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Die Arthrose als weltweit haufigste Gelenkerkrankung des erwachsenen Menschen beschreibt die fortlaufende Zerstorung eines Gelenks entweder als primare Erkrankung bei altersbedingter Degeneration oder auf der Grundlage sekundarer Ursachen. Die Erkrankung nimmt ihren Ausgang in der Regel vom Gelenkknorpel und erfasst im Verlauf alle artikularen und periartikularen Strukturen der gelenkigen Funktionseinheit. Fur den betroffenen Patienten resultiert regelhaft ein zunehmender schmerzhafter Funktionsverlust mit einer wesentlichen Reduktion der Lebensqualitat. Vielfach kann eine Behandlung uber viele Jahre erfolgreich mit konservativen Masnahmen gestaltet werden. Sollte hiermit keine ausreichende Kontrolle des Leidensdrucks mehr erreichbar sein, muss die Option einer operativen Intervention diskutiert werden. Die aktuellen Bemuhungen der Grundlagenforschung fokussieren derzeit auf das Ziel einer moglichst fruhzeitigen Unterbrechung und bestenfalls vollstandigen Vorbeugung des Degenerationsprozesses.

Contrast agents for magnetic resonance imaging (MRI) are essential for evidential visualization of soft tissues pathologies. Contrast-enhanced MRI can be carried out with T

Objectives: To investigate the technical feasibility of whole-body intravoxel incoherent motion (IVIM) imaging. Materials and Methods: Whole-body MR images of eight healthy volunteers were acquired at 3T using a spin-echo echo-planar imaging sequence with eight b-values. Coronal parametrical whole-body maps of diffusion (D), pseudodiffusion (D*), and the perfusion fraction (Fp) were calculated. Image quality was rated qualitatively by two independent radiologists, and inter-reader reliability was tested with intra-class correlation coefficients (ICCs). Region of interest (ROI) analysis was performed in the brain, liver, kidney, and erector spinae muscle. Results: Depiction of anatomic structures was rated as good on D maps and good to fair on D* and Fp maps. Exemplary mean D (10−3mm2/s), D* (10−3mm2/s) and Fp (%) values (± standard deviation) of the renal cortex were as follows: 1.7 ± 0.2; 15.6 ± 6.5; 20.9 ± 4.4. Inter-observer agreement was "substantial” to "almost perfect” (ICC = 0.80 - 0.92). The coefficient of variation of D* was significantly lower with the proposed algorithm compared to the conventional algorithm (p

Ultrashort pulse micromachining has found a rising number of applications in a variety of scientific and industrial fields. In order to address the growing field of applications, target materials and customer requirements, a high degree of pulse parameter flexibility and ease of integration is needed. The newest generation of the TruMicro Series 2000 delivers unique features such as fast tunable pulse duration, MHz- up to GHz-burst modes in combination with flexible Pulse on Demand and elevated average power of 100W for improved productivity scaling. Three available wavelengths (343nm, 515nm, 1030nm), an integrated hollow-core fiber interface, as well as a new advanced ultrashort pulse laser control, all combined into a new one box optomechanical design with identical interfaces and dimensions opens new paths for cutting-edge applications. The improved flexibility enables fast (

Ultrafast micromachining has found broad applications in a variety of scientific and industrial fields. Different materials and competing customer requirements (surface quality vs. processing speed vs. surface structure etc.) call for parameter studies prior to volume production as well as pulse parameter flexibility during operation. Up to now, often a nonoptimized point of operation for either best speed or quality had to be chosen due to limited laser source flexibility. TruMicro Series 2000 introduces true inter- and intra-process flexibility for pulse parameters such as pulse duration, pulse energy and pulse spacing up to GHz bursts. As of now, switching the pulse duration is possible within 300 fs and 20 ps in less than 600 ms without affecting beam pointing or energy stability. Therefore, intra-process pulse parameter changes allow maximization of the ablation-volume efficiency in one step and surface-quality optimization in a second, finalizing step. Additionally, inter-process pulse parameter changes enable material changes in between workpieces. In this contribution, we show how this novel flexibility for the first time leads to comprehensive and automated parameter studies that allow for next-generation process understanding and the clear selection of enhanced points of operation. We demonstrate how ablation of various materials can be increased by employing bursts on a nanosecond timescale where a simple increase in fluence would result in cone-like protrusions. Choosing the suitable timescale for energy deposition can either maximize energy efficiency of ablation or optimize ablation quality. With the TruMicro Series 2000, both optima can be combined to one efficient, high-quality process.

High-Z metal oxide nanoparticles hold promise as imaging probes and radio-enhancers. Hafnium dioxide nanoparticles have recently entered clinical evaluation. Despite promising early clinical findings, the potential of HfO2 as a matrix for multimodal theranostics is yet to be developed. Here, we investigate the physicochemical properties and the potential of HfO2-based nanoparticles for multimodal theranostic imaging. Undoped and lanthanide (Eu3+, Tb3+, and Gd3+)-doped HfO2 nanoparticles were synthesized and functionalized with various moieties including poly(vinylpyrrolidone) (PVP), (3-aminopropyl)triethoxysilane (APTES), and folic acid (FA). We show that different synthesis routes, including direct precipitation, microwave-assisted synthesis, and sol-gel chemistry, allow preparation of hafnium dioxide particles with distinct physicochemical properties. Sol-gel based synthesis allows preparation of uniform nanoparticles with dopant incorporation efficiencies superior to the other two methods. Both luminescence and contrast properties can be tweaked by lanthanide doping. We show that MRI contrast can be unified with radio-enhancement by incorporating lanthanide dopants in the HfO2 matrix. Importantly, ion leaching from the HfO2 host matrix in lysosomal-like conditions was minimal. For Gd:HfO2 nanoparticles, leaching was reduced >10× compared to Gd2O3, and no relevant cytotoxic effects have been observed in monocyte-derived macrophages for nanoparticle concentrations up to 250 μg/mL. Chemical surface modification allows further tailoring of the cyto- and hemocompatibility and enables functionalization with molecular targeting entities, which lead to enhanced cellular uptake. Taken together, the present study illustrates the manifold properties of HfO2-based nanomaterials with prospective clinical utility beyond radio-enhancement.

Water flow in partially oriented intravoxel compartments mimics an anisotropic fast-diffusion regime, which contributes to the signal attenuation in diffusion-weighted images. In the abdominal organs, this flow may reflect physiological fluid movements (eg, tubular urine flow in kidneys, or bile flow through the liver) and have a clinical relevance. This study investigated the influence of anisotropic intravoxel water flow on diffusion tensor imaging (DTI) of the abdominal organs. Diffusion-weighted images were acquired in five healthy volunteers using an EPI sequence with diffusion preparation (TR/TE: 1000 ms/71 ms; b-values: 0, 10, 20, 40, 70, 120, 250, 450, 700, 1000 s/mm2 ; 12 noncollinear diffusion-encoding directions). DTI of liver and kidneys was performed assuming (i) monoexponential decay of the diffusion-weighted signal, and (ii) accounting for potential anisotropy of the fast-diffusion compartments using a tensorial generalization of the IVIM model. Additionally, potential dependency of the metrics of the tensors from the anatomical location was evaluated. Significant differences in the metrics of the diffusion tensor (DT) were found in both liver and kidneys when comparing the two models. In both organs, the trace and the fractional anisotropy of the DT were significantly higher in the monoexponential model than when accounting for perfusion. The comparison of areas of the liver proximal to the hilum with distal regions and of renal cortex with the medulla also proved a location dependency of the size of the fast-diffusion compartments. Pseudo-diffusion correction in DTI enables the assessment of the solid parenchyma regardless of the organ perfusion or other pseudo-diffusive fluid movements. This may have a clinical relevance in the assessment of parenchymal pathologies (eg, liver fibrosis). The fast pseudo-diffusion components present a detectable anisotropy, which may reflect the hepatic microcirculation or other sources of mesoscopic fluid movement in the abdominal organs.

Purpose To determine whether magnetization transfer (MT) magnetic resonance (MR) imaging may serve as a quantitative measure of the degree of fiber formation during differentiation of muscle precursor cells into engineered muscle tissue as a potential noninvasive monitoring tool in mice. Materials and Methods The study was approved by the local ethics committee (no. StV 01/2008) and the local Veterinary Office (license no. 99/2013). Human muscle progenitor cells (hMPCs) derived from rectus abdominis muscles were subcutaneously injected into CD-1 nude mice (CD-1 nude mice, Crl:CD1-Foxn1

To investigate the feasibility of magnetization transfer (MT) imaging in mice in vivo for the assessment of cortical bone. MT-zero echo time data were acquired at 4.7 T in six mice using MT preparation pulses with two different flip angles (FAs) and a series of ten different off-resonance frequencies (500–15000 Hz). Regions of interest were drawn at multiple levels of the femoral cortical bone. The MT ratio (MTR) was computed for each combination of FAs and off-resonance frequencies. T1 measurements were used to estimate the direct saturation (DS) using a Bloch equation simulation. Estimation of the absorption line width of cortical bone from T2* measurements was also performed. MTR values were higher using 3000° FA than 1000° FA. MTR values decreased toward higher off-resonance frequencies. Maximum mean MTR ± standard deviation (SD) of 58.57 ± 5.22 (range 50.44–70.61) was measured with a preparation pulse of 3000° and off-resonance frequency of 500 Hz. Maximum “true” MT effect was estimated at around 2–3 and 5 kHz, respectively, for 1000° and 3000° FA. Mean full width at half maximum ± SD of 577 ± 91 Hz was calculated for the absorption spectral line of the cortical bone. MT imaging can be used for the assessment of cortical bone in mice in vivo. DS effects are negligible using preparation pulses with off-resonance frequencies greater than 3 kHz.

PURPOSE Cortical bone mechanical properties are related to the collagen-bound water (CBW) and pore water (PW) components of cortical bone. The study evaluates the feasibility of zero-echo-time imaging in mice in vivo for longitudinal relaxation time (T1) measurements in cortical bone and separation of CBW and PW components. METHODS Zero-echo-time data were acquired at 4.7 Tesla in six mice with 14 different inversion times (0-2,600 ms). Region-of-interest analysis was performed at level of femur diaphysis. The T1 of cortical bone and of CBW (T1cbw) and PW (T1pw) as well as the CBW fraction (cbwf) was computed using a mono-exponential and a bi-exponential fitting approach, respectively. The sum of the squared residuals (Res) to the fit was provided for both approaches. RESULTS For the mono-exponential model, mean T1 ± standard deviation (SD) was 1,057 ± 160 ms. The bi-exponential approach provided a reliable separation of two different bone-water components, with a mean T1cbw of 213 ± 95 ms, T1pw of 2,152 ± 894 ms, and cbwf of 7.4 ± 2.7 %. Lower Res was obtained with bi-exponential approach (P

The separation and quantification of collagen-bound water (CBW) and pore water (PW) components of the cortical bone signal are important because of their different contribution to bone mechanical properties. Ultrashort TE (UTE) imaging can be used to exploit the transverse relaxation from CBW and PW, allowing their quantification. We tested, for the first time, the feasibility of UTE measurements in mice for the separation and quantification of the transverse relaxation of CBW and PW in vivo using three different approaches for T2 * determination. UTE sequences were acquired at 4.7 T in six mice with 10 different TEs (50-5000 μs). The transverse relaxation time T2 * of CBW (T2 *cbw ) and PW (T2 *pw ) and the CBW fraction (bwf) were computed using a mono-exponential (i), a standard bi-exponential (ii) and a new multi-step bi-exponential (iii) approach. Regions of interest were drawn at multiple levels of the femur and vertebral body cortical bone for each mouse. The sum of the normalized squared residuals (Res) and the homogeneity of variance were tested to compare the different methods. In the femur, approach (i) yielded mean T2 * ± standard deviation (SD) of 657 ± 234 μs. With approach (ii), T2 *cbw , T2 *pw and bwf were 464 ± 153 μs, 15 777 ± 10 864 μs and 57.6 ± 9.9%, respectively. For approach (iii), T2 *cbw , T2 *pw and bwf were 387 ± 108 μs, 7534 ± 2765 μs and 42.5 ± 6.2%, respectively. Similar values were obtained from vertebral bodies. Res with approach (ii) was lower than with the two other approaches (p

Advanced Healthcare Materials, 7 (19), ISSN:2192-2640, ISSN:2192-2659

Contrast agents for magnetic resonance imaging (MRI) are essential for evidential visualization of soft tissues pathologies. Contrast-enhanced MRI can be carried out with T1- and T2-weighted sequences that require as contrast agents paramagnetic and superparamagnetic materials, respectively. The T1-weighted imaging is frequently preferred over T2-, as it induces a bright contrast for sharper image analysis and allows more rapid image acquisition. Commonly used and FDA-approved T1 contrast agents, however, were shown to be associated with nephrogenic systematic fibrosis due to Gd3+ release from the injected complexes. Here, ultrasmall iron oxide nanocrystals are produced by scalable flame aerosol technology and investigated as T1 MRI contrast agents by focusing on structure–function relationships and cytocompatibility. The optimized nanocrystals are shown to be a promising cytocompatible alternative to commercial Gd-complexes as they attain comparable relaxivities with no apparent cytotoxicity at clinicall...

Posthepatectomy liver failure (PHLF) remains challenging to diagnose and difficult to treat. The extent of transient regeneration-associated steatosis (TRAS) differs between successful liver regeneration and PHLF. This study aims to quantify TRAS by magnetic resonance imaging (MRI) after hepatectomy in mice.Mice (C57BL/6) underwent either extended hepatectomy (EH) or standard hepatectomy (SH). Serial MRI on postoperative days 1-7 was used to compare TRAS and liver remnant growth between groups. Survival was also assessed.EH was associated with decreased survival and impaired proliferation when compared to SH (p = 0.02 and p = 0.03). MRI showed increased TRAS 48 h after EH compared to SH (11.8 ± 6% vs. 4.3 ± 2%, p 0.001). Compared to EH survivors, death after EH was associated with increased TRAS 48 h postoperatively (16.4 ± 6% vs. 9.2 ± 5%, p = 0.02).EH is associated with increased TRAS and inferior outcomes when compared to SH. MRI may help to predict PHLF after hepatectomy.

This study aimed to monitor the course of liver regeneration by multiparametric magnetic-resonance imaging (MRI) after partial liver resection characterizing Small-for-Size Syndrome (SFSS), which frequently leads to fatal post-hepatectomy liver failure (PLF). Twenty-two C57BL/6 mice underwent either conventional 70% partial hepatectomy (cPH), extended 86% partial hepatectomy (ePH) or SHAM operation. Subsequent MRI scans on days 0, 1, 2, 3, 5 and 7 in a 4.7T MR Scanner quantified longitudinal and transverse relaxation times, apparent diffusion coefficient (ADC) and the magnetization-transfer ratio (MTR) of the regenerating liver parenchyma. Histological examination was performed by hematoxylin-eosin staining. After hepatectomy, an increase of T1 time was detected being larger for ePH on day 1: 18% for cPH vs. 40% for ePH and on day 2: 24% for cPH vs. 49% for ePH. An increase in T2 time, again greater in ePH was most pronounced on day 5: 21% for cPH vs. 41% for ePH. ADC and MTR showed a decrease on day 1: 21% for ePH vs. 13% for cPH for ADC, 15% for ePH vs. 11% for cPH for MTR. Subsequently, all MR parameters converged towards initial values in surviving animals. Dying PLF animals exhibited the strongest increase of T1 relaxation time and most prominent decreases of ADC and MTR. The retrieved MRI biomarkers indicate SFSS and potentially developing PLF at an early stage, likely reflecting cellular hypertrophy with extended water content and concomitantly diluted cellular components as features of liver regeneration, appearing more intense in ePH as compared to cPH.

Large-scale and reproducible synthesis of nanomaterials is highly sought out for successful translation into clinics. Flame aerosol technology with its proven capacity to manufacture high purity materials (e.g., light guides) up to kg h(-1) is explored here for the preparation of highly magnetic, nonstoichiometric Zn-ferrite (Zn0.4 Fe2.6 O4 ) nanoparticles coated in situ with a nanothin SiO2 layer. The focus is on their suitability as magnetic multifunctional theranostic agents analyzing their T2 contrast enhancing capability for magnetic resonance imaging (MRI) and their magnetic hyperthermia performance. The primary particle size is closely controlled from 5 to 35 nm evaluating its impact on magnetic properties, MRI relaxivity, and magnetic heating performance. Most importantly, the addition of Zn in the flame precursor solution facilitates the growth of spinel Zn-ferrite crystals that exhibit superior magnetic properties over iron oxides typically made in flames. These properties result in strong MRI T2 contrast agents as shown on a 4.7 T small animal MRI scanner and lead to a more efficient heating with alternating magnetic fields. Also, by injecting Zn0.4 Fe2.6 O4 nanoparticle suspensions into pork tissue, MR-images are acquired at clinically relevant concentrations. Furthermore, the nanothin SiO2 shell facilitates functionalization with polymers, which improves the biocompatibility of the theranostic system.

Bartonella henselae is a slow growing, fastidious and facultative intracellular pathogen causing cat scratch disease and vasculoproliferative disorders. To date, knowledge about the pathogenicity of this human pathogenic bacterium is limited and, additionally, serodiagnosis still needs further improvement. Here, we investigated the proteome of B. henselae using 2-D SDS-PAGE and MALDI-TOF-MS. We provide a comprehensive 2-D proteome reference map of the whole cell lysate of B. henselae with 431 identified protein spots representing 191 different proteins of which 16 were formerly assigned as hypothetical proteins. To unravel immunoreactive antigens, we applied 2-D SDS-PAGE and subsequent immunoblotting using 33 sera of patients suffering from B. henselae infections. The analysis revealed 79 immunoreactive proteins of which 71 were identified. Setting a threshold of 20% seroreactivity, 11 proteins turned out to be immunodominant antigens potentially useful for an improved Bartonella-specific serodiagnosis. Therefore, we provide for the first time (i) a comprehensive 2-D proteome map of B. henselae for further proteome-based studies focussed on the pathogenicity of B. henselae and (ii) an integrated view into the humoral immune responses targeted against this newly emerged human pathogenic bacterium.

To the Editors: Lung function abnormalities are often present when patients are first diagnosed with pulmonary sarcoidosis, and most studies to date indicate that the predominant pattern is of restriction or normal airways, with a truly obstructive pattern in a minority [1]. The largest case–control study of sarcoidosis to date, the ACCESS (A Case Control Etiologic Study of Sarcoidosis) trial, showed that the biggest group of patients in that particular cohort (46.9%) presented with a forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio of >80% and only 13.2% presented with a ratio of 50–69% [2]. Of the 215 patients from the ACCESS trial who were followed up for a further 2 yrs, the majority showed no change in pulmonary function, radiographic stage or dyspnoea score [3]. A more recent European study showed that patients with sarcoidosis had impaired lung compliance and a reduced diffusing capacity of the lung for carbon monoxide ( D L,CO) and, while there was no predominance of restrictive lung defects, airway obstruction was only present in 11.7% of patients [4]. Over the past 3 yrs, we have noticed that an increasing number of patients who present to our clinics in West London, UK with a new diagnosis of pulmonary sarcoidosis have a predominantly obstructive lung defect. A detailed analysis of lung function in sarcoidosis with respect to stratification by patient demographics has, to our knowledge, not been previously reported. We present the results of a systematic retrospective analysis of 164 consecutive patients presenting with a new diagnosis of pulmonary sarcoidosis over a 10-yr period and in whom formal lung function was recorded at the time of presentation. All patients had a clinically definite diagnosis, with supportive histology …

Diffusion-weighted magnetic resonance imaging (DW-MRI) combined with intravoxel incoherent motion (IVIM) analysis may be applied for assessment of organ lesions, diffuse parenchymal pathologies, and therapy monitoring. The aim of this study was to determine IVIM reference parameters of abdominal organs for translational research in a large cohort of C57Bl/6 laboratory mice. Anesthetized mice (n = 29) were measured in a 4.7 T small-animal MR scanner with a diffusion-weighted echo-planar imaging sequence at the $$b$$ -values 0, 13, 24, 55, 107, 260, 514, 767, 1020 s/mm2. IVIM analysis was conducted on the liver, spleen, renal medulla and cortex, pancreas, and small bowel with computation of the true tissue diffusion coefficient $$D_{\text{t}}$$ , the perfusion fraction $$f_{\text{p}}$$ , and the pseudodiffusion coefficient $$D_{\text{p}}$$ . Microvessel density (MVD) was assessed by immunohistochemistry (IHC) against panendothelial cell antigen CD31. Mean values of the different organs [ $$D_{\text{t}}$$ (10−3 mm2/s); $$f_{\text{p}}$$ (%); $$D_{\text{p}}$$ (10−3 mm2/s); MVD (MV/mm2)]: liver 1.15 ± 0.14; 14.77 ± 6.15; 50.28 ± 33.21, 2008.48 ± 419.43, spleen 0.55 ± 0.12; 9.89 ± 5.69; 24.46 ± 17.31; n.d., renal medulla 1.50 ± 0.20; 14.63 ± 4.07; 35.50 ± 18.01; 1231.88 ± 290.61, renal cortex 1.34 ± 0.18; 10.83 ± 3.70; 16.74 ± 6.74; 810.09 ± 193.50, pancreas 1.23 ± 0.22; 20.12 ± 7.46; 29.35 ± 17.82, 591.15 ± 86.25 and small bowel 1.06 ± 0.13; 16.48 ± 3.63; 15.31 ± 7.00; 420.50 ± 168.42. Unlike $$D_{\text{t}}$$ and $$f_{\text{p}}$$ , $$D_{\text{p}}$$ correlates significantly with MVD (r = 0.90, p = 0.037). This systematic evaluation of murine abdominal organs with IVIM and MVD analysis allowed to establish reference parameters for future DW-MRI translational research studies on small-animal disease models.

Advanced Functional Materials, 25 (48), ISSN:1616-3028, ISSN:1616-301X

We report the case of a 31-year-old, otherwise healthy man with a large intra-articular meniscal ganglion cyst (27.7 x 13.5 mm) originating from the dorsal horn of the lateral meniscus. Clinically, the patient presented with knee pain in a squatting position. Magnetic resonance imaging revealed a large intra-articular cyst in the posterior compartment. At arthroscopic surgery, the ganglion cyst was found in the intercondylar space posteriorly to the posterior cruciate ligament. After removal of the ganglion cyst, a horizontal tear in the dorsal horn of the lateral meniscus was revealed and treated by partial meniscectomy. To our knowledge, a meniscal ganglion cyst originating from the lateral meniscus and extending into the joint is an extremely rare event, with only two previous reported cases. We review the current literature on the pathogenesis, distribution, and treatment of meniscal ganglion cysts.

In 1890 Themistokles Gluck, a German surgeon, was the first who implanted an endoprosthesis made from ivory into a human joint. Unfortunately, this event was also the beginning of history of periprosthetic infections because Gluck selected a knee joint destroyed by infection from tuberculosis.

Bartonella henselae causes a variety of human diseases (e.g. cat scratch disease and the vasculoproliferative disorders, bacillary angiomatosis and peliosis hepatis). The laboratory diagnosis of B. henselae infections is usually based on the detection of anti-B. henselae antibodies by an indirect immunofluorescence assay (IFA) which, unfortunately, suffers from a significant amount of cross-reactivity and hence is prone to deliver false-positive results. In this pilot study, we evaluated the use of a potential two-step serodiagnosis of B. henselae infections by combining IFA and anti-Bartonella adhesin A (BadA) immunoblotting. Our data revealed that approximately 75% of the IFA-positive sera of patients with a suspected B. henselae infection reacted specifically with BadA but only approximately 25% of the IFA-negative sera of healthy blood donors. Although Yersinia adhesin A (YadA) is structurally closely related to BadA, no cross-reactivity of sera from patients suffering from a Yersinia enterocolitica or Y. pseudotuberculosis infection with BadA was detected in immunoblotting. Unfortunately, recombinantly expressed BadA domains (head, connector, stalk fragment) were not suitable for immunoblotting. Finally, the best resolution for full-length BadA immunoblotting was obtained when whole cell lysates of B. henselae were separated using continuous 4-15% sodium dodecyl sulfate polyacrylamide gels. In summary, our results show that BadA antibodies are detectable in the sera of B. henselae-infected patients and, therefore, this pilot study suggests to include BadA immunoblotting in the laboratory diagnosis of B. henselae infections.

Penicillin-binding protein 3 (PBP3; also called FtsI) is a transpeptidase that catalyzes cross-linking of the peptidoglycan cell wall in the division septum of Escherichia coli . To determine whether the catalytic activity of PBP3 is activated during division, we assayed acylation of PBP3 with three β-lactams (cephalexin, aztreonam, and piperacillin) in growing cells. Acylation of PBP3 with cephalexin, but not aztreonam or piperacillin, appeared to be stimulated by cell division. Specifically, cephalexin acylated PBP3 about 50% faster in a population of dividing cells than in a population of filamentous cells in which division was inhibited by inactivation or depletion of FtsZ, FtsA, FtsQ, FtsW, or FtsN. However, in a simpler in vitro system using isolated membranes, acylation with cephalexin was not impaired by depletion of FtsW or FtsN. A conflicting previous report that the ftsA3 (Ts) allele interferes with acylation of PBP3 was found to be due to the presence of a thermolabile PBP3 in the strain used in that study. The new findings presented here are discussed in light of the hypothesis that the catalytic activity of PBP3 is stimulated by interaction(s) with other division proteins. We suggest that there might be allosteric activation of substrate binding.

Objectives: This study aims to quantify the response of the transverse relaxation rate of the magnetic resonance (MR) signal of the cerebral tissue in healthy volunteers to the administration of air with step-wise increasing percentage of oxygen. Materials and Methods: The transverse relaxation rate (R2*) of the MR signal was quantified in seven volunteers under respiratory intake of normobaric gas mixtures containing 21, 50, 75, and 100% oxygen, respectively. End-tidal breath composition, arterial blood saturation (SaO2), and heart pulse rate were monitored during the challenge. R2* maps were computed from multi-echo, gradient-echo magnetic resonance imaging (MRI) data, acquired at 3.0T. The average values in the segmented white matter (WM) and gray matter (GM) were tested by the analysis of variance (ANOVA), with Bonferroni post-hoc correction. The GM R2*-reactivity to hyperoxia was modeled using the Hill's equation. Results: Graded hyperoxia resulted in a progressive and significant (P < 0.05) decrease of the R2* in GM. Under normoxia the GM-R2* was 17.2 ± 1.1 s-1. At 75% O2 supply, the R2* had reached a saturation level, with 16.4 ± 0.7 s-1 (P = 0.02), without a significant further decrease for 100% O2. The R2*-response of GM correlated positively with CO2 partial pressure (R = 0.69 ± 0.19) and negatively with SaO2 (R = -0.74 ± 0.17). The WM showed a similar progressive, but non-significant, decrease in the relaxation rates, with an increase in oxygen intake (P = 0.055). The Hill's model predicted a maximum R2* response of the GM, of 3.5%, with half the maximum at 68% oxygen concentration. Conclusions: The GM-R2* responds to hyperoxia in a concentration-dependent manner, suggesting that monitoring and modeling of the R2*-response may provide new oxygenation biomarkers for tumor therapy or assessment of cerebrovascular reactivity in patients.

Objectives: This study aims to quantify the response of the transverse relaxation rate of the magnetic resonance (MR) signal of the cerebral tissue in healthy volunteers to the administration of air with step-wise increasing percentage of oxygen. Materials and Methods: The transverse relaxation rate (R2FNx01) of the MR signal was quantified in seven volunteers under respiratory intake of normobaric gas mixtures containing 21, 50, 75, and 100% oxygen, respectively. End-tidal breath composition, arterial blood saturation (SaO 2 ), and heart pulse rate were monitored during the challenge. R2FNx01 maps were computed from multi-echo, gradient-echo magnetic resonance imaging (MRI) data, acquired at 3.0T. The average values in the segmented white matter (WM) and gray matter (GM) were tested by the analysis of variance (ANOVA), with Bonferroni post-hoc correction. The GM R2FNx01-reactivity to hyperoxia was modeled using the Hill′s equation. Results: Graded hyperoxia resulted in a progressive and significant (P < 0.05) decrease of the R2FNx01 in GM. Under normoxia the GM-R2FNx01 was 17.2 ± 1.1 s -1 . At 75% O 2 supply, the R2FNx01 had reached a saturation level, with 16.4 ± 0.7 s -1 (P = 0.02), without a significant further decrease for 100% O 2 . The R2FNx01-response of GM correlated positively with CO 2 partial pressure (R = 0.69 ± 0.19) and negatively with SaO 2 (R = -0.74 ± 0.17). The WM showed a similar progressive, but non-significant, decrease in the relaxation rates, with an increase in oxygen intake (P = 0.055). The Hill′s model predicted a maximum R2FNx01 response of the GM, of 3.5%, with half the maximum at 68% oxygen concentration. Conclusions: The GM-R2FNx01 responds to hyperoxia in a concentration-dependent manner, suggesting that monitoring and modeling of the R2FNx01-response may provide new oxygenation biomarkers for tumor therapy or assessment of cerebrovascular reactivity in patients.