VQE-generated Quantum Circuit Dataset for Machine Learning

Quantum machine learning has the potential to computationally outperform classical machine learning, but it is not yet clear whether it will actually be valuable for practical problems. While some artificial scenarios have shown that certain quantum machine learning techniques may be advantageous compared to their classical counterpart, it is unlikely that quantum machine learning will outclass traditional methods on popular classical datasets such as MNIST. In contrast, dealing with quantum data, such as quantum states or circuits, may be the task where we can benefit from quantum methods. Therefore, it is important to develop practically meaningful quantum datasets for which we expect quantum methods to be superior. In this paper, we propose a machine learning task that is likely to soon arise in the real world: clustering and classification of quantum circuits. We provide a dataset of quantum circuits optimized by the variational quantum eigensolver. We utilized six common types of Hamiltonians in condensed matter physics, with a range of 4 to 16 qubits, and applied ten different ans\"{a}tze with varying depths (ranging from 3 to 32) to generate a quantum circuit dataset of six distinct classes, each containing 300 samples. We show that this dataset can be easily learned using quantum methods. In particular, we demonstrate a successful classification of our dataset using real 4-qubit devices available through IBMQ. By providing a setting and an elementary dataset where quantum machine learning is expected to be beneficial, we hope to encourage and ease the advancement of the field.Comment: 9 pages, 6figure

猫の肥大型心筋症の診断と治療に関する研究

【第1章】緒言　猫で最も多く認められる心疾患は心筋症である。心筋症の中でも、肥大型心筋症（以下HCM）の発症が多いとされている。しかしながら、猫のHCMに対する診断および治療はいまだ十分に確立されていないのが現状である。このことから、本研究は猫のHCMの診断および治療の確立を目的に、特に早期診断、内科治療に注目し検討することとした。【第2章】猫の心筋症の診断および病態に関する検討第1項　心拍数が左心室壁厚・内腔径に与える影響〔目的〕猫では、心エコーで拡張末期左心室壁厚が6mmを越え、かつ代償性肥大が除外された場合にHCMと診断される。一方、猫では緊張・興奮などにより心拍数が大きく変動することが知られており、心拍数の変化に伴い拡張期時間が変動した場合、壁厚もその影響を受けることが予想されるが、これについて今まで検討されていない。そこで、本研究では心拍数の心エコー図検査値に及ぼす影響を検討することを目的とし、心拍数変動に伴う左心室壁厚・内腔径の変化を評価した。〔方法〕実験には臨床上正常な実験猫6頭を用いた。全身麻酔下で左頸静脈より右心房にペーシングリードを挿入し、特定の心拍数を維持できるようにした。心拍数の設定は10bpmきざみで120～180bpmまで、計8群を設定し、個々の猫ごとに群の順序をランダムに変化させ、左心室拡張末期壁厚および左心室拡張末期径を測定した。〔結果および小括〕心拍数の増加に伴い壁厚は有意に増大し、左心室内腔径は有意に縮小した。このことから、心拍数は壁厚の測定値に影響を与える因子であることが明らかとなった。以上より、壁厚の測定はHCMの診断に必要不可欠であるものの、心拍数を考慮する必要があり、したがって壁厚だけに頼る診断方法には限界があることが示唆された。そこで、形態（壁厚）のみならず心機能などその他の評価法との総合判断が必要であると考えられた。第2項　HCM症例における心機能評価〔目的〕猫のHCMの診断には形態の把握、すなわち心エコー図検査による壁厚の測定が重要であるが、初期の病態では、壁厚がボーダーラインであることや、第一項での実験で示されたような検査値に影響を及ぼす因子の関与があることが現在の問題点である。HCMでは拡張機能が低下するとされているが、これまでの報告ではどの心エコー指標が適切でかつ猫で評価可能なのか不明であった。そこで本項では本疾患に罹患した猫の早期診断法の確立を目的とし、壁厚のみならず心機能評価を行い比較検討した。〔方法〕麻布大学附属動物病院に来院したHCM猫のうち、左房拡大の認められない症例に対し、組織ドプラ法（以下TDI）とスペックルトラッキングエコー法（以下STE）を用い心機能検査を行った。症例は全周性肥大群（以下D-HCM群、5例）と中隔壁のみ肥大している部分壁肥大群（以下S-HCM群、17例）に分類し、正常群（臨床上正常である猫13頭）と比較検討した。〔結果および小括〕S-HCM群、D-HCM群の長軸方向の拡張期strain rateにおいて、Globalと全ての分画で有意な低下が認められ、TDIで拡張機能の低下が明らかでない場合でもSTEでは拡張機能の低下が評価可能であることが明らかとなった。さらに、S-HCM群とD-HCM群間では有意差は認められなかったことから、HCMでは病態初期より肥大している心筋だけではなく、肥大していない心筋でも拡張機能が低下していることが示唆された。第3項　HCM症例における左心房拡大と左心室機能の関連について〔目的〕HCMでは拡張機能の低下によって左心房の拡大が進行することが知られている。第二項では猫のHCMでは病態初期より左心室全体で拡張機能が低下していることが明らかとなったが、拡張機能が著しく低下している症例でも左心房の拡大は認められなかった。そのことから、本項ではHCMにおける左心房拡大と左心室の拡張機能との関連について明らかにすることを目的とし、経時的に心機能評価を行い、左心室の拡張機能低下と左心房拡大の関連を調べた。〔方法〕麻布大学附属動物病院に来院し、HCMと診断された症例で、半年以上の追跡調査が可能であった症例を用い、TDI、STEを用い心機能評価を行った。症例は初診時に左心房の拡大が認められず、追跡期間に左心房の拡大が認められた左心房拡大群（6例）と期間中に拡大が認められなかった左心房非拡大群（14例）に分類し、比較検討を行った。〔結果および小括〕両群共に初診時の心機能に差は認められなかった。左心房非拡大群では再診時に心機能の変化は認められなかった。左心房拡大群では、再診時に心房収縮期strain rateの有意な低下が認められたが、拡張期strain rateに変化は認められなかった。このことから、猫のHCMにおける左心房の拡大は左心室の拡張機能の低下だけではなく、左心房の機能低下も関連している可能性が示唆された。【第3章】猫の心筋症の治療に関する研究第1項　各種ACE阻害剤による血清ACE活性阻害率、降圧作用の比較〔目的〕猫の心筋症では、心不全時にアンジオテンシン変換酵素阻害剤（以下ACE阻害剤）の投与が有用であるとされている。現在、日本では数種類のACE阻害剤が販売されているが、猫に投与する場合どの薬剤がより効果的で有用であるか定かではない。そこで本実験では、代表的なACE阻害剤間において血清ACE活性阻害率および降圧作用に差があるかどうか検討することとした。〔方法〕正常実験猫6頭を用い、クロスオーバー試験とした。ACE阻害剤はベナゼプリル、エナラプリル、アラセプリルを用いた。投与は単回とし、血清ACE活性阻害率、および血圧測定を投与前、投与後2、4、6、8、12、24、36、48、72時間後に行った。〔結果および小括〕全ての薬剤において24時間後の血清ACE活性阻害率は50%以上を示し、効果的な血清ACE活性の阻害が認められた。特にベナゼプリル群で他群と比較して有意な血清ACE活性の阻害が認められた。血圧に群間、投与時間において有意差は認められなかった。　本実験からどの薬剤も良好な血清ACE活性阻害率を呈していることが示された。しかし血清中と組織中のACE活性は同一ではない可能性がある。すなわち実際の血圧上昇機構の抑制を伴うかどうかは不明である。そこで実際の薬効を評価するため、以下の第二項の実験を実施した。第2項　血清ACE活性阻害下におけるアンジオテンシンⅠ投与に対する血圧の変化（昇圧機構阻害作用）について〔目的〕血清中のACE活性阻害率と実際の薬効との関連性を解明することを目的とし、ACE阻害剤投与後、アンジオテンシンⅠ投与による昇圧作用がどの程度抑制されるか検討した。〔方法〕正常実験猫10頭を用い、クロスオーバー試験とした。ACE阻害剤はベナゼプリルとアラセプリルを用い、1週間連続で経口投与を行った。最終投与より24時間後に全身麻酔下で観血的に血圧の測定を行ったうえでアンジオテンシンⅠを投与し、昇圧反応を比較した。〔結果および小括〕両群共に昇圧の抑制程度に一定の傾向は認められず、血清中のACE活性阻害率と昇圧反応に相関は認められなかった。このことから、血清ACE阻害率と実際の薬効は必ずしも相関しないことが示された。第3項　個体ごとのアンジオテンシン受容体、ACE、キマーゼの差異について〔目的〕第二項において血清ACE阻害率と実際の薬効が相関しない理由として、個体ごとのアンジオテンシン受容体（AT-1受容体）の差異や、ACE阻害剤の組織移行性の差異などがあると仮説を立てた。そこで、本項では個体ごとのAT1受容体、ACE、キマーゼの遺伝的差異についての検討を行うことを目的とし、遺伝子配列の比較を行った。〔方法〕正常実験猫10頭を用い、全血からゲノムDNAの抽出を行った。AT-1受容体、ACE、キマーゼの各エクソン領域をダイレクトシークエンス法により解析を行い、個体ごとに比較を行った。〔結果および小括〕AT-1受容体、ACE、キマーゼの各エクソン領域に個体ごとで多型性は認められなかった。このことから、血清ACE阻害率と薬効が相関しない理由として、これらの遺伝的差異ではなく、受容体のタンパク質発現量の違いやACE阻害剤の組織移行性の差異などその他の要因が関連している可能性があると思われた。【第4章】総括　猫のHCMでは、心エコー検査による心臓の形態評価が診断の上で重要とされているが、形態は様々な因子に左右される。本研究では、心拍数もその因子のひとつであり、形態のみに依存する診断法には限界があることを指摘した。そこで診断に心機能検査を加えることで診断が向上するのではないかと考え、初期の病態と思われるHCM症例の拡張機能を評価した。その結果病態初期より、肥大している心筋だけではなく肥大していない心筋でも拡張機能が低下していることが明らかとなった。さらに、病態の進行とともに認められる左心房の拡大は、左心室の拡張機能の低下に加え、左心房機能の低下が関与していることが明らかとなった。心機能評価、特に拡張機能に関しては、TDIよりもSTEのほうが検査法として有用であることも見出された。　猫の心筋症の治療で汎用されているACE阻害薬を数種類比較したところ、血清ACE活性阻害率に有意な差はあるものの、全ての薬剤投与後に良好な血清ACE活性の阻害が確認された。しかしながら、血清ACE活性阻害率と昇圧機構阻害作用の間に明らかな関連性は見出されなかった。この理由として、猫のAT-1受容体、ACE、キマーゼに多型性があるかどうか評価したが、差異は認められなかった。Chapter 1 Introduction Cardiomyopathy is one of the common heart diseases in cats, and hypertrophic cardiomyopathy (HCM) is the most common type of cardiomyopathy. However, diagnosis and management of HCM in cats are still controversial. The aims of this study were to establish diagnostics and treatment methods, especially early diagnosis and medical management in cats with HCM.Chapter 2 Diagnosis and pathophysiology in cats with HCMParagraph 1 Influence of alternations in heart rate on left ventricular echocardiographic measurements in healthy catsBackground：Diagnosis of left ventricular (LV) hypertrophy is made when the intervetricular septum (IVS) thickness and/or left ventricular free wall (LVFW) thickness at the end-diastole was 6 mm ore more on echocardiography under the absence of pressure overload or systemic diseases known to cause LV hypertrophy. Therefore, morphologic assessment by echocardiography is very important to make a tentative diagnose in cats with HCM. Heart rate (HR) was known to be greatly changed due to excitement in cats. It had been reported that HR influenced ventricular size, and inverse correlation between HR and LV size was found in healthy cats. However, degree of changes in LV wall thickness due to sudden changes of HR has not been assessed in cats yet. We hypothesized that when HR increased, resulting in shortening of diastolic period, LV thickness at the end-diastole increased. The purpose of this study was to evaluate the effect of sudden alternations in HR on left ventricular wall thickness and dimension determined by echocardiography in healthy cats.Methods: Six experimental cats were used. All cats were anesthetized and HR was controlled with right atrial pacing. The interventricular septum, left ventricular free wall thickness at the end-diastole (IVSd and LVFWd, respectively), left ventricular end-diastolic and end-systolic diameter (LVIDd and LVIDs, respectively) and shortening fraction (FS) of each cat was assessed using echocardiography at pacing rates of 120, 130, 140, 150, 160, 170 and 180 ppm. Results: There was a significant positive correlation between wall thickness or FS and HR, and there were significant negative correlations between LVIDd or LVIDs and HR. Conclusion: Wall thickness and LV dimensions were significantly influenced by sudden changes in HR. The wall thickness could have been overestimated or underestimated by alternations in HR. The echocardiographic changes may be sufficient to confound the diagnosis or severity assessment of HCM in some cats.Paragraph 2 Assessment of left ventricular diastolic function using TDI and STE in cats with HCMBackground： Echocardiography is one of important examinations to diagnose HCM in cats. As indicated above, morphological assessment would not be sufficient to make a diagnosis since wall thickness was known to be influenced by many factors including sudden changes in HR. HCM in cats is characterized by both diastolic and systolic dysfunction. Although impaired cardiac function detected by tissue Doppler imaging (TDI) in cats with HCM was previously reported, reference ranges of TDI in normal cats and cats with HCM have been reported as widely variable. Two-dimensional speckle tracking echocardiography (STE) was useful for assessment of cardiac function in human patients with HCM, but clinical utility was not known in cats. The aim of this study was to assess global and segmental LV myocardial function using STE in cats with HCM whose TDI variables were within the reference range.Methods: A total of 35 cats of different breeds were enrolled in this study. The HCM group (n=22) included cats diagnosed as HCM without left atrial enlargement and with normal TDI measurements. HCM cats were further divided into a segmental hypertrophy (S-HCM) group and a diffuse hypertrophy (D-HCM) group. The control group consisted of 13 clinically healthy cats. No cats in any group showed any clinical symptoms. Conventional echocardiography, TDI, and global and segmental STE indices were evaluated and compared between groups. Results: Only the longitudinal strain rate during early diastole was significantly decreased in both HCM groups, even in all segments including those without hypertrophy in S-HCM group. Conclusion: This study suggests that STE parameters are the more sensitive variables compared with conventional TDI parameters to detect early myocardial diastolic dysfunction in cats with HCM.Paragraph 3 Relationship between left ventricular dysfunction and left atrial enlargement Background: Although it was hypothesized that LV diastolic dysfunction resulted in LA enlargement, Left atrial (LA) enlargement is not always seen in cats with impaired diastolic function. The purpose of this study was to assess the correlation between LV dysfunction and LA enlargement. Methods: Total 20 cats enabling to follow-up more than six months were enrolled in this study. All cats were diagnosed as HCM without left atrial enlargement at the first visit. Physical examination and echocardiography was performed at recheck examination to assess cardiac function including LA size. The cats were divided into 2 groups on the basis of LA size at the recheck examination; the cats with LA enlargement (LAD group, n = 6) and the cats without LA enlargement group (no LAD group, n = 14). Conventional echocardiography, TDI, and STE indices were evaluated and compared between groups.Results: There were not significant differences in cardiac function at the first medical examination between both groups. There was no significant difference in cardiac function between first and recheck examination in no LAD group. On the other hand, the strain rate at atrial systole was significantly decreased in recheck examination in LAD group compared with that of first examination, despite the strain rate at early diastole was not significantly decreased at recheck examination compared with that of first examination.Conclusion: This study suggested that LA enlargement was possibly relating to LA dysfunction in addition to LV diastolic dysfunction. Accurate assessment of LA function in cats would be helpful to assess the progression of disease process in cats with HCM. Chapter 3 Studies of medical treatments in catsParagraph 1 Pharmacodynamics of angiotensin converting enzyme inhibitor in healthy catsBackground： Angiotensin converting enzyme (ACE) inhibitors are one of the most commonly used medications in veterinary medicine for chronic cardiovascular disease. Several ACE inhibitor are available in Japan, however, it is not clear which ACE inhibitor is more effective and useful for cats. The aims of this study were to investigate the differences of pharmacodynamics among the ACE inhibitors in cats.Methods: Six experimental cats were used. Each cat received a single dose of benazepril, enalapril or alacepril orally at a dosage of 0.5 mg/kg, 1 mg/kg and 3 mg/kg, respectively. Blood samples were collected before administration, 2, 4, 6, 8, 12, 24, 36, 48 and 72 h after administration to measure serum ACE activity. Systolic blood pressure (SBP) was also measured at the same time point.Results: Inhibition of ACE activity was seen, and more than 50% of inhibition rate was sustained for 24 h in all ACE inhibitors. The inhibitory rate of serum ACE activity in Benazepril group was significantly higher, compared with enalapril and alacepril groups. There were no significant differences in SBP among groups at any time-point.Conclusion: ACE activity was favorably inhibited in all ACE inhibitors. Although ACE activity at the blood level was suppressed, tissue level inhibition may not be equally suppressed since differences of renin-angiotensin-aldosterone system between plasma and tissues in cats were reported. Therefore following experiment was conducted to assess the pharmacokinetics of ACE inhibitor. Paragraph 2 Attenuation of the pressor response to exogenous angiotensin by ACE inhibitors in healthy catsBackground： The aims of this study was to compare the attenuation of the angiotensin I–induced blood pressure response by ACE inhibitor administration. Methods: Ten experimental cats were administered either placebo, benazepril or alacepril once daily for 7 days orally. Twenty-four hours after last administration, each cat was generally anesthetized, and direct arterial blood pressure measurements were recorded before and after IV administration of each 3 boluses of angiotensin I (20, 100 and 500ng/kg). Differences in the angiotensin I–induced change in blood pressure among different ACE inhibitors and correlation between the inhibitory rate of serum ACE activity and pressor response were determined.Results: There was no certain tendency in blood pressure response in any ACE inhibitors. There was not significant correlation between the inhibitory rate of serum ACE activity and pressor response. Conclusion: There was no correlation between inhibitory rate of serum ACE activity and pressor response.Paragraph 3 Assessment of polymorphism of angiotensin II type 1 receptor, ACE and chymase in catsBackground： The reason why the difference between serum ACE activity and pharmacodynamics of ACE inhibitor was unclear. We hypothesized that the reasons could be the polymorphisms of angiotensin receptor (AT-1 receptor), or differences of ACE inhibitor transferability to tissues, etc. The aim of this study was to assess the gene polymorphisms of AT-1 receptor, ACE and chymase for each individual cats. Materials: Ten experimental cats were used. They are the same cats used in the previous study (Chapter 3, paragraph 2). Genomic DNA samples were prepared from whole blood samples. We perform genetic polymorphism analysis using direct sequencing for these exons of the AT-1 receptor, ACE and chymase. Results: No polymorphisms were identified within these genes. Conclusion: The reason for the difference between serum ACE activity and drug efficacy (blood pressure suppression) was not due to the genetic polymorphism. Further study was warranted to investigate other factors, including for example, differences of expression amount of gene, ACE inhibitor transferability to tissues, and so on.Chapter 4 SummaryAlthough morphologic assessment by echocardiography is very important to make a tentative diagnose in cats with HCM, it is influenced by various factors. This study revealed that HR was one of the factors to influence LV wall thickness, therefore diagnosis only on the basis of morphological feature is not appropriate to make an accurate diagnosis. Accordingly, this study demonstrated that diagnostic accuracy was improved by adding the assessment of diastolic function in cats with preclinical HCM. Diastolic function was significantly decreased in all segments including those without hypertrophy. Moreover, LA enlargement observed as disease progresses was caused by LA dysfunction in addition to LV diastolic dysfunction. STE is the more useful modality compared with conventional TDI to detect early myocardial dysfunction.ACE inhibitors were often used in cats with HCM. Several ACE inhibitors were available in Japan. Although there were significant differences among ACE inhibitors, this study confirmed that they were effectively inhibited serum ACE activity in healthy cats. On the other hand, the inhibitory rate of serum ACE activity was not correlated with efficacy (suppression of blood pressure raise after administration of Angiotensin I) of ACE inhibitor. The reason for the difference was not due to the genetic polymorphism of AT-1 receptor, ACE and chymase.博士(獣医学)麻布大

Tubulointerstitial nephritis complicating IVIG therapy for X-linked agammaglobulinemia

BACKGROUND: Patients with X-linked agammaglobulinemia (XLA) develop immune-complex induced diseases such as nephropathy only rarely, presumably because their immunoglobulin (Ig) G concentration is low. We encountered a patient with XLA who developed tubulointerstitial nephritis during treatment with intravenous immunoglobulin (IVIG). CASE PRESENTATION: A 20-year-old man was diagnosed with XLA 3 months after birth and subsequently received periodic γ-globulin replacement therapy. Renal dysfunction developed at 19 years of age in association with high urinary β2-microglobulin (MG) concentrations. A renal biopsy specimen showed dense CD3-positive lymphocytic infiltration in the tubulointerstitium and tubular atrophy, while no IgG4-bearing cell infiltration was found. Fibrosclerosis and crescent formation were evident in some glomeruli. Fluorescent antibody staining demonstrated deposition of IgG and complement component C3 in tubular basement membranes. After pulse steroid therapy was initiated, urinary β2-MG and serum creatinine concentrations improved. CONCLUSION: Neither drug reactions nor collagen disease were likely causes of tubular interstitial disorder in this patient. Although BK virus was ruled out, IgG in the γ-globulin preparation might have reacted with a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane

Effects of levocabastine on lipid mediator release from guinea pig lung fragments.

The effects of levocabastine, a novel histamine H1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10(-4) M. On the other hand, levocabastine produced no effect on the release of leukotriene E4 or thromoboxane B2. From these findings, it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C4 release.</p

老年者気管支喘息における気道炎症細胞.喘息重症度と関連した気道細胞反応の特徴

Cellular composition of bronchoalveolar lavage (BAL) fluid was examined in 11 elderly asthmatics over the age of 70, and the results were compared with those of 11 younger asthmatics under the age of 50. In the subjects with mild asthma, the proportion of BAL cells in the elderly subjects was 86.2% macrophages, 11.0% lymphocytes, 1.9% neutrophils, 0.9% eosinophils and 0.08% basophilic cells. The proportion of neutrophils and eosinophils in the BAL fluid was slightly higher in younger subjects with mild asthma compared with that in elderly subjects, although no significant difference was found between the two groups. In subjects with severe asthma, the proportions of lymphocytes, neutrophils, eosinophils and basophilic cells were more increased in both younger and older patients compared to those with mild asthma, and a significant increase in the number of BAL eosinophils was found in younger subjects with severe asthma compared to those with mild asthma (p < 0.05). However, no significant difference was present in the proportion of BAL cells between younger and older patients with severe asthma. The results reveal that BAL cells are more increased in subjects with suvere asthma than in those with mild asthma in both younger and older subjects, and show the possibility that this increase is more predominant in neutrophils in older subjects and in eosinophils in younger subjects.70才以上の老年者気管支喘息11例(平均年齢71.4才)を対象に,重症度と気道細胞反応との関連について検討を加えた｡なお,対照として50才以下の喘息症例11例(平均年齢33.5才)を選んだ｡1.老年者の軽症型喘息における気管支肺胞洗浄(BAL)液中の出現細胞の頻度は,マクロファージが86.2%,リンパ球が11.0%,好中球が1.9%,好酸球が0.9%,好塩基性細胞が0.08%であった｡BAL液中の好中球,好酸球の頻度は若青年症例でやや高い傾向が見られたが,両群間に有意の差は見られなかった｡重症例では,老年症例,若青年症例とも,軽症例に比べリンパ球,好中球,好酸球などのBAL細胞の出現頻度が増加しており,特に好酸球では若青年症例の重症例で軽症例に比べ有意に高い頻度が観察された｡これらの結果は, リンパ球,好中球,好酸球などのBAL細胞は,軽症例に比べ重症例で増加してくること,そして,その増加は老年症例では好中球,若青年症例では好酸球の増加が特徴的であることを示唆しているものと考えられた