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Associations between polymorphisms in leptin and leptin receptor genes and colorectal cancer survival

Cancer Biology & Medicine 2023年第6期20卷 438-451页

作者： Meizhi Du Yu Wang Jillian Vallis Matin Shariati Patrick S.Parfrey john r.Mclaughlin Peizhong Peter Wang Yun Zhu Department of Epidemiology and Biostatistics School of Public HealthTianjin Medical UniversityTianjin 300070China Division of Community Health and Humanities Faculty of MedicineMemorial University of NewfoundlandSt.John's A1B 3V6Canada Clinical Epidemiology Unit Faculty of MedicineMemorial University of NewfoundlandSt.John's A1B 3V6Canada Dalla Lana School of Public Health University of TorontoToronto M5T 3M7Canada Beatrice Hunter Cancer Institute Halifax B3H 4R2Canada Centre for New Immigrant Wellbeing Markham L3R 9V1Canada

Objective:Leptin(LEP)is an obesity-associated adipokine associated with tumor cell *** examined the relevance of genetic variants of LEP and leptin receptor(LEPr)to colorectal cancer(CrC)survival by using data from the Newfoundland Familial Colorectal Cancer ***:A total of 532 patients newly diagnosed with CrC between 1997 and 2003 were followed up until April *** on their demographics and lifestyles were collected via *** of blood samples was performed with the Illumina Human Omni-Quad Bead *** Cox models were used to assess the relationships of 35 tag single-nucleotide polymorphisms(SNPs)in LEP and LEPr with overall survival(OS),disease-free survival(DFS),and CrC-specific ***:At the gene level,LEP was associated with DFS(P=0.017),and LEPr was associated with both DFS(P=0.021)and CrCspecific survival(P=0.013)in patients with *** single-SNP analysis,LEP rs11763517,LEPr rs9436301,and LEPr rs7602 were associated with DFS after adjustment for multiple *** LEPr haplotypes G-C-T(rs7534511-rs9436301-rs1887285)and A-A-G(rs7602-rs970467-rs9436748)were associated with prolonged OS among patients with CrC overall(G-C-T:Hr,0.63;95%CI,0.43–0.93;A-A-G:Hr,0.59;95%CI,0.38–0.91)and those diagnosed with colon cancer(G-C-T:Hr,0.54;95%CI,0.34–0.86;A-A-G:Hr,0.49;95%CI,0.29–0.83).Similar results were observed for ***,significant interactions were found among LEPr rs7602(A vs.G),LEPr rs1171278(T vs.C),red meat intake,and BMI status:the associations between these variants and prolonged DFS were limited to patients with below-median red meat consumption and body mass index(BMI)rphic variations in the LEP and LEPr genes were associated with survival of patients after CrC *** LEP/LEPr-CrC survival association was modified by participants’red meat intake and BMI.

关键词： colorectal cancer intake

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Transport receptor occupancy in nuclear pore complex mimics

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Nano research 2022年第11期15卷 9689-9703页

作者： Alessio Fragasso Hendrik W.de Vries john Andersson Eli Ovan der Sluis Erik van der Giessen Patrick r.Onck Cees Dekker Department of Bionanoscience Kavli Institute of NanoscienceDelft University of TechnologyVan der Maasweg 9Delft 2629 HZThe Netherlands Zernike Institute for Advanced Materials University of GroningenNijenborgh 4Groningen 9747AGThe Netherlands Department of Chemistry and Chemical Engineering Chalmers University of TechnologyKemivägen 10Gothenburg SE-41296Sweden

Nuclear pore complexes(NPCs)regulate all molecular transport between the nucleus and the cytoplasm in eukaryotic *** disordered Phe-Gly nucleoporins(FG-Nups)line the central conduit of NPCs to impart a selective barrier where large proteins are excluded unless bound to a transport receptor(karyopherin;Kap).Here,we assess“Kap-centric”NPC models,which postulate that Kaps participate in establishing the selective *** combine biomimetic nanopores,formed by tethering Nsp1 to the inner wall of a solid-state nanopore,with coarse-grained modeling to show that yeast Kap95 exhibits two populations in Nsp1-coated pores:one population that is transported across the pore in milliseconds,and a second population that is stably assembled within the FG mesh of the *** current measurements show a conductance decrease for increasing Kap concentrations and noise data indicate an increase in rigidity of the *** reveals an accumulation of Kap95 near the pore wall,yielding a conductance *** find that Kaps only mildly affect the conformation of the Nsp1 mesh and that,even at high concentrations,Kaps only bind at most 8%of the FG-motifs in the nanopore,indicating that Kap95 occupancy is limited by steric constraints rather than by depletion of available *** data provide an alternative explanation of the origin of bimodal NPC binding of Kaps,where a stable population of Kaps binds avidly to the NPC periphery,while fast transport proceeds via a central FG-rich channel through lower affinity interactions between Kaps and the cohesive domains of Nsp1.

关键词： nuclear pore complex intrinsically disordered proteins nuclear transport receptors karyopherins nanopores biomimetics molecular dynamics coarse-grained modeling

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Vector Affine Quantization Can Create Valid Quantum Field Theories

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Journal of High Energy Physics, Gravitation and Cosmology 2022年第1期8卷 237-242页

作者： john r. Klauder Department of Physics and Department of Mathematics University of Florida Gainesville USA

Affine quantization, a parallel procedure to canonical quantization, needs to use its principal quantum operators, specifically D = (PQ+QP)/2 and Q ≠ 0, to represent appropriate kinetic factors, such as P2, which involves only one canonical quantum operator. The need for this requirement stems from path integral quantizations of selected problems that affine quantization can solve but canonical quantization fails to solve. This task is resolved for simple examples, as well as examples that involve scalar, and vector, quantum field theories.

关键词： Affine Quantization Vector Field Models Flexibility of the Dilation Variable

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Quantum Physics Has a New, and remarkable, Expansion

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Journal of High Energy Physics, Gravitation and Cosmology 2023年第2期9卷 467-474页

作者： john r. Klauder Department of Physics and Department of Mathematics University of Florida Gainesville USA

Canonical quantization has taught us great things. A common example is that of the harmonic oscillator, which is like swinging a ball on a string back and forth. However, the half-harmonic oscillator blocks the ball at the bottom and then it quickly bounces backwards. This second model cannot be correctly solved using canonical quantization. Now, there is an expansion of quantization, called affine quantization, that can correctly solve the half-harmonic oscillator, and offers correct solutions to a grand collection of other problems, which even reaches to field theory and gravity. This paper has been designed to introduce affine quantization: what it is, and what it can do.

关键词： Canonical and Affine Quantization Different Simple Examples Comments regarding Field Theory and Gravity

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A Conceptual Model of Our Universe Derived from the Fine Structure Constant (α)

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American Journal of Computational Mathematics 2023年第4期13卷 524-532页

作者： john r. Crary Independent researcher Lake Zurich IL USA

The Fine Structure Constant (α) is a dimensionless value that guides much of quantum physics but with no scientific insight into why this specific number. The number defines the coupling constant for the strength of the electromagnetic force and is precisely tuned to make our universe functional. This study introduces a novel approach to understanding a conceptual model for how this critical number is part of a larger design rather than a random accident of nature. The Fine Structure Constant (FSC) model employs a Python program to calculate n-dimensional property sets for prime number universes where α equals the whole number values 137 and 139, representing twin prime universes without a fractional constant. Each property is defined by theoretical prime number sets that represent focal points of matter and wave energy in their respective universes. This work aims to determine if these prime number sets can reproduce the observed α value, giving it a definable structure. The result of the FSC model produces a α value equal to 137.036, an almost exact match. Furthermore, the model indicates that other twin prime pairs also have a role in our functional universe, providing a hierarchy for atomic orbital energy levels and alignment with the principal and azimuthal quantum numbers. In addition, it construes stable matter as property sets with the highest ratio of twin prime elements. These results provide a new perspective on a mathematical structure that shapes our universe and, if valid, has the structural complexity to guide future research.

关键词： Fine Structure Constant Conceptual Model Prime Numbers Property Sets Quantum Physics Universe

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Solving Major Problems Using Vector Affine Quantization

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Journal of High Energy Physics, Gravitation and Cosmology 2022年第1期8卷 178-183页

作者： john r. Klauder Department of Physics and Department of Mathematics University of Florida Gainesville USA

Affine quantization is a parallel procedure to canonical quantization, which is ideally suited to deal with special problems. Vector affine quantization introduces multiple degrees of freedom which find that working t... 详细信息

关键词： Affine Quantization Vector Field Models Canonical Quantization

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Using a Toy Model to Improve the Quantization of Gravity and Field Theories

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Journal of High Energy Physics, Gravitation and Cosmology 2022年第2期8卷 303-308页

作者： john r. Klauder Department of Physics and Department of Mathematics University of Florida Gainesville USA

A half-harmonic oscillator, which gets its name because the position coordinate is strictly positive, has been quantized and determined that it was a physically correct quantization. This positive result was found using affine quantization (AQ). The main purpose of this paper is to compare results of this new quantization procedure with those of canonical quantization (CQ). Using Ashtekar-like classical variables and CQ, we quantize the same toy model. While these two quantizations lead to different results, they both would reduce to the same classical Hamiltonian if ħ→ 0. Since these two quantizations have differing results, only one of the quantizations can be physically correct. Two brief sections also illustrate how AQ can correctly help quantum gravity and the quantization of most field theory problems.

关键词： Toy Model Affine Quantization (AQ) Canonical Quantization (CQ)

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Aripiprazole and Cariprazine for Bipolar Disorder?

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Open Journal of Medical Psychology 2022年第4期11卷 254-273页

作者： john r. rossiter School of Psychology Charles Sturt University Wagga Wagga Australia

In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for treating bipolar disorder. The main problem with the trials is that they were conducted mainly with outpatients, who on average were only moderately manic in the mania studies and only moderately depressed in the depression studies. The effectiveness of aripiprazole and cariprazine in treating moderate mania, most likely hypomania, and moderate depression, was far from encouraging. Aripiprazole produced just 7% greater reduction of mania symptoms than did placebo treatment, and just 1% greater reduction of depression symptoms than did placebo treatment when administered, as is common practice, with an SSrI or SNrI antidepressant. Cariprazine proved to be not much better because at the high dosage level of 3.0 mg/day to 12.0 mg/day, cariprazine produced only 9% greater reduction of mania symptoms than did placebo treatment, and at the typical low dosage of 1.5 to 3.0 mg/day produced just 4% greater reduction of depression symptoms than did placebo treatment. Moreover, as the pharmaceutical industry has long suspected, there is a massive placebo effect associated with these two drugs, especially for depression. These findings imply that government regulatory authorities’ approval of aripiprazole and cariprazine as mood stabilizers for treating bipolar disorder is dubious. Nevertheless, the possibility remains that the purported mood-stabilizing mechanism of these two medicines is activated only with patients presently experiencing severe mania or severe depression, a possibility that requires an in-hospital clinical trial or, at the very least, a longitudinal analysis of bipolar patients’ treatment records. Furthermore, an appendix to the present article demonstrates that the measures used in the trials, the Young Mania rating Scale and the Montgomery-Asberg

关键词： Bipolar Disorder Mania Depression Mood Stabilizers Clinical Trials Problems with Current Measures

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A New Proposal to Create a Valid Quantization of Einstein’s Gravity

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Journal of High Energy Physics, Gravitation and Cosmology 2022年第4期8卷 1164-1170页

作者： john r. Klauder Department of Physics and Department of Mathematics University of Florida Gainesville FL USA

Canonical quantization has created many valid quantizations that require infinite-line coordinate variables. However, the half-harmonic oscillator, which is limited to the positive coordinate half, cannot receive a valid canonical quantization because of the reduced coordinate space. Instead, affine quantization, which is a new quantization procedure, has been deliberately designed to handle the quantization of problems with reduced coordinate spaces. Following examples of what affine quantization is, and what it can offer, a remarkably straightforward quantization of Einstein’s gravity is attained, in which a proper treatment of the positive definite metric field of gravity has been secured.

关键词： Affine Quantization Valid results Quantum Gravity

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Valid Quantization: The Next Step

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Journal of High Energy Physics, Gravitation and Cosmology 2022年第3期8卷 628-634页

作者： john r. Klauder Department of Physics and Department of Mathematics University of Florida Gainesville USA

Canonical quantization is a wonderful procedure for selected problems, but there are many problems for which it fails. Affine quantization is a different procedure that has shown that it can solve many problems that canonical quantization cannot. Here, words like succeed and fail to refer to whether the quantization results are correct or incorrect. This paper offers two simple examples that serve to introduce affine quantization, and compare studies of two different quantization procedures. Brief comments about field theory and gravity problems undergoing quantization by affine procedures complete the paper.

关键词： Half-Harmonic Oscillator Affine Quantization Particle in a Box

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