Heterogeneous integration approach based on flip-chip bonding and misalignment self-correction elements for electronics-optics integration applications

This paper presents a high precision bonding approach, capable of submicron alignment accuracy, based on the thermosonic flip-chip bonding technique and misalignment self-correction elements. The precision of the bonding technique is guaranteed by using of misalignment self-correction bump (convex) and hollow (concave) elements. Metal cone bump and conductive sloped hollow bonding pad elements are created using micro-machining techniques, on a chip specimen and substrate, respectively. The chip and substrate are bonded face-to-face using of an ultrasonic-enhanced flip-chip bonder. By introducing of misalignment self-correction elements, repeatable bonding accuracies of less than 500 nm were confirmed through experimental investigation. Bond properties, including electrical and mechanical properties, are also characterized to confirm the success of the bonding approach. With the obtained results, the proposed bonding approach is capable of being use in electronics-optics heterogeneous integration applications

Identification of a novel motif responsible for the distinctive transforming activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2 Tax2

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia (ATL), whereas its relative HTLV-2 is not associated with any malignancies including ATL. HTLV-1 Tax1 transformed a T-cell line from interleukin (IL)-2-dependent growth to IL-2-independent growth, with an activity that was much more potent in comparison to HTLV-2 Tax2. This distinction was mediated by at least two Tax1 specific functions, an interaction with host cellular factors through the PDZ domain binding motif (PBM) and the activation of NF-kappaB2 (NF-κB2)/p100.</p> <p>Results</p> <p>Using a series of Tax1 chimeric proteins with Tax2, we found that amino acids 225-232 of Tax1, the Tax1(225-232) region, was essential for the activation of NF-κB2 as well as for the high transforming activity. The strict amino acid conservation of Tax1(225-232) among HTLV-1 and simian T-cell leukemia virus type 1 (STLV-1), but not HTLV-2 and STLV-2, indicates that function(s) through the Tax1(225-232) region are biologically significant. Interestingly, another HTLV-1 relative, HTLV-3, has a PBM, but does not conserve the Tax1(225-232) motif in Tax3, thus indicating that these two motifs classify the three HTLVs into the separate groups.</p> <p>Conclusion</p> <p>These results suggest that the combinatory functions through Tax1(225-232) and PBM play crucial roles in the distinct biological properties of the three HTLVs, perhaps also including their pathogenesis.</p

Adhesion of aerosol deposition traces targeted for flexible electronics applications

•Emergence of wearable electronics - from medical to consumer products. •Requirement: To realise conductive traces on flexible substrates. •Common printing techniques: screen printing and inkjet printing. •Aerosol deposition (AD)1 is an emerging potential technology as it offers room temperature deposition. •From literature others have used AD to deposit metal base layers onto flexible substrates. To the authors’ best knowledge, there has been no work reported on the deposition of copper onto flexible substrates. •Copper is an attractive option as it is relatively cheap compared to other metals (eg. silver)

Induction of cyclooxygenase-2 in human synovial cells by β2-microglobulin

Induction of cyclooxygenase-2 in human synovial cells by β2-microglobulin.BackgroundProstaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cyclooxygenase-2 (COX-2) enzyme, which regulates PG biosynthesis, in osteoarthropathy associated with hemodialysis-associated amyloidosis (HAA) by characterizing COX-2 expression in β2-microglobulin–treated human synovial cells.MethodsWe examined the effects of β2-microglobulin (β2m), a major constituent protein of amyloid fibrils in HAA, on the COX-2 protein and mRNA expression in human synovial cells using Western blot and reverse transcriptase-polymerase chain reaction.Resultsβ2m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of β2m–containing media by anti-β2m–specific antibody abrogated β2m–mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in β2m–stimulated synovial cells.ConclusionsOur results suggest that induction of COX-2 expression by β2m may be an important component of the inflammatory process in hemodialysis-associated osteoarthropathy

30-GHz high-frequency application of screen printed interconnects on an organic substrate

Printed conductive traces on flexible substrates offer many potential applications in the area of wearable electronics, ranging from search and rescue operations to health and physiological monitoring. Literature abounds on the effect of sintering conditions on the DC electrical resistivity of printed traces, due to the applications considered which fall in the lower frequency domain (megahertz range). There is a growing interest to investigate Wireless Body Area Networks (WBANs) for wearable electronics operating in the higher frequencies, due to the advantages involved. At present there is little information available on the radio frequency (RF) performance of printed interconnects, and this work seeks to investigate the effect of the paste property on the DC conductivity and high frequency performance (≤ 30 GHz) of interconnects. The results obtained suggest that paste levelling has a significant influence on the DC electrical performance. In addition, the DC conductivity values are possibly affected by the adhesion of the paste onto the particular substrate during the printing process, which was observed to have a significant effect on the quality and thicknesses of the traces printed. Lastly, the influence of the DC conductivity on the high frequency performance of interconnects is investigated, where the measured results are validated with simulation results

High Mobility Group Box 1 Expression in Oral Inflammation and Regeneration

High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein of about 30 kDa. It is released from a variety of cells into the extracellular milieu in response to inflammatory stimuli and acts on specific cell-surface receptors, such as receptors for advanced glycation end-products (RAGE), Toll-like receptor (TLR)2, TLR4, with or without forming a complex with other molecules. HMGB1 mediates various mechanisms such as inflammation, cell migration, proliferation, and differentiation. On the other hand, HMGB1 enhances chemotaxis acting through the C-X-C motif chemokine ligand (CXCL)12/C-X-C chemokine receptor (CXCR)4 axis and is involved in regeneration. In the oral cavity, high levels of HMGB1 have been detected in the gingival tissue from periodontitis and peri-implantitis patients, and it has been shown that secreted HMGB1 induces pro-inflammatory cytokine expression, such as interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, which prolong inflammation. In contrast, wound healing after tooth extraction or titanium dental implant osseointegration requires an initial acute inflammation, which is regulated by secreted HMGB1. This indicates that secreted HMGB1 regulates angiogenesis and bone remodeling by osteoclast and osteoblast activation and promotes bone healing in oral tissue repair. Therefore, HMGB1 can prolong inflammation in the periodontal tissue and, conversely, can regenerate or repair damaged tissues in the oral cavity. In this review, we highlight the role of HMGB1 in the oral cavity by comparing its function and regulation with its function in other diseases. We also discuss the necessity for further studies in this field to provide more specific scientific evidence for dentistry

A complex rearrangement between APC and TP63 associated with familial adenomatous polyposis identified by multimodal genomic analysis: a case report

Genetic testing of the APC gene by sequencing analysis and MLPA is available across commercial laboratories for the definitive genetic diagnosis of familial adenomatous polyposis (FAP). However, some genetic alterations are difficult to detect using conventional analyses. Here, we report a case of a complex genomic APC-TP63 rearrangement, which was identified in a patient with FAP by a series of genomic analyses, including multigene panel testing, chromosomal analyses, and long-read sequencing. A woman in her thirties was diagnosed with FAP due to multiple polyps in her colon and underwent total colectomy. Subsequent examination revealed fundic gland polyposis. No family history suggesting FAP was noted except for a first-degree relative with desmoid fibromatosis. The conventional APC gene testing was performed by her former doctor, but no pathogenic variant was detected, except for 2 variants of unknown significance. The patient was referred to our hospital for further genetic analysis. After obtaining informed consent in genetic counseling, we conducted a multigene panel analysis. As insertion of a part of the TP63 sequence was detected within exon16 of APC, further analyses, including chromosomal analysis and long-read sequencing, were performed and a complex translocation between chromosomes 3 and 5 containing several breakpoints in TP63 and APC was identified. No phenotype associated with TP63 pathogenic variants, such as split-hand/foot malformation (SHFM) or ectrodactyly, ectodermal dysplasia, or cleft lip/palate syndrome (EEC) was identified in the patient or her relatives. Multimodal genomic analyses should be considered in cases where no pathogenic germline variants are detected by conventional genetic testing despite an evident medical or family history of hereditary cancer syndromes

Characterization of the sequence specificity of the R1Bm endonuclease domain by structural and biochemical studies

R1Bm is a long interspersed element (LINE) inserted into a specific sequence within 28S rDNA of the silkworm genome. Of two open reading frames (ORFs) of R1Bm, ORF2 encodes a reverse transcriptase (RT) and an endonuclease (EN) domain which digests specifically both top and bottom strand of the target sequence in 28S rDNA. To elucidate the sequence specificity of EN domain of R1Bm (R1Bm EN), we examined the cleavage tendency for the target sequences, and found that 5′-A(G/C)(A/T)!(A/G)T-3′ is the consensus sequence (! = cleavage site). We also determined the crystal structure of R1Bm EN at 2.0 Å resolution. Its structure was basically similar to AP endonuclease family, but had a special β-hairpin at the edge of the DNA binding surface, which is a common feature among EN of LINEs. Point-mutations on the DNA binding surface of R1Bm EN significantly decreased the cleavage activities, but did not affect the sequence recognition in most residues. However, two mutants Y98A and N180A had altered cleavage patterns, suggesting an important role of these residues (Y98 and N180) for the sequence recognition of R1Bm EN. In addition, Y98A mutant showed another cleavage pattern, that implies de novo design of novel sequence-specific EN

Molecular Characteristics of Extended-Spectrum Beta-Lactamases and qnr Determinants in Enterobacter Species from Japan

The incidence of extended-spectrum β-lactamases (ESBLs) has been increasing worldwide, but screening criteria for detection of ESBLs are not standardized for AmpC-producing Enterobacteriaceae such as Enterobacter species. In this study, we investigated the prevalence of ESBLs and/or AmpC β-lactamases in Japanese clinical isolates of Enterobacter spp. and the association of plasmid-mediated quinolone resistance (PMQR) determinants with ESBL producers. A total of 364 clinical isolates of Enterobacter spp. collected throughout Japan between November 2009 and January 2010 were studied. ESBL-producing strains were assessed by the CLSI confirmatory test and the boronic acid disk test. PCR and sequencing were performed to detect CTX-M, TEM, and SHV type ESBLs and PMQR determinants. For ESBL-producing Enterobacter spp., pulsed-field gel electrophoresis (PFGE) was performed using XbaI restriction enzyme. Of the 364 isolates, 22 (6.0%) were ESBL producers. Seven isolates of Enterobacter cloacae produced CTX-M-3, followed by two isolates producing SHV-12. Two isolates of Enterobacter aerogenes produced CTX-M-2. Of the 22 ESBL producers, 21 had the AmpC enzyme, and six met the criteria for ESBL production in the boronic acid test. We found a significant association of qnrS with CTX-M-3-producing E. cloacae. The 11 ESBL-producing Enterobacter spp. possessing blaCTX-M, blaSHV, or blaTEM were divided into six unique PFGE types. This is the first report about the prevalence of qnr determinants among ESBL-producing Enterobacter spp. from Japan. Our results suggest that ESBL-producing Enterobacter spp. with qnr determinants are spreading in Japan

Association between mental health and bone mass among community-dwelling adults: Nagasaki Islands Study on bone health

Osteoporosis and its related fractures are important public health issues. This study examined the association between the Kessler Psychological Distress Scale (K6) and low bone mass in middle-aged community-dwelling men and women. A crosssectional study was nested in a prospective observational study of 1,101 participants (median age: 57 [49-62] years in men and 58 [50-62] years in women) residing in a rural city in western Japan. Participants were recruited during medical check-ups in 2016 and 2017 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. Of the participants, 56 men (14.9%) and 144 women (19.9%) had a bone mass of less than 70% of the mean of young adults. Univariate analysis revealed that there was a trend toward lower body mass index (BMI) and higher prevalence of low bone mass with an increase in K6 scores in men but not in women. Logistic regression analysis, adjusting for possible confounders(age, BMI, smoking, drinking habits, exercise habits, diabetes, hyperlipidemia, and hypertension), showed significant associations between the K6 scores and low bone mass (odds ratio (OR) = 2.66 for the men with 5 to 12 points of K6, OR = 7.51 for men with ≥ 13 of K6, not for women). We showed an association between psychological distress and low bone mass independent of cofounders among community-dwelling middle-aged men but not women. This suggests that healthy mental health in middle-aged men may be a possible target for the prevention of consequent osteoporosis or fragile bone fractures