Generalized Low-Rank Update: Model Parameter Bounds for Low-Rank Training Data Modifications

In this study, we have developed an incremental machine learning (ML) method that efficiently obtains the optimal model when a small number of instances or features are added or removed. This problem holds practical importance in model selection, such as cross-validation (CV) and feature selection. Among the class of ML methods known as linear estimators, there exists an efficient model update framework called the low-rank update that can effectively handle changes in a small number of rows and columns within the data matrix. However, for ML methods beyond linear estimators, there is currently no comprehensive framework available to obtain knowledge about the updated solution within a specific computational complexity. In light of this, our study introduces a method called the Generalized Low-Rank Update (GLRU) which extends the low-rank update framework of linear estimators to ML methods formulated as a certain class of regularized empirical risk minimization, including commonly used methods such as SVM and logistic regression. The proposed GLRU method not only expands the range of its applicability but also provides information about the updated solutions with a computational complexity proportional to the amount of dataset changes. To demonstrate the effectiveness of the GLRU method, we conduct experiments showcasing its efficiency in performing cross-validation and feature selection compared to other baseline methods

Gene Gunを用いた生体神経細胞内への持続的薬剤投与実験系の確立

金沢大学医薬保健研究域医学系神経系の発達過程に関与する分子機構を解明するためには、ある特定の分子機構をある程度長期にわたって実験操作することが必要であり、生きている動物でおこなうには難しい点がある。そこで我々は、Gene Gunを用いて、生きている動物の神経細胞内に機能分子を阻害、修飾する分子を効率的に打ち込むことが出来る実験系を確立したいと考えた。実験の結果、生体動物細胞にGene Gunを用いて試薬を打ち込むことは可能ではあるが、我々が意図した実験に適用するためにはいくつか問題があることが明らかになった。1、Gene Gunによる蛍光染料の生体細胞内への投与昨年度成功した生体の脳への蛍光染料の打ち込み方法の改良を行った。ヘリウムガスの圧力が100psiでは金粒子が軟膜表面を通過できない確率が高く、300psiでは白質にまで到達するので、その間で打ち込み圧を調整する必要があることが分かった。また、蛍光染料をまぶした金粒子をそのまま射出すると、金粒子がいくつか結合して細胞体よりも大きな塊となり組織の障害や非選択的な染色の原因となるが、脳組織とGene Gun本体の間にフィルターをかますことで軽減できることが分かった。2、実験に適用する際の問題点電気生理学的実験を行うために、生体脳に蛍光染料を打ち込んだのち一定期間の後スライスにして観察したところ、実験可能なスライス表面に生存しているプルキンエ細胞の数がほとんどいない傾向があった。染色されていても、スライス表面から深いところに存在している例が多かった。これは恐らく染色されている細胞の密度が低すぎてスライス表面で運良く生き残る細胞数が極端に少なくなるためであると考えられる。この点が改善されないと、我々の実験への適用は難しいと思われる。研究課題/領域番号:15650057, 研究期間(年度):2003 – 2004出典：「Gene Gunを用いた生体神経細胞内への持続的薬剤投与実験系の確立」研究成果報告書　課題番号15650057（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15650057/)を加工して作

発達期小脳における神経活動に依存した機能的シナプス結合形成のメカニズム

金沢大学医薬保健研究域医学系生体の情報処理を司る神経回路網は、その形成過程においてまず余分な回路網を多数形成し、必要なもののみ残して不必要なものを排除するという戦略をとる。我々は同様の発達過程を経ることが知られている、小脳登上線維-プルキンエ細胞投射系においてこの現象を解析し、これまでに過剰な登上線維シナプス除去の過程に、mGluR1-Gαq-PLCβ4-PKCγを介する細胞内シグナル伝達が必要であることを明らかにした。しかし、mGluR1-Gαq-PLCβ4-PKCγのあとに来る経路は何か、また、最終的な標的は何かという点に関しては未だ不明であった。この原因の一つとして、登上線維-プルキンエ細胞シナプス伝達の発達過程に起こる変化に関する基礎的な研究がほとんどされていないため、制御の対象となる機構を推定できないという点があげられる。このため、我々は発達に伴う登上線維応答の電気生理学的な変化を詳細に解析する実験を行った。その結果、将来排除されると思われる弱い入力を持つ登上線維は、残存すると思われる強い入力に比べて,シナプス間隙の伝達物質濃度の減少が起こっていることが分かった。しかし、伝達物質放出の基本単位であるシナプス小胞一個の放出により誘発される反応に変化はみられなかった。これらの結果より、登上線維の排除に先立つ過程として、一回の刺激で放出されるシナプス小胞の数が減少して,プルキンエ細胞に与える影響が小さくなっていることが推測された。これは、登上線維の排除過程の少なくとも一部分にはシナプス前終末(登上線維側)の機構が関与していることをあらわしていると思われる。研究課題/領域番号:11780576, 研究期間(年度):2001-2005出典：「発達期小脳における神経活動に依存した機能的シナプス結合形成のメカニズム」研究成果報告書　課題番号11780576（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （ https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-11780576/ ）を加工して作

A Cadmium-Free Cu2ZnSnS4/ZnO Hetrojunction Solar Cell Prepared by Practicable Processes

A cadmium-free Cu2ZnSnS4/ZnO hetrojunction solar cell with conversion efficiency of 4.29% has been obtained. The Cu2ZnSnS4 absorber film was formed utilizing sulfurization of laminated metallic precursors, and the ZnO buffer layer was then deposited on it by ultrasonic spray pyrolysis. In comparison with a conventional Cu2ZnSnS4/CdS hetrojunction solar cell, the open circuit voltage as well as the relative quantum efficiency at the short-wavelength regions was increased. The in-plane homogeneity of p-n junction was improved by depositing the ZnO layer on Cu2ZnSnS4 film via ultrasonic spray pyrolysis. (C) 2011 The Japan Society of Applied PhysicsArticleJAPANESE JOURNAL OF APPLIED PHYSICS. 50(3): 032301 (2011)journal articl

Identification of hypoxia-inducible factor 1 ancillary sequence and its function in vascular endothelial growth factor gene induction by hypoxia and nitric oxide.

Transcription of hypoxia-inducible genes is regulated by hypoxia response elements (HREs) located in either the promoter or enhancer regions. Analysis of these elements reveals the presence of one or more binding sites for hypoxia-inducible factor 1 (HIF-1). Hypoxia-inducible genes include vascular endothelial growth factor (VEGF), erythropoietin, and glycolytic enzyme genes. Site-directed mutational analysis of the VEGF gene promoter revealed that an HIF-1 binding site (HBS) and its downstream HIF-1 ancillary sequence (HAS) within the HRE are required as cis-elements for the transcriptional activation of VEGF by either hypoxia or nitric oxide (NO). The core sequences of the HBS and the HAS were determined as TACGTG and CAGGT, respectively. These elements form an imperfect inverted repeat, and the spacing between these motifs is crucial for activity of the promoter. Gel shift assays demonstrate that as yet unknown protein complexes constitutively bind to the HAS regardless of the presence of these stimuli in several cell lines, in contrast with hypoxia- or NO-induced activation of HIF-1 binding to the HBS. A common structure of the HRE, which consists of the HBS and the HAS, is seen among several hypoxia-inducible genes, suggesting the presence of a novel mechanism mediated by the HAS for the regulation of these genes

Effectiveness of Extending Treatment Duration in Therapy with Pegylated Interferon and Ribavirin for Genotype 2 Hepatitis C Virus Infection

The effectiveness of extending treatment duration as response guided therapy was previously reported for chronic hepatitis C (CHC) genotype 1, but is still controversial for genotype 2. The present study is a retrospective cohort study to investigate the effectiveness of extending treatment duration in therapy with pegylated interferon and ribavirin for patients with CHC genotype 2 by focusing on the timing at which patients obtained undetectable HCV RNA. A total of 306 patients who obtained undetectable HCV RNA by week 24 of treatment and completed 24 weeks of treatment were enrolled. Rapid virological response (RVR) to standard therapy was achieved by 122 patients (51ｵ), and 89ｵ of them obtained sustained virological response (SVR), while 69ｵ of non-RVR patients achieved SVR. Non-RVR patients with undetectable HCV RNA at week 8, and insufficient adherence＜80ｵ pegylated interferon and ribavirin during the first 24 weeks, significantly improved their SVR rate by extended therapy. Among patients receiving extended therapy, drug adherences did not differ between SVR and non-SVR patients, indicating that extending treatment duration might compensate for insufficient antiviral effects due to insufficient drug adherences. This finding might be useful in creating a guideline for extending treatment duration for patients with CHC genotype 2

Control of synaptic transmission in the CNS through endocannabinoid-mediated retrograde signaling

Psychological and physiological effects of marijuana are caused by binding of its active component (Δ9-tetrahydrocannabinol) to cannabinoid receptors. The cannabinoid receptors belong to a family of G protein-coupled seven-transmembrane-domain receptors, and consist of type 1 (CBl) and type 2 (CB2) receptors with different distributions (Matsuda et al., 1990; Munro et al., 1993; Felder and Glass, 1998). The CBl receptor is expressed in the CNS, whereas the CB2 receptor is found in the immune system of the periphery (Klein et al., 1998). Activation of the CBl receptor induces various effects on neural functions (Di Marzo et al, 1998; Felder and Glass, 1998), including suppression of neurotransmitter release (Gifford and Ashby, 1996; Ishac et al., 1996; Shen et al., 1996; Katona et al, 1999; Hoffman and Lupica, 2000). Several molecules are identified as candidate endogenous ligands for cannabinoid receptors (endocannabinoids). Arachidonylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG), two major endocannabinoids, are reported to be synthesized from membrane phospholipids in an activity- and a Ca2+-dependent manner (Cadas et al, 1996; Stella et al, 1997; Di Marzo et al, 1998; Bisogno et al, 1999; PiomeUi et al, 2000). It is thought that they can diffuse out across the cell membrane. The released endocanabinoids are removed from the extracellular space through uptake and enzymatic degradation (Mechoulam et al, 1998). All these findings suggest that endocannabinoids can work as a diffusible and short-lived mediator that is released from activated neurons, binds to cannabinoid receptors on neighboring neurons to modulate their functions. Recent electrophysiological studies have revealed that endocannabinoids play an important role in retrograde modulation of synaptic transmission in the CNS (Kreitzer and Regehr, 2001b; Maejima et al, 2001a; Ohno-Shosaku et al, 2001; Wilson and NicoU, 2001). Endocannabinoids are released from postsynaptic neurons in response to either depolarization or activation of Gq/11-coupled receptors such as group I metabotropic glutamate receptors (mGluRs) and M1/M3 muscarinic acetylcholine receptors. The released endocannabinoids then activate presynaptic cannabinoid receptors and suppress transmitter release (Maejima et al, 2001b; Alger, 2002; Kano et al, 2002; Kreitzer and Regehr, 2002; Wilson and Nicoll, 2002; Freund et al, 2003; Kano et al., 2003; PiomelU, 2003). Thus, the endocannabinoid signaling is an important mechanism by which postsynaptic neuronal activity can retrogradely influence presynaptic functions. In this review, we introduce recent electrophysiological studies on endocannabinoidmediated retrograde modulation and discuss its possible physiological roles in the CNS.Dendritic neurotransmitter release, edited by Mike Ludwig, Springer, c2005, 269-281, (A part of the memoirs

Intralesional steroid infusion using a spray tube to prevent stenosis after endoscopic submucosal dissection of esophageal cancer

Background/Aims Intralesional steroid injections have been administered as prophylaxis for stenosis after esophageal endoscopic submucosal dissection. However, this method carries a risk of potential complications such as perforation because a fine needle is used to directly puncture the postoperative ulcer. We devised a new method of steroid intralesional infusion using a spray tube and evaluated its efficacy and safety. Methods Intralesional steroid infusion using a spray tube was performed on 27 patients who underwent endoscopic submucosal dissection for superficial esophageal cancer with three-quarters or more of the lumen circumference resected. The presence or absence of stenosis, complications, and the number of endoscopic balloon dilations (EBDs) performed were evaluated after treatment. Results Although stenosis was not observed in 22 of the 27 patients, five patients had stenosis and dysphagia requiring EBD. The stenosis in these five patients was relieved after four EBDs. No complications related to intralesional steroid infusion using the spray tube were observed. Conclusions Intralesional steroid infusion using a spray tube is a simple and safe technique that is adequately effective in preventing stenosis (clinical trial number, UMIN000037567)

The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

SummaryEndocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase α (DGLα) and β (DGLβ). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLα knockout mice, whereas the retrograde suppression was intact in DGLβ knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLα knockout brains, whereas the 2-AG content was normal in DGLβ knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLα, but not by DGLβ, mediates retrograde suppression at central synapses