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A novel approach to Parkinson's disease treatment with a potentially dual-acting therapeutic agent that targetsα-synuclein aggregation and neuron death

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Neural Regeneration Research 2024年第12期19卷 2577-2578页

作者： allison RBalaj Hiroaki Kaku Department of Investigative Medicine Western Michigan University Homer Stryker MD School of MedicineKalamazooMIUSA

Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy *** the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.

关键词： aggregation death therapeutic

Two-Layer High-Throughput:Effective Mass Calculations Including Warping

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Engineering 2022年第3期8卷 74-80页

作者： Andrew Supka Nicholas A.Mecholsky Marco Buongiorno Nardelli Stefano Curtarolo Marco fornari Department of Physics&Science of Advanced Materials Program Central Michigan UniversityMount PleasantMI 48859USA Department of Physics&Vitreous State Laboratory The Catholic University of AmericaWashingtonDC 20064USA Department of Physics&Department of Chemistry University of North TexasDentonTX 76203USA Center for Autonomous Materials Design Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA

In this paper,we perform two-layer high-throughput *** the first layer,which involves changing the crystal structure and/or chemical composition,we analyze selected Ⅲ-Ⅴ semiconductors,filled and unfilled skutterudites,as well as rock salt and layered *** second layer searches the full Brillouin zone(BZ)for critical points within 1.5 eV(1 eV=1.602176×10^(-19)j)of the Fermi level and characterizes those points by computing the effective *** introduce several methods to compute the effective masses from first principles and compare them to each *** approach also includes the calculation of the density-of-states effective masses for warped critical points,where traditional approaches fail to give consistent results due to an underlying non-analytic behavior of the critical *** demonstrate the need to consider the band structure in its full complexity and the value of complementary approaches to compute the effective *** also provide computational evidence that warping occurs only in the presence of degeneracies.

关键词： High-throughput Electronic structure Band warping Effective mass

Multi-Institutional US Experience of the Occlutech AFR Device in Congenital and Acquired Heart Disease

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Congenital Heart Disease 2022年第1期17卷 107-116页

作者： Barry O’Callaghan jenny Zablah joseph Vettukattil Daniel Levi Morris Salem allison Cabalka jason Anderson Makram Ebeid Ryan Alexy Gareth j.Morgan The Heart Institute Children’s Hospital ColoradoAuroraUSA Pediatric Cardiology Helen DeVos Children’s HospitalGrand RapidsUSA Pediatric Cardiology UCLA HealthMattel Children’s HospitalLos AngelesUSA Pediatric Cardiology UCLA Medical CentreLos AngelesUSA Pediatric Cardiology Mayo ClinicRochesterUSA Pediatric Cardiology University of Mississippi Medical CenterJacksonUSA Pediatric Cardiology Riley Hospital for Children at Indiana University HealthIndianapolisUSA

Objectives:To detail the US multi-institutional experience with the Occlutech©(Occlutech International AB,Helsingborg,Sweden)atrial flow regulator(AFR)in children and adults with acquired or congenital heart ***:The creation of a long-term atrial communication is desirable in several cardiovascular disease phenotypes,most notably pulmonary arterial hypertension,disorders of increased left ventricular filling and increased cavopulmonary pressures in patients with a Fontan type ***:Patients were identified for inclusion from the AFR device manufacturer *** was collected using a RedCap database following IRB approval.8 weeks of follow up data was sought for each patient based on available *** was analyzed and summarized using ***:We report the experience of 6 US centers in the implantation of AFR devices in 15 patients,across a wide age range,with different disease phenotypes and a variety of *** was technically successful in all patients and improvement was noted in both clinical and hemodynamic *** were no immediate or intermediate term complications reported.3 patients died remote from *** deaths were not felt to be related to the AFR device or related procedural ***:Compassionate use of the AFR device in children and adults with congenital&acquired heart disease is technically feasible and produces beneficial short term hemodynamic and symptomatic *** uptake of this technique and treatment at specialist centers has the potential to provide significant benefits to a variety of complex patients with currently limited treatment options and indeterminate prognosis.

关键词： Congenital heart disease pulmonary hypertension left atrial hypertension single ventricle palliation diastolic heart failure

ShapeShifter： a novel approach for identifying and quantifying stable lariat intronic species in RNAseq data

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Frontiers of Electrical and Electronic Engineering in China 2018年第3期6卷 267-274页

作者： allison j Taggart William G Fairbrother Department of Molecular Biology Cell Biology and Biochemistry Brown University Providence RI 02912 USA. Center for Computational Molecular Biology Brown University Providence RI 02912 USA.

Background： Most intronic lariats are rapidly turned over after splicing. However, new research suggests that some introns may have additional post-splicing functions. Current bioinformatics methods used to identify lariats require a sequencing read that traverses the lariat branchpoint. This method provides precise branchpoint sequence and position information, but is limited in its ability to quantify abundance of stabilized lariat species in a given RNAseq sample. Bioinformatic tools are needed to better address these emerging biological questions. Methods： We used an unsupervised machine learning approach on sequencing reads from publicly available ENCODE data to learn to identify and quantify lariats based on RNAseq read coverage shape. Results： We developed ShapeShifter, a novel approach for identifying and quantifying stable lariat species in RNAseq datasets. We learned a characteristic ＂lariat＂ curve from ENCODE RNAseq data and were able to estimate abundances for introns based on read coverage. Using this method we discovered new stable introns in these samples that were not represented using the older, branchpoint-traversing read method. Conclusions： ShapeShifter provides a robust approach towards detecting and quantifying stable lariat species.

关键词： splicing RNA lariat

Management of symptomatic neuromas:a narrative review of the most common surgical treatment modalities in amputees

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Plastic and Aesthetic Research 2022年第1期9卷 120-132页

作者： Sahand C.Eftekari Peter j.Nicksic allison j.Seitz D’Andrea T.Donnelly Aaron M.Dingle Samuel O.Poore Division of Plastic Surgery University of Wisconsin School of Medicine and Public HealthG5-347 Clinical Sciences CenterMadisonWI 53711USA

Symptomatic neuromas are an all-too-common complication following limb amputation or extremity trauma,leading to chronic and debilitating pain for *** resection of symptomatic neuromas has proven to be the superior method of intervention,but traditional methods of neuroma resection do not address the underlying pathophysiology leading to the formation of a future symptomatic neuroma and lead to high reoperation *** approaches employ the physiology of peripheral nerve injury to harness the regeneration of nerves to their *** review explores the underlying pathophysiology of neuroma formation and centralization of pain *** compares the traditional surgical approach for symptomatic neuroma resection and describes three novel surgical strategies that harness this pathophysiology of neuroma formation to their *** traditional resection of symptomatic neuromas is currently the standard of care for amputation patients,but new techniques including the regenerative peripheral nerve interface,targeted muscle reinnervation,and intraosseous transposition have shown promise in improving patient pain outcomes for postamputation pain and residual limb *** neuromas are a chronic and debilitating complication following amputation procedures and trauma,and the current standard of care does not address the underlying pathophysiology leading to the formation of the *** techniques are under development that may provide improved patient pain outcomes and a higher level of care for symptomatic neuroma resection.

关键词： Neuromas regenerative peripheral nerve interface targeted muscle reinnervation osseointegrated neural interface amputation

Child Abuse during the Pandemic and Trauma-Informed Care: A Review of Evidence-Based Literature

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Health 2023年第9期15卷 1003-1012页

作者： allison j. DiPlacido Linda Leitzel Brayden Kameg Betty j. Braxter Rose Constantino School of Nursing University of Pittsburgh Pittsburgh USA

Abuse of infants and children is a public health problem that warrants immediate attention. It is estimated that over 7 million children are affected by child abuse yearly, with the highest rate of abuse in those less than one year of age. Approximately 60% of child abuse victims are children under the age of three years, making infants and young children a particularly vulnerable population. Interventions targeting the perinatal period can be effective in mitigating child abuse, including parent education programs and trauma-informed care services. This paper provides an overview of the current evidence base related to child abuse following the COVID-19 pandemic, with a focus on prevention and intervention strategies that can be utilized to increase caregiver support and reduce child abuse rates during the perinatal period.

关键词： Neonates Newborn Infant Child Abuse Perinatal Trauma-Informed Care

Macrophage polarization in response to wear particles in vitro

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Cellular & Molecular Immunology 2013年第6期10卷 471-482页

作者： joseph K Antonios Zhenyu Yao Chenguang Li allison j Rao Stuart B Goodman Orthopaedic Research Laboratories Department of Orthopaedic Surgery Stanford University School of Medicine Stanford CA USA

Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant （periprosthetic osteolysis）. Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory （M 1） macrophage phenotype rather than an anti-inflammatory pro-tissue healing （M2） macrophage phenotype. While it has been shown that interleukin-4 （IL-4） selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through I L-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate （PMMA） particles, lipopolysaccharide （LPS） and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase （iNOS） production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M 1 phenotype rather than to uncommitted （MO） macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

关键词： IL-4 macrophage polarization osteolysis PMMA particles total joint replacement

An efficient and accurate framework for calculating lattice thermal conductivity of solids:AFLOW-AAPL Automatic Anharmonic Phonon Library

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npj Computational Materials 2017年第1期3卷 79-88页

作者： jose j.Plata Pinku Nath Demet Usanmaz jesus Carrete Cormac Toher Maarten de jong Mark Asta Marco fornari Marco Buongiorno Nardelli Stefano Curtarolo Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Institute of Materials Chemistry TU WienA-1060 ViennaAustria Department of Materials Science and Engineering University of CaliforniaBerkeley210 Hearst Memorial Mining BuildingBerkeleyUSA SpaceX 1 Rocket RoadHawthorneCA 90250USA Department of Physics and Science of Advanced Materials Program Central Michigan UniversityMount PleasantMI 48859USA Department of Physics and Department of Chemistry University of North TexasDentonTXUSA Materials Science Electrical EngineeringPhysics and ChemistryDuke UniversityDurhamNC 27708USA

One of the most accurate approaches for calculating lattice thermal conductivity,κ_(l),is solving the Boltzmann transport equation starting from third-order anharmonic force *** addition to the underlying approximations of ab-initio parameterization,two main challenges are associated with this path:high computational costs and lack of automation in the frameworks using this methodology,which affect the discovery rate of novel materials with ad-hoc ***,the Automatic Anharmonic Phonon Library(AAPL)is *** efficiently computes interatomic force constants by making effective use of crystal symmetry analysis,it solves the Boltzmann transport equation to obtain κ_(l),and allows a fully integrated operation with minimum user intervention,a rational addition to the current high-throughput accelerated materials development framework ***“experiment ***”study of the approach is shown,comparing accuracy and speed with respect to other available packages,and for materials characterized by strong electron localization and *** AAPL with the pseudo-hybrid functional ACBN0 is possible to improve accuracy without increasing computational requirements.

关键词： properties. harmonic calculating

Mechanistic insights of enhanced spin polaron conduction in CuO through atomic doping

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npj Computational Materials 2018年第1期4卷 154-161页

作者： Tyler j.Smart allison C.Cardiel Feng Wu Kyoung-Shin Choi Yuan Ping Department of Physics University of CaliforniaSanta CruzCA 95064USA Department of Chemistry University of WisconsinMadisonWI 53706USA Department of Chemistry and Biochemistry University of CaliforniaSanta CruzCA 95064USA

The formation of a“spin polaron”stems from strong spin-charge-lattice interactions in magnetic oxides,which leads to a localization of carriers accompanied by local magnetic polarization and lattice *** example,cupric oxide(CuO),which is a promising photocathode material and shares important similarities with high Tc superconductors,conducts holes through spin polaron hopping with flipped spins at Cu atoms where a spin polaron has *** formation of these spin polarons results in an activated hopping conduction process where the carriers must not only overcome strong electron−phonon coupling but also strong magnetic ***,these effects cause low carrier conduction in CuO and hinder its *** overcome this fundamental limitation,we demonstrate from first-principles calculations how doping can improve hopping conduction through simultaneous improvement of hole concentration and hopping mobility in magnetic oxides such as ***,using Li doping as an example,we show that Li has a low ionization energy that improves hole concentration,and lowers the hopping barrier through both the electron−phonon and magnetic couplings'reduction that improves hopping ***,this improved conduction predicted by theory is validated through the synthesis of Li-doped CuO electrodes which show enhanced photocurrent compared to pristine CuO *** conclude that doping with nonmagnetic shallow impurities is an effective strategy to improve hopping conductivities in magnetic oxides.

关键词： conduction doping polaron