Capacitated Network Design Games on a Generalized Fair Allocation Model

The cost-sharing connection game is a variant of routing games on a network. In this model, given a directed graph with edge-costs and edge-capacities, each agent wants to construct a path from a source to a sink with low cost. The cost of each edge is shared by the users based on a cost-sharing function. One of simple cost-sharing functions is defined as the cost divided by the number of users. In fact, most of the previous papers about cost-sharing connection games addressed this cost-sharing function. It models an ideal setting, where no overhead arises when people share things, though it might be quite rare in real life; it is more realistic to consider the setting that the cost paid by an agent is the original cost per the number of the agents plus the overhead. In this paper, we model the more realistic scenario of cost-sharing connection games by generalizing cost-sharing functions. The arguments on the model do not depend on specific cost-sharing functions, and are applicable for a wide class of cost-sharing functions satisfying the following natural properties: they are (1) non-increasing, (2) lower bounded by the original cost per the number of the agents, and (3) upper bounded by the original cost, which enables to represent various scenarios of cost-sharing. We investigate the Price of Anarchy (PoA) and the Price of Stability (PoS) under sum-cost and max-cost criteria with the generalized cost-sharing function. In spite of the generalization, we obtain the same bounds of PoA and PoS as the cost-sharing with no overhead except PoS under sum-cost. Note that these bounds are tight. In the case of sum-cost, the lower bound on PoS increases from $\log n$ to $n+1/n-1$ by the generalization, which is also almost tight because the upper bound is $n$.Comment: 13 pages, 2 figure

Metal Preferences of Zinc-Binding Motif on Metalloproteases

Almost all naturally occurring metalloproteases are monozinc enzymes. The zinc in any number of zinc metalloproteases has been substituted by some other divalent cation. Almost all Co(II)- or Mn(II)-substituted enzymes maintain the catalytic activity of their zinc counterparts. However, in the case of Cu(II) substitution of zinc proteases, a great number of enzymes are not active, for example, thermolysin, carboxypeptidase A, endopeptidase from Lactococcus lactis, or aminopeptidase B, while some do have catalytic activity, for example, astacin (37%) and DPP III (100%). Based on structural studies of various metal-substituted enzymes, for example, thermolysin, astacin, aminopeptidase B, dipeptidyl peptidase (DPP) III, and del-DPP III, the metal coordination geometries of both active and inactive Cu(II)-substituted enzymes are shown to be the same as those of the wild-type Zn(II) enzymes. Therefore, the enzyme activity of a copper-ion-substituted zinc metalloprotease may depend on the flexibility of catalytic domain

Bilateral male breast cancer with male potential hypogonadism

<p>Abstract</p> <p>Background</p> <p>Male breast cancer is a comparatively rare disease, and simultaneous bilateral male breast cancer is considered to be an extremely rare event. Risk factors are said to be genetic factors and hormonal abnormalities due to obesity or testicular diseases.</p> <p>Case presentation</p> <p>The patient was a 47-year-old Japanese male. His family had no history of female breast cancer. This patient also had hypospadias and hormonal examination indicated the presence of primary testicular potential hypogonadism, and these hormonal abnormalities seemed to be present since childhood or the fetal period. The bilateral breast cancer developed in this man at a comparatively young age, and histopathological studies of multiple sections showed that there was almost no normal epithelial cell in the ducts, while the ducts were almost completely filled with breast cancer cells.</p> <p>Conclusion</p> <p>It is thought that male breast cancer is caused by an imbalance between estrogen and testosterone. We cannot rule out the possibility that the breast cancer developed due to the effect of the slight elevation of estrogen over a long period of time, but the actual causative factors in this patient were unable to be definitively identified. In the future, we hope to further elucidate the causes of male breast cancer.</p

A case of matrix-producing carcinoma of the breast

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Pauson-Khand型反応を基盤とするアプローチ : 8員環骨格構築と(+)-achalensolideの全合成

取得学位：博士(薬学），学位授与番号：博甲第1029号，学位授与年月日：平成20年3月22

In rat dipeptidyl peptidase III, His⁵⁶⁸ is essential for catalysis, and Glu⁵⁰⁷ or Glu⁵¹² stabilizes the coordination bond between His⁴⁵⁵ or His⁴⁵⁰ and zinc ion.

Dipeptidyl peptidase (DPP) III is a zinc-dependent exopeptidase that has a unique motif, "HELLGH," as the zinc-binding site. In the present study, a three-dimensional (3D) model of rat DPP III was generated with the X-ray crystal structure of human DPP III (PDB: 3FVY [Dobrovetsky E. et al. (2009) SGC]) as a template. The replacement of the seven charged amino acid residues with a hydrophobic amino acid around the zinc ion did not cause any significant changes in K(m) values or in the substrate specificity. However, the k(cat) values of H568R and H568Y were remarkably reduced, by factors of 50 and 400, respectively. The His⁵⁶⁸ residue of rat DPP III is essential for enzyme catalysis. The k(cat) values of the mutants E507A and E512A were 2.38 and 3.88 s⁻¹ toward Arg-Arg-NA, and 0.097 and 0.59 s⁻¹ toward Phe-Arg-NA, respectively. These values were markedly lower than those of the wild-type DPP III. Furthermore, the zinc contents of E507A and E512A were 0.29 and 0.08 atom per mol of protein, respectively, and those mutations caused remarkable increases in the dissociation constants of the zinc ions from DPP III by factors of 5 x 10³ to 2 x 10⁴. The 3D model of the catalytic domain of rat DPP III showed that the carboxyl oxygen atoms of Glu⁵⁰⁷ and Glu⁵¹² form the hydrogen bonds to the nitrogen atoms of His⁴⁵⁵ and His⁴⁵⁰. All of these results showed that Glu⁵⁰⁷ or Glu⁵¹² stabilizes the coordination bond between the zinc ion and His⁴⁵⁵ or His⁴⁵⁰.Dipeptidyl peptidase (DPP) III is a zinc-dependent exopeptidase that has a unique motif, "HELLGH," as the zinc-binding site. In the present study, a three-dimensional (3D) model of rat DPP III was generated with the X-ray crystal structure of human DPP III (PDB: 3FVY [Dobrovetsky E. et al. (2009) SGC]) as a template. The replacement of the seven charged amino acid residues with a hydrophobic amino acid around the zinc ion did not cause any significant changes in K(m) values or in the substrate specificity. However, the k(cat) values of H568R and H568Y were remarkably reduced, by factors of 50 and 400, respectively. The His⁵⁶⁸ residue of rat DPP III is essential for enzyme catalysis. The k(cat) values of the mutants E507A and E512A were 2.38 and 3.88 s⁻¹ toward Arg-Arg-NA, and 0.097 and 0.59 s⁻¹ toward Phe-Arg-NA, respectively. These values were markedly lower than those of the wild-type DPP III. Furthermore, the zinc contents of E507A and E512A were 0.29 and 0.08 atom per mol of protein, respectively, and those mutations caused remarkable increases in the dissociation constants of the zinc ions from DPP III by factors of 5 x 10³ to 2 x 10⁴. The 3D model of the catalytic domain of rat DPP III showed that the carboxyl oxygen atoms of Glu⁵⁰⁷ and Glu⁵¹² form the hydrogen bonds to the nitrogen atoms of His⁴⁵⁵ and His⁴⁵⁰. All of these results showed that Glu⁵⁰⁷ or Glu⁵¹² stabilizes the coordination bond between the zinc ion and His⁴⁵⁵ or His⁴⁵⁰