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This volume focuses on the grammaticalization of the definite article in German. It contains eight empirically-based papers which examine individual stages of the grammaticalization path from its beginnings as a demonstrative to the definite article and beyond. Focusing on cognitive, pragmatic, semantic and syntactic factors, the contributions not only address the development from pragmatic to semantic definiteness, but also deal with functional and formal changes starting as soon as the linguistic unit has acquired the function of marking semantic definiteness. Based on corpora spanning the entire history of the German language, from Old High German (750-1050) to present-day German, the analyses challenge the traditional linear model of grammaticalization and provide alternative pathways. What all the contributions have in common is the idea that the main grammaticalization path is accompanied or crossed by several side roads which lead to different destinations such as preposition-article-clitics, generic usages or onymic articles.

Djungarian hamsters (Phodopus sungorus) living at constant 15 °C T a in short photoperiod (8:16 h L:D) showed pronounced ultradian rhythms (URs) of metabolic rate (MR), body temperature (T b ) and locomotor activity. The ultradian patterns differed between individuals and varied over time. The period length of URs for MR, T b and activity was similar although not identical. Wavelet analysis showed that three different URs are existing in parallel, URs of small amplitude and short duration (UR small ), URs of medium amplitude and medium duration (UR medium ) and URs of large amplitude (UR large ), superimposed on each other. UR large were accompanied by an increase in locomotor activity, whereas UR small and UR medium were of metabolic origin with lacking or delayed responses of activity. An energetic challenge to cold which raised total energy requirements by about 50% did not accelerate the period length of URs, but extended the amplitude of UR small and UR medium . UR large corresponds with the URs of activity, feeding and drinking, sleep and arousal as described in previous studies, which are related to midbrain dopaminergic signalling and hypothalamic ultradian signalling. The cause and control of UR medium and UR small is unknown. Their periods are similar to periods of central and peripheral endocrine ultradian signalling, suggesting a link with URs of metabolism.

Ultradian rhythms of metabolism, body temperature and activity are attenuated or disappear completely during torpor in Djungarian hamsters, for all three ultradian periodicities (UR small , UR medium and UR large ). UR small and UR medium disappear during entrance into torpor, whereas UR large disappear later or continue with a low amplitude. This suggests a tight functional link between torpor and the expression of ultradian rhythms, i.e. torpor is achieved by suppression of metabolic rate as well as silencing of ultradian rhythms. Spontaneous torpor is often initiated after an ultradian burst of activity and metabolic rate, beginning with a period of motionless rest and accompanied by a decrease of metabolic rate and body temperature. To extend previous findings on the potential role of the adrenergic system on torpor induction we analysed the influence of the ß3-adrenergic agonist Mirabegron on torpor in Djungarian hamsters, as compared to the influence of the ß-adrenergic antagonist Propranolol. Hamsters were implanted with 10 day release pellets of Mirabegron (0.06 mg day −1 ) or Propranolol (0.3 mg day −1 ). Mirabegron transiently supressed and accelerated ultradian rhythms but had no effect on torpor behaviour. Propranolol did not affect torpor behaviour nor the expression of ultradian rhythms with the dosage applied during this study.

The paper introduces the implementation and application of the German Constructicon hosted at the University of Düsseldorf ( ). The ultimate goal of the German Constructicon Project (GCP) is not only to identify and describe oftentimes overlooked grammatical constructions, but also to offer comprehensive descriptions in a dictionary-like online repository. Based on constructicographic analyses of the construction family negating_connector, including (‘let alone’), the paper reports on the annotation categories and the computational work routine yielding construction entries.

Prat, M., Demarquay, C., Frick, J., Dudoignon, N., Thierry, D. and Bertho, J. M. Use of Flt3 Ligand to Evaluate Residual Hematopoiesis after Heterogeneous Irradiation in Mice. Radiat. Res. 166, 504–511 (2006). We evaluated the possibility of using plasma Flt3 ligand (FL) concentration as a biological indicator of bone marrow function after heterogeneous irradiation. Mice were irradiated with 4, 7.5 or 11 Gy with 25, 50, 75 or 100% of the bone marrow in the field of irradiation. This model of irradiation resulted in graded and controlled damage to the bone marrow. Mice exhibited a pancytopenia correlated with both the radiation dose and the percentage of bone marrow irradiated. The FL concentration in the blood increased with the severity of bone marrow aplasia. Nonlinear regression analysis showed that the FL concentration was strongly correlated with the total number of residual colony-forming cells 3 days after irradiation, allowing a precise estimate of residual hematopoiesis. Moreover, the FL concentration on day 3 postirradiation was correlated with the duration and severity of subsequent pancytopenia, suggesting that variations in FL concentrations might be used as a predictive indicator of bone marrow aplasia, especially by the use of linear regression equations describing these correlations. Our results provide a rationale for the use of FL concentration as a biological indicator of residual hematopoiesis after heterogeneous irradiation.

PurposeShock is a life-threatening condition characterized by substantial alterations in the microcirculation. This study tests the hypothesis that considering sublingual microcirculatory perfusion variables in the therapeutic management reduces 30-day mortality in patients admitted to the intensive care unit (ICU) with shock.MethodsThis randomized, prospective clinical multicenter trial-recruited patients with an arterial lactate value above two mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of the cause of shock. All patients received sequential sublingual measurements using a sidestream-dark field (SDF) video microscope at admission to the intensive care unit (± 4 h) and 24 (± 4) hours later that was performed blindly to the treatment team. Patients were randomized to usual routine or to integrating sublingual microcirculatory perfusion variables in the therapy plan. The primary endpoint was 30-day mortality, secondary endpoints were length of stay on the ICU and the hospital, and 6-months mortality.ResultsOverall, we included 141 patients with cardiogenic (n = 77), post cardiac surgery (n = 27), or septic shock (n = 22). 69 patients were randomized to the intervention and 72 to routine care. No serious adverse events (SAEs) occurred. In the interventional group, significantly more patients received an adjustment (increase or decrease) in vasoactive drugs or fluids (66.7% vs. 41.8%, p = 0.009) within the next hour. Microcirculatory values 24 h after admission and 30-day mortality did not differ [crude: 32 (47.1%) patients versus 25 (34.7%), relative risk (RR) 1.39 (0.91–1.97); Cox-regression: hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.90–2.66, p = 0.118)].ConclusionIntegrating sublingual microcirculatory perfusion variables in the therapy plan resulted in treatment changes that do not improve survival at all.