FuSSI-Net: Fusion of Spatio-temporal Skeletons for Intention Prediction Network

Pedestrian intention recognition is very important to develop robust and safe autonomous driving (AD) and advanced driver assistance systems (ADAS) functionalities for urban driving. In this work, we develop an end-to-end pedestrian intention framework that performs well on day- and night- time scenarios. Our framework relies on objection detection bounding boxes combined with skeletal features of human pose. We study early, late, and combined (early and late) fusion mechanisms to exploit the skeletal features and reduce false positives as well to improve the intention prediction performance. The early fusion mechanism results in AP of 0.89 and precision/recall of 0.79/0.89 for pedestrian intention classification. Furthermore, we propose three new metrics to properly evaluate the pedestrian intention systems. Under these new evaluation metrics for the intention prediction, the proposed end-to-end network offers accurate pedestrian intention up to half a second ahead of the actual risky maneuver.Comment: 5 pages, 6 figures, 5 tables, IEEE Asilomar SS

Murine Polyomavirus Virus-Like Particles Carrying Full-Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor

Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies

CD4+ and CD8+ T Cells Can Act Separately in Tumour Rejection after Immunization with Murine Pneumotropic Virus Chimeric Her2/neu Virus-Like Particles

BACKGROUND: Immunization with murine pneumotropic virus virus-like particles carrying Her2/neu (Her2MPtVLPs) prevents tumour outgrowth in mice when given prophylactically, and therapeutically if combined with the adjuvant CpG. We investigated which components of the immune system are involved in tumour rejection, and whether long-term immunological memory can be obtained. METHODOLOGY AND RESULTS: During the effector phase in BALB/c mice, only depletion of CD4+ and CD8+ in combination, with or without NK cells, completely abrogated tumour protection. Depletion of single CD4+, CD8+ or NK cell populations only had minor effects. During the immunization/induction phase, combined depletion of CD4+ and CD8+ cells abolished protection, while depletion of each individual subset had no or negligible effect. When tumour rejection was studied in knock-out mice with a C57Bl/6 background, protection was lost in CD4-/-CD8-/- and CD4-/-, but not in CD8-/- mice. In contrast, when normal C57Bl/6 mice were depleted of different cell types, protection was lost irrespective of whether only CD4+, only CD8+, or CD4+ and CD8+ cells in combination were eradicated. No anti-Her2/neu antibodies were detected but a Her2/neu-specific IFNgamma response was seen. Studies of long-term memory showed that BALB/c mice could be protected against tumour development when immunized together with CpG as long as ten weeks before challenge. CONCLUSION: Her2MPtVLP immunization is efficient in stimulating several compartments of the immune system, and induces an efficient immune response including long-term memory. In addition, when depleting mice of isolated cellular compartments, tumour protection is not as efficiently abolished as when depleting several immune compartments together

Vaccination against Her2/neu - expressing cancer using chimeric virus-like particles

Thanks to the development of vaccines, children are these days protected against infectious diseases like polio, diphtheria and tetanus simply by receiving a few injections. Imagine a scenario where these injections would also result in protection against cancer. Vaccines against virus-induced cancer such as liver and cervical cancer are indeed already in use. Intense research is now focused on the generation of vaccines for protection also against cancer not induced by viruses. The overall aim of this thesis was to develop and determine the pre-clinical efficacy of a vaccine against tumours expressing the antigen Her2/neu. Polyomaviruses are small non-enveloped viruses that are widespread in the population, and probably harmless as long as the immune system is normal. The viral capsid is composed of three structural proteins, the major structural protein VP1, and the two minor proteins VP2 and VP3. The mouse is host to two known polyomaviruses, murine polyomavirus (MPyV) and murine pneumotropic virus (MPtV), respectively. It was known from before that VP1 of MPyV could self-assemble into viral capsids known as virus-like particles (VLPs), named so because of their morphological resemblance to natural viruses. In paper I, we showed that VP1 of MPtV could also self-assemble into VLPs, which were rapidly internalized by all tested cell types, including dendritic cells. However, the VLPs were not very efficient as vectors for gene therapy, possibly due to poor delivery of DNA into the nucleus of target cells. The combination of efficient cellular uptake and poor nuclear delivery indicated that the VLPs could be more efficient as carriers of proteins for presentation to the immune system, since delivery into the cytoplasm would be sufficient in that case. We therefore attached Her2/neu to the inside of VLPs of both MPyV and MPtV and obtained so-called chimeric VLPs (cVLPs). In papers II and III, we showed that Her2/neu-cVLPs could protect against outgrowth of transplantable Her2/neu-expressing tumours in normal mice, as well as against spontaneously arising Her2/neu-positive carcinomas in transgenic mice. Her2/neu-cVLPs from MPtV also induced immunological memory and protected against tumour out-growth in a therapeutic setting. The purpose of paper IV was to determine the immune mechanisms responsible for tumour protection. We could demonstrate that Her2/neu-cVLPs induced Her2/neu-specific CD8+ T cells, but did not induce anti-Her2/neu antibodies. However, we observed that mice were protected against tumour development also after depletion of either CD8+, or CD4+ T cells, but not after combined depletion of CD4+ and CD8+ T cells. This indicated that CD4+ T cells could compensate for the absence of CD8+ T cells and mediate tumour protection by a yet not fully clarified mechanism independent of both antibodies and CD8+ T cells. In conclusion, in this thesis it is shown that Her2/neu-cVLPs based on both MPyV and MPtV are efficient as prophylactic and therapeutic vaccines against Her2/neu-expressing tumours in mice, and that protection involves both CD4+ and CD8+ T cells

Low risk of complications in patients with first-time acute uncomplicated diverticulitis

First-time acute uncomplicated diverticulitis (AUD) has been considered to have an increased risk of complication, but the level of evidence is low. The aim of the present study was to evaluate the risk of complications in patients with first-time AUD and in patients with a history of diverticulitis. This paper is a population-based retrospective study at Vastmanland's Hospital, VasterA<yen>s, Sweden, where all patients were identified with a diagnosis of colonic diverticular disease ICD-10 K57.0-9 from January 2010 to December 2014. The records of all patients were surveyed and patients with a computed tomography (CT)-verified AUD were included. Complications defined as CT-verified abscess, perforation, colonic obstruction, fistula, or sepsis within 1 month from the diagnosis of AUD were registered. Of 809 patients with AUD, 642 (79%) had first-time AUD and 167 (21%) had a previous history of AUD with no differences in demographic or clinical characteristics. In total, 16 (2%) patients developed a complication within 1 month irrespective of whether they had a previous history of diverticulitis (P = 0.345). In the binary logistic regression analysis, first-time diverticulitis was not associated with increased risk of complications (OR 1.58; CI 0.52-4.81). The rate of antibiotic therapy was about 7-10% during the time period and outpatient management increased from 7% in 2010 to 61% in 2014. The risk for development of complications is low in AUD with no difference between patients with first-time or recurrent diverticulitis. This result strengthens existing evidence on the benign disease course of AUD

Long-term IFNγ responses after Her2MPtVLP immunization.

<p>BALB/c mice were immunized with Her2MPtVLPs with CpG either 10 weeks (a), 6 weeks (b) or 1 week (d) before ELISPOT analysis, or with Her2MPtVLPs without CpG 6 weeks (c) or 1 week (e) before ELISPOT. Unimmunized mice were included as negative controls (f). Splenocytes were stimulated with the immunodominant CD8⁺ peptide Her2_63–71 or the control peptide NP_118–126. Average values of triplicates from 4 animals are shown. Background values (stimulation in the absence of peptide) have been subtracted. Error bars represent S.E.</p

Induction of long-term tumour rejection responses.

<p>BALB/c mice were immunized with Her2MPtVLPs alone (*) or Her2MPtVLPs in combination with CpG (Δ) and challenged 6 weeks later with 5×10⁴ D2F2/E2 cells. Unimmunized mice (x) and mice immunized with MPtVLPs and CpG (•) were included as negative controls, while mice immunized with Her2MPtVLPs 2 weeks prior to challenge were used as positive controls (□).</p

IFNγ responses following depletion of immune cells in BALB/c mice.

<p>Mice were depleted of CD4⁺ and/or CD8⁺ cells 5 and 2 days before immunisation with Her2MPtVLPs. The IFNγ response was measured 7 days later by stimulating splenocytes with the immunodominant CD8⁺ peptide Her2_63–71 or the control peptide NP_118–126. Average values of triplicates from six animals are shown. Background values (stimulation in the absence of peptide) have been subtracted. Error bars represent S.E.</p

Tumour takes after immunization of BALB/c mice 6 and 10 weeks before challenge with 5×104 D2F2/E2 cells.

a<p>p-values calculated using Fisher's exact two-tailed test, compared to unimmunized mice.</p>b<p>experiment.</p>c<p>not done.</p>d<p>not significant.</p