Publications by authors named "J Javor"

35 Publications

Autoinflammatory process in the pathogenesis of generalized pustular psoriasis and perspectives of its targeted therapy.

Epidemiol Mikrobiol Imunol 2021 ;70(3):199-207

The dysregulated inflammatory process not only plays an important role in the development of chronic plaque psoriasis but also is a major pathogenetic mechanism behind the generalized pustular psoriasis (GPP) and other rare pustular forms of the disease. The key players in this process are the cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), IL-12/23, IL-17A and especially IL-36. Their excessive activity or production in some GPP patients is due to mutations in genes that encode molecules involved in inhibiting the action of IL-36 (IL-36Ra) or in intracellular inflammatory signaling (CARD14, AP1S3). Knowledge about the pathological role of inflammatory cytokines in the development of pustular forms of psoriasis has also found application in their biological therapy with monoclonal antibodies that neutralize the action of IL-12/23, IL-17A, TNF or IL-1β. Other promising agents are monoclonal antibodies against the interleukin 36 receptor, which have already successfully gone through the first phases of clinical trials and are currently being tested for their long-term efficacy, safety and tolerability.
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October 2021

Analysis of a Casimir-driven parametric amplifier with resilience to Casimir pull-in for MEMS single-point magnetic gradiometry.

Microsyst Nanoeng 2021 7;7:73. Epub 2021 Sep 7.

Department of Mechanical Engineering, Boston University, Boston, MA 02215 USA.

The Casimir force, a quantum mechanical effect, has been observed in several microelectromechanical system (MEMS) platforms. Due to its extreme sensitivity to the separation of two objects, the Casimir force has been proposed as an excellent avenue for quantum metrology. Practical application, however, is challenging due to attractive forces leading to stiction and device failure, called Casimir pull-in. In this work, we design and simulate a Casimir-driven metrology platform, where a time-delay-based parametric amplification technique is developed to achieve a steady-state and avoid pull-in. We apply the design to the detection of weak, low-frequency, gradient magnetic fields similar to those emanating from ionic currents in the heart and brain. Simulation parameters are selected from recent experimental platforms developed for Casimir metrology and magnetic gradiometry, both on MEMS platforms. While a MEMS offers many advantages to such an application, the detected signal must typically be at the resonant frequency of the device, with diminished sensitivity in the low frequency regime of biomagnetic fields. Using a Casimir-driven parametric amplifier, we report a 10,000-fold improvement in the best-case resolution of MEMS single-point gradiometers, with a maximum sensitivity of 6 Hz/(pT/cm) at 1 Hz. Further development of the proposed design has the potential to revolutionize metrology and may specifically enable the unshielded monitoring of biomagnetic fields in ambient conditions.
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http://dx.doi.org/10.1038/s41378-021-00289-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433440PMC
September 2021

Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue.

Microsyst Nanoeng 2021 27;7:10. Epub 2021 Jan 27.

Department of Mechanical Engineering, Boston University, Boston, MA 02215 USA.

The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. The contractile force is found to correlate with both the scattering intensity (  = 0.44) and lattice spacing (  = 0.46). The scattering intensity also correlates with lattice spacing (  = 0.81), suggestive of lower noise in our structural measurement than in the functional measurement. Notably, we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy (HCM). Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs.
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http://dx.doi.org/10.1038/s41378-020-00234-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433147PMC
January 2021

100 pT/cm single-point MEMS magnetic gradiometer from a commercial accelerometer.

Microsyst Nanoeng 2020 10;6:71. Epub 2020 Aug 10.

Department of Mechanical Engineering, Boston University, Boston, MA 02215 USA.

Magnetic sensing is present in our everyday interactions with consumer electronics and demonstrates the potential for the measurement of extremely weak biomagnetic fields, such as those of the heart and brain. In this work, we leverage the many benefits of microelectromechanical system (MEMS) devices to fabricate a small, low-power, and inexpensive sensor whose resolution is in the range of biomagnetic fields. At present, biomagnetic fields are measured only by expensive mechanisms such as optical pumping and superconducting quantum interference devices (SQUIDs), suggesting a large opportunity for MEMS technology in this work. The prototype fabrication is achieved by assembling micro-objects, including a permanent micromagnet, onto a postrelease commercial MEMS accelerometer using a pick-and-place technique. With this system, we demonstrate a room-temperature MEMS magnetic gradiometer. In air, the sensor's response is linear, with a resolution of 1.1 nT cm, spans over 3 decades of dynamic range to 4.6 µT cm, and is capable of off-resonance measurements at low frequencies. In a 1 mTorr vacuum with 20 dB magnetic shielding, the sensor achieves a 100 pT cm resolution at resonance. This resolution represents a 30-fold improvement compared with that of MEMS magnetometer technology and a 1000-fold improvement compared with that of MEMS gradiometer technology. The sensor is capable of a small spatial resolution with a magnetic sensing element of 0.25 mm along its sensitive axis, a >4-fold improvement compared with that of MEMS gradiometer technology. The calculated noise floor of this platform is 110 fT cm Hz, and thus, these devices hold promise for both magnetocardiography (MCG) and magnetoencephalography (MEG) applications.
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http://dx.doi.org/10.1038/s41378-020-0173-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433323PMC
August 2020

Impact of rs243865 and rs3025058 Polymorphisms on Clinical Findings in Alzheimer's Disease Patients.

Mediators Inflamm 2021 19;2021:5573642. Epub 2021 Apr 19.

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of rs243865 and rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of rs243865 (-1306 C>T) and rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44 ± 6.28 vs. 76.36 ± 6.39, = 0.036). The results of rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61 ± 5.88 vs. 78.57 ± 6.79, = 0.045). In conclusion, our results suggest that rs243865 and rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.
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http://dx.doi.org/10.1155/2021/5573642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079184PMC
April 2021
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