Formation of negative and positive ions in the radiosensitizer nimorazole upon low-energy electron collisions.

A comprehensive investigation of low-energy electron attachment and electron ionization of the nimorazole radiosensitizer used in cancer radiation therapy is reported by means of a gas-phase crossed beam experiment in an electron energy range from 0 eV to 70 eV. Regarding negative ion formation, we discuss the formation of fifteen fragment anions in the electron energy range of 0 eV-10 eV, where the most intense signal is assigned to the nitrogen dioxide anion NO2 -. The other fragment anions have been assigned to form predominantly from a common temporary negative ion state close to 3 eV of the nitroimidazole moiety, while the morpholine moiety seems to act only as a spectator in the dissociative electron attachment event to nimorazole. Quantum chemical calculations have been performed to help interpreting the experimental data with thermochemical thresholds, electron affinities, and geometries of some of the neutral molecules. As far as positive ion formation is concerned, the mass spectrum at the electron energy of 70 eV shows a weakly abundant parent ion and C5H10NO+ as the most abundant fragment cation. We report appearance energy (AE) measurements for six cations. For the intact nimorazole molecular cation, the AE of 8.16 ± 0.05 eV was obtained, which is near the presently calculated adiabatic ionization energy.

Low-energy electron-induced decomposition of 5-trifluoromethanesulfonyl-uracil: A potential radiosensitizer.

5-trifluoromethanesulfonyl-uracil (OTfU), a recently proposed radiosensitizer, is decomposed in the gas-phase by attachment of low-energy electrons. OTfU is a derivative of uracil with a triflate (OTf) group at the C5-position, which substantially increases its ability to undergo effective electron-induced dissociation. We report a rich assortment of fragments formed upon dissociative electron attachment (DEA), mostly by simple bond cleavages (e.g., dehydrogenation or formation of OTf-). The most favorable DEA channel corresponds to the formation of the triflate anion alongside with the reactive uracil-5-yl radical through the cleavage of the O-C5 bond, particularly at about 0 eV. Unlike for halouracils, the parent anion was not detected in our experiments. The experimental findings are accounted by a comprehensive theoretical study carried out at the M06-2X/aug-cc-pVTZ level. The latter comprises the thermodynamic thresholds for the formation of the observed anions calculated under the experimental conditions (383.15 K and 3 × 10-11 atm). The energy-resolved ion yield of the dehydrogenated parent anion, (OTfU-H)-, is discussed in terms of vibrational Feshbach resonances arising from the coupling between the dipole bound state and vibrational levels of the transient negative ion. We also report the mass spectrum of the cations obtained through ionization of OTfU by electrons with a kinetic energy of 70 eV. The current study endorses OTfU as a potential radiosensitizer agent with possible applications in radio-chemotherapy.

The situation of sanitary systems in rural areas in the Miyun catchment, China.

The Miyun Reservoir provides most of Beijing's drinking water. Despite its importance, the Miyun reservoir suffers from decreasing water quality caused by uncontrolled wastewater discharges, inadequate land use and over fertilization, which increase the pressure on soil and water resources. The major pollutants are nitrogen and phosphorus which emanate to some extent from untreated sewage. So far there is little data about the existing wastewater quantity and quality in rural settlements in northern China. This study was conducted in typical villages situated along upstream rivers in the catchment of the Miyun Reservoir. The main objective was to determine the current situation and efficiency of the wastewater treatment system in rural settlements.

Strategies to mitigate diffuse phosphorus pollution during rewetting of fen peat soils.

The cultivation of fen peat soils (Eutric Histosols) for agricultural purposes, started in Europe about 250 years ago, resulting in decreased soil fertility, increased oxidation of peat and corresponding greenhouse gas fluxes to the atmosphere, nutrient transfer to aquatic ecosystems and losses in total area of the former native wetlands. To prevent these negative environmental effects set-aside programs and rewetting measures were promoted in recent years. Literature results and practical experiences showed that large scale rewetting of intensively used agricultural Histosols may result in mobilisation of phosphorus (P), its transport to adjacent surface waters and an accelerated eutrophication. The paper summarises results from an international European Community sponsored research project and demonstrates how results obtained at different scales and from different scientific disciplines were compiled to derive a strategy to carry out rewetting measures. Based on this findings a simple decision support system (DSS) for a hydrologically sensitive area in the Droemling catchment in north-eastern Germany was developed and since 2005 practically used to prevent freshwater resources from non point P pollution.

Autoencapsulation through intermolecular forces: a synthetic self-assembling spherical complex.

The synthesis and characterization of a system for the study of molecular recognition phenomena are described. The system involves a tetraurea molecule that is capable of assembly into various associated states through hydrogen bonding. In organic solvents, the dynamic transition between a low-ordered (aggregate) state and a highly ordered dimeric assembly can be induced by the introduction of smaller molecules of appropriate size and shape. These smaller molecules, such as benzene, adamantanes, and ferrocenes, act as guests that occupy the pseudospherical capsule formed by the dimeric host. Among various guests, those that best fill the cavity and offer chemical complementarity to the host are preferentially encapsulated.

Seismic data from man-made impacts on the moon.

Unusually long reverberations were recorded from two lunar impacts by a seismic station installed on the lunar surface by the Apollo 12 astronauts. Seismic data from these impacts suggest that the lunar mare in the region of the Apollo 12 landing site consists of material with very low seismic velocities near the surface, with velocity increasing with depth to 5 to 6 kilometers per second (for compressional waves) at a depth of 20 kilometers. Absorption of seismic waves in this structure is extremely low relative to typical continental crustal materials on earth. It is unlikely that a major boundary similar to the crustmantle interface on earth exists in the outer 20 kilometers of the moon. A combination of dispersion and scattering of surface waves probably explains the lunar seismic reverberation. Scattering of these waves implies the presence of heterogeneity within the outer zone of the mare on a scale of from several hundred meters (or less) to several kilometers. Seismic signals from 160 events of natural origin have been recorded during the first 7 months of operation of the Apollo 12 seismic station. At least 26 of the natural events are small moonquakes. Many of the natural events are thought to be meteoroid impacts.

Impact of the Conformational Variability of Oligopeptides on the Computational Prediction of Their CD Spectra.

Although successful in the structural determination of ordered biomolecules, the spectroscopic investigation of oligopeptides in solution is hindered by their complex and rapidly changing conformational ensemble. The measured circular dichroism (CD) spectrum of an oligopeptide is an ensemble average over all microstates, severely limiting its interpretation, in contrast to ordered biomolecules. Spectral deconvolution methods to estimate the secondary structure contributions in the ensemble are still mostly based on databases of larger ordered proteins. Here, we establish how the interpretation of CD spectra of oligopeptides can be enhanced by the ability to compute the same observable from a set of atomic coordinates. Focusing on two representative oligopeptides featuring a known propensity toward an α-helical and ß-hairpin motif, respectively, we compare and cross-validate the structural information coming from deconvolution of the experimental CD spectra, sequence-based de novo structure prediction, and molecular dynamics simulations based on enhanced sampling methods. We find that small conformational variations can give rise to significant changes in the CD signals. While for the simpler conformational landscape of the α-helical peptide de novo structure prediction can already give reasonable agreement with the experiment, an extended ensemble of conformers needs to be considered for the ß-hairpin sequence.

Evaluation of the polymorphisms in the exons 2 to 4 of the TP53 in cervical carcinoma patients from a Brazilian population.

The majority of TP53 polymorphisms and cervical cancer association studies have only analyzed codon 72 polymorphism. Eight polymorphisms were reported in the region encompassing exon 2 to 4 of TP53 that codify the aminoterminal p53 region containing domains involved in the transcription transactivation and apoptosis induction. We investigated if the polymorphisms present in this region were associated with cervical cancer risk. A total of 140 samples (83 from Brazilian patients with cervical carcinoma and 57 from Brazilian healthy women) were analyzed by PCR and DNA sequencing. Only three from the eight TP53 polymorphisms described in the analyzed region were polymorphic within our samples: the 11827 base from intron 2, the 16bp duplication in the intron3 and the codon 72 (Arg>Pro) from exon 4. No statistically significant association was observed between polymorphisms from intron 2 and the 16bp duplication from intron 3 with cervical cancer. No statistically significant difference in the frequency of homozygotes for Arg in relation to other genotypes was found when comparing patient and healthy groups (OR=0.70; 95% CI= 0.31-1.56; p= 0.222). However, Arg/Pro heterozygotes were more frequent within HPV positive cancer patients than in healthy women (p=0.023; OR (Arg/Pro:Pro/Pro)= 5.82; 95% CI: 1.22-30.78; p=0.024).

Effect of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--I. Growth hormone.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced growth hormone (GH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). DMI-induced GH stimulation was not significantly different after DMI i.v. alone (n = 12) than after three days' pretreatment with 12 mg methysergide p.o. in another group of subjects (n = 12). Following combined administration of DMI and propranolol (15 mg i.v.), GH secretion was significantly increased by 25 mg DMI (p less than 0.05) and 50 mg DMI (incomplete block design, n = 18). GH secretion was significantly lower (p less than 0.01) after DMI in combination with 60 mg phentolamine i.v. compared to that after administration of DMI alone in the same group (n = 12). Following 10 mg yohimbine i.v. in combination with DMI (n = 6), the DMI-induced GH increase was also significantly less (p less than 0.05) than that after DMI alone. The DMI-induced GH increase following DMI plus 1 mg prazosin p.o. (n = 12) was comparable to that after DMI alone. The results indicate that the GH-stimulating effect of DMI is primarily related to the ability of DMI to inhibit noradrenaline (NA) reuptake. Should serotonergic receptors be involved in the DMI-induced GH secretion at all, they transmit a positive stimulus. The alpha-1 receptors are most likely not (or not essentially) involved, whereas alpha-2 receptors affect the DMI-induced secretion positively, and beta receptors have an inhibitory effect.

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--II. Prolactin.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced prolactin (PRL) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). Following administration of methysergide (12 mg p.o., n = 12), a significantly lower (p less than 0.01) DMI-induced PRL secretion compared to DMI alone in another group of subjects (n = 12) was observed. Combined administration with propranolol (15 mg i.v.) significantly enhanced the DMI-induced PRL secretion compared to DMI 50 mg i.v. alone (n = 18, incomplete block design) (p less than 0.01). Neither combined administration with phentolamine (60 mg i.v., n = 12), yohimbine (10 mg i.v., n = 6), nor prazosin (1 mg p.o., n = 12) significantly influenced the DMI-induced PRL secretion compared to DMI alone in the same subjects. The results of the present study, especially the inhibitory effect on DMI-induced PRL secretion of methysergide, indicate that the primarily noradrenaline (NA) and lesser serotonin (5-HT) reuptake inhibiting antidepressant DMI stimulates PRL secretion via 5-HT neurons. Furthermore, the significantly enhanced PRL release following combined administration of DMI and propranolol suggests that a noradrenergic inhibitory effect also may be involved in the transmission of the PRL stimulus.

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--III. Hypothalamo-pituitary-adrenocortical axis.

In this report the effects of various receptor blockers on the desimipramine (DMI)-induced cortisol (ACTH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker, i.e. methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). In addition, the effect of prazosin on DMI-induced ACTH stimulation was examined. DMI-induced cortisol stimulation was not significantly different after DMI alone (n = 12) from that after three days pretreatment with methysergide (12 mg p.o.) in another group of subjects (n = 12). Neither the combination of DMI plus propranolol (15 mg i.v. n = 18, incomplete block design) nor that of DMI plus phentolamine (60 mg i.v. n = 12) had a significant influence on DMI-induced cortisol secretion. Following combined administration with yohimbine (10 mg i.v.), cortisol secretion was higher compared to that after DMI alone in the same group (n = 6). DMI-induced cortisol secretion was significantly lower (p less than 0.01) following combined administration with prazosin (1 mg p.o. n = 12), as was DMI-induced ACTH secretion (p less than 0.05) in these subjects. The findings of these trials, especially those of the prazosin trial, indicate that DMI-induced stimulation of cortisol and ACTH secretion is attributable to the noradrenaline (NA) reuptake inhibiting effect of DMI, and that the stimulus is transmitted with the aid of noradrenergic alpha-1 receptors. Alpha-2 receptors possibly exert a negative influence on this effect.

The impact of pulse pressure on the accuracy of wrist blood pressure measurement.

There is an increasing number of wrist blood pressure measurement devices that successfully passed the validation procedures of the British Hypertension Society (BHS) and the European Society of Hypertension (ESH). It remains unknown, however, whether pulse pressure as a marker of arterial stiffness and vascular ageing affects the accuracy of these devices. An ESH protocol validated wrist device was compared with the upper arm mercury sphygmomanometry in a study population (33 patients, 99 measurements) including a relevant number of subjects with pulse pressure >50 mm Hg (84.8%) and isolated systolic hypertension (27.3%). Mean systolic bias was 10.2 mm Hg with 95% limits of agreement of -13.1 and 33.6 mm Hg, mean diastolic bias was 4.8 mm Hg with limits of agreement of -11.0 and 20.7 mm Hg. The impact of body mass index, age, systolic blood pressure and pulse pressure on the absolute value of blood pressure bias was tested by stepwise multiple regression analysis. The systolic bias significantly depended on pulse pressure, whereas there was no significant effect of the independent variables on the diastolic bias. Separate correlation analysis showed a significant correlation between pulse pressure and both absolute systolic bias (Pearson r=0.48, P<0.001) and relative systolic bias (systolic bias divided by systolic blood pressure, Pearson r=0.29, P=0.003). Even well-validated wrist blood pressure devices can show a clinically relevant bias in patients with elevated pulse pressure. Increased arterial stiffness may impair the accuracy of oscillometric blood pressure measurement at the wrist.

[Nystagmus findings during sudden deafness and their estimation (author's transl)]. / Vestibularisbefunde bei der plötzlichen einseitigen Innenohrhörstörung und ihre Bewertung.

Seventy-three of 172 patients with sudden deafness had a vestibular participation. The found forms of spontaneous and provoked nystagmus, their partial combination with thermic under- or non-excitability of the labyrinth as well as vertigo complaints of the patients are described, especially in their temporal course during the illness. The frequent vestibular participation during sudden deafness entitles to introduce the term "range of forms of peripheral-vascular conditioned labyrinthine disturbances", whose cornerstones are the sudden isolated peripheral deafness and the sudden isolated peripheral vestibular loss with a number of intermediate forms. In addition to this, the stronger consideration of the vestibular findings during sudden deafness facilitates the otherwise often difficult differential diagnosis of Menière's syndrome: that one differs by the lacking increase of direction-fixed spontaneous or positional nystagmus to the cochlearly injured ear, incidences of central forms of nystagmus, and the possibility of temporal occurrence of the vestibular findings after the cochlear damage.

Behavior of the nystagmus in Menière's attack.

Continuous controls of the nystagmus were carried out from the beginning of Menière's attack. There are four different forms of development. As to the direction of the nystagmus and the directional change of nystagmus during an attack, respectively, a possible neurophysiologic explanation can be offered: due to an increased concentration of potassium in the perilymphatic space during a Menière attack there is a depolarization of the synapse between the vestibular receptive cell and the afferent nerve fiber. The potassium concentration determines the extent of depolarization and thus the direction of the nystagmus.

[Double-sided central hearing-loss owing to bitemporal infarct of brain (author's transl)]. / Doppelseitige zentrale Hörstörung infolge bitemporalen Hirninfarktes.

Information about a sudden bilateral hearing-loss in form of sudden deafness due to bitemporal infarct of brain. The difficulties of diagnosis of cortical and subcortical hearing-disturbances are presented in detail.

[Symptomatology of sphenoid sinus mucoceles]. / Beitrag zur Symptomatologie der Keilbeinhöhlenmukozelen.

Two rare cases of sphenoid sinus mucoceles are reported. The main complaints of both patients were headache, palsies of eye movements and loss of vision. The usually long anamnesis, the clinical and radiological signs and the findings of computed tomography are described. The only therapy is the operation which aims to create a large discharge to the nose.

[Secondary transurethral surgery of the bladder neck]. / Transurethrale Zweiteingriffe am Blasenhals.

In the period from 1970 to 1978 24 patients after transvesical adenomectomy and 76 patients after TUR of the prostate gland underwent a secondary transurethral surgical intervention. Causes were residual adenomas, stenoses of the vesical neck and recidivations of the adenoma. Explanations are given for the differences in the course of the temporary coordination to the primary intervention. The preoperative situation concerning infections, problems of the operation technique and in the case of the TUR the qualification of the resectionists are mentioned. After the TUR as primary intervention clearly less carcinomas were proved in the electro-resectate in comparison to the transvesical adenomectomy.