Fitting the linear-quadratic model using time of occurrence as the end-point for quantal response multifraction experiments

A statistical technique is given for fitting the linear-quadratic model to experimental quantal response multifraction data using the time of the response as the end-point. The analysis used is based on the Cox Proportional Hazards model. The technique is useful for late effects where the time of occurrence of the response is dose dependent. The technique is compared to logistic regression analysis and the advantages and disadvantages are discussed. Both methods are applied to a lung pneumonitis experiment and a kidney experiment.     

A systematic approach to isomorphous replacement using a series of simple charged mercurials.

Three novel mercury derivatives bearing different electronic charges have been synthesized and used to prepare useful heavy atom derivatives of crystals of glycogen phosphorylase $\text{a}$. While exhibiting some common binding sites on the exterior of the molecule, their internal binding sites are determined primarily by their charge as predicted. Their ease of preparation and general applicability makes them useful candidates for the preparation of heavy atom derivatives of any protein crystals in X-ray crystallographic studies.     

Metabolic depression and Na+/K+ gradients in the aestivating Australian goldfields frog,Neobatrachus wilsmorei

During aestivation the metabolic rate of the Australian goldfields frog Neobatrachus wilsmorei was reduced by 80% from its standard metabolic rate. The in vitro rate of oxygen consumption of isolated muscle and skin from aestivating frogs was up to 50% lower than that of the non-aestivating frogs. This in vitro rate of oxygen consumption was maintained for 6–12 h, indicating an intrinsic metabolic depression of tissues during aestivation. Frogs became dehydrated during aestivation. Muscle, skin and liver also became dehydrated during aestivation, but brain and kidney did not. Na⁺ and K⁺ contents and extracellular space measurement for muscle indicated that ion gradients were maintained across the muscle cell membrane during aestivation. Increases in plasma concentrations of Na⁺ and K⁺ were matched with similar increases in muscle intracellular ion concentrations. Extracellular space measurements were unsuccessful in the other tissues, but K⁺ content in all tissues (per dry weight) was maintained during aestivation, and the concentration of plasma K⁺ did not increase above that which can be accounted for by dehydration, indicating that K⁺ gradients were maintained.Abbreviations bm body mass - DPM disintegrations per minute - dw dry weight - MR metabolic rate - vO₂ rate of oxygen consumption - ww wet weight     

Bacillus spp. in the rumen ecosystem. Hemicellulose depolymerases and glycoside hydrolases of Bacillus spp. and rumen isolates grown under anaerobic conditions

Bacillus spp. were isolated from the rumen contents of animals fed on hay. The bacilli were present in the vegetative form in the microbial populations of the liquid phase and in those associated with the particulate material in the digesta. Thirty-six isolates were identified as strains of B. licheniformis (14), B. circulans (14), B. coagulans (2), B. laterosporus (3) and three isolates were facultative anaerobes that resembled B. pumilus. All were able to utilize isolated Lolium perenne hemicellulose B as a carbon source when grown aerobically or anaerobically at 39°C. A survey of 17 Bacillus species (24 strains including 5 rumen isolates) confirmed that enzymes capable of releasing reducing sugars from hemicelullosic polysaccharides were present in many anaerobically grown bacilli; in addition, the range and specific activities of 20 glycoside hydrolases were also monitored in these crude enzyme preparations. The presence and possible role of Bacillus spp. in the rumen digesta particle-associated microbial population is discussed.     

Dissection of nucleophilic and acid–base catalysis in glycosidases

A startling array of added anions have been observed to function as replacement catalytic nucleophiles in mutant glycosidases, including formate, azide, fluoride and other halides. Likewise, the mechanism of acid–base catalysis is somewhat plastic. The carboxylic acids can be substituted by a sulfenic acid or by ascorbate, and the effective acid strength enhanced by the introduction of strong hydrogen bonds. These studies provide an interesting bridge between enzymes and models thereof.     

Corynebacterium parvum: Effect on radiocurability of murine tumors

Summary In continuation of our earlier studies (Milas et al., 1975c) we have investigated whether treatment of mice with Corynebacterium parvum augments the curative response of a fairly immunogenic fibrosarcoma (FSa) and a weakly immunogenic mammary carcinoma (MDAH-MCa-4) to fractionated v-irradiation. Tumors were 8 mm in diameter at the commencement of radiation treatment. The FSa was exposed to 500 and the MDAH-MCa-4 to 750 rads daily for 3, 6, or 10 consecutive days. The dose of CP was 0.25 mg and was given intravenously (IV), in most experiments within 2 h after the first irradiation dose. In one experiment involving FSa, CP administration varied from 4 days before to 14 days after the start of irradiation. CP greatly augmented FSa radiocurability, especially when applied before irradiation. The effect was evident from the increase in the cure rate, and, in mice that were not cured, from tumor growth retardation, which resulted in prolonged survival of mice. CP also reduced the incidence of pulmonary metastases in mice in which the combination of treatments failed to produce local tumor control. CP was less effective in augmenting radiation response of MDAH-MCa-4. In this case, CP slowed the growth of irradiated tumors and prolonged the survival of mice. The effect of IV CP on FSa radiocurability was not further increased by including intralesional (IL) injection of CP, intraperitoneal (IP) injection of vitamin A, or the radiosensitizer of hypoxic tumor cells misonidazole (Ro-07-0582). Misonidazole, however, significantly improved the effect of 2000 rads on the growth retardation of mammary carcinoma, but CP did not further enhance this effect.     

Dissection of nucleophilic and acid-base catalysis in glycosidases.

A startling array of added anions have been observed to function as replacement catalytic nucleophiles in mutant glycosidases, including formate, azide, fluoride and other halides. Likewise, the mechanism of acid-base catalysis is somewhat plastic. The carboxylic acids can be substituted by a sulfenic acid or by ascorbate, and the effective acid strength enhanced by the introduction of strong hydrogen bonds. These studies provide an interesting bridge between enzymes and models thereof.