1,190 research outputs found
Nondestructive Measurement Material Characterization of Thermal Sprayed Nickel Aluminum Coatings by using Laser Ultrasound Technique
AbstractThis research focused on characterization of mechanical properties in Nickel-Aluminum coating with different thermal technique and processing parameters at high temperature environment up to 295°C. With the laser ultrasound technique (LUT), guided acoustic waves are generated to propagate on the Ni-Al sprayed coatings. By measuring dispersive phase velocity followed by SCE-UA inversion algorithm. The Young's modulus of coatings which fabricated by HVOF technique is higher than APS technique. This technique is potentially useful to probe the material characterization at high temperature environment in a remote and non-destructive way
Enhancement of Cancer Immunotherapy Using Immune Modulating Peptides
poster abstractImmune Peptide Therapeutics (IPT) LLC, an Indiana-based small business and its research partner Indiana University previously identified a novel property of lunasin as a distinct class of immune modulating agent that enhances anti-tumor immunity, which may promote disease-free survival by limiting tumor progression, and thus prolong lives of cancer patients. Lunasin, a synthetic 43-amino acid peptide, was originally isolated from soybeans. Our studies have demonstrated that lunasin exerts robust synergistic effects with cytokines on augmenting IFNγ and granzyme B expression by Natural Killer (NK) cells, which is associated with increased tumoricidal activity of NK cells. In addition, this combination regimen is capable of rescuing IFNγ production ex vivo by NK cells from chemotherapy-treated Non-Hodgkin’s Lymphoma (NHL) patients who are immunocompromised with acquired immune deficiency. The long-term goal is to develop an efficacious immunotherapy which will impact the treatment and improve the clinical outcomes for NHL patients. The dose-response study indicates the optimum concentration of lunasin is at the range of μM, which would undermine its use in clinical studies. To enhance the medicinal value lunasin must be optimized for in vitro and in vivo efficacy. The objective is to develop a second generation of lunasin, which will increase its potency to improve the performance. In this study we have implemented several strategies to design and modify the prototype. The newly developed peptide called IPT.103 has 15 amino acids that are in the D-isoform configuration. Activity of IPT.103 has been tested in vitro with EC50 of 0.78 μM as compared to 4.54 μM for lunasin. IPT.103 also has in vivo activity on enhancing the serum levels of IFNγ production using a mouse model. Taken together, we have developed a peptide derivative (IPT.103) that deviates from its parental type lunasin to increase intellectual merit for commercialization as well as support clinical application
Modulating NK-mediated Immunity by Lunakine
poster abstractDespite the plethora of immune modulating agents available in cancer treatment, their effectiveness relies on a functional immune system. However, the adverse side effects by chemotherapy impede the therapeutic benefits from immunotherapy. It remains a major challenge to prevent relapse for cancer patients who have already undergone rigorous chemotherapy. Lunasin, a 43-amino acid peptide, was originally isolated from soybeans. Our team has recently discovered a novel function of lunasin as an immune modulating agent that exerts robust synergistic effects imposed by several therapeutic cytokines. Such synergism strongly augments IFNγ and granzyme B expression by Natural Killer (NK) cells, which is associated with increased tumoricidal activity. The combination regimen with lunasin and cytokine is capable of restoring NK activation from lymphoma patients with chemotherapy-induced immune dysfunction. Our results support the potential application of lunasin to improve the therapeutic effects of existing cytokine treatment that has been used to eliminate residual tumors cells from lymphoma patients after chemotherapy. We designate lunakine as new formulation by combing lunasin and selected cytokine (filed for US Patent Cooperation Treat). In working with Indiana University and Technology Corporation (IURTC), we have started a startup company, Immune Peptide Therapeutics (IPT), LLC. Our mission is to develop a more efficacious immunotherapy that prevents relapse and confers progression-free survival for cancer patients. With the support from FORCES, our team has successfully developed a second generation of lunasin called IPT.103 that deviates from its parental type. Activity of IPT.103 has been tested in vitro with EC50 of 0.78 μM as compared to 4.54 μM for lunasin, indicating an improved potency to induce IFNγ production by NK cells. The newly developed peptide IPT.103 is expected to strengthen the intellectual property (IP) position for commercialization. We are currently working on tumor models for preclinical assessment of IPT’s regimens in immunotherapy for lymphoma
Single-crystalline δ-Ni2Si nanowires with excellent physical properties
[[abstract]]In this article, we report the synthesis of single-crystalline nickel silicide nanowires (NWs) via chemical vapor deposition method using NiCl2·6H2O as a single-source precursor. Various morphologies of δ-Ni2Si NWs were successfully acquired by controlling the growth conditions. The growth mechanism of the δ-Ni2Si NWs was thoroughly discussed and identified with microscopy studies. Field emission measurements show a low turn-on field (4.12 V/μm), and magnetic property measurements show a classic ferromagnetic characteristic, which demonstrates promising potential applications for field emitters, magnetic storage, and biological cell separation.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子版[[booktype]]紙
A strong-motion hot spot of the 2016 Meinong, Taiwan, earthquake (M_w = 6.4)
Despite a moderate magnitude, M_w = 6.4, the 5 February 2016 Meinong, Taiwan, earthquake caused significant damage in Tainan City and the surrounding areas. Several seismograms display an impulsive S-wave velocity pulse with an amplitude of about 1 m s-1, which is similar to large S-wave pulses recorded for the past several larger damaging earthquakes, such as the 1995 Kobe, Japan, earthquake (M_w = 6.9) and the 1994 Northridge, California, earthquake (M_w = 6.7). The observed PGV in the Tainan area is about 10 times larger than the median PGV of M_w = 6.4 crustal earthquakes in Taiwan. We investigate the cause of the localized strong ground motions. The peak-to-peak ground-motion displacement at the basin sites near Tainan is about 35 times larger than that at a mountain site with a similar epicentral distance. At some frequency bands (0.9 - 1.1 Hz), the amplitude ratio is as large as 200. Using the focal mechanism of this earthquake, typical “soft” and “hard” crustal structures, and directivity inferred from the observed waveforms and the slip distribution, we show that the combined effect yields an amplitude ratio of 17 to 34. The larger amplitude ratios at higher frequency bands can be probably due to the effects of complex 3-D basin structures. The result indicates that even from a moderate event, if these effects simultaneously work together toward amplifying ground motions, the extremely large ground motions as observed in Tainan can occur. Such occurrences should be taken into consideration in hazard mitigation measures in the place with frequent moderate earthquakes
Molecular genetic analysis reveals that a nonribosomal peptide synthetase-like (NRPS-like) gene in Aspergillus nidulans is responsible for microperfuranone biosynthesis
Genome sequencing of Aspergillus species including Aspergillus nidulans has revealed that there are far more secondary metabolite biosynthetic gene clusters than secondary metabolites isolated from these organisms. This implies that these organisms can produce additional secondary metabolites, which have not yet been elucidated. The A. nidulans genome contains 12 nonribosomal peptide synthetase (NRPS), one hybrid polyketide synthase/NRPS, and 14 NRPS-like genes. The only NRPS-like gene in A. nidulans with a known product is tdiA, which is involved in terrequinone A biosynthesis. To attempt to identify the products of these NRPS-like genes, we replaced the native promoters of the NRPS-like genes with the inducible alcohol dehydrogenase (alcA) promoter. Our results demonstrated that induction of the single NRPS-like gene AN3396.4 led to the enhanced production of microperfuranone. Furthermore, heterologous expression of AN3396.4 in Aspergillus niger confirmed that only one NRPS-like gene, AN3396.4, is necessary for the production of microperfuranone
The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.
Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation
Establishment of a Knock-In Mouse Model with the SLC26A4 c.919-2A>G Mutation and Characterization of Its Pathology
Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4tm1Dontuh/tm1Dontuh mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4tm1Dontuh/tm1Dontuh mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4tm1Dontuh/tm1Dontuh mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4tm1Dontuh/tm1Dontuh mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4tm1Dontuh/tm1Dontuh mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4−/− mice and Slc26a4loop/loop mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains
A strong-motion hot spot of the 2016 Meinong, Taiwan, earthquake (M_w = 6.4)
Despite a moderate magnitude, M_w = 6.4, the 5 February 2016 Meinong, Taiwan, earthquake caused significant damage in Tainan City and the surrounding areas. Several seismograms display an impulsive S-wave velocity pulse with an amplitude of about 1 m s-1, which is similar to large S-wave pulses recorded for the past several larger damaging earthquakes, such as the 1995 Kobe, Japan, earthquake (M_w = 6.9) and the 1994 Northridge, California, earthquake (M_w = 6.7). The observed PGV in the Tainan area is about 10 times larger than the median PGV of M_w = 6.4 crustal earthquakes in Taiwan. We investigate the cause of the localized strong ground motions. The peak-to-peak ground-motion displacement at the basin sites near Tainan is about 35 times larger than that at a mountain site with a similar epicentral distance. At some frequency bands (0.9 - 1.1 Hz), the amplitude ratio is as large as 200. Using the focal mechanism of this earthquake, typical “soft” and “hard” crustal structures, and directivity inferred from the observed waveforms and the slip distribution, we show that the combined effect yields an amplitude ratio of 17 to 34. The larger amplitude ratios at higher frequency bands can be probably due to the effects of complex 3-D basin structures. The result indicates that even from a moderate event, if these effects simultaneously work together toward amplifying ground motions, the extremely large ground motions as observed in Tainan can occur. Such occurrences should be taken into consideration in hazard mitigation measures in the place with frequent moderate earthquakes
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