Persistence and enrichment of dominant T cell clonotypes in expanded tumor-infiltrating lymphocytes of breast cancer.

BACKGROUND: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood. METHODS: We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood. Additionally, we examined differences in TCR repertoire between CD4+ and CD8+ REP TILs. RESULTS: In descending order of proportion, average of 60% of the top 10% clonotypes of FFPE was retained in 2W TIL (60% in TRB, 64.7% in TRA). Among the overlapped clonotypes between 2W TILs and REP TILs, 69.9% was placed in top 30% of 2W TIL. The proportion of clonotypes in 2W TIL and REP TIL showed a significant positive correlation. CD4+ and CD8+ T cells show similar results in diversity and CDR3 length. CONCLUSIONS: Our study traces the changes in TILs repertoire from FFPE to 2W TIL and REP TIL and confirmed that clonotypes with high frequencies in TILs have a high likelihood of maintaining their priority throughout culture process.

Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy.

BACKGROUND: Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes. METHODS: TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes. The cancer tissues were cut into small pieces (1-2 mm) and underwent initial expansion for 2 weeks. Tumor location, smoking history, stromal TIL percentage, human papillomavirus infection, and programmed death-ligand 1 score were examined for their impact on successful expansion of TILs. Expanded TILs were evaluated by flow cytometry using fluorescence-activated cell sorting. A second round of TIL expansion following the rapid expansion protocol was performed on a subset of samples with successful TIL expansion. RESULTS: TILs were successfully expanded from 36.2% samples. Failure was due to contamination (27.6%) or insufficient expansion (36.2%). Only the stromal TIL percentage was significantly associated with successful TIL expansion (p = 0.032). The stromal TIL percentage also displayed a correlation with the expanded TILs per fragment (r = 0.341, p = 0.048). On flow cytometry analysis using 13 samples with successful TIL expansion, CD4 + T cell dominancy was seen in 69.2% of cases. Effector memory T cells were the major phenotype of expanded CD4 + and CD8 + T cells in all cases. CONCLUSION: We could expand TILs from approximately one-third of HNSCC samples. TIL expansion could be applicable in HNSCC samples with diverse clinicopathological characteristics.

Overcoming Downscaling Limitations in Organic Semiconductors: Strategies and Progress.

Organic semiconductors have great potential to revolutionize electronics by enabling flexible and eco-friendly manufacturing of electronic devices on plastic film substrates. Recent research and development led to the creation of printed displays, radio-frequency identification tags, smart labels, and sensors based on organic electronics. Over the last 3 decades, significant progress has been made in realizing electronic devices with unprecedented features, such as wearable sensors, disposable electronics, and foldable displays, through the exploitation of desirable characteristics in organic electronics. Neverthless, the down-scalability of organic electronic devices remains a crucial consideration. To address this, efforts are extensively explored. It is of utmost importance to further develop these alternative patterning methods to overcome the downscaling challenge. This review comprehensively discusses the efforts and strategies aimed at overcoming the limitations of downscaling in organic semiconductors, with a particular focus on four main areas: 1) lithography-compatible organic semiconductors, 2) fine patterning of printing methods, 3) organic material deposition on pre-fabricated devices, and 4) vertical-channeled organic electronics. By discussing these areas, the full potential of organic semiconductors can be unlocked, and the field of flexible and sustainable electronics can be advanced.

The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound.

HucR is a MarR family protein of Deinococcus radiodurans, which binds tightly to the intergenic region of HucR and the uricase gene to inhibit their expression. Urate (or uric acid) antagonizes the repressor function of HucR by binding to HucR to impede its association with the cognate DNA. The previously reported crystal structure of HucR was without the bound urate showing significant structural homology to other MarR structures. In this paper, we report the crystal structure of HucR determined with the urate bound. However, despite the fact that the urate is found at a site well-known to harbor ligands in other MarR family proteins, the overall HucR structure indicates that no significant change in structure takes place with the urate bound. Structure analysis further suggests that the urate interaction in HucR is mediated by histidine/glutamate side chains and ordered water molecules stabilized by various residues. Such interaction is quite unique compared to other known structural interactions between urate and its binding proteins. Furthermore, structural comparison of the apo- and the urate bound forms allows us to hypothesize that the Trp20-mediated water network in the apo-form stabilizes the proper HucR fold for cognate DNA binding, and that urate binding, also via Trp20, and the consequent reorganization of water molecules in the binding pocket, likely disrupts the DNA binding configuration to result in the attenuated DNA binding.

Self-Powered Low-Cost UVC Sensor Based on Organic-Inorganic Heterojunction for Partial Discharge Detection.

Power outages caused by the aging of high-voltage power facilities can cause significant economic and social damage. To prevent such problems, it is necessary to implement a widespread and sustainable monitoring system. Partial discharge (PD) is a preliminary symptom of power equipment aging accompanying the light, typically in the UV range. UVC (200-280 nm) is more useful than UVA and UVB because of low interference from the environment owing to its solar-blindness by the stratosphere. Therefore, to realize a wide-range and durable diagnosis system, it is necessary to develop sensors that can selectively detect UVC, while enabling mass production at low-cost and low power consumption. Here, a solution-processable photodiode sensor that is inexpensive, mass-producible, and self-powered with selective UVC detection is developed. The optoelectronic characteristics of photodiode consisting of organic p-polymer and inorganic n-ZnO nanoparticles are systematically studied to determine the optimum p-type polymer and its thickness. The device shows high-performance: fast response time (rise/fall time: 36.6/37.0 ms) and high spectral response in the UVC region (maximum responsivity of 20 mA W-1 ) under self-powered operation. Furthermore, the practical application of the device to detect PD signals with a visual alarm system under UVC release conditions is demonstrated.

Synthesis of Lead-Free CaTiO3 Oxide Perovskite Film through Solution Combustion Method and Its Thickness-Dependent Hysteresis Behaviors within 100 mV Operation.

Perovskite is attracting considerable interest because of its excellent semiconducting properties and optoelectronic performance. In particular, lead perovskites have been used extensively in photovoltaic, photodetectors, thin-film transistors, and various electronic applications. On the other hand, the elimination of lead is essential because of its strong toxicity. This paper reports the synthesis of lead-free calcium titanate perovskite (CaTiO3) using a solution-processed combustion method. The chemical and morphological properties of CaTiO3 were examined as a function of its thickness by scanning electron microscopy, X-ray diffraction (XRD), atomic force microscopy, X-ray photoelectron spectroscopy, and ultraviolet-visible spectrophotometry. The analysis showed that thicker films formed by a cumulative coating result in larger grains and more oxygen vacancies. Furthermore, thickness-dependent hysteresis behaviors were examined by fabricating a metal-CaTiO3-metal structure. The electrical hysteresis could be controlled over an extremely low voltage operation, as low as 100 mV, by varying the grain size and oxygen vacancies.

Polymeric tunable wavelength filter with two-stage cascaded tilted Bragg gratings.

Wavelength-division multiplexed optical communication systems used in 5G networks require tunable wavelength filters with narrow bandwidth for 100 GHz channel spacing, wide wavelength range to cover 16 channels, and a side mode suppression ratio (SMSR) exceeding 30 dB. To fabricate wavelength filters satisfying these specifications, tunable Bragg grating filters based on polymeric optical waveguides are proposed. The combination of mode-sorting waveguide and tilted Bragg grating enables the extraction of Bragg reflected signals to another path, without using an external circulator. Moreover, the double reflection by the two-stage cascaded structure produces narrower reflection bandwidth, improved SMSR characteristics, and reduced adjacent-channel crosstalk through the suppression of undesired mode coupling. The proposed device exhibits a 20 dB bandwidth of 1.0 nm and SMSR of 35 dB, over the entire wavelength-tuning range.

Temporal response of polymer waveguide beam scanner with thermo-optic phase-modulator array.

Solid-state light detection and ranging, capable of performing beam scanning without using any mechanical moving parts, requires a phase-modulator array. Polymers facilitate the fabrication of efficient phase modulators with low drive power, owing to their high thermo-optic (TO) effect and low thermal conductivity. We designed and fabricated a polymeric phase-modulator array and analyzed the temporal response of the TO phase modulator. The frequency response of the phase modulator was measured for a Mach-Zehnder interferometer (MZI), and the transfer function was modeled in terms of multiple poles and zeros. The frequency response of a fabricated beam-scanning device incorporating the TO phase modulator was also measured. The temporal response of the beam scanner was confirmed to coincide well with that of the MZI modulator. The device exhibited a fast rise time of 12 ms, accompanied by slight power variations appearing for a long period (over hundreds of seconds), which originated from the inherent viscoelastic effect of the polymer materials.

Development of Adverse Outcome Pathway for PPARγ Antagonism Leading to Pulmonary Fibrosis and Chemical Selection for Its Validation: ToxCast Database and a Deep Learning Artificial Neural Network Model-Based Approach.

Exposure to certain chemicals such as disinfectants through inhalation is suspected to be involved in the development of pulmonary fibrosis, a lung disease in which lung tissue becomes damaged and scarred. Pulmonary fibrosis is known to be regulated by transforming growth factor ß (TGF-ß) and peroxisome proliferator-activated receptor gamma (PPARγ). Here, we developed an adverse outcome pathway (AOP) to better define the linkage of PPARγ antagonism to the adverse outcome of pulmonary fibrosis. We then conducted a systematic analysis to identify potential chemicals involved in this AOP, using the ToxCast database and deep learning artificial neural network models. We identified chemicals bearing a potential inhalation hazard and exposure hazards from the database that could be related to this AOP. For chemicals that were not present in the ToxCast database, multilayer perceptron models were developed based on the ToxCast assays related to the AOP. The reactivity of ToxCast untested chemicals was then predicted using these deep learning models. Both approaches identified a set of chemicals that could be used to validate the AOP. This study suggests that chemicals categorized using an existing database such as ToxCast can be used to validate an AOP and that deep learning approaches can be used to characterize a range of potential active chemicals for an AOP of interest.

Bias-free optical current sensors based on quadrature interferometric integrated optics.

A reflective quadrature interferometer was constructed by integrating polymeric optical waveguide components, to demonstrate an optical current sensor that could operate without bias feedback control. In order to obtain two interference signals with a phase difference of 90°, half-wave and quarter-wave plates were inserted in the polymeric optical waveguide chip, and a polarization-dependent birefringence modulator was used for the initialization of the optical sensor, including detector gain adjustment. During the bias-free operation of the sensor, the measurement error was less than ± 0.2%, and it was confirmed that the sensor output was stable for 15 h even if the operating point was not maintained.

Polymer waveguide WDM channel selector operating over the entire C and L bands.

A tunable channel selector operating over both the C and L bands of wavelength-division-multiplexing optical network is proposed based on a thermo-optic tunable Bragg grating device in a polymer waveguide. A tilted Bragg grating cascaded with an asymmetric Y-branch waveguide effectively implements a small Bragg-reflection wavelength filter that does not require an external circulator. To increase the operating wavelength span of the channel selector, two Bragg gratings with different periods are fabricated on a single substrate for covering C and L bands, respectively. A wide tuning range over 80 nm along with a narrow bandwidth is demonstrated. Moreover, the polarization dependence of the reflection spectrum is observed to be less than 0.1 nm.

Anisotropic temperature-dependent thermal conductivity by an Al2O3 interlayer in Al2O3/ZnO superlattice films.

The thermal conductivity of superlattice films is generally anisotropic and should be studied separately in the in-plane and cross-plane directions of the films. However, previous works have mostly focused on the cross-plane thermal conductivity because the electrons and phonons in the cross-plane direction of superlattice films may result in much stronger interface scattering than that in the in-plane direction. Nevertheless, it is highly desirable to perform systematic studies on the effect of interface formation in semiconducting superlattice films on both in-plane and cross-plane thermal conductivities. In this study, we determine both the in-plane and cross-plane thermal conductivities of Al2O3 (AO)/ZnO superlattice films grown by atomic layer deposition (ALD) on SiO2/Si substrates in the temperature range of 50-300 K by the four-point-probe 3-ω method. Our experimental results indicate that the formation of an atomic AO layer (0.82 nm) significantly contributes to the decrease of the cross-plane thermal conductivity of the AO/ZnO superlattice films compared with that of AO/ZnO thin films. The cross-plane thermal conductivity (0.26-0.63 W m-1 K-1 of the AO/ZnO superlattice films (with an AO layer of ∼0.82 nm thickness) is approximately ∼150%-370% less than the in-plane thermal conductivity (0.96-1.19 W m-1 K-1) of the corresponding film, implying significant anisotropy. This indicates that the suppression of the cross-plane thermal conductivity is mainly attributed to the superlattice, rather than the nanograin columnar structure in the films. In addition, we theoretically analyzed strong anisotropic behavior of the in-plane and cross-plane thermal conductivities of the AO/ZnO superlattice films in terms of temperature dependence.

Tunable channel drop filters consisting of a tilted Bragg grating and a mode sorting polymer waveguide.

Optical wavelength filters with large tuning range and narrow bandwidth are crucial for enhancing the capability of WDM communication systems. A polymeric tunable filter for C-band, comprising a tilted Bragg grating and a mode sorting waveguide junction is proposed in this work. For dropping a certain wavelength signal, the tilted Bragg grating reflects an odd mode into an even mode and then the reflected even mode propagates towards an output port of the asymmetric Y-junction due to the mode sorting. Consequently, the output port is separated from the input port, which is not possible in an ordinary Bragg reflector. The tilted Bragg reflector with an odd-even mode coupling efficiency of 61% exhibited a maximum reflectivity of 95% for a grating of 6 mm. A linear wavelength tuning of over 10 nm was achieved for an applied thermal power of 312 mW.

Integrated optic polarization splitter based on total internal reflection from a birefringent polymer.

An integrated optic polarization splitter with large fabrication tolerance and high reliability is required for optical signal processing in quantum-encrypted communication systems. A polarization splitter based on total internal reflection from a highly birefringent polymer-reactive mesogen-is proposed and demonstrated in this work. The device consists of a mode expander for reducing the wave vector distribution of the guided mode, and an interface with a large birefringence. Several polymers with suitable refractive indexes were used for fabricating the device. We obtained a polarization splitter with a low crosstalk (less than -30 dB), and a large fabrication tolerance.

Surface relief apodized grating tunable filters produced by using a shadow mask.

To produce a compact low-cost tunable filter required for WDM optical communications, a polymeric Bragg reflection filter with an apodized grating structure is proposed. A high-contrast polymeric waveguide is incorporated in order to obtain high reflectivity from a short Bragg grating. To overcome the bandwidth broadening, an apodized grating with a gradually changing depth of surface relief grating along the propagation direction is fabricated through the dry etching with a shadow mask. The apodized polymer grating exhibits 3-dB, 20-dB bandwidths of 0.36 nm, and 0.72 nm, respectively with a 95% reflection. The reflection wavelength is tunable over 14 nm for an applied thermal power of 500 mW.

Optimizing an airborne mass-balance methodology for accurate emission rate quantification of industrial facilities: A case study of industrial facilities in South Korea.

Accurate estimation of emissions from industrial point sources is crucial in understanding the effectiveness of reduction efforts and establishing reliable emission inventories. In this study, we employ an airborne Chemical Ionization Mass Spectrometry (CIMS) instrument to quantify sulfur dioxide (SO2) emissions from prominent industrial facilities in South Korea, including power plants, a steel mill, and a petrochemical facility. Our analysis utilizes the box mass balance technique to derive SO2 emissions and associated uncertainty. We evaluate the interpolation methods between 2D kriging and 3D radial basis function. The results demonstrate that the total uncertainty of the box mass balance technique ranges from 5 % to 28 %, with an average of 20 %. Mixing ratio ground extrapolation from the lowest altitude of the airborne sampling to the ground emerges as the dominant source of uncertainty, followed by the determination of the boundary layer height. Adequate sampling at multiple altitudes is found to be essential in reducing the overall uncertainty by capturing the full extent of the plume. Furthermore, we assess the uncertainty of the single-height transect mass balance method commonly employed in previous studies. Our findings reveal an average precision of 47 % for this method, with the potential for overestimating emissions by up to 206 %. Samplings at fewer altitudes or with larger altitude gaps increase the risk of under-sampling and elevate method uncertainties. Therefore, this study provides a quantitative basis to evaluate previously airborne observational emission constraints.

Functional analysis of a class I holin, P2 Y.

Y is the putative holin gene of the paradigm coliphage P2 and encodes a 93-amino-acid protein. Y is predicted to be an integral membrane protein that adopts an N-out C-in membrane topology with 3 transmembrane domains (TMDs) and a highly charged C-terminal cytoplasmic tail. The same features are observed in the canonical class I lambda holin, the S105 protein of phage lambda, which controls lysis by forming holes in the plasma membrane at a programmed time. S105 has been the subject of intensive genetic, cellular, and biochemical analyses. Although Y is not related to S105 in its primary structure, its characterization might prove useful in discerning the essential traits for holin function. Here, we used physiological and genetic approaches to show that Y exhibits the essential holin functional criteria, namely, allele-specific delayed-onset lethality and sensitivity to the energization of the membrane. Taken together, these results suggest that class I holins share a set of unusual features that are needed for their remarkable ability to program the end of the phage infection cycle with precise timing. However, Y holin function requires the integrity of its short cytoplasmic C-terminal domain, unlike for S105. Finally, instead of encoding a second translational product of Y as an antiholin, as shown for lambda S107, the P2 lysis cassette encodes another predicted membrane protein, LysA, which is shown here to have a Y-specific antiholin character.

Modeling of misalignment effects in microfluidic interconnects for modular bio-analytical chip applications.

Minimizing misalignments during the interconnection of microfluidic modules is extremely critical to develop a fully integrated microfluidic device. Misalignments arising during chip-to-chip or world-to-chip interconnections can be greatly detrimental to efficient functioning of microfluidic devices. To address this problem, we have performed numerical simulations to investigate the effect of misalignments arising in three types of interconnection methods: (i) end-to-end interconnection (ii) channel overlap when chips are stacked on top of each other, and (iii) tube-in-reservoir misalignment occurring due to the offset between the external tubing and the reservoir. For the case of end-to-end interconnection, the effect of misalignment was investigated for 0, 13, 50, 58, and 75% reduction in the available flow area at the location of geometrical misalignment. In the channel overlap interconnection method, various possible misalignment configurations were simulated by maintaining the same amount of misalignment (75% flow area reduction). The effect of misalignment in a tube-in-reservoir interconnection was investigated by positioning the tube at an offset of 164 µm from the reservoir center. All the results were evaluated in terms of the equivalent length of a straight pipe. The effect of Reynolds number (Re) was also taken into account by performing additional simulations of aforementioned cases at Re ranging between 0.075 ≤ Re ≤ 75. Correlations were developed and the results were interpreted in terms of equivalent length (Le ). Equivalent length calculations revealed that the effect of misalignment in tube-in-reservoir interconnection method was the least significant when compared to the other two methods of interconnection.

Augmentation method of triple phase boundary in thin film solid oxide fuel cell via physical vapor deposition.

Triple phase boundaries (TPBs) where electrode, electrolyte, and reactant meet altogether were augmented in thin film solid oxide fuel cell when Pt cathode was deposited on yttrium-doped barium zirconate electrolyte (BZY) via sputter. The augmented TPBs were observed to exist as three-dimensional structures, which is different from what are known to exist as two-dimensional planes or interfaces, by using energy dispersive spectroscopy (EDS). The permeating phenomenon of sputtered Pt into BZY was found to depend on dc sputtering power. Polarization curves showed increasing tendency of maximum powers in accordance with increasing thickness of Pt cathode and spectra of ac impedances showed decreasing tendency of faradaic resistances. If TPBs were located as an interfacial structure between electrode and electrolyte, oxygen could not diffuse well into TPBs, causing radius of semicircle in impedance spectra to decrease. The results are violating this expectation. As a result, as long as charge transfer resistance is a function of temperature, reactant concentration, activation barrier and TPB length, TPB must be only a factor to affect the results in this experiment.

Evidence integration on health damage for humidifier disinfectant exposure and legal presumption of causation.

OBJECTIVES: Inhalation exposure to humidifier disinfectants has resulted to various types of health damages in Korea. To determine the epidemiological correlation necessary for presuming the legal causation, we aimed to develop a method to synthesize the entire evidence. METHODS: Epidemiological and toxicological studies are systematically reviewed. Target health problems are selected by criteria such as frequent complaints of claimants. Relevant epidemiologic studies are reviewed and the risk of bias and confidence level of the total evidence are evaluated. Toxicological literature reviews are conducted on three lines of evidence including hazard information, animal studies, and mechanistic studies, considering the source-to-exposure-to-outcome continuum. The confidence level of the body of evidence is then translated into the toxicological evidence levels for the causality between humidifier disinfectant exposure and health effects. Finally, the levels of epidemiological and toxicological evidence are synthesized. RESULTS: Under the Special Act revised in 2020, if the history of exposure and the disease occurred/worsened after exposure were approved, and the epidemiological correlation between the exposure and disease was verified, the legal causation is presumed unless the company proves the evidence against it. The epidemiological correlation can be verified through epidemiological investigations, health monitoring, cohort investigations and/or toxicological studies. It is not simply as statistical association as understood in judicial precedents, but a general causation established by the evidence as a whole, i.e., through weight-of-the-evidence approach. CONCLUSIONS: The weight-of-the-evidence approach differs from the conclusive single study approach and this systematic evidence integration can be used in presumption of causation.