External communication of automated shuttles: Results, experiences, and lessons learned from three European long-term research projects.

Automated shuttles are already seeing deployment in many places across the world and have the potential to transform public mobility to be safer and more accessible. During the current transition phase from fully manual vehicles toward higher degrees of automation and resulting mixed traffic, there is a heightened need for additional communication or external indicators to comprehend automated vehicle actions for other road users. In this work, we present and discuss the results from seven studies (three preparatory and four main studies) conducted in three European countries aimed at investigating and providing a variety of such external communication solutions to facilitate the exchange of information between automated shuttles and other motorized and non-motorized road users.

The Bispecific Tumor Antigen-Conditional 4-1BB x 5T4 Agonist, ALG.APV-527, Mediates Strong T-Cell Activation and Potent Antitumor Activity in Preclinical Studies.

4-1BB (CD137) is an activation-induced costimulatory receptor that regulates immune responses of activated CD8 T and natural killer cells, by enhancing proliferation, survival, cytolytic activity, and IFNγ production. The ability to induce potent antitumor activity by stimulating 4-1BB on tumor-specific cytotoxic T cells makes 4-1BB an attractive target for designing novel immuno-oncology therapeutics. To minimize systemic immune toxicities and enhance activity at the tumor site, we have developed a novel bispecific antibody that stimulates 4-1BB function when co-engaged with the tumor-associated antigen 5T4.

Dataset of bond enthalpies (ε, ε, ε) in 975 binary intermetallic compounds.

The concept of a bond energy between a pair of atoms is well-established in chemistry and physics. In materials science, it is a fundamental parameter in the development of thermodynamic models such as the regular, quasi-chemical and sub-regular solution models, as well as the central atoms model. Accurate bond dissociation enthalpies are available for gaseous molecular compounds, but these values are likely to differ significantly from single bond strengths between atoms in liquids and solids.

A novel care guide for personalised palliative care - a national initiative for improved quality of care.

Background: Even when palliative care is an integrated part of the healthcare system, the quality is still substandard for many patients and often initiated too late. There is a lack of structured guidelines for identifying and caring for patients; in particular for those with early palliative care needs. A care guide can act as a compass for best practice and support the care of patients throughout their palliative trajectory.

Thrombin-Derived C-Terminal Peptide Reduces -Induced Inflammation and Infection and .

Infections due to the opportunistic fungus Candida have been on the rise in the last decades, especially in immunocompromised individuals and hospital settings. Unfortunately, the treatments available today are limited. Thrombin-derived C-terminal peptide (TCP-25) is an antimicrobial peptide (AMP) with antibacterial and immunomodulatory effects.

Physiological and Cognitive Performance in F-22 Pilots During Day and Night Flying.

Many workers routinely transition between day and night shiftsincluding pilots, where night flights are commonly considered more stressful. The physiological toll from this transition is not fully understood, though fatigue is a factor in many aviation accidents. This research investigated the changes in physiological markers of stress and cognitive performance as F-22 pilots transitioned from day flying to night flying.

The effects of exercise training on hypothalamic-pituitary-adrenal axis reactivity and autonomic response to acute stress-a randomized controlled study.

Background: Exercise training is suggested to have a stress-buffering effect on physiological reactions to acute stress. The so-called cross-stressor adaptation hypothesis is one of many theories behind the plausible effects, proposing that the attenuated physiological reaction seen in trained individuals in response to acute exercise is also seen when the individual is exposed to acute psychosocial stress. However, few randomized controlled trials (RCT) are available in this field.

The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.

Background: The CTLA-4 blocking antibody ipilimumab has demonstrated substantial and durable effects in patients with melanoma. While CTLA-4 therapy, both as monotherapy and in combination with PD-1 targeting therapies, has great potential in many indications, the toxicities of the current treatment regimens may limit their use. Thus, there is a medical need for new CTLA-4 targeting therapies with improved benefit-risk profile.

Exercise training and physiological responses to acute stress: study protocol and methodological considerations of a randomised controlled trial.

Background: This paper describes the protocol and methodological prerequisites for a randomised controlled exercise intervention. Selected baseline data from the study are also presented, demonstrating some methodological challenges related to exercise intervention trials. The aim of the trial was to study the effects of exercise training on physiological responses to acute psychosocial stress in untrained individuals.

Simultaneous Targeting of Two Distinct Epitopes on MET Effectively Inhibits MET- and HGF-Driven Tumor Growth by Multiple Mechanisms.

Increased MET activity is linked with poor prognosis and outcome in several human cancers currently lacking targeted therapies. Here, we report on the characterization of Sym015, an antibody mixture composed of two humanized IgG antibodies against nonoverlapping epitopes of MET. Sym015 was selected by high-throughput screening searching for antibody mixtures with superior growth-inhibitory activity against MET-dependent cell lines.

Sym015: A Highly Efficacious Antibody Mixture against -Amplified Tumors.

Activation of the receptor tyrosine kinase MET is associated with poor clinical outcome in certain cancers. To target MET more effectively, we developed an antagonistic antibody mixture, Sym015, consisting of two humanized mAbs directed against nonoverlapping epitopes of MET. We screened a large panel of well-annotated human cancer cell lines and identified a subset with highly elevated MET expression.

In vivo imaging of therapy response to a novel pan-HER antibody mixture using FDG and FLT positron emission tomography.

Purpose: Overexpression of the human epidermal growth factor receptor (HER) family and their ligands plays an important role in many cancers. Targeting multiple members of the HER family simultaneously may increase the therapeutic efficacy. Here, we report the ability to image the therapeutic response obtained by targeting HER family members individually or simultaneously using the novel monoclonal antibody (mAb) mixture Pan-HER.

Pan-HER, an Antibody Mixture Simultaneously Targeting EGFR, HER2, and HER3, Effectively Overcomes Tumor Heterogeneity and Plasticity.

Purpose: Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members.

Experimental Design/results: We have generated Pan-HER, a mixture of six antibodies targeting each of the HER family members EGFR, HER2, and HER3 with synergistic pairs of antibodies, which simultaneously remove all three targets, thereby preventing compensatory tumor promoting mechanisms within the HER family. Pan-HER induces potent growth inhibition in a range of cancer cell lines and xenograft models, including cell lines with acquired resistance to therapeutic antibodies.

Targeting Three Distinct HER2 Domains with a Recombinant Antibody Mixture Overcomes Trastuzumab Resistance.

HER2 plays an important role in the development and maintenance of the malignant phenotype of several human cancers. As such, it is a frequently pursued therapeutic target and two antibodies targeting HER2 have been clinically approved, trastuzumab and pertuzumab. It has been suggested that optimal inhibition of HER2 is achieved when utilizing two or more antibodies targeting nonoverlapping epitopes.

Teenage outcomes after speech and language impairment at preschool age.

Aim: Ten years ago, we published developmental data on a representative group of children (n = 25) with moderate or severe speech and language impairment, who were attending special preschools for children. The aim of this study was to perform a follow-up of these children as teenagers.

Methods: Parents of 23 teenagers participated in a clinical interview that requested information on the child's current academic achievement, type of school, previous clinical assessments, and developmental diagnoses.

Galiellalactone inhibits stem cell-like ALDH-positive prostate cancer cells.

Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+) prostate cancer cells.

Cysteine-rich secretory protein 3 and β-microseminoprotein on prostate cancer needle biopsies do not have predictive value for subsequent prostatectomy outcome.

Objectives: • To investigate whether cysteine-rich secretory protein 3 (CRISP-3) and/or β-microseminoprotein (β-MSP) expression in diagnostic prostate needle biopsies have predictive value for prostate cancer (PC) on radical prostatecomy (RP). • To evaluate their potential clinical implementation in a preoperative setting.

Patients And Methods: • In total, 174 participants from the European Randomized Study of Screening for Prostate Cancer, Rotterdam section, treated by RP for PC were included in the present study.

Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis.

Despite prostate cancer being the most frequent cancer in men in the Western world, tissue biomarkers for predicting disease recurrence after surgery have not been incorporated into clinical practice. Our group has previously identified β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) as independent predictors of biochemical recurrence after radical prostatectomy. The purpose of the present study was to use automated image analysis, enabling quantitative determination of MSMB and CRISP3 expressions in a large cohort and to validate the previous findings.

LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer.

The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer.

Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3.

We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy.

Galiellalactone is a novel therapeutic candidate against hormone-refractory prostate cancer expressing activated Stat3.

Background: Signal transducer and activator of transcription 3 (Stat3) is constitutively active (phosphorylated) in several forms of cancer, including prostate cancer (PCa). Stat3 signaling may be an interesting target for cancer therapy since inhibition of this pathway mediates growth inhibition and apoptosis of these cells. In this study we investigated the in vitro and in vivo effects of the fungal metabolite galiellalactone, a direct inhibitor of Stat3, on PCa cells.

Outbreak of invasive aspergillosis among renal transplant recipients.

Invasive aspergillosis (IA) is rare among renal transplant recipients (RTRs). We investigated a cluster of IA among RTRs at a California hospital from January to February 2001, when construction was ongoing. We conducted a cohort study among RTRs who were hospitalized between January 1 and February 5, 2001, to determine risk factors for IA.

Immune response against ovalbumin in rats colonized with an ovalbumin-producing Escherichia coli and the influence of feeding ovalbumin.

The influence of feeding ovalbumin (OA) on the development of IgE/IgG antibodies and delayed-type hypersensitivity (DTH) against OA was studied in rats colonized from birth with an Escherichia coli genetically manipulated to produce OA. At 21 days of age, colonized pups and pups with a normal intestinal flora were weaned onto either an OA-containing or a conventional diet without OA. At 2 months of age the colonized rats showed an increased DTH reaction to OA, but they did not have any anti-OA antibodies in serum.