The use of peptides to reconstruct conformational determinants; a brief review

In many biological processes, defined regions of proteins are involved in selective recognition. These regions can often be mimicked with peptides and are the main targets for vaccine and drug development. The authors review the use of peptides, to define and ultimately mimic defined protein regions of interest. Especially the role of the Pepscan method is emphasized. This method has been proven to be a useful and fast tool in defining protein regions of interest. It is based on the simultaneously synthesis of multiple peptides coupled to solid supports. Hundreds of peptides can be produced and tested in a relatively short period of time. With the construction of random peptide libraries in recombinant DNA systems, it is now even possible to screen for peptidic determinants without the requirement of preliminary knowledge of primary structure. Having this information, the affinity of peptides can be further enhanced with the Pepscan approach. The power of this approach will be illustrated with results from studies on the development of synthetic vaccines and hormone analogues.     

Experimental verification of a model describing the occupied volume by polymers in solution

A relation is proposed which yields the occupied volume by macromolecular chains in solution. The experimental verification of the model is carried out by a viscometric study of the ternary system polymer A/polymer B/solvent. More precisely the viscometric study permits the determination of the critical concentration c^** corresponding to the incipient overlap of spherical coils.     

Prior image constrained compressed sensing (PICCS): a method to accurately reconstruct dynamic CT images from highly undersampled projection data sets

When the number of projections does not satisfy the Shannon/Nyquist sampling requirement, streaking artifacts are inevitable in x-ray computed tomography (CT) images reconstructed using filtered backprojection algorithms. In this letter, the spatial-temporal correlations in dynamic CT imaging have been exploited to sparsify dynamic CT image sequences and the newly proposed compressed sensing (CS) reconstruction method is applied to reconstruct the target image sequences. A prior image reconstructed from the union of interleaved dynamical data sets is utilized to constrain the CS image reconstruction for the individual time frames. This method is referred to as prior image constrained compressed sensing (PICCS). In vivo experimental animal studies were conducted to validate the PICCS algorithm, and the results indicate that PICCS enables accurate reconstruction of dynamic CT images using about 20 view angles, which corresponds to an under-sampling factor of 32. This undersampling factor implies a potential radiation dose reduction by a factor of 32 in myocardial CT perfusion imaging.     

Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer's disease

Although the presence of amyloid deposits is required to establish the neuropathologic diagnosis of Alzheimer's disease, from a clinical point of view, a direct contribution of these cerebral lesions to cognitive deficits is still controversial. The development and standardization of quantitative and accurate biochemical and neuropathologic methods may be critical to improve the postmortem diagnosis and clinicopathologic correlations. Here, we used a point counting method, based on the Cavalieri principle, to estimate the volume occupied by amyloid deposits in a discrete region of the prefrontal cortex and in the hippocampal formation, in brains from patients with cognitive status ranging from normal to severely demented. We demonstrate that the assessment of the total volume occupied by the amyloid deposits in the entorhinal cortex and subiculum can be considered an effective predictor of dementia severity. We also reveal the existence of a high degree of regional and interindividual heterogeneity in amyloid distribution and relative volume.Our data suggest that even though a correlation was observed between the stereologic point counting method and a non-stereologic random field thresholding approach, in most cases non-stereologic methods may not provide adequate samples of the tissue and may lead to unreliable estimates of amyloid burden due to the inhomogeneous distribution of amyloid in the cerebral cortex and the large variability among brains.     

Joint edge detection and motion estimation of cardiac MR image sequence by a phase field method

In this paper a variational framework for joint segmentation and motion estimation is employed for inspecting heart in Cine MRI sequences. A functional including Mumford-Shah segmentation and optical flow based dense motion estimation is approximated using the phase-field technique. The minimizer of the functional provides an optimum motion field and edge set by considering both spatial and temporal discontinuities. Exploiting calculus of variation principles, multiple partial differential equations associated with the Euler-Lagrange equations of the functional are extracted, first. Next, the finite element method is used to discretize the resulting PDEs for numerical solution. Several simulation runs are used to test the convergence and the parameter sensitivity of the method. It is further applied to a comprehensive set of clinical data in order to compare with conventional cascade methods. Developmental constraints are identified as memory usage and computational complexities, which may be resolved utilizing sparse matrix manipulations and similar techniques. Based on the results of this study, joint segmentation and motion estimation outperforms previously reported cascade approaches especially in segmentation. Experimental results substantiated that the proposed method extracts the motion field and the edge set more precisely in comparison with conventional cascade approaches. This superior result is the consequence of simultaneously considering the discontinuity in both motion field and image space and including consequent frames (usually five) in our joint process functional.     

Chiral separation by simultaneous use of vancomycin as stationary phase chiral selector and chiral mobile phase additive

Improved chiral selectivity was observed for numerous compounds when vancomycin was added to the mobile phase on a Chirobiotic-V column. This chiral mobile phase additive (CMPA) is the same chiral selector as that bonded to the stationary phase of this Chirobiotic-V column. A substantial increase in the difference in enthalpy of transfer, deltadeltaH, and in the difference in entropy of transfer, deltadeltaS, for two enantiomers was observed when vancomycin was used as both the mobile phase and the stationary phase chiral selector. The importance of mobile phase composition, analytical column, CMPA concentration was investigated. Also, higher resolution was observed for the separations of acidic compounds when a fluidity enhancing solvent, such as fluoroform, was added into the mobile phase. However, the most commonly used fluidity enhancement solvent, CO2, was ineffective.     

The use of hand held mobile phones by drivers

The use of mobile phones by drivers has been shown to be associated with an increased risk of motor vehicle crashes. The aim of this study was to identify the use of hand held mobiles phones by drivers in Ireland. Their use was investigated by a direct observation survey of drivers. The study showed that 3.6% of drivers were using hand held mobile phones while driving. This rate is high compared to other studies. Van drivers were three times more likely than other drivers to use a mobile phone whilst driving. Legislation needs to be introduced to ban their use and thereby reduce the risk of crashes.     

补片在髋关节融合后全髋置换重建软组织张力中的应用

背景：越来越多的髋关节融合后患者要求行全髋置换,但此类患者长期软组织失用,为防止置换后假体脱位,置换过程中往往需要进行软组织张力的重建。 目的：探讨医用聚丙烯疝修补网在髋关节融合后全髋关节置换重建软组织张力中的应用。 方法：2007-01/2011-01对21例髋关节融合患者进行了全髋关节置换,置换过程中纠正下肢的不等长,恢复患者股骨的偏心距后,肌肉无法缝合,采用补片重建软组织的张力。 结果与结论：置换后1年Harris评分(83.8±6.4)分,屈髋活动度(79.5±4.6)°。置换后有2例行走时仍需要手杖,置换前伴有的下腰痛、同侧膝关节痛和对侧髋关节痛的症状均明显缓解,仅有2例患者仍有肢体不等长。置换时间超过5年的9例患者均未见假体松动表现。结果可见在重建软组织张力的过程中应用补片对患者置换后髋关节功能恢复及假体的稳固非常重要。 关键词：补片;髋关节融合;全髋置换;张力重建;聚丙烯 doi:10.3969/j.issn.1673-8225.2012.09.004     

The development and use of a new methodology to reconstruct courses of admission and ambulatory care based on the Danish National Patient Registry

IntroductionThe Danish National Patient Registry (DNPR) contains clinical and administrative data on all patients treated in Danish hospitals. The data model used for reporting is based on standardized coding of contacts rather than courses of admissions and ambulatory care.MethodsTo reconstruct a coherent picture of courses of admission and ambulatory care, we designed an algorithm with 28 rules that manages transfers between departments, between hospitals and inconsistencies in the data, e.g., missing time stamps, overlaps and gaps. We used data from patients admitted between 1 January 2010 and 31 December 2014.ResultsAfter application of the DNPR algorithm, we estimated an average of 1,149,616 courses of admission per year or 205 hospitalizations per 1000 inhabitants per year. The median length of stay decreased from 1.58 days in 2010 to 1.29 days in 2014. The number of transfers between departments within a hospital increased from 111,576 to 176,134 while the number of transfers between hospitals decreased from 68,522 to 61,203.ConclusionsWe standardized a 28-rule algorithm to relate registrations in the DNPR to each other in a coherent way. With the algorithm, we estimated 1.15 million courses of admissions per year, which probably reflects a more accurate estimate than the estimates that have been published previously. Courses of admission became shorter between 2010 and 2014 and outpatient contacts longer. These figures are compatible with a cost-conscious secondary healthcare system undertaking specialized treatment within a hospital and limiting referral to advanced services at other hospitals.     

The use of concanavalin A to measure acute phase proteins by laser nephelometry

Concanavalin A (con A) binds specifically to α-d-glucosyl, α-d-mannosyl and sterically related structures. Many serum glycoproteins contain such residues and will therefore bind and precipitate con A. Using this principle, a nephelometric method was developed for measuring total con A binding proteins in serum. The effect of parameters such as con A to glycoprotein ratio, polymer enhancement, reaction time, stability of the complexes and potential inhibitory molecules such as glucose and calcium were assessed. A brief clinical evaluation of the assay in human sera showed that con A binding correlates well with specific acute phase protein-changes in inflammatory disease and may be used as an index of disease activity. Preliminary studies show that con A binding also reflects disease activity in a number of animal species and thus may provide a much needed index of inflammation in the experimental animal and in veterinary practice, where species specific antisera to acute phase proteins are not widely available and protein analyses have been rather neglected. The assay is rapid, cheap and may be performed on automated nephelometric systems.     

Clinical impact of the tumor volume doubling time on sarcoma patients with lung metastases

The volume doubling time (VDT) is an accurate and reproducible method for the quantitation of the rate and pattern of tumor growth in individual patients. The purpose of this study is to investigate the tumor VDT using chest CT in individual sarcoma patients with lung metastasis and to determine whether VDT is associated with survival after lung metastasis in bone and soft tissue sarcomas. Forty patients had measurable lung metastases in at least two sequential chest CT images taken at least 14 days apart. The VDT was calculated using the method originally described by Schwartz. The median and mean VDT in all 40 patients was 21.5 and 53 days, respectively. Similarly, the median and average VDT in 29 soft tissue sarcoma patients was 26 and 57 days, respectively. The median and mean VDT in 11 bone sarcoma patients was 13 and 42 days, respectively. The current univariate analysis revealed significantly poorer predictive values for VDT in all 40 sarcoma patients and 29 soft tissue sarcoma patients. A multivariate analysis showed the VDT to be an independent predictor of survival in 29 soft tissue sarcoma patients. These results suggest that patients with a shorter VDT and consequently a more rapid rate of tumor growth have a significantly lower chance for long term survival especially in soft tissue sarcoma. The patients with lung metastasis that have a longer VDT should therefore be considered for aggressive treatment even if the lesions are multiple and/or bilateral.     

Computed tomographic-pathologic correlation of gross tumor volume and clinical target volume in non-small cell lung cancer: a pilot experience.

CONTEXT: Computed tomographic (CT) scan data are used regularly in radiation treatment planning for patients with lung cancer. To our knowledge, the relationship of the CT images of tumors and their corresponding microscopic extent has not yet been studied in detail. OBJECTIVE: To correlate tumor sizes on CT with tumor sizes measured microscopically (ie, the gross tumor volume [GTV]-clinical target volume margin) in non-small cell lung cancers. DESIGN: Prospective pilot study. SETTING: Single institution. PATIENTS: Patients with operable non-small cell lung cancer were identified preoperatively. INTERVENTIONS: Once the surgical specimen was available, it was oriented with the surgeon and the pathologist. Seven whole-mount, cross-sectional histologic glass slides were made from 5 tumors using formalin fixation and hematoxylin-eosin staining. The pathologist then outlined the cancer-containing area under the microscope (Micro-GTV) and the area of surrounding inflammatory response (Micro-GTV + inflammation). Preoperative CT scans were used for outlining tumor on the corresponding slice (CT-GTV). MAIN OUTCOME MEASURES: Correlation of the areas of Micro-GTV, Micro-GTV + inflammation, and CT-GTV was performed. RESULTS: There was an obvious trend that the CT-GTV was bigger than the Micro-GTV, except in specimen 1, in which the 2 areas were about equal. However, on comparing the values for the CT-GTV and the Micro-GTV + inflammation, the difference between the 2 areas became smaller. CONCLUSIONS: Modern CT scans might overestimate the GTV in non-small cell lung cancer. The GTV-clinical target volume margin could actually be zero or even a negative value. The findings in this small study are interesting and provoking. Further study with a larger number of patients and more rigid quality control is warranted to confirm our findings.     

Evoked corticospinal output to the human scalene muscles is altered by lung volume

Increases in lung volume inhibit the inspiratory output from the medulla, but the effect of lung inflation on the voluntary control of breathing in humans is not known. We tested corticospinal excitability using transcranial magnetic stimulation (TMS) to evoke a response in the scalene muscles. TMS was delivered at rest at three different lung volumes between functional residual capacity (FRC) and total lung capacity (TLC) during incremental inspiratory and incremental expiratory manoeuvres. Motor evoked potentials (MEPs) in scalenes were ～50% larger at a high lung volume (FRC+～90% inspiratory capacity [IC]) compared to lower lung volumes (FRC and FRC+～40% IC) in both inspiratory and expiratory manoeuvres (p<0.001). The change in MEP size was not due to differences in pre-stimulus EMG amplitude (p=0.29). The results suggest a differential effect of lung inflation on the automatic and voluntary control of breathing in humans.     

Some problems in the use of the Coulter counter for erythrocyte total counts and volume distribution

Normal erythrocytes were subject to swelling and some haemolysis when suspended in a NaCl-formaldehyde-Na(2)EDTA diluent of pH 4.9 for routine blood-cell counting in the Coulter counter. A phosphate-buffered saline of pH 7.4 was substituted and has proven satisfactory for total erythrocyte counts.Polyvinyltoluene latex was unsuitable for volume calibration of the counter, because of aggregation of the particles in saline. Ragweed pollen grains gave a calibration factor that agreed well with that for fresh erythrocytes. Recent batches of Dade's Erythro-Trol (a suspension of fixed erythrocytes) were satisfactory for both total counts and volume calibration.