Новые языковые реальности употребления претерита в немецком гипотаксисе

Целью статьи являются обобщение и теоретическое обоснование нового употребления претерита в относительном значении в конкретных видах придаточных предложений с презенсом в главном предложении. В статье анализируются коннотативные нюансы относительного значения претерита, регулярность замены префекта-пассива и перфекта именного составного сказуемого с глаголом "sein" на претеритальные формы в гипотаксисе, а также особое место претерита в системе немецких временных форм.Метою статті є узагальнення та теоретичне обґрунтування нового вживання претериту у релятивному значенні у конкретних видах сурядно-підрядних речень з презентом у сурядному реченні. У статті подано аналіз конототивні нюанси претериту і регулярність зміни перфекту пасиву та іменного присудка з дієсловом "sein" на претеритальні форми у гіпотаксису, а також особливе місце претериту у системі німецьких часових форм.The article aims at generalization and theoretical Explanation of modern preterit usage in relative meaning in certain types of clauses, with the Present tense in the main clause. The article deals with the analysis of connotative component meanings of the relative preterit and the regularity of substitution of preterit forms in hypotaxes for the passive perfect tense and the perfect form of the nominal compound predicate with the verb 'sein' as well as the specificity of preterit in the system of German tenses

A blood based 12-miRNA signature of Alzheimer disease patients

Background: Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples. Results: We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies. Conclusions: The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases

CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer

Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit the access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA tumor microenvironment promote concomitant chemotherapy delivery and increased antineoplastic response in murine models of PDA. Prior studies could not determine whether chemotherapy delivery or microenvironment modulation per se were the dominant features in treatment response, and such information could guide the optimal translation of these preclinical findings to patients. To distinguish between these possibilities, we used a chemical inhibitor of cytidine deaminase to stabilize and thereby artificially elevate gemcitabine levels in murine PDA tumors without disrupting the tumor microenvironment. Additionally, we used the FG-3019 monoclonal antibody (mAb) that is directed against the pleiotropic matricellular signaling protein connective tissue growth factor (CTGF/CCN2). Inhibition of cytidine deaminase raised the levels of activated gemcitabine within PDA tumors without stimulating neoplastic cell killing or decreasing the growth of tumors, whereas FG-3019 increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. The response to FG-3019 correlated with the decreased expression of a previously described promoter of PDA chemotherapy resistance, the X-linked inhibitor of apoptosis protein. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models, and by extension in PDA patients

Recent magnetic views of the Antarctic lithosphere

Magnetic anomaly investigations are a key tool to help unveil subglacial geology, crustal architecture and the tectonic and geodynamic evolution of the Antarctic continent. Here, we present the second generation Antarctic magnetic anomaly compilation ADMAP 2.0 (Golynsky et al., 2018), that now includes a staggering 3.5 million line-km of aeromagnetic and marine magnetic data, more than double the amount of data available in the first generation effort. All the magnetic data were corrected for the International Geomagnetic Reference Field, diurnal effects, high-frequency errors and leveled, gridded,and stitched together. The new magnetic anomaly dataset provides tantalising new views into the structure and evolution of the Antarctic Peninsula and the West Antarctic Rift System within West Antarctica, and Dronning Maud Land, the Gamburtsev Subglacial Mountains, the Prince Charles Mountains, Princess Elizabeth Land, and Wilkes Land in East Antarctica, as well as key insights into oceanic gateways. Our magnetic anomaly compilation is helping unify disparate regional geologic and geophysical studies by providing larger-scale perspectives into the major tectonic and magmatic processes that affected Antarctica from Precambrian to Cenozoic times, including e.g. the processes of subduction and magmatic arc development, orogenesis, accretion, cratonisation and continental rifting, as well as continental margin and oceanic basin evolution. The international Antarctic geomagnetic community remains very active in the wake of ADMAP 2.0, and we will showcase some of their key ongoing study areas, such as the South Pole and Recovery frontiers, the Ross Ice Shelf, Dronning Maud Land and Princess Elizabeth Land

Quantum computing in optical microtraps based on the motional states of neutral atoms

We investigate quantum computation with neutral atoms in optical microtraps where the qubit is implemented in the motional states of the atoms, i.e., in the two lowest vibrational states of each trap. The quantum gate operation is performed by adiabatically approaching two traps and allowing tunneling and cold collisions to take place. We demonstrate the capability of this scheme to realize a square-root of swap gate, and address the problem of double occupation and excitation to other unwanted states. We expand the two-particle wavefunction in an orthonormal basis and analyze quantum correlations throughout the whole gate process. Fidelity of the gate operation is evaluated as a function of the degree of adiabaticity in moving the traps. Simulations are based on rubidium atoms in state-of-the-art optical microtraps with quantum gate realizations in the few tens of milliseconds duration range.Comment: 11 pages, 7 figures, for animations of the gate operation, see http://www.itp.uni-hannover.de/~eckert/na/index.htm

Optical dipole traps and atomic waveguides based on Bessel light beams

We theoretically investigate the use of Bessel light beams generated using axicons for creating optical dipole traps for cold atoms and atomic waveguiding. Zeroth-order Bessel beams can be used to produce highly elongated dipole traps allowing for the study of one-dimensional trapped gases and realization of a Tonks gas of impentrable bosons. First-order Bessel beams are shown to be able to produce tight confined atomic waveguides over centimeter distances.Comment: 20 pages, 5 figures, to appear in Phys. Rev.

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Theoretical Directional and Modulated Rates for Direct SUSY Dark Matter Detection

Exotic dark matter together with the vacuum energy (cosmological constant) seem to dominate in the flat Universe. Thus direct dark matter detection is central to particle physics and cosmology. Supersymmetry provides a natural dark matter candidate, the lightest supersymmetric particle (LSP). Furthermore from the knowledge of the density and velocity distribution of the LSP, the quark substructure of the nucleon and the nuclear structure (form factor and/or spin response function), one is able to evaluate the event rate for LSP-nucleus elastic scattering. The thus obtained event rates are, however, very low. So it is imperative to exploit the two signatures of the reaction, namely the modulation effect, i.e. the dependence of the event rate on the Earth's motion, and the directional asymmetry, i.e. the dependence of the rate on the the relative angle between the direction of the recoiling nucleus and the sun's velocity. These two signatures are studied in this paper employing various velocity distributions and a supersymmetric model with universal boundary conditions at large tan(beta).Comment: 11 LATEX pages, 1 table and 4 ps figures included. Paper presented in DARK2002, Fourth Heidelberg International Conference on Dark Matter in Astro- and Particle Physics, Cape Town, South Africa, 4-9 February, 2002, to appear in the proceedings (to be published by Springer Verlag

K-Ras Mediated Murine Epidermal Tumorigenesis Is Dependent upon and Associated with Elevated Rac1 Activity

A common goal for potential cancer therapies is the identification of differences in protein expression or activity that would allow for the selective targeting of tumor vs. normal cells. The Ras proto-oncogene family (K-Ras, H-Ras and N-Ras) are amongst the most frequently mutated genes in human cancers. As a result, there has been substantial effort dedicated to determining which pathways are activated by Ras signaling and, more importantly, which of these contribute to cancer. Although the most widely studied Ras-regulated signaling pathway is the Raf/mitogen-activated protein kinase cascade, previous research in model systems has revealed that the Rac1 GTP-binding protein is also required for Ras-induced biological responses. However, what have been lacking are rigorous in vivo Rac1 target validation data and a clear demonstration that in Ras-driven hyperplastic lesions, Rac1 activity is increased. Using a combination of genetically-modified mouse models that allow for the tissue-selective activation or deletion of signaling molecules and an activation-state sensitive Rac1 antibody that detects GTP-bound Rac1, we found that Rac1 contributes to K-Ras induced epidermal papilloma initiation and growth and that Rac1 activity is elevated by oncogenic K-Ras in vivo. Previously, it was not practical to assess Rac1 activation status in the most commonly used format for clinical tumor specimens, formalin-fixed paraffin embedded (FFPE) tissues samples. However, this study clearly demonstrates that Rac1 is essential for K-Ras driven epithelial cell hyperproliferation and that Rac1 activity is elevated in tissues expressing mutant oncogenic K-Ras, while also characterizing the activation-state specific Rac1-GTP antibody as a probe to examine Rac1 activation status in FFPE samples. Our findings will facilitate further research on the status of Rac1 activity in human tumors and will help to define the tumor types of the patient population that could potentially benefit from therapies targeting Rac activation or downstream effector signaling pathways