bluuebunny/crossref_metadata_2025 huggingface dataset:
Infrared diode laser spectroscopy of the 5g–4f Rydberg transition of nitric oxide
Authors: Martin P. A. , Stickland R. J. , Martin C. S. B. , Davies P. B.
Published: October 2010

The 5g – 4f Rydberg transition of nitric oxide has been recorded by high-resolution diode laser absorption spectroscopy. The excited states were generated in a low-pressure ac discharge and studied with population modulation detection. The spectra have been assigned and analysed using the multipole-polarization, or long-range interaction model, and the theoretical background is given, including terms up to . Values of the quadrupole moment and polarizability terms of the NO+ (X1Σ+) ion core, as well as a core penetration factor, have been determined in a least-squares fitting procedure. Experimental values for the core properties are compared with recent ab initio calculations.
The infrared spectrum of H2S from 1 to 5 μm
Authors: Bykov Alexander D. , Naumenko Olga V. , Smirnov Maxim A. , Sinitsa Leonid N. , Brown Linda R. , Crisp Joy , Crisp David
Published: October 2010

The absorption spectra of H2S from 2000 to 11 147 cm−1 have been obtained with spectral resolutions of 0.006, 0.012, and 0.021 cm−1 using the Fourier transform spectrometer at Kitt Peak National Observatory. The transitions of 21 bands have been assigned for the first time and 9 others reanalyzed so that accurate energy levels, band origins, and rotational parameters could be determined. The analysis of these data revealed some remarkable features in the energy spectrum, e.g., fourfold clustering of rotational levels belonging to the symmetric and asymmetric components of local mode manifolds at a high degree of stretching excitation. This paper reports fitted vibrational parameters and predicted band origins of H232S up to 12 735 cm−1. It also presents the degenerate rotational constants and upper state energies of (301)–(202) and (311)–(212) at 1 μm as illustrations of clustering in the local mode limit.
The laser magnetic resonance spectrum of the ν1 band of the CCN radical in its state
Authors: Gillett David A. , Brown John M.
Published: October 2010

Vibration–rotation transitions in the ν1, band of the CCN free radical in the [Formula: see text] state have been observed by CO laser magnetic resonance (LMR) spectroscopy. The observations have been combined with existing diode laser data to determine the parameters of an N2 effective Hamiltonian modified to include the Renner–Teller effect in the [Formula: see text] state explicitly. The LMR observations are well modelled by estimated Zeeman parameters that take into account non-adiabatic vibronic interactions. The analysis suggests a small systematic error in the diode laser measurements and leads to a revision of the band origin, ν1, to 1923.252 92 (42) cm−1.
New observations and analysis of the infrared vibration–rotation spectrum of H3+
Authors: Majewski W. A. , McKellar A. R. W. , Sadovskii D. , Watson J. K. G.
Published: October 2010

The coverage of the infrared spectrum of the [Formula: see text] molecular ion is extended by further measurements of the emission from a small high-pressure hollow-cathode electrical discharge cell, using the pressure-dependence of the intensities to distinguish the lines of [Formula: see text] from the many lies due to electronic transitions of H2 in the same region. The lines were assigned by means of calculations with a large vibration–rotation basis, using a Morse-based discrete variable representation for the vibrations. Eight coefficients in the Meyer–Botschwina–Burton ab initio potential were adjusted in order to fit 621 lines of [Formula: see text] from this and previous work with a standard deviation of 0.118 cm−1.
Analysis of the ν1 fundamental of NF3 combining FT and laser side-band saturation spectroscopy. A secondary standard for the 1000–1060 cm−1 region
Authors: Höhe W. , Häring U. , Kreiner W. A. , Essig H. , Ruoff A.
Published: October 2010

The ν1, fundamental of NF3 at 1032 cm−1 has been investigated by Fourier transform (FT) spectroscopy (1295 transitions; J, K up to 43, 41, respectively) and with the saturation technique using CO2 laser side bands as a tunable infrared source. In the latter case, 158 transitions between J = 2 and J = 41 have been observed, with a resolution of 250 kHz and an absolute accuracy of ±200 kHz. The FT spectrum was calibrated using the saturation dips as a frequency standard. From a combined fit the transition frequency has been determined to ν0 = 1032.001 237 50(47) cm−1. All measured lines are available for use as a secondary standard in the 1000 – 1060 cm−1 region.
Millimetre-wave laboratory detection of H2COH+
Authors: Chomiak D. , Taleb-Bendiab A. , Civis S. , Amano T.
Published: October 2010

The ground-state rotational spectrum of protonated formaldehyde, H2COH+, has been identified and assigned following the infrared detection by Amano and Warner using a magnetically confined extended negative glow discharge as a production source. The molecular constants have been determined more accurately. These parameters provide the pure rotational transition frequencies that are accurate enough for radio astronomical searches for this ion in interstellar molecular clouds.
An examination of centrifugal barrier effects in iodine pentafluoride by inner shell electron energy loss spectroscopy
Authors: Cooper Glyn , Zhang Wenzhu , Brion C. E.
Published: October 2010

Electron energy loss spectroscopy was used to study the core (I 4d, I 3d, and F Is) level electronic excitation spectra of IF5. The spectra were collected under experimental conditions such that dipole transitions were dominant (high electron impact energy (3 keV) and 0° scattering angle). The spectra were assigned using term value arguments, and by analogy with those of the isoelectronic molecules TeF6 and XeF4. In common with the spectra of TeF6 and XeF4, the spectra of IF5 show features that are consistent with a centrifugal potential-barrier model. In particular, transitions to virtual valence orbitals and to above-edge shape resonance channels are relatively intense, whereas transitions to Rydberg orbitals are, in comparison, very weak or absent. As in the case of TeF6, it was necessary to include atomic 4f orbitals in the molecular orbital basis to adequately account for the continuum resonance features observed in the IF5 spectra. The valence shell electron energy loss spectrum of IF5 from 5 to 35 eV was also obtained.
Measurement of rovibrational ΔJ = 0, 4, and 6 transitions in solid H2 together with their associated pair spectra
Authors: Steinhoff Ronald A. , Apparao K. V. S. R. , Ferguson David W. , Rao K. Narahari , Winnewisser Brenda P. , Winnewisser Manfred
Published: October 2010

Weak features in the infrared spectum of solid para-hydrogen containing a small amount of orth-hydrogen impurity were measured with high resolution (0.01–0.036 cm−1) and high sensitivity using a Fourier transform spectrometer. Effective absorption path lengths in the solid of 3.75 cm (for the range 4 000–10 000 cm−1) and 15.0 cm (for the range 5000–8000 cm−1) were used to observe the discrete zero-phonon rovibrational transitions U1←0(0), U1←0(1), and W1←0(0), for which accurate line positions and intensity parameters are given. Line positions for the associated satellite spectra for each of those transitions and for the Q1←0(0) and Q1←0(1) transitions were also determined. New features in the satellite spectra of the Q1←0(0), Q1←0(1), U1←0(0), and U1←0(1) transitions are reported. A novel ortho-hydrogen to para-hydrogen converter allowed convenient variation of the temperature for conversion. A multipass optical system external to the head of the cryostat was designed to extend the absorption path length through the hydrogen crystal.
The high-resolution infrared spectrum of cyanobutadiyne, HC5N: The ν7 band centered at 642 cm
Authors: Haas Sybille , Winnewisser Gisbert , Yamada Koichi M.T.
Published: October 2010

The ν7 infrared band of cyanobutadiyne (HC5N) was recorded for the first time with high resolution by FTIR spectroscopy using a sample produced by gas electric discharge. The fundamental band and the hot bands arising from the ν11 = and 2 states are identified. The molecular parameters, including the rotational and vibrational ℓ-type doubling constants, have been determined accurately by analyzing the spectra together with the available microwave and millimetre wave data. The intensity perturbation caused by the ℓ-type resonance in the (ν7,ν11) = (1,1) state has been clearly observed and discussed.
High-resolution UV spectroscopy of vibronic bands in p-difluorobenzene and p-difluorobenzene–Ar: The role of Herzberg–Teller coupling
Authors: Sussmann R. , Neuhauser R. , Neusser H. J.
Published: October 2010

Rotationally resolved spectra of two bands in the S1 → S0 transition of the p-difluorobenzene molecule and its van der Waals complex with Ar have been measured by mass-selective resonance-enhanced two-photon ionization. The rotational structure of the 000 and the 2710 bands in the monomer as well as in the complex differ from each other. They can be theoretically reproduced assuming a transition moment oriented along the short in-plane axis of the molecule in the case of the 000 transition and the long in-plane axis in the case of the 2710 transition. Since the magnitude of the moments of inertia is changed in the complex by adding an Ar atom, complexation leads to a change of rotational structures of the same band. The analysis of the rotational structure points to Herzberg–Teller coupling by vibronic interaction with the S2 (1B1u) state as the mechanism responsible for the appearance of the 2710 band. The rotational constants determined from a fit of the spectra yield an effective van der Waals distance of 3.55 (2) Å (1 Å = 10−10 m) of the Ar atom from the p-difluorobenzene plane, which decreases by 0.06 Å on electronic excitation to the S1 state.
High-resolution spectroscopy of the (000)–(000) band of the CaOD radical
Authors: Li Mingguang , Coxon John A.
Published: October 2010

The [Formula: see text] (000)–(000) band of the gas-phase CaOD radical has been rotationally analyzed using high-resolution laser spectroscopy. The technique of intermodulated fluorescence was employed to resolve the small spin-rotation splittings in the ground state. The measurement accuracy of the rotational line positions was 0.003 cm−1. The measured line positions have been employed in a least-squares estimation of the molecular constrants for both electronic states. Isotope relations between the constants of CaOH and CaOD are examined, and the constants AD and γ for the Ã2Π(000) level were separated using isotope effects.
UV spectra of ArH and ArD as emitted by a neutralized ion beam
Authors: Wunderlich Ch. , Witzel B. , Bruckmeier R. , Figger H.
Published: October 2010

UV spectra of ArH and ArD can be observed after neutralizing an ionic beam of ArH+ and ArD+, respectively, in Cs vapor. The spectra are continuous and range in wavelength from 200 to 450 nm. Earlier lifetime measurements suggested that at least the E2Π and B2Π states contribute to the UV continua, which is supported by simulating the UV spectra starting from ab initio calculated potential curves and dipole transition moments supplied by Theodorakopoulos and Petsalakis. Using the original potentials, the short-wavelength part [Formula: see text] of the spectra could be fitted well, but for longer wavelengths a discrepancy between theoretical and experimental spectra remained. A change of the dissociative ground-state potential curve improved the fit decisively for both ArH and ArD.
The absorption spectrum of C2H2 around ν1 + ν3: energy standards in the 1.5 μm region and vibrational clustering
Authors: Kou Q. , Guelachvili G. , Temsamani M. Abbouti , Herman M.
Published: October 2010

We have recorded the Fourier transform absorption spectrum of acetylene, C2H2, at high resolution, around 6500 cm−1. The positions of the strongest rovibrational lines are measured with respect to the rovibrational lines in 3-0 of CO. They provide secondary calibration standards in that range with an accuracy of 3 × 10−4 cm−1. The rotational analysis of the data gives evidence of five vibrational levels of [Formula: see text] symmetry, in addition to the bright combination level (1010000). This is demonstrated to strictly fit the predicted anharmonic resonance pattern in that region, which permits the vibrational assignment of those extra transitions. Study of the relative intensities of the reported vibrational transitions suggests the need to include new quartic anharmonic couplings. This is supported by the rovibrational analysis of the cold bands around 8500 cm−1, involving the (1110000) bright level, which is also presented.
The high-resolution Fourier transform infrared spectrum of isocyanogen, CNCN: rovibrational analysis of the ν1 and ν2 stretching band systems
Authors: Stroh F. , Winnewisser M. , Winnewisser B. P.
Published: October 2010

The high-resolution gas phase Fourier transform infrared spectrum of the linear molecule isocyanogen, CNCN, has been measured in the 2000–2400 cm−1 region. The C≡N stretching band systems ν1 and ν2 located around 2302.0 and 2059.7 cm−1, respectively, were observed with an unapodized resolution of 0.003 cm−1. In the analysis of these band systems hot bands originating from the states with up to 3 quanta of ν5, the singly excited ν4, and the combination state (ν4 ν5) = (11) were assigned. Effective spectroscopic constants of the numerous subbands as well as constants of an effective Hamiltonian are presented. An analysis of rotation–vibration interaction in CNCN as well as a complete valence force field are presented. The equilibrium rotational constant Be of CNCN was found to be 5172.66 (18) MHz, the diagonal valence force constants determined for C=N–C≡N are for the Σ modes (in aJ/Å2): fC=N− = 15.1, f=N−C≡ = 8.3, f−C=N = 17.1, and for the Π modes (in aJ): fC=N−C≡ = 0.141, f=N−C≡N = 0.361.
Rotationally resolved threshold photoelectron spectroscopy of O2 using coherent XUV: formation of vibrationally excited ions in the Franck–Condon gap
Authors: Kong W. , Hepburn J. W.
Published: October 2010

The rotationally resolved photoelectron spectrum of high vibrational levels of O2+ in the Franck–Condon gap was investigated using pulsed field ionization, zero kinetic energy photoelectron spectroscopy. By using a coherent extreme ultraviolet light source for single-photon excitation, the ν+ = 6–24 vibrational levels of O2+X2Πg were studied. This is the first time levels higher than ν+ = 14 have been observed with rotational resolution. The highest level studied in the present work had a vibrational energy corresponding to 70% of the well depth. Along with the novelty of the spectroscopic technique, the present results reveal interesting and new ionization dynamics. All levels observed are Franck–Condon forbidden, and are not observed in a conventional photoelectron spectrum. There was no direct relation between the vibrational bands and the autoionizing states observed in the photoionization efficiency spectrum in the same energy region, and the rotational line intensities observed in the various bands in the current threshold photoelectron spectra were all similar. The mechanism of this process was different from the "resonant autoionization" model, which involves coupling between a Rydberg state with a low principal quantum number, a dissociative state, arid the Rydberg series converging to the vibrationally excited ion states. Instead, the excitation process was believed to be more direct, involving mainly a dissociative state (or states) and the Rydberg states with a vibrationally excited ion core. Further investigation of this mechanism is still necessary, but the formation of these highly vibrationally excited ions opens a new horizon in state-selective reaction dynamics. With the coherent XUV light source and the PFI-ZEKE technique, a wide range of vibrational energies (up to 4 eV) can be deposited into the O2+ reactant with rovibrational selectivity.
The rQ3 branch of HSSD at 656 GHz: Example of a frequency-tripled backward wave oscillator
Authors: Etzenbach W. , Saleck A. H. , Liedtke M. , Winnewisser G.
Published: October 2010

The rQ3 branch of HSSD with its band head located in the submillimetre-wave region at about 656.5 GHz has been measured up to J = 28 for the ground and for the first excited stretching state. Commencing with medium J quantum numbers (J > 11) the inertial asymmetry splitting is observed, whereas for J > 27 each K-split line separates further into equally strong b- and c-type transitions. For the first time it has been possible to assign Q-branch rotational lines of HSSD to an excited vibrational state, the first excited stretching state νs = 1, which yield differences in the rotational constants: (i) A – B = 93 731.204 (71) MHz and (ii) B – C = 149.69 (14) MHz. The rotational spectra have been recorded with a newly designed wave-guide multiplier, optimized for providing local oscillator power at 660 GHz for astrophysical applications when pumped at 220 GHz. The input radiation was provided by a carcinotron (backward wave oscillator).
Study of In2P/In2P− and InP2/InP2− using negative ion zero electron kinetic energy spectroscopy
Authors: Arnold Caroline C. , Neumark Daniel M.
Published: October 2010

The zero electron kinetic energy (ZEKE) spectra of In2P− and InP2− are presented and compared to their previously obtained photoelectron spectra (PES) as well as ab initio calculations on analogous species. The threshold spectra, which give high-accuracy electron affinities of 2.400 ± 0.001 eV for In2P and 1.617 ± 0.001 eV for InP2, show well-resolved vibrational structure in the transitions from the ground anion states to the various neutral states. The ZEKE spectrum of In2P− exhibits a fairly extended, 47 cm−1 progression that we assign to the symmetric bend (ν2) in the ground 2B2 neutral state. There is also a 204 cm−1 progression that we assign to the symmetric stretch. The InP2− ZEKE spectrum shows transitions to two electronic states of the neutral. For the ground state, the symmetric stretch mode is the most active in the spectrum, whereas in the excited state, the symmetric bend mode is most active. The InP2 ground-state symmetric stretch frequency is 190 cm−1, and the excited-state symmetric bend frequency is 287 cm−1. An anion ground-state frequency is determined to be 227 cm−1. The term energy of the excited state is determined to be 1.280 ± 0.001 eV. Based on molecular orbital arguments, these frequencies suggest a 2B2 ground InP2 state, a 2A1 first excited state, and a 1A1 anion ground state.
ENTROPY CONSERVATIVE SCHEMES AND ADAPTIVE MESH SELECTION FOR HYPERBOLIC CONSERVATION LAWS
Authors: ARVANITIS CHRISTOS , MAKRIDAKIS CHARALAMBOS , SFAKIANAKIS NIKOLAOS I.
Published: October 2010

We consider numerical schemes which combine non-uniform, adaptively redefined spatial meshes with entropy conservative schemes for the evolution step for shock computations. We observe that the resulting adaptive schemes yield approximations free of oscillations in contrast to known fully discrete entropy conservative schemes on uniform meshes. We conclude that entropy conservative schemes are transformed to entropy diminishing schemes when combined with the proposed geometrically driven mesh adaptivity.
DECAY ESTIMATES OF SOLUTIONS TO A SEMI-LINEAR DISSIPATIVE PLATE EQUATION
Authors: SUGITANI YOUSUKE , KAWASHIMA SHUICHI
Published: October 2010

We study the initial value problem for a semi-linear dissipative plate equation in n-dimensional space. We observe that the dissipative structure of the linearized equation is of the regularity-loss type. This means that we have the optimal decay estimates of solutions under the additional regularity assumption on the initial data. This regularity-loss property causes the difficulty in solving the nonlinear problem. For our semi-linear problem, this difficulty can be overcome by introducing a set of time-weighted Sobolev spaces, where the time-weights and the regularity of the Sobolev spaces are determined by our regularity-loss property. Consequently, under smallness condition on the initial data, we prove the global existence and optimal decay of the solution in the corresponding Sobolev spaces.
ON LeFLOCH'S SOLUTIONS TO THE INITIAL-BOUNDARY VALUE PROBLEM FOR SCALAR CONSERVATION LAWS
Authors: FRANKOWSKA HÉLÈNE
Published: October 2010

We consider the initial-boundary value problem for scalar conservation laws on the strip (0, ∞) × [0, 1] with strictly convex smooth flux of a superlinear growth. We show that an associated Hamilton–Jacobi equation with initial and (appropriately defined) boundary conditions has a unique generalized solution V that can be obtained as minimum of three value functions of the calculus of variation. Each of these functions, in turn, can be expressed using Lax's formula. The traces of the gradients Vxsatisfy generalized boundary conditions (as in LeFloch (1988)) in a pointwise manner when the initial and boundary data are continuous and in a weak sense when they are discontinuous. It is also shown that Vxis continuous almost everywhere, and a result concerning the traces of the sign of f′(Vx(t, ⋅)) is proven.
NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines
Authors: Fernandez Luis E. , Gabri Mariano R. , Guthmann Marcelo D. , Gomez Roberto E. , Gold Silvia , Fainboim Leonardo , Gomez Daniel E. , Alonso Daniel F.
Published: October 2010

Active specific immunotherapy is a promising field in cancer research. N‐glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti‐NGc‐containing gangliosides anti‐idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc‐gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included.
Targeted Radiosensitization of Cells Expressing Truncated DNA Polymerase β
Authors: Neijenhuis Sari , Verwijs-Janssen Manon , van den Broek Lenie J. , Begg Adrian C. , Vens Conchita
Published: October 2010

Ionizing radiation (IR) is an effective anticancer treatment, although failures still occur. To improve radiotherapy, tumor-targeted strategies are needed to increase radiosensitivity of tumor cells, without influencing normal tissue radiosensitivity. Base excision repair (BER) and single-strand break repair (SSBR) contribute to the determination of sensitivity to IR. A crucial protein in BER/SSBR is DNA polymerase β (polβ). Aberrant polβ expression is commonly found in human tumors and leads to inhibition of BER. Here, we show that truncated polβ variant (polβ-Δ)–expressing cells depend on homologous recombination (HR) for survival after IR, indicating that a considerable fraction of polβ-Δ–induced lesions are subject to repair by HR. Increased sensitization was found not to result from involvement in DNA-dependent protein kinase–dependent nonhomologous end joining, the other major double-strand break repair pathway. Caffeine and the ATM inhibitor Ku55933 cause polβ-Δ–dependent radiosensitization. Consistent with the observed HR dependence and the known HR-modulating activity of ATM, polβ-Δ–expressing cells showed increased radiosensitization after BRCA2 knockdown that is absent under ATM-inhibited conditions. Our data suggest that treatment with HR modulators is a promising therapeutic strategy for exploiting defects in the BER/SSBR pathway in human tumors. Cancer Res; 70(21); 8706–14. ©2010 AACR.
Characterization of a Candidate Tumor Suppressor Gene Uroplakin 1A in Esophageal Squamous Cell Carcinoma
Authors: Kong Kar Lok , Kwong Dora L. , Fu Li , Chan Tim Hon Man , Chen Leilei , Liu Haibo , Li Yan , Zhu Ying-Hui , Bi Jiong , Qin Yan-Ru , Law Simon Ying Kit , Guan Xin-Yuan
Published: October 2010

Esophageal squamous cell carcinoma (ESCC) is increasing in incidence, but the knowledge of the genetic underpinnings of this disease remains limited. In this study, we identified the tetraspanin cell surface receptor uroplakin 1A (UPK1A) as a candidate tumor suppressor gene (TSG), and we investigated its function and mechanism in ESCC cells. UPK1A downregulation occurred in 68% of primary ESCCs examined, where it was correlated significantly with promoter hypermethylation (P < 0.05). Ectopic expression of UPK1A in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation in nude mice. Mechanistic investigations suggested that these effects may be mediated by inhibiting nuclear translocation of β-catenin and inactivation of its downstream targets, including cyclin-D1, c-jun, c-myc, and matrix metalloproteinase 7 (MMP7). Cell cycle arrest elicited by UPK1A at the G1-S checkpoint was associated with downregulation of cyclin D1 and cyclin-dependent kinase 4, whereas metastasis suppression was associated with reduction of MMP7. These findings were consistent with evidence derived from clinical samples, where UPK1A downregulation was correlated with lymph node metastasis (P = 0.009), stage (P = 0.015), and overall survival (P < 0.0001). Indeed, multivariate cyclooxygenase regression analysis showed that UPK1A was an independent prognostic factor for overall survival. Taken together, our findings define a function for UPK1A as an important TSG in ESCC development. Cancer Res; 70(21); 8832–41. ©2010 AACR.
A Major Role of p95/611-CTF, a Carboxy-Terminal Fragment of HER2, in the Down-modulation of the Estrogen Receptor in HER2-Positive Breast Cancers
Authors: Parra-Palau Josep Lluís , Pedersen Kim , Peg Vicente , Scaltriti Maurizio , Angelini Pier Davide , Escorihuela Marta , Mancilla Sandra , Sánchez Pla Alexandre , Ramón y Cajal Santiago , Baselga José , Arribas Joaquín
Published: October 2010

Current classification of breast cancers depends in great part on the expression of human epidermal growth factor receptor 2 (HER2), a cell surface tyrosine kinase receptor, and estrogen receptor (ER), the nuclear receptor for estrogen. In addition to reliable biomarkers, these receptors are targets of effective and widely used antitumor drugs. During malignant progression, HER2 and ER can establish an intricate cross-talk. In some cases, HER2 overexpression leads to the downregulation of ER and undermining of anti-ER therapies. A subgroup of HER2-positive breast cancer patients with poor prognosis expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTF) collectively known as p95HER2. One of these fragments, 611-CTF, is oncogenic in a variety of preclinical models. However, because of the lack of an appropriate tool to specifically analyze its levels in the clinical setting, the value of 611-CTF as a biomarker has not been established yet. Here, we show that 611-CTF induces resistance to antiestrogen therapy and a more pronounced down-modulation of ER than that induced by full-length HER2. To validate this effect in breast cancer samples, we developed specific anti–611-CTF antibodies. With these antibodies, we showed that, whereas the frequency of ER positivity in HER2-positive/611-CTF–negative tumors (72.6%) is similar to that reported for HER2-negative tumors (70–80%), the number of ER-positive tumors in the 611-CTF–positive subgroup is very low (31.2%). These results reveal a mechanism of ER regulation mediated by HER2, which suggests a new strategy to improve responses to endocrine therapy in breast cancer. Cancer Res; 70(21); 8537–46. ©2010 AACR.
A Phase I Study of a Tropism-Modified Conditionally Replicative Adenovirus for Recurrent Malignant Gynecologic Diseases
Authors: Kimball Kristopher J. , Preuss Meredith A. , Barnes Mack N. , Wang Minghui , Siegal Gene P. , Wan Wen , Kuo Huichien , Saddekni Souheil , Stockard Cecil R. , Grizzle William E. , Harris Raymond D. , Aurigemma Rosemarie , Curiel David T. , Alvarez Ronald D.
Published: October 2010

Purpose: To determine the maximum tolerated dose (MTD), toxicity spectrum, clinical activity, and biological effects of the tropism-modified, infectivity-enhanced conditionally replicative adenovirus (CRAd), Ad5–Δ24–Arg-Gly-Asp (RGD), in patients with malignant gynecologic diseases.

Experimental Design: Cohorts of eligible patients were treated daily for 3 days through an i.p. catheter. Vector doses ranged from 1 × 109 to 1 × 1012 viral particles per day. Toxicity was evaluated using CTCv3.0. CA-125 and Response Evaluation Criteria in Solid Tumors (RECIST) criteria were used to determine clinical efficacy. Corollary biological studies included assessment of CRAd replication, wild-type virus generation, viral shedding, and neutralizing antibody response.

Results: Twenty-one patients were treated. Adverse clinical effects were limited to grade 1/2 fever, fatigue, or abdominal pain. No vector-related grade 3/4 toxicities were noted. No clinically significant laboratory abnormalities were noted. The maximum tolerated dose was not reached. Over a 1 month follow-up, 15 (71%) patients had stable disease and six (29%) had progressive disease. No partial or complete responses were noted. Seven patients had a decrease in CA-125; four had a >20% drop. RGD-specific PCR showed the presence of study vector in ascites of 16 patients. Seven revealed an increase in virus after day 3, suggesting replication of Ad5-Δ24-RGD. Minimal wild-type virus generation was detected. Viral shedding studies showed insignificant shedding in the serum, saliva, and urine. Anti-adenoviral neutralizing antibody effects were prevalent.

Conclusions: This study, the first to evaluate an infectivity-enhanced CRAd in human cancer, shows the feasibility, safety, potential antitumor response, and biological activity of this approach in ovarian cancer. Further evaluation of infectivity enhanced virotherapy approaches for malignant gynecologic diseases is warranted. Clin Cancer Res; 16(21); 5277–87. ©2010 AACR.
Lenalidomide in Nonmetastatic Biochemically Relapsed Prostate Cancer: Results of a Phase I/II Double-Blinded, Randomized Study
Authors: Keizman Daniel , Zahurak Marianna , Sinibaldi Victoria , Carducci Michael , Denmeade Samuel , Drake Charles , Pili Roberto , Antonarakis Emmanuel S. , Hudock Susan , Eisenberger Mario
Published: October 2010

Purpose: To evaluate the safety and activity of 6 months of treatment with lenalidomide at 5 or 25 mg/d in nonmetastatic biochemically relapsed prostate cancer.

Experimental Design: Sixty men with non-castrate, nonmetastatic, biochemically relapsed prostate cancer were stratified by prostate-specific antigen (PSA) doubling time, surgery/radiation therapy, prior androgen deprivation therapy (ADT), and randomized to lenalidomide 5 mg (n = 26) or 25 mg/d (n = 34) for 3 weeks repeated monthly for 6 months or until dose-limiting toxicity or disease progression. Toxicity was evaluated monthly, and PSAs and X-rays/scans every 6 months. Study size was determined to detect a progression rate of 40% at 6 months in either arm with 85% power (compared with a rate of 80% in the population receiving no treatment). Changes in PSA slopes were calculated using the regression of the log PSA for each patient before and during the initial 6 months and compared by t test.

Results: Baseline variables were balanced between arms. Grade 3/4 toxicity rates were 12% (n = 3) with 5 mg and 29% (n = 10) with 25 mg (P = 0.1), most commonly neutropenia (five patients, all on 25 mg). Two patients per arm had thromboembolic events. The change in PSA slope was greater with 25 mg versus 5 mg [−0.172 (−0.24 to −0.11) versus −0.033 (−0.11 to 0.04); P = 0.005]. With a mean follow-up of 31.4 months (range 14-44), five patients on 25 mg and one patient on 5 mg remain on the study.

Conclusions: Lenalidomide has acceptable toxicity and is associated with long-term disease stabilization and PSA declines. Randomized studies evaluating conventional clinical disease end points in this patient population are planned. Clin Cancer Res; 16(21); 5269–76. ©2010 AACR.
Thiocolchicoside Exhibits Anticancer Effects through Downregulation of NF-κB Pathway and Its Regulated Gene Products Linked to Inflammation and Cancer
Authors: Reuter Simone , Prasad Sahdeo , Phromnoi Kanokkarn , Ravindran Jayaraj , Sung Bokyung , Yadav Vivek R. , Kannappan Ramaswamy , Chaturvedi Madan M. , Aggarwal Bharat B.
Published: October 2010

The discovery of new uses for older, clinically approved drugs is one way to expedite drug development for cancer. Thiocolchicoside, a semisynthetic colchicoside from the plant Gloriosa superba, is a muscle relaxant and used to treat rheumatologic and orthopedic disorders because of its analgesic and anti-inflammatory mechanisms. Given that activation of the transcription factor NF-κB plays a major role in inflammation and tumorigenesis, we postulated that thiocolchicoside would inhibit NF-κB and exhibit anticancer effects through the modulation of NF-κB–regulated proteins. We show that thiocolchicoside inhibited proliferation of leukemia, myeloma, squamous cell carcinoma, breast, colon, and kidney cancer cells. Formation of tumor colonies was also suppressed by thiocolchicoside. The colchicoside induced apoptosis, as indicated by caspase-3 and poly(ADP-ribose) polymerase cleavage, and suppressed the expression of cell survival [e.g., Bcl-2, X-linked inhibitor of apoptosis (XIAP), MCL-1, bcl-xL, cIAP-1, cIAP-2, and cFLIP] proteins. Cell proliferation biomarkers such as c-MYC and phosphorylation of phosphoinositide 3-kinase and glycogen synthase kinase 3β were also blocked by thiocolchicoside. Because most cell survival and proliferation gene products are regulated by NF-κB, we studied the effect of thiocolchicoside on this transcription factor and found that thiocolchicoside inhibited NF-κB activation, degradation of inhibitory κBα (IκBα), IκBα ubiquitination, and phosphorylation, abolished the activation of IκBα kinase, and suppressed p65 nuclear translocation. This effect of thiocolchicoside on the NF-κB pathway led to inhibition of NF-κB reporter activity and cyclooxygenase-2 promoter activity. Our results indicate that thiocolchicoside exhibits anticancer activity through inhibition of NF-κB and NF-κB–regulated gene products, which provides novel insight into a half-century old drug. Cancer Prev Res; 3(11); 1462–72. ©2010 AACR.
Making Sense of Missense in Lynch Syndrome: The Clinical Perspective
Authors: Lynch Henry T. , Jascur Thomas , Lanspa Stephen , Boland C. Richard
Published: October 2010

The DNA mismatch repair (MMR) system provides critical genetic housekeeping, and its failure is associated with tumorigenesis. Through distinct domains on the DNA MMR proteins, the system recognizes and repairs errors occurring during DNA synthesis, but signals apoptosis when the DNA damage cannot be repaired. Certain missense mutations in the MMR genes can selectively alter just one of these functions. This affects the clinical features of tumors associated with defective DNA MMR activity. New work reported by Xie et al. in this issue of the journal (beginning on page 1409) adds to the understanding of DNA MMR. Cancer Prev Res; 3(11); 1371–4. ©2010 AACR.
Breaking the NF-κB and STAT3 Alliance Inhibits Inflammation and Pancreatic Tumorigenesis
Authors: Surh Young-Joon , Bode Ann M. , Dong Zigang
Published: October 2010

This perspective on Liby et al. (beginning on page 1427 in this issue of the journal) discusses the importance of the finding that two synthetic triterpenoids prolonged survival in a pancreatic cancer mouse model. This finding is significant because pancreatic cancer is one of the deadliest human cancers. These compounds inhibited the interaction between NF-κB and signal transducer and activator of transcription 3, and determining the mechanisms underlying this inhibition will help to rapidly move these compounds into phase I clinical trials. Cancer Prev Res; 3(11); 1379–81. ©2010 AACR.
Venous thromboembolism in medical outpatients – a cross-sectional survey of risk assessment and prophylaxis
Authors: Lawall Holger , Matthiessen Andreas , Hohmann Volker , Bramlage Peter , Haas Sylvia , Schellong Sebastian
Published: October 2010

The degree of thromboprophylaxis in medical outpatients is low despite a substantial risk for venous thromboembolism (VTE). This may be attributable to difficulties in assessing risk. Assessment tools like the Haas’ scorecard aid in determining the need for thromboprophylaxis. We aimed at evaluating how the use of this tool may aid physicians in appropriately using anticoagulants. This was an epidemiological, cross-sectional survey of acute medically ill patients with limited mobility treated by general practitioners and internists. Risk assessment for VTE by the treating physician was compared to calculated risk. Of 8,123 patients evaluated between August 2006 and April 2008, 7,271 fulfilled the in- and exclusion criteria. Mean age was 69.4 ± 13.6 years, and 45.2% were male. Of these 82.8% were high risk based on their acute medical condition, 37.9% based on their underlying chronic condition. Immobilisation, heart failure, pneumonia, age, obesity, and major varicosis were the most frequently encountered risk factors. The agreement between the Haas’ scorecard and physician indicated risk was high. At least 94.1% of patients with high risk received adequate anticoagulation mostly as low molecular weight heparins for a mean duration of 15.1 ± 30.5 days. There is a substantial risk for VTE in medical out-patients. Using a simple structured scorecard resulted in an overall appropriate risk assessment and high degree of anticoagulation. The scorecard may provide a tool to improve the overall awareness for VTE risk in medical outpatients, substantially improving the degree of prophylaxis in a patient population with largely underestimated risk.
Effects of Aggrenox and aspirin on plasma endothelial nitric oxide synthase and oxidised low-density lipoproteins in patients after ischaemic stroke
Authors: Sani Yanti , Eisert Christian , Schevchuck Alex , Fong Alan , Hanley Dan , Serebruany Victor
Published: October 2010

Plasma endothelial nitric oxide synthase (eNOS), and oxidised low-density lipoproteins (oxLDL) are established biomarkers of atherosclerosis. We defined the time course and magnitude of changes of plasma eNOS and oxLDL after Aggrenox or aspirin in post-stroke patients. Baseline pretreatment eNOS levels were significantly diminished (110 ± 66pg /ml vs. 374 ± 88 pg/ml, p=0.0001), while oxLDL was twice higher (58 ± 9 mg/l vs. 23 ± 7 mg/l, p=0.004) in post-stroke survivors when compared to controls. Both Aggrenox and aspirin similarly increased plasma eNOS activity. However, oxLDL levels were static after aspirin, but inhibited late after Aggrenox. In the small randomised study, both aspirin and Aggrenox produced fast and sustained recovery of plasma eNOS levels, while only therapy with Aggrenox was associated with oxLDL inhibition late in the trial.
Human endothelial and platelet septin SEPT11: Cloning of novel variants and characterisation of interaction partners
Authors: Bartsch Ingrid , Bläser Susanne , Röseler Sabrina , Sandrock Kirstin , Busse Anja , Huber Michael , Rempp Hansjörg , Lieber Mareike , Horn Julia , Brendle Cornelia , Zieger Barbara
Published: October 2010

Septins are cytoskeletal GTPases forming heteropolymeric complexes involved in processes characterised by active membrane movement such as cytokinesis, vesicle trafficking, and exocytosis. Septins are expressed in non-mitotic cells such as neurons and platelets. SEPT11 belongs to the SEPT6 group and was identified as interaction partner of SEPT5. We cloned and characterised novel SEPT11 variants and investigated interaction partners of SEPT11 in platelets and human umbilical vein endothelial cells. An endothelial cell library was used for cloning novel SEPT11 variants. Using Northern analysis the different SEPT11 transcripts were illustrated. Interaction studies were performed using yeast two-hybrid system, precipitation, FRET, and immunofluorescence microscopy. We demonstrate that SEPT11 partners with SEPT2, SEPT4 and SEPT7 using yeast two-hybrid system and precipitation. The interaction of SEPT11 with SEPT7 is also demonstrated by FRET. In addition to the known SEPT11 transcript (SEPT11_v1) we identified a novel SEPT11 variant (SEPT11_v2) as interaction partner of SEPT4 and SEPT7. Library screening of an endothelial cell library also revealed the presence of this novel SEPT11_v2 transcript. In addition, a third SEPT11 variant (SEPT11_v3) was identified. Expression of SEPT11_v1 and of SEPT11_v2 and SEPT11_v3 in human brain regions was investigated by Northern analysis. Further interaction partners of SEPT11 are characterised using immunofluorescence. Co-localisation of SEPT2, SEPT4, SEPT7 and SEPT11 with tubulin and transferrin receptor (endocytotic marker) is demonstrated. In addition, co-localisation of SEPT4 and SEPT11 with the vesicle-associated protein synaptobrevin 1 (VAMP1), but not clearly with actin, was shown. Only SEPT2 and SEPT7 definitely co-localised with actin, but not clearly with VAMP1.
The 2008 World Financial Crisis and Market Quality Theory
Authors: Yano Makoto
Published: October 2010

The present study demonstrates that the current world financial crisis is attributable to, among other things, the failure to coordinate Japanese and U.S. monetary policies in 2004, allowing Japan to abandon its currency intervention while pegging its interest rate at zero at the same time that the United States departed from its low interest rate policy. At a deeper level, these factors can be explained by the productivity increases resulting from the internet technology revolution, which lowered market quality by rendering obsolete the market infrastructure built in the latter half of the twentieth century.
United States, Japanese, and Korean FDI and Intra–East Asian Trade
Authors: Fung Kwong-Chiu , Iizaka Hitomi , Siu Alan
Published: October 2010

This paper documents the growing importance of intra–East Asian trade of parts and components. Our empirical analysis shows that foreign direct investment (FDI) does play an important and independent role in facilitating the trade of parts and components in East Asia. This is true for FDI from all three source countries: the United States, Japan, and South Korea. Furthermore, our empirical studies show that compared with U.S. and Korean FDI, FDI from Japan has a particularly strong influence on trade in parts and components as well as trade in capital goods. One policy implication is that economies need to improve their physical infrastructure as well as the quality of their institutions to integrate further into the East Asian production network.
‘Duty to Act’ and ‘Commission by Omission’ in International Criminal Law
Authors: Berster Lars C.
Published: October 2010

Whether a general rule on omission exists in international criminal law has long been fraught with controversy. It has recently met with increasing acceptance, most prominently by the ICTY Appeals Chamber’s judgement of 5 May 2009 (Prosecutor v. Mrkšić et al.). In view of the likely further consolidation of the law, this study deals with the material requirements of ‘commission by omission’ more comprehensively. It tests several possible ways to give meaning to the offender’s duty to prevent the incriminated action, as the ‘duty to act’ is widely seen as the key to criminal liability for omission. In particular, the present article challenges the prevailing trend in international case law and scholarship to derive individual duties to act from duties under international humanitarian law or domestic law. The alternative approach put forward herein is to derive duties to act genuinely from international criminal law.This is done by extending the ‘principle of control’, which according to ICC case law constitutes the underlying base for ‘commission by action’, to the sphere of omission. There, the overarching criterion of control can be broken down into a set of clear-cut duties to act and thus be reconciled with the requirements of legal certainty. Eventually, it is shown that pursuant to the present approach ‘commission by omission’, albeit not explicitly contemplated by the ICC Statute, falls within the jurisdiction of the ICC.
‘Only One Step Away From Genocide’:The Crime of Persecution in International Criminal Law
Authors: Fournet Caroline , Pégorier Clotilde
Published: October 2010

The law of persecutions has given rise to a certain definitional instability and judicial unease, notably due to the fact that the crime itself falls short of a definitive and comprehensive definition. As this article proposes to argue, this legal opacity could be unveiled by revisiting the law of Nuremberg, which, through the creation of the new crime against humanity of ‘persecutions’, might have in reality marked the birth in positive international law of the concept of ‘genocide’ itself. By keeping the crime of persecutions within the definitional ambit of crimes against humanity while simultaneously emancipating and recognizing genocide as a separate and distinct crime, contemporary international law has generated legal uncertainty and misconceptions as well as judicial unease, so much so that persecutions now found themselves somewhere between crimes against humanity and genocide. Not only is this definitional floating and opacity troublesome from a legality perspective, it also misunderstands the Nuremberg precedent and ultimately risks trivializing the essence of the crime of genocide itself.
Negotiated History:The Historical Record in International Criminal Law and Plea Bargaining
Authors: Rauxloh Regina E.
Published: October 2010

One of the most important functions of the international criminal trial is to create an accurate and accessible historical record. This paper analyses to what extent plea bargaining can hinder or facilitate the establishment of the historical record. Drawing on the experience of the ICTY and the ICTR the author makes a number of proposals as to what how and to extent plea bargaining should be used at the ICC to advance rather than to obstruct the historical record.
Quelques apports des Tribunaux pénaux internationaux, ad hoc et notamment le TPIR, à la lutte contre les violences sexuelles subies par les femmes Durant les génocides et les conflits armés
Authors: Ayat Mohammed
Published: October 2010

Sexual assault is amongst the most outrageous and rampant weapons of armed conflicts and mass crimes. During the Rwandan genocide in 1994, sexual violence and rape of women were the rule rather than the exception. The international penal tribunals were established with the main objective of fighting impunity of core crimes including the area of sexual violence. This article presents some of the major contributions of international criminal justice, notably the ICTR, to the latter area. It is divided into two parts. The first one deals with the procedure. The analysis notably covers: investigation, witness protection and the rules of evidence used to prove sexual violence. The second part examines the contributions in substantial criminal law. The most salient is the elaboration of an international definition of rape, and the labelling of rape as an act of genocide.