A Cooperative Coalitional Game in Duopolistic Supply-Chain Competition

Cooperative coalitional games study the selection of chain partners, the formation of supply chains and outcome allocations. The chain value of a coalition depends on the outcome of inter-chain competition. Subsequently, chain partners may accept their payoffs or decide to defect to another coalition that has made a higher tender offer. The formation and defection continues until a stable Cournot-Nash equilibrium is reached. This is the state where no player may unilaterally defect to another coalition and earn a higher profit. We formulate the cooperative coalitional game as a variational inequality problem and propose an iterative diagonalization algorithm to determine the steady state for the game. The computational results illustrated that (1) supply-chain competition may not necessarily preserve the same level of social welfare; (2) internalization of resources and costs may distort the general competition economy; and (3) wielding the power in a supply chain does not necessarily translate into higher profits.     

Multilayer high-aspect-ratio RF coil for NMR applications

Microcoils offer a high degree of mass sensitivity and high magnetic field gradient strength in magnetic resonance microscopy applications. This paper presents a novel multilayer high-aspect-ratio metal fabrication process that can be used to fabricate a nanoliter-volume radio frequency (RF) saddle coil with an embedded flow-through fluidic channel for nuclear magnetic resonance (NMR) applications. The fabrication process is based on repeated electroplating processes and structure release processes. The achieved aspect ratio of the developed RF saddle coil is 4 with a structure line width of 25 μm. The resistance of the RF coil and the ¹H spectrum line width have been measured and are found to be 0.7 Ω and 350 Hz, respectively. Our results indicate that this novel fabrication process for RF microcoils is feasible for NMR applications.     

Example‐based Multiple Local Color Transfer by Strokes

This paper investigates a new approach for color transfer. Rather than transferring color from one image to another globally, we propose a system with a stroke‐based user interface to provide a direct indication mechanism. We further present a multiple local color transfer method. Through our system the user can easily enhance a defect (source) photo by referring to some other good quality (target) images by simply drawing some strokes. Then, the system will perform the multiple local color transfer automatically. The system consists of two major steps. First, the user draws some strokes on the source and target images to indicate corresponding regions and also the regions he or she wants to preserve. The regions to be preserved which will be masked out based on an improved graph cuts algorithm. Second, a multiple local color transfer method is presented to transfer the color from the target image(s) to the source image through gradient‐guided pixel‐wise color transfer functions. Finally, the defect (source) image can be enhanced seamlessly by multiple local color transfer based on some good quality (target) examples through an interactive and intuitive stroke‐based user interface.     

T Cells in Multisystem Inflammatory Syndrome in Children (MIS-C) Have a Predominant CD4+ T Helper Response to SARS-CoV-2 Peptides and Numerous Virus-Specific CD4− CD8− Double-Negative T Cells

We studied SARS-CoV-2-specific T cell responses in 22 subacute MIS-C children enrolled in 2021 and 2022 using peptide pools derived from SARS-CoV-2 spike or nonspike proteins. CD4+ and CD8+ SARS-CoV-2-specific T cells were detected in 5 subjects, CD4+ T helper (Th) responses alone were detected in 12 subjects, and CD8+ cytotoxic T cell (CTL) responses alone were documented in 1 subject. Notably, a sizeable subpopulation of CD4− CD8− double-negative (DN) T cells out of total CD3+ T cells was observed in MIS-C (median: 14.5%; IQR 8.65–25.3) and recognized SARS-CoV-2 peptides. T cells bearing the Vβ21.3 T cell receptor (TcRs), previously reported as pathogenic in the context of MIS-C, were detected in high frequencies, namely, in 2.8% and 3.9% of the CD4+ and CD8+ T cells, respectively. However, Vβ21.3 CD8+ T cells that responded to SARS-CoV-2 peptides were detected in only a single subject, suggesting recognition of nonviral antigens in the majority of subjects. Subjects studied 6–14 months after MIS-C showed T cell epitope spreading, meaning the activation of T cells that recognize more SARS-CoV-2 peptides following the initial expansion of T cells that see immunodominant epitopes. For example, subjects that did not recognize nonspike proteins in the subacute phase of MIS-C showed good Th response to nonspike peptides, and/or CD8+ T cell responses not appreciable before arose over time and could be detected in the 6–14 months’ follow-up. The magnitude of the Th and CTL responses also increased over time. In summary, patients with MIS-C associated with acute lymphopenia, a classical feature of MIS-C, showed a physiological response to the virus with a prominent role for virus-specific DN T cells.     

Exploration of Diazaspiro Cores as Piperazine Bioisosteres in the Development of σ2 Receptor Ligands

A series of σ2R compounds containing benzimidazolone and diazacycloalkane cores was synthesized and evaluated in radioligand binding assays. Replacing the piperazine moiety in a lead compound with diazaspiroalkanes and the fused octahydropyrrolo[3,4-b] pyrrole ring system resulted in a loss in affinity for the σ2R. On the other hand, the bridged 2,5-diazabicyclo[2.2.1]heptane, 1,4-diazepine, and a 3-aminoazetidine analog possessed nanomolar affinities for the σ2R. Computational chemistry studies were also conducted with the recently published crystal structure of the σ2R/TMEM97 and revealed that hydrogen bond interactions with ASP29 and π-stacking interactions with TYR150 were largely responsible for the high binding affinity of small molecules to this protein.     

Antitumor agents. 178. Synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubulin polymerization

As part of our continuing search for potential anticancer drug candidates in the 2-aryl-1,8-naphthyridin-4(1H)-one series, we have synthesized two series of 3'-substituted 2-phenyl-1,8-naphthyridin-4(1H)-ones and 2-naphthyl-1,8-naphthyridin-4(1H)-ones. All compounds showed significant cytotoxic effects (log GI50 < -4.0; log molar drug concentration required to cause 50% growth inhibition) against a variety of human tumor cell lines of the National Cancer Institute's in vitro screen, including cells derived from solid tumors such as non-small cell lung, colon, central nervous system, melanoma, ovarian, prostate, and breast cancers. All 3'-substituted compounds demonstrated strong cytotoxic effects in almost all tumor cell lines. Introduction of an aromatic ring at the 2'- and 3'-positions also generated compounds with potent antitumor activity. Incorporation of an aromatic ring at the 3'- and 4'-positions produced compounds with reduced activity. Interestingly, introduction of a halogen at the 3'-position yielded compounds with different selectivity for the tumor cell lines tested. All 3'-halogenated compounds (29-36) and compounds 38 and 42-44 were potent inhibitors of tubulin polymerization with activities nearly comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. Active agents also inhibited the binding of [3H]colchicine to tubulin.     

Gastrodin and p-hydroxybenzyl alcohol facilitate memory consolidation and retrieval, but not acquisition, on the passive avoidance task in rats

This study evaluated synthetic trehalose dicorynomycolate (S-TDCM), an immunomodulator, for its survival enhancing capacity and behavioral toxicity in B6D2F1 female mice. In survival experiments, mice were administered S-TDCM (25-400 micrograms/mouse i.p.) 20-24 hr before 5.6 Gy mixed-field fission-neutron irradiation (n) and gamma-photon irradiation. The 30-day survival rates for mice treated with 100-400 micrograms/mouse S-TDCM were significantly enhanced compared to controls. Toxicity of S-TDCM was measured in nonirradiated mice by locomotor activity, food intake, water consumption, and alterations in body weight. A dose-dependent decrease was noted in all behavioral measures in mice treated with S-TDCM. Doses of 100 and 200 micrograms/mouse S-TDCM significantly reduced motor activity beginning 12 hr postinjection with recovery by 24 hr. A dose of 400 micrograms/mouse significantly decreased activity within the first 4 hr after administration and returned to control levels by 32 hr following injection. Food and water intake were significantly depressed at doses of 200 and 400 micrograms/mouse on the day following drug administration, and were recovered in 24 hr. Body weight was significantly decreased in the 200 micrograms/mouse group for 2 days and in the 400 micrograms/mouse group for 4 days following injection. A dose of 100 micrograms/mouse effectively enhanced survival after fission-neutron irradiation with no adverse effect on food consumption, water intake, or body weight and a minimal, short-term effect on locomotor activity.     

Disease burden and the advancement of biomedical knowledge

Despite the importance and magnitude of biomedical research, little is known about its development and responsiveness to current health needs. Herein, we characterized the evolution of disease specific biomedical research and assess the alignment of research and translational efforts with disease burden. Publication patterns for approximately 2700 diseases indicated a fluid landscape of modern biomedical interests. In studying a subset of diseases with available data, overall measures of disease burden explained a large fraction of publication variance but only a small portion of NIH funding variance. In addition, discrete measures of mortality and morbidity differentially impacted NIH funding levels, research efforts, and the number of clinical trials in the US. Our findings not only scrutinize the relevance of our current biomedical enterprise, but may also serve as a resource for fostering strategies that adequately prepare the scientific community to address future health needs and promote accountability in the allocation of resources.     

Effects of a graphene nanosheet conductive additive on the high-capacity lithium-excess manganese–nickel oxide cathodes of lithium-ion batteries

This study examines the effects of a graphene nanosheet (GNS) conductive additive on the performance of a highly packed (2.5 g cm^?3) lithium-ion battery cathode containing 92 wt% Li_1.1(Mn_0.6Ni_0.4)_0.9O₂ microspheres (approximately 6 μm in diameter). GNSs, approximately 2.0 nm thick and 0.5–1.0 μm in width, are introduced into an electrode slurry in the form of a dispersion in N-Methyl-2-pyrrolidone. They are substantially smaller than the oxide particles; therefore, their presence exerts no adverse influence on the packing density of the electrode. A small quantity of the GNS additive (≤200 ppm relative to the oxide mass) can significantly increase the overall electronic conductance and improve the conductance uniformity of the oxide electrode, leading to reduced polarization and enhanced specific capacity and rate performance. However, the GNS additive also promotes solid-electrolyte interphase formation, resulting in resistance buildup and capacity deterioration upon cycling. This study is the first to identify such an adverse effect caused by a graphene additive. The interplay between the positive and negative effects has led to an optimal GNS additive content of approximately 100 ppm, enhancing both the rate and cycle life performance.