Richard Di Rocco | University of Pennsylvania (original) (raw)

Papers by Richard Di Rocco

Consilience, Truth and the Mind of God, 2019

Science and religion seek an explanation for the basis of reality, but neither has the ability to... more Science and religion seek an explanation for the basis of reality, but neither has the ability to objectively decide the ultimate question concerning God’s existence. Theism and atheism are both based on faith; and, in the absence of convincing arguments, proponents of each have polarized in the heat of debate. The essential ontological question about God has been overshadowed by irrelevant arguments. The literal truth of the Bible, as well as the effectiveness of science as a method of understanding natural phenomena, have become proxy issues that are completely irrelevant to the existence of God. Consilience, which posits the unitary nature and coherence of all knowledge (Knowledge is known truth), assures us that the reconciliation of science and religion is possible insofar as practitioners of each discover the truth in varying degrees. A key insight provided by John Dewey’s and Arthur Bentley’s theory of knowledge, as described in “Knowing and the Known”, is that the apprehensi...

The field of abiogenesis explores the mystery concerning how life arose on Earth from non-living ... more The field of abiogenesis explores the mystery concerning how life arose on Earth from non-living matter. We must assume that this happened in accordance with the laws of physics and chemistry. How chemical evolution led to the appearance of self-replicating polynucleotides has not been determined, but significant progress has been made. Uncertainty likewise remains concerning how the enzyme-driven reactions of metabolism arose, as well as how metabolic reactions and polynucleotide-based genetic mechanisms of inheritance were encapsulated together within the membranes of the first cells. This chapter examines a broad outline of molecular biology, and how this information provides retrospective insight into life’s beginning by asking what kind of beginning is consistent with life’s current state of affairs. Information gleaned from this exercise is then integrated with information derived from a prospective exercise that asks how self-replicating polynucleotides, could have formed fro...

The modern human mind confronts many existential questions as it contemplates the vast external r... more The modern human mind confronts many existential questions as it contemplates the vast external reality of the universe in which it exists, and the internal reality of its own perception, thought and self-awareness. Humanity is faced with many unanswered questions about the origin of the universe, life and mind. Most significantly, owing to our faculty of advanced intelligence, humans are confronted with the daunting implications of mortality, and this is the stuff of which existential crises are made. Defense mechanisms protect against the fear of the ego’s annihilation in death, but fear of the ultimate unknown also provides motivation in the quest for understanding. This is inherently disquieting because it requires an admission of profound ignorance. Humility in the face of the unknown is essential, however, because without it the questions that lead to learning go unasked and unanswered. This chapter provides a broad overview of the scope of the epistemological, ontological and...

The vital role of entropy and information in the origin of life from non-living matter, and the e... more The vital role of entropy and information in the origin of life from non-living matter, and the evolution of living matter once it was established on Earth, are examined in this chapter. The origin of human and animal learning and memory in the signal transduction mechanisms of pre-Cambrian single-celled organisms of the primordial oceans is described. This phenomenon offers one of the strongest examples of conserved cell and molecular mechanisms in biology. The subsequent rise of multicellular organisms during the Cambrian explosion approximately 500 million years ago is discussed in the context of predator-prey relationships among the invertebrate animals that were living at that time. The predator-prey dynamic provided the intense selective pressure for the evolution of neural networks that were optimized for effective escape and predatory behaviors, as well as for the mechanisms of synaptic plasticity that underlie learning and memory. The rise of the vertebrates, and mechanisms...

How is truth discovered and proved? One approach to answering this question begins by focusing th... more How is truth discovered and proved? One approach to answering this question begins by focusing the question more narrowly to ask whether new mathematics is invented or discovered. Opinions differ on the answer to this question, but everyone agrees that “new mathematics” must be expressed in the form of true mathematical statements. Are statements of mathematical truth discovered or invented? When the question is posed this way, it is clear that mathematical truth may be discovered, but never invented. This follows from the fact that true statements can be proved using deductive reasoning that leads from a statement already known to be true to the hypothesized mathematical truth which is to be proved. The key point about a sequence of deductive logical statements is that the conclusion is necessarily true if the premises of the argument are true. Mathematical truth, indeed all truth, must exist before it is discovered. It exists eternally and cannot be invented. In what does necessar...

As the title implies, this chapter will review the main conclusions of the preceding chapters as ... more As the title implies, this chapter will review the main conclusions of the preceding chapters as a prelude to consideration of the essential ontological question concerning the existence of God. We begin with “The Metaphysical Poem of Parmenides”, which in its own right provides an intriguing basis for belief in a necessary Being that is the source of all being. The main philosophical arguments for the existence of God are briefly presented, beginning with St. Augustine’s original “Argument from Truth”, which is then followed in historical order by Boethius’ “Argument for the Necessity of a Supreme Good”, and detailed explanation of St. Anselm’s “Ontological Argument”. The five arguments of St. Thomas are then mentioned with particular attention given to “The Argument of the First Cause” and “The Argument of Contingency”, which together lead to the existence of a Necessary Being that is the Self-Sufficient First Cause all that exists. St. Thomas’s “Argument of the First Cause” and “...

Consilience, Truth and the Mind of God

Jnm the Journal of Nuclear Medicine, Sep 1, 1994

In vitro transendothelial permeability was compared to in vivo rat single-pass cerebral extractio... more In vitro transendothelial permeability was compared to in vivo rat single-pass cerebral extractions to evaluate which method would best estimate the blood-brain barrier (BBB) permeability of sev eral SPECT imaging agents. Method: Six "Te complexes and seven non-Tc complexes were tested in vitro using monolayers of primary bovine brain microvessel endothelial cells and in vivo using the rat single-pass cerebral extraction model. In vitro transendothelial permeability indices (PI) were determined by measuring the average percent of radioactivity traversing the monolayers as a function of time. In vivo single-pass cerebral extractions were determined using an indicator fractionation method. Results: A positive correlation between extraction and PI was found for the non-Tc complexes (r2 = 0.96). The CBF imaging agents Tc-ECD and ""Tc-PnAO have high values for E and PI, demonstrating that these agents penetrate the BBB and have a high membrane permeability, while the heart imaging agent "Tc-sestamibi had low values for both E and PI. The low PI and E values for ""Tc-sestamibi are consistent with a low brain uptake for this agent, except in cases of disruption of the BBB. In contrast to "'"Tc-ECD, ""Tc-PnAO and ""Tc-sestamibi, which had concordant values for E and PI, two highly lipophilic boronic acid adducts of technetium dioxime (BATOs), ""Tc-teboroxime and 99nTTcCI(DMG)32MP,had low negative values for PI, but high values for E. In addition, after 3 hr of incubation, the monolayer-to-medium concentration ratio of the BATOs was 642:1 and 744:1, respectively. This compares with values of 89:1 (Tc-PnAO), 25:1 f^Tc-ECD) and 34:1 (""Tc-sestamibi). Conclusion: These data suggest that the high in vivo single-pass extraction of the BATOs may be ex plained by a hydrophobic interaction with the luminal surface of the capillary endothelial cell plasma membrane. We conclude that a high single-pass extraction cannot necessarily be used to infer high BBB or membrane permeability.

Computerized Medical Imaging and Graphics, 1989

Since the inception of the 14C-deoxyglucose method and its extension to in vivo imaging of region... more Since the inception of the 14C-deoxyglucose method and its extension to in vivo imaging of regional cerebral glucose metabolism in humans by positron emission tomography, uncertainty has persisted concerning the type of work to which regional metabolism is coupled, as well as the distribution of this work within the neuron. "C-deoxyglucose studies indicate that functionally-coupled neural metabolism is more apparent in axon terminals and perhaps dendrites than neuronal perikarya. Moreover, it appears that most of the metabolism in axon terminals is accounted for by Na+-K+-ATPase activity. Nevertheless, cytochrome oxidase hi&chemistry reveals the presence of intensely reactive mitochondria in soma-dendrite regions opposite presynaptic axon terminals, thereby indicating that continuous temporal and spatial summation of postsynaptic graded potentials is associated with increased metabolism. While the situation concerning the relative postsynaptic metabolic prices of EPSP's and IpSP's remains uncertain, the presence of elevated levels of cytochrome oxidase activity within certain classes of presynaptic terminals indicates that active excitation and inhibition is associated with increases in presynaptic metabolism. This observation has been confirmed in 14C-deoxyglucose studies. Nevertheless, studies of neonatal hippocampus indicate that, before metabolic activity shifts to dendritic and telodendritic regions of electrophysiological activity, metabolism is high in somal foci of biosynthesis.

Journal of Nuclear Medicine, Apr 1, 1993

Single-Pass Cerebral Extraction â€¢ Di Rocco et al.

Journal of Neurochemistry, 1998

p38 MAPK has been implicated in the regulation of prom-flammatory cytokines and apoptosis in vitr... more p38 MAPK has been implicated in the regulation of prom-flammatory cytokines and apoptosis in vitro. To understand its role in neurodegeneration, we determined the time course and localization of the dually phosphorylated active form of p38 MAPK in hippocampus after global forebrain ischemia. Phosphorylated p38 MAPK and mitogen-activated protein kinase-activated protein 2 activity increased over 4 days after ischemia. Phosphorylated p38 MAPK immunoreactivity was observed in microglia in regions adjacent to, but not in, the dying CAl neurons. In contrast, neither c-Jun N-terminal kinase 1 nor p42/p44M~activity was altered after ischemia. These results provide the first evidence for localization of activated p38 MAPK in the CNS and support a role for p38 MAPK in the microglial response to stress.

SCIENCE, 1979

The reduction of glycolysis by hypoglycemia or the glucose analog 2-deoxy-in-glucose (2DG) stimul... more The reduction of glycolysis by hypoglycemia or the glucose analog 2-deoxy-in-glucose (2DG) stimulates compensatory sympathetic alterations of metabolism. Considerable attention has been focused on the hypothalamus as the probable locus of requisite metabolic signal detection. We report, however, that unanesthe-tized chronically decerebrate rats are capable of exhibiting sympathoadrenal hyper-glycemia in response to the metabolic challenge presented by 2DG. Thisfinding demonstrates that theforebrain is not necessary for glucoprivic stimulation ofthis reflex. Since cervical cord transection has been shown to eliminate hyperglycemia induced by 2DG, we conclude that the caudal brainstem contains an essential part of the neural mechanism which both detects metabolic need and ameliorates that need through the, release of stored fuels. Deficits in metabolic fuels produce compensatory ingestive and metabolic responses that maintain adequate concentrations of plasma glucose (1-3). Attempts to define the neural organization of energy homeostasis have generally fo-cused on the hypothalamus as the locus of elements sensitive to signals of metabolic need (4-6), Recently, however, several lines of evidence have converged to call attention to the importance of ex-trahypothalamic mechanisms for energy homeostasis (7, 8). Since considerable uncertainty persists concerning the af-ferent dimension of metabolic homeo-stasis, our strategy has been to examine a metabolic reflex whose efferent mechanisms are well specified in order to localize its mediating afferents.

Journal of Neuroscience, 1996

Although the interleukin-1␤ converting enzyme (ICE)/CED-3 family of proteases has been implicated... more Although the interleukin-1␤ converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell death in vitro and in ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this question, we examined the in vivo expression of one of these genes, Ice, after global forebrain ischemia in gerbils. Using RT-PCR and Western immunoblot techniques, we detected an increase in the mRNA and protein expression of ICE in hippocampus during a period of 4 d after ischemia. Chromatin condensation was observed in CA1 neu-rons within 2 d after ischemia. Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3 and 4 d after ischemia, a period during which CA1 neuronal death is maximal. In nonischemic brains, ICE-like immunoreactivity was relatively low in CA1 pyramidal neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like immunore-activity was not altered in these neurons. ICE-like immunore-activity, however, was observed in microglial cells in the regions adjacent to the CA1 layer as early as 2 d after ischemic insult. The increase in ICE-like immunoreactivity was robust at 4 d after ischemia, a period that correlates with the DNA fragmentation observed in hippocampal homogenates of isch-emic brains. These results provide the first evidence for the localization and induction of ICE expression in vivo after isch-emia and suggest an indirect role for ICE in ischemic damage through mediation of an inflammatory response.

Journal of Cerebral Blood Flow and Metabolism, 1993

Autoradiograms obtained after middle cere bral artery occlusion (MCAO) in spontaneously hyperten ... more Autoradiograms obtained after middle cere bral artery occlusion (MCAO) in spontaneously hyperten sive rats show that the 99mTc complex of a 2-nitroimid azole-derivatized propylene amine oxime (BMS-181321) is selectively retained in acutely ischemic brain before disruption of the blood-brain barrier (BBB), but not in the ischemic infarct. BMS-181321 is therefore a marker of ischemic tissue at risk of infarction and its uptake, unlike that of x-ray and magnetic resonance contrast agents, does not require disruption of the BBB. In keeping with this conclusion, we have found that the single-pass cere bral extraction fraction of BMS-181321 is 0.67 at normal rat whole-brain blood flow. Sequential single-photon

Journal of Nuclear Medicine, 1994