Macro-routing: a new hierarchical routing protocol

In a continually evolving Internet, tools such as quality of service routing must be used in order to accommodate user demands. QoS routing raises scalability issues within very large networks, which can he avoided by using hierarchical routing strategies. However, such strategies can lead to inaccurate path selection due to the aggregation process. To avoid such problems, we propose a hierarchical routing protocol, called macro-routing, which can distribute the route computation more efficiently throughout the network using mobile agents. It processes more detailed information than conventional hierarchical routing protocols, so is more likely to find the best path between source and destination. Also, by using mobile agents, more than one available path can be found. This provides a fast recovery mechanism, where no protocol restart is needed in a failure situation

Širenje pajasena (Ailanthus altissima (Mill.) Swingle) u urbanom području: primjer grada Osijeka (Republika Hrvatska)

Three-of-heaven (Ailanthus altissima (Mill.) Swingle) is considered as one of the most invasive plant species worldwide in rural and urban environment. Although tree-of-heaven is commonly observed throughout the city of Osijek (Croatia), its prevalence and frequency has not been documented. This study has been conducted from May to September 2022 in the streets of Osijek to determine the distribution, abundance and competitive advantage of this species. A survey was performed by sampling randomly selected 20 quadrats in each city district, having together 140 phytocoenological records, and presence-absence of tree-of heaven was recorded in each plot. Where present at urban habitats, the number of threes were recorded and categorized approximately by the diameter at breast height (dbh). Habitats were distinguished as follows: alleys, abandoned private areas, public areas, ruderal sites, cracked walls and road edges. Risk assessment analysis were prepared by combining quantitative (number of trees per plots) and qualitative (four categories: biological characteristics and dispersal abilities, ecological amplitude and distribution, ecological impact, and difficulty to control) data. There was e recorded a total of 189 tree-of-heaven, occurring both as solitary plants or in developed stands. The habitat types with the highest rate of tree-of-heaven are abandoned private areas (34%) followed by public areas (31%). Out of the total, 55% of the recorded tree-of heaven are young individuals belonging to the very small and small diameter classes, and are mainly present on abandoned private and public areas. Ecological impact and biological characteristics are primary course of its landscape spread.Pajasen (Ailanthus altissima (Mill.) Swingle) je jedna od najinvazivnijih biljnih vrsta širom svijeta kako u ruralnim, tako i u urbanim područjima. Premda je pajasen široko rasprostranjen na području grada Osijeka (Hrvatska), njegova prevalencija i frekvencija još do sada nije zabilježena. Istraživanje je sprovedeno od svibnja do rujna 2022. na osječkim ulicama kako bi se utvrdila njegova distribucija, abundacija i kompetitivna sposobnost. Istraživanje je obavljeno metodom slučajno odabranih kvadrata unutar svakog gradskog kvarta, što je ukupno iznosilo 140 fitocenoloških snimaka. Na plohama gdje je utvrđen pajasen, pobrojane su sve individue i kategorizirane su prema obujmu prsnog promjera stabla. Plohe su razvrstane kao: ulice, napušteni privatni posjedi, javne površine, ruderalna staništa, napuknuti zidovi i rubovi puteva. Procjena rizika pripremljena je kombinacijom kvantitativnih (broj individua po plohi) i kvalitativnih kategorija (biološka obilježja i sposobnost širenja, ekološke amplitude i rasprostranjenost, ekološki utjecaj i poteškoće u suzbijanju). Utvrdili smo ukupno 189 stabala pajesena, koji su bili prisutni i kao solitarna drva a također i oblikujući nakupine. Od urbanih staništa, s najvećim postotkom (34 %) pajasen je utvrđen na napuštenim privatnim posjedima a zatim slijede javne površine (31 %). Od ukupno zabilježenih vrsta, 55 % pajasena su mladice koje pripadaju kategoriji stabala s vrlo malim ili malim promjerom debla i uglavnom su rašireni na napuštenim privatnim posjedima i javnim površinama. Ekološka i biološka obilježja pajasena primarno su zaslužna za njegovo širenje urbanim prostorima grada Osijeka

Immunization with a Peptide Containing MHC Class I and II Epitopes Derived from the Tumor Antigen SIM2 Induces an Effective CD4 and CD8 T-Cell Response

Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens. Based on our prior genome-wide interrogation of human prostate cancer tissues to identify genes over-expressed in cancer and absent in the periphery, we targeted SIM2 as a prototype autologous tumor antigen for these studies. Using humanized transgenic mice we found that the 9aa HLA-A*0201 epitope, SIM2237–245, was effective at inducing an antigen specific response against SIM2-expressing prostate cancer cell line, PC3. Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-γ response in CD8 T cells to the HLA-A*0201-restricted SIM2237–245 epitope, and an IL-2 response by CD4 T cells to the SIM2240–254 epitope. This peptide was also effective at inducing CD8+ T-cells that responded specifically to SIM2-expressing tumor cells. Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers

The Role of the Transcription Factor SIM2 in Prostate Cancer

Background: Recent reports have suggested a possible involvement of Single-minded homolog 2 (SIM2) in human solid cancers, including prostate cancer. However, the exact role of SIM2 in cancer in general, and in prostate cancer in particular, remains largely unknown. This study was designed to elucidate the role of SIM2 in prostate cancer using a shRNA-based approach in the PC3 prostate cancer cell line. Methods: Lentiviral shRNAs were used to inhibit SIM2 gene and protein levels in PC3 cells. Quantitative RT-PCR and branched DNA were performed to evaluate transcript expression. SIM2 protein expression level was measured by western blot. Profiling of gene expression spanning the whole genome, as well as polar metabolomics of several major metabolic pathways was performed to identify major pathway dysregulations. Results: SIM2 gene and protein products were significantly downregulated by lenti-shRNA in PC3 cell line. This low expression of SIM2 affected gene expression profile, revealing significant changes in major signaling pathways, networks and functions. In addition, major metabolic pathways were affected. Conclusion: Taken together, our results suggest an involvement of SIM2 in key traits of prostate tumor cell biology an

A safety-modified SV40 Tag developed for human cancer immunotherapy

Simian virus 40 (SV40)-like DNA sequences have been found in a variety of human tumors, raising the possibility that strategies targeting SV40 may provide a potential avenue for immunotherapy directed against SV40 large T Antigen (Tag)-expressing tumors. We generated a recombinant vaccinia (vac-mTag) expressing mTag and herein assessed the ability of mTag to transform cells and to interact with anti-oncoproteins, as well as screened for the presence of potential HLA-A2.1-restricted epitopes within mTag. We found that transfection of cells with mTag did not lead to their transformation. Also, we demonstrated that mTag protein is degraded rapidly in cells. In addition, our work revealed that mTag did not physically interact with certain anti-oncoproteins. Finally, two potential HLA-A2.1-restricted functional epitopes within mTag sequence were identified. Our results show that mTag lacks the oncogenecity of full-length Tag and harbors potential HLA-A2.1-restricted immunogenic epitopes, hence suggesting the safety of vac-mTag for use in cancer immunotherapy

Detection of prostate cancer-specific transcripts in extracellular vesicles isolated from post-DRE urine

Background: The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient’s risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder- specific transcripts and known prostate cancer biomarkers in urine EVs. Methods: Cell pellets and EVs were recovered from post-DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder- associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. Results: RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE urine EVs indicated that prostate-specific transcripts were more abundant than kidney- or bladder-specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer-associated genes PCA3 and ERG. Conclusions: Post-DRE urine EVs are a viable source of prostate-derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre- biopsy prostate cancer detection

Localized prostate cancer in Norway, the United States, and Spain: between-country differences of variables before treatment among patients eligible for curative treatment

Between-country differences in medical and sociodemographic variables, and patient-related outcomes (PROs) before treatment might explain published variations of side effects after radical prostatecomy (RP) or radiotherapy (RAD) for prostate cancer (PCa). This hypothesis was tested among 1908 patients from the United States, Spain, and Norway. Significant between-country differences were observed for most factors investigated before treatment. The observations should be considered in comparison of the frequency and severity of internationally published studies. Background: In men with PCa, large variations of PROs after RP or high-dose RAD might be related to betweencountry differences of medical and sociodemographic variables, and differences in PROs before treatment in the sexual and urinary domains. Patients and Methods: In 1908 patients with localized PCa from Norway, the United States, or Spain, the relation between medical (prostate-specific antigen, Gleason score, cT-category) and sociodemographic variables (age, education, marital status) before treatment was investigated. Using the Expanded Prostate Cancer Index Composite questionnaire, PROs before treatment within the sexual and urinary domains were also considered. Results: Compared with the European patients, American patients were younger, fewer had comorbid conditions, and more had a high education level. Fifty-three percent of the US men eligible for RP had low-risk tumors compared with 42% and 31% among the Norwegian and the Spanish patients, respectively. Among the Spanish RAD patients, 54% had had low-risk tumors compared with 34% of the American and 21% of the Norwegian men planned for RAD, respectively. Compared with the European patients, significantly fewer US patients reported moderate or severe sexual dysfunction and related problems. In most subgroups, the number of patients with sexual or urinary dysfunction exceeded that of patients with bother related to the reported dysfunction. Conclusion: Statistically significant between-country differences were observed in medical and sociodemographic variables, and in PROs before treatment within the sexual and urinary domains. Large differences between reported dysfunction and related problems within the sexual and urinary domains indicate that dysfunction and bother should be reported separately in addition to calculation of summary scores. The documented differences, not at least regarding PROs, might in part explain the large variation of side effects after treatment evident in the medical literatur

Antigen-specific tumor vaccine efficacy in vivo against prostate cancer with low class I MHC requires competent class II MHC

BACKGROUND Cancers can escape immune recognition by means of evading class I major histocompatibility complex (MHC) -mediated recognition by cytotoxic T lymphocytes. However, immunization strategies targeting defined tumor-associated antigens have not been extensively characterized in murine prostate cancer models. Therefore, we evaluated antigen-specific, antitumor immunity after antigen-encoding vaccinia immunization against mouse prostate cancer cells expressing a model tumor-associated antigen (Β-galactosidase) and exhibiting partially deficient class I MHC. METHODS AND RESULTS Low class I MHC expression in Β-galactosidase–expressing D7RM-1 prostate cancer cells was shown by fluorescence activated cell sorting, and deficient class I MHC-mediated antigen presentation was shown in resistance of D7RM-1 to cytolysis by Β-galactosidase–specific cytotoxic T lymphocytes (CTL). Despite partially deficient class I MHC presenting function, immunization with vaccinia encoding Β-galactosidase conferred antigen-specific protection against D7RM-1 cancer. Antigen-specific immunity was recapitulated in Β 2 m knockout mice (with deficient class I MHC and CTL function), confirming that class I MHC antigen presentation was not required for immunity against tumor partially deficient in class I MHC. Conversely, antigen-specific antitumor immunity was abrogated in A b Β knockout mice (with deficient class II MHC and helper T cell function), demonstrating a requirement for functional class II MHC. Resistant tumors from the otherwise effectively immunized Β 2 m knockout mice (among which tumor progression had been reduced or delayed) showed reduced target antigen expression, corroborating antigen-specificity (and showing an alternative immune escape mechanism), whereas antigen expression (like tumor growth) was unaffected among A b Β knockout mice. CONCLUSION Our results demonstrate that class I MHC-restricted antigen presentation and CTL activity is neither necessary nor sufficient for antigen-encoding vaccinia immunization to induce protective immunity against class I MHC-low tumors, whereas host class II MHC-mediated antigen presentation facilitates antigen-specific immunity against prostate cancer in vivo. Reduced expression of the target antigen developed rapidly in vivo as an immune escape mechanism for such cancers. Prostate 53: 183–191, 2002. © 2002 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34762/1/10136_ftp.pd