Accountability in patenting of federally funded research

Bayh-Dole allows academic grantees to patent federally-funded research for purposes of promoting the commercialization of this research. To ensure commercialization goals are achieved, the Act requires grantees to report to funding agencies not only the existence of federally-funded patents but also utilization efforts they and their licensees/assignees are making. Although reporting is a cornerstone of accountability under Bayh-Dole, information about grantee compliance with reporting requirements is incomplete and dated. In fact, the last significant study of the question dates back to the late 1990s and analyzes only 633 patents. Since that time, concerns have emerged that federally-funded university patents are being asserted improperly against independent commercializers or even assigned to so-called “patent trolls.” This article provides fresh evidence indicating substantial under-reporting of the existence of federal funding in over 30,000 academic biomedical patents issued between 1980 to 2007. The article finds substantial under-reporting of federal funding even in the case of patents on FDA-approved drugs, which should presumably receive significant attention from universities. Grantees’ failure to report federal funding suggests similar, or even more significant, noncompliance with requirements to report utilization information. However, compliance with reporting requirements on utilization cannot be assessed because of secrecy associated with relevant government databases. Accordingly, the article makes a fresh argument that the Commerce Department, which has the requisite regulatory authority, work with funding agencies, to improve transparency. Greater transparency would not only motivate grantees to improve reporting but would also allow assessment of whether grantee patent management is actually achieving Bayh-Dole\u27s utilization goals

Formulation of Thermosensitive Hydrogel Containing Cyclodextrin for Controlled Drug Delivery of Camptothecin

Purpose: To formulate and evaluate temperature-sensitive, controlled-release camptothecin hydrogel for anticancer drug delivery.Method: Temperature-sensitive hydrogel based on chitosan/β-glycerophosphate (β-GP)/β-cyclodextrin (β-CD) was prepared by crosslinking method. The formulations were characterized by Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), gelation time, and viscometry, as well as for controlled release. The formulation, containing camptothecin, was studied by MTT assay on tumor cell MCF-7. The effectiveness of treatment was measured in terms of controlled tumor growth inhibition (TGI).Results: The hydrogel formulation showed good properties in terms of pH, gelation, viscosity and invitro release. The gelation temperature and viscosity of the formulation was optimum. Camptothecin (CPT) released from the hydrogel (TF8) over 8 h in pH 7.4 buffer ranged from 38.97 - 92.5 %, and varied according to the composition of the hydrogels. Release of camptothecin was lowest from preparations without cyclodextrins. Tumor growth inhibition activity of CPT in MCF-7 cell was highest for the formulation containing 1 % chitosan, 8 % β-GP and 1 % β-CD while no inhibition was observed for the blank temperature sensitive hydrogel formulation.Conclusion: These formulations are a promising and more effective delivery system that can be developed to serve as an alternative to the conventional system for anticancer drug delivery.Keywords: Hydrogel, Chitosan, β-Glycerophosphate, β-Cyclodextrin, Camptothecin, MCF-7 cell lin

Rhizosphere of rice plants harbor bacteria with multiple plant growth promoting features

114 diazotrophic bacteria from the rice rhizosphere of five districts of Eastern Uttar Pradesh (India) were isolated and screened for plant growth promoting (PGP) activities employing standard microbiological and biochemical techniques. All these isolates showed nitrogenase activity in the range of 0.23 to 1.72 μmol C2H4 mg-1 protein h-1. Further analysis showed that 84 (73.68%) isolates were Indole-3-acetic acid (IAA) producer; the value of IAA production ranged from 10.1 to 353.0 μg IAA mg-1 protein. IAA production occurred solely in the medium supplemented with tryptophan. P solubilization activity was observed in 28 (24.56%) isolates, the activity being in the range of 38.50 to 321.0 P released μg mg-1 protein. 45 (39.46%) isolates were capable of producing siderophore, the range of production being 4.50 to 223.26 μg mg-1 protein. Analysis of molecular diversity was made by amplified ribosomal DNA restriction analysis (ARDRA) and denaturating gradient gel electrophoresis (DGGE), which exhibited distinct differences among all the isolates. Of the 114 isolates, twenty one (21) isolates showed multiple plant growth promoting traits and were potent in terms of PGP activities. These isolates were identified on the basis of 16S rDNA sequencing and belonged to the genera Pantoea, Bacillus, Microbacterium, Pseudomonas, Sphingomonas, Ancylobacter, Enterobacter, Advenella, γ-proteobacterium strain VA3S1, Rhizobium and Agrobacterium. Findings of this study suggest that certain isolates may be exploited for developing a potential source of biofertilizer.Key words: Plant growth promoting rhizobacteria, N2 fixation, amplified ribosomal DNA restriction analysis, indole-3-acetic acid, siderophore, denaturing gradient gel electrophoresis, temperature gradient gel electrophoresi

Effect of Interlayer Composition on the Properties of Laser-Directed-Energy-Deposition-Based Additively Manufactured Copper-Stainless Steel Wall Structures

Laser-directed energy deposition (LDED) is one of the advanced techniques used for the sustainable manufacturing of engineering components with minimal material wastage and higher performance. This paper reports an investigation on LDED-based additive manufacturing of compositionally graded Copper (Cu)-stainless steel (SS) wall structures for improved performance of tooling components. Three different approaches, such as Cu-SS direct joint, 20% graded Cu-SS, and 50% graded Cu-SS, are used to build the wall structures. Optical microscopy of LDED-built graded samples reveals defect-free deposition of Cu-SS direct joint and 50% graded Cu-SS wall structures at identified process parameters, whereas the 20%-graded wall yields micro-cracks in the lower Cu region. The elemental distribution shows gradual traditions in the weight percentages of Cu and Fe along the built wall. Furthermore, the ultimate tensile strengths of the direct Cu-SS joint wall structure and the 50%-graded Cu-SS wall structure are higher than the strength of LDED-deposited Cu, while the 20%-graded Cu-SS wall structure has lower ultimate tensile strength than the strength of LDED-deposited Cu. Lower ultimate strength and failure in the lower-Cu zone of 20% graded Cu-SS wall structure can be attributed to the presence of micro-cracks in the Cu 20SS 80 zone of 20%-graded Cu-SS wall structures. The study establishes LDED as a technique for building multi-material components promoting sustainability in terms of manufacturing and component performance.</p

Does BCR/ABL1 positive Acute Myeloid Leukaemia Exist?

The BCR/ABL1 fusion gene, usually carried by the Philadelphia chromosome (Ph) resulting from t(9;22)(q34;q11) or variants, is pathognomonic for chronic myeloid leukaemia (CML). It is also occasionally found in acute lymphoblastic leukaemia (ALL) mostly in adults and rarely in de novo acute myeloid leukaemia (AML). Array Comparative Genomic Hybridization (aCGH) was used to study six Ph(+)AML, three bi-lineage and four Ph(+)ALL searching for specific genomic profiles. Surprisingly, loss of the IKZF1 and/or CDKN2A genes, the hallmark of Ph(+)ALL, were recurrent findings in Ph(+)AML and accompanied cryptic deletions within the immunoglobulin and T cell receptor genes. The latter two losses have been shown to be part of 'hot spot' genome imbalances associated with BCR/ABL1 positive pre-B lymphoid phenotype in CML and Ph(+)ALL. We applied Significance Analysis of Microarrays (SAM) to data from the 'hot spot' regions to the Ph(+)AML and a further 40 BCR/ABL1(+) samples looking for differentiating features. After exclusion of the most dominant markers, SAM identified aberrations unique to de novo Ph(+)AML that involved relevant genes. While the biological and clinical significance of this specific genome signature remains to be uncovered, the unique loss within the immunoglobulin genes provides a simple test to enable the differentiation of clinically similar de novo Ph(+) AML and myeloid blast crisis of CML. © 2013 John Wiley & Sons Ltd and Crown

Mortality from external causes in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System Sites.

BACKGROUND: Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings. OBJECTIVE: To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories. DESIGN: All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex. CONCLUSIONS: The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

The Changing Life Science Patent Landscape

What have we learned from 20 tumultuous years of patent law in the life sciences? Is patenting likely to be as important for the industry in the future?Ope