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mark dickson

George Whitefield College, Philosophy, Faculty Member

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I am convinced the Bible is God's word and as such speaks to us about how to know God and the reality in which we live. I am interested in theology, science, philosophy, organizational leadership, children's books, and musical theatre.

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Philippe Ailleris

VICENTE-JUAN BALLESTER OLMOS

SUNY: University at Albany

Christopher Golightly

Institut für Grenzgebiete der Psychologie und Psychohygiene e.V.

Massimo Teodorani

Taylor A Cisco, Jr.

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Papers by mark dickson

Ormia’s ears call for a fresh hearing - a biomimetic and philomimetic challenge

The concept of irreducible complexity has been proposed as a property of human-designed multipart... more The concept of irreducible complexity has been proposed as a property of human-designed multipart systems that require the operational presence of all parts for overall unified function. Although these systems are complex – they are composed of several parts working together - there is nevertheless an overarching functional unity. This system unity cannot be achieved with fewer parts and can therefore be described by the property known as irreducible complexity (IC). Any proposed reduction of the number of parts so as to reduce the complexity brings about an irretrievable loss of function.
Given the existence of biomimesis where engineers can be inspired by certain biological systems thereby designing novel innovative technology, the question can arise: “Is not IC a true property of those biological systems as well?” If an engineer can argue that a certain ‘design’ is truly instanced in a particular living sub-system, then can that engineer, having implemented that ‘design’ in some technology, not say “The IC present in the design of my piece of technology surely can be ascribed to the design I ‘copied’ from nature?” If this can be said, then IC could be seen as a property of biological systems.

Introduction to Archaeology for theological students

This article outlines some major contours of archaeology insofar as it impacts upon theological s... more

Philomimesis: Updated -A New Perspective on the Overlap of Biosphere and Technosphere

Self, 2023

Technological applications of structures observed in nature (biomimesis) have increased dramatica... more Technological applications of structures observed in nature (biomimesis) have increased dramatically in the past few decades. Engineers drawn into the study of natural design notice a conceptual issue arising from biological emphases on etiology. The gap between biosphere and technosphere can be narrowed via a recognition of the anticipation of human designs that exist (and have existed) within the living world. The fullness of such anticipated natural design is termed Philomimesis.

Philomimetics: A New Perspective on the Overlap of Biosphere and Technosphere

Self, 2023

Technological applications of structures observed in nature (biomimesis) have increased dramatica... more Technological applications of structures observed in nature (biomimesis) have increased dramatically in the past few decades. Engineers drawn into the study of natural design notice a conceptual issue arising from biological emphases on etiology. The gap between biosphere and technosphere can be narrowed via a recognition of the anticipation of human designs that exist (and have existed) within the living world. The fullness of such anticipated natural design is termed Philomimesis.

The NASA UAP (unidentified anomalous phenomena report; cf UFO) and the question of bias in science

self, 2023

NASA has recently released (Sept 2023) the result of a year-long investigation by sixteen panelis... more NASA has recently released (Sept 2023) the result of a year-long investigation by sixteen panelists into the UFO or UAP phenomena and the report has on its front digital cover the title: 'NASA UNIDENTIFIED ANOMALOUS PHENOMENA Independent Study Team Report.' This article discusses the problem of collecting data when the panel does not include a wide enough membership of rival theorists.

CoastalME version 1.0: a Coastal Modelling Environment for simulating decadal to centennial morphological changes

Geoscientific Model Development Discussions, 2016

Modelling coastal morphological changes at decadal to centennial time scales is required to suppo... more Modelling coastal morphological changes at decadal to centennial time scales is required to support sustainable coastal management world-wide. One approach involves coupling of landform-specific components (e.g. cliff, beach, dunes, estuaries, etc.) that have been independently developed. An alternative, and novel approach explored in this paper is to capture the essential characteristics of the landform-specific models using a common spatial representation within an appropriate software-environment. In the proposed Coastal Modelling Environment (CoastalME), change in coastal morphology is formulated by means of dynamically linked raster and geometrical objects. A grid of raster cells provides the data structure for representing quasi-3D spatial heterogeneity and sediment conservation. Other geometrical objects (lines, areas and volumes) that are consistent with, and derived from, the raster structure represent a library of coastal elements (e.g. shoreline, beach profiles and estuar...

Irreducible complexity as a nexus for an interdisciplinary dialogue between machine logic, molecular biology and theology

The claim that a principle known as Irreducible Complexity (IC) is empirically discoverable is in... more The claim that a principle known as Irreducible Complexity (IC) is empirically discoverable is investigated successively from the perspective of engineering, then molecular biology and finally theology, with the aim of evaluating the utility of IC for an interdisciplinary dialogue between all three. In the process, IC is subjected to the principle objections presented against it in the literature, leading to the conclusion that IC is sufficiently resistant to scientific criticism to be accepted as a true property of certain living systems. The ubiquity of machine descriptors in the professional literature of molecular biology is scrutinised in the context of the role of metaphor in science, as well as in the context of entailment models. A Biblical Theological approach to the Bible is harnessed to establish a framework for estimating the extent to which the story of Christ warrants expectation of first order design formalisms in nature, and whether that story within itself provides ...

Biomimetics and Biomimesis in the the academy: the clash between engineering and biology in the university (PhD dissertation: Irreducible Complexity and the problem of Underdetermination in the Created Order)

This dissertation problematises the presence of biomimetics or biomimesis in the academy. In sho... more This dissertation problematises the presence of biomimetics or biomimesis in the academy. In short, I have written about a deep seated and profound clash between engineering and biology in the university (engineering interdisciplinarity). Additionally, I explore an approach to the analysis of many bio-systems I have termed The Biomimetic Machine Thesis, which attempts to explore several different ways in which a designer assumption currently provides scientific utility. The extent of the anticipation within the biosphere of functionally equivalent designs exhibited in the technosphere leads to the formulation of the concept I have called ‘philomimesis’, where the latter implies a strong anthropic shaping of the natural world. Theological concepts are also involved, but the key stance adopted in this book is not to ask whether a designed-by-a-designer gloss can be placed over all of the reality we see, but rather to ask about the scientific utility of assuming that design in natural is designed-by-a-designer even if the metaphysics of the actual existence of such a designer is bracketed out.

Kaposi Sarcoma of Childhood: Inborn or Acquired Immunodeficiency to Oncogenic HHV-8

Pediatric Blood & Cancer, 2015

Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection... more Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single-gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV-8.

Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015

Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (ir... more Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF). We reviewed retrospectively the medical records of patients with melanoma who had received treatment between April 2011 and July 2013 with ipilimumab at the standard dose of 3 mg/kg. We collected data on patient demographics, previous and subsequent treatments, number of ipilimumab doses, irAEs and how they were treated, and overall survival. Of the 298 patients, 254 (85%) experienced an irAE of any grade. Fifty-six patients (19%) discontinued therapy because of an irAE, most commonly diarrhea. Overall, 103 patients (35%) required systemic corticoste...

Impact of surgery, radiation and systemic therapy on the outcomes of patients with dendritic cell and histiocytic sarcomas

European Journal of Cancer, 2015

Neoplasms of histiocytic and dendritic cell origin, including follicular dendritic cell sarcoma (... more Neoplasms of histiocytic and dendritic cell origin, including follicular dendritic cell sarcoma (FDCS), histiocytic sarcoma (HS) and interdigitating dendritic cell sarcoma (IDCS), are extremely rare, and data on their natural history and treatment outcomes are sparse. We evaluated the impact of surgery, radiation and systemic therapies on overall survival (OS). We conducted a retrospective chart review of patients with FDCS, IDCS and HS treated at Memorial Sloan Kettering Cancer Center between 1995 and 2014. We identified 31, 15 and 7 patients with FDCS, HS and IDCS, respectively. Median age was 48.7, 42.3 and 58.8years for FDCS, HS and IDCS, respectively. Only a slight disparity in gender distribution existed for FDCS and HS; however, IDCS predominantly affected males (6:1). The most common sites of presentation were abdomen and pelvis (42%), extremities (33%) and head and neck (57%) for FDCS, HS and IDCS, respectively. At diagnosis, 74%, 40% and 86% of patients presented with localised disease in FDCS, HS and IDCS, respectively. Patients with localised disease had significantly improved OS than those with metastatic disease in FDCS (P=0.04) and IDCS (P=0.014) but not in HS (P=0.95). In FDCS and HS, adjuvant or neo-adjuvant therapy was not associated with improved OS compared with observation. In IDCS, surgery alone provided a 5-year overall survival rate of 71%. Adjuvant or neo-adjuvant treatment in FDCS and HS did not affect OS. Patients with IDCS had an excellent outcome with surgery. In the metastatic setting, chemotherapy and small molecule inhibitors may provide benefit.

MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition

Oncotarget, Jan 10, 2015

CDK4 inhibitors (CDK4i) earned Breakthrough Therapy Designation from the FDA last year and are en... more CDK4 inhibitors (CDK4i) earned Breakthrough Therapy Designation from the FDA last year and are entering phase III clinical trials in several cancers. However, not all tumors respond favorably to these drugs. CDK4 activity is critical for progression through G1 phase and into the mitotic cell cycle. Inhibiting this kinase induces Rb-positive cells to exit the cell cycle into either a quiescent or senescent state. In this report, using well-differentiated and dedifferentiated liposarcoma (WD/DDLS) cell lines, we show that the proteolytic turnover of MDM2 is required for CDK4i-induced senescence. Failure to reduce MDM2 does not prevent CDK4i-induced withdrawal from the cell cycle but the cells remain in a reversible quiescent state. Reducing MDM2 in these cells drives them into the more stable senescent state. CDK4i-induced senescence associated with loss of MDM2 is also observed in some breast cancer, lung cancer and glioma cell lines indicating that this is not limited to WD/DDLS cel...

HOX clusters of Latimeria: Complete characterization provides further evidence for slow evolution of the coelacanth genome

The living coelacanth is a lobe-finned fish that represents an early evolutionary departure from ... more The living coelacanth is a lobe-finned fish that represents an early evolutionary departure from the lineage that led to land vertebrates, and is of extreme interest scientifically. It has changed very little in appearance from fossilized coelacanths of the Cretaceous (150-65 million years ago), and is often referred to as a "living fossil." An important general question is whether long term stasis in morphological evolution is associated with stasis in genome evolution. To this end we have used targeted genome sequencing for acquiring 1,612,752 bp of high-quality finished sequence encompassing the four HOX clusters of the Indonesian coelacanth, Latimeria menadoensis. Detailed analyses were carried out on genomic structure, gene and repeat contents, conserved non-coding regions, and relative rates of sequence evolution in both coding and non-coding tracts. Our results demonstrate conclusively that the coelacanth HOX clusters are comparatively slowly evolving and that this taxon should serve as a viable outgroup for interpretating the genomes of tetrapod species.

Phase II Trial of Gemcitabine and Docetaxel with Bevacizumab in Soft Tissue Sarcoma

Sarcoma, 2015

Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sar... more Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sarcoma. This study tested the hypothesis that outcomes would be improved by addition of bevacizumab (B). The initial design was randomized double-blind trial of G + D + B versus G + D + placebo. Due to slow accrual this was modified to single-arm open-label G + D + B. Eligible patients had diagnosis of leiomyosarcoma, pleomorphic undifferentiated sarcoma, pleomorphic liposarcoma, or angiosarcoma. Treatment was B 15 mg/kg on d1, G 900 mg/m(2) on d1 and d8, and D 75 mg/m(2) on d8, q21d. Primary endpoint was progression-free survival (PFS) at 6 months and would be met if ≥17 patients were progression-free at 6 m. Secondary endpoints are response rate, PFS at 3 m, overall survival, and toxicity. Of 44 patients enrolled, 35 were treated with GDB and evaluable for safety and efficacy. Median age was 55, 50% male, most ECOG 0. Toxicity is mostly myelosuppression with one deep vein thrombosis and one small bowel perforation possibly related to B. There were 17 partial responses (49%) by RECIST 1.1. Among 35 patients, the number who remained on study and progression-free was 24 at 3 m and 15 at 6 m. 9 withdrew prior to 6 m for reasons other than toxicity or progression. PFS at 6 m was 65% (95% CI: 51-85%). The primary endpoint of 6 m PFS was not met due to censoring of patients who withdrew. However PFS at 3 m (76%) was promising and response rate was higher than expected from G + D.

Acute myeloid leukemia arising from a donor derived premalignant hematopoietic clone: A possible mechanism for the origin of leukemia in donor cells

Leukemia research reports, 2014

During recent years, it has become increasingly evident that donor leukemia following allogeneic ... more During recent years, it has become increasingly evident that donor leukemia following allogeneic transplant may be more common then realized in the past. We identified five cases of potential donor leukemia cases during past five years. The precise mechanism of the origin of such leukemias, however, remains poorly defined. In this short communication, we report a well documented case of donor-derived de novo acute myeloid leukemia (AML) that developed fourteen years after allogeneic stem cell transplantation for treatment induced AML for his primary malignancy Immunoblastic lymphoma. This case allows us to postulate a possible mechanism of the origin of donor leukemia. The de novo AML clone contained a distinct cytogenetic abnormality, trisomy 11, which was simultaneously detected in preserved peripheral blood obtained at the time of transplantation as well as in the current bone marrow from an otherwise clinically and phenotypically normal donor. The findings from this unique case,...

Development of cell-cycle inhibitors for cancer therapy

Current oncology (Toronto, Ont.), 2009

The cell cycle governs the transition from quiescence through cell growth to proliferation. The k... more The cell cycle governs the transition from quiescence through cell growth to proliferation. The key parts of the cell cycle machinery are the cyclin-dependent kinases (CDKS) and the regulatory proteins called cyclins. The CDKS are rational targets for cancer therapy because their expression in cancer cells is often aberrant and their inhibition can induce cell death. Inhibitors of CDKS can also block transcription.Several drugs targeting the cell cycle have entered clinical trials. These agents include flavopiridol, indisulam, AZD5438, SNS-032, bryostatin-1, seliciclib, PD 0332991, and SCH 727965. Phase i studies have demonstrated that these drugs can generally be administered safely. Phase ii studies have shown little single-agent activity in solid tumors, but combination studies with cytotoxic chemotherapy have been more promising. In hematologic malignancies, reports have shown encouraging single-agent and combination activity. Pharmacodynamic studies show that the dose and sched...

Phase I study of XL281 (BMS-908662), a potent oral RAF kinase inhibitor, in patients with advanced solid tumors

Investigational New Drugs, 2014

Background XL281 is a potent and selective inhibitor of wild-type and mutant RAF kinases with ant... more Background XL281 is a potent and selective inhibitor of wild-type and mutant RAF kinases with anti-tumor activity in multiple xenograft models. Mutations in KRAS or BRAF can activate the RAF/MEK/ERK pathway in human tumors and may confer sensitivity to RAF kinase inhibitors. Methods We performed a phase I study of XL281 in patients with advanced solid tumors. Patients were enrolled in successive cohorts of XL281 orally once daily in 28-day cycles. Twice daily dosing, different formulations, and the effect of food and famotidine were also studied. At the MTD expanded cohorts with defined mutations were treated. Results In total, 160 patients were treated. The MTD on the QD schedule was 150 mg. The most common toxicities were diarrhea, nausea, and fatigue. Plasma Cmax and AUC increased with dose. Famotidine resulted in lower AUC while food had no effect. Two patients had partial responses by RECIST: One with papillary thyroid cancer with NRAS mutation and one with uveal melanoma. Another nine patients had tumor decrease of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 % but did not meet RECIST criteria for PR. Matched tumors pairs from 33 patients showed evidence of RAF inhibition with significant decreases in pERK, pMEK and pAKT. Conclusions XL281 was generally well tolerated and the MTD was established at 150 mg/day. Partial responses and clinical benefit were observed in several patients. Tumor biopsies demonstrated effective target inhibition.

$Research paper thumbnail of Evidence for color coherence in $p\bar{p}$ collisions at $\sqrt{s} = 1.8$ TeV$

Evidence for color coherence in $p\bar{p}$ collisions at $\sqrt{s} = 1.8$ TeV

Color coherence effects in pp¯ collisions are observed and studied with CDF, the Collider Detecto... more Color coherence effects in pp¯ collisions are observed and studied with CDF, the Collider Detector at the Fermilab Tevatron collider. We demonstrate these effects by measuring spatial correlations between soft and leading jets in multijet events. Variables sensitive to interference are identified by comparing the data to the predictions of various shower Monte Carlo programs that are substantially different with

Jet Classification at CDF

International Journal of Neural Systems, 1992

Results for the classification of jets obtained with the use feed-forward neural networks are rev... more Results for the classification of jets obtained with the use feed-forward neural networks are reviewed with particular attention to model-dependence, flavor sensitivity and Et-dependence. First results obtained with a Kohonen-type network are also presented and both are compared with those obtained with a Fisher discriminant.

Broad-Scale Analysis of Morphological and Climate Impacts on Coastal Flood Risk

Coastal Dynamics 2005, 2006

A system of hydrodynamic, morphodynamic and reliability models have been coupled to generate insi... more

Ormia’s ears call for a fresh hearing - a biomimetic and philomimetic challenge

The concept of irreducible complexity has been proposed as a property of human-designed multipart... more The concept of irreducible complexity has been proposed as a property of human-designed multipart systems that require the operational presence of all parts for overall unified function. Although these systems are complex – they are composed of several parts working together - there is nevertheless an overarching functional unity. This system unity cannot be achieved with fewer parts and can therefore be described by the property known as irreducible complexity (IC). Any proposed reduction of the number of parts so as to reduce the complexity brings about an irretrievable loss of function.
Given the existence of biomimesis where engineers can be inspired by certain biological systems thereby designing novel innovative technology, the question can arise: “Is not IC a true property of those biological systems as well?” If an engineer can argue that a certain ‘design’ is truly instanced in a particular living sub-system, then can that engineer, having implemented that ‘design’ in some technology, not say “The IC present in the design of my piece of technology surely can be ascribed to the design I ‘copied’ from nature?” If this can be said, then IC could be seen as a property of biological systems.

Introduction to Archaeology for theological students

This article outlines some major contours of archaeology insofar as it impacts upon theological s... more

Philomimesis: Updated -A New Perspective on the Overlap of Biosphere and Technosphere

Self, 2023

Technological applications of structures observed in nature (biomimesis) have increased dramatica... more Technological applications of structures observed in nature (biomimesis) have increased dramatically in the past few decades. Engineers drawn into the study of natural design notice a conceptual issue arising from biological emphases on etiology. The gap between biosphere and technosphere can be narrowed via a recognition of the anticipation of human designs that exist (and have existed) within the living world. The fullness of such anticipated natural design is termed Philomimesis.

Philomimetics: A New Perspective on the Overlap of Biosphere and Technosphere

Self, 2023

Technological applications of structures observed in nature (biomimesis) have increased dramatica... more Technological applications of structures observed in nature (biomimesis) have increased dramatically in the past few decades. Engineers drawn into the study of natural design notice a conceptual issue arising from biological emphases on etiology. The gap between biosphere and technosphere can be narrowed via a recognition of the anticipation of human designs that exist (and have existed) within the living world. The fullness of such anticipated natural design is termed Philomimesis.

The NASA UAP (unidentified anomalous phenomena report; cf UFO) and the question of bias in science

self, 2023

NASA has recently released (Sept 2023) the result of a year-long investigation by sixteen panelis... more NASA has recently released (Sept 2023) the result of a year-long investigation by sixteen panelists into the UFO or UAP phenomena and the report has on its front digital cover the title: 'NASA UNIDENTIFIED ANOMALOUS PHENOMENA Independent Study Team Report.' This article discusses the problem of collecting data when the panel does not include a wide enough membership of rival theorists.

CoastalME version 1.0: a Coastal Modelling Environment for simulating decadal to centennial morphological changes

Geoscientific Model Development Discussions, 2016

Modelling coastal morphological changes at decadal to centennial time scales is required to suppo... more Modelling coastal morphological changes at decadal to centennial time scales is required to support sustainable coastal management world-wide. One approach involves coupling of landform-specific components (e.g. cliff, beach, dunes, estuaries, etc.) that have been independently developed. An alternative, and novel approach explored in this paper is to capture the essential characteristics of the landform-specific models using a common spatial representation within an appropriate software-environment. In the proposed Coastal Modelling Environment (CoastalME), change in coastal morphology is formulated by means of dynamically linked raster and geometrical objects. A grid of raster cells provides the data structure for representing quasi-3D spatial heterogeneity and sediment conservation. Other geometrical objects (lines, areas and volumes) that are consistent with, and derived from, the raster structure represent a library of coastal elements (e.g. shoreline, beach profiles and estuar...

Irreducible complexity as a nexus for an interdisciplinary dialogue between machine logic, molecular biology and theology

The claim that a principle known as Irreducible Complexity (IC) is empirically discoverable is in... more The claim that a principle known as Irreducible Complexity (IC) is empirically discoverable is investigated successively from the perspective of engineering, then molecular biology and finally theology, with the aim of evaluating the utility of IC for an interdisciplinary dialogue between all three. In the process, IC is subjected to the principle objections presented against it in the literature, leading to the conclusion that IC is sufficiently resistant to scientific criticism to be accepted as a true property of certain living systems. The ubiquity of machine descriptors in the professional literature of molecular biology is scrutinised in the context of the role of metaphor in science, as well as in the context of entailment models. A Biblical Theological approach to the Bible is harnessed to establish a framework for estimating the extent to which the story of Christ warrants expectation of first order design formalisms in nature, and whether that story within itself provides ...

Biomimetics and Biomimesis in the the academy: the clash between engineering and biology in the university (PhD dissertation: Irreducible Complexity and the problem of Underdetermination in the Created Order)

This dissertation problematises the presence of biomimetics or biomimesis in the academy. In sho... more This dissertation problematises the presence of biomimetics or biomimesis in the academy. In short, I have written about a deep seated and profound clash between engineering and biology in the university (engineering interdisciplinarity). Additionally, I explore an approach to the analysis of many bio-systems I have termed The Biomimetic Machine Thesis, which attempts to explore several different ways in which a designer assumption currently provides scientific utility. The extent of the anticipation within the biosphere of functionally equivalent designs exhibited in the technosphere leads to the formulation of the concept I have called ‘philomimesis’, where the latter implies a strong anthropic shaping of the natural world. Theological concepts are also involved, but the key stance adopted in this book is not to ask whether a designed-by-a-designer gloss can be placed over all of the reality we see, but rather to ask about the scientific utility of assuming that design in natural is designed-by-a-designer even if the metaphysics of the actual existence of such a designer is bracketed out.

Kaposi Sarcoma of Childhood: Inborn or Acquired Immunodeficiency to Oncogenic HHV-8

Pediatric Blood & Cancer, 2015

Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection... more Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single-gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV-8.

Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015

Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (ir... more Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF). We reviewed retrospectively the medical records of patients with melanoma who had received treatment between April 2011 and July 2013 with ipilimumab at the standard dose of 3 mg/kg. We collected data on patient demographics, previous and subsequent treatments, number of ipilimumab doses, irAEs and how they were treated, and overall survival. Of the 298 patients, 254 (85%) experienced an irAE of any grade. Fifty-six patients (19%) discontinued therapy because of an irAE, most commonly diarrhea. Overall, 103 patients (35%) required systemic corticoste...

Impact of surgery, radiation and systemic therapy on the outcomes of patients with dendritic cell and histiocytic sarcomas

European Journal of Cancer, 2015

Neoplasms of histiocytic and dendritic cell origin, including follicular dendritic cell sarcoma (... more Neoplasms of histiocytic and dendritic cell origin, including follicular dendritic cell sarcoma (FDCS), histiocytic sarcoma (HS) and interdigitating dendritic cell sarcoma (IDCS), are extremely rare, and data on their natural history and treatment outcomes are sparse. We evaluated the impact of surgery, radiation and systemic therapies on overall survival (OS). We conducted a retrospective chart review of patients with FDCS, IDCS and HS treated at Memorial Sloan Kettering Cancer Center between 1995 and 2014. We identified 31, 15 and 7 patients with FDCS, HS and IDCS, respectively. Median age was 48.7, 42.3 and 58.8years for FDCS, HS and IDCS, respectively. Only a slight disparity in gender distribution existed for FDCS and HS; however, IDCS predominantly affected males (6:1). The most common sites of presentation were abdomen and pelvis (42%), extremities (33%) and head and neck (57%) for FDCS, HS and IDCS, respectively. At diagnosis, 74%, 40% and 86% of patients presented with localised disease in FDCS, HS and IDCS, respectively. Patients with localised disease had significantly improved OS than those with metastatic disease in FDCS (P=0.04) and IDCS (P=0.014) but not in HS (P=0.95). In FDCS and HS, adjuvant or neo-adjuvant therapy was not associated with improved OS compared with observation. In IDCS, surgery alone provided a 5-year overall survival rate of 71%. Adjuvant or neo-adjuvant treatment in FDCS and HS did not affect OS. Patients with IDCS had an excellent outcome with surgery. In the metastatic setting, chemotherapy and small molecule inhibitors may provide benefit.

MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition

Oncotarget, Jan 10, 2015

CDK4 inhibitors (CDK4i) earned Breakthrough Therapy Designation from the FDA last year and are en... more CDK4 inhibitors (CDK4i) earned Breakthrough Therapy Designation from the FDA last year and are entering phase III clinical trials in several cancers. However, not all tumors respond favorably to these drugs. CDK4 activity is critical for progression through G1 phase and into the mitotic cell cycle. Inhibiting this kinase induces Rb-positive cells to exit the cell cycle into either a quiescent or senescent state. In this report, using well-differentiated and dedifferentiated liposarcoma (WD/DDLS) cell lines, we show that the proteolytic turnover of MDM2 is required for CDK4i-induced senescence. Failure to reduce MDM2 does not prevent CDK4i-induced withdrawal from the cell cycle but the cells remain in a reversible quiescent state. Reducing MDM2 in these cells drives them into the more stable senescent state. CDK4i-induced senescence associated with loss of MDM2 is also observed in some breast cancer, lung cancer and glioma cell lines indicating that this is not limited to WD/DDLS cel...

HOX clusters of Latimeria: Complete characterization provides further evidence for slow evolution of the coelacanth genome

The living coelacanth is a lobe-finned fish that represents an early evolutionary departure from ... more The living coelacanth is a lobe-finned fish that represents an early evolutionary departure from the lineage that led to land vertebrates, and is of extreme interest scientifically. It has changed very little in appearance from fossilized coelacanths of the Cretaceous (150-65 million years ago), and is often referred to as a "living fossil." An important general question is whether long term stasis in morphological evolution is associated with stasis in genome evolution. To this end we have used targeted genome sequencing for acquiring 1,612,752 bp of high-quality finished sequence encompassing the four HOX clusters of the Indonesian coelacanth, Latimeria menadoensis. Detailed analyses were carried out on genomic structure, gene and repeat contents, conserved non-coding regions, and relative rates of sequence evolution in both coding and non-coding tracts. Our results demonstrate conclusively that the coelacanth HOX clusters are comparatively slowly evolving and that this taxon should serve as a viable outgroup for interpretating the genomes of tetrapod species.

Phase II Trial of Gemcitabine and Docetaxel with Bevacizumab in Soft Tissue Sarcoma

Sarcoma, 2015

Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sar... more Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sarcoma. This study tested the hypothesis that outcomes would be improved by addition of bevacizumab (B). The initial design was randomized double-blind trial of G + D + B versus G + D + placebo. Due to slow accrual this was modified to single-arm open-label G + D + B. Eligible patients had diagnosis of leiomyosarcoma, pleomorphic undifferentiated sarcoma, pleomorphic liposarcoma, or angiosarcoma. Treatment was B 15 mg/kg on d1, G 900 mg/m(2) on d1 and d8, and D 75 mg/m(2) on d8, q21d. Primary endpoint was progression-free survival (PFS) at 6 months and would be met if ≥17 patients were progression-free at 6 m. Secondary endpoints are response rate, PFS at 3 m, overall survival, and toxicity. Of 44 patients enrolled, 35 were treated with GDB and evaluable for safety and efficacy. Median age was 55, 50% male, most ECOG 0. Toxicity is mostly myelosuppression with one deep vein thrombosis and one small bowel perforation possibly related to B. There were 17 partial responses (49%) by RECIST 1.1. Among 35 patients, the number who remained on study and progression-free was 24 at 3 m and 15 at 6 m. 9 withdrew prior to 6 m for reasons other than toxicity or progression. PFS at 6 m was 65% (95% CI: 51-85%). The primary endpoint of 6 m PFS was not met due to censoring of patients who withdrew. However PFS at 3 m (76%) was promising and response rate was higher than expected from G + D.

Acute myeloid leukemia arising from a donor derived premalignant hematopoietic clone: A possible mechanism for the origin of leukemia in donor cells

Leukemia research reports, 2014

During recent years, it has become increasingly evident that donor leukemia following allogeneic ... more During recent years, it has become increasingly evident that donor leukemia following allogeneic transplant may be more common then realized in the past. We identified five cases of potential donor leukemia cases during past five years. The precise mechanism of the origin of such leukemias, however, remains poorly defined. In this short communication, we report a well documented case of donor-derived de novo acute myeloid leukemia (AML) that developed fourteen years after allogeneic stem cell transplantation for treatment induced AML for his primary malignancy Immunoblastic lymphoma. This case allows us to postulate a possible mechanism of the origin of donor leukemia. The de novo AML clone contained a distinct cytogenetic abnormality, trisomy 11, which was simultaneously detected in preserved peripheral blood obtained at the time of transplantation as well as in the current bone marrow from an otherwise clinically and phenotypically normal donor. The findings from this unique case,...

Development of cell-cycle inhibitors for cancer therapy

Current oncology (Toronto, Ont.), 2009

The cell cycle governs the transition from quiescence through cell growth to proliferation. The k... more The cell cycle governs the transition from quiescence through cell growth to proliferation. The key parts of the cell cycle machinery are the cyclin-dependent kinases (CDKS) and the regulatory proteins called cyclins. The CDKS are rational targets for cancer therapy because their expression in cancer cells is often aberrant and their inhibition can induce cell death. Inhibitors of CDKS can also block transcription.Several drugs targeting the cell cycle have entered clinical trials. These agents include flavopiridol, indisulam, AZD5438, SNS-032, bryostatin-1, seliciclib, PD 0332991, and SCH 727965. Phase i studies have demonstrated that these drugs can generally be administered safely. Phase ii studies have shown little single-agent activity in solid tumors, but combination studies with cytotoxic chemotherapy have been more promising. In hematologic malignancies, reports have shown encouraging single-agent and combination activity. Pharmacodynamic studies show that the dose and sched...

Phase I study of XL281 (BMS-908662), a potent oral RAF kinase inhibitor, in patients with advanced solid tumors

Investigational New Drugs, 2014

Background XL281 is a potent and selective inhibitor of wild-type and mutant RAF kinases with ant... more Background XL281 is a potent and selective inhibitor of wild-type and mutant RAF kinases with anti-tumor activity in multiple xenograft models. Mutations in KRAS or BRAF can activate the RAF/MEK/ERK pathway in human tumors and may confer sensitivity to RAF kinase inhibitors. Methods We performed a phase I study of XL281 in patients with advanced solid tumors. Patients were enrolled in successive cohorts of XL281 orally once daily in 28-day cycles. Twice daily dosing, different formulations, and the effect of food and famotidine were also studied. At the MTD expanded cohorts with defined mutations were treated. Results In total, 160 patients were treated. The MTD on the QD schedule was 150 mg. The most common toxicities were diarrhea, nausea, and fatigue. Plasma Cmax and AUC increased with dose. Famotidine resulted in lower AUC while food had no effect. Two patients had partial responses by RECIST: One with papillary thyroid cancer with NRAS mutation and one with uveal melanoma. Another nine patients had tumor decrease of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 % but did not meet RECIST criteria for PR. Matched tumors pairs from 33 patients showed evidence of RAF inhibition with significant decreases in pERK, pMEK and pAKT. Conclusions XL281 was generally well tolerated and the MTD was established at 150 mg/day. Partial responses and clinical benefit were observed in several patients. Tumor biopsies demonstrated effective target inhibition.

$Research paper thumbnail of Evidence for color coherence in $p\bar{p}$ collisions at $\sqrt{s} = 1.8$ TeV$

Evidence for color coherence in $p\bar{p}$ collisions at $\sqrt{s} = 1.8$ TeV

Color coherence effects in pp¯ collisions are observed and studied with CDF, the Collider Detecto... more Color coherence effects in pp¯ collisions are observed and studied with CDF, the Collider Detector at the Fermilab Tevatron collider. We demonstrate these effects by measuring spatial correlations between soft and leading jets in multijet events. Variables sensitive to interference are identified by comparing the data to the predictions of various shower Monte Carlo programs that are substantially different with

Jet Classification at CDF

International Journal of Neural Systems, 1992

Results for the classification of jets obtained with the use feed-forward neural networks are rev... more Results for the classification of jets obtained with the use feed-forward neural networks are reviewed with particular attention to model-dependence, flavor sensitivity and Et-dependence. First results obtained with a Kohonen-type network are also presented and both are compared with those obtained with a Fisher discriminant.

Broad-Scale Analysis of Morphological and Climate Impacts on Coastal Flood Risk

Coastal Dynamics 2005, 2006

A system of hydrodynamic, morphodynamic and reliability models have been coupled to generate insi... more

Ghost at the feast by Herbert Hammond.pdf

The author argues that there were inconsistencies in the way Anglican leaders in England treated ... more

Dr Cecil Keen research into UFO UAP CUFOS and a curious lecture

This short article is a recollection of my brief friendship with Dr Cecil Keen in Cape Town, Sout... more This short article is a recollection of my brief friendship with Dr Cecil Keen in Cape Town, South Africa in the late 1970’s and 80’s. I first met him through a lecture he gave at the University of Cape Town on his experiences of UFO activity. This was my first introduction to an academic side of the subject because Dr Keen brought his training and critical thinking skills as a meteorologist and climatologist to bear on this topic.

George Whitefield, Google , Equiano and slavery

A few years ago Google began its project to connect West Africa to Europe via an undersea cable, ... more A few years ago Google began its project to connect West Africa to Europe via an undersea cable, naming this project "Equiano" after the abolitionist Olaudah Equiano who was sold into slavery from Nigeria as an 11 year old. Equiano became a Christian after hearing the ministry of George Whitefield, but never criticised Whitefield for owning slaves. From 1730 (the evangelical awakening) to 1770 blindness to slavery remained, but in the late 1700's that all changed. Had Whitefield lived longer, he would have renounced slavery.

A brief examination of TRIZ, biological vs engineering problem solving and the Meta-engineer

A Russian engineer Genrich Altshuller invented a system that makes it possible for an innovator s... more A Russian engineer Genrich Altshuller invented a system that makes it possible for an innovator seeking a solution to a particular design problem today to derive assistance from the past. This is achieved by examining similar problems encountered previously and the way engineers actually solved such problems in days gone by. The application of TRIZ to biological problem solving is not straightforward. It is argued nevertheless that TRIZ does not need to be re-formulated especially if design in the living world is considered from a meta-engineering perspective

Birds are flying machines article Long form (Biomimetics and biomimicry assisting with aviation design. Nature-based patterns for improving aircraft)

Birds are flying machines 'It is not with metal that the pilot is in contact. Contrary to the vul... more Birds are flying machines 'It is not with metal that the pilot is in contact. Contrary to the vulgar illusion, it is thanks to the metal, and by virtue of it, that the pilot rediscovers nature…the machine does not isolate man from the great problems of nature but plunges him more deeply into them.' Antoine Saint-Exupery (1967: 22) A bird is an instrument working according to a mathematical law. It lies within the power of man to make this instrument with all its motions.

Birds are flying machines Short Form (Bimiometics & biomimesis in the service of aviation and aircraft design)

virtue of it, that the pilot rediscovers nature…the machine does not isolate man from the great p... more virtue of it, that the pilot rediscovers nature…the machine does not isolate man from the great problems of nature but plunges him more deeply into them." Antoine Saint-Exupery. "A bird is an instrument working according to a mathematical law. It lies within the power of man to make this instrument with all its motions." Leonardo da Vinci.