maré. Our analysis contributes to a more nuanced understanding of the roles the arts can play in encouraging democratic agency and possibility among favela citizens despite adverse political and social conditions exacerbated by neoliberal beliefs and policies. [ABSTRACT FROM AUTHOR]

United States law charges America's asylum officers with providing humanitarian protection for refugees while simultaneously securing the nation from external threats. This mandate requires that asylum officers balance potentially conflicting claims as they seek to ensure just treatment of claimants. This article explores how officers charged with that responsibility can develop a regime-centred subjectivity that often conditions them to view applicants with fraud and security concerns foremost in mind. This analysis also examines the potential efficacy of practical strategies linked to aesthetic, cognitive, affective, and moral imagination that may allow officials to become more aware of their statecentred subjectivity and how it influences their perceptions of threats to national security and to fraud. This analysis encourages adjudication officers to strive for a more nuanced understanding of what constitutes fraud and national security concerns and what are instead presuppositions created by the United States population-protection agenda. [ABSTRACT FROM AUTHOR]

This article examines the case of the Community Foundation for Northern Ireland's (CFNI) experience as a primary recipient of peacebuilding aid from the European Union (EU) under the Special EU Programmes Body Special Support Programme for Peace and Reconciliation in Northern Ireland (SEUPB- EUSSPPR). The case serves as a lens into the tensions that such efforts create for community-based organizations as they seek both to honor their funder's accountability claims and their own needs to ensure legitimacy and efficacy with those with whom they interact so as to secure space and discretion to seek to catalyze social experimentation and learning. This paper argues the Foundation's experience and frustrations with EU accountability claims point up a difficulty with the SEUPB's comprehensive conceptualization of peacebuilding: It tends in practice to favor Union-prescribed aims and objectives over those its 'partners' derive from their daily efforts. [ABSTRACT FROM AUTHOR]

Background: Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function. Methods: Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment). Results: Forty-nine patients received ≥1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary “sludge” in Arms A/B/C was 39%/36%/27%. Conclusions: Motesanib treatment was associated with increased [ABSTRACT FROM AUTHOR]

The article presents information on the appointments and selection of the judges in the Supreme Court of the U.S. with respect to the books published in and about the judges and the Supreme Court of the U.S. the appointments of the Justices is through the decision of the Presidents of the country where the Justices can be from either the Democratic party or the Republican party. Information on the books published that includes "Courtwatchers: Eyewitness Accounts in Supreme Court History," by Clare Cushman, "The Supreme Court under Morrison R. Waite 1874-1888," by Paul Kens and "William Howard Taft: The Travails of a Progressive Conservative," by Jonathan Lurie is also presented.

This paper addresses the increasing use of network forms of governance and the challenges would-be network managers confront, including the persistent need network structures create to secure a modicum of internal goal alignment among participating members, the difficulty of establishing and maintaining trust among collaborating organizational representatives, and the problematic of ensuring alignment of internal and external accountability claims in interorganizational and often multi-sectoral collaboratives. The paper reviews the literature and discusses the significance of communication management within network arrangements, including the role of technology for effective communication and subsequent coordination efforts. It concludes by arguing that networks are de facto distributed environments and working across them requires developing learning strategies to enhance member capacities to work collaboratively to address common concerns. [ABSTRACT FROM AUTHOR]

This article focuses on the question of what role community-based organization leaders play in shaping the possibility for the emergence of new social imaginaries. It argues that deep social conflicts and efforts to secure purposive change are likely to demand strong civil society organization response and that certain forms of imagination are necessary and must be actively employed among community-based leaders if new imaginaries are to be discerned and effectively shared in ways that encourage sustained dialogue and the development of new social understandings. The article explores these briefly and draws illustratively upon two relevant examples from the peacebuilding literature to contend that such imagination- led leadership is necessary to catalyze new social imaginaries that can lead to more resilient social orders. [ABSTRACT FROM AUTHOR]

Change at the Supreme Court may be most visible and frequent in the progression of statutory and constitutional questions the Justices resolve collectively, but it may also be equally highlighted by an individual Justice's decision. This reality became plainly apparent in a letter that Justice John Paul Stevens sent to the White House on April 9, 2010, just eleven days shy of his 90 birthday: 'My dear Mr. President: Having concluded that it would be in the best interests of the Court to have my successor appointed and confirmed well in advance of the commencement of the Court's next Term, I shall retire from regular active service as an Associate Justice ... effective the next day after the Court rises for the summer recess this year.' His statement was dated almost a year after Justice David Souter dispatched a similar notice to President Obama on May 1, 2009, announcing his intention to leave the Bench. Thus, for the fifth time in as many years, the machinery of executive nomination and senatorial advice and consent for the High Court churned again. [ABSTRACT FROM AUTHOR]

Millions were reminded on January 20, 2009, that the inauguration of an American President is as remarkable as it is routine. In this distinctly republican rite, the chief executive publicly subordinates himself to the fundamental law of the land. As the Constitution dictates, “[b]efore he enters on the Execution of his Office, he shall take the following Oath or Affirmation: ‘I do solemnly swear (or affirm) that I will faithfully execute the Office of President of the United States, and will to the best of my Ability, preserve, protect and defend the Constitution of the United States.’” 1 This display of constitutional fealty was remarkable because the variety of political systems, experiences, and cultures across today's globe graphically illustrates that the seamless and peaceful transfer of authority from one political party or individual to another, as was witnessed at President Barack Obama's inauguration and at President George W. Bush's inauguration in 2001, is not always a foregone occurrence everywhere. January's event was routine in that, from the outset of government under the Constitution and with the notable and tragic exception of 1860, the defeated party or individual has accepted, if not welcomed, the verdict rendered by the electoral process. That was the outcome even in 1800, when the notion of a violence-free shift of control in a country founded on the principle of government by the “consent of the governed” 2 was first put to the test at the presidential level. The assumption of authority by Thomas Jefferson and the Democratic-Republicans from John Adams and the Federalists marked the world's first peaceful transfer of power from the vanquished to the victors as the result of an election. 3 Given the stark national partisan differences that had crystallized in the short time since ratification of the Constitution and the fact that finalization of the election required extraordinary intervention by the House of Representatives to break an Electoral College tie, this outcome was a greater achievement than is sometimes acknowledged. “Partisanship prevailed to the bitter end and showed no signs of abating,” according to one historian who has recently revisited this critical and precedent-setting election. “Over the campaign's course, George Washington's vision of elite consensus leadership had died, and a popular two-party republic .. was born.” 4 [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue including one by Betsy Taylor on forestry in Appalachia, one by Leach, Lichtern, Taylor and Rothschild on civil rights and another by Neera Chandhole on civil society in India.

The coordination of relief in international humanitarian crises has long been viewed as fraught with problems of inadequate oversight and coordination. Contrary to this claim, this article argues that the international relief system, viewed as interdependent actors, is better understood on the basis of the principle of polycentricity. The authors sketch the conditions necessary to secure a polycentric social order and compare these to the international humanitarian relief framework. They argue that polycentricity may be a more apt aspiration for participants in the international relief system than are calls for new and more stringent forms of monocentric coordination, but its conditions too may be difficult for the relevant participants to realize. The authors explore the tensions and possibilities implicit in this reframing at both the strategic and operating scales. [ABSTRACT FROM AUTHOR]

Little scholarly attention has focused on understanding the impact of large gifts for small nonprofit organizations or on the mechanisms by which those institutions respond to such events. The authors studied the organizational and governance stresses mega-gifts create by examining the case of the $175 million Ruth Lilly gift to the Modern Poetry Association. The association's governing board successfully adapted to its changed circumstances by self-consciously learning and realigning its responsibilities relative to those of the organization's executive, which required individual and organizational learning. The authors chart the changes and actions that prompted that self-education and draw on the nonprofit organization governance, organizational learning, sense making, and adaptive change literatures to contend that nonprofit organization leaders must recognize that large-scale change will demand adaptive organizational work and require concomitant shifts in the routines of governance, management, and leadership so as to encourage and capture the learning necessary for successful organizational adjustment. [ABSTRACT FROM AUTHOR]

The first meeting of Politics 514 for fall semester 1964 was scheduled for Thursday afternoon, September 24, coincidentally the 209th anniversary of the birth of Chief Justice John Marshall. As an exceedingly green first-year student in the Graduate School, I made my way to "A" level (one floor below the first floor) of Princeton University's Firestone Library a few minutes before two o'clock. A short distance from the stairwell, I found the Politics Department seminar room and took a seat at the table. Promptly on the hour, Professor Alpheus Thomas Mason entered the room, greeted the dozen beginning and continuing students present, and occupied a chair with his back to the window. There followed an hour's discourse from this celebrated judicial biographer on what awaited us during the Term: an adventure in American constitutional law. Without notes and with the captivating voice of an orator, he drew from the words of James Madison, JamesWilson, Alexander Hamilton, Thomas Jefferson, and Marshall so extensively and with such familiarity that I wondered whether, during nearly four decades of teaching, he had somehow divined a way to commune directly with the founding generation. After he made clear his expectations and explained how the course would proceed, I then grasped why this seminar, although deservedly praised as one of the best taught in the Graduate School, was rarely heavily enrolled: He expected each student, each week, to write a research paper of nine to twelve pages. [ABSTRACT FROM AUTHOR]

This article explores the potential of doctoral student mentoring programs to serve as one bridge in the academic-practitioner divide in nonprofit education. This disconnect manifests itself in critiques regarding the marginalization of practitioners and lack of knowledge sharing. The article examines the potential role of nonprofit doctoral student mentoring as a possible avenue for addressing the divide by developing the intellectual capacities of graduates to interact effectively in both the academic and practitioner domains. It stresses the importance of a particular form of mentoring and its ties to multiple, reinforcing opportunities for students if analytical, praxis-centered capacities are to be successfully developed. Ultimately, this article aims to stimulate discussion on the role and forms of mentoring of scholars who must develop praxis capacities rather than to offer definitive evidence of the superiority of one or another approach of ensuring that result. [ABSTRACT FROM AUTHOR]

I discuss the implications of the SNO neutral current result for the allowed Δm2 values of pseudo-Dirac pairs. In particular, for certain parameter ranges, adiabatic MSW may occur in reverse as solar neutrinos traverse the earth's atmosphere. [ABSTRACT FROM AUTHOR]

This article briefly explores the thought of the seminal thinkers Edmund Burke, Russell Kirk and Charles Taylor to argue that conceptions of public and nonprofit leadership ought properly to be (re)founded and rethought on the basis of a profound regard for the principle of alterity as this is realized in the exercise of the moral imagination in the pursuit of human dignity; one of T. S. Eliot's "permanent things." The article contends that whether or not one accepts the idea of moral absolutes, this set of capacities is critical to the effective functioning of many nonprofit organizations and may constitute a basis on which these may legitimate and distinguish themselves from for-profit and public entities. Using Taylor's work, the paper provides a means by which to justify this stance that does not assume the existence of moral absolutes. [ABSTRACT FROM AUTHOR]

This article examines one university's efforts to institutionalize a graduate nonprofit curriculum. It does so through the lens of situational analysis and with an eye to five key challenges that have dogged the effort--operating in an inauspicious organizational environment, creating an interdisciplinary program in a discipline-rich context, securing a praxis analytical focus and shared pedagogical stance, ensuring a comparative analytical focus, and developing a sustainable balance between student needs and expert claims. These concerns are examined for what might be learned from each that may hold broader significance for nonprofit curriculum design, program development, and implementation. While some of these conditions are unique, what they suggest about the challenges for those seeking institutionalization of nonprofit curricula are not. The essay seeks to suggest how and why that might be so. The paper argues that, regardless of the case-specific factors at play in the present analysis, would-be nonprofit program builders would be wise to be attentive to their operating context, to the nature of existing program curricula and organizational cultures, and to the clear specification of their own curricular aims. [ABSTRACT FROM AUTHOR]

This article examines the frequently cited argument that coordination issues in humanitarian relief can be addressed more effectively with greater centralized authority and argues for a new conceptualization of aid delivery. The former position suggests a hierarchical, top-down view of the humanitarian relief theater, while this analysis contends that the relief implementation structure may be better conceived as consisting of a network of loosely coupled semiautonomous organizations (Weick, 1976). A network approach allows examination of aid coordination dynamics at multiple levels of analysis: individual (professional and personal), organizational and interorganizational (operational), and strategic (structural/contextual). So viewed, factors that influence relief delivery, including contextual or strategic conditions and organization-scale concerns, may either encourage or dissuade coordination across institutional boundaries. We argue that trust is a key precondition to coordination and that its extension is in turn conditioned by a number of strategic and operating-level factors. We concentrate on operational coordination, as strategic concerns are not often open to the control of lone organizational actors. Our analysis rests in part on in-depth interviews (each consisted of open-ended questions and lasted an average of ninety to one hundred minutes) with a small sample of experienced international nongovernmental organization relief professionals who were engaged in aid efforts in Kosovo following the 1999 intervention by the North Atlantic Treaty Organization in that region. [ABSTRACT FROM AUTHOR]

Effective coordination of humanitarian assistance activities remains elusive. This paper briefly addresses some of the reasons for what is widely perceived as a coordination dilemma in humanitarian affairs and argues for a new conceptualisation of the issue. Rather than continue to request that more authority be vested in a single organisation to secure coordination through top-down control, it contends that it may be timely to consider whether relief agencies involved in an emergency should be reconceived as social networks and efforts made to achieve changes in their organizational cultures that encourage operational coordination across institutional lines. Since such labours imply the need to trust, this article explores what forms of trust might be employed to promote improved coordination among relief institutions and how those relationships could themselves be conceptualised. Finally, while acknowledging that coordination is not costless, it suggests that its effective pursuit may be advantageous even in scenarios where aid organisations balk at cooperating to secure it. [ABSTRACT FROM AUTHOR]

If the sterile neutrino mass matrix in an otherwise conventional see-saw model has a rank less than the number of flavors, it is possible to produce pseudo-Dirac neutrinos. In a two-flavor, sterile rank 1 case, we demonstrate analytic conditions for large active mixing induced by the existence of (and coupling to) the sterile neutrino components. For the three-flavor, rank 1 case, "3+2" scenarios with large mixing also devolve naturally as we show by numerical examples. We observe that, in this approach, small mass differences can develop naturally without any requirement that masses themselves are small. Additionally, we point out that significant three-channel mixing and limited experimental resolution can combine to produce extracted two-channel mixing parameters at variance with the actual values. [ABSTRACT FROM AUTHOR]

We discuss the implications of a new scalar field coupled to neutrinos. [ABSTRACT FROM AUTHOR]

The traditional approach to the identification of peptides in complex biological samples integrally involves the use of tandem mass spectrometry to generate a unique fragmentation pattern in order to accurately assign its identity to a particular protein. In this article we describe the theoretical basis for a new paradigm for the identification of peptides and proteins. This methodology employs the use of accurate mass and peptide isoelectric point (pI) as identification criteria, and represents a change in focus from current tandem mass spectrometry- dominated approaches. A mathematical derivation of the false positive rate associated with accurate mass and pI measurements is presented to demonstrate the utility of the technique. The equations for calculation of the experimental false positive rate allow for the determination of the validity of the data. The false positive rate issue examined in detail here is not restricted to accurate mass-based approaches, but also has application to the tandem mass spectrometry community as well. The theoretical proteomes of Escherichia coli and Rattus norvegicus are used to evaluate the efficacy of this approach. The power of the technique is demonstrated by analyzing a series of peptides with the same monoisotopic masses but with differing isoelectric points. Finally, the speed of algorithm when combined with the experimental peptide analysis has the potential to rapidly accelerate the protein identification process. [ABSTRACT FROM AUTHOR]