Layout Dependence Stress Investigation in through Glass via Interposer Architecture Using a Submodeling Simulation Technique and a Factorial Design Approach.

The multi-chiplet technique is expected to be a promising solution to achieve high-density system integration with low power consumption and high usage ratio. This technique can be integrated with a glass interposer to accomplish a competitive low fabrication cost compared with the silicon-based interposer architecture. In this study, process-oriented stress simulation is performed by the element activation and deactivation technique in finite element analysis architecture. The submodeling technique is also utilized to mostly conquer the scale mismatch and difficulty in mesh gridding design. It is also used to analyze the thermomechanical responses of glass interposers with chiplet arrangements and capped epoxy molding compounds (EMC) during curing. A three-factor, three-level full factorial design is applied using the analysis of variance method to explore the significance of various structural design parameters for stress generation. Analytic results reveal that the maximum first principal stresses of 130.75 and 17.18 MPa are introduced on the sidewall of Cu-filled via and the bottom of the glass interposer, respectively. Moreover, the EMC thickness and through glass via pitch are the dominant factors in the adopted vehicle. They significantly influence the stress magnitude during heating and cooling.

Hyperbaric Oxygen Therapy Alleviates Paclitaxel-Induced Peripheral Neuropathy Involving Suppressing TLR4-MyD88-NF-κB Signaling Pathway.

Paclitaxel (PAC) results in long-term chemotherapy-induced peripheral neuropathy (CIPN). The coexpression of transient receptor potential vanilloid 1 (TRPV1) and Toll-like receptor 4 (TLR4) in the nervous system plays an essential role in mediating CIPN. In this study, we used a TLR4 agonist (lipopolysaccharide, LPS) and a TLR4 antagonist (TAK-242) in the CIPN rat model to investigate the role of TLR4-MyD88 signaling in the antinociceptive effects of hyper-baric oxygen therapy (HBOT). All rats, except a control group, received PAC to induce CIPN. Aside from the PAC group, four residual groups were treated with either LPS or TAK-242, and two of them received an additional one-week HBOT (PAC/LPS/HBOT and PAC/TAK-242/HBOT group). Mechanical allodynia and thermal hyperalgesia were then assessed. The expressions of TRPV1, TLR4 and its downstream signaling molecule, MyD88, were investigated. The mechanical and thermal tests revealed that HBOT and TAK-242 alleviated behavioral signs of CIPN. Immunofluorescence in the spinal cord dorsal horn and dorsal root ganglion revealed that TLR4 overexpression in PAC- and PAC/LPS-treated rats was significantly downregulated after HBOT and TAK-242. Additionally, Western blots showed a significant reduction in TLR4, TRPV1, MyD88 and NF-κB. Therefore, we suggest that HBOT may alleviate CIPN by modulating the TLR4-MyD88-NF-κB pathway.

Reliability Assessment of Thermocompressed Epoxy Molding Compound through Glass via Interposer Architecture by the Submodeling Simulation Approach.

In glass interposer architecture and its assembly process, the mechanical responses of interposer structure under thermocompression process-induced thermal loading and generated shrinkage of molding material are regarded as a major reliability issue. Thousands of metal-filled via are involved in glass interposers and are regarded as a potential risk that can lead to cracking and the failure of an entire vehicle. In this study, a finite element-based submodeling approach is demonstrated to overcome the complexity of modeling and the relevant convergence issue of interposer architecture. Convergence analysis results revealed that at least four via pitch-wide regions of a local simulation model were needed to obtain the stable results enabled by the submodeling simulation approach. The stress-generation mechanism during thermocompression, the coefficient of thermal expansion mismatch, and the curing process-induced shrinkage were separately investigated. The critical stress location was explored as the outer corner of the chip, and the maximum first principal stress during the thermocompression process generated on the chip and glass interposer were 34 and 120 MPa, respectively.

Hyperbaric Oxygen Therapy Attenuates Burn-Induced Denervated Muscle Atrophy.

Background: Neuronal apoptosis and inflammation in the ventral horn of the spinal cord contribute to denervated muscle atrophy post-burn. Hyperbaric oxygen therapy (HBOT) exerts anti-inflammation and neuroprotection. Furthermore, hypoxia-inducible factor (HIF)-1α has been reported to promote inflammation and apoptosis. We investigated the therapeutic potential of HBOT and the role of HIF-1α post-burn. Methods: Sprague-Dawley rats were divided into three groups: a control group, an untreated burn group receiving burn and sham treatment, and a HBOT group receiving burn injury and HBOT. The burn injury was induced with 75ºC ± 5ºC at the right hindpaw. HBOT (100% oxygen at 2.5 atmosphere, 90 min/day) and sham HBOT (21% oxygen at 1 atmosphere, 90 min/day) was started on day 28 after burn injury and continued for 14 treatments (days 28-41). Incapacitance (hind limb weight bearing) testing was conducted before burn and weekly after burn. At day 42 post-burn, the gastrocnemius muscle and the spinal cord ventral horn were analyzed. Results: HBOT improved burn-induced weight bearing imbalance. At day 42 post-burn, less gastrocnemius muscle atrophy and fibrosis were noted in the HBOT group than in the untreated burn group. In the ventral horn, HBOT attenuated the neuronal apoptosis and glial activation post-burn. The increases in phosphorylated AKT/mTOR post-burn were reduced after HBOT. HBOT also inhibited HIF-1α signaling, as determined by immunofluorescence and western blot. Conclusions: HBOT reduces burn-induced neuronal apoptosis in the ventral horn, possibly through HIF-1α signaling.

Simultaneous hyperbaric oxygen therapy during systemic chemotherapy reverses chemotherapy-induced peripheral neuropathy by inhibiting TLR4 and TRPV1 activation in the central and peripheral nervous system.

BACKGROUND AND OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is considered one of the most common sequelae in patients with cancer who experience consistent abnormal sensations or pain symptoms during or after paclitaxel (PAC) chemotherapy. Transient receptor potential vanilloid 1 (TRPV1) and toll-like receptor 4 (TLR4) have been reported to interact in the nervous system in patients with CIPN. The antinociceptive effects of hyperbaric oxygen therapy (HBOT) on CIPN was demonstrated in this study through behavior tests. Using a CIPN rat model, we examined the effects of simultaneous HBOT (SHBOT) administration during chemotherapy and discovered that SHBOT achieved better reversal effects than chemotherapy alone. MATERIALS AND METHODS: Twenty-four rats were randomly allocated to four groups: control, PAC, SHBOT, and HBOT after PAC groups. Behavior tests were performed to evaluate mechanical allodynia and thermal hyperalgesia status. Tissues from the spinal cord and dorsal root ganglions were collected, and TLR4 and TRPV1 expression and microglial activation were investigated through immunofluorescence (IF) staining. RESULTS: The mechanical and thermal behavior tests revealed that HBOT intervention during PAC treatment led to the early alleviation of CIPN symptoms and inhibited CIPN deterioration. IF staining revealed that TLR4, TRPV1, and microglial activation were all upregulated in PAC-injected rats and exhibited early and significant downregulation in SHBOT-treated rats. CONCLUSION: This study is the first to demonstrate that the use of SHBOT during PAC treatment has potential for the early suppression of CIPN initiation and deterioration, indicating that it can alleviate CIPN symptoms and may reverse CIPN in patients undergoing systemic chemotherapy.

A decentralized framework for cultivating research lifecycle transparency.

Research transparency has been advocated as a key means of addressing the current crisis of reproducibility. This article proposes an enhanced form of research transparency, termed lifecycle transparency. Over the entire lifecycle of a research effort, this approach captures the syntactical contexts of artifacts and stakeholders, such as timestamps, agreements, and/or dependency requirements for completing each research phase. For example, such contexts might include when, where, and from whom patients' consent and institutional review board approvals were received before a clinical trial was carried out. However, as existing open-science tools are often dedicated to certain research phases or disciplines, and thus insufficient to support lifecycle transparency, we propose a novel decentralized framework to serve as a common medium for interaction among open-science tools, and produces irrefutable and immutable proofs of progress that can be verified automatically.

Simultaneous detection of two growth factors from human single-embryo culture medium by a bead-based digital microfluidic chip.

The measurement of growth factors released in a culture medium is considered to be an attractive non-invasive approach, apart from the embryo morphology, to identify the condition of an embryo development after fertilization in vitro (IVF), but the available embryo culture medium in the current method is only a few microlitres. This small sample volume, also of small concentration, makes difficult the application of a conventional detection method, such as an enzyme-linked immunosorbent assay (ELISA). A reliable detection of the growth factor from each embryo culture medium of such a small concentration hence remains a challenge. Here for the first time we report the results of measurement of not just one, but two, growth factors, human IL-1ß and human TNF-α, from an individual droplet of embryo culture medium with a bead-based digital microfluidic chip. The required sample volume for a single measurement is only 520 nL; the total duration of the on-chip process is less than 40 min. Using the culture media of human embryos with normal morphologic features, we found that the concentrations of TNF-α change little from day 3 to day 5-6, but the concentrations of IL-1ß for some embryos might double from day 3 to day 5-6. For other embryos even with similar normal morphologic features, some growth factors, such as IL-1ß, might exhibit different expressions during the culture period. Those growth factors could serve to distinguish the development conditions of each embryo, not merely from an observation of embryo morphology.

Bimodal Biometric Verification Using the Fusion of Palmprint and Infrared Palm-Dorsum Vein Images.

In this paper, we present a reliable and robust biometric verification method based on bimodal physiological characteristics of palms, including the palmprint and palm-dorsum vein patterns. The proposed method consists of five steps: (1) automatically aligning and cropping the same region of interest from different palm or palm-dorsum images; (2) applying the digital wavelet transform and inverse wavelet transform to fuse palmprint and vein pattern images; (3) extracting the line-like features (LLFs) from the fused image; (4) obtaining multiresolution representations of the LLFs by using a multiresolution filter; and (5) using a support vector machine to verify the multiresolution representations of the LLFs. The proposed method possesses four advantages: first, both modal images are captured in peg-free scenarios to improve the user-friendliness of the verification device. Second, palmprint and vein pattern images are captured using a low-resolution digital scanner and infrared (IR) camera. The use of low-resolution images results in a smaller database. In addition, the vein pattern images are captured through the invisible IR spectrum, which improves antispoofing. Third, since the physiological characteristics of palmprint and vein pattern images are different, a hybrid fusing rule can be introduced to fuse the decomposition coefficients of different bands. The proposed method fuses decomposition coefficients at different decomposed levels, with different image sizes, captured from different sensor devices. Finally, the proposed method operates automatically and hence no parameters need to be set manually. Three thousand palmprint images and 3000 vein pattern images were collected from 100 volunteers to verify the validity of the proposed method. The results show a false rejection rate of 1.20% and a false acceptance rate of 1.56%. It demonstrates the validity and excellent performance of our proposed method comparing to other methods.