On the reaction mechanism of l-lactate oxidase: Quantitative structure-activity analysis of the reaction with para-substituted l-mandelates

The rate constants for reduction of the flavoenzyme, l-lactate oxidase, and a mutant (in which alanine 95 is replaced by glycine), by a series of para-substituted mandelates, in both the 2-1H- and 2-2H- forms, have been measured by rapid reaction spectrophotometry. In all cases, significant isotope effects (1H/2H = 3–7) on the rate constants of flavin reduction were found, indicating that flavin reduction is a direct measure of α-C-H bond breakage. The rate constants show only a small influence of the electronic characteristics of the substituents, but show a good correlation when combined with some substituent volume parameters. A surprisingly good correlation is found with the molecular mass of the substrate. The results are compatible with any mechanism in which there is little development of charge in the transition state. This could be a transfer of hydride to the flavin N(5) position or a synchronous mechanism in which the α-C-H is formally abstracted as a H+ while the resulting charge is simultaneously neutralized by another event.

Plasticity of the neoplastic phenotype in vivo is regulated by epigenetic factors

Age of host and transplantation-site microenvironment influence the tumorigenic potential of neoplastically transformed liver epithelial cells. Tumorigenic BAG2-GN6TF rat liver epithelial cells consistently form tumors at ectopic sites, but differentially express tumorigenicity or hepatocytic differentiation in the liver depending on host age and route of cell transplantation into the liver. Direct inoculation into host livers concentrates tumor cells locally, resulting in undifferentiated tumors near the transplantation site in both young (3-month-old) and old (18-month-old) rats. Transplantation-site tumors regress within 1 month in the livers of young rats, but grow progressively in old rats. However, inoculation of cells into the spleen distributes transplanted cells individually throughout the liver, resulting in hepatocytic differentiation by tumor cells with concomitant suppression of their tumorigenicity in young rats. When transplanted into livers of old rats by splenic inoculation, or when young hepatic-transplant recipients are allowed to age, hepatocytic progeny of BAG2-GN6TF cells proliferate to form foci, suggesting that the liver microenvironment of old rats incompletely regulates the proliferation and differentiation of tumor cell-derived hepatocytes. Upon removal from the liver, BAG2-GN6TF-derived hepatocytes revert to an undifferentiated, aggressively tumorigenic phenotype. We posit that the spectrum between normal differentiation and malignant potential of these cells reflects the dynamic interaction of the specific transformation-related genotype of the cells and the characteristics of the tissue microenvironment at the transplantation site. Changes in the tissue milieu, such as those that accompany normal aging, may determine the ability of a genetically aberrant cell to produce a tumor.

Purification, molecular cloning, and expression of the mammalian sigma1-binding site.

Sigma-ligands comprise several chemically unrelated drugs such as haloperidol, pentazocine, and ditolylguanidine, which bind to a family of low molecular mass proteins in the endoplasmic reticulum. These so-called sigma-receptors are believed to mediate various pharmacological effects of sigma-ligands by as yet unknown mechanisms. Based on their opposite enantioselectivity for benzomorphans and different molecular masses, two subtypes are differentiated. We purified the sigma1-binding site as a single 30-kDa protein from guinea pig liver employing the benzomorphan(+)[3H]pentazocine and the arylazide (-)[3H]azidopamil as specific probes. The purified (+)[3H]pentazocine-binding protein retained its high affinity for haloperidol, pentazocine, and ditolylguanidine. Partial amino acid sequence obtained after trypsinolysis revealed no homology to known proteins. Radiation inactivation of the pentazocine-labeled sigma1-binding site yielded a molecular mass of 24 +/- 2 kDa. The corresponding cDNA was cloned using degenerate oligonucleotides and cDNA library screening. Its open reading frame encoded a 25.3-kDa protein with at least one putative transmembrane segment. The protein expressed in yeast cells transformed with the cDNA showed the pharmacological characteristics of the brain and liver sigma1-binding site. The deduced amino acid sequence was structurally unrelated to known mammalian proteins but it shared homology with fungal proteins involved in sterol synthesis. Northern blots showed high densities of the sigma1-binding site mRNA in sterol-producing tissues. This is also in agreement with the known ability of sigma1-binding sites to interact with steroids, such as progesterone.

Robotic control systems based on bioinspired multi-agent systems: application of the principles of neuroscience to robotics

Robotics is a field that presents a large number of problems because it depends on a large number of disciplines, devices, technologies and tasks. Its expansion from perfectly controlled industrial environments toward open and dynamic environment presents a many new challenges, such as robots household robots or professional robots. To facilitate the rapid development of robotic systems, low cost, reusability of code, its medium and long term maintainability and robustness are required novel approaches to provide generic models and software systems who develop paradigms capable of solving these problems. For this purpose, in this paper we propose a model based on multi-agent systems inspired by the human nervous system able to transfer the control characteristics of the biological system and able to take advantage of the best properties of distributed software systems.

Members of the General Court, 1798-1799

Notebook with paper cover containing a handwritten list of the members of the Massachusetts General Court arranged by county and town. Pearson identified characteristics of the politicians including whether they were chosen by the people or Legislature, were for or against the College, were for or against the Virginia Resolutions, and whether they were "a good Federalist."

Patenting Strategies of the EU Pharmaceutical Industry -Crossroad between Patent Law and Competition Policy. Research Papers in Law, 1/2011

From the Introduction. The pharmaceutical sector inquiry carried out by the European Commission in 2008 provides a useful framework for assessing the relationship between the patent system on the one hand and competition policy and law on the other hand. The pharmaceutical market is not only specifically regulated. It is also influenced by the special characteristics of the patent system which enables pharmaceutical companies engaged in research activities to enter into additional arrangements to cope with the competitive pressures of early patent application and the delays in drug approval. Patents appear difficult to reconcile with the need for sufficient and adequate access to medicines, which is why competition expectations imposed on the pharmaceutical sector are very high. The patent system and competition law are interacting components of the market, into which they must both be integrated. This can result in competition law taking a very strict view on the pharmaceutical industry by establishing strict functional performance standards for the reliance on intellectual property rights protection granted by patent law. This is in particular because in this sector the potential welfare losses are not likely to be of only monetary nature. In brief, the more inefficiencies the patent system produces, the greater the risk of an expansive application of competition law in this field. The aim of the present study is to offer a critical and objective view on the use or abuse of patents and defensive strategies in the pharmaceutical industry. It shall also seek to establish whether patents as presently regulated offer an appropriate degree of protection of intellectual property held by the economic operators in the pharmaceutical sector and whether there is a need or, for that matter, scope for improvement. A useful starting point for the present study is provided by the pharmaceutical sector competition inquiry (hereafter “the sector inquiry”) carried out by the European Commission during the first half of 2008. On 8 July 2008, the Commission adopted its Final Report pursuant to Article 17 of Regulation 1/2003 EC, revealing a series of “antitrust shortcomings” that would require further investigation1.

A Contribution to The Study of Global Competition for Talent: the determinants of student mobility and its consequences for the internationalization of the labor market. Bruges European Economic Policy (BEEP) Briefing 27/2013

In a globalized economy the skills of the workforce are a key determinant of the competitiveness of a country. One of the goals of Higher Education is precisely to develop the students’ skills in order to allow them to match the increasing demand for highly qualified workers while it is simultaneously the best period of life to acquire multicultural skills. For this reason, the European Union has fostered student mobility through several programs: the Erasmus program and the Bologna process are the best known among them. Although student mobility is a growing phenomenon, publications and research on the subject remain relatively scarce. This paper aims to contribute to that literature through an empirical analysis which exploits a questionnaire submitted to university alumni and focuses on two research questions: what drives studies abroad and what drives expatriation of graduates. Our empirical analysis first shows that exposure to international experiences before entering tertiary education and family background are the main factors influencing student mobility. A second conclusion is that studying abroad increases the international mobility on the labor market. Both confirm previous studies. Moreover, by making a distinction between participating in the Erasmus program and in other exchange programs or internships abroad, we found that the Erasmus program and the other programs or internships have an equivalent influence on the international mobility on the labor market: they increase by 9 to 12.5 percentage points a student’s chance to be mobile on the international labor market. This result shows the legitimacy of the Erasmus program, but it also reveals the important impact of other forms of experience abroad. It provides support for policy makers to encourage mobility programs, in order to foster integration of the European labor market.

(Table 2) pH and concentrations of dissolved and particulate chemical elements in the mixing zone of the Yur'eva River water and the Okhotsk Sea water

Data on behavior of iron, manganese, nickel, copper, and zinc in the zone where acidic volcanic waters of the Yur'eva River (Paramushir Island, Kuril Islands) mix with sea water are presented. Distributions of dissolved and particulate forms of these elements indicate that the mixing zone acts as a pH-based geochemical barrier, at which almost all dissolved iron and smaller amounts of other metals are precipitated. When chemogenic particulate matter formed in the mixing zone enters the open ocean, it can sorb trace elements from sea water.

Lithologic, mineral, chemical and isotopic compositions of altered rocks with increasing distance across the eastern flank of the Juan de Fuca Ridge, ODP Leg 168 data

During ODP Leg 168, 10 sites were drilled across the eastern flank of the Juan de Fuca Ridge (JdFR), to examine the conditions of fluid-rock interaction in three distinct hydrothermal regimes (referred to as the Hydrothermal Transition (HT), Buried Basement (BB) and Rough Basement (RB) transects), extending over a ~120 km linear transect perpendicular to the spreading ridge. This was carried out in an attempt to constrain the conditions and processes that control the location, style and magnitude of low temperature (<150°C) fluid-rock interaction within this setting. This paper presents new data on the petrology, mineral chemistry and whole rock strontium and oxygen isotopic compositions of basalts from the eastern flank of the JdFR, in order to investigate the extent, style and sequence of low-temperature hydrothermal alteration and to establish how the hydrothermal regime evolved with time. Throughout the flank, a progressive sequence of low-temperature hydrothermal alteration has been identified, marked by changes in the dominant secondary mineral assemblage, changing from: chlorite+chlorite/smectite; to iron oyxhydroxide+celadonite; to saponite+/-pyrite; culminating at present with Ca- to CaMg(+/-Fe,Mn)-carbonate. The changes in secondary mineralogy have been used to infer a series of systematic shifts in the conditions of alteration that occurred as the basement moved off-axis and was progressively buried by sediment. In general, hydrothermal alteration of the uppermost oceanic crust commenced under open, oxidative conditions, with interaction between unmodified to slightly modified seawater and basaltic crust, to a regime in which circulation of a strongly modified seawater-derived fluid was more restricted, and alteration occurred under non-oxidative conditions. Across the flank, petrological observations and microprobe analyses indicate that the observed ranges in secondary mineral composition are directly related to changes in the geochemical and textural characteristics of the basement, as well as to interaction between fluids and phases from the four stages of alteration. This is suggestive of an increase in fluid-rock increased with time. Whole rock 87Sr/86Sr and d18O analyses of basalts from across the eastern flank of the JdFR reinforce petrological observations, with 87Sr/86Sr and d18O values slightly elevated above accepted pristine MORB values for this region. These results are consistent with an increase in the amount of fluid-rock interaction with time. Across the flank, enrichment in the 87Sr/86Sr and d18O relative to MORB, is influenced by a number of factors, including: local and regional variations in the crustal lithology and structure; the age of the crust; the extent of bulk rock alteration; and theoretically, the relative abundance of different isotopically-enriched secondary mineral phases in the crust.

(Table 1) Age determination of sediment cores of the Labrador Sea

A close look at the sedimentology of Heinrich event 4 from the northwest Labrador Sea indicates that an extended ice margin, perhaps greater than before Heinrich events 1 or 2 (H-1 and H-2), existed in the Hudson Strait region pre-Heinrich event 4 (H-4) and, that on the basis of characteristics of the sediment unit, Heinrich event-4 was different than Heinrich events 1 or 2 (i.e., larger ice sheet collapse(?), longer duration(?), "dirtier" icebergs(?)). Other data from across the southern and eastern margin of the Laurentide Ice Sheet, as well as Greenland and the North Atlantic, support this interpretation, possibly indicating a relative mid-Wisconsin glacial maximum pre-Heinrich event 4. Many of these data also indicate that Heinrich event 4 (35 ka) resulted in serious climatic and oceanographic reorganizations. We suggest that Heinrich event 4 gutted the Hudson Strait, leaving it devoid of ice for Heinrich event 3. We further hypothesize that Heinrich event 3 did not originate from axial ice transport along the Hudson Strait; thus Heinrich event 3 may be more analogous to the proposed northward advancing ice from Ungava Bay during Heinrich event 0 than to the more typical down-the-strait flow during H-1, H-2, and H-4. Consequently, the climatic and oceanographic impacts resulting from Heinrich events are highly susceptible to the type, origin, and magnitude of ice sheet collapse, something which varied per Heinrich event during the last glacial period.

Fourteenth census of the United States taken in the year 1920 ... [Reports]

At head of title: Department of commerce. Bureau of the census ... Sam. L. Rogers, director. Resigned April 13, 1921. W. M. Steuart, director. Appointed April 14, 1921.

Petrographical investigation of the Salt Wash sediments : final report /

This report represents an attempt to use quantitative petrography to elucidate criteria for differentiating ore-bearing from barren sediments in the Salt Wash member of the Morrison formation of the Colorado Plateau. The main premise upon which this approach is based is that the factors which determine whether a sediment contains ore or not is a function largely, if not solely, of the characteristics of the sedimentary rock. It follows that if this premise is true, then the petrographic characteristics of a sediment containing ore should differ from those of the sediments which are barren.

Geometry of profiles across Inner Continental Shelves of the Atlantic and Gulf coasts of the United States /

Along most of the U.S. east and gulf coasts from Long Island to the Mexican Border, bottom profiles extending over the Inner Continental Shelves normal from the coast display a characteristic two-sector shape. Near the coast, the 'shoreface' profile sector is steep and concave-up; the seaward 'ramp' sector is planar with a gradual slope away from the coast. As part of the Beach Evaluation Program at this Center, 9 profiles extending from the coast 30.5 km (19 miles) seaward at each of 49 localities were averaged to mathematically characterize the profiles and to develop and test criteria for discriminating among groups of profiles. Results indicate Inner Continental Shelf profiles can be mathematically defined by 4 parameters: a = ramp slope (0 - 0.00107); b = depth of the ramp at the shoreline, when the ramp is extended as a straight line below the shoreface sector (0 - 24.7 meters, 0 - 81 feet); c = distance from the shoreline to the shoreface-ramp boundary (0.2 - 20.6 km, 0.12 - 12.9 miles); and f = index of concavity of the shoreface sector (0.21 - 1.72). Values in parentheses are the range of values obtained for the 49 averaged profiles. An equation was developed to define bottom depth as a function of distance from shore incorporating these four parameters. Computed depths using the equation were found to be generally within 5% of actual profile depths. In most cases, no relationship was found between the geometric characteristics of the shoreface and the ramp.

Fifteenth census of the United States: 1930 ... : [Reports].

At head of title: U.S. Department of commerce ... Bureau of the census ...