Validation of Inference Procedures for Gene Regulatory Networks

The availability of high-throughput genomic data has motivated the development of numerous algorithms to infer gene regulatory networks. The validity of an inference procedure must be evaluated relative to its ability to infer a model network close to the ground-truth network from which the data have been generated. The input to an inference algorithm is a sample set of data and its output is a network. Since input, output, and algorithm are mathematical structures, the validity of an inference algorithm is a mathematical issue. This paper formulates validation in terms of a semi-metric distance between two networks, or the distance between two structures of the same kind deduced from the networks, such as their steady-state distributions or regulatory graphs. The paper sets up the validation framework, provides examples of distance functions, and applies them to some discrete Markov network models. It also considers approximate validation methods based on data for which the generating network is not known, the kind of situation one faces when using real data.Key Words: Epistemology, gene network, inference, validation.     

Combined Schiff Procedures

The usefulness of the PAS reaction in histological investigation is frequently enhanced when it can be combined with other procedures. This is frequently difficult to accomplish due to adverse interaction of the more numerous reagents necessary for combined techniques. Details are given for methods of combining PAS staining with iron hematoxylin, direct silver, and aldehyde fuchsin and for the use of the Feulgen reaction to provide nuclear staining for Sudan black preparations.     

Computer-Intensive Statistical Procedures

The overall goal of this review is to summarize the current body of knowledge about the structure and function of major proteins of Bacillus anthracis and/or similar spore-forming organisms. B. anthracis is a key spore-forming biological threat agent, as well as human and animal Gram-positive bacterial pathogen. The structural information described here is limited to approximately the last 5 years. This information is then related to the role of the selected proteins in pathogenesis and in the possible development of novel vaccine and/or other antimicrobial agents against spore-forming organisms, including anthrax, a disease caused by B. anthracis.

Among spore-forming bacteria, Bacillus and Clostridium species are the predominant spore-forming bacilli that cause serious diseases. The biochemical properties and mechanism of catalysis of the novel spore germination protease that degrades small, acid-soluble proteins protecting DNA against damage, a cofactor independent phosphoglycerate mutase, NAD⁺ synthetase, and the three know B. anthracis toxins, protective antigen, lethal factor, and edema factor are described. The studies described in this work review and unify selected information critical for the prevention of microbial diseases such as anthrax. A strategy for the structure-guided development of new prophylactic and therapeutic agents is discussed.     

Technical Procedures for the Study of the Nucleolonema

In a recent paper¹ the authors have shown filamentous structures within the nucleolus of all cells. This structure was named the nucleolonema. In the present paper the technical procedures which prove their existence are described in detail.

There are two groups: a) Silver impregnation procedures and iron-pyrogallic stain for fixed material; b) phase contrast microscopy, dark-field illumination and oblique transillumination for fresh material.

The suitable objects are mentioned in every case in order to obtain the best results.     

Technical Procedures for the Study of the Nucleolonema

In a recent paper¹ the authors have shown filamentous structures within the nucleolus of all cells. This structure was named the nucleolonema. In the present paper the technical procedures which prove their existence are described in detail.

There are two groups: a) Silver impregnation procedures and iron-pyrogallic stain for fixed material; b) phase contrast microscopy, dark-field illumination and oblique transillumination for fresh material.

The suitable objects are mentioned in every case in order to obtain the best results.     

Regulatory GTPases

The past year has witnessed a tremendous increase in our understanding of the structures and interactions of the GTPases. The highlights include crystal structures of Gα subunits, as well as the first complex between a GTPase (Rap1A) and an effector molecule (c-Raf1 Ras-binding domain). In the field of elongation factors (EFs), three very important structures have been determined: EF-G, the ternary complex of EF-Tu·GTP with aminoacyl-tRNA, and the EF-Tu·EF-Ts complex.     

On the Applicability of Multidimensional Classification Procedures

An example from the EEG-analysis shows that particularly in using the R-error estimation the variance analysis and discrimination might indicate contradictory results. Therefore the use of results of MANOVA for a subsequent discrimination appears not to be advisable as a rule. If the number of test persons per class does not amount to at least the five-fold of the number of characters, the error estimation according to the R-method is not applicable. Since the feature selection by the methods investigated in this paper only pretend an improvement of the classification, producing even misleading results in single cases, it should not be used, at least not with smaller random samples.     

Surgical Procedures in Nonagenarians

During the hospital course of 225 nonagenarian patients who underwent 285 major operations—80% on the general, vascular, orthopedic and urologic services—overall morbidity was 37% and mortality 7.5%. The 100 emergency operations were associated with a higher morbidity and mortality rate. Nonsurvivors were more likely to have associated cardiac or cerebral medical conditions, higher utilization of intraoperative invasive hemodynamic monitoring and greater use of surgical intensive care units. Compared with all surgical patients, the nonagenarians were admitted twice as often to the surgical intensive care unit, required twice the number of hospital days, underwent intraoperative hemodynamic monitoring twice as frequently and incurred 200% greater hospital charges. We conclude that with careful evaluation and management, a nonagenarian patient presenting with a surgical condition can safely undergo necessary operative procedures.     

Diagnostic Procedures in Sarcoidosis

One hundred consecutive patients suspected of having sarcoidosis were examined by means of available diagnostic procedures and the results of the examinations were compared. While Kveim tests and/or lymphocyte transformation tests gave the most significant results in cases of less than two years'' standing, a combination of these and organ biopsies is required for the diagnosis of cases of more than two years'' duration.An interpretation of the immunological deviations observed in sarcoidosis is attempted on the basis of observations made on leukocyte cultures and on isolations of mycobacteriophages from patients with sarcoidosis.