AlphaZero Gomoku

In the past few years, AlphaZero's exceptional capability in mastering intricate board games has garnered considerable interest. Initially designed for the game of Go, this revolutionary algorithm merges deep learning techniques with the Monte Carlo tree search (MCTS) to surpass earlier top-tier methods. In our study, we broaden the use of AlphaZero to Gomoku, an age-old tactical board game also referred to as "Five in a Row." Intriguingly, Gomoku has innate challenges due to a bias towards the initial player, who has a theoretical advantage. To add value, we strive for a balanced game-play. Our tests demonstrate AlphaZero's versatility in adapting to games other than Go. MCTS has become a predominant algorithm for decision processes in intricate scenarios, especially board games. MCTS creates a search tree by examining potential future actions and uses random sampling to predict possible results. By leveraging the best of both worlds, the AlphaZero technique fuses deep learning from Reinforcement Learning with the balancing act of MCTS, establishing a fresh standard in game-playing AI. Its triumph is notably evident in board games such as Go, chess, and shogi

Glomerular permeability to macromolecules in the Necturus kidney

Tanner GA, Rippe C, Shao Y, Evan AP, Williams JC, Jr. Glomerular permeability to macromolecules in the Necturus kidney. Am J Physiol Renal Physiol 296: F1269-F1278, 2009. First published April 1, 2009; doi: 10.1152/ajprenal.00371.2007.-Many aspects of the glomerular filtration of macromolecules remain controversial, including the location of the major filtration barrier, the effects of electrical charge, and the reason the filtration barrier does not clog. We examined these issues in anesthetized Necturus maculosus, using fluorescently labeled probes and a two-photon microscope. With the high resolution of this system and the extraordinary width (similar to 3.5 mu m) of the glomerular basement membrane (GBM) in this salamander, we were able to visualize fluorescent molecules in the GBM in vivo. GBM/plasma concentration ratios for myoglobin, ovalbumin, and serum albumin did not differ from that of inulin, indicating that the GBM does not discriminate among these molecules. The GBM/plasma concentration ratios for fluoresceinated dextran 500 and 2,000 kDa were significantly below that of inulin. Glomerular sieving coefficients (GSCs) for various macromolecules decreased as molecular mass increased, and the GSCs for bovine or human serum albumin were extremely low. The effect of electrical charge on filterability of a macromolecule was also examined. The GSCs for native (anionic) and neutral human serum albumin were not significantly different, nor did GSCs for anionic and neutral dextran 40 kDa differ, indicating that charge has no detectable effect on filterability of these macromolecules. These studies indicate that the main filtration barrier to albumin is the podocyte slit diaphragm. Electron microscopic studies revealed many cell processes within the GBM. Macromolecules that penetrated the GBM were taken up by mesangial cells and endothelial cells, suggesting that these cells help to prevent clogging of the filter

<i>De Novo</i> Design of Tetranuclear Transition Metal Clusters Stabilized by Hydrogen-Bonded Networks in Helical Bundles

<i>De novo</i> design provides an attractive approach to test the mechanism by which metalloproteins define the geometry and reactivity of their metal ion cofactors. While there has been considerable progress in designing proteins that bind transition metal ions including iron–sulfur clusters, the design of tetranuclear clusters with oxygen-rich environments has not been accomplished. Here, we describe the design of tetranuclear clusters, consisting of four Zn²⁺ and four carboxylate oxygens situated at the vertices of a distorted cube-like structure. The tetra-Zn²⁺ clusters are bound at a buried site within a four-helix bundle, with each helix donating a single carboxylate (Glu or Asp) and imidazole (His) ligand, as well as second- and third-shell ligands. Overall, the designed site consists of four Zn²⁺ and 16 polar side chains in a fully connected hydrogen-bonded network. The designed proteins have apolar cores at the top and bottom of the bundle, which drive the assembly of the liganding residues near the center of the bundle. The steric bulk of the apolar residues surrounding the binding site was varied to determine how subtle changes in helix–helix packing affect the binding site. The crystal structures of two of four proteins synthesized were in good agreement with the overall design; both formed a distorted cuboidal site stabilized by flanking second- and third-shell interactions that stabilize the primary ligands. A third structure bound a single Zn²⁺ in an unanticipated geometry, and the fourth bound multiple Zn²⁺ at multiple sites at partial occupancy. The metal-binding and conformational properties of the helical bundles in solution, probed by circular dichroism spectroscopy, analytical ultracentrifugation, and NMR, were consistent with the crystal structures

Histopathology and surgical anatomy of patients with primary hyperparathyroidism and calcium phosphate stones

Using a combination of intra-operative digital photography and micro-biopsy we measured renal cortical and papillary changes in five patients with primary hyperparathyroidism and abundant calcium phosphate kidney stones. Major tissue changes were variable papillary flattening and retraction, dilation of the ducts of Bellini, and plugging with apatite deposits of the inner medullary collecting ducts and ducts of Bellini. Some of the papillae in two of the patients contained plentiful large interstitial deposits of Randall's plaque and where the deposits were most plentiful we found overgrowth of the attached stones. Hence, this disease combines features previously described in brushite stone formers – dilation, plugging of ducts and papillary deformity – with the interstitial plaque and stone overgrowth characteristic of routine idiopathic calcium oxalate stone formers, suggesting that these two patterns can coexist in a single patient

Randall’s plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle

Our purpose here is to test the hypothesis that Randall’s plaques, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative biopsies of plaques in kidneys of idiopathic-calcium-stone formers and patients with stones due to obesity-related bypass procedures and obtained papillary specimens from non–stone formers after nephrectomy. Plaque originates in the basement membranes of the thin loops of Henle and spreads from there through the interstitium to beneath the urothelium. Patients who have undergone bypass surgery do not produce such plaque but instead form intratubular hydroxyapatite crystals in collecting ducts. Non–stone formers also do not form plaque. Plaque is specific to certain kinds of stone-forming patients and is initiated specifically in thin-limb basement membranes by mechanisms that remain to be elucidated