Using Valuation-Based Decision Making to Increase the Efficiency of China\u27s Patent Subsidy Strategies

[Excerpt] “The Chinese government has grown concerned that its patent fee subsidy programs have not funded the most deserving patents, and thus they no longer wish to spend public resources to promote low-value patents. Instead, the government would prefer subsidy programs that encourage the most deserving patents. The Patent Strategy reflects this desire, as the fourth strategic focus of the Patent Strategy recognizes the need to “[o]ptimize [China’s] patent subsidy policy and further define the orientation to enhance patent quality.”19 This Article explains how a disciplined and transparent valuation-based decision making process can help the Chinese government design patent fee subsidy programs that allocate funds more consistently to deserving patents. In addition, this Article offers the outline of a practical valuation model the Chinese government could use to filter patent fee subsidy requests.

'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection.

Natural killer (NK) cells expressing inhibitory receptors that bind to self major histocompatibility complex (MHC) class I are 'licensed', or rendered functionally more responsive to stimulation, whereas 'unlicensed' NK cells lacking receptors for self MHC class I are hyporesponsive. Here we show that contrary to the licensing hypothesis, unlicensed NK cells were the main mediators of NK cell-mediated control of mouse cytomegalovirus infection in vivo. Depletion of unlicensed NK cells impaired control of viral titers, but depletion of licensed NK cells did not. The transfer of unlicensed NK cells was more protective than was the transfer of licensed NK cells. Signaling by the tyrosine phosphatase SHP-1 limited the proliferation of licensed NK cells but not that of unlicensed NK cells during infection. Thus, unlicensed NK cells are critical for protection against viral infection

Kennesaw State University - Maintenance Optimization and Cost Analysis

The Department of Housing and Residence Life was looking for ways to improve the quality of their work while saving costs at the same time. The department allowed the team to look over their work orders where the team noticed over 50% of the work orders were related to room turnover. After this discovery, the team focused all efforts on room turnover and went over the process in detail with management. The team asked to see the standard operating procedure for room turnover and learned that most of the staff did not know they had one. The team wanted to investigate why the staff was not aware of the SOP, so the team met with the assistant director of housing facilities to discuss why the SOP was not in use. He expressed that the SOP was not specific enough to direct the technicians in what the department was looking for. This led the team to begin thinking about creating a new SOP. After some research, the team learned that reducing variability was a good way of saving costs and that standard operating procedures were a reliable way of reducing variability. The team spoke with the department and reached the decision that a new SOP was the right decision for the department. The team began by shadowing the technicians to learn how the procedure should be done and where improvements could be made. As the team shadowed, they learned that resident assistants were supposed to be performing the inspections. This inspired the team to continue with creating the SOP but to also fully shift inspection duties to the resident assistants. After discussions with the housing department management, the new SOP created by the team was accepted and the trial runs with resident directors performing the inspections began. The team recommended that the department make the new SOP available to all resident and student assistants to ensure that each inspection was done in the same manner to reduce variability and rework

14-An Archaeological Survey along Portage River and Dorrance Creek above Indian Lake in Pavilion Township, Kalamazoo County, Michigan

For three weeks during the 1982 field season, the Western Michigan University archaeological field school was located near Indian Lake in Pavilion Township, T3S RlOW, Kalamazoo County, Michigan (Map 1). As part of the research program, systematic site location survey was planned for this area;one which had not received any prior archaeological attention. With the cooperation of area landowners and the assistance of several local artifact collectors, more than 20 parcels of cultivated land aggregating 3.9 km2 were evaluated by means of surface re~onnaissance or walk-over survey. There follows a report of survey activity, together with descriptions of the archaeological sites recorded

Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells

The double-stranded RNA (dsRNA) analogue poly(I:C) is a promising adjuvant for cancer vaccines because it activates both dendritic cells (DCs) and natural killer (NK) cells, concurrently promoting adaptive and innate anticancer responses. Poly(I:C) acts through two dsRNA sensors, Toll-like receptor 3 (TLR3) and melanoma differentiation-associated protein-5 (MDA5). Here, we investigated the relative contributions of MDA5 and TLR3 to poly(I:C)-mediated NK cell activation using MDA5−/−, TLR3−/−, and MDA5−/−TLR3−/− mice. MDA5 was crucial for NK cell activation, whereas TLR3 had a minor impact most evident in the absence of MDA5. MDA5 and TLR3 activated NK cells indirectly through accessory cells and induced the distinct stimulatory cytokines interferon-α and interleukin-12, respectively. To identify the relevant accessory cells in vivo, we generated bone marrow chimeras between either wild-type (WT) and MDA5−/− or WT and TLR3−/− mice. Interestingly, multiple accessory cells were implicated, with MDA5 acting primarily in stromal cells and TLR3 predominantly in hematopoietic cells. Furthermore, poly(I:C)-mediated NK cell activation was not notably impaired in mice lacking CD8α DCs, providing further evidence that poly(I:C) acts through diverse accessory cells rather than solely through DCs. These results demonstrate distinct yet complementary roles for MDA5 and TLR3 in poly(I:C)-mediated NK cell activation

Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor

Background Carboxylesterases (CES) perform diverse metabolic roles in mammalian organisms in the detoxification of a broad range of drugs and xenobiotics and may also serve in specific roles in lipid, cholesterol, pheromone and lung surfactant metabolism. Five CES families have been reported in mammals with human CES1 and CES2 the most extensively studied. Here we describe the genetics, expression and phylogeny of CES isozymes in the opossum and report on the sequences and locations of CES1, CES2 and CES6 'like' genes within two gene clusters on chromosome one. We also discuss the likely sequence of gene duplication events generating multiple CES genes during vertebrate evolution. Results We report a cDNA sequence for an opossum CES and present evidence for CES1 and CES2 like genes expressed in opossum liver and intestine and for distinct gene locations of five opossum CES genes,CES1, CES2.1, CES2.2, CES2.3 and CES6, on chromosome 1. Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and Drosophila CES gene products. Phylogenetic analyses produced congruent phylogenetic trees depicting a rapid early diversification into at least five distinct CES gene family clusters: CES2, CES1, CES7, CES3, and CES6. Molecular divergence estimates based on a Bayesian relaxed clock approach revealed an origin for the five mammalian CES gene families between 328-378 MYA. Conclusion The deduced amino acid sequence for an opossum cDNA was consistent with its identity as a mammalian CES2 gene product (designated CES2.1). Distinct gene locations for opossum CES1 (1: 446,222,550-446,274,850), three CES2 genes (1: 677,773,395-677,927,030) and a CES6 gene (1: 677,585,520-677,730,419) were observed on chromosome 1. Opossum CES1 and multiple CES2 genes were expressed in liver and intestine. Amino acid sequences for opossum CES1 and three CES2 gene products revealed conserved residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.Full Tex

Canine and Feline Parvoviruses Can Use Human or Feline Transferrin Receptors to Bind, Enter, and Infect Cells

Canine parvovirus (CPV) enters and infects cells by a dynamin-dependent, clathrin-mediated endocytic pathway, and viral capsids colocalize with transferrin in perinuclear vesicles of cells shortly after entry (J. S. L. Parker and C. R. Parrish, J. Virol. 74:1919–1930, 2000). Here we report that CPV and feline panleukopenia virus (FPV), a closely related parvovirus, bind to the human and feline transferrin receptors (TfRs) and use these receptors to enter and infect cells. Capsids did not detectably bind or enter quail QT35 cells or a Chinese hamster ovary (CHO) cell-derived cell line that lacks any TfR (TRVb cells). However, capsids bound and were endocytosed into QT35 cells and CHO-derived TRVb-1 cells that expressed the human TfR. TRVb-1 cells or TRVb cells transiently expressing the feline TfR were susceptible to infection by CPV and FPV, but the parental TRVb cells were not. We screened a panel of feline-mouse hybrid cells for susceptibility to FPV infection and found that only those cells that possessed feline chromosome C2 were susceptible. The feline TfR gene (TRFC) also mapped to feline chromosome C2. These data indicate that cell susceptibility for these viruses is determined by the TfR