280 research outputs found
BREAKDOWN PRODUCTS OF GASEOUS POLYCYCLIC AROMATIC HYDROCARBONS INVESTIGATED WITH INFRARED ION SPECTROSCOPY
Probing the competition among different coordination motifs in metal-ciprofloxacin complexes through IRMPD spectroscopy and DFT calculations
The vibrational spectra of ciprofloxacin complexes with monovalent (Li+, Na+, K+, Ag+) and polyvalent (Mg2+, Al3+) metal ions are recorded in the range 1000-1900 cm(-1) by means of infrared multiple-photon dissociation (IRMPD) spectroscopy. The IRMPD spectra are analyzed and interpreted in the light of density functional theory (DFT)-based quantum chemical calculations in order to identify the possible structures present under our experimental conditions. For each metal-ciprofloxacin complex, four isomers are predicted, considering different chelation patterns. A good agreement is found between the measured IRMPD spectrum and the calculated absorption spectrum of the most stable isomer for each complex. Metal ion size and charge are found to drive the competition among the different coordination motifs: small size and high charge density metal ions prefer to coordinate the quinolone between the two carbonyl oxygen atoms, whereas large-size metal ions prefer the carboxylate group as a coordination site. In the latter case, an intramolecular hydrogen bond compensates the weaker interaction established by these cations. The role of the metal cation on the stabilization of ionic and nonionic structures of ciprofloxacin is also investigated. It is found that large-size metal ions preferentially stabilize charge separated motifs and that the increase of metal ion charge has a stabilizing effect on the zwitterionic form of ciprofloxacin
Action spectroscopy of gas-phase carboxylate anions by multiple photon IR electron detachment/attachment
We report on a form of gas-phase anion action spectroscopy based on infrared
multiple photon electron detachment and subsequent capture of the free
electrons by a neutral electron scavenger in a Fourier Transform Ion Cyclotron
Resonance (FTICR) mass spectrometer. This method allows one to obtain
background-free spectra of strongly bound anions, for which no dissociation
channels are observed. The first gas-phase spectra of acetate and propionate
are presented using SF6 as electron scavenger and a free electron laser as
source of intense and tunable infrared radiation. To validate the method, we
compare infrared spectra obtained through multiple photon electron
detachment/attachment and multiple photon dissociation for the benzoate anion.
In addition, different electron acceptors are used, comparing both associative
and dissociative electron capture. The relative energies of dissociation (by
CO2 loss) and electron detachment are investigated for all three anions by DFT
and CCSD(T) methods. DFT calculations are also employed to predict vibrational
frequencies, which provide a good fit to the infrared spectra observed. The
frequencies of the symmetric and antisymmetric carboxylate stretching modes for
the aliphatic carboxylates are compared to those previously observed in
condensed-phase IR spectra and to those reported for gas-phase benzoate,
showing a strong influence of the solution environment and a slight substituent
effect on the antisymmetric stretch.Comment: Revised version, Submitted to J Phys Chem
Novel cerebrospinal fluid biomarkers of glucose transporter type 1 deficiency syndrome: Implications beyond the brain's energy deficit
We used next-generation metabolic screening to identify new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS), comparing metabolic cerebrospinal fluid (CSF) profiles from 12 patients to those of 116 controls. This confirmed decreased CSF glucose and lactate levels in patients with GLUT1DS and increased glutamine at group level. We identified three novel biomarkers significantly decreased in patients, namely gluconic + galactonic acid, xylose-α1-3-glucose, and xylose-α1-3-xylose-α1-3-glucose, of which the latter two have not previously been identified in body fluids. CSF concentrations of gluconic + galactonic acid may be reduced as these metabolites could serve as alternative substrates for the pentose phosphate pathway. Xylose-α1-3-glucose and xylose-α1-3-xylose-α1-3-glucose may originate from glycosylated proteins; their decreased levels are hypothetically the consequence of insufficient glucose, one of two substrates for O-glucosylation. Since many proteins are O-glucosylated, this deficiency may affect cellular processes and thus contribute to GLUT1DS pathophysiology. The novel CSF biomarkers have the potential to improve the biochemical diagnosis of GLUT1DS. Our findings imply that brain glucose deficiency in GLUT1DS may cause disruptions at the cellular level that go beyond energy metabolism, underlining the importance of developing treatment strategies that directly target cerebral glucose uptake
Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study
Treatment decisions after diagnosis of clinically localised prostate cancer are difficult due to variability in tumour behaviour. We therefore examined one of the most promising biomarkers in prostate cancer, Ki-67, in a cohort of 808 patients diagnosed with prostate cancer between 1990 and 1996 and treated conservatively. Ki-67 expression was assessed immunohistochemically, in two laboratories, by two different scoring methods and the results compared with cancer-specific and overall survival. The power of the biomarker was compared with Gleason score and initial serum prostate-specific antigen (PSA). Both methods showed that Ki-67 provided additional prognostic information beyond that available from Gleason score and PSA: for the semi-quantitative method, Δχ2 (1 d.f.)=24.6 (P<0.0001), overall survival χ2=20.5 (P<0.0001), and for the quantitative method, Δχ2 (1 d.f.)=15.1 (P=0.0001), overall survival χ2=10.85 (P=0.001). Ki-67 is a powerful biomarker in localised prostate cancer and adds to a model predicting the need for radical or conservative therapy. As it is already in widespread use in routine pathology, it is confirmed as the most promising biomarker to be applied into routine practice
Extramuscular myofascial force transmission alters substantially the acute effects of surgical aponeurotomy: assessment by finite element modeling
Effects of extramuscular myofascial force transmission on the acute effects of aponeurotomy were studied using finite element
modeling and implications of such effects on surgery were discussed. Aponeurotomized EDL muscle of the rat was modeled in
two conditions: (1) fully isolated (2) with intact extramuscular connections. The specific goal was to assess the alterations
in muscle length-force characteristics in relation to sarcomere length distributions and to investigate how the mechanical
mechanism of the intervention is affected if the muscle is not isolated. Major effects of extramuscular myofascial force transmission
were shown on muscle length-force characteristics. In contrast to the identical proximal and distal forces of the aponeurotomized
isolated muscle, substantial proximo-distal force differences were shown for aponeurotomized muscle with extramuscular connections
(for all muscle lengths F
dist > F
prox after distal muscle lengthening). Proximal optimal length did not change whereas distal optimal length was lower (by 0.5 mm).
The optimal forces of the aponeurotomized muscle with extramuscular connections exerted at both proximal and distal tendons
were lower than that of isolated muscle (by 15 and 7%, respectively). The length of the gap separating the two cut ends of
the intervened aponeurosis decreases substantially due to extramuscular myofascial force transmission. The amplitude of the
difference in gap length was muscle length dependent (maximally 11.6% of the gap length of the extramuscularly connected muscle).
Extramuscular myofascial force transmission has substantial effects on distributions of lengths of sarcomeres within the muscle
fiber populations distal and proximal to the location of intervention: (a) Within the distal population, the substantial sarcomere
shortening at the proximal ends of muscle fibers due to the intervention remained unaffected however, extramuscular myofascial
force transmission caused a more pronounced serial distribution towards the distal ends of muscle fibers. (b) In contrast,
extramuscular myofascial force transmission limits the serial distribution of sarcomere lengths shown for the aponeurotomized
isolated muscle in the proximal population. Fiber stress distributions showed that extramuscular myofascial force transmission
causes most sarcomeres within the aponeurotomized muscle to attain lengths favorable for higher force exertion. It is concluded
that acute effects of aponeurotomy on muscular mechanics are affected greatly by extramuscular myofascial force transmission.
Such effects have important implications for the outcome of surgery performed to improve impeded function since muscle in
vivo is not isolated both anatomically and mechanically
Protomers of Benzocaine: Solvent and Permittivity Dependence
The immediate environment of a molecule can have a profound influence on its properties. Benzocaine, the ethyl ester of para-aminobenzoic acid, which finds an application as a local anesthetic (LA), is found to adopt in its protonated form at least two populations of distinct structures in the gas phase and their relative intensities strongly depend on the properties of the solvent used in the electrospray ionization (ESI) process. Here we combine IR-vibrational spectroscopy with ion mobility-mass spectrometry (IM-MS) to yield gas-phase IR spectra of simultaneously m/z and drift-time resolved species of benzocaine. The results allow for an unambiguous identification of two protomeric species - the N- and O-protonated form. Density functional theory (DFT) calculations link these structures to the most stable solution and gas-phase structures, respectively, with the electric properties of the surrounding medium being the main determinant for the preferred protonation site. The fact that the N-protonated form of benzocaine can be found in the gas phase is owed to kinetic trapping of the solution phase structure during transfer into the experimental setup. These observations confirm earlier studies on similar molecules where N- and O-protonation has been suggested
The structure of deprotonated tri-alanine and its a 3− fragment anion by IR spectroscopy
Formation of polycyclic aromatic hydrocarbon grains using anthracene and their stability under UV irradiation
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