The Telmarc Group

A Technology Investment and Management Company

White Papers

This section provides a listing of the most recent white papers prepared by Telmarc principals. The Telmarc White Papers are now almost monthly reports on current topics in genomics, medicine, Health Care policy, telecommunications, economics, economic policy and technology. In general, Telmarc may also publishes a detailed report accompanying each of the Telmarc White Papers.

NOTE:

THE DOCUMENTS CONCERNING MEDICAL RELATED TOPICS ARE DRAFT AND SUBJECT TO REVISION AND ARE NOT IN ANY MANNER TO BE CONSIDERED FOR MEDICAL PURPOSES. THEY REFLECT RESEARCH AND OPINION ONLY. THEY ARE SUBJECT TO REVIEW, REVISION AND CORRECTION. NO MEDICAL ADVICE IS INTENDED OR IMPLIED.

No. 144 Platelets and Check Point Inhibitors

April 2017 Platelets have been demonstrated as a vehicle to disseminate various check point inhibitors locally to treat cancer excisions and remove lingering cells. We examine this in some detail.

No. 143 PARP, DNA and PCa

February 2017 We have reviewed some recent work on PARP which is a single strand DNA repair protein and PCa. PARP inhibitors can eliminate the double strand DNA repair defects when BRCA -/- tumors are present. 

No. 142 Immune Set Points

February 2017 We examine the recent work regarding the existence of set points in the activity of T cells and in their use against cancers. The paper examines multiple points and presents some extensions.

No 141 Gene Drive

December 2016 Gene Drives are genetically engineered mechanisms which effectively insert a desired gene segment into a species. The supersaturate the species genetic makeup by inserting a gene along with a CRISPR/Cas9 or similar self-replicating mechanism.

No. 140 CAR T Cells and Cancer

November 2016 The introduction of chimeric antigen receptor or CAR T cells has provided an interesting and powerful new tool in cancer therapy. We provide a brief summary of this new area.

No. 139 A Proposed Metric for Measuring Bacterial Growth

September 2016 This paper discusses some novel methods to ascertain variations in bacterial growth rates from a hypothesis testing perspective. 

No. 138 NKX3.1 and PCa

July 2016 NKX3.1 is a homeobox gene which has been identified as a factor in PCa. We examine its effects and do so in the context of some recent research results. 

No. 137 Biofilm Growth and Infiltration

May 2016 We have examined the growth of biofilms with a focus on remediating drinking water systems such as those in Flint, MI. Biofilms are factors that both impair the flow systems and present putative health risks. Our focus is on trying to explain their establishment and mitigate against such establishment by surface modifications such as nano Se and surface nano treatments. 

No. 136 Cancer Stem Cells and Cells of Origin Redux

May 2016 There is an ongoing debate regarding the cancer cell of origin CCO and the cancer stem cell CSC in PCa. This paper reexamines the issue which we first looked at some four years ago. We suggest an alternative view, using system metrics and stochastic spatio-temporal models. 

No. 135 Seven Types of PCa

April 2016 A recent paper identified some 7 gene fusions or mutations found in the initial stages of PCa. We examine these in some detail.

No. 134 CHK2, AR, and PCa

February 2016 This is a discussion of a new paper which argues that CHK2 gene product down regulates AR expression and this its absence is seen in various CRPC.

No. 133 LY6 and Prognostic Markers

February 2016 This is a discussion of a new paper discussing LY6 markers for prognostic values in many cancers and their use to identify cancer stem cells.

No. 132 More PCa Markers

February 2016 This is a discussion of a new proposed set of markers for PCa detection.

No. 131 pro-NPY and PCa

February 2016 This is a discussion of a proposed new marker for PCa progression.

No. 130 SPOP and Prostate Cancer

November 2015 This paper examines some recent studies examine the role of SPOP and PCa.

No. 129 Trust but Verify: The PSA Saga

November 2015 This is a case study which demonstrates the various swings when using PSA. It looks at its use in a Markovian manner and considers its ability to predict.

No. 128 Prostate Cancer Prognostics

October 2015 This paper examines the many PCa diagnostic and prognostic tests. It adds significantly to the basic PSA which we believe is still a valuable tool.

No. 127 STAT3 and PCa: Of Mice and Men

August 2015: STAT3 is a gene expression that can be activated by IL-6 and previously was considered a driver in metastatic growth. A recent paper presents an alternative picture which we consider herein. This presentation demonstrates the complexity of genetic dynamic pathways as well as the issue of mouse models versus human reality.  

No. 126 Prostate Cancer Metastasis: A Simple Example

July 2015 This report provides more detail on our cancer models and focuses on recent observations by Gundem et al on multiple gene expression states and cell proliferation rates.

No. 125  CRISPR and Cancer Revised

April 2015 This is a revision of the WP 111 and includes details on CRISPR functions 

No. 124 CRISPR Cas9: A Genomic Tool

April 2015 We examine CRISPR as a tool to be used in genomic engineering. This paper looks at basic principles in the utilization of this as a tool for editing genes. 

No. 123 Metformin, Statins and PCa

February 2015 Recent results demonstrating the efficacy of combined metformin and statin use in prostate cancer is reviewed and analyzed. This work demonstrates the impact of inflammatory processes on cancer. 

No. 122 MDS and DNMT1 Pathway Control

February 2015 MDS, Myelodysplastic Syndrome, is a complex hematopoietic disorder that appears to be driven by epigenetic methylation of transcription factor regions in various cell lines. A standard procedure has been to use high doses of DNMT1 suppressors and these have demonstrated efficacy in almost all cases for a period of time. However there is the question of what targets are methylated, how and what the proper dosages should be. Recent research has argued for a substantially lowered dose, which may have substantial efficacy in view of the fact that system demethylation could be problematic. We examine this process herein.  

No. 121 Sirt1, Exosomes and Prostate Cancer

January 2015: We use a recent paper regarding the suppression of the gene in Sirt1 in mice to examine a set of issues. First, we examine the issue of putative exaggeration of the extensibility of results from mice to humans. Second, we examine the relationship of miRNAs to a control mechanism in the process. Third, we consider the impact of exosomes as a putative mechanism for metastasis.

No. 120 CNVs and Prostate Cancer

This paper discusses some recent research on the use of CNVs for prognostic measures in prostate cancer. We examine this work and others. We also remark upon how the Press reports on these types of findings and ask what is the duty of the researchers to assure reporting clarity. 

No. 119 SNPs and Prostate Cancer

This is a continuation of analyses of SNPs as means for assessing PCa.

No. 118 Vitamin D and Prostate Cancer

We examine the use of Vitamin D as both a preventative of and treatment for Prostate Cancer. The results are not clear.

No. 117 SPDEF, ETS Transcription Factors and PCa

We examine the transcription factor ETS and its related pathway elements in the progression of metastatic prostate cancer. 

No. 116 Methylation, Prostate Cancer, Prognostics

August 2014 This paper examines some recent work on methylation markers and their use in ascertain prognostic measures for progression of PCa. 

No. 115 Endosomes and Melanoma

July 2014 This paper examines some recent work on Rab7 and the enosome process in metastatic melanoma cells. Endosomes may bring in nutrients that feed proliferation.

No. 114 NOTCH, miR-146a and Melanoma

June 2014 This paper examines the recent reports of the identification of a miRNA that blocks a control element, NUMB, and thus activates a transcription factor in the Notch receptor.

No. 113 Wealth

May 2014 This paper considers the recent work by Piketty and the commentary by Francis both regarding wealth and inequality. It does so in the context of the entrepreneurial economy and historical precedents.

No. 112 Prostate Cancer: miR-34, p53, MET and Methylation

May 2014 The interaction between pathway elements, receptors, methylation and miRNAs is well played out in these recent observations on PCa.

No. 111 CRISPR and Cancer

April 2014 This is a brief paper on the use of CRISPR-Cas9 complex to deal with genetic changes causing cancer. This is an interesting tool for the genomic engineering toolkit. 

No. 110 ERG and Prostate Cancer

January 2014 This is a discussion based upon some recently reported results linking aggressive prostate cancer to ERG fusion with TMPRSS2 in HGPIN.

No. 109 Reading Marx on a Cold Day

January 2014 This is a short paper examining Marx and his theories in light of the massive upheaval in means of production. Namely, following Wiener and his analysis it is clear that labor is a smaller element of anything produced and this the core assumptions of Marx should be re-examined.

No. 108 Cancer Cell Dynamics

January 2014 We have revised our work on cancer cell dynamics and placed them in a single white paper. There is both editing and new material here.

No. 107  Prostate Cancer Genetic Metrics

January 2014 We have examined and integrated studies of PCa genetic tests and we argue that many of them may be merely correlations and not causations.

No. 106 Divergent Transcription

December 2013 Divergent Transcription is the transcription of RNA segments not part of the normal process of gene to protein. Many of the RNA segments do not become proteins but do set up a network process enabling the creation of new genes. We examine this process herein. 

No. 104 Prostate Cancer and Blood Borne Markers

December 2013 There has been continuing work on blood borne markers. We discuss two approaches here based on recent work. 

No. 103 Prostate Cancer Indolence

December 2013 There has been some recent work examining the putative markers to determine prostate cancer indolence and aggressiveness. This paper examines that work and makes some detailed observations. This is a critical tool for managing this disease. 

No. 102 MDS and Methylation

August 2013 MDS is a disorder of the blood forming cells due to methylation. This paper investigates the literature and progress made in multi-tiered treatment using methylating suppressing therapeutics, bone marrow transplants and cytokine induced killer cells. 

No. 101 Exosomes and Cancer

August 2013 Exosomes a vesicles which are ejected by cells and contain RNA which may be reflective of the state of a cell's health. Recent work has shown that using exosome RNA may provide improved diagnostic capabilities in several areas of cancer detection. This paper discusses some of these issues.

No. 100 lncRNA and Prostate Cancer

long non-coding RNA is one of several epigenetic factors which can change gene expression. This short paper presents new results which show its effect in prostate cancer. This represents s significant advancement in epigenetic factors.

No. 99 SNPs and Cancer Prognostics

 July 2013 SNP and Cancer Prognostics  (July 2013) We have examined SNPs and cancer prognostics for several cases. The arguments are we believe somewhat shaky and we explain why. SNP use is general done without any causative basis and at best it is correlative but oftentimes irreproducible. 

No. 98 CCP and Prostate Cancer

CCP and Prostate Cancer  (July 2013) Recent work on using a collection of genes related to cell cycle progression, CCP, has resulted in a metric for prostate cancer prognostics. We examine this metric and in our opinion show significant concern as to reproducibility. 

No. 97 ATF2 and Melanoma

ATF2 and Melanoma  (July 2013) Multiple target genes and their products have been focused on for controlling melanoma. ATF2 is a transcription factor which is of interest because when in the nucleus it results in proliferation and when in the cytoplasm results in apoptosis.

No. 96  PD-1 and Melanoma Therapeutics

PD-1 and Melanoma Therapeutics (June 2013) There has been a great deal of development of therapeutics for melanoma utilizing the immune system against the metastatic cells. We discuss here two new therapeutics both of which target PD-1 receptors, inhibiting them and thus allowing the activation of the T cell against the melanoma.

No. 95  MER Tyrosine Kinase Receptors and Inhibition

MER TK Receptors (June 2013) is a discussion of a specific receptor and its impact on metastatic melanoma. It uses this specific pathway to discuss issues regarding inhibitors.

No. 94 Melanoma Therapeutics

Melanoma Therapeutics  (May 2013)  This White Papers discusses the many new and innovative therapeutics useful for melanoma.

No. 93 Cancer Cell Dynamics Methylation and Cancer

Cancer Cell Dynamics  (April 2013)  We extend our examination of cancer spatio-temporal dynamics and add a Markov chain model for malignant cellular transitions. From this we are able to develop a simple and closed form solvable model for the average number of malignant cells of a specific type at a specific location at a specific time. We examine the diagnostic, prognostic and therapeutic implications of this methodology.

No. 92 Wireless Vs. Fiber

Wireless Vs. Fiber  (April 2013)  The competition between wireless and fiber has become more intense over the past few years. In addition it can be seen in the actual deployment of fiber that companies such as Verizon have limited the deployment to high end business applications and also to the inter-connection backbone for the wireless plant. This paper examines the changes in the technology that allow for potential deployment of an all wireless plant for both residential and commercial usage. The reasons for such a change are several fold; technological, operational, and financial. Our conclusion is that technology has progressed in wireless at a high competitive manner and that bandwidth is readily available. Using wireless may now be the means to provide voice and data as well as bandwidth intensive uses such as video as well. 

No. 91 Methylation and Cancer

Methylation and Cancer  (March 2013)  We examine methylation and several cancers. There has been statements that all cancers are epigenetic and we have discussed several of these previously. One of the epigenetic factors is methylation, a somewhat understood phenomenon often seen in cancers, and often indicate as causative rather than a consequence. Recent work in anti-methylation therapeutics has raised interest here as well as preventative measures as ways to reduce methylation. methylation.

No. 90 Telomeres and Melanoma

Telomeres and Melanoma (February 2913)  Telomeres are the end points of chromosomes and they tend to shorten each mitotic doubling and are often the life limiting factor in cell lifetimes. Several researchers have discovered in a high percentage of melanomas a changed gene which creates an excess of TERT the protein that ensures Telomere survival. We examine this finding and consider some consequences.

No. 89 miRNA and Melanoma

miRNA and Melanoma (January 2013) is a brief report discussing the importance miRNA in melanoma and to a degree to other cancers. The report focuses on the growing significance of miRNAs in understanding cancer and potentially in developing therapeutics.

No. 88 Extracellular Matrix vs. Intracellular Pathways

Extracellular Matrix vs. Intracellular Pathways is a brief report discussing the importance of the ECM in cancer dynamics. It uses the recent paper from Fisher's Lab Team looking at melanoma metastasis.

No. 87 Prostate Cancer Prognostic Markers

Prostate Cancer Prognostic Markers is a brief report on some recent work detailing two papers presenting prognostic markers. The markers are mostly immune system markers for late stage PCa. They at best can tell when death is short term, 10 months, or long term, 30-36 months. It is our opinion that the result does not provide patient or clinical value. 

No. 86 Cancer Models for Understanding, Prediction, and Control

Cancer Models is a review and development of an integrated. Intracellular pathway based model along with a full body distributed propagation model of cancer cells. It links the two together and demonstrates how the constants may be determined and how the models may be used for prognostic value and treatment. The underlying cancer being considered is melanoma.

No. 85 Prostate Cancer Stem Cells

Prostate Cancer Stem Cells is an analysis of the current state of thinking of cancer stem cells as they apply to prostate cancer. The document reviews many of the current papers and provides a detailed analysis of the process of cell cycle management and control. In addition is poses a number of significant questions regarding these theories. NOTE: This paper was highlighted by MD Anderson Cancer Center, Tang Lab, in it Highlights for 2012.

No. 84 Epistemology of Cancer Genomics

Epistemology of Cancer Genomics is a study of some of the underlying principles, philosophic and otherwise, regarding the building of cancer genomic models.

No. 83 Prostatic Intraepithelial Neoplasia

This is a study of HG PIN as a vehicle leading to PCa. We examine its genetic development and then look at the issue of cancer stem cells and HGPIN conversion. AVAILABLE UPON REQUEST.

No 82 Prostate Cancer: Metastatic Pathway Identification

Prostate Cancer: Metastatic Pathway Identification (February 2011) This White Paper looks at some recent work done at Dana Farber and examines it from the perspective of pathways. The work at Farber is in line with what we were looking at a couple of years ago as we saw the needs for such developments in health care and its costs management. We examine their result in the light of it being an early step as well as in needing additional development and clarification.

No 81 Backscatter Radiation and Cancer

Backscatter Radiation and Cancer (December 2010) This is a White Paper which presents an analysis of the issue of Backscatter Radiation and its impact on cancer in the human. It focuses on melanoma since the backscatter is primarily in the top 1 cm of the human exposed. It shows that there should be considerable concern regarding the widespread use of this technology.

No 80 PSA Evaluation Methodologies

Evaluation Methodologies (December 2010) This is a White Paper which develops a new PSA evaluation methodology using a system model for prostate cell growth based upon measurable constants. It uses a maximum likelihood approach and is both verifiable and predictable. The paper looks at specific examples but does not provide any clinical recommendations.

No 79 The PSA Controversy

The PSA Controversy (November 2010) This is a White Paper which looks in detail at the PSA test and the many controversies surrounding it. We argue that the development of a CMS CER process will cause significant morbidity and mortality to seniors on Medicare as a result of the confusion regarding the effectiveness of the process.

No 78 Progressivism, Individualism and the Public Intellectual

Progressivism and Individualism (August 2010) This book is a draft of a work in progress which compares neo-individualism to neo-progressivism. It attempts to place a light on the political issues of the current day by placing them in historical context.

No 77 Obesity and Type 2 Diabetes: Cause and Effect

Obesity and Diabetes  (June 2010) This paper is a length analysis of the cause and effects in the chain of sequelae of Obesity and Type 2 Diabetes and includes a financial analysis and discussion on policy implications.

No 75 The Rowe Conjecture and the Efficient Market Hypothesis

The Rowe Conjecture and the EMH  (February 2010) This White Paper looks at the efficient market hypothesis and bubbles employing a conjecture of Nick Rowe. It combines true market behavior with buyer perception and demonstrates cycles.

No 74 A Comparison of HR 3962 and HR 3200

A Comparison of HR 3962 and HR 3200 (November 2009) This White Paper looks at both Bills and presents details from several key sections.

No 73 Economic Dynamics of the Public Option in Health Care

Economic Dynamics of the Public Option (November 2009) This White Paper looks at the Public Option from a dynamic economic perspective including attractants and repellants for both patients and providers. It demonstrates an analytical tool which can be used to ascertain the dynamic and interactive behavior of the PO. It also shows how the CBO estimate may be well off the mark due to these factors.

No 72 Some Ideas on a Health Care Plan

Some Ideas on a Health Care Plan (September 2009) This is a White Paper which develops a Health Care Plan in a simple and straight forward manner and shows how it can be fully funded providing universal service and coverage from existing funds.

No 71 Medicare Myths and Realities: A Précis Revised

 Medicare Myths and Realities  (July 2011) This is a Revised White Paper which looks at the myths and realities of Medicare. It builds on prior work and puts in one short White Paper the main argument for Medicare and against the cynics and critics who are attacking it.

No 70 Health Care Cost Reductions

Health Care Cost Reductions  (September 2009) This is a White Paper which focuses on specific areas for cost reductions in health care. We estimate a $650 Billion dollar reduction in the 2008 health care costs which can be readily carried forward. We examine a set of specific areas and propose strategies and action plans.

No 68 Medicare: Some Facts Amongst the Fiction

Medicare: Some Facts Amongst the Fiction  (September 2009) This is a White Paper which looks at the many issues surrounding Medicare. We show that the average worker contribute 65% more to Medicare than they will ever collect. The problem with Medicare is NOT Medicare but that Congress "steal" the money which has been contributed. This is a clear precedent against ever considering a Government sponsored plan.

No 67 The FED Balance Sheet and Inflation

The FED Balance Sheet and Inflation (August 2009) is a White Paper in which we examine the current explosion in monetary base and its impact on long term inflation. We see a doubling of the monetary base with no change yet in M2 and we expect the M2 growth to explode in the next few years. Inflation well in excess of 15% is anticipated. The new proposed Stimulus, Stimulus II will exacerbate this along with the additional spending proposed by the current Administration.

No 66 Quality: A Challenge for Healthcare

Quality: A Challenge for Healthcare (August 2009) is a White Paper in which we examine the issue of quality. All the legislation purports to provide quality care but there are no definitions. Everyone BUT the patient is involved in determining quality. The Brits define quality by a single number and then ration health care accordingly. The use of that system here we believe would be a death sentence for many.

No 65 Health Care Delivery Options and Strategies

Health Care Options (May 2009) is a current White Paper which looks at the Obama and Baucus Plans and does so in the context of two philosophical schools, overall decision elements and then examines several key weaknesses, namely the Comparative Clinical Effectiveness issue and the issue of Bundling payments. The philosophical schools are the Rawls schools of Justice and the Fleck school of thought collectives. We have examined the Rawls approach a decade ago in the context of Universal service in telephony and we expand that to health care. The Fleck analysis is interesting in that it brings into question the very existence of the "facts" that are used in the underlying arguments and presents the construct of the thought collective.

No 64 Galbraithian (April 2009)

Galbraitianistic (April 2009) is a White Paper where we look at the current Administration, and indirectly others, from the eyes of a Galbraithian and attempt to deconstruct their world view and the paradigms which shape it.

No 63 Remediable Diseases (April 2009)

Remediable Diseases (April 2009) is a White Paper which examines a set of cancers which can be detected in many cases in early stages. However for many of these there is little support for ensuring that this is accomplished resulting a three times increase in health care costs due to the failure to capture at an early state. The failure to capture at a early state is an economic and psychological problem. We believe that the issue can be re-mediated by addressing both issues. Further this analysis brings out an interesting and quite important observation about almost all health care proposals, namely that they merely project the past forward assuming that there will be no fundamental change in medicine and medical techniques. We believe that for many cancers in the 2010-2030 time period that significant genetic modalities of detection and therapeutics will alter the very structure of the health care delivery system.

No 62 Cap and Trade (March 2009)

Cap and Trade (March 2009) is a recent White Paper which looks at the cap and trade proposals of the Administration. It does so by developing a simple but accurate model for the process. It shows that on one hand it is achievable if everything works but that in any political environment there will be so many counter-forces that it will suffer significant litigious lag. In addition we examine the many unintended consequences and it is this analysis which is grossly lacking for all other studies.

No. 61 Type 2 Diabetes: A Controllable Epidemic (March 2009)

Type 2 Diabetes: A Controllable Epidemic (March 2009) is a White Paper which demonstrates the potential impact an economic control of behavior can have in reducing a major health care cost. Type 2 Diabetes is caused by obesity in almost all cases. It currently, in 2008 costs, accounts for almost $275 billion annually or 12% of all health care costs. We estimate that by 2020 it will account for 25% of health care costs and is growing at 10-11% per annum. It is possible to control this at the source by taxing "carbs" as we have taxed tobacco. This paper presents the case from the perspective of the medical evidence, costs factors and economic control models.

No 58 Observations on HR1: The Stimulus Package (February 2009)

Observations on HR1: The Stimulus Package (February 2009) is a White Paper we have prepared to analyze the Stimulus Package HR1 passed by the US House last week. We wish to make several key observations. The more than $350 billion in new Appropriations are massive Pork with tails which will end up costing the taxpayer much more than the Bill itself. They will create massive un-funded mandates and there has been de minimis discussion of any of them. Second, the additions to existing Appropriations, increases in spending, of $250 billion are a mix of support and handouts. The Tax portion of $187 billion is slow to get deployed and does nothing to create a single job!

No 57 Healthcare Policy Redux (February, 2009)

Healthcare Policy Redux (February 2009) is a White Paper which reviews the current Healthcare dilemma and in turn compares some of the current plans including the Obama Plan and goes back and looks at the Hillary Healthcare Plan of 1993. The latter is a benchmark in how not to do anything. We bring up to data many of the issues make recommendations of Demand Control in Healthcare as well as Supply improvement, especially on the cost side.

No. 49 The Electronic Medical Record

The Electronic Medical Record (January 2009) This is a White Paper which looks at the proposed Obama Plan for the Electronic Medical Record, EMR, as an key element in the economic stimulus package. We argue from our more than twenty years of work in this area that an EMR is an evolving thing and that just throwing money at it may not just be a waste of money but could actually create real harm.

1990 Harvard Architecture Paper

The Harvard Architecture paper was the primary first step paper which established the Kuhn approach that we now broadly use.