Quantitative Science Policy and Management by Using Scientometrics and Scientometric Indicators

IntroductionThere arc many proofs indicating that economicgrowth in the modern era has been grounded on theexploitation of scientific knowledge. The sphere ofhuman activities, which can be identified as "The Re-public of Science" has grown too important for therest of society to leave alone. Most of the industrialnations and many among the LDC's acknowledge thistoday, and virtually all societies in which modern sci-ence is practiced pay at least lip service to the beliefthat it is important …     

Electrically driven directional motion of a four-wheeled molecule on a metal surface

Propelling single molecules in a controlled manner along an unmodified surface remains extremely challenging because it requires molecules that can use light, chemical or electrical energy to modulate their interaction with the surface in a way that generates motion. Nature's motor proteins have mastered the art of converting conformational changes into directed motion, and have inspired the design of artificial systems such as DNA walkers and light- and redox-driven molecular motors. But although controlled movement of single molecules along a surface has been reported, the molecules in these examples act as passive elements that either diffuse along a preferential direction with equal probability for forward and backward movement or are dragged by an STM tip. Here we present a molecule with four functional units--our previously reported rotary motors--that undergo continuous and defined conformational changes upon sequential electronic and vibrational excitation. Scanning tunnelling microscopy confirms that activation of the conformational changes of the rotors through inelastic electron tunnelling propels the molecule unidirectionally across a Cu(111) surface. The system can be adapted to follow either linear or random surface trajectories or to remain stationary, by tuning the chirality of the individual motor units. Our design provides a starting point for the exploration of more sophisticated molecular mechanical systems with directionally controlled motion.     

Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation

Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors.     

Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.