New structures of allosteric proteins revealing remarkable conformational changes

New three-dimensional structures of allosteric proteins reveal they have a flexible architecture that is instrumental to the regulation of protein function. Highlights are the structures of GroEL, pyruvate kinase, D-3-phosphoglycerate dehydrogenase and the acetylcholine receptor. Furthermore, significant progress in understanding the nature of the intermediates involved in an allosteric reaction has been achieved through recent spectroscopic and crystallographic studies on haemoglobin.     

一种付费搜索无嫉妒均衡策略

在付费拍卖的展示空间使用无嫉妒均衡策略,是取得广告主和竞拍者双赢重要方法.通过建立评价矩阵,实现了竞拍者在理性和独立前提下达到相互无嫉妒和各自的效率,并给出相应定理和实例.     

Permethylation alters the conformational transitions and the complexing ability of melittin: a model for methylated proteins

A number of researches have used factor analyses and principal components analyses on handedness questionnaire data in order to learn something about handedness. However, these researchers have analyzed pooled data from righthanders and lefthanders. The practice of pooling groups that are known in advance to be heterogeneous is highly questionable because it is not possible to disentangle the sources of variance that are contributed by within group differences from those that arise from between group differences. The factor structure and item loadings that result from pooled data are misleading and cannot inform meaningfully about the relation of hand preference to handedness. Similar problems can be anticipated in other neuropsychological applications of factor analysis, where data from heterogeneous groups is pooled.     

A two-term MEDLINE search strategy for identifying randomized trials in obstetrics and gynecology

In this study, we examined whether endothelin (ET) plays a role in the short-term increase in mean arterial pressure (MAP) after nitric oxide synthase (NOS) inhibition with N(omega)-nitro-L-arginine methyl ester (L-NAME) in stroke-prone spontaneously hypertensive rats (SHRSPs). Experiments were performed by using Inactin-anesthetized male SHRSPs that were pretreated with chlorisondamine to block reflex autonomic cardiovascular effects. Injection of L-NAME (10 mg/kg, i.v.), but not D-NAME, produced rapid and marked increases (74 +/- 3 mm Hg) in MAP that were sustained for >1 h. In SHRSPs that were treated with the ET(A/B) receptor antagonist, L-754,142 (15 mg/kg + 15 mg/kg/h), L-NAME increased MAP by 45 +/- 4 mm Hg (p < 0.0001 compared with L-NAME alone). L-754,142 blocked pressor responses to big ET-1 by >90% but was without effect on pressor responses to norepinephrine. Plasma levels of ET-1 averaged 5 +/- 1 pg/ml in animals given vehicle and were slightly increased in animals given either L-NAME alone (7 +/- 2 pg/ml) or L-754,142 alone (7 +/- 2 pg/ml) but increased markedly when L-NAME and L-754,142 were given together (114 +/- 18 pg/ml). This may relate to an effect of L-754,142 to block ET-receptor-mediated clearance of ET-1. We conclude that ET plays a role in the short-term pressor response after NOS inhibition in SHRSPs.     

Revising and validating the random search model for competitive search

The aim of the present study is a comparison of family relations in families with an obese adolescent and families with a normal-weight adolescent. Particularly, we studied the parents' and children's perceptions of some crucial areas of their relationship, e.g., communication, support, and some factors of "psychosocial risk" for the adolescents. We compared 30 family triads each with an obese child and 30 family triads each with a normal-weight child. We used a questionnaire aimed to evaluate some crucial variables of family functioning such as communication, family climate, support and satisfaction. A multivariate analysis of variance yielded no difference between obese and nonobese adolescents concerning communication with their mothers and fathers and concerning support given and received from them. In particular, analysis indicated no difference between parents of obese adolescents and parents of normal-weight adolescents regarding openness and problems in communication. As a protective factor against psychosocial risk, in both the samples the relationship with the mother arises as relevant, but, for the nonobese adolescents, both support and communication with this parent were important, whereas for the obese adolescents only support seemed to be really important. The results are discussed with respect to this approach which considered the family as the unit of analysis both from a theoretical and a methodological point of view.     

A training model in search of a rationale.

Comments on D. R. Peterson's (see PA, 73:10245) analysis of professional nonscientist-practitioner psychology programs by noting that Peterson's observations suggest that the nonscientist-practitioner training model lacks adequate rationale in that there is no evidence to suggest that this type of professional preparation produces better clinicians and by voicing the contention that until practitioners are trained to contribute to the knowledge base of the discipline, no rapid progress will be made toward an empirically based clinical discipline. (2 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Determinants of side chain conformational preferences in protein structures

A discriminatory function based on a statistical analysis of atomic contacts in protein structures is used for selecting side chain rotamers given a peptide main chain. The function allows us to rank different possible side chain conformations on the basis of contacts between side chain atoms and atoms in the environment. We compare the differences in constructing side chain conformations using contacts with only the local main chain, using the entire main chain, and by building pairs of side chains simultaneously with local main chain information. Using only the local main chain allows us to construct side chains with approximately 75% of the chi1 angles within 30 degrees of the experimental value, and an average side chain atom r.m.s.d. of 1.72 A in a set of 10 proteins. The results of constructing side chains for the 10 proteins are compared with the results of other side chain building methods previously published. The comparison shows similar accuracies. An advantage of the present method is that it can be used to select a small number of likely side chain conformations for each residue, thus permitting limited combinatorial searches for building multiple protein side chains simultaneously.     

A model for the interaction of trifluoroethanol with peptides and proteins

Scaphoid or longitudinal arch pads are frequently prescribed pedorthics for foot and ankle rehabilitation. These pedorthics are reported to be effective in mechanically supporting the medial longitudinal arch while reducing plantar and medial soft tissue strain. The objective of this study was to measure alterations in ambulatory plantar pressure metrics in a group of adults secondary to scaphoid pad application. The biomechanical rationale of this study was that the geometry of foot contact would be altered secondary to foot inversion. Ten adult male subjects with biomechanically normal feet were evaluated during multiple trials. A Holter type microprocessor-based portable in-shoe plantar pressure data acquisition system was used to record the dynamic data. Pressures were recorded from eight discrete plantar locations at the hindfoot, midfoot, and forefoot regions of the insole. Statistically significant (p < or = 0.05) increases in peak pressures were seen laterally with scaphoid pad application, while significant decreases in peak pressures with pad usage occurred at the hallux and the calcaneal region of the foot. At the medial longitudinal arch, peak pressures increased from near 0 to 115.3 kPa, contact durations increased from near 0 to 438 ms, and pressure-time integrals increased from near 0 to 33.4 kPa.s.     

Guided search: An alternative to the feature integration model for visual search.

Subjects searched sets of items for targets defined by conjunctions of color and form, color and orientation, or color and size. Set size was varied and reaction times (RTs) were measured. For many unpracticed subjects, the slopes of the resulting RT?×?Set Size functions are too shallow to be consistent with A. Treisman's (see record 1988-00255-001) and A. Treisman and G. Gelade's (see record 1980-04680-001) feature integration model, which proposes serial, self-terminating search for conjunctions. Searches for triple conjunctions (Color?×?Size?×?Form) are easier than searches for standard conjunctions and can be independent of set size. A guided search model similar to J. E. Hoffman's (see record 1981-04707-001) two-stage model can account for these data. In the model, parallel processes use information about simple features to guide attention in the search for conjunctions. Triple conjunctions are found more efficiently than standard conjunctions because three parallel processes can guide attention more effectively than two. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Roles of salience and strategy in conjunction search.

In some cases, the search for a conjunction target proceeds through the smaller group of elements in a display, whereas in others, search is limited to those elements that share a particular feature with the target. In 6 experiments, participants searched for a conjunction target among displays consisting of various proportions of 2 distractor types. Smaller-group search was more prevalent than target-feature search with denser displays and with features that were highly discriminable. Explicit instructions to limit search to a specific feature affected performance only when the discriminability of the guiding feature was much greater than the other target feature. Together, these experiments show that bottom-up factors have more influence in guiding conjunction searches than previously thought. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A windowless 13N production target for use with low energy deuteron accelerators

The recent development of low energy accelerators for positron emission tomography has necessitated the development of new targets for 13N production. 12C(d,n)13N reaction yields in graphite at low deuteron beam energies (0.8-3.2 MeV) are presented and a new technique for the in situ extraction of 13N activity from solid graphite and subsequent conversion to [13N] ammonia is described. The target is windowless and is reusable for multiple isotope production runs. This technique utilizes radio frequency induction heating to rapidly heat the graphite to combustion temperatures in an O2 gas stream. The conversion of activity induced in the target to [13N] ammonia in under 10 min with an overall decay-corrected efficiency of 45% is reported.     

组合柔性结构非线性柔性模型

根据组合柔性结构的结构参数对其变形特性的影响,对组合柔性结构进行了分类,并给出了组合柔性结构中柔性杆存在非线性变形的条件.考虑柔性结构的变截面特征和非线性变形的问题,对组合柔性结构的变形特性进行了分析,建立了变形求解的非线性柔性模型.最后设计并加工了一种柔性铰链-柔性杆组合结构,分别采用伪刚体模型、拟柔性模型和非线性柔性模型对其变形进行理论计算,同时采用静电驱动方式对组合柔性结构的变形进行测试.结果表明,非线性柔性模型的计算结果与实验测试结果最接近,证明了此模型和分析方法的有效性.     

Spectroscopic evidence for a conformational transition in horseradish peroxidase at very low pH

Resonance Raman (RR), electronic absorption, and circular dichroism (CD) spectroscopies of the ferric, ferrous, and ferrous-CO forms of horseradish peroxidase (HRP-C) at pH 3.1 are reported. The CD spectra in the UV region show only a small decrease in the alpha-helical content upon pH lowering, whereas dramatic changes are observed in the Soret region. The final form of ferric HRP-C is 5-coordinate high-spin heme whose histidine ligand is replaced by a water ligand with a polar character. The electronic and CD spectra show the presence of an intermediate form with a 6-coordinate heme. Therefore, the cleavage of the proximal Fe-imidazole bond is preceded by the binding of a distal water molecule. For the ferrous form of HRP-C, the pH-dependence of the absorption spectra revealed only the native form in the range pH 5-7 and an unfolded form with a Soret maximum at 383 nm at pH 3.1. An intermediate state, characterized by a Soret maximum at 424 nm, was observed only in a transient way, within a few milliseconds. A metastable and a final species are observed also for the ferrous-CO complex at pH 3.1, as proved by isosbestic points in the electronic absorption spectra. The two forms show different RR nu(Fe-C) and IR nu(CO) modes. The metastable form corresponds to a heme where histidine is replaced by water. The final form is due to the displacement of the water ligand by the proximal histidine. We propose a kinetic model to account for our results at pH 3.1 for the ferric, ferrous, and ferrous-CO forms.     

A technique for the fast calculation of three-dimensional photon dose distributions using the superposition model

Techniques for reducing computation time in 3D photon dose calculations are addressed with specific emphasis given to the convolution/superposition approach. A single polyenergetic superposition model calculating absorbed dose per incident photon fluence (Gy cm2) was developed in terms of TERMA and a total energy deposition kernel (a total point spread function). A novel approach was devised for reducing calculation time. The method, named the CF method, was based on the use of a conventional, fast model (here a modified power-law method was used) for the generation of 3D dose distributions on a fine dose matrix. Superposition calculations were carried out on a coarse matrix and calculation speed was increased simply by reducing the number of calculations. A set of correction factors was derived on the coarse grid from the ratio of the dose values from superposition to those from the conventional algorithm. These were interpolated onto the fine matrix and used to modify the dose calculation from the conventional algorithm. The method was tested in a worst-case example where large dose gradients were present and in a clinically relevant irradiation geometry. It is shown that the time required for the generation of a 3D matrix with superposition can be reduced by at least a factor of 100 with no significant loss in accuracy.