A new approach to isotonic agglomerative hierarchical clustering

Hierarchical clustering methods must be isotonic for the construction of ultrametric. We present a general strategy to widen the class of isotonic methods implemented by agglomerative algorithms. At each step of the agglomeration we allow one of several admissible pairs to be chosen. Then under mild assumptions an appropriate definition of admissibility guarantees isotony. Moreover we consider the use of the new methods to compute locally optimal ultrametrics. Two examples demonstrate the ability to define new agglomerative methods superior to their traditional competitors.     

Über Helligkeitsbestimmungen an Gesteinen

Ohne Zusammenfassung     

Möglicher Einfluß chemischer Gleichgewichte auf Viskosität und Relaxationszeit im Erdinnern

Summary A thermodynamic consideration shows that SiO₂ may be reduced to Si by hydrogen at the temperatures present in the earth's interior. The reaction can be expected to involve a rapid change of viscosity with depth inside the earth, required for the explanation of the seismic discontinuity at 2,900 km.     

New concepts in regulation and function of the insulin-like growth factors: implications for understanding normal growth and neoplasia

The insulin-like growth factors (IGFs) are a ubiquitous family of growth factors, binding proteins and receptors that are involved in normal growth and development. They are also implicated in numerous pathological states, including malignancy. IGF-II is a commonly expressed growth factor in many tumors and may enhance tumor growth, acting via the overexpressed IGF-I receptor, a cell-surface tyrosine kinase receptor. The IGF-I receptor may be overexpressed due to mutations in tumor suppression gene products such as p53 and WT-1 or growth factors such as bFGF and PDGF. Thus, this family of growth factors, especially the IGF-I receptor, may present an excellent target for new therapeutic agents in the treatment of cancer and other disorders of excessive cellular proliferation.     

Inhibition of arylpyruvate oxidase by chelating agents

Zusammenfassung Die Hemmung der Phenylpyruvat- undp-Hydroxyphenylpyruvat-Oxydasen durch Chelat-Wirkstoffe wurde offenbar durch die Bildung eines Enzym-Wirkstoff-Komplexes verursacht, der bei Behandlung mit Kationen oder mit Sephadex trennbar ist. Die Reinigung des Enzyms führt zur Kupferanreicherung des Präparates, welches eine scheinbar funktionelle Einheit mit dem Enzym bildet.

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This work was supported in part by Research Grant No. MH-02278 from the National Institute of Mental Health, U.S.P.H.S.

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We wish to thank Dr.W. A. Bulen for helpful discussions about the mechanism of inhibition, and Dr.M. D. Armstrong for his encouragement during this project.     

Spontaneous miniature activity and gradation of transmission at the neuromuscular junction

Zusammenfassung Aus den bisher veröffentlichten experimentellen Befunden über presynaptische, für die neuromuskuläre Erregungsübertragung massgeblich erscheinende Vorgänge wird geschlossen, dass die Förderung der Erregungsübertragung in direkter Beziehung zur Grösse des Aktionspotentials in den motorischen Nervenendigungen steht, während die Frequenz der spontanen Miniaturentladungen an sich kein eindeutiges Mass für die Intensität des Übertragungsvorganges von Nervimpulsen zum Muskel darstellt.     

Suppression and enhancement of humoral immune response toToxoplasma gondii by passive antibody

Summary Anti-toxoplasma antibodies administered passively to mice may lead to suppression or enhancement (reported for the first time with Protozoan parasites) of subsequent antibody response when these animals are later infected withToxoplasma gondii. The outcome is dependent on infecting strain of Toxoplasma and the antigen-antibody ratio.     

Dihydrobenzothiadiazine dioxides with potent diuretic effect

Zusammenfassung Die Gewinnung eines neuen, tierexperimentell und klinisch hochwirksamen Diureticums der Formel III (6-Chlor-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazin-1,1-dioxyd) wird beschrieben.      

Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice

Williams syndrome is a neurodevelopmental disorder caused by the hemizygous deletion of 1.6 Mb on human chromosome 7q11.23. This region comprises the gene CYLN2, encoding CLIP-115, a microtubule-binding protein of 115 kD. Using a gene-targeting approach, we provide evidence that mice with haploinsufficiency for Cyln2 have features reminiscent of Williams syndrome, including mild growth deficiency, brain abnormalities, hippocampal dysfunction and particular deficits in motor coordination. Absence of CLIP-115 also leads to increased levels of CLIP-170 (a closely related cytoplasmic linker protein) and dynactin at the tips of growing microtubules. This protein redistribution may affect dynein motor regulation and, together with the loss of CLIP-115-specific functions, underlie neurological alterations in Williams syndrome.     

Nonlinear dynamics of ice-wedge networks and resulting sensitivity to severe cooling events

Patterns of subsurface wedges of ice that form along cooling-induced tension fractures, expressed at the ground surface by ridges or troughs spaced 10 30 m apart, are ubiquitous in polar lowlands. Fossilized ice wedges, which are widespread at lower latitudes, have been used to infer the duration and mean temperature of cold periods within Proterozoic and Quaternary climates, and recent climate trends have been inferred from fracture frequency in active ice wedges. Here we present simulations from a numerical model for the evolution of ice-wedge networks over a range of climate scenarios, based on the interactions between thermal tensile stress, fracture and ice wedges. We find that short-lived periods of severe cooling permanently alter the spacing between ice wedges as well as their fracture frequency. This affects the rate at which the widths of ice wedges increase as well as the network's response to subsequent climate change. We conclude that wedge spacing and width in ice-wedge networks mainly reflect infrequent episodes of rapidly falling ground temperatures rather than mean conditions.