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The family of ADAM (a disintegrin and metalloproteinase) proteins has been implicated in tumor initiation and progression. ADAM17/tumor necrosis factor-α (TNFα)-converting enzyme (TACE) has been initially recognized to release TNFα as well as its receptors (TNFRs) from the membrane. ADAM17, TNFα and TNFR have been found upregulated in cancer patients, although the underlying mechanisms remain largely unknown. As hypoxia is a hallmark of cancer that can lead to severe stress conditions accumulating in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), we investigated the role of these stress conditions in the regulation of ADAM17 and release of TNFR1.We found that severe hypoxia induced ADAM17 expression and activity. Although hypoxia-inducible factor 1α (HIF1α) was important to maintain basal ADAM17 mRNA levels during moderate hypoxia, it was not sufficient to induce ADAM17 levels under severe hypoxia. Instead, we found that ADAM17 induction by severe hypoxia can be mimicked by ER stressors such as Thapsigargin and occurs as a consequence of the activation of the PERK/eIF2α/ATF4 and activating transcription factor 6 (ATF6) arms of UPR in several tumor cell lines. ADAM17 expression was also increased in xenografts displaying ER stress because of treatment with the vascular endothelial growth factor (VEGF) inhibitory antibody Bevacizumab. Additionally, severe hypoxia and ER stress activated ADAM17 and ectodomain shedding of TNFR1 involving mitogen-activated protein (MAP) kinases and reactive oxygen species (ROS). Collectively, these results show that ADAM17 is a novel UPR-regulated gene in response to severe hypoxia and ER stress, which is actively involved in the release of TNFR1 under these conditions. These data provide a novel link between severe hypoxic stress conditions and inflammation in the tumor environment.

SummaryThe use of recombinant ® hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor Ila assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin- spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 µg/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin- spiked blood samples obtained from 50 healthy blood donors. CV- values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 µg/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.

With the Q3D magnetic spectrograph of the Maier-Leibnitz-Laboratorium at M\"unchen at a resolution of about 3 keV, angular distributions and excitation functions of the reaction $^{208}\mathrm{Pb}$($p,{p}^{\ensuremath{'}}$) were measured at some scattering angles ${20}^{\ifmmode^\circ\else\textdegree\fi{}}$--${138}^{\ifmmode^\circ\else\textdegree\fi{}}$ for several proton energies $14.8$--$18.1$ MeV. All seven known isobaric analog resonances in $^{209}\mathrm{Bi}$ are covered. By the excitation near the $j{}_{15/2}$ intruder resonance in $^{209}\mathrm{Bi}$, several new positive parity states in $^{208}\mathrm{Pb}$ with excitation energies $4.6$--$6.2$ MeV are identified by comparison of the mean cross section to the known single particle widths. The dominant configuration for 27 positive parity states is determined and compared to the schematic shell model.

(1946). “Freezing” Behavior in Rats and Its Social Causation. The Journal of Social Psychology: Vol. 24, No. 2, pp. 249-251.

Excited states in {sup 219}Ra were studied by means of the {sup 208}Pb({sup 14}C, 3{ital n}) reaction at 65 MeV. The investigation was made with 12 Compton-suppressed Ge detectors and a multicounter array. Transitions in {sup 219}Ra were selected by requiring appropriate conditions on fold and sum energy. The proposed level scheme shows two sidebands with alternating parity structure decaying to the ground-state band. It is consistent with a recent description of {sup 219}Ra in the framework of the reflection-asymmetric mean-field approach, which predicts a {ital K}=1/2 ground-state band and two low-lying bands with quantum numbers {ital K}=3/2 and {ital K}=5/2.

The lifetimes of the yrast 6+, 8+, 10+ and 13- states in 216Ra and the 27/2+ state in 217Ra have been measured using direct timing and pulsed beams. The resulting B(E2) values cannot be explained by simple shell model configurations. Analysis of these transition strengths and those from similar states in related nuclei provides evidence for a relatively smooth increase in collectivity, correlated with the product of the numbers of valence protons and neutrons outside 208Pb.

High-spin states in 221Ra were studied by the 210Pb(14C, 3n) reaction at beam energies between 61 and 75 MeV. Excitation functions, multiplicity distributions and γγ-coincidences were measured. The level scheme of 221Ra is found to be composed of two bands of alternating parity, characterized by the simplex numbers s = +i and s = −i, which could be followed up to I π = 27 2 + and I π = 27 2 − , respectively. The presence of parity doublets as well as enhanced E1 transactions suggests a reflection-asymmetric shape for this nucleus.

The use of recombinant (r) hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor IIa assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin-spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 micrograms/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin-spiked blood samples obtained from 50 healthy blood donors. CV-values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 micrograms/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.

The high-spin state structure of the nucleus 221 Ac was investigated by means of the 209 Bi( 14 C, 2n) reaction at 63 and 65 MeV. Measurements consisted of in-beam γγ coincidences using the Château de Cristal multidetector array and of e − γ coincidences. Two alternating parity bands could be established in 221 Ac up to spin 35 2 h . Almost all of the states may be regrouped into parity doublets and the origin of these doublets is discussed.

In continuation of our previous work describing the localization of the collagens type I, III, VI, and IV the present study describes the localization of vimentin, laminin, and fibronectin in human myocardium obtained as left ventricular needle biopsies during cardiac surgery. Myocardium from normal pigs served for comparison. Monoclonal antibodies against the various proteins were used on frozen sections, labeled with fluorescein and viewed in the fluorescence microscope. Vimentin, the intermediate filament of mesenchymal cells, is present in fibroblasts, fibrocytes, and endothelial cells. Laminin is observed in the basal membrane of myocytes, smooth muscle and endothelial cells. The staining intensity for the B1-chain is higher in and around myocytes as compared with the B2-chain antibody, but more blood vessels were stained with the latter. The antibody against the A-chain only stained the basal lamina of vascular cells but not that of myocytes. Fibronectin was localized homogeneously throughout the extracellular space as matrix material in which the cellular elements and the various other proteins such as collagens are embedded. Intracellular staining in myocytes (T-tubules) was commonly observed. Both parts of this study show the distribution of extracellular proteins in normal human cardiac tissue and are intended to be the basis for investigations of pathological changes in diseased human myocardium.

The composition of the extracellular matrix in normal human myocardium obtained at open-heart surgery was investigated using monoclonal antibodies against the collagens I, III, IV, and VI, and fluorescence microscopy. The aim of the study was to provide information on normal myocardium that could be used in the evaluation of pathological changes. Porcine myocardium was used for comparison, and both tissues showed a perfect agreement of the results, apart from collagen IV. This was negative in pig myocardium, due to the species specificity of the antibody. Collagens I and III were localized in the extracellular space as either coarse or fine fibrillar structures; the cellular elements of the interstitium, except for the endothelial cells, were also stained. Labeling for collagen VI was much finer than for the other collagens, and was present throughout the interstitium. Collagen IV stained the basement membranes of myocytes and capillary endothelial cells, and also labeled the T-tubular system in the myocytes. The second part of this communication will describe the localization of fibronectin, laminin and vimentin in normal human myocardium.

The reactions 40 Ar + KCl at eight energies from 0.36 to 1.8 GeV/u, 4 He + KCl at 977 and 40 Ar + Balg and 40 Ar + Pb 3 O 4 at 772 GeV/u measured in a Streamer Chamber experiment have been analyzed to determine the stopping power of nuclei, the degree of isotropy and thermalization achieved in central collisions, to search for collective expansion effects and to obtain compressional energies of bulk nuclear matter. Observables used were pion and proton exclusive final state measurements, ratios of total transverse to longitudinal momentum per event, momentum flux and Λ production. From the systematic discrepancy of the π − multiplicities produced in central collisions with respect to an intranuclear cascade model, compressional energies are extracted which fit a parabolic form of the nuclear matter equation of state with a compressibility constant of K = 240 MeV.

The decay sequence based on the 5/2+(402) proton orbital has been identified in 171Re up to spin 41/2. An anomalous upbend in the alignment is observed below the expected backbend, a phenomenon similar to that observed in the yrast sequence of 172Os. The properties of the 5/2+(402) band can be understood in terms of two crossings, one at low spin with a band based on a deformed intruder configuration, the second at higher spin with a band composed of aligned i13/2 neutrons.

The high-spin level structure of 217Ra has been established up to a spin of ( 47 2 ) by means of in-beam γ-ray and conversion electron spectroscopy with (12,13C, xn) reactions on 208Pb. Positive parity levels up to case27 2 + and negative-parity states up to ( case31 2 − ) can be qualitatively understood in terms of neutron excitations arising out of the shell-model configurations v g 3 9 2 , v g 2 9 2 i 11 2 and v g 2 9 2 j 15 2 . The isomeric 33 2 + state at 2.4 Me V and the levels above it require both neutron and proton excitations. The El transitions between the negative-parity and the v g 3 9 2 states suggest the presence of octupole-deformed configurations. Our shell-model calculations provide only a qualitative description of the levels. The experimental level spacings and their moderate agreement with the calculated ones suggest also the onset of deformation and of collective vibrational characteristics.

Theγ-rays following the radioactive decay of160Lu into160Yb have been studied. The Lu source was produced in the144Sm(19F, 3n) reaction at 85 MeV. Excitation functions, half-lives,γ-γ andγ-X-ray coincidences and conversion electrons were measured. Twoβ+ decaying states in160Lu were found with half-lives of 36.2(3) s and 40(1) s.160Yb levels deduced from the decay of160Lu are presented.

Yrast states in the nucleus 220 Ra were studied by means of the 208 Pb( 14 C, 2n) reaction at 61 and 64 MeV. A staggering sequence of levels of positive and negative parity has been observed up to spin and parity I π = 16 + (18 + ) and from I π = 5 − to I π = 17 − , respectively. These states are connected by strong E1 transitions competing with the stretched E2 transitions, the B( E 1) B( E 2) ratio being ~ 10 −6 fm −2 . The ratio of the excitation energy of the 4 + state to that of the 2 + state is close to the vibrational limit. The moment of inertia associated with the negative-parity yrast states is slightly increasing with the rotational frequency ω. It is considerably higher than that of the positive-parity states at lower spins, the difference decreasing monotonically with increasing ω. The data are discussed with reference to the octupole vibrational picture as well as to the results of recent models predicting reflection-asymmetric shapes in the Ra-Th region.

The g-factor of the 480 ns, 9− isomer at 2.237 MeV in 200Pb was measured by the time-differential perturbed angular distribution method. The result, g = −0.0285±0.0011 confirms the rather pure ( f 5 2 −1 i 13 2 −1 ) quasiparticle structure of this state. Half-lives of 480±20 ns, 43±3 ns and 42±4 ns have been measured for the 2237 keV 9−, 2154 keV 7− states in 200Pb and the 2208 keV state in 202Pb, respectively; E2 transitions and g-factors of negative-parity states in even, neutron-deficient Pb isotopes are discussed.

The lifetime of the yrast 15 2 − state in 215 Ra was measured using pulsed beams and γ-ray and electron techniques. Transition multipolarities were established from measured conversion coefficients. The B (E3) of the 15 2 − → 9 2 + transition is found to be considerably larger than previously reported. A candidate for the corresponding transition in 217 Th was also observed. The E3 strength of the 15 2 − → 9 2 + transition in the N = 127 isotones is evaluated in the light of these and other recent results. Interpretation in the framework of particle-octupole vibration coupling requires a systematic lowering of the core 3 − vibration as proton pairs are added to 208 Pb.

The kinematically reversed reaction 13 C( 208 Pb, 3n) 218 Ra was used at 5.31 MeV/u to measure lifetimes of states with spins up to 15 − in 218 Ra, employing the Doppler shift recoil distance method. The higher spin states in 218 Ra exhibit enhanced E1 decays with B (E1)≈6×10 −3 W.u.. These enhanced B (E1)'s suggest a new form of collective dipole deexcitation arising from a reflection asymmetric intrinsic state. The measured B (E1)'s increase with spin between the I π =6 + , 7 − and 8 + states. It is suggested that, at higher spins, reflection asymmetry is enhanced as a consequence of octupole deformations stabilized by rotations or equivalently because of larger wavefunction admixture from cluster states.

Yrast states in 218Ra up to spin and parity Iπ = 17− were identified by means of the 208Pb(13C, 3n) reaction and standard γ-ray spectroscopic techniques. The level scheme is characterized by two bands of opposite parity with nearly constant level spacing. A cascade of strong E1 interband transitions connects both bands. The results are discussed within the systematics of the even Ra isotopes. The negative-parity band which is observed from the Iπ = 5− to the Iπ = 17− state, is interpreted as an octupole vibrational band. The level scheme can be well reproduced in the vibrational limit of the interacting boson approximation (IBA1) which fails, however, to explain the strong E1 feeding of the negative-parity band from the ground-state band

An event by event analysis is carried out for all charged particles observed in central collisions of $^{40}\mathrm{Ar}$ + KCl and $^{40}\mathrm{Ar}$ + Pb at 1.808 and 0.772 GeV/nucleon, respectively. Total transverse energy is used for impact parameter selection within the central trigger condition. The central Ar + KCl reaction exhibits a forward-backward oriented momentum flux. The flux distribution of the most central Ar + Pb events is approximately isotropic in the fireball center of mass.NUCLEAR REACTIONS $^{40}\mathrm{Ar}$ + KCl, $\frac{E}{A}=1.808$ GeV, and $^{40}\mathrm{Ar}$ + Pb, $\frac{E}{A}=0.772$ GeV. Central collision trigger, all charged particles measured event by event, streamer chamber. Momentum flux distribution parameters deduced.

The giant electric dipole resonances based on the ground state (${0}^{+}$) and first excited state (${2}^{+}$) of $^{8}\mathrm{Be}$ have been studied with the reactions $^{7}\mathrm{Li}(p,{\ensuremath{\gamma}}_{0})^{8}\mathrm{Be}$ and $^{7}\mathrm{Li}(p,{\ensuremath{\gamma}}_{1})^{8}\mathrm{Be}$ over the range ${E}_{p}=0.8 \mathrm{to} 17.6$ MeV. Both resonances show a simple resonant shape with little fine structure. The ${\ensuremath{\gamma}}_{1}$ giant resonance is displaced upward from the ${\ensuremath{\gamma}}_{0}$ resonance by an energy of 2.2 MeV which is approximately equal to the excitation of the ${2}^{+}$ state. The reduced ($\ensuremath{\gamma},{p}_{0}$) strengths of the two resonances are approximately equal and each exhausts about 10% of the $E1$ sum rule. The angular distributions for both ${\ensuremath{\gamma}}_{0}$ and ${\ensuremath{\gamma}}_{1}$ are quite constant over the giant resonance structure and are predominantly dipole in character. A simple model can be invoked to explain the dominant $E1$ features. The presence of ${P}_{1}(cos\ensuremath{\theta})$ and ${P}_{3}(cos\ensuremath{\theta})$ terms in both angular distributions indicates $E2$ strength which probably increases above the $E1$ resonances. Some parameters for the narrow levels at 18.15 and 19.06 MeV in $^{8}\mathrm{Be}$ are given.NUCLEAR REACTIONS $^{7}\mathrm{Li}(p,\ensuremath{\gamma})$, $E=0.8\ensuremath{-}17.6$ MeV; measured $\ensuremath{\sigma}(E;{E}_{\ensuremath{\gamma}},\ensuremath{\theta})$. Deduced properties $^{8}\mathrm{Be}$ levels at ${E}_{x}=18.15,19.06$ MeV and ${\ensuremath{\gamma}}_{0}$, ${\ensuremath{\gamma}}_{1}$ giant resonances. 99% enriched $^{7}\mathrm{Li}$ target.

(1976). Family Therapy as Seen by a Group Therapist. International Journal of Group Psychotherapy: Vol. 26, No. 3, pp. 301-309.

We have studied the pre-yrast $\ensuremath{\gamma}$ decay of high-spin states in Yb isotopes excited highly above the yrast line in oxygen-induced $\mathrm{xn}$ reactions on Sm targets. We measured energy spectra, $\ensuremath{\gamma}$-ray multiplicities, angular correlations, and feeding times. The multiplicities increase with the $\ensuremath{\gamma}$ de-excitation energy. The $\ensuremath{\gamma}$-ray anisotropy indicates a dominant quadrupole character of the de-excitation $\ensuremath{\gamma}$ continuum. Hindered feeding times into the ground-band states were observed for $^{158}\mathrm{Yb}$ but not for the decoupled states in $^{159}\mathrm{Yb}$.

The static quadrupole moment of the first excited 2+ state in32S was determined by comparing, in coincidence with32S ions backscattered from60Ni, the gamma-ray yields of the 2 1 + →0 1 + transitions in both nuclei for bombarding energies around 70MeV. Depending on the sign of the interference term for transitions via the second excited 2+ state in32S, the following two values were determined:Q 2 + =(−18±4)e·fm2 andQ2+=(−15±4)e·fm2.

The 2.79, 3.66, 3.73 and 3.88 MeV states in 21 Ne have been studied with the 18 O(α, nγ) 21 Ne reaction at E α = 4.9 to 6.6 MeV. Both neutrons and γ-rays were observed. The investigation involved measurements of γ-ray angular distributions as well as nγ and γγ angular correlations for procuring spin and multipole mixing information. The results of this investigation combined with previous work lead to respective J π assignments of 1 2 − , 3 2 − , 5 2 + and 5 2 − . The states above 4 MeV excitation energy have been studied at E α = 7.5 to 11.5 MeV with a Ge(Li)-NaI(Tl) pair spectrometer. Two new states at E x = 5525.0 ± 1.5 and 5682 ± 2 keV have been found. Evidence is also presented for a doublet comprising the states with excitation energies 5821 ± 3 and 5823 ± 3 keV. Excitation energies, γ-ray decay schemes, mean-lives and limits on spin assignments to all the states are reported. Some of the results are compared with the available data for the mirror nucleus 21 Na and discussed in terms of the rotational model.