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The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

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Open j.urnal of Immunology 2024年第3期14卷 60-86页

作者： Kenneth Blum Igor Elman David Han Colin Hanna David Baron Ashim Gupta Shan Kazmi j.g Khalsa Debasis Bagchi Thomas McLaughlin Raj.ndra D. Badgaiyan Edward j. Modestino Drew Edwards Catherine A. Dennen Eric R. Braverman Abdalla Bowirrat Keerthy Sunder Kevin Murphy Nicole j.fari Fooj.n Zeine Paul R. Carney mark S. Gold Kai-Uwe Lewandowski Alireza Sharafshah Aryeh R. Pollack Panayotis K. Thanos Division of Addiction Research & Education Center for Sports and Mental Health Western University of Health Sciences Pomona CA USA Department of Psychiatry Boonshoft School of Medicine Wright State University and Dayton VA Medical Centre Dayton OH USA Division of Nutrigenomics Victory Nutrition International Lederoch PA USA Institute of Psychology ELTE Etvs Lornd University Budapest Hungary Department of Psychiatry School of Medicine University of Vermont Burlington VT USA The Kenneth Blum Behavioral & Neurogenetic Institute LLC. Austin TX USA Department of Molecular Biology Adelson School of Medicine Ariel University Ariel Israel Division of Neuromodulation Research Karma Doctors & Karma TMS Palm Springs CA USA Division of Personalized Interventions Peak Logic Del Mar CA USA Division of Personalized Medicine Cross-Cultural Research & Educational Institute San Clemente CA USA Awareness Integration Institute San Clemente CA USA Division of Personalized Pain Therapy Center for Advanced Spine Care of Southern Arizona Tucson AZ USA Department of Psychiatry Harvard School of Medicine Cambridge MA USA Department of Management Science and Statistics University of Texas San Antonio TX USA Behavioral Neuropharmacology and Neuroimaging Laboratory Clinical Research Institute on Addictions Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA Future Biologics Lawrenceville GA USA Department of Microbiology Immunology & Tropic Diseases School of Medicine Georgetown University Washington DC USA Department of Pharmaceutical Sciences College of Pharmacy Texas Southern University Houston TX USA Department of Psychiatry School of Medicine Case Western University Cleveland OH USA Brain and Behavior Laboratory Curry College Milton MA USA The Neurogenesis Proj.ct Jacksonville FL USA Department of Family Medicine Jefferson Health Northeast Philadelphia PA USA Departmen

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as

关键词： PANDAS CANS Genetic Addiction Risk Testing (GARS) Pro-Dopamine Regulation Hypodopaminergia Polymorphisms Antibacterial Therapy Infections

TREM2 marks tumor-associated macrophages

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Signal Transduction and Targeted Therapy 2020年第1期5卷 493-494页

作者： Kyohei Nakamura mark j.Smyth QIMR Berghofer Medical Research Institute Herston 4006 QLDAustralia

Immunosuppressive myeloid cells are recognized as a key barrier for cancer *** an integrated technology for single-cell RNA-sequencing and intracellular protein measurements,A recent paper published in Cell provides e... 详细信息

关键词： tumor immunotherapy myeloid

Dielectric confinement on exciton binding energy and nonlinear optical properties in a strained Zn_(1-x_(in))Mg_(x(in))Se/Zn_(1-x(out))Mg_(x(out))Se quantum well

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j.urnal of Semiconductors 2012年第9期33卷 1-7页

作者： j.Abraham Hudson mark A.j.hn Peter Department of Physics NPR Arts&Science CollegeNathamDindigul-624401India Department of Physics Government Arts CollegeMelur-625106MaduraiIndia

The band offsets for a Zn1-xin Mgxin Se/Zn1-xout Mgxout Se quantum well heterostructure are determined using the model solid theory. The heavy hole exciton binding energies are investigated with various Mg alloy contents. The effect of mismatch between the dielectric constants between the well and the barrier is taken into account. The dependence of the excitonic transition energies on the geometrical confinement and the Mg alloy is discussed. Non-linear optical properties are determined using the compact density matrix approach. The linear, third order non-linear optical absorption coefficient values and the refractive index changes of the exciton are calculated for different concentrations of magnesium. The results show that the occurred blue shifts of the resonant peak due to the Mg incorporation give the information about the variation of two energy levels in the quantum well width.

关键词： interband emission energy exciton binding energy quantum well

Patient Characteristics, Safety, and Tolerability With Telaprevir Treatment for HCV in the Clinic:a Retrospective, Multicenter Study

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j.urnal of Clinical and Translational Hepatology 2014年第2期2卷 65-73页

作者： Steven L. Flamm Paul j. Pockros Leif Bengtsson mark Friedman Northwestern University Feinberg School of Medicine Chicago Illinois USA Scripps Clinic and Scripps Translational Science Institute La Jolla California USA Vertex Pharmaceuticals Incorporated Boston Massachusetts USA

Background and Aims: There is a paucity of information regarding similarities and differences between patients from the phase 3 studies of telaprevir and those receiving telaprevir in clinical practice. Methods: This retrospective chart review evaluated baseline characteristics and follow-up safety and tolerability data for patients with hepatitis C virus (HCV) infection treated with telaprevir and peginterferon alfa and ribavirin (PR) in clinical practice. Results: In total, 338 charts from patients at four academic and three community US treatment centers who received telaprevir and PR and had at least 12 weeks of follow-up data were included;62%were from academic centers and 38% were from community centers. Of the 338 patients, 269 completed 12 weeks of telaprevir and PR;32 discontinued due to adverse events. Mean age was 55 years;patients were predominantly white (79.3%) males (58.9%) with genotype 1a HCV infection (61.8%);35.5%were reported to have cirrhosis at baseline;and 55.3%previously received PR. Hypertension and depres-sion were the most common comorbidities. Patient charac-teristics outside the per-protocol minimum criteria used in the phase 3 studies of telaprevir were, e.g., hemoglobin, 9.2%;albumin, 5.3%;platelets, 11.5%;and neutrophil count, 5.6%. Adverse events occurred in 329/338 (97.3%) patients, with anemia, fatigue, nausea, and rash being the most common. Of 38 hospitalizations, 26 were deemed related to telaprevir and PR. Three patients died due to pneumonia, septic shock, and hepatorenal syndrome (n=1 each). Conclusions: These findings complement those reported from rigorous, randomized controlled studies with telaprevir-based treatment and provide a general assess-ment of similarities and/or differences between patients from the phase 3 studies of telaprevir and those treated with telaprevir in clinical practice.

关键词： Hepatitis C virus Combination drug therapy Protease inhibitors Liver diseases

Phase Invariant Proper Orthogonal Decomposition for the Study of a Compressed Vortex

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j.urnal of Thermal Science 2005年第2期14卷 108-113页

作者： j.lien MOREAU mark FOGLEMAN G.CHARNAY j.BOREE Institut de Mécanique des Fluides UMR CNRS/INPT-UPS 5502 Allée du Pr Soula 31400 Toulouse FranceCornell University IthacaNew York 14853U.S.A.Institut de Mécanique des Fluides UMR CNRS/INPT-UPS 5502 Allée du Pr Soula 31400 ToulouseFranceLEA ENSMA UMR 6609 CNRS Futuroscope France

We propose here an experimental investigation of a vortex submitted to a radial perturbation while being compressed. This experiment reproduces a model situation of the complex flows that take place in a real engine cylinder. An isolated tumbling flow is first submitted to an inj.ction of fluid and then compressed and measurements are realised by Particle Image Velocimetry (PIV). The Proper Orthogonal Decomposition is known to be an unbiased method to identify the coherent structures of turbulent flows. It is possible to make this decomposition for a given phase or to create a set of basis functions with the whole set of compression stroke velocity ***, the experimental set-up will be presented, then the second part provides the POD principle. Results of phased POD decomposition of the compression of the unperturbated vortex will be presented. Finally results from the time invariant POD will be discussed to study the influence of the j.t perturbation in the compression of a vortex.

关键词： turbulence POD PIV cycle to cycle fluctuations.

Alternative expressions for stand diameter in complex forests

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Forest Ecosystems 2023年第3期10卷 328-336页

作者： mark j.Ducey j.hn A.Kershaw j.. Department of Natural Resources and the Environment University of New HampshireDurhamNHUSA Faculty of Forestry and Environmental Management University of New BrunswickFrederictonNBCanada

Quadratic mean diameter is the most frequently reported descriptor of the diameter distribution of *** such,it is often used as an indicator of forest stand structure,developmental stage,and ecological and economic ***,quadratic mean diameter can be heavily influenced by the presence or absence of large numbers of small stems in lower canopy strata,and it is also sensitive to left-truncation of the diameter distribution,making its interpretation across inventories with different protocols ***,we examine three alternative expressions of stand diameter:the arithmetic and quadratic mean diameter of the thickest 100 trees per hectare,and the basal area-weighted mean *** data from the United States Forest Inventory and Analysis program for New York and New England,these alternative expressions showed closer correlation with multiple stand structural variables than did quadratic mean diameter,including merchantable cubic and board foot volume per hectare,aboveground live tree carbon per hectare,and total number of live and dead standing trees greater than 40 cm diameter at breast height per hectare(previously proposed as an index of old-growth structure).Arithmetic and quadratic mean diameter of the thickest 100 trees per hectare showed nearly identical performance,and the strongest correlations across the *** develop closed-form expressions for these variables when the diameter distribution is a Weibull,and illustrate their behavior relative to quadratic mean diameter for that *** the reasons for prevalence of quadratic mean diameter as an indicator remain valid,we suggest that these alternative measures should be more widely reported and analyzed to give a more informative depiction of stand structure and development in complex forests.

关键词： Forest structure Diameter at breast height Weibull distribution

Mass Spectrometric Analyses Reveal a Central Role for Ubiquitylation in Remodeling the Arabidopsis Proteome during Photomorphogenesis

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Molecular Plant 2017年第6期10卷 846-865页

作者： Victor Aguilar-Hernandez Do-Young Kim Robert j. Stankey mark Scalf Lloyd M. Smith Richard D. Vierstra Department of Biology Washington University in St. Louis Campus Box 1137 One Brookings Drive St. Louis MO 63130 USA Department of Genetics 425-G Henry Mall Department of Chemistry 1101 University Avenue University of Wisconsin-Madison Madison WI 53706 USA Advanced Bio Convergence Center Pohang Technopark Gyeong-Buk South Korea 37668

The switch from skotomorphogenesis to photomorphogenesis is a key developmental transition in the life of seed plants. While much of the underpinning proteome remodeling is driven by light-induced changes in gene expression, the proteolytic removal of specific proteins by the ubiquitin-26S proteasome system is also likely paramount. Through mass spectrometric analysis of ubiquitylated proteins affinity-purified from etiolated Arabidopsis seedlings before and after red-light irradiation, we identified a number of influential proteins whose ubiquitylation status is modified during this switch. We observed a substantial enrichment for proteins involved in auxin, abscisic acid, ethylene, and brassinosteroid signaling, peroxisome function, disease resistance, protein phosphorylation and light perception, including the phytochrome （Phy） A and phototropin photoreceptors. Soon after red-light treatment, PhyA becomes the dominant ubiquitylated species, with ubiquitin attachment sites mapped to six lysines. A PhyA mutant protected from ubiquitin addition at these sites is substantially more stable in planta upon photoconversion to Pfr and is hyperactive in driving photomorphogenesis. However, light still stimulates ubiquitylation and degradation of this mutant, implying that other attachment sites and/or proteolytic pathways exist. Collectively, we expand the catalog of ubiquitylation targets in Arabidopsis and show that this post- translational modification is central to the rewiring of plants for photoautotrophic growth.

关键词： Arabidopsis ubiquitin mass spectrometry photomorphogenesis phytochrome degradation

A Review of Deepwater Pipeline Construction in the U.S. Gulf of Mexico-Contracts, Cost, and Installation Methods

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j.urnal of Marine Science and Application 2016年第3期15卷 288-306页

作者： mark j. Kaiser Center for Energy Studies Louisiana State University Baton Rouge 70803 USA

The offshore pipeline network in the U.S. Gulf of Mexico is the largest and most transparent system in the world. A review of deepwater proj.cts in the region provides insight into construction cost and installation methods and the evolution of contract strategies. Pipeline proj.cts are identified as export systems, infield flowline systems, and combined export and infield systems, and three dozen deepwater pipeline installations from 1980–2014 are described based on Offshore Technology Conference(OTC) and Society of Petroleum Engineers(SPE) industry publications and press release data. Export lines and infield flowlines are equally represented and many proj.cts used a combination of j.lay, S-lay and reel methods with rigid steel, flexible line, and pipe-in-pipe systems. The average 2014 inflation-adj.sted cost for pipeline proj.cts based on OTC/SPE publications was $2.76 million/mi and ranged from $520 000/mi to $12.94 million/mi. High cost pipelines tend to be short segments or specialized pipeline. Excluding the two cost endpoints, the maj.rity of proj.cts ranged from $1 to $6 million/mi. The average inflation-adj.sted cost to install deepwater pipelines in the U.S. Gulf of Mexico based on available public data is estimated at $3.1 million/mi.

关键词： construction cost contract type empirical statistics installation methods deepwater pipeline review

Robust Adaptive Model Tracking for Distributed Parameter Control of Linear Infinite-dimensional Systems in Hilbert Space

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IEEE/CAA j.urnal of Automatica Sinica 2014年第3期1卷 294-301页

作者： mark j.Balas Susan A.Frost the Embry-Riddle Aeronautical University the NASA Ames Research Center

This paper is focused on adaptively controlling a linear infinite-dimensional system to track a finite-dimensional reference *** a linear continuous-time infinite-dimensional plant on a Hilbert space with disturbances of known waveform but unknown amplitude and phase,we show that there exists a stabilizing direct model reference adaptive control law with the properties of certain disturbance rej.ction and *** plant is described by a closed,densely defined linear operator that generates a continuous semigroup of bounded operators on the Hilbert space of *** central result will show that all errors will converge to a prescribed neighborhood of zero in an infinitedimensional Hilbert *** result will not require the use of the standard Barbalat’s lemma which requires certain signals to be uniformly *** result is used to determine conditions under which a linear infinite-dimensional system can be directly adaptively controlled to follow a reference *** particular,we examine conditions for a set of ideal traj.ctories to exist for the tracking *** results are applied to adaptive control of general linear diffusion systems described by self-adj.int operators with compact resolvent.

关键词： Robustness Adaptation models Adaptive control Hilbert space Traj.ctory Learning (artificial intelligence)