126 research outputs found
Piloting a scale-up platform for high-quality human T-cells production
Copyright \ua9 2024 Selvarajan, Teo, Chang, Ng, Cheong, Sivalingam, Khoo, Wong and Loo. Cell and gene therapies are an innovative solution to various severe diseases and unfulfilled needs. Adoptive cell therapy (ACT), a form of cellular immunotherapies, has been favored in recent years due to the approval of chimeric antigen receptor CAR-T products. Market research indicates that the industry’s value is predicted to reach USD 24.4 billion by 2030, with a compound annual growth rate (CAGR) of 21.5%. More importantly, ACT is recognized as the hope and future of effective, personalized cancer treatment for healthcare practitioners and patients worldwide. The significant global momentum of this therapeutic approach underscores the urgent need to establish it as a practical and standardized method. It is essential to understand how cell culture conditions affect the expansion and differentiation of T-cells. However, there are ongoing challenges in ensuring the robustness and reproducibility of the manufacturing process. The current study evaluated various adoptive T-cell culture platforms to achieve large-scale production of several billion cells and high-quality cellular output with minimal cell death. It examined factors such as bioreactor parameters, media, supplements and stimulation. This research addresses the fundamental challenges of scalability and reproducibility in manufacturing, which are essential for making adoptive T-cell therapy an accessible and powerful new class of cancer therapeutics
Spinal Stenosis Presenting with Scrotal and Perianal Claudication
A 63-year-old gentleman presented with a one-year duration of progressive neurogenic claudication. However, unlike most patients who presents with leg symptoms, his pain was felt in his scrotal and perianal region. This was exacerbated with walking and standing, but he had immediate relief with sitting. An magnetic resonance imaging (MRI) was performed which showed severe central canal stenosis. An L3/4 and L4/5 surgical decompression and a transforaminal lumbar interbody fusion was performed, and the patient made good recovery with immediate resolution of symptoms. Although rare, spinal stenosis should be considered a differential when approaching a patient with perianal and scrotal claudication, even in the absence of leg claudication. An MRI is useful to confirm the diagnosis. This rare symptom may be a sign of severe cauda equina compression and we recommend decompression with predictable good results
Clinical and physiological effects of transcranial electrical stimulation position on motor evoked potentials in scoliosis surgery
<p>Abstract</p> <p>Background</p> <p>During intraoperative monitoring for scoliosis surgery, we have previously elicited ipsilateral and contralateral motor evoked potentials (MEP) with cross scalp stimulation. Ipsilateral MEPs, which may have comprised summation of early ipsilaterally conducted components and transcallosally or deep white matter stimulated components, can show larger amplitudes than those derived purely from contralateral motor cortex stimulation. We tested this hypothesis using two stimulating positions. We compared intraoperative MEPs in 14 neurologically normal subjects undergoing scoliosis surgery using total intravenous anesthetic regimens.</p> <p>Methods</p> <p>Trancranial electrical stimulation was applied with both cross scalp (C3C4 or C4C3) or midline (C3Cz or C4Cz) positions. The latter was assumed to be more focal and result in little transcallosal/deep white matter stimulation. A train of 5 square wave stimuli 0.5 ms in duration at up to 200 mA was delivered with 4 ms (250 Hz) interstimulus intervals. Averaged supramaximal MEPs were obtained from the tibialis anterior bilaterally.</p> <p>Results</p> <p>The cross scalp stimulating position resulted in supramaximal MEPs that were of significantly higher amplitude, shorter latency and required lower stimulating intensity to elicit overall (Wilcoxon Signed Rank test, p < 0.05 for all), as compared to the midline stimulating position. However, no significant differences were found for all 3 parameters comparing ipsilaterally and contralaterally recorded MEPs (p > 0.05 for all), seen for both stimulating positions individually.</p> <p>Conclusions</p> <p>Our findings suggest that cross scalp stimulation resulted in MEPs obtained ipsilaterally and contralaterally which may be contributed to by summation of ipsilateral and simultaneous transcallosally or deep white matter conducted stimulation of the opposite motor cortex. Use of this stimulating position is advocated to elicit MEPs under operative circumstances where anesthetic agents may cause suppression of cortical and spinal excitability. Although less focal in nature, cross scalp stimulation would be most suitable for infratentorial or spinal surgery, in contrast to supratentorial neurosurgical procedures.</p
Ripple modulated electronic structure of a 3D topological insulator
3D topological insulators, similar to the Dirac material graphene, host
linearly dispersing states with unique properties and a strong potential for
applications. A key, missing element in realizing some of the more exotic
states in topological insulators is the ability to manipulate local electronic
properties. Analogy with graphene suggests a possible avenue via a topographic
route by the formation of superlattice structures such as a moir\'e patterns or
ripples, which can induce controlled potential variations. However, while the
charge and lattice degrees of freedom are intimately coupled in graphene, it is
not clear a priori how a physical buckling or ripples might influence the
electronic structure of topological insulators. Here we use Fourier transform
scanning tunneling spectroscopy to determine the effects of a one-dimensional
periodic buckling on the electronic properties of Bi2Te3. By tracking the
spatial variations of the scattering vector of the interference patterns as
well as features associated with bulk density of states, we show that the
buckling creates a periodic potential modulation, which in turn modulates the
surface and the bulk states. The strong correlation between the topographic
ripples and electronic structure indicates that while doping alone is
insufficient to create predetermined potential landscapes, creating ripples
provides a path to controlling the potential seen by the Dirac electrons on a
local scale. Such rippled features may be engineered by strain in thin films
and may find use in future applications of topological insulators.Comment: Nature Communications (accepted
The space group classification of topological band insulators
Topological band insulators (TBIs) are bulk insulating materials which
feature topologically protected metallic states on their boundary. The existing
classification departs from time-reversal symmetry, but the role of the crystal
lattice symmetries in the physics of these topological states remained elusive.
Here we provide the classification of TBIs protected not only by time-reversal,
but also by crystalline symmetries. We find three broad classes of topological
states: (a) Gamma-states robust against general time-reversal invariant
perturbations; (b) Translationally-active states protected from elastic
scattering, but susceptible to topological crystalline disorder; (c) Valley
topological insulators sensitive to the effects of non-topological and
crystalline disorder. These three classes give rise to 18 different
two-dimensional, and, at least 70 three-dimensional TBIs, opening up a route
for the systematic search for new types of TBIs.Comment: Accepted in Nature Physic
Two-dimensional Dirac fermions in a topological insulator: transport in the quantum limit
Pulsed magnetic fields of up to 55T are used to investigate the transport
properties of the topological insulator Bi_2Se_3 in the extreme quantum limit.
For samples with a bulk carrier density of n = 2.9\times10^16cm^-3, the lowest
Landau level of the bulk 3D Fermi surface is reached by a field of 4T. For
fields well beyond this limit, Shubnikov-de Haas oscillations arising from
quantization of the 2D surface state are observed, with the \nu =1 Landau level
attained by a field of 35T. These measurements reveal the presence of
additional oscillations which occur at fields corresponding to simple rational
fractions of the integer Landau indices.Comment: 5 pages, 4 figure
Fully gapped topological surface states in BiSe films induced by a d-wave high-temperature superconductor
Topological insulators are a new class of materials, that exhibit robust
gapless surface states protected by time-reversal symmetry. The interplay
between such symmetry-protected topological surface states and symmetry-broken
states (e.g. superconductivity) provides a platform for exploring novel quantum
phenomena and new functionalities, such as 1D chiral or helical gapless
Majorana fermions, and Majorana zero modes which may find application in
fault-tolerant quantum computation. Inducing superconductivity on topological
surface states is a prerequisite for their experimental realization. Here by
growing high quality topological insulator BiSe films on a d-wave
superconductor BiSrCaCuO using molecular beam epitaxy,
we are able to induce high temperature superconductivity on the surface states
of BiSe films with a large pairing gap up to 15 meV. Interestingly,
distinct from the d-wave pairing of BiSrCaCuO, the
proximity-induced gap on the surface states is nearly isotropic and consistent
with predominant s-wave pairing as revealed by angle-resolved photoemission
spectroscopy. Our work could provide a critical step toward the realization of
the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274
One-dimensional Topological Edge States of Bismuth Bilayers
The hallmark of a time-reversal symmetry protected topologically insulating
state of matter in two-dimensions (2D) is the existence of chiral edge modes
propagating along the perimeter of the system. To date, evidence for such
electronic modes has come from experiments on semiconducting heterostructures
in the topological phase which showed approximately quantized values of the
overall conductance as well as edge-dominated current flow. However, there have
not been any spectroscopic measurements to demonstrate the one-dimensional (1D)
nature of the edge modes. Among the first systems predicted to be a 2D
topological insulator are bilayers of bismuth (Bi) and there have been recent
experimental indications of possible topological boundary states at their
edges. However, the experiments on such bilayers suffered from irregular
structure of their edges or the coupling of the edge states to substrate's bulk
states. Here we report scanning tunneling microscopy (STM) experiments which
show that a subset of the predicted Bi-bilayers' edge states are decoupled from
states of Bi substrate and provide direct spectroscopic evidence of their 1D
nature. Moreover, by visualizing the quantum interference of edge mode
quasi-particles in confined geometries, we demonstrate their remarkable
coherent propagation along the edge with scattering properties that are
consistent with strong suppression of backscattering as predicted for the
propagating topological edge states.Comment: 15 pages, 5 figures, and supplementary materia
PDADMAC/Alginate-Coated Gold Nanorod For Eradication of Staphylococcus Aureus Biofilms
Malarmugila Manimaran,1,* Yin Yin Teo,2 James Chen Yong Kah,3 Adilet Beishenaliev,1 Yean Leng Loke,2 Yiing Yee Foo,1 Shiow-Fern Ng,4 Chin Fei Chee,5 Sek Peng Chin,6 Farid Nazer Faruqu,1 Chia-Yu Chang,7 Misni Misran,2 Lip Yong Chung,6 Bey Fen Leo,8,* Shih-Hwa Chiou,9,10 Chia-Ching Chang,7,11– 13 Sun Tee Tay,14 Lik Voon Kiew1,7 1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Centre for Drug Delivery Technology and Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5Nanotechnology Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia; 7Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 8Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 9Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 10Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China; 11Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 12Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 13Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China; 14Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia*These authors contributed equally to this workCorrespondence: Chia-Ching Chang; Lik Voon Kiew, Email [email protected]; [email protected]: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV–Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 μM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.Keywords: biofilm, gold nanorod, S. aureus, PDADMAC, MRSA, MSS
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