Cancer cell-immune cell hybrids and cancer immunotherapy have attracted much attention in recent years. The design of efficient cell pairing and fusion chips for hybridoma generation has been, ...subsequently, a subject of great interest. Here, we report a three-layered integrated Microfluidic Flip-Chip (MFC) consisting of a thin through-hole membrane sandwiched between a mirrored array of microfluidic channels and saw-tooth shaped titanium electrodes on the glass. We discuss the design and operation of MFC and show its applicability for cell fusion. The proposed device combines passive hydrodynamic phenomenon and gravitational sedimentation, which allows the transportation and trapping of homotypic and heterotypic cells in large numbers with pairing efficiencies of 75~78% and fusion efficiencies of 73%. Additionally, we also report properties of fused cells from cell biology perspectives, including combined fluorescence-labeled intracellular materials from THP1 and A549, mixed cell morphology, and cell viability. The MFC can be tuned for pairing and fusion of cells with a similar protocol for different cell types. The MFC can be easily disconnected from the test setup for further analysis.
Abstract
In this work, we integrated a periodic seed layer and oblique deposition method to fabricate a stochastically-distributed oblique-flat-sheet metamaterial perfect absorber (MPA). Such design ...could increase its absorption bandwidth and tolerance to high angle-incidence due to the fact that various oblique flat sheets offer different resonance conditions while even a single oblique flat sheet could provide different optical paths for resonance. On the other hand, a seed layer could reduce uncertainty regarding to direct oblique deposition and provide abilities to manipulate the bandwidth of the MPA. We also setup a simulation model in the aids of Visual Basic Application and examined the absorption behavior of the MPA under TM and TE oblique incidence that could achieve high absorbance under 80° and 60° incidence, respectively. Finally, in measurement, the fabricated sample owns 65% absorbance within 80–250 THz and over 90% absorbance within 250–320 THz at x-polarization normal incidence; as for the y-polarization normal incidence, we could achieve overall 70% absorbance within 80–300 THz. The measured results reveal similar tendency compared to the simulated ones.
This article presents a computing-in-memory (CIM) structure aimed at improving the energy efficiency of edge devices running multi-bit multiply-and-accumulate (MAC) operations. The proposed scheme ...includes a 6T SRAM-based CIM (SRAM-CIM) macro capable of: 1) weight-bitwise MAC (WbwMAC) operations to expand the sensing margin and improve the readout accuracy for high-precision MAC operations; 2) a compact 6T local computing cell to perform multiplication with suppressed sensitivity to process variation; 3) an algorithm-adaptive low MAC-aware readout scheme to improve energy efficiency; 4) a bitline header selection scheme to enlarge signal margin; and 5) a small-offset margin-enhanced sense amplifier for robust read operations against process variation. A fabricated 28-nm 64-kb SRAM-CIM macro achieved access times of 4.1-8.4 ns with energy efficiency of 11.5-68.4 TOPS/W, while performing MAC operations with 4- or 8-b input and weight precision.
Recent concern about mainland China's intentions towards Taiwan, and more general concern about the risk of instability in the region, has led to growing interest in Taiwan's military strategy, in ...how Taiwan perceives threats to itself, and in how the Taiwanese military are reacting to these perceived threats. This book, which includes contributions by leading Taiwanese military thinkers, explores current military strategy in Taiwan and how it is evolving. It discusses Taiwan's military modernisation, and the implications of the recent defeat after fifty years in power of the Kuomintang Party, implications which include a move away from an authoritarian garrison state culture, and the beginnings of a more open debate about defence. The book concludes with an overall appraisal of Taiwan's defence vision and makes recommendations on how Taiwan's defence might be enhanced.
Congenital cytomegalovirus (cCMV) infection is the most prevalent cause of non-genetic sensorineural hearing loss (SNHL) in children. However, the prognostic determinants of SNHL remain unclear. ...Children with cCMV infection in a tertiary hospital were enrolled. The presence of cCMV-related symptoms at birth, the newborn hearing screening (NHS) results, and the blood viral loads were ascertained. Audiologic outcomes and initial blood viral loads were compared between different groups. Of the 39 children enrolled, 16 developed SNHL. SNHL developed in 60% of children who were initially symptomatic, and in 34.5% of those who were initially asymptomatic with normal hearing or isolated hearing loss, respectively. Failuire in NHS was a reliable tool for early detection of SNHL. The initial viral loads were higher in children who were symptomatic at birth, those who failed NHS, and those who developed SNHL. We observed SNHL deterioration in a patient after CMV DNAemia clearance was achieved, and in another patient with the flare-up of viral load. The presence of cCMV-related symptoms at birth, failure in NHS, and blood viral load might be the prognostic factors for hearing outcomes. Regular audiologic examinations are necessary in all children with cCMV infection even after CMV DNAemia clearance.
Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) ...assays were utilized to assay plasma Aβ
and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aβ
were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aβ
and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aβ
in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aβ
in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aβ
in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aβ
in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aβ
in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers.
Tumor hypoxia is associated with disease progression and treatment failure, but the hypoxia signaling mechanism is not fully understood. Here, we show that KLHL20, a Cullin3 (Cul3) substrate adaptor ...induced by HIF-1, coordinates with the actions of CDK1/2 and Pin1 to mediate hypoxia-induced PML proteasomal degradation. Furthermore, this PML destruction pathway participates in a feedback mechanism to maximize HIF-1α induction, thereby potentiating multiple tumor hypoxia responses, including metabolic reprogramming, epithelial-mesenchymal transition, migration, tumor growth, angiogenesis, and chemoresistance. In human prostate cancer, overexpression of HIF-1α, KLHL20, and Pin1 correlates with PML down-regulation, and hyperactivation of the PML destruction pathway is associated with disease progression. Our study indicates that the KLHL20-mediated PML degradation and HIF-1α autoregulation play key roles in tumor progression.
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► The HIF-1-inducible KLHL20 mediates hypoxia-induced PML proteasomal degradation ► Targeting PML to KLHL20 requires PML modifications by CDK1/2 and Pin1 ► The KLHL20-PML pathway is part of a feedback mechanism to amplify HIF-1 signaling ► Hyperactivation of the KLHL20-PML pathway correlates with high-grade prostate tumors
In this paper, we demonstrate the design and fabrication of a high-power, high-speed flip-chip vertical cavity surface emitting laser (VCSEL) for light detection and ranging (LiDAR) systems. The ...optoelectronic characteristics and modulation speeds of vertical and flip-chip VCSELs were investigated numerically and experimentally. The thermal transport properties of the two samples were also numerically investigated. The measured maximum output power, slope efficiency (SE) and power conversion efficiency (PCE) of a fabricated flip-chip VCSEL array operated at room-temperature were 6.2 W, 1.11 W/A and 46.1%, respectively. The measured L-I-V curves demonstrated that the flip-chip architecture offers better thermal characteristics than the conventional vertical structure, especially for high-temperature operation. The rise time of the flip-chip VCSEL array was 218.5 ps, and the architecture of the flip-chip VCSEL with tunnel junction was chosen to accommodate the application of long-range LiDAR. The calculated PCE of such a flip-chip VCSEL was further improved from 51% to 57.8%. The device design concept and forecasting laser characteristics are suitable for LiDAR systems.
We investigated gas adsorption and diffusion in an emerging pillared-bilayer metal–organic framework (MOF), Zn-AIP-AZPY (aip, 5-aminoisophthalic acid; azpy, 4,4′-azobipyridine). This work ...demonstrated that the crystal structure of this flexible MOF could be controlled by two different activation methods: the thermal activation and the chemical activation. The pore limiting diameter of the thermally activated compound was ∼3.7 Å, whereas that of the fully activated one via methanol extraction was 2.92 Å. Although the aperture size of the fully activated structure was smaller than the kinetic diameter of CO2 and CH4, Zn-AIP-AZPY still presented fair adsorption quantity to these two gases. In situ XRD experiments under various gases at different pressures also suggest a minor breathing effect when Zn-AIP-AZPY was exposed to CO2 and no breathing effect under CH4. These results imply the possible ligand rotation occurring during the adsorption of CO2 and CH4 in Zn-AIP-AZPY. The Zn-AIP-AZPY membranes were further prepared using the seeded growth method, and these membranes showed an exceptionally high H2 permeability (over 105 barrer) with a good H2/CO2 selectivity (ideal selectivity beyond 8). A reverse CO2/CH4 selectivity, i.e., CH4 permeates faster than CO2, was surprisingly found. Monte Carlo simulations were conducted for probing the adsorption properties of CO2 and CH4, as well as their adsorption energy landscape in Zn-AIP-AZPY. It was found that this MOF energetically favored the adsorption of CO2 over CH4 by nearly 10 kJ/mol. Such a strong adsorption is anticipated to create high energy barriers for CO2 hopping between neighboring adsorption sites.
Staphylococcus aureus is one of most common pathogens in humans. Methicillin-resistant S. aureus (MRSA) accounts for 64 % of S. aureus bacteremia isolated in intensive care units (ICUs), and ...heteroresistant vancomycin-intermediates S. aureus (hVISA) is a phenotype of MRSA. However, studies focusing on the hVISA impact on critically ill patients are scarce.
This was a retrospective study conducted in a tertiary medical center from January 2009 to December 2010. All adult patients in ICUs with MRSA bloodstream infection were eligible. A modified population analysis profile and area under the curve method was applied to all isolates to confirm hVISA phenotype. Multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) and the accessory gene regulator (agr) typing were performed individually. Clinical outcomes including in-hospital mortality, length of stay in intensive care unit and hospital after MRSA bacteremia of the patients were also analyzed.
A total of 48 patients were enrolled and 14 patients were confirmed to have the hVISA phenotype. The prevalence of hVISA was 29.2 %. There was no difference in the age, sex, comorbidity, Charlson's comorbidity score and previous vancomycin therapy between the hVISA and VSSA groups. The hVISA group had a significantly higher in-hospital mortality than the VSSA group (13/14 versus 22/34; p = 0.046). All of the 14 hVISA patients had an MIC = 2 mg/L by E-test and this represented a significant association between high MIC and the development of hVISA (p < 0.001). MLST analysis showed all the isolates in the hVISA group were ST239, while ST239 (14/34; 41.2 %) and ST5 (12/34; 35.3 %) were predominant in the VSSA group (p = 0.007). A comparison of the survivor and non-survivor group showed that the hVISA phenotype (OR 11.8; 95 % CI 1.1-126.99; p = 0.042) and sequential organ failure assessment (SOFA) score (OR 1.39; 95 % CI 1.07-1.81; p = 0.014) were independent factors significantly associated with in-hospital mortality.
Patients in ICUs with MRSA bacteremia may have a higher in-hospital mortality if they have the hVISA phenotype. SOFA score is also predictor of mortality.
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