Reviews

Review of The working class and welfare: reflections on the political development of the welfare state in Australia and New Zealand 1890- 1980, Dismissed, The new working class? White-collar workers and their organisations, White-collar unionism, Full employment without inflation : Manifesto for a governed economy, Labour relations: a student handbook, Dismissal and redundancy procedures, Comparative industrial relations: an introduction to cross/national perspectives, and The Mediator

Visual perception system and method for a humanoid robot

A robotic system includes a humanoid robot with robotic joints each moveable using an actuator(s), and a distributed controller for controlling the movement of each of the robotic joints. The controller includes a visual perception module (VPM) for visually identifying and tracking an object in the field of view of the robot under threshold lighting conditions. The VPM includes optical devices for collecting an image of the object, a positional extraction device, and a host machine having an algorithm for processing the image and positional information. The algorithm visually identifies and tracks the object, and automatically adapts an exposure time of the optical devices to prevent feature data loss of the image under the threshold lighting conditions. A method of identifying and tracking the object includes collecting the image, extracting positional information of the object, and automatically adapting the exposure time to thereby prevent feature data loss of the image

Heterogeneity of human melanoma-associated antigens defined by monoclonal antibodies and conventional xenoantisera

Immunochemical analysis of cultured human melanoma cell detergent extracts and spent culture medium with conventional xenoantisera and monoclonal antibodies identified four types of 94,000 (94K) dalton molecules and two types of high-molecular-weight melanoma-associated antigens by the following characteristics: (1) association with other components, (2) mobility in SDS-PAGE under reducing and nonreducing conditions, (3) antigenicity, and (4) presence in spent culture medium. Conventional xenoantisera were found to contain antibody populations to antigenically distinct structures, some of which have similar apparent molecular weights. Immunodepletion studies showed that the antigenic determinant detected by the monoclonal antibody 225.28S to a high-molecular-weight melanoma-associated antigen was expressed on a subpopulation of the antigens defined by the conventional xenoantiserum #8995. These data prove that antibodies reactive with antigens of similar molecular weight cannot be assumed to identify the same structures, and indicate that tumor-associated antigens may be heterogeneous in the expression of antigenic determinants defined by monoclonal antibodies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46848/1/262_2004_Article_BF00200204.pd

Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.

The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice

Full genome re-sequencing reveals a novel circadian clock mutation in Arabidopsis

Map based cloning in Arabidopsis thaliana can be a difficult and time-consuming process, specifically if the phenotype is subtle and scoring labour intensive. Here, we have re-sequenced the 120-Mb genome of a novel Arabidopsis clock mutant early bird (ebi-1) in Wassilewskija (Ws-2). We demonstrate the utility of sequencing a backcrossed line in limiting the number of SNPs considered. We identify a SNP in the gene AtNFXL-2 as the likely cause of the ebi-1 phenotype

Tissue distribution and molecular profile of a differentiation antigen detected by a monoclonal antibody (345.134S) produced against human melanoma cells

The mouse IgG2a monoclonal antibody (MoAb) 345.134S, secreted by a hybridoma derived from a mouse immunized with cultured human melanoma cells, reacts with an 85,000-dalton glycopolypeptide which is disulfide-bridged to a 30,000-dalton polypeptide having little if any covalently attached carbohydrate. The 115,000-dalton complex is peripheral rather than integral in its association with the plasma cell membrane. Indirect immunofluorescence of cryostat thin sections of human tissues with the MoAb 345.134S showed (1) strong staining of the sebaceous glands and basal layer of normal hyperpigmented skin; (2) weak staining of the basal layer of normal pigmented skin and epithelial cells of the gastrointestinal tract, parotid, renal proximal tubules, thyroid, and urinary bladder; and (3) no staining of melanocytes, mammary gland, lung, brain cortex, or liver. The staining pattern of tissues from a 20-week-old fetus is similar to that of tissues from adults. The MoAb 345.134S stained some cases of virtually all tumors tested, including some derived from normal tissues non-reactive with the antibody; intensity of staining of tumors was in general much greater than in normal tissues. The expression of the antigen detected by MoAb 345.134S in a panel of cultured human tumor cells did not correlate with the expression of other tumor-associated antigens or with HLA-A,B or Ia-like antigens. The MoAb 345.134S can mediate complement- and cell-dependent lysis of cultured human tumor cells. The lack of correlation between the extent of immune lysis and the expression of the antigen detected by MoAb 345.134S as well as the effect of puromycin on antibody-mediated cell-dependent lysis indicated that factors other than antigen density play a significant role in the outcome of immune lytic reactions mediated by this monoclonal antibody.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46847/1/262_2004_Article_BF00205375.pd

Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis

B-Chronic Lymphocytic Leukemia (CLL) is an incurable disease predominantly characterized by apoptosis resistance. We have previously described a VEGF signaling pathway that generates apoptosis resistance in CLL B cells. We found induction of significantly more apoptosis in CLL B cells by co-culture with an anti-VEGF antibody. To increase the efficacy of these agents in CLL therapy we have focused on the use of gold nanoparticles (GNP). Gold nanoparticles were chosen based on their biocompatibility, very high surface area, ease of characterization and surface functionalization. We attached VEGF antibody (AbVF) to the gold nanoparticles and determined their ability to kill CLL B cells. Gold nanoparticles and their nanoconjugates were characterized using UV-Visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). All the patient samples studied (N = 7) responded to the gold-AbVF treatment with a dose dependent apoptosis of CLL B cells. The induction of apoptosis with gold-AbVF was significantly higher than the CLL cells exposed to only AbVF or GNP. The gold-AbVF treated cells showed significant down regulation of anti-apoptotic proteins and exhibited PARP cleavage. Gold-AbVF treated and GNP treated cells showed internalization of the nanoparticles in early and late endosomes and in multivesicular bodies. Non-coated gold nanoparticles alone were able to induce some levels of apoptosis in CLL B cells. This paper opens up new opportunities in the treatment of CLL-B using gold nanoparticles and integrates nanoscience with therapy in CLL. In future, potential opportunities exist to harness the optoelectronic properties of gold nanoparticles in the treatment of CLL

Ibrutinib-based therapy reinvigorates CD8 T cells compared to chemoimmunotherapy: immune-monitoring from the E1912 trial

Bruton's tyrosine kinase Inhibitors (BTKis) that target B cell receptor signaling have led to a paradigm shift in CLL treatment. BTKis have been shown to reduce abnormally high CLL-associated T cell counts and the expression of immune checkpoint receptors concomitantly with tumor reduction. However, the impact of BTKi therapy on T cell function has not been fully characterized. Here, we performed longitudinal immunophenotypic and functional analysis of pre- and on-treatment (6- and 12-months) peripheral blood samples from patients in the phase 3 E1912 trial comparing ibrutinib-rituximab to fludarabine, cyclophosphamide and rituximab (FCR). Intriguingly, we report that despite reduced overall T cell counts, higher numbers of T cells including effector CD8+ subsets at baseline and at the 6-month time-point associated with no infections and favorable progression-free survival (PFS) in the ibrutinib-rituximab arm. Assays demonstrated enhanced anti-CLL T cell killing function during ibrutinib-rituximab, including a switch from predominantly CD4+ T-cell:CLL immune synapses at baseline to increased CD8+ lytic synapses on-therapy. Conversely, in the FCR arm, higher T cell numbers correlated with adverse clinical responses and showed no functional improvement. We further demonstrate the potential of exploiting rejuvenated T cell cytotoxicity during ibrutinib-rituximab using the bispecific antibody glofitamab - supporting combination immunotherapy approaches