The Global Rescue Alarm Net (GRAN): Concept and approaches

The GRAN Experiment is designed to prove a world-wide search and rescue (SAR) system utilizing Omega navigation system signals and geo-synchronous satellites. In order to develop a SAR system, the original NASA Omega Position Locating Equipment (OPLE) experiments have been expanded by the Naval Air Test Center, Patuxent River. Specifically, a fourth frequency (10.880 KHz) has been added experimentally to two Omega transmitters. This will increase line of position (LOP) ambiguities from 72 nautical miles to 360 nmi apart. Algorithms have been developed to resolve the 360 nmi ambiguities. During September and October 1974, two series of tests were conducted with Lincoln Experimental Satellite 6 (LES-6) to demonstrate the position locating potential of the four-frequency Omega concept

Anti-Rods/Rings: A Human Model of Drug-Induced Autoantibody Generation

In recent years, autoantibodies targeting subcellular structures described as the rods and rings pattern in HEp-2 ANA have been presented as a unique case of autoantibody generation. These rod and ring structures (RR) are at least partially composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors, including some IMPDH2 inhibitors. Autoantibodies targeting these relatively unknown structures have been almost exclusively observed in hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferon-alpha/ribavirin (IFN/RBV) combination therapy. To date, anti-RR antibodies have not been found in treatment-naive HCV patients or in patients from any other disease groups, with few reported exceptions. Here, we describe recent advances in characterizing the RR structure and the strong association between anti-RR antibody response and HCV patients treated with IFN/RBV, detailing why anti-RR can be considered a human model of drug-induced autoantibody generation

Surgical Approach for Long-term Survival of Patients With Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 434 Patients.

OBJECTIVES To examine the outcomes of a hepatectomy for intrahepatic cholangiocarcinoma (IHC) and to clarify the prognostic impact of a lymphadenectomy and the surgical margin. Large series of patients who were surgically treated for IHC are scarce. Thus, prognostic factors and long-term survival after resection of IHC remain uncertain. DESIGN Prospective study of patients who were surgically treated for IHC. Clinicopathologic, operative, and long-term survival data were analyzed. SETTING Prospectively collected data of all consecutive patients with pathologically confirmed IHC who had undergone liver resection with a curative intent at 1 of 16 tertiary referral centers were entered into a multi-institutional registry. PATIENTS All consecutive patients who underwent a hepatectomy with a curative intent for IHC (1990-2008) were identified from a multi-institutional registry. RESULTS A total of 434 patients were included in the analysis. Most patients underwent a major or extended hepatectomy (70.0%) and a systematic lymphadenectomy (62.2%). The incidence of lymph node metastases (overall, 36.9%) increased with increased tumor size, with 24.4% of patients with a small IHC (diameter 643 cm) having N1 disease. Almost one-third of patients required an additional major procedure to obtain a R0 resection in 84.6% of the cases. In these patients, the median time of survival was 39 months, and the 5-year survival rate was 39.8%. Lymph node metastases (hazard ratio, 2.21; P < .001), multiple tumors (hazard ratio, 1.50; P = .009), and an elevated preoperative cancer antigen 19.9 level (hazard ratio, 1.62; P = .006) independently predicted an adverse prognosis. Conversely, survival was not influenced by the width of a negative resection margin (P = .61). The potential survival benefit of a lymphadenectomy was assessed with the therapeutic value index, which was calculated to be 5.9 points. CONCLUSIONS Survival rates after a hepatectomy with a curative intent for IHC at tertiary referral centers exceed the survival rates reported in most study series in single institutions, which strengthens the value of an aggressive approach to radical resection. Lymph node metastases and multiple tumors are associated with decreased survival rates, but they should not be considered selection criteria that prevent other patients from undergoing a potentially curative resection. Lymphadenectomy should be considered for all patients

Characterization of the Apical Testis and Fusome Patterning in Drosophila melanogaster, Drosophila simulans, Drosophila pseduoobscura, Drosophila affinis, and Drosophila sechellia

This study uses five different species across the family of Drosophila as a tool to compare the structures of the stem cell niche and fusome within the testes of these species. Three species from Drosophila melanogaster group, D. melanogaster, D. simulans and D. sechellia, and two species from D. obscura group, D. pseudoobscura and D. affinis were observed using confocal microscopy In addition to a general comparison of male reproductive system structure and anatomy, the species were also analyzed for the presence of Fasciclin-III and α-Spectrin. As expected, species from the D. melanogaster group had the same expression pattern for Fasciclin III and α-Spectrin. Species of the obscura group also exhibited the characteristic morphology for the apical complex and fusomes. Interestingly, the testes of D. affinis exhibited the melanogaster group coiled testicular morphology, but the obscura group pattern for the apical complex. We also detected a novel actin structure (which we are calling the “actin cage”) in the apical end of D. sechellia and D. simulans, but not D. melanogaster, that appears to overlap with the hub in the apical testis. The actin cage was not detected in D. affinis or D. pseudoobscura. This work represents the first analysis of testis structures in species other than D. melanogaster

Anti-rods/rings autoantibody generation in hepatitis C patients during interferon-alpha/ribavirin therapy

Chronic inflammation associated with hepatitis C virus (HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon a (IFN-alpha) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies (ANA). Between 20% to 40% of HCV patients treated with IFN-a and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings (RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings (anti-RR) autoantibody production by HCV patients after IFN-alpha/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i. e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5 ' n-monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. RibavirinBrazilian government research foundations National Council for Research and TechnologySao Paulo Government agency Sao Paulo State Research FoundationUniv Fed Sao Paulo, Escola Paulista Med, Div Rheumatol, Rua Botucatu 740, BR-04023062 Sao Paulo, SP, BrazilUniv Florida, Dept Oral Biol, Gainesville, FL 32610 USAFleury Med & Hlth Labs, Div Immunol, BR-04102050 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Div Rheumatol, Rua Botucatu 740, BR-04023062 Sao Paulo, SP, BrazilFAPESP: 2011/12448-0FAPESP: 9028-11-0FAPESP: 305064/2011-8FAPESP: 232711/2014-3Web of Scienc

Immune Response-Dependent Assembly of IMP Dehydrogenase Filaments

Inosine monophosphate dehydrogenase (IMPDH) catalyzes the conversion of IMP to xanthosine monophosphate, the rate-limiting step in de novo guanosine monophosphate (GMP) synthesis. In cultured cells, IMPDH polymerizes into micron-scale filamentous structures when GMP synthesis is inhibited by depletion of purine precursors or by various drugs, including mycophenolic acid, ribavirin, and methotrexate. IMPDH filaments also spontaneously form in undifferentiated mouse embryonic stem cells and induced pluripotent stem cells, hinting they might function in various highly proliferative cell types. Therefore, we investigated IMPDH filament formation in human and murine T cells, which rely heavily on de novo guanine nucleotide synthesis to rapidly proliferate in response to antigenic challenge. We discovered extensive in vivo IMPDH filament formation in mature T cells, B cells, and other proliferating splenocytes of normal, adult B6 mice. Both cortical and medullary thymocytes in young and old mice also showed considerable assembly of IMPDH filaments. We then stimulated primary human peripheral blood mononuclear cells ex vivo with T cell mitogens phytohemagglutinin (PHA), concanavalin A (ConA), or antibodies to CD3 and CD28 for 72 h. We detected IMPDH filaments in 40–60% of T cells after activation compared to 0–10% of unstimulated T cells. Staining of activated T cells for the proliferation marker Ki-67 also showed an association between IMPDH filament formation and proliferation. Additionally, we transferred ovalbumin-specific CD4+ T cells from B6.OT-II mice into B6.Ly5a recipient mice, challenged these mice with ovalbumin, and harvested spleens 6 days later. In these spleens, we identified abundant IMPDH filaments in transferred T cells by immunofluorescence, indicating that IMPDH also polymerizes during in vivo antigen-specific T cell activation. Overall, our data indicate that IMPDH filament formation is a novel aspect of T cell activation and proliferation, and that filaments might be useful morphological markers for T cell activation. The data also suggest that in vivo IMPDH filament formation could be occurring in a variety of proliferating cell types throughout the body. We propose that T cell activation will be a valuable model for future experiments probing the molecular mechanisms that drive IMPDH polymerization, as well as how IMPDH filament formation affects cell function

Partners in the Parks: Field Guide to an Experiential Program in the National Parks (1st edition)

When Joan Digby first proposed taking collegiate honors students into our national parks, I jumped at the chance. Within minutes of reading her email, I not only responded with an enthusiastic “Yes!” but went so far as to volunteer the resources of the Southern Utah University Honors Program to get things started. Nestled among 5 national parks in southwestern Utah, I felt our campus would be a natural focal point for the kind of program Joan envisioned. Within weeks we had laid the groundwork for a proof-of-concept pilot project at nearby Bryce Canyon National Park. Little did I know at the time, but I was taking the first steps on a nationwide journey that would introduce me to 11 amazing national parks, some 47 park rangers, and over 100 outstanding college students—with the prospect of these numbers growing annually. The aim of Partners in the Parks (PITP) from its inception has been to introduce, or reintroduce, collegiate honors students to this country: not the transformed environment that we have constructed on its surface but the bedrock world upon which it rests. Like de Toqueville, Jefferson, Thoreau, Emerson, and so many others, we recognized that the unique place that is America cannot be separated from the land upon which it was built. One valuable way to study and understand it, then, is to visit places where the bones of America lie exposed, often without the veneer of civilization, cultivation, or modernization: places protected by the people to preserve for this and future generations, original American landscapes, and important historical landmarks that illustrate and define what America was, is, and can be. PITP takes students deep into America’s national parks. PITP is a see-America-first program. While we recognize the importance of a global perspective in an overall honors education, our goal is to help students see and understand America before or in addition to going abroad. Indeed, for students without the desire or resources to leave the country, PITP offers many of the same kinds of personal development that make study abroad so valuable. In the Field Notes to Chapter 2, “Growing from Within,” Bill Atwill and Kathleen King, share their experience in Acadia National Park, observing how their students demonstrated valuable growth in the same four key areas that researchers of study abroad programs have identified in their alumni: personal discovery, academic commitment, cultural development, and career development. The student writings in this volume, such as Andy Grube’s “soul expanding” talk with Juste Gatari on the rocky coast of Mount Desert Island, aptly illustrate this important facet of the PITP experience. (See the Field Notes to Chapter 5, “Sitting There in Silence.”

Correction to: Diffusion, outcomes and implementation of minimally invasive liver surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Luca Aldrighetti, Francesca Ratti, Umberto Cillo, Alessandro Ferrero, Giuseppe Maria Ettorre, Alfredo Guglielmi, Felice Giuliante, Fulvio Calise on behalf of the Italian Group of Minimally Invasive Liver Surgery (I GO MILS) The collaborators are: Raffaele Dalla Valle, AOU Parma, Parma; Vincenzo Mazzaferro, Istituto Nazionale Tumori, Milano; Elio Jovine, Ospedale Maggiore, Bologna; Luciano Gregorio De Carlis, Ospedale Niguarda Ca\u2019 Granda, Milano; Ugo Boggi, AOU Pisana, Pisa; Salvatore Gruttadauria, ISMETT, Palermo; Fabrizio Di Benedetto, AOU Policlinico di Modena, Modena; Paolo Reggiani, Ospedale Maggiore Policlinico, Milano; Stefano Berti, Ospedale Civile S.Andrea, La Spezia; Graziano Ceccarelli, Ospedale San Donato, Arezzo; Leonardo Vincenti, AOU Consorziale Policlinico, Bari; Giulio Belli, Ospedale SM Loreto Nuovo, Napoli; Guido Torzilli, Istituto Clinico Humanitas, Rozzano; Fausto Zamboni, Ospedale Brotzu, Cagliari; Andrea Coratti, AOU Careggi, Firenze; Pietro Mezzatesta, Casa di Cura La Maddalena, Palermo; Roberto Santambrogio, AO San Paolo, Milano; Giuseppe Navarra, AOU Policlinico G. Martino, Messina; Antonio Giuliani, AO R.N. Cardarelli, Napoli; Antonio Daniele Pinna, Policlinico Sant\u2019Orsola Malpighi, Bologna; Amilcare Parisi, AO Santa Maria di Terni, Terni; Michele Colledan, AO Papa Giovanni XXIII, Bergamo; Abdallah Slim, AO Desio e Vimercate, Vimercate; Adelmo Antonucci, Policlinico di Monza, Monza; Gian Luca Grazi, Istituto Nazionale Tumori Regina Elena, Roma; Antonio Frena, Ospedale Centrale, Bolzano; Giovanni Sgroi, AO Treviglio-Caravaggio, Treviglio; Alberto Brolese, Ospedale S.Chiara, Trento; Luca Morelli, AOU Pisana, Pisa; Antonio Floridi, AO Ospedale Maggiore, Crema; Alberto Patriti, Ospedale San Matteo degli Infermi, Spoleto; Luigi Veneroni, Ospedale Infermi AUSL Romagna, Rimini; Giorgio Ercolani, Ospedale Morgagni Pierantoni, Forl\uec; Luigi Boni, AOU Fondazione Macchi, Varese; Pietro Maida, Ospedale Villa Betania, Napoli; Guido Griseri, Ospedale San Paolo, Savona; Andrea Percivale, Ospedale Santa Corona, Pietraligure; Marco Filauro, AO Galliera, Genova; Silvio Guerriero, Ospedale San Martino, Belluno; Giuseppe Tisone, Policlinico Tor Vergata, Roma; Raffaele Romito, AOU Maggiore della Carit\ue0, Novara; Umberto Tedeschi, AOU Integrata Verona, Verona; Giuseppe Zimmitti, Fondazione Poliambulanza, Brescia

Evaluación del target strength de juveniles de atún rojo (Thunnus thynnus) en jaulas marinas

En los últimos años, el Instituto Español de Oceanografía (IEO) ha maximizado sus esfuerzos en desarrollar mecanismos para la cría en cautividad del atún rojo (Thunnus thynnus), cuyo ciclo completo está a punto de cerrarse. Este trabajo presenta los resultados obtenidos tras realizar mediciones acústicas con una ecosonda científica y un transductor split-beam en jaulas marinas donde los atunes, nacidos en cautividad, se separan en tres tamaños. La combinación de los datos acústicos y de los muestreos biométricos (obtenidos ópticamente) permite establecer una relación entre la longitud de los peces y el valor del target stregth (TS) devuelto por dichos peces.In recent years, the Spanish Institute of Oceanography (IEO) has maximized its efforts on developing mechanisms for the breeding of bluefin tuna (Thunnus thynnus), whose complete cycle is near to be closed. In this paper, acoustic measurements performed on young tuna cages (with scientific echosounder and split-beam transducer) are presented. Tuna housed in the cages were born in captivity and they are divided in three cages according to their size. The combination of the acoustic and biometric data (obtained with stereoscopic system) allow to establish a relationship between representative tuna length in each cage and the target strength (TS)