This book gives a comprehensive description of the physics and applications of resonant tunnelling diodes. The opening chapters of the book set out the basic principles of coherent tunnelling theory. The effects of impurity scattering, femtosecond dynamics, non-equilibrium distribution and intrinsic bistabilities are then described in detail. The applications of RTDs, such as in high-frequency signal generation and multi-valued data storage, are also reviewed. The book closes with a chapter devoted to the more recent field of resonant tunnelling through laterally confined zero-dimensional structures. Covering all the key theoretical and experimental aspects of this stimulating area of research, the book will be of great value to graduate students of quantum transport physics and device engineering, as well as to researchers in both these fields.

We describe the results of conservative treatment for complete midsubstance tears of the anterior cruciate ligament (ACL) in 18 skeletally immature patients, followed for a minimum of 36 months. Six patients had an ACL reconstruction during the follow-up period and were assessed immediately before their operation. The average time from initial injury to evaluation was 51 months. All patients had symptoms when reviewed. The modified Lysholm knee score showed one excellent result, one good, eight fair, and eight poor with a mean score of 64.3. Only one patient had returned to her preinjury level of athletics. Secondary meniscal tears were confirmed in six patients, and three more had the clinical signs of a tear at follow-up. Radiological evidence of degenerative changes was found in 11 of the 18 patients. We conclude that the results of non-operative treatment for ACL injuries in this age group are poor and not acceptable.

Objective-To elucidate whether and how the endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP) pathway in macrophages is involved in the rupture of atherosclerotic plaques. Methods and Results-Increases in macrophage-derived foam cell death in coronary atherosclerotic plaques cause the plaque to become vulnerable, thus resulting in acute coronary syndrome. The ER stress-CHOP/growth arrest and DNA damage-inducible gene-153 (GADD153) pathway is induced in the macrophage-derived cells in atherosclerotic lesions and is involved in plaque formation. However, the role of CHOP in the final stage of atherosclerosis has not been fully elucidated. Many CHOP-expressing macrophages showed apoptosis in advanced ruptured atherosclerotic lesions in wild-type mice, whereas few apoptotic cells were observed in Chop Ϫ/Ϫ mice. The rupture of atherosclerotic plaques was significantly reduced in high cholesterol-fed Chop Ϫ/Ϫ /Apoe Ϫ/Ϫ mice compared with Chop ϩ/ϩ /Apoe Ϫ/Ϫ mice. Furthermore, using mice that underwent bone marrow transplantation, we showed that expression of CHOP in macrophages significantly contributes to the formation of ruptures. By using primary cultured macrophages, we further showed that unesterified free cholesterol derived from incorporated denatured low-density lipoprotein was accumulated in the ER and induced ER stress-mediated apoptosis in a CHOP-Bcl2-associated X protein (Bax) pathway-dependent manner. Key Words: acute coronary syndrome Ⅲ CHOP Ⅲ ER stress Ⅲ Bax Ⅲ apoptosis A cute coronary syndrome, including myocardial infarction and unstable angina, is most frequently caused by an occlusive coronary thrombosis at the site of a preexisting atherosclerotic plaque. [1][2][3][4][5] The formation of coronary thrombosis is generally the result of the rupture of an atherosclerotic plaque, followed by the aggregation of platelets and the formation of fibrin. Therefore, clarification of the mechanisms by which an atherosclerotic plaque becomes vulnerable to rupture would be useful for preventing the onset of acute coronary syndrome. Atherosclerosis is a chronic inflammatory disease of the arterial wall. [1][2][3]6 Macrophages ingest an excess amount of oxidized low-density lipoprotein (LDL) and are converted into foam cells, which then secrete various inflammatory cytokines. Metalloproteinases secreted by macrophages and apoptosis of macrophage-derived foam cells affect the stability of plaques. Thus, monocytes/macrophages play a key role in the instability of atherosclerotic plaques. Conclusion-TheRecently, Myoishi et al 5 reported that the induction of apoptosis and the activation of the endoplasmic reticulum (ER) stress pathway, including the induction of C/EBP homologous protein (CHOP)/growth arrest and DNA damage-inducible gene0153 (GADD153), a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors, were detected in macrophages and smooth muscle cells within ruptured plaques, but not within stable fibrous plaques, in humans. They also reported that the levels of ...

The tumor microenvironment can enhance the invasive capacity of tumor cells. We showed that expression of angiopoietin-like protein 2 (ANGPTL2) in osteosarcoma (OS) cell lines increased and the methylation of its promoter decreased with time when grown as xenografts in mice compared with culture. Compared with cells grown in normal culture conditions, the expression of genes encoding DNA demethylation-related enzymes increased in tumor cells implanted into mice or grown in hypoxic, serum-starved culture conditions. ANGPTL2 expression in OS cell lines correlated with increased tumor metastasis and decreased animal survival by promoting tumor cell intravasation mediated by the integrin α5β1, p38 mitogen-activated protein kinase, and matrix metalloproteinases. The tolloid-like 1 (TLL1) protease cleaved ANGPTL2 into fragments in vitro that did not enhance tumor progression when overexpressed in xenografts. Expression of TLL1 was weak in OS patient tumors, suggesting that ANGPTL2 may not be efficiently cleaved upon secretion from OS cells. These findings demonstrate that preventing ANGPTL2 signaling stimulated by the tumor microenvironment could inhibit tumor cell migration and metastasis.

The purpose of our study was to investigate whether quantitative diffusion-weighted images (DWI) were useful for monitoring the therapeutic response of primary bone tumors. We encountered 18 osteogenic and Ewing sarcomas. Magnetic resonance (MR) images were performed in all patients before and after therapy. We measured the apparent diffusion coefficient (ADC) values, contrast-to-noise ratio (CNR), and tumor volume of the bone tumors pre- and posttreatment. We determined change in ADC value, change in CNR on T2-weighted images (T2WI), change in CNR on gadopentetate dimeglumine (Gd)-T1-weighted images (Gd-T1WI), and change in tumor volume. The bone tumors were divided into two groups: group A was comprised of tumors with less than 90% necrosis after treatment and group B of tumors at least with 90%. Changes in ADC value, tumor volume, and CNR were compared between the groups. Change in the ADC value was statistically greater in group B than that in the group A (p = 0.003). There was no significant difference in the changes in CNR on T2WI (p = 0.683), in CNR on Gd-T1WI (p = 0.763), and tumor volume (p = 0.065). The ADC value on DWI is a promising tool for monitoring the therapeutic response of primary bone sarcomas.

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These findings provide clues regarding the clinical development of regenerative repair strategies for RC injury.

Purpose: To determine the relationship between changes in the extracellular matrix (ECM) and T 1r and T 2 values in vivo. The ECM is composed of proteoglycan (PG), collagen, and water. It has been unclear which of the ECM constituents affects T 1r and T 2 mapping in living human cartilage.Materials and Methods: Sagittal T 1r and T 2 maps were preoperatively obtained from 20 knee osteoarthritis patients. Osteochondral samples harvested from the resected tibial plateaus during total knee arthroplasty were consistent with the MRIs of the patients' knees. Parameters that included histological grading of cartilage degeneration, glycosaminoglycan (GAG) content (which constitutes PG), presence of collagen anisotropy and water content were evaluated along with T 1r and T 2 values, and statistical analysis was performed using multiple regression analysis.Results: T 1r and T 2 values were significantly correlated with the degree of cartilage degeneration (b ¼ 0.397 and 0.357, respectively) and the GAG content (b ¼ À0.340 and À0.244, respectively). Conclusion:The present study demonstrated that T 1r and T 2 values reflect the GAG content of the cartilage and can indicate cartilage degeneration in vivo. Use of these parameters can facilitate the noninvasive diagnosis and evaluation of cartilage degeneration. OSTEOARTHRITIS (OA) IS a degenerative disease that affects the hyaline cartilage at the articular surface.Cartilage matrix breakdown is characterized by changes in the content of glycosaminoglycan (GAG), type II collagen, and water (1). It is difficult to detect these changes in the cartilage matrix using plain radiography or conventional magnetic resonance imaging (MRI) techniques (2,3). However, new MRI techniques that can detect changes in the extracellular matrix (ECM) have recently been developed. In particular, T 1r and T 2 mapping can quantify the ECM of the articular cartilage.The T 1r parameter describes the spin-lattice relaxation in the rotating frame (4). A ''spin-lock'' (SL) pulse is applied to the magnetization in the transverse plane at extremely low fields, and this spin-locked magnetization reflects the changes in the magnetic fields caused by water spin dynamics, such as the chemical exchange of protons. T 1r mapping is most sensitive to changes in the GAG content in the ECM (5-7). A previous in vitro study using a model with selective degradation of GAG by trypsinization revealed that increases in T 1r values correlated with decreases in the GAG content (6,7). The chemical exchanges between bulk water and the hydroxyl and amine groups of proteoglycan (PG) are considered important for the T 1r parameter's relaxation mechanism in articular cartilage (8). In addition, the chemical exchanges between the hydroxyl and amino groups of collagen and the water protons may affect the T 1r parameter; a previous study demonstrated that T 1r shows approximately exponential dependencies on molecular concentration using collagen solutions (9).The T 2 parameter is a spin-spin relaxation method related to the energy ch...