Contract Formation Jurisdiction of the United States Claims Court

This new United States Court of Appeals for the Federal Circuit has jurisdiction over appeals in contract and patent infringement cases. The former Court of Claims\u27 trial division has also been replaced with a new United States Claims Court. This court, inter alia, has been invested with the jurisdiction to conduct trials in contract and patent cases. Of particular interest to the government contracting community, is the provision of the Act regarding the contract formation or pre-award jurisdiction of the new Claims Court. The Claims Court has the potential to provide the most effective forum for the resolution of protests against the award of federal government contracts. Early decisions by the Claims Court defining both the court\u27s jurisdiction over pre-award issues and the scope of review in cases found to be within the court\u27s jurisdiction, however, raised substantial fears whether that potential ever would be reached. The March 23, 1983 decision of the new Court of Appeals for the Federal Circuit in United States v. Grimberg Co. and subsequent Claims Court opinions applying that decision now confirm those fears. Section I looks at the situation in government contracts cases before the creation of the new court. Section II briefly acknowledges the limitations of the former system, and how Congress sought to fix these problems in the Federal Courts Improvement Act. Then Section II turns to discuss the decision in US v. Grimberg

Contract Formation Jurisdiction of the United States Claims Court

This new United States Court of Appeals for the Federal Circuit has jurisdiction over appeals in contract and patent infringement cases. The former Court of Claims\u27 trial division has also been replaced with a new United States Claims Court. This court, inter alia, has been invested with the jurisdiction to conduct trials in contract and patent cases. Of particular interest to the government contracting community, is the provision of the Act regarding the contract formation or pre-award jurisdiction of the new Claims Court. The Claims Court has the potential to provide the most effective forum for the resolution of protests against the award of federal government contracts. Early decisions by the Claims Court defining both the court\u27s jurisdiction over pre-award issues and the scope of review in cases found to be within the court\u27s jurisdiction, however, raised substantial fears whether that potential ever would be reached. The March 23, 1983 decision of the new Court of Appeals for the Federal Circuit in United States v. Grimberg Co. and subsequent Claims Court opinions applying that decision now confirm those fears. Section I looks at the situation in government contracts cases before the creation of the new court. Section II briefly acknowledges the limitations of the former system, and how Congress sought to fix these problems in the Federal Courts Improvement Act. Then Section II turns to discuss the decision in US v. Grimberg

Plant genetic resources for agriculture, plant breeding, and biotechnology: Experiences from Cameroon, Kenya, the Philippines, and Venezuela

"Local farming communities throughout the world face binding productivity constraints, diverse nutritional needs, environmental concerns, and significant economic and financial pressures. Developing countries address these challenges in different ways, including public and private sector investments in plant breeding and other modern tools for genetic crop improvement. In order to measure the impact of any technology and prioritize investments, we must assess the relevant resources, human capacity, clusters, networks and linkages, as well as the institutions performing technological research and development, and the rate of farmer adoption. However, such measures have not been recently assessed, in part due to the lack of complete standardized information on public plant breeding and biotechnology research in developing countries. To tackle this void, the Food and Agricultural Organization of the United Nations (FAO), in consultation with the International Food Policy Institute (IFPRI) and other organizations, designed a plant breeding and biotechnology capacity survey for implementation by FAO consultants in 100 developing countries. IFPRI, in collaboration with FAO and national experts contracted by FAO to complete in-country surveys, identified and analyzed plant breeding and biotechnology programs in four developing countries: Cameroon, Kenya, the Philippines, and Venezuela. Here, we use an innovation systems framework to examine the investments in human and financial resources and the distribution of resources among the different programs, as well as the capacity and policy development for agricultural research in the four selected countries. Based on our findings, we present recommendations to help sustain and increase the efficiency of publicly- and privately-funded plant breeding programs, while maximizing the use of genetic resources and developing opportunities for GM crop production. Policy makers, private sector breeders, and other stakeholders can use this information to prioritize investments, consider product advancement, and assess the relative magnitude of the potential risks and benefits of their investments." from Author's Abstractplant breeding, biotechnology, public research, Funding, Innovation systems, Capacity building, Biosafety,

Nitric Oxide-Releasing Nanoparticles Prevent Propionibacterium acnes-Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response.

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we used an established nanotechnology capable of generating/releasing NO over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, although human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, tumor necrosis factor-α (TNF-α), IL-8, and IL-6 from human monocytes, and IL-8 and IL-6 from human keratinocytes, respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α nor IL-6 secretion, nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1β secretion was through inhibition of caspase-1 and IL-1β gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response

Development of Dromedary Antibody-based Enzyme Linked Immunosorbent Assay for Detecting Chikungunya virus Infections

Background: Chikungunya virus (CHIKV) is an arthropod-borne Togavirus belonging to the genus Alphavirus that is responsible for sporadic worldwide outbreaks of Chikungunya fever, an acute febrile illness often associated with severe polyarthralgia. In Kenya, Chikungunya virus is of great epidemiological concern, with the last major outbreak occurring in 2016 in North Eastern Kenya. Reliable detection of CHIKV infections is key to controlling this re-emerging pathogen, for which no cure currently exists.  Current diagnostic methods for CHIKV employ a combination of tests, particularly immunologic, serologic or virologic techniques.  However, the independent scientific reviews on the validity and sensitivity of currently available commercial assays have been conflicting. Objective: This study aimed to develop and validate a dromedary antibody-based enzyme linked immunosorbent assay for detecting Chikungunya virus infections. Methods: To produce sufficient antigen for camel immunization, Chikungunya virus (strain Lamu 33) was propagated in confluent C6-36 E2 cells using Cytodex microcarrier system. Purified and inactivated CHIKV immunogen was used to inoculate two camels reared at the University of Nairobi farm in Kibwezi, Kenya. Camel serum samples collected over the entire immunization period were assayed for the presence of anti-Chikungunya IgG by indirect ELISA. Purification of camel Heavy Chain IgG antibodies was performed by lectin affinity chromatography on protein A and protein G-Sepharose columns; then conjugated with horse radish peroxidase (HRP). The HRP-conjugated camel Heavy Chain IgG2 and IgG3 were optimized for ELISA, with optical density measured using a microplate reader set at 492nm.   A total of 188 human sera samples were assayed using the developed dromedary-based enzyme linked immunosorbent assay to determine Chikungunya virus infections. Results: The sensitivity of the dromedary HCAb IgG2 assay was 91.3% (95% CI: 0.831 - 0.994); while that for HCAb IgG3 assay was 95.7% (95% CI: 0.898 - 1.01).  The specificity of HCAb IgG2 assay was 92.3% (95% CI: 0.879 - 0.967); while the specificity of HCAb IgG3 method was 90% (95% CI: 0.851 - 0.949). For HCAb IgG2 and IgG3 based assays, the positive predictive values were 79.2% and 75.8 % respectively; while the negative predictive values were 97% and 98.4% for HCAb IgG2 and IgG3 based assays respectively. Conclusion: The camel antibody based assay was found to be reliable assay with very good sensitivity and specificity, and can be deployed for detection of Chikungunya virus infections. Key words: Chikungunya, ELISA, camel antibodies, diagnosi

Safety and immunogenicity of ChAdOx1 85A prime followed by MVA85A boost compared with BCG revaccination among Ugandan adolescents who received BCG at birth: a randomised, open-label trial

Background BCG confers reduced, variable protection against pulmonary tuberculosis. A more effective vaccine is needed. We evaluated the safety and immunogenicity of candidate regimen ChAdOx1 85A–MVA85A compared with BCG revaccination among Ugandan adolescents. Methods After ChAdOx1 85A dose escalation and age de-escalation, we did a randomised open-label phase 2a trial among healthy adolescents aged 12–17 years, who were BCG vaccinated at birth, without evident tuberculosis exposure, in Entebbe, Uganda. Participants were randomly assigned (1:1) using a block size of 6, to ChAdOx1 85A followed by MVA85A (on day 56) or BCG (Moscow strain). Laboratory staff were masked to group assignment. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 28 and serious adverse events (SAEs) throughout the trial; and IFN-γ ELISpot response to antigen 85A (day 63 [geometric mean] and days 0–224 [area under the curve; AUC). Findings Six adults (group 1, n=3; group 2, n=3) and six adolescents (group 3, n=3; group 4, n=3) were enrolled in the ChAdOx1 85A-only dose-escalation and age de-escalation studies (July to August, 2019). In the phase 2a trial, 60 adolescents were randomly assigned to ChAdOx1 85A–MVA85A (group 5, n=30) or BCG (group 6, n=30; December, 2019, to October, 2020). All 60 participants from groups 5 and 6 were included in the safety analysis, with 28 of 30 from group 5 (ChAdOx1 85A–MVA85A) and 29 of 30 from group 6 (BCG revaccination) analysed for immunogenicity outcomes. In the randomised trial, 60 AEs were reported among 23 (77%) of 30 participants following ChAdOx1 85A–MVA85A, 31 were systemic, with one severe event that occurred after the MVA85A boost that was rapidly self-limiting. All 30 participants in the BCG revaccination group reported at least one mild to moderate solicited AE; most were local reactions. There were no SAEs in either group. Ag85A-specific IFN-γ ELISpot responses peaked on day 63 in the ChAdOx1 85A–MVA85A group and were higher in the ChAdOx1 85A-MVA85A group compared with the BCG revaccination group (geometric mean ratio 30·59 [95% CI 17·46–53·59], p<0·0001, day 63; AUC mean difference 57 091 [95% CI 40 524–73 658], p<0·0001, days 0–224). Interpretation The ChAdOx1 85A–MVA85A regimen was safe and induced stronger Ag85A-specific responses than BCG revaccination. Our findings support further development of booster tuberculosis vaccines. Funding UK Research and Innovations and Medical Research Council. Translations For the Swahili and Luganda translations of the abstract see Supplementary Materials section