The history of Ervin Bauer's publications on the theory of life.

Ervin Bauer (1890-1938) made historical contributions to contemporary biology, provided a new definition of life, defined the contents of theoretical biology. He worked in different countries, perturbed by deep historical events. These historical events necessarily impacted his fate and finally led to the violent loss of his life and the life of his wife. His work and with it his theory of life had a no less complicated history than the history of his personal life. Bauer's main work "Theoretical Biology" was published in 1935 in Russian. The author and his wife Stefánia became victims of the Great Purge. They were executed in 1938, all their publications were banned and most copies of "Theoretical Biology" destroyed. Ervin and Stefánia Bauer were rehabilitated in 1956 but renewed publication of Bauer's works was delayed. The first reprint edition of "Theoretical Biology" of 1967 was not in Russian, but was a translation into Hungarian, the native language of Bauer. The first Russian reprint of "Theoretical Biology", in which the original Russian chapters are followed by short English summaries, was published in Hungary in 1982. This edition was prepared by Hungarian and Russian scientists. The best-known Russian edition of "Theoretical Biology" was published in 2002 in St. Petersburg. A complete English translation of Bauer's main work "Theoretical Biology" is still outstanding.

Ervin Bauer's concept of biological thermodynamics and its different evaluations.

The development of biological concepts in the 19th century was followed by the emergence of approaches to formulate the principles of theoretical biology. Ervin Bauer in 1920, and in more detail in 1935, suggested the basic principle that can be accepted as the fundamental law of biology: "The living systems are never in equilibrium; at the expense of their free energy they constantly perform work to avoid the equilibrium required by the laws of physics and chemistry under existing external conditions." Many researchers interpreted biology with the help of physical quantities but Bauer was the first to build a general and already molecular-based biological theory. The main point of Bauer's concept is not the non-equilibrium, but the function of organism producing the non-equilibrium, the capacity for self-adaptation, and the power for changing its functions in such a way that the system gets the state of non-equilibrium always anew. We will discuss Bauer's theorem, the contemporaneous objections, and the divergent opinions about his work by succeeding generations of scientists.

Modular Synthesis of (Borylmethyl)silanes through Orthogonal Functionalization of a Carbon Atom.

(Borylmethyl)trimethylsilanes are important building blocks in organic synthesis displaying a unique reactivity. Yet, the synthesis of more advanced derivatives is limited by the advanced silicon intermediates required for their preparation. Herein, a one-pot synthesis of (borylmethyl)silanes is developed, sourced on available alkyl-, aryl-, alkoxy-, aryloxy-, and silyl-hydrosilane materials. The privileged reactivity of N-hydroxyphthalimidyl diazoacetate (NHPI-DA) in Si-H insertion and α-silyl redox-active esters in different decarboxylative borylation reactions are scrutinized.

Aerobic Oxidations in Asymmetric Synthesis: Catalytic Strategies and Recent Developments.

Despite the remarkable advances in the area of asymmetric catalytic oxidations over the past decades, the development of sustainable and environmentally benign enantioselective oxidation techniques, especially with the efficiency level similar to natural enzymes, still represents a challenge. The growing demand for enantiopure compounds and high interest to industry-relevant green technological advances continue to encourage the research pursuits in this field. Among various oxidants, molecular oxygen is ubiquitous, being available at low cost, environmentally benign and easy-to-handle material. This review highlights recent achievements in catalytic enantioselective oxidations utilizing molecular oxygen as the sole oxidant, with focus on the mechanisms of dioxygen activation and chirogenesis in these transformations.

Generation of Mixed Anhydrides via Oxidative Fragmentation of Tertiary Cyclopropanols with Phenyliodine(III) Dicarboxylates.

Oxidative fragmentation of tertiary cyclopropanols with phenyliodine(III) dicarboxylates in aprotic solvents (dichloromethane, chloroform, toluene) produces mixed anhydrides. The fragmentation reaction is especially facile with phenyliodine(III) reagents bearing electron-withdrawing carboxylate ligands (trifluoroacetyl, 2,4,6-trichlorobenzoyl, 3-nitrobenzoyl), and affords 95-98% yields of the corresponding mixed anhydride products. The latter can be straightforwardly applied for the acylation of various nitrogen, oxygen and sulfur-centered nucleophiles (primary and secondary amines, hydroxylamines, primary alcohols, phenols, thiols). Intramolecular acylation yielding macrocyclic lactones can also be performed. The developed transformation has bolstered the synthetic utility of cyclopropanols as pluripotent intermediates in diversity-oriented synthesis of bioactive natural products and their synthetic congeners. For example, it was successfully applied for the last-stage modification of a cyclic peptide to produce a precursor of a known histone deacetylase inhibitor.

Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via a Late-Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin.

A unified step-economical strategy for accessing histone deacetylase inhibitory peptides is proposed, based on the late-stage installation of multiple zinc-binding functionalities via the cleavage of the strained cyclopropane ring in the common pluripotent cyclopropanol precursor. The efficacy of the proposed diversity-oriented approach has been validated by short stereoselective synthesis of natural product chlamydocin, containing a challenging-to-install fragment of (2S,9S)-2-amino-8-oxo-9,10-epoxydecanoic acid (Aoe) and a range of its analogues, derivatives of 2-amino-8-oxodecanoic and 2-aminosuberic acids.

Synthesis of γ-keto sulfones by copper-catalyzed oxidative sulfonylation of tertiary cyclopropanols.

Tertiary cyclopropanols undergo ring-opening oxidative sulfonylation to afford γ-keto sulfones when reacting with sulfinate salts in the presence of a copper(ii) acetate catalyst and an oxidant (tert-butyl hydroperoxide or atmospheric oxygen). Various fluoroalkyl, aryl and alkyl sulfinate salts are successfully employed as sulfonylation reagents, affording the corresponding sulfones in up to 94% yields. The experimental protocol is mild and tolerates a number of functionalities in the cyclopropanol substrate. The reaction proceeds via a one-pot oxidation-Michael addition mechanism and can serve as a useful addition to the existing methods for the preparation of γ-keto sulfones based on the sulfa-Michael reaction.

Enantioselective One-Pot Synthesis of α,ß-Epoxy Ketones via Aerobic Oxidation of Cyclopropanols.

An efficient, mild, and environmentally benign method was developed for the asymmetric synthesis of 2-oxyranyl ketones from easily available tertiary cyclopropanols. The one-pot protocol includes the aerobic oxidation of cyclopropanol derivatives catalyzed by Mn(III) complexes followed by the poly-l-leucine-assisted stereoselective elimination of water from the intermediate peroxides with DBU to afford the corresponding epoxy ketones in high yields and good-to-excellent enantioselectivities (up to 97%).

The living matter according to Ervin Bauer (1890-1938), (on the 75th anniversary of his tragic death) (History).

Ervin Bauer is one of the first theoretical biologists distancing his ideas both from vitalism and mechanicism. He formulated the principle of permanent non-equilibrium of living systems (Bauer's principle) in terms of thermodynamics in 1920. Bauer's scientific path can be divided into three periods. In the early 1920s he proposed his principle as an axiom that cannot be derived from contemporary natural sciences. In the late 1920s he reformulated it in a way that it could be subjected to experimental testing. Summarizing his views in the 1930s in his book, Theoretical Biology, he tried to show that his axiom is indeed the fundamental principle of biology. This later view was anachronistic in spite of many striking insights of Bauer. The energetic formulation of Bauer's principle is, however, a realistic characterization of living organisms and it can be derived from the theory of open systems - in fact it contributed to the formulation of that theory. Bauer's principle can be incorporated into non-linear thermodynamics of irreversible processes.

A path or a new road in laboratory diagnostics? Biological mass spectrometry: facts and perspectives.

Proteins in tissues and biofluids and their many attributes define the proteome. Proteome can be directly correlated to known diseases and histological regions allowing the diagnosis and monitoring of disease progression as well predicting the patient's response to specific treatments. Proteomics performs large-scale, high-throughput characterization of the human proteome, among others by biological mass spectrometry. Proteinchip technology coupled with bioinformatics is able to screen any protein source for putative disease biomarkers from a small sample volume (microliter range) by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). This article discusses on a basic level both the technology and reliability of these methods.

Early diagnosis of pancreatobiliary duct malignancies by brush cytology and biopsy.

Two hundred and five preoperative intraductal samplings (brushing and biopsy) were evaluated from 113 patients with biliary or Wirsung duct strictures. One hundred and three strictures could be specified by histology of the operative specimens, autopsy, or by the patients' clinical course. Preoperative diagnostic efficacy depended on the tumor location (it was the best for ampullary and para-papillary tumors), but the average quantitative indices for sensitivity, absolute sensitivity, specificity, positive and negative predictive values, diagnostic accuracy of cytology were 53%, 20%, 100%, 100%, 25%, 59%, respectively. The same values for biopsy were 43%, 34%, 100%, 100%, 36% and 56%. These figures improved after simultaneous cytology and biopsy. Close cooperation with the endoscopist was necessary in cases of negative, inconclusive and dysplastic (27%) samples. Repetition of sampling improved the results by 8%. Among the 26 preoperative false negative cases, sampling-, technical- and interpretative errors occurred in 84%, 4% and 12%, respectively. Revision of samples revealed 4 malignant cases among the false negative cytologic brushings. Reclassification of specimens considering the latest criteria - primary and secondary malignant features, pancreatic intraepithelial neoplasia (PanINs), etc. - resulted in improvement of the diagnostic efficiency.

[Subtotal colectomy in the course of gallstone-ileus surgery]. / Subtotalis colectomia epekó-ileus mütétje során.

A big gallstone penetrating through a bilio-digestive fistula into the bowel can make a complete obstruction of it in the majority of the cases requiring an urgent operation. It is a rare situation that a fistula like this leads into the colon and the stone makes a large bowel obstruction. A 72-year-old male patient was admitted to our department with the symptoms of colon obstruction. After the examinations he underwent an explorative laparotomy. During the course of the operation an obstruction was found in the proximal third of the descending colon. A subtotal colectomy was carried out. At the opening of the resected colon a big gallstone was found as the cause of the obstruction, which simulated a tumorous obstruction. We present through this case the possibilities and results of the diagnosis and treatment of gallstone ileus. We conclude that in the prevention of gallstone ileus, the early operative treatment of detected gallstone is essential.

Histological evaluation of preoperative biopsies from ampulla vateri.

Frequency of the lesions of the papilla Vateri is increasing in Hungary because of epidemiological reasons. Over two years nearly 300 ampullary endoscopic biopsies were taken in our hospital. In 36 percent of the patients the papillary specimens demonstrated acute or chronic inflammation, in 44 percent adenoma, including 5 percent with severe dysplasia, in 5 percent adenomatous hyperplasia and in 7 percent adenomyosis or other benign tumors (2%) were found. Around 7 percent of the ampullary samples proved to be malignant, but only in 2.6 percent were the malignancy of intraampullary origin. Nearly 25 percent of biopsies were repeated once and 10 percent twice or more. Concordance of endoscopic and pathologic diagnoses was 69 percent on average but it increased to 83 percent after including repeated biopsies. In the adenoma-carcinoma group the concordance was 90 percent. The sensitivity of the pathological diagnosis with forceps biopsy was only 77 percent, but it became at least 86 percent following papillectomy. In order to improve diagnostic reliability more extensive use of papillectomy is proposed with close cooperation between the endoscopist and pathologist.

[Sphincter of Oddi dysfunction--prolonged medical therapy or early endoscopic sphincter ablation]. / Oddi-sphincter-dyskinesis--elhúzódó gyógyszeres kezelés vagy korai endoszkópos papillotomia.

INTRODUCTION: Sphincter of Oddi dysfunction is a real challenge from both diagnostic and therapeutic point of view. PATIENTS AND METHODS: In the last two years the authors have performed ERCP and EST in 29 patients with positive evocative test results, who had important enzyme elevations and/or did not respond to prolonged medical treatment. RESULTS: Endoscopic findings were positive in 25/29 patients (86.2%): 8 adenoma of p. Vateri, 17 papillitis were identified, and in 4 cases the papilla was intact. Histopathology obtained in 12 patients supported the diagnosis. In 6 patients, who underwent a postpapillotomy evocative test, after an average of 10 months follow up the results have been converted from positive to negative response in all but two cases. The two patients continued to have abdominal symptoms with persistent positive provocation tests because of restenosis, were treated with repapillotomy. CONCLUSIONS: The Debray and Nardi tests are useful screening tests for hypertonic biliary or pancreatic dyskinesia. Structural endoscopic and histological findings are frequent already in the functional cases. Early sphincter ablation should be considered in failure of medical therapy for preventing the transformation of this functional disorder into an organic, potentially precancerous state.

On the Brain-State-in-a-Convex-Domain Neural Models.

We propose and investigate new types of neural network models. They can be viewed as discrete linear systems operating on closed and bounded, that is, compact, convex domains. We first analyze the dynamic behavior of a neural network model on an arbitrary convex domain. Then, we analyze two specific cases: when the convex domain is a ball, and the case when the convex domain is a simplex. The equilibrium points of the proposed neural models are located and their stability is investigated. Copyright 1996 Elsevier Science Ltd