New Measurement Base De-embedded CPU Load Model for Power Delivery Network Design

CPU load model including on-chip wiring and package interconnection has been required for printed circuit board (PCB) design of digital products according to the improvement in the speed of CPU operation in recent years. Especially, accurate power delivery network (PDN) information inside CPU is indispensable for PCB design according to requirement of low-impedance and the broadband (from DC to GHz) from the inside of CPU to DC-DC converter. While the detailed impedance information inside CPUs is not disclosed to PCB board designers with the complicated back-end and front-end production design for CPU chip and package. This paper aims to establish new methodology to extract CPU load model with combination of measurement and simulation. The method is simple yet powerful for high-end CPU board design.2015 9th International Conference on Power Electronics and ECCE Asia (ICPE-ECCE Asia 2015), June 1-5, 2015, Seoul, South Kore

Versatile Roles of LKB1 Kinase Signaling in Neural Development and Homeostasis

Kinase signaling pathways orchestrate a majority of cellular structures and functions across species. Liver kinase B1 (LKB1, also known as STK11 or Par-4) is a ubiquitously expressed master serine/threonine kinase that plays crucial roles in numerous cellular events, such as polarity control, proliferation, differentiation and energy homeostasis, in many types of cells by activating downstream kinases of the AMP-activated protein kinase (AMPK) subfamily members. In contrast to the accumulating evidence for LKB1 functions in nonneuronal tissues, its functions in the nervous system have been relatively less understood until recently. In the brain, LKB1 initially emerged as a principal regulator of axon/dendrite polarity in forebrain neurons. Thereafter, recent investigations have rapidly uncovered diverse and essential functions of LKB1 in the developing and mature nervous system, such as migration, neurite morphogenesis, myelination and the maintenance of neural integrity, demonstrating that LKB1 is also a multifunctional master kinase in the nervous system. In this review article, we summarize the expanding knowledge about the functional aspects of LKB1 signaling in neural development and homeostasis

Cloning of CRP2, a novel member of the cysteine-rich protein family with two repeats of an unusual LIM/double zinc-finger motif

AbstractThe cDNA coding for a novel member of the cysteine-rich protein family was isolated from a rat brain cDNA library. It encodes a protein, denoted cysteine-rich protein 2 (CRP2), of 208 amino acid residues containing two tandem repeats of an unusual LIM/double zinc-finger-like motif. The ubiquitous tissue distribution and high level of expression of CRP2 mRNA suggest an important role for CRP2 in cell functions

Subpial Lipoma at the Conus Medullaris Level

We report a rare case of adult subpial spinal lipoma at the conus medullaris level. A 61-year-old man presented with lower back pain, numbness in his legs, difficulty walking and a sensation of residual urine. T1- and T2-weighted magnetic resonance imaging showed a well-demarcated hyperintense intradural tumor level with the lower part of the T12 vertebra. Laminectomy at the T12 level and partial removal of the tumor using ultrasonic aspiration were performed. Pathologically, the excised mass was composed of mature adipose tissue with no evidence of inflammatory cell invasion or malignancy. Symptoms other than numbness and hypoesthesia in the left leg were relieved postoperatively. This case report indicated that partial tumor removal and ultrasonic aspiration are useful methods for removing tumors with significant adhesion to the spinal cord

Comparison of FGF1 (aFGF) Expression between the Dorsal Motor Nucleus of Vagus and the Hypoglossal Nucleus of Rat

Neurons in the dorsal motor nucleus of the vagus (DMNV) are more severely affected by axonal injury than most other nerves, such as those of the hypoglossal nucleus. However, the mechanism underlying such a response remains unclear. In this study, we compared the expression of fibroblast growth factor 1 (FGF1), a neurotrophic factor, between the DMNV and the hypoglossal nucleus by RT-PCR and immunohistochemical analyses. RT-PCR showed that the level of FGF1 mRNA expression in the DMNV was lower than that in the hypoglossal nucleus (P<0.01). Immunohistochemistry revealed that FGF1 was localized to neurons. FGF1-positive neurons in large numbers were evenly distributed in the hypoglossal nucleus, whereas FGF1-positive neurons were located in the lateral part of the DMNV. Double immunostaining for FGF1 and choline acetyltransferase demonstrated that 22.7% and 78% of cholinergic neurons were positive for FGF1 in the DMNV and hypoglossal nucleus, respectively. A tracing study with cholera toxin B subunit (CTb) demonstrated that cholinergic neurons sending their axons from the DMNV to the superior laryngeal nerve were FGF1-negative. The results suggest that the low expression of FGF1 in the DMNV is due to severe damage of neurons in the DMNV

Establishment of anti-DKK3 peptide for the cancer control in head and neck squamous cell carcinoma (HNSCC)

Background: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck. We identified cancer‑specific genes in HNSCC and focused on DKK3 expression. DKK3 gene codes two iso‑forms of proteins (secreted and non‑secreted) with two distinct cysteine rich domains (CRDs). It is reported that DKK3 functions as a negative regulator of oncogenic Wnt signaling and, is therefore, considered to be a tumor suppressor gene. However, our series of studies have demonstrated that DKK3 expression is specifically high in HNSCC tissues and cells, and that DKK3 might determine the malignant potentials of HNSCC cells via the activation of Akt. Further analyses strongly suggested that both secreted DKK3 and non‑secreted DKK3 could activate Akt signaling in discrete ways, and consequently exert tumor promoting effects. We hypothesized that DKK3 might be a specific druggable target, and it is necessary to establish a DKK3 inhibitor that can inhibit both secreted and non‑secreted isoforms of DKK3.Methods: Using inverse polymerase chain reaction, we generated mutant expression plasmids that express DKK3 without CRD1, CRD2, or both CRD1 and CRD2 (DKK3ΔC1, DKK3ΔC2, and DKK3ΔC1ΔC2, respectively). These plasmids were then transfected into HNSCC‑derived cells to determine the domain responsible for DKK3‑mediated Akt activation. We designed antisense peptides using the MIMETEC program, targeting DKK3‑specific amino acid sequences within CRD1 and CRD2. The structural models for peptides and DKK3 were generated using Raptor X, and then a docking simulation was performed using CluPro2. Afterward, the best set of the peptides was applied into HNSCC‑derived cells, and the effects on Akt phosphorylation, cellular proliferation, invasion, and migration were assessed. We also investigated the therapeutic effects of the peptides in the xenograft models.Results: Transfection of mutant expression plasmids and subsequent functional analyses revealed that it is necessary to delete both CRD1 and CRD2 to inhibit Akt activation and inhibition of proliferation, migration, and invasion. The inhibitory peptides for CRD1 and CRD2 of DKK3 significantly reduced the phosphorylation of Akt, and consequently suppressed cellular proliferation, migration, invasion and in vivo tumor growth at very low doses.Conclusions: This inhibitory peptide represents a promising new therapeutic strategy for HNSCC treatment

Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>Rho-associated coiled-coil containing protein kinase (Rho-kinase/ROCK) is involved in various cellular functions including cell proliferation, and is generally considered to be oncogenic, while some studies show that ROCK functions as a negative regulator of cancer progression. As a result, the precise role of ROCK remains controversial. We have previously reported that Rho-kinase/ROCK negatively regulates epidermal growth factor (EGF)-induced cell proliferation in SW480 colon cancer cells. In the present study, we investigated the role of ROCK in EGF receptor (EGFR) signaling in the pancreatic cancer cell lines, Panc1, KP3 and AsPc1.</p> <p>Results</p> <p>In these cells, Y27632, a specific ROCK inhibitor, enhanced EGF-induced BrdU incorporation. The blockade of EGF stimulation utilizing anti-EGFR-neutralizing antibodies suppressed Panc1 cell proliferation. EGF induced RhoA activity, as well as the phosphorylation of cofilin and myosin light chain (MLC), both targets of ROCK signaling, and Y27632 suppressed both of these processes, indicating that the phosphorylation of cofilin and MLC by EGF occurs through ROCK in Panc1 cells. EGF-induced phosphorylation of EGFR at tyrosine residues was augmented when the cells were pretreated with Y27632 or were subjected to gene silencing using ROCK-siRNA. We also obtained similar results using transforming growth factor-α. In addition, EGF-induced phosphorylation of p44/p42 mitogen-activated protein kinase and Akt were also enhanced by Y27632 or ROCK-siRNA. Moreover, an immunofluorescence microscope study revealed that pretreatment with Y27632 delayed EGF-induced internalization of EGFR. Taken together, these data indicate that ROCK functions to switch off EGFR signaling by promoting the internalization of the EGFR.</p> <p>Conclusions</p> <p>While EGF first stimulates the activation of the EGFR and subsequently increases cancer cell proliferation, EGF concurrently induces the activation of ROCK, which then turns off the activated EGFR pathway via a negative feedback system.</p

Successful Endoscopic Injection Sclerotherapy of High-Risk Gastroesophageal Varices in a Cirrhotic Patient with Hemophilia A

A 68-year-old man with hemophilia A and liver cirrhosis caused by hepatitis C virus was referred to our hospital to receive prophylactic endoscopic treatment for gastroesophageal varices (GOV). He had large, tense, and winding esophageal varices (EV) with cherry red spots extending down to lesser curve, predicting the likelihood of bleeding. Esophageal endoscopic injection sclerotherapy (EIS) was performed with a total 15 mL of 5% ethanolamine oleate with iopamidol (EOI). Radiographic imaging during EIS demonstrated that 5% EOI reached the afferent vein of the varices. He was administered sufficient factor VIII concentrate before and after EIS to prevent massive bleeding from the varices. Seven days after EIS, upper gastrointestinal endoscopy (UGIE) showed that the varices were eradicated almost completely. Eighteen months after EIS, the varices continued to diminish. We report a successful case of safe and effective EIS for GOV in a high-risk cirrhotic patient with hemophilia A

Surgical Outcomes of Posterior Short Segment Fixation for Thoracolumbar Burst Fractures: A Study of Patients Treated without Vertebroplasty

There is no widespread agreement regarding the treatment of thoracolumbar burst fractures. While performing posterior short segment fixation of thoracolumbar burst fractures, we evaluated therapeutic outcomes in patients treated with screw insertion into fractured vertebral bodies without vertebroplasty. We also investigated the limitations associated with the treatment of burst fractures when vertebroplasty is not performed. Twenty-one of 51 patients with thoracolumbar burst fractures who were treated surgically in Ohta Nishinouchi Hospital were evaluated in the present study. These patients underwent posterior short segment fixation with screw insertion into the fractured vertebral bodies (only pedicle screws were inserted one level above and one level below the fractured vertebral bodies) without vertebroplasty. Vertebral angles were measured before surgery, immediately after surgery, and at the final follow-up examination. Changes in vertebral angles were compared and analyzed. The mean vertebral angles before and after surgery and at the final follow-up examination were 15.4°, 6.6°, and 9.1°, respectively. The mean postoperative correction loss was 2.5°. The therapeutic outcomes of posterior short segment fixation with screw insertion into fractured vertebral bodies without vertebroplasty were generally favorable