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The article announces the winners of the Molecules Best Paper Award 2013 in the U.S., including Thomas J. Schmidt, Reto Brun, and Holger Trojan.

Breast cancer is one of the most leading deadly diseases in the world whose ranks first among all oncological diseases in women and it is the second spearheading reason of cancer deadness after lung cancer in the United States. Researchers from all over the world are working for finding better ways for preventing, identifying, and treating breast cancer. Topological indices are the functions generating a numerical value from the molecular graph of compounds and they are also a useful tool to estimate the pyhsicochemical and biological properties of molecules in the quantitative structure-property (activity) relationship (QSPR/QSAR) studies. In this paper, some drugs are studied which are used for the treatment of breast cancer. CoM-polynomials based on degree are occurred for chemical graphs of these drugs and the values of some variable topological coindices are calculated via these polynomials. The results obtained by regression analysis show that the correlations of the chosen coindices with the physicochemical properties of the determined drugs are good even strong for some of them. The QSPR models are constructed using the curvilinear regression method with topological coindices. [ABSTRACT FROM AUTHOR]

The article offers a look at various issues concerning the influence of American physicist Richard Feynman on the history of nanotechnology. It discusses Feynman's 1959 lecture on controlling single atoms and molecules. The disagreements about the relevance of Feynman's scientific lecture to the field of nanotechnology are explored. The author also discusses why Feynman's lecture was released only after his death in 1991.

Schizophrenia is a debilitating psychiatric disorder, leading to both physical and social morbidity. Worldwide 1% of the population is struggling with the disease, with 100,000 new cases annually only in the United States. Despite its importance, the goal of finding effective treatments for schizophrenia remains a challenging task, and previous work conducted expensive large-scale phenotypic screens. This work investigates the benefits of Machine Learning for graphs to optimize drug phenotypic screens and predict compounds that mitigate abnormal brain reduction induced by excessive glial phagocytic activity in schizophrenia subjects. Given a compound and its concentration as input, we propose a method that predicts a score associated with three possible compound effects, i.e., reduce, increase, or not influence phagocytosis. We leverage a high-throughput screening to prove experimentally that our method achieves good generalization capabilities. The screening involves 2218 compounds at five different concentrations. Then, we analyze the usability of our approach in a practical setting, i.e., prioritizing the selection of compounds in the SWEETLEAD library. We provide a list of 64 compounds from the library that have the most potential clinical utility for glial phagocytosis mitigation. Lastly, we propose a novel approach to computationally validate their utility as possible therapies for schizophrenia. Author summary: Phagocytosis is a fundamental biological process to protect biological organisms from exogenous infectious particles as well as to preserve equilibrium and efficiency of the host by removing its unwanted cells. A dysregulation of the phagocytic activity can lead to severe consequences for the host. In this study, we focus on a recent theory that relates an excessive phagocytic activity in brain cells, and a consequent abnormal reduction in brain volume, to the development of schizophrenia. Our working hypothesis is that pharmaceutical compounds that can reduce excessive of phagocytic activity might prove effective as a schizophrenia treatment. Rather than attempting to develop ex-novo such a chemical compound, we rely on a more cost-effective and efficient approach that seeks candidate therapies in a set of approved chemical compounds. To achieve this, we train a machine learning model capable of predicting, with good accuracy, the ability of a molecular compound to increase or decrease phagocytosis in the target brain cells. Our approach leverages learning models capable of directly processing the molecular graph of the compound, leading to the identification of 64 candidate drugs of potential clinical utility. [ABSTRACT FROM AUTHOR]

Since the inception of the modern atomic theory, chemists have used physical models to represent the structure of molecules. The goal of this paper is to bring molecular modelling into focus as a constitutive yet overlooked element of chemical practices. It begins with a short technical introduction to molecular models, and then moves into a participant- centred analysis of molecular modelling. Central points of this analysis include, first, a discussion of the dichotomy between graphical and material forms of representation, with suggestions about its consequences for a semiotically-centred view of scientific activity; and, second, a look at the problem of the interpretation of molecular models, as discussed in the chemical literature. The last section focuses on the design of modelling systems through two related historical case studies - namely, the production of two space-filling modelling kits developed in the United States between the late 1930s and the late 1960s. [ABSTRACT FROM AUTHOR]

Purpose: Molecular markers in environmental geochemistry include natural product or pollutant chemicals in sediments that are indicative of discharge sources or emission pathways. Four classes of molecular marker compounds, including fatty acids, sterols, PCBs, and PAHs, in surficial sediments (top 2 cm) collected along a downstream transect of the Potomac River within the US mid-Atlantic region were analyzed and correlated with potential pollution discharge sources in close proximity to the sampling sites.Materials and methods: Thirty-five surficial sediment samples were collected using a petite Ponar grab sampler along a 320-km longitudinal transect of the Potomac River (mid-Atlantic USA), a major tributary of Chesapeake Bay, ranging from the upland fluvial river to its confluence with the Bay. The sediments were collected along the transect at approximately equidistant points. The marker chemicals were extracted from sediments using microwave-assisted extraction and quantified on a dry weight basis by gas chromatography or gas chromatography-mass spectrometry. Sediment moisture, texture, and organic carbon and nitrogen content were also determined.Results and discussion: Fatty acids and sterols were well correlated with ecological factors in the Potomac River, while the sterol ratio epi+brassicasterol/stigmasterol showed moderate spatial correlation with nearby waste treatment plants (WTPs) and city locations, especially in the upland and tidal freshwater river. The fecal sterol coprostanol also showed moderate spatial correlation with some WTPs in both the upland and tidal river. PCB and PAH concentrations were primarily correlated with urban and large military installations. PCBs in sediments appeared to be predominantly derived from Aroclors while PAHs showed a strong pyrogenic origin. Retene and perylene were unique markers for PAHs in sediment and were indicative of aged organic matter in sediments.Conclusions: The marker chemicals had utility in identifying pollution emission sources and pathways in the Potomac River. For PCB pollutants, sediment profiles reflected localized source emissions from industrial sites. PAHs showed a downstream plume effect derived from urban Washington, DC. Fatty acids and sterols were most useful for identifying ecological shifts (i.e., terrestrial versus aquatic origin), but showed spatial correlations with wastewater treatment plants and cities. [ABSTRACT FROM AUTHOR]

The article discusses the need to strengthen and make universal the U.S. National Institute of Health (NIH) guidelines on research involving recombinant DNA molecules to protect the public. The author illustrates an example of how a well-intentioned R-DNA experiment could go astray. He also discusses different considerations pertaining to the physical and biological containment systems described in the NIH guidelines. He also argues that well-defined controls are entirely appropriate for recombinant DNA research based on the NIH guidelines.

The FDA has authority to license manufacture of biosimilar and interchangeable biologics that are expected to compete at lower prices with the most successful and important modern pharmaceuticals, and make those life-saving medicines more accessible. Based on scientific evidence, FDA can only license such biosimilars if it finds that they are “highly similar” to licensed reference products and that they are safe, pure, and potent treatments. FDA has received at least 22 investigational new drugs for biosimilar development programs, and it has held scores of meetings with biosimilar sponsors, relating to more than a dozen reference products. Patent and statutory exclusivities protecting those reference products from competition have begun to expire. Reference product manufacturers have adopted new strategies to eliminate or delay competition for their valuable product franchises. They have asked FDA to require biosimilars to bear non-proprietary (identical non-proprietary name) names different from those assigned to a reference product. These requests are unwarranted and will impede the legislative purpose to make biologic medicines more affordable and accessible. This article addresses the background of these new naming strategies and the several arguments made by reference product manufacturers. It contends that use of different identical non-proprietary names will create undesirable barriers to acceptance of biosimilar products, effectively deterring investment in safe, effective, and affordable biosimilar and interchangeable medicines. The article contends that no scientific reasons exist for use of different identical non-proprietary names to label the “highly similar” active drug substance in reference products and their corresponding biosimilars; that is, there is no evidence that medical and pharmaceutical professionals, in light of all of the available data, are likely to be confused; and that all of the needs of robust pharmacovigilance are already met, without use of differential identical non-proprietary names. It offers a naming solution that meets all these needs. [ABSTRACT FROM AUTHOR]

Background: While there has been much discussion by policymakers and stakeholders about the effects of "secondary patents" on the pharmaceutical industry, there is no empirical evidence on their prevalence or determinants. Characterizing the landscape of secondary patents is important in light of recent court decisions in the U.S. that may make them more difficult to obtain, and for developing countries considering restrictions on secondary patents. Methodology/Principal Findings: We read the claims of the 1304 Orange Book listed patents on all new molecular entities approved in the U.S. between 1988 and 2005, and coded the patents as including chemical compound claims (claims covering the active molecule itself) and/or one of several types of secondary claims. We distinguish between patents with any secondary claims, and those with only secondary claims and no chemical compound claims ("independent" secondary patents). We find that secondary claims are common in the pharmaceutical industry. We also show that independent secondary patents tend to be filed and issued later than chemical compound patents, and are also more likely to be filed after the drug is approved. When present, independent formulation patents add an average of 6.5 years of patent life (95% C.I.: 5.9 to 7.3 years), independent method of use patents add 7.4 years (95% C.I.: 6.4 to 8.4 years), and independent patents on polymorphs, isomers, prodrug, ester, and/or salt claims add 6.3 years (95% C.I.: 5.3 to 7.3 years). We also provide evidence that late-filed independent secondary patents are more common for higher sales drugs. Conclusions/Significance: Policies and court decisions affecting secondary patenting are likely to have a significant impact on the pharmaceutical industry. Secondary patents provide substantial additional patent life in the pharmaceutical industry, at least nominally. Evidence that they are also more common for best-selling drugs is consistent with accounts of active "life cycle management" or "evergreening" of patent portfolios in the industry. [ABSTRACT FROM AUTHOR]

Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future. [ABSTRACT FROM AUTHOR]

This study aimed at assessing the effectiveness of 4 wastewater treatment plants of the Gauteng Province, namely Zeekoegat, Baviaanspoort, Rayton and Refilwe Water Care Works (WCW), in the removal of Cryptosporidium and Giardia (oo)cysts. Wastewater influent and treated effluent samples were taken weekly between January and April 2008. Cryptosporidium and Giardia (oo)cysts were detected by immunofluorescence and immunomagnetic separation, according to a modified US EPA 1623 method. Effluent samples were subjected to a molecular study for the identification of Cryptosporidium parvum Genotype I and Giardia lamblia Assemblage A. The 18S rRNA gene for restriction digests was therefore used to characterise these (oo)cysts. Cryptosporidium oocysts were repeatedly detected in effluent samples collected from all wastewater treatments at lower concentration (range <1 to 40 oocysts/L) levels than Giardia cysts (range <1 to 175 cysts/ℓ). The mean removal efficiencies of Cryptosporidium and Giardia at the 4 wastewater treatment plants ranged from 67.40% to 98.26% and from 86.81% to 99.96%, respectively. For all effluent samples, except Zeekoegat WCW, 29% and 41% contained oocysts of Cryptosporidium parvum Genotype I and cysts of Giardia lamblia Assemblage A, respectively. Both C. Parvum and G. lamblia are human pathogens. This stresses the potential risk of discharging these parasites into receiving water bodies. [ABSTRACT FROM AUTHOR]

There is a widespread and growing concern that patents hinder access to life-saving drugs in developing countries. Recent student movements and legislative initiatives emphasize the potential role that research universities in developed countries could have in ameliorating this "access gap." These efforts are based on the assumption that universities own patents on a substantial number of drugs and that patents on these drugs are currently filed in developing countries. I provide empirical evidence regarding these issues and explore the feasibility and desirability of proposals to change university patenting and licensing practices to promote access to medicines in the developing world. (Am J Public Health. 2009;99: 9-17. doi:10.2105/AJPH.2007. 128769) [ABSTRACT FROM AUTHOR]

Focuses on the research on molecules and viral diseases in the U.S. Activities of protein C in diseases; Dynamics of hemostatis; Role of tissue factor as a therapeutic agent; Consideration on the development of inhibitors as a major complication of hemophilic treatment.

Focuses on the use of small interfering RNA-based molecules in treating several types of diseases in the U.S. Assessment on the response of the immune system from the treatment; Analysis on the level of gene expression; Elimination of foreign nucleic acids from the body.

The article focuses on the genetic research about the nuclear pore complex (NPC) between nucleus and cytoplasm in the U.S. It notes several features of the nanopores and its appropriate diameters. According to Brian Chiat, responsible to engineer a nanosorter that mimics the NPC, the absence of conventional molecular motors and moving parts means that the NPC is an unusual gate. The researchers envision to improve molecular sorting.

The article reports on the research conducted on the implication of molecules to endurance exercise training in the U.S. Researchers found that the adaptation of the muscle to endurance exercise training involves the coordinated expression of genes involved in oxidative metabolism, resulting in increased endurance. Studies show that small-molecule activators of two pathways are believed to transduce these effects, thus enhancing the effects of training, or even substitute for it.

The article discusses the effect that the U.S. Board of Patent Appeals and Interferences decision in "Ex parte Kubin" will have on biotechnology patents that claim DNA sequences. The application in this case claimed that isolated nucleic acid molecules encoding ploypeptides that are at least 80% identical to specific amino acids could be patented. The U.S. Patent and Trademark Office (USPTO) rejected this claim, and this decision was subsequently upheld by the board. This decision conflicts with U.S. Court of Appeals for the Federal Circuit precedent stating that obvious methods of isolating a DNA molecule do not preclude claims to the molecule itself. The nature of this conflict and the USPTO's ruling are evaluated.

The article discusses the rule of three (RO3)3 in drug discovery in the U.S. The author mentions that the guidelines detail molecules' physicochemical properties associated with the fragment-based drug discovery (FBDD) screening. Moreover, they believed that FBDD would help in boosting the success rates of the drug discovery sector.