Chiral-Yang-Mills theory, non commutative differential geometry, and the need for a Lie super-algebra

In Yang-Mills theory, the charges of the left and right massless Fermions are independent of each other. We propose a new paradigm where we remove this freedom and densify the algebraic structure of Yang-Mills theory by integrating the scalar Higgs field into a new gauge-chiral 1-form which connects Fermions of opposite chiralities. Using the Bianchi identity, we prove that the corresponding covariant differential is associative if and only if we gauge a Lie-Kac super-algebra. In this model, spontaneous symmetry breakdown naturally occurs along an odd generator of the super-algebra and induces a representation of the Connes-Lott non commutative differential geometry of the 2-point finite space.Comment: 17 pages, no figur

AceView: a comprehensive cDNA-supported gene and transcripts annotation

BACKGROUND: Regions covering one percent of the genome, selected by ENCODE for extensive analysis, were annotated by the HAVANA/Gencode group with high quality transcripts, thus defining a benchmark. The ENCODE Genome Annotation Assessment Project (EGASP) competition aimed at reproducing Gencode and finding new genes. The organizers evaluated the protein predictions in depth. We present a complementary analysis of the mRNAs, including alternative transcript variants. RESULTS: We evaluate 25 gene tracks from the University of California Santa Cruz (UCSC) genome browser. We either distinguish or collapse the alternative splice variants, and compare the genomic coordinates of exons, introns and nucleotides. Whole mRNA models, seen as chains of introns, are sorted to find the best matching pairs, and compared so that each mRNA is used only once. At the mRNA level, AceView is by far the closest to Gencode: the vast majority of transcripts of the two methods, including alternative variants, are identical. At the protein level, however, due to a lack of experimental data, our predictions differ: Gencode annotates proteins in only 41% of the mRNAs whereas AceView does so in virtually all. We describe the driving principles of AceView, and how, by performing hand-supervised automatic annotation, we solve the combinatorial splicing problem and summarize all of GenBank, dbEST and RefSeq into a genome-wide non-redundant but comprehensive cDNA-supported transcriptome. AceView accuracy is now validated by Gencode. CONCLUSION: Relative to a consensus mRNA catalog constructed from all evidence-based annotations, Gencode and AceView have 81% and 84% sensitivity, and 74% and 73% specificity, respectively. This close agreement validates a richer view of the human transcriptome, with three to five times more transcripts than in UCSC Known Genes (sensitivity 28%), RefSeq (sensitivity 21%) or Ensembl (sensitivity 19%)

A tailored approach in lymph node positive perihilar cholangiocarcinoma

Introduction: Surgical resection or liver transplantation remain the only curative treatments that can offer long-term survival for perihilar cholangiocarcinoma (PHC). PHC involves the confluence of the bilateral hepatic ducts where the main portal and hepatic arterial branches are near one another, thereby requiring an extended hepatectomy for achieving a negative resection margin (R0). Whenever feasible, extended right hepatectomy is believed to be superior to extended left hepatectomy to obtain R0 status, for anatomical reasons. However, right hepatectomy is associated with significantly higher postoperative morbidity and mortality. Patients with lymph node metastases (N+) are at high risk for tumor recurrence, even after radical surgical resection. Therefore, it remains unclear whether the current surgical principles of extended right hepatectomy outweigh the high morbidity and mortality of this approach in N+ patients. Patients and methods: Between 2005 and 2015, 231 patients with a newly PHC received a curative intended major hepatectomy (MH) at the department of visceral surgery at Charité – Universitätsmedizin Berlin, Campus Virchow or Campus Mitte. In this retrospective cohort study, all data were collected from medical records, and long-term survival was analyzed using the Kaplan-Meier method. Results: The 231 patients included in this study underwent MH for PHC with 1-, 3-, and 5-year overall survival (OS) rates and disease-free survival (DFS) rates of 72%, 48%, 36% and 60%, 22%, 12%, respectively. Within the whole cohort, patients with R0 status had significantly better OS and DFS compared to patients with a positive resection margin (R1; both p 0.05). Extended left hepatectomy was associated with improved OS and DFS when compared to extended right hepatectomy (p = 0.008 and p = 0.003) within this N+ subgroup. Furthermore, patients undergoing extended left hepatectomy were more likely to receive adjuvant chemotherapy (p = 0.022). This is of great importance as adjuvant chemotherapy, in addition to histopathological grading (p = 0.041), was the only independent prognostic factor for N+ patients (p = 0.002). Conclusions: Patients with PHC and N+ status might benefit more from locally less aggressive operation concepts, as this involves a lower morbidity and therefore offers the chance to improve the survival rate through adjuvant chemotherapy. Preoperative lymph node sampling might help to identify patients who actually benefit from radical surgery approaches.Einleitung Die chirurgische Resektion oder Lebertransplantation stellen immer noch die einzige kurative Behandlungsmöglichkeit des Perihilären Cholangiokarzinoms (PHC) dar, die Langzeitüberleben ermöglichen. Das PHC befindet sich an der Bifurkation des Ductus choledochus in unmittelbarer Nähe der Portalvene und Aa. hepaticae, sodass in der Regel eine erweiterte Leberresektion erforderlich ist, um einen freien Resektionsrand zu erhalten. Wann immer es technisch möglich ist, gilt die erweiterte Rechtsresektion der erweiterten Linksresektion gegenüber aus anatomischen Gründen als überlegen, um einen Tumor-freien Resektionsrand zu erhalten. Patienten mit Lymphknotenmetastasen (N+) haben ein hohes Risiko für ein Tumor- Rezidiv, auch nach einer radikalen Resektion. Daher bleibt unklar, ob die gegenwärtige radikale Operationsstrategie der erweiterten Rechtsresektion die hohe Morbidität und Mortalität dieses Ansatzes bei N+ Patienten überwiegt. Patienten und Methodik Zwischen 2005 und 2015 erhielten 231 Patienten mit neu diagnostiziertem PHC eine kurativ intendierte Major Hepatektomie (MH) in der Abteilung für Viszeralchirurgie am Universitätsklinikum Charité Campus Virchow und Campus Mitte. In dieser retrospektiven Kohortenstudie wurden alle Daten aus Krankenakten erhoben und das Langzeitüberleben mit Hilfe der Kaplan Meier Methode ausgewertet. Ergebnisse Die 231 Patienten, die in dieser Studie eingeschlossen wurden, unterzogen sich einer MH für PHC mit 1,-3-, und 5-Jahres Gesamtüberlebensrate (OS) und Rezidivfreien Überlebensraten (DFS) von jeweils 72%, 48%, 36% und 60%, 22%, 12%. Dabei waren innerhalb der gesamten Kohorte das OS und das DFS bei Patienten mit Tumor-freiem Resektionsrand (R0) signifikant besser, verglichen mit dem der Patienten mit befallenem Resektionsrand (R1). Von Bedeutung war, dass sich in der N+ Patientenuntergruppe (n = 109, 47%) das Gesamtüberleben und das Rezidivfreie Überleben hinsichtlich eines R0 oder R1 Resektionsrandes nicht unterschied (beide p > 0,05). Die erweiterte Linksresektion war mit einem besseren OS und DFS assoziiert, verglichen mit der erweiterten Rechtsresektion (p = 0,008 und p = 0,003) innerhalb dieser N+ Untergruppe. Darüber hinaus war es bei Patienten, die einer erweiterten Linksresektion unterzogen wurden wahrscheinlicher, dass sie eine adjuvante Chemotherapie erhielten (p = 0,022). Dies ist von großer Bedeutung, da die adjuvante Chemotherapie, neben der histologischen Graduierung (p = 0,041), der einzige unabhängige prognostische Faktor für N+ Patienten (p = 0,002) war. Schlussfolgerung Patienten mit PHC und positivem Lymphknotenstatus profitieren möglicherweise mehr von weniger aggressiven Operationsmethoden, da diese mit einer geringeren Morbidität einhergehen und damit die Chance eines besseren Überlebens durch adjuvante Chemotherapie ermöglicht. Präoperative Lymphknoten-Diagnostik könnte dazu beitragen, diejenigen Patienten zu identifizieren, die tatsächlich von einer radikalen Herangehensweise profitieren

Infectivity decline of an RNA plant virus by increased mutagenesis supports the lethal defection model in vivo

Lethal mutagenesis is a new antiviral therapy based on increasing the mutation rate by using mutagenic base and nucleoside analogues whose molecular mechanisms are not fully understood. Most of the research has been conducted on animal RNA viruses in cell culture and, to a lesser extent, in vivo. There is experimental evidence supporting the model of lethal defection for lethal mutagenesis of RNA viruses. In this model, viral genomes with a low degree of mutation and low specific infectivity, termed "defectors", exert an interfering activity leading to virus loss. Lethal mutagenesis of plant viruses has not been addressed yet despite being excellent in vivo model systems that develop systemic infections, undergo rapid bottlenecks and pose no ethical issues. Here, we address lethal mutagenesis in vivo of Tobacco mosaic virus (TMV), a single-stranded positive RNA virus of 6.4 Kb. Nicotiana tabacum plants cultured in vitro were treated with 25, 50 and 100 µg/ml of the base analogue 5-fluorouracil (FU) and 24 h later were inoculated with 50 lesion forming units (lfu) of TMV. We analyzed the infectivity, viral load and mutant spectra of viral populations after 5 and 10 days of treatment, as well as of populations that went 10 days of treatment followed by 21 days of ex vitro growth in the absence of FU. The results show that TMV infectivity decreases when treated with 50 and 100 µg/ml FU for 10 days. TMV mutagenized populations grown without FU reach infectivity values higher than untreated populations. Predominant mutations in FU-treated populations with decreased infectivity at 10 dpi are U→C, A→G and G→A transitions, which are expected due to the action of FU. TMV replication is not affected by FU at any dose and there are no imbalances of ribonucleotide triphosphate pools measured by HPLC. No differences in mutation frequencies and Shannon Entropies between control and FU-treated populations with declined infectivity were found. However, we did found a dose-dependent decrease of specific infectivity in FU-treated populations, but not in untreated samples, as well as dominance of molecules with a low degree of mutation. Specific infectivity recovered to control levels after 21 days of growth without the analogue. Altogether, our results suggest that TMV defector molecules mediate the decrease in TMV infectivity. This is the first report that addresses the molecular basis of lethal defection in vivo using an RNA plant virus.Junta de Andalucía (P09-CVI-5428 y P10-CVI-6561), Plan Nacional I+D+i (BFU2007-65080 BMC) y Universidad de Málaga (Plan propio

Topologically massive nonabelian BF models in arbitrary space-time dimensions

This work extends to the D-dimensional space-time the topological mass generation mechanism of the nonabelian BF model in four dimensions. In order to construct the gauge invariant nonabelian kinetic terms for a (D-2)-form B and a 1-form A, we introduce an auxiliary (D-3)-form V. Furthermore, we obtain a complete set of BRST and anti-BRST transformation rules of the fields using the so called horizontality condition, and construct a BRST/anti-BRST invariant quantum action for the model in D-dimensional space-time.Comment: 7 page

Extension of the osp(m|n)~ so(m-n) Correspondence to the Infinite-Dimensional Chiral Spinors and Self Dual Tensors

The spinor representations of the orthosymplectic Lie superalgebras osp(m|n) are considered and constructed. These are infinite-dimensional irreducible representations, of which the superdimension coincides with the dimension of the spinor representation of so(m-n). Next, we consider the self dual tensor representations of osp(m|n) and their generalizations: these are also infinite-dimensional and correspond to the highest irreducible component of the $p^{th}$ power of the spinor representation. We determine the character of these representations, and deduce a superdimension formula. From this, it follows that also for these representations the osp(m|n)~ so(m-n) correspondence holds