双波长/双光束分光光度计数据处理系统的改进

通过加入计算机和设计新软件,双波长/双光束分光光度计数据处理能力得到大大增强.仪器原来依靠绘图仪输出,手量手算,数据处理能力弱,限制了它的使用,尤其是在动力学测定上.现在由计算机控制数据采集,显示多条曲线,显示数值,在曲线上自动寻峰,光滑曲线,任意缩放图形,并用激光打印机输出.介绍了升级后的系统结构,及其在关于磷脂酰乙醇(PE)对Ca²⁺-ATPase的Ca²⁺转运能力影响的研究中的应用.     

Muscle and sarcomere lengths in the hind limb of the rabbit (Oryctolagus cuniculus) during a galloping stride

Rabbits were filmed galloping, and the length changes of the principal hind limb muscles were determined. Sarcomere lengths were measured in carcasses set by rigor mortis in four of the positions adopted during a stride. These sarcomere lengths were measured by means of a diffraction technique, devised for the purpose, using an ordinary microscope. Expected sarcomere lengths for three of the positions were predicted from that observed in the fourth, together with muscle length changes. A theoretical length-tension curve for rabbit muscle was constructed, using A and I filament lengths, it was shown that when the muscles were active, their sarcomere lengths corresponded to the plateau of the length-tension curve.     

SPLINT: a cubic spline interpolation program for the analysis of fragment sizes in one-dimensional electrophoresis gels.

SPLINT (SPLine INTerpolation) is a BASIC microcomputer program that uses electrophoretic data on the migration distances of DNA fragments of known size to approximate the relationship between distance moved and DNA fragment size by a piecewise cubic spline function. This function places all standards exactly on the calibration curve and then determines from it the sizes of other fragments in the gel. Special advantages of this program include the use of a digitizer to enter the fragment positions directly from a gel photograph and the optional generation of a graph of the approximating function plus the placement on it of points from any specified gel lanes.     

Film recording of the kinematics of dolphin swimming

An ingenious method for recording the forward motion of dolphins and decoding the pictures was elaborated. The method makes it possible to reproduce the trajectories of body points of a swimming dolphin from their positions on pictures.     

荒漠珍稀灌木半日花种群的年龄结构与生命表分析

根据对不同坡位的半日花种群的调查资料,分析了其年龄结构,编制了静态生命表,分析了存活曲线和死亡率曲线、损失度曲线,并利用生存分析理论进行了函数分析。结果表明：不同坡位的半日花种群存在下降趋势。幼龄级和老龄级个体少,中龄级个体多。不同坡位的半日花种群密度存在差异,坡上部种群密度最大,坡下部最小,坡中部居中。不同坡位半日花种群在Ⅰ龄级时期望寿命达到最大,并在Ⅶ、Ⅷ龄级时期望寿命出现波动;不同坡位的半日花种群的存活曲线整体上趋于Deevy Ⅱ～Ⅲ型之间;在第Ⅵ~Ⅷ龄级半日花种群死亡率较高,且坡中部和坡下部种群死亡率峰值比坡上部种群滞后一个龄级。生存分析引入生命表中的4个函数能较好地说明不同坡位半日花种群的结构和动态变化。     

Control and oscillation in ligand receptor interactions according to the law of mass action

The law of mass action is almost universally applied to interactions of both endogenous ligands and drugs with their specific receptors and results in the familiar hyperbolic equilibrium binding curve of bound (y) vs free (z) concentrations. Whereas the concentration of a drug molecule is governed by its pharmacokinetic properties and, possibly, by intrinsic control mechanisms, natural ligands are certainly controlled since their concentrations normally remain within specific limits. This paper represents a further study of control of this kinetic process in a model based on ligand production (rate F), first-order elimination (rate constant E) and a feedback function of occupancy, phi(y), that modulates these. In the controlled situation the system equilibrium occurs at states called critical points (yc,zc) at which both dy/dt and dz/dt are simultaneously zero. There are only a finite number of such points along the hyperbolic binding curve and these may be either stable or unstable. The basal state is the normal operating point of the system and is necessarily stable; that is, perturbations producing states away from it will return in time to this point. We have previously shown that phi'(y) less than or equal to 0 is a sufficient condition for stability. Accordingly, for a continuous control curve, an adjacent critical point will be unstable, and have phi'(y) greater than 0. If the system coordinates get sufficiently close to such an unstable point there is propulsion to extreme states and loss of control. The distance between the stable and unstable points determines whether a dose (or release) of the ligand will be controlled or not. The current paper focuses on the geometrical properties of the binding and control curves and how these relate to the stability of critical points and the overall control of ligand doses. In particular we show how the magnitude of the (negative) slope of the control curve at the basal point affects the frequency of oscillation about the basal state. It is further shown that high frequency control results in lower receptor occupancy, a result that may explain desensitization.     

Relationship between quiet standing position and perceptibility of standing position in the anteroposterior direction

We investigated the relationship between an individual's center of pressure in the anteroposterior direction in quiet standing (QS) and perceptibility of different standing positions. The position of the center of pressure in the anteroposterior direction (CoPy position) while standing was represented as the percentage distance (%FL) from the hindmost point of the heel in relation to foot length. CoPy position in QS was located from 31 to 58%FL. Perceptibility of standing position was evaluated by the difference between the reference position and the subject's attempt to reproduce that position. Subjects were tested for their ability to reproduce reference positions selected randomly from a total of 13 positions at 5%FL increments from 20 to 80%FL. Using an approximation formula curve, we identified the relationship between reference position and reproduction absolute error. The standing position range with reproduction error exceeding 90% of the difference between the maximum and minimum errors was defined as the low perceptibility range of standing position. The approximation curve had one peak near QS. CoPy positions in QS were located in the low perceptibility range, except for five subjects with a more posterior location. The correlation coefficient between CoPy positions in QS (x) and reference position (y) showing maximum error was 0.70 and the regression line was y=0.464x+28.2; the intersection point with y=x was 53%FL. Reproduction absolute errors in reference positions at 20-30%FL and 70-80%FL were significantly smaller than those at 40-60%FL (p<0.05). We concluded the following. (1) Standing positions showing the lowest perceptibility are located close to the QS position; however, in subjects whose QS position is located more posteriorly, the standing position showing maximum error is more anterior. (2) Perceptibility of extreme forward- and backward-leaning positions is very high and independent of individual QS position.     

The conservation profile of a protein bears the imprint of the molecule that is evolutionarily coupled to the protein

The conservation profile of a protein is a curve of the conservation levels of amino acids along the sequence. Biologists are usually more interested in individual points on the curve (namely, the conserved amino acids) than the overall shape of the curve. Here, we show that the conservation curves of proteins bear the imprints of molecules that are evolutionarily coupled to the proteins. Our method is based on recent studies that a sequence conservation profile is quantitatively linked to its structural packing profile. We find that the conservation profiles of nucleic acid (NA) binding proteins are better correlated with the packing profiles of the protein–NA complexes than those of the proteins alone. This indicates that a nucleic acid binding protein evolves to accommodate the nucleic acid in such a way that the residues involved in binding have their conservation levels closely coupled with the specific nucleotides. Proteins 2015; 83:1407–1413. © 2015 Wiley Periodicals, Inc.     

Generic properties of edges and “corners” on smooth greyvalue surfaces

The edge line on a smooth greyvalue surface, defined as locus of maximal slope, is a curve embedded in the negatively curved part of the greyvalue surface. For an open and dense set of greyvalue functions the edge line has transverse double points as its only singular points, meets the parabolic curve tangentially at isolated points, and intersects the zero crossings of the Laplacean of the greyvalue function transversely. Defining a greyvalue corner as a curvature extremum of the edge line one can show that, again for an open and dense set of greyvalue functions, these corners are isolated points in the image corresponding to ordinary curvature extrema of the edge. Detecting such corners in greyvalue images requires differential operators containing partial derivatives of order five, which raises some doubts about the existence of numerically robust algorithms for detecting these features in digital images.     

On the dangers of making scientific models ontologically independent: taking Richard Levins’ warnings seriously

Levins and Lewontin have contributed significantly to our philosophical understanding of the structures, processes, and purposes of biological mathematical theorizing and modeling. Here I explore their separate and joint pleas to avoid making abstract and ideal scientific models ontologically independent by confusing or conflating our scientific models and the world. I differentiate two views of theorizing and modeling, orthodox and dialectical, in order to examine Levins and Lewontin’s, among others, advocacy of the latter view. I compare the positions of these two views with respect to four points regarding ontological assumptions: (1) the origin of ontological assumptions, (2) the relation of such assumptions to the formal models of the same theory, (3) their use in integrating and negotiating different formal models of distinct theories, and (4) their employment in explanatory activity. Dialectical is here used in both its Hegelian–Marxist sense of opposition and tension between alternative positions and in its Platonic sense of dialogue between advocates of distinct theories. I investigate three case studies, from Levins and Lewontin as well as from a recent paper of mine, that show the relevance and power of the dialectical understanding of theorizing and modeling.     

Reproducible Peak Clusters on Differential Mouse Mortality Curves and Their Relation to the Gompertz Model

It is shown that differentiation of mouse mortality curves (number of animals that died at a certain age plotted versus their lifespan) results in the appearance of eight clearly distinguished clusters of peaks corresponding to increased mortality rates. Smoothing of the original mortality curves and subsequent transformation of the differential mortality curves according to the Gompertz model makes the peaks and the corresponding clusters less pronounced and drives the logarithm of the force mortality curve toward a straight line. The positions of the clusters on the lifespan axis (expressed in days) were calculated as weighted means by dividing the sum of the products of multiplication of the peak heights and their position on the lifespan axis by the sum of the peak heights within a cluster. To prove that the peaks and their clusters are not random, we have demonstrated that the positions of the clusters on the lifespan axis do not depend on the extent of mortality curve smoothing or the group of mice analyzed.     

Position fine-tuning of caudal primary motoneurons in the zebrafish spinal cord

In zebrafish embryos, each myotome is typically innervated by three primary motoneurons (PMNs): the caudal primary (CaP), middle primary (MiP) and rostral primary (RoP). PMN axons first exit the spinal cord through a single exit point located at the midpoint of the overlying somite, which is formed beneath the CaP cell body and is pioneered by the CaP axon. However, the placement of CaP cell bodies with respect to corresponding somites is poorly understood. Here, we determined the early events in CaP cell positioning using neuropilin 1a (nrp1a):gfp transgenic embryos in which CaPs were specifically labeled with GFP. CaP cell bodies first exhibit an irregular pattern in presence of newly formed corresponding somites and then migrate to achieve their proper positions by axonogenesis stages. CaPs are generated in excess compared with the number of somites, and two CaPs often overlap at the same position through this process. Next, we showed that CaP cell bodies remain in the initial irregular positions after knockdown of Neuropilin1a, a component of the class III semaphorin receptor. Irregular CaP position frequently results in aberrant double exit points of motor axons, and secondary motor axons form aberrant exit points following CaP axons. Its expression pattern suggests that sema3ab regulates the CaP position. Indeed, irregular CaP positions and exit points are induced by Sema3ab knockdown, whose ectopic expression can alter the position of CaP cell bodies. Results suggest that Semaphorin-Neuropilin signaling plays an important role in position fine-tuning of CaP cell bodies to ensure proper exit points of motor axons.     

Derivation of the space horopter.

The horopter--the locus of those points in space that would stimulate corresponding points on the retinae of the two eyes--has been previously considered to be a plane curve lying in the horizontal plane. The two-dimensional character of this curve arises as a consequence of limiting all considerations to two dimensions only. However, by considering the retina as a two-dimensional surface in 3-space, geometric analysis reveals the horopter to be a non-planar curve: a twisted cubic curve in space. The classical horopter experiments can then be seen to be plotting self-corresponding lines rather than self-corresponding points, and these lines are found to be the chords of this cubic curve. The equations determining the horopter curve in parametric form have been found expressing each point of the curve as a function of the coordinates of the point of fixation.     

A reaction-diffusion model for interference in meiotic crossing over

One crossover point between a pair of homologous chromosomes in meiosis appears to interfere with occurrence of another in the neighborhood. It has been revealed that Drosophila and Neurospora, in spite of their large difference in the frequency of crossover points, show very similar plots of coincidence-a measure of the interference-against the genetic distance of the interval, defined as one-half the average number of crossover points within the interval. We here propose a simple reaction-diffusion model, where a "randomly walking" precursor becomes immobilized and matures into a crossover point. The interference is caused by pair-annihilation of the random walkers due to their collision and by annihilation of a random walker due to its collision with an immobilized point. This model has two parameters-the initial density of the random walkers and the rate of its processing into a crossover point. We show numerically that, as the former increases and/or the latter decreases, plotted curves of the coincidence vs. the genetic distance converge on a unique curve. Thus, our model explains the similarity between Drosophila and Neurospora without parameter values adjusted finely, although it is not a "genetic model" but is a "physical model," specifying explicitly what happens physically.     

Analytical morphometry of seminiferous tubules in maturation arrest: Fourier analysis of the internal contours of tubules

Shape of seminiferous tubuli in maturation arrest, is investigated by harmonic Fourier analysis and upper degree polynomials as attempt to find morphometric parameters useful in morphological diagnosis. Inner luminal contour is considered as a closed curve in a reference system and scattered in a series of points whose coordinates are automatically calculated. Then a software named S.A.M. (Shape Analytical Morphometry) is utilized to find the Kth-order equation and calculate the best-fit curve. Moreover an ellypse is drawn with the same barycenter and axes of original curve. These three curves (real curve, best-fit curve and ellypse) are considered as periodic functions and submitted to Fourier analysis to evaluate the coefficients of the series and the spectrum of harmonics. Among 20 contributors, the subsets of greatest amplitude are selected for comparison and classification in terms of fundamental shape and its perturbations.     

Detection of pectic enzymes in pectin-acrylamide gels

A rapid, sensitive slab gel electrophoretic method for the study of pectic enzymes is described. By incorporating pectin in acrylamide gels and subsequent staining with ruthenium red, simultaneous detection of esterases, glycosidases, and lyases was possible due to their differing staining reactions. Application of the method to the study of the thermal stability of enzymes is described. Approximate isoelectric points of the enzymes could be determined from their positions in the gel.     

A method for reconstructing three-dimensional positions of swarming mosquitoes

We developed a new field method for reconstructing the three-dimensional positions of swarming mosquitoes. This method overcame certain inherent difficulties accompanied by conventional stereoscopic methods and is applicable to three-dimensional measurements of other insect species. Firstly, we constructed a probabilistic model for stereoscopy; if mosquitoes and six reference points with known coordinates were photographed simultaneously from two or more perspectives, then from the positions of images of mosquitoes and the reference points on the photographs, 1) the position of each camera with respect to the reference points is estimated; 2) stereo images which correspond to an identical real mosquito are matched; and 3) the spatial positions of the mosquitoes are determined. We automated the processes 1), 2) and 3), developing computer programs based on our model. We then constructed a portable system for three-dimensional measurements of swarming mosquitoes in the field. Initial data that illustrate the application of our method to studying mosquito swarming were presented.     

Optimization of peptidic HIV‐1 fusion inhibitor T20 by phage display

The HIV fusion inhibitor T20 has been approved to treat those living with HIV/AIDS, but treatment gives rise to resistant viruses. Using combinatorial phage‐displayed libraries, we applied a saturation scan approach to dissect the entire T20 sequence for binding to a prefusogenic five‐helix bundle (5HB) mimetic of HIV‐1 gp41. Our data set compares all possible amino acid substitutions at all positions, and affords a complete view of the complex molecular interactions governing the binding of T20 to 5HB. The scan of T20 revealed that 12 of its 36 positions were conserved for 5HB binding, which cluster into three epitopes: hydrophobic epitopes at the ends and a central dyad of hydrophilic residues. The scan also revealed that the T20 sequence was highly adaptable to mutations at most positions, demonstrating a striking structural plasticity that allows multiple amino acid substitutions at contact points to adapt to conformational changes, and also at noncontact points to fine‐tune the interface. Based on the scan result and structural knowledge of the gp41 fusion intermediate, a library was designed with tailored diversity at particular positions of T20 and was used to derive a variant (T20v1) that was found to be a highly effective inhibitor of infection by multiple HIV‐1 variants, including a common T20‐escape mutant. These findings show that the plasticity of the T20 functional sequence space can be exploited to develop variants that overcome resistance of HIV‐1 variants to T20 itself, and demonstrate the utility of saturation scanning for rapid epitope mapping and protein engineering.