33 research outputs found

    An analysis of experimental data on entrance effects in circular thrust bearings

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    Empirical method for considering entrance effects in computing flow rates and load capacities of circular thrust bearing

    Investigation of new methods for increasing thermal contact conductance in a vacuum Final report

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    Increasing thermal contact conductance in vacuu

    Review of literature on thermal contact conductance in a vacuum Final report

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    Conductive heat transfer across solid-solid interface in vacuu

    Putative role of circulating human papillomavirus DNA in the development of primary squamous cell carcinoma of the middle rectum: A case report

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    Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines. In the stroma nearby the tumor mass we were able to demonstrate the presence of virus DNA in the stromal compartment, supporting its potential to be transferred from epithelial cells to the stromal ones. Thus, this case report favors the notion that human papillomavirus DNA can be vehiculated by exosomes in the blood of neoplastic patients and that it can be transferred, at least in vitro, to normal and neoplastic cells. Furthermore, we showed the presence of viral DNA and RNA in pluripotent stem cells of non-tumor tissue, suggesting that after viral integration (as demonstrated by p16 and RNA in situ hybridization positivity), stem cells might have been activated into cancer stem cells inducing neoplastic transformation of normal tissue through the inactivation of p53, p21, and Rb. It is conceivable that the virus has elicited its oncogenic effect in this specific site and not elsewhere, despite its wide anatomical distribution in the patient, for a local condition of immune suppression, as demonstrated by the increase of T-regulatory (CD4/CD25/FOXP3 positive) and T-exhausted (CD8/PD-1positive) lymphocytes and the M2 polarization (high CD163/CD68 ratio) of macrophages in the neoplastic microenvironment. It is noteworthy that our findings depicted a static picture of a long-lasting dynamic process that might evolve in the development of tumors in other anatomical sites

    Phase Ib study of poly-epitope peptide vaccination to thymidylate synthase (TSPP) and GOLFIG chemo-immunotherapy for treatment of metastatic colorectal cancer patients

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    ABSTRACT: Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication and main 5′-fluorouracil (5′-FU) target. TSPP/VAC1 is a multi-arm trial phase-Ib trial program aimed to investigate the toxicity and biomodulatory activity of a poly-epitope-peptide vaccine to TS (TSPP) in cancer patients (pts). Here, we present the results of the TSPP/VAC1/arm C trial aimed to evaluate TSPP in combination with chemo-immunotherapy in pretreated metastatic colo-rectal cancer (mCRC) pts. Twenty-nine pts, 14 males and 15 females, received poly-chemotherapy with gemcitabine [GEM; 1,000 mg/sqm, day-1], oxaliplatin [OX; 80 mg/sqm, day-2], levofolinate [100 mg/sqm, days 1–2], bolus/infusional 5′-FU [400 mg/800 mg/sqm, days 1–2], sargramostim [50 ÎĽg, days 3–7/q30], and interleukin-2 [sc. 0.5 MIU twice a day, days 8–14/18–30] [GOLFIG-regimen]. Seventeen pts received sc. TSPP injections at escalating dosage [3 pts, 100 Âµg (DL-1); 3 pts, 200 Âµg (DL-2) and 11pts, 300 Âµg (DL-3)] one week after each chemotherapy cycle (concomitant module), while 10 out 12 pts received TSPP (300 Âµg) after 12 GOLFIG courses [dose level (DL)-0] (sequential module). TSPP MTD was not achieved. Adverse events consisted in swelling/erythema at injection sites (17 cases), G1–2 haematological (16 cases) and gastro-enteric events (12), fever, rhinitis, conjunctivitis, and poly-arthralgia and rise in auto-antibodies [ANA, ENA, c-ANCA, p-ANCA in the DL1–3 pts]. Both treatment-modules showed immunomodulating and antitumor activity (disease-control-rate, DL1–3 and DL0 were 70.6% and 83.3%, respectively) with a better survival recorded in the second group [median OS DL1–3 vs. DL0 = 8 vs. 16 mo, p = 0.049]. The promising long-term survival produced by the sequential treatment module deserves further phase II evaluation

    Growing Opportunities for Equitable, Interdisciplinary Undergraduate Food Systems Education: A Review of Food Systems Education at Land-Grant Institutions and Development of Open-Access Materials

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    Post-secondary coursework related to agriculture and the food supply has been at the core of the United States' land-grant system for more than 150 years. However, as the complexity of food systems has grown, so too have critiques that the education provided in these programs is too narrow to adequately prepare graduates to address pressing food systems issues. In response, some higher education institutions have developed degrees in food systems. To support development of this burgeoning field, we created, tested, and refined four evidence-informed, interdisciplinary, equity-oriented, open-access teaching modules. These modules are based on our experience conducting a multi-site, multi-year transdisciplinary investigation of subsidized, or “cost-offset”, community supported agriculture and a survey asking instructors at land-grant institutions (n = 66) about topic offerings and current unmet needs for instructional materials. Our collaboration illuminated the potential and challenges of food systems research; underscored the value of transdisciplinary research teams; and identified several equity-oriented topics related to the design, implementation, and evaluation of local food initiatives suitable for advancing sustainable foods systems education. Instructors reported that the most helpful teaching aids would be case studies, lesson plans with active learning components, and reference lists with relevant peer-reviewed publications. The final modules seek to shed light on the complexity of food systems projects and build knowledge, vocabularies, and skills across disciplines engaged with food systems. Per instructor-defined needs, each module features a case study, active-learning activities, and references. We anticipate that the adaptable modules will be suitable for a wide range of students and courses

    Adhesive bonded orthotropic structures with a part-through crack

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