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1.
ACS Appl Electron Mater ; 6(2): 748-760, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38435803

ABSTRACT

Aerosol jet printing (AJP) is an advanced manufacturing technique for directly writing nanoparticle inks onto target substrates. It is an emerging reliable, efficient, and environmentally friendly fabrication route for thin film electronics and advanced semiconductor packaging. This fabrication technique is highly regarded for its rapid prototyping, the flexibility of design, and fine feature resolution. Nickel is an attractive high-temperature packaging material due to its electrical conductivity, magnetism, and corrosion resistance. In this work, we synthesized nickel nanoparticles and formulated an AJP ink, which was printed on various material surfaces. Thermal sintering experiments were performed on the samples to explore the redox behavior and to optimize the electrical performance of the devices. The nickel devices were heated to failure under an argon atmosphere, which was marked by a loss of reflectance and electrical properties due to the dewetting of the films. Additionally, a reduction mechanism was observed from these studies, which resembled that of nucleation and coalescence. Finally, multilayer graphene was grown on a custom-printed nickel thin film using chemical vapor deposition (CVD), establishing a fully additive manufacturing route to patterned graphene.

2.
ACS Appl Bio Mater ; 6(9): 3717-3725, 2023 09 18.
Article in English | MEDLINE | ID: mdl-37655758

ABSTRACT

Three-dimensional (3D) tissue engineering (TE) is a prospective treatment that can be used to restore or replace damaged musculoskeletal tissues, such as articular cartilage. However, current challenges in TE include identifying materials that are biocompatible and have properties that closely match the mechanical properties and cellular microenvironment of the target tissue. Visualization and analysis of potential 3D porous scaffolds as well as the associated cell growth and proliferation characteristics present additional problems. This is particularly challenging for opaque scaffolds using standard optical imaging techniques. Here, we use graphene foam (GF) as a 3D porous biocompatible substrate, which is scalable, reproducible, and a suitable environment for ATDC5 cell growth and chondrogenic differentiation. ATDC5 cells are cultured, maintained, and stained with a combination of fluorophores and gold nanoparticles to enable correlative microscopic characterization techniques, which elucidate the effect of GF properties on cell behavior in a 3D environment. Most importantly, the staining protocol allows for direct imaging of cell growth and proliferation on opaque scaffolds using X-ray MicroCT, including imaging growth of cells within the hollow GF branches, which is not possible with standard fluorescence and electron microscopy techniques.


Subject(s)
Graphite , Metal Nanoparticles , Gold , Tissue Engineering , Cell Culture Techniques, Three Dimensional , Optical Imaging
3.
EBioMedicine ; 75: 103760, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34929494

ABSTRACT

BACKGROUND: Dyskeratosis congenita (DC) is a telomere biology disorder associated with high rates of bone marrow failure (BMF) and other medical complications. Oral androgens are successfully used to treat BMF in DC but often have significant side effects, including elevation of serum lipids. This study sought to determine the extent to which oral androgen therapy altered lipid and lipoprotein levels. METHODS: Nuclear magnetic resonance (NMR) was used to evaluate serum lipid profiles, and lipoprotein particle number and size in nine androgen-treated individuals with DC, 45 untreated individuals with DC, 72 unaffected relatives of DC patients, and 19 untreated individuals with a different inherited BMF syndrome, Fanconi anaemia (FA). FINDINGS: Androgen-treated individuals with DC had significantly decreased serum HDL cholesterol, HDL particle number and HDL particle size (p < 0·001, p < 0·001 and p < 0·001, respectively); significantly increased serum LDL cholesterol and LDL particle number (p < 0·001, p < 0·001, respectively), decreased apoA-I and increased apoB (p < 0⋅001, p < 0⋅05 respectively) when compared with untreated individuals with DC. There were no significant lipid profile differences between untreated DC and untreated FA participants; or between untreated DC participants and their unaffected relatives. Branched chain amino acids and lipoprotein insulin resistance were not significantly different with androgen treatment. GlycA, an inflammatory acute phase reactant, was significantly increased with androgen treatment (p < 0⋅001). INTERPRETATION: Androgen treatment in DC creates an atherogenic lipoprotein profile, raising concern for the potential of elevated cardiovascular disease risk. Clinical guidelines for individuals on androgens for DC-related BMF should include cardiovascular disease monitoring. These findings could be relevant in individuals treated with androgen for other indications. FUNDING: Intramural research programs of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute and National Heart, Lung, and Blood Institute.


Subject(s)
Androgens , Dyskeratosis Congenita , Androgens/adverse effects , Apolipoproteins B , Dyskeratosis Congenita/drug therapy , Dyskeratosis Congenita/genetics , Dyskeratosis Congenita/metabolism , Humans , Lipoproteins , Telomere/metabolism
4.
Polymers (Basel) ; 12(11)2020 Oct 30.
Article in English | MEDLINE | ID: mdl-33143261

ABSTRACT

The objective of this work is to predict the morphology and material properties of crosslinking polymers used in aerospace applications. We extend the open-source dybond plugin for HOOMD-Blue to implement a new coarse-grained model of reacting epoxy thermosets and use the 44DDS/DGEBA/PES system as a case study for calibration and validation. We parameterize the coarse-grained model from atomistic solubility data, calibrate reaction dynamics against experiments, and check for size-dependent artifacts. We validate model predictions by comparing glass transition temperatures measurements at arbitrary degree of cure, gel-points, and morphology predictions against experiments. We demonstrate for the first time in molecular simulations the cure-path dependence of toughened thermoset morphologies.

5.
Ann Clin Transl Neurol ; 7(1): 126-131, 2020 01.
Article in English | MEDLINE | ID: mdl-31808320

ABSTRACT

Myotonic dystrophy type I (DM1) is an autosomal dominant disease of which clinical manifestations resemble premature aging. We evaluated the contribution of telomere length in pathogenesis in 361 DM1 patients (12 with serial measurements) and 223 unaffected relative controls using qPCR assay. While no differences in baseline leukocyte relative telomere length (RTL) was noted, the data suggested an accelerated RTL attrition in DM1 (discovery cohort: T/S change/year = -0.013 in DM1 vs. -0.005 in controls, P = 0.04); similar trend was noted in validation cohort. Further investigations are needed to examine the role of TL in the pathophysiology of DM1.


Subject(s)
Leukocytes , Myotonic Dystrophy/genetics , Telomere Shortening/genetics , Adult , Female , Humans , Male , Middle Aged , Pilot Projects
6.
Development ; 143(19): 3591-3603, 2016 10 01.
Article in English | MEDLINE | ID: mdl-27702787

ABSTRACT

Insulin signaling plays key roles in development, growth and metabolism through dynamic control of glucose uptake, global protein translation and transcriptional regulation. Altered levels of insulin signaling are known to play key roles in development and disease, yet the molecular basis of such differential signaling remains obscure. Expression of the insulin receptor (InR) gene itself appears to play an important role, but the nature of the molecular wiring controlling InR transcription has not been elucidated. We characterized the regulatory elements driving Drosophila InR expression and found that the generally broad expression of this gene is belied by complex individual switch elements, the dynamic regulation of which reflects direct and indirect contributions of FOXO, EcR, Rbf and additional transcription factors through redundant elements dispersed throughout ∼40 kb of non-coding regions. The control of InR transcription in response to nutritional and tissue-specific inputs represents an integration of multiple cis-regulatory elements, the structure and function of which may have been sculpted by evolutionary selection to provide a highly tailored set of signaling responses on developmental and tissue-specific levels.


Subject(s)
Drosophila Proteins/metabolism , Receptor, Insulin/metabolism , Animals , Drosophila , Drosophila Proteins/genetics , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Developmental/genetics , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Receptor, Insulin/genetics , Receptors, Steroid/genetics , Receptors, Steroid/metabolism , Regulatory Sequences, Nucleic Acid/genetics , Retinoblastoma Protein/genetics , Retinoblastoma Protein/metabolism , Signal Transduction/genetics , Signal Transduction/physiology , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription, Genetic/genetics
7.
Am J Transplant ; 15(5): 1162-72, 2015 May.
Article in English | MEDLINE | ID: mdl-25707744

ABSTRACT

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.


Subject(s)
Hepatitis B virus/immunology , Hepatitis B/prevention & control , Liver Transplantation/methods , Tissue Donors , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Cost-Benefit Analysis , Heart Transplantation/methods , Hepatitis B/virology , Hepatitis B Antibodies/immunology , Hepatitis B Core Antigens/immunology , Humans , Kidney Transplantation/methods , Lamivudine/therapeutic use , Societies, Medical , Tissue and Organ Procurement , United States
8.
Am J Transplant ; 12(6): 1598-602, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22443186

ABSTRACT

Organ procurement organizations (OPOs) report a nearly fourfold difference in donor availability as measured by eligible deaths per million population (PMP) based on hospital referrals. We analyzed whether mortality data help explain geographic variation in organ supply as measured by the number of eligible deaths for organ donation. Using the 2007 National Center for Health Statistics' mortality data, we analyzed deaths occurring in acute care hospitals, aged ≤ 70 years from cerebrovascular accidents and trauma. These deaths were mapped at the county level and compared to eligible deaths reported by OPOs. In 2007, there were 2 428 343 deaths reported in the United States with 42 339 in-hospital deaths ≤ 70 years from cerebrovascular accidents (CVA) or trauma that were correlated with eligible deaths PMP (r(2) = 0.79.) Analysis revealed a broad range in the death rate across OPOs: trauma deaths: 44-118 PMP; deaths from CVA: 34-118 PMP; and combined CVA and trauma: 91-229 PMP. Mortality data demonstrate that deaths by neurologic criteria of people who are likely to be suitable deceased donors are not evenly distributed across the nation. These deaths are correlated with eligible deaths for organ donation. Regional availability of organs is affected by deaths which should be accounted for in the organ allocation system.


Subject(s)
Geography , Tissue Donors , Humans
9.
Transplant Proc ; 40(4): 1029-31, 2008 May.
Article in English | MEDLINE | ID: mdl-18555107

ABSTRACT

Many factors, such as donor risk factors and renal function, have been shown to be associated with an increased likelihood of discard after recovering kidneys from deceased donors. When these factors are insufficient for assessment, renal biopsy is often performed at the time of harvest to assess suitability. Our aims were to identify factors that predict the discard of a biopsied kidney and to assess the impact of machine perfusion (MP) on kidney discard. We biopsied 678 kidneys from deceased donors aged >or=40 years from 2001 to 2006. We used a logistic regression model to estimate the adjusted odds ratios for kidney discard. Thirty-nine percent (n = 261) of biopsied kidneys were discarded. Kidneys with glomerulosclerosis (GS) > 20% had the highest likelihood of discard. Other significant predictors of discard included extreme donor age, final resistance (>40), atherosclerosis, interstitial fibrosis, arteriolosclerosis, and terminal serum creatinine value (SCr) > 1.5 mg/dL. MP kidneys (n = 69) were less likely to be discarded than cold storage (CS) kidneys after adjusting for other factors (adjusted odds ratio = .13, P < .001). In conclusion, abnormal biopsy findings were associated with the highest likelihood of discard. MP was used in only 10% of the cases; however, the use of MP was associated with a decreased likelihood of discard among biopsied kidneys.


Subject(s)
Kidney , Organ Preservation/methods , Adult , Aged , Aged, 80 and over , Biopsy , Cause of Death , Humans , Kidney/pathology , Middle Aged , Multivariate Analysis , Organ Preservation/instrumentation , Patient Selection , Regression Analysis , Retrospective Studies , Tissue Donors/statistics & numerical data
10.
Transplant Proc ; 40(4): 1032-4, 2008 May.
Article in English | MEDLINE | ID: mdl-18555108

ABSTRACT

We reviewed diseased donor (DD) kidney usage at a single Organ Procurement Organization in Southern California to more closely examine factors associated with discard. From 2001 to 2006, 3863 kidneys from 1959 DDs were recovered, but 454 (11.8%) were subsequently discarded. Among the discarded kidneys, 211 (46.5%) were discarded based upon biopsy findings, 19 (4.2%) due to anatomical abnormalities, 16 (3.5%) based on donor quality, and 14 (3.1%) because they were felt to be too old to be pumped. Multivariate logistic regression analysis was performed using significant prognostic factors upon univariate analyses. According to the magnitude of the adjusted odds ratio (AOR), significant prognostic factors for discard were extreme donor age (AOR = 24.1 of age 70-80 years, P < .001; AOR = 6.34 age 50-69 years, P < .001; AOR = 2.77 age 40-49 years, P < .001; and AOR = 3.09 age <10 years, P < .001 vs age 10-39 years), high final resistance (AOR = 8.86 of >40 vs others, P = .006), glomerulosclerosis (GS) > 20% (AOR = 5.94 vs GS 0%-5%/no biopsy, P < .001), severe atherosclerosis (AOR = 4.66, P = .003), abnormal anatomy (AOR = 2.7, P < .001), and moderate or severe arteriolosclerosis (AOR = 2.2 vs none/mild/no biopsy, P < .001). Among biopsy findings, the presence of GS > 20% was associated with the highest likelihood of discard. A high final resistance increased the likelihood of discard as well. In conclusion, these findings may help to set the groundwork toward a more uniform approach to organ utilization in donor service areas.


Subject(s)
Kidney , Patient Selection , Tissue and Organ Procurement/methods , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Biopsy , California , Child , Female , Humans , Kidney/abnormalities , Kidney/pathology , Kidney Transplantation/statistics & numerical data , Likelihood Functions , Male , Middle Aged , Multivariate Analysis , Prognosis , Regression Analysis , Retrospective Studies , Tissue and Organ Procurement/standards
11.
Am J Transplant ; 8(4 Pt 2): 922-34, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18336696

ABSTRACT

Deceased organ donation has increased rapidly since 2002, coinciding with implementation of the Organ Donation Breakthrough Collaborative. The increase in donors has resulted in a corresponding increase in the numbers of kidney, liver, lung and intestinal transplants. While transplants for most organs have increased, discard and nonrecovery rates have not improved or have increased, resulting in a decrease in organs recovered per donor (ORPD) and organs transplanted per donor (OTPD). Thus, the expansion of the consent and recovery of incremental donors has frequently outpaced utilization. Meaningful increases in multicultural donation have been achieved, but donations continue to be lower than actual rates of transplantation and waiting list registrations for these groups. To counteract the decline in living donation, mechanisms such as paired donation and enhanced incentives to organ donation are being developed. Current efforts of the collaborative have focused on differentiating ORPD and OTPD targets by donor type (standard and expanded criteria donors and donors after cardiac death), utilization of the OPTN regional structure and enlisting centers to increase transplants to match increasing organ availability.


Subject(s)
Tissue Donors/statistics & numerical data , Tissue and Organ Procurement/statistics & numerical data , Tissue and Organ Procurement/trends , Cadaver , Humans , Intestines , Kidney , Liver , Living Donors/statistics & numerical data , Lung , Organ Preservation/methods , Organ Preservation/trends , Patient Selection , Registries , United States , United States Dept. of Health and Human Services
12.
J Viral Hepat ; 12(6): 627-34, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16255764

ABSTRACT

Hepatitis C virus (HCV) transmission by both seropositive and seronegative cadaver organ donors has been documented, yet nucleic acid testing is not routinely used to identify active infection in these donors prior to transplantation. Between November 2001 and February 2004, we screened 1445 cadaver organ donors for anti-HCV antibodies with either HCV EIA-2.0 (Abbott Diagnostics, Chicago, IL, USA) and/or Ortho HCV Version 3.0 ELISA (Ortho-Clinical Diagnostics, Raritan, NJ, USA) and confirmed seropositive samples with Chiron RIBA3.0 SIA (Chiron Corporation, Emeryville, CA, USA). Samples with sufficient volume (n = 726) were tested by the VERSANT HCV [transcription-mediated amplification (TMA)] Qualitative assay (Bayer Healthcare LLC, Tarrytown, NY, USA) which can be performed in approximately 5 h. Those with detectable HCV RNA and sufficient volume were quantified by the VERSANT HCV 3.0 (bDNA) Assay (Bayer Healthcare LLC) and/or the HCV RNA TMA Quantitative Assay (n = 23) and genotyped (n = 57). Seventy-seven of 1445 (5.3%) donors were seropositive, reactive by either one or both anti-HCV assays. Fifty-two of 63 (82.5%) of the seropositive samples had detectable HCV RNA and were genotyped. Seventeen of these samples had quantifications ranging from 128,123 to >7,692,307 IU/mL. Six of 663 (0.9%) seronegative samples had detectable HCV RNA. Their quantifications ranged from <9.3 to 1,464,799 IU/mL, and five of these six were successfully genotyped. As HCV RNA was demonstrated in samples from both our seropositive and seronegative cadaver organ donors, we are now incorporating nucleic acid testing into our donor screening/diagnostic algorithm.


Subject(s)
Cadaver , Donor Selection , Hepacivirus/isolation & purification , Hepatitis C/diagnosis , Nucleic Acid Amplification Techniques/methods , RNA, Viral/blood , Tissue Donors , Algorithms , Hepacivirus/genetics , Hepatitis C/virology , Hepatitis C Antibodies/blood , Humans , Transcription, Genetic
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