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Sumoylation is a reversible post-translational modification of proteins by small ubiquitin-like modifier (SUMO) that regulates protein function and contributes to cellular response to stress. Sumoylation is an essential pathway for all cells and is involved in diverse processes such as inflammation, DNA damage response, signaling and cell survival/apoptosis. Due to its involvement in such cellular functions, sumoylation intersects with the majority of the hallmarks of cancer. Many cancers display elevated expression of SUMO pathway components, a mechanism co-opted by tumors to survive under stressful conditions. In addition to its tumor intrinsic functions, sumoylation has emerged as a novel target for activating anti-tumor immunity due to its role in regulating type I interferon (IFN) signaling. Targeting sumoylation is a compelling anti-cancer strategy due to the multiple mechanisms of action that may drive anti-tumor activity for cancer patients. We report the discovery of SB-4826, a novel, orally active, covalent small molecule inhibitor of the Sumo Activating Enzyme (SUMO E1), the initiating enzyme of the sumoylation cascade. SB-4826 selectively and irreversibly binds an allosteric pocket of SUMO E1 and drives potent biochemical and cellular activity. SB-4826 inhibits global sumoylation in cells and blocks proliferation across a broad panel (100+) of cancer cell lines. Cysteine-proteome profiling by mass spectrometry indicated that Cys-30 of SUMO E1 was the only cysteine-containing peptide (out of 14,541 measured) that met the criteria for covalent engagement indicating exquisite selectivity across the cellular proteome. In an in vivo pharmacodynamic model measuring IFN signaling SB-4826 treatment led to dose- and time-dependent induction of IFN regulated cytokines. SB-4826 treatment resulted in significant tumor growth inhibition in multiple in vivo models. In a syngeneic A20 lymphoma model SB-4826 led to tumor stasis. In a human RAJI xenograft model, SB-4826 induced near-complete inhibition of tumor growth as a single agent and resulted in tumor regression when combined with rituximab. In a mouse CT-26 colorectal tumor model which is generally refractory to anti-PD-1 treatment, SB-4826 significantly inhibited tumor growth as monotherapy and led to 60% complete tumor responses when combined with anti-PD-1. SB-4826 caused increased CD8+ T cell infiltration in CT-26 tumors supporting the role of SB-4826 in inducing IFN signaling and leading to a tumor microenvironment that is more responsive to immune checkpoint inhibition. SUMO E1 is a clinically validated cancer target as evidenced by recent data showing encouraging responses to TAK-981, an IV-administered, ATP-competitive inhibitor. SB-4826 is a differentiated and optimized SUMO E1 inhibitor that is administered orally and demonstrated improved activity in preclinical models. SB-4826 has favorable properties for development, is a new and promising cancer therapy, and is entering phase 1 clinical studies in 2023. Citation Format: Jude R. Canon, Ashley Callinan, Sarah Bradley, Laurie Wang, Mackenzie Kui, Ariel Wein, Gabriele Sulli, Peter Buchowiecki, Fang-Tsao Hong, Miles Kubota, Mary Walton, Victor J. Cee. SB-4826, a first-in-class oral, covalent inhibitor of SUMO E1 that induces IFN signaling and inhibits tumor growth as monotherapy and in combination with immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB318.

The native prairie of the southern Great Plains has been especially modified by two related forces: conversion of native prairie to agricultural forms of land use and removal of black-tailed prairie dogs (Rodentia: Sciuridae, Cynomys ludovicianus (Ord, 1815)) that act as ecosystem engineers via their burrowing and grazing activities. It is unknown how these changes have affected the native bee community. We surveyed the bee communities in relatively intact native prairie at two National Wildlife Refuges in Texas, quantifying bee community structure as a function of the presence/absence of grazing by prairie dogs. Over a 5-mo sampling period in spring-summer 2013, we found high overall bee diversity (180 species, mostly solitary ground-nesters), with differences detected in diversity between Muleshoe and Buffalo Lake National Wildlife Refuges as well as on and off prairie dog colonies. Although the same three species dominated the bee community at both refuges, most species were represented by relatively few individuals, leading to overall differences in diversity (richness, evenness, and effective number of species) by refuge. Bee diversity differed between sites on and off prairie dog colonies, but in trends that differed by refuge and by index, suggesting that location was more important than prairie dog presence. These results represent a reference fauna against which other regional bee communities in other land-cover types can be compared, but the high spatial heterogeneity we found indicates that detecting effects of landscape change on native bees will be challenging.

Recent experience with damage and failure due to graphitization in electric power plant piping of carbon (C) and carbon-molybdenum (C-Mo) steel suggests that the previously developed time-temperature curves for graphitization prediction, first published over two decades ago, merit review. Recent data were combined with an exhaustive review of available literature. As with the earlier research, available experience data with reported approximate extent of graphitization and nominal service exposure conditions were analyzed for the predictions. When the data were combined, the database consisted of 281 data points. The data are in contrast to the roughly 40 points used in the prior research. The nature of the expanded C steel weldment database was such that the analysis could not effectively discriminate between all of the five graphitization levels used in previous research efforts. In this analysis, it was found that the level of graphitization as a function of time and temperature could be categorized into three broad “risk” ranges—defined as low, moderate, and significant, and that the curves delineating these ranges could be developed in a statistically conservative manner. These conservative time-temperature prediction curves are offered as an update to the previous time-temperature curves. Although the data for C-Mo steel base metal and weldments and on C steel base metal were inadequate for a full quantitative analysis, the experience with these materials cases is presented within the context of the C steel weldment risk curves and preliminary time-temperature conditions warranting concern for graphitization are offered. Finally, a partial validation of the risk curves is presented in examination of power plant piping that had operated for over 400,000 h.

We intensively sampled fishes from two reaches of the Rio Grande within the Albuquerque Basin (Albuquerque and Belen valleys) during 1998–2001, compared our findings with those from 1984, and compiled a list of all fishes known from the two reaches. Structure of assemblages (richness, diversity, abundance distributions–taxon dominance versus rank abundance) was similar between reaches in 1998–2001, but the faunas had low taxonomic similarity. The nonnative white sucker (Catostomus commersonii), western mosquitofish (Gambusia affinis), and native red shiner (Cyprinella lutrensis) dominated the Albuquerque Valley. Faunal change in the Albuquerque Valley between 1984 and 1998–2001 indicated all native fishes besides the red shiner declined, particularly the Rio Grande silvery minnow (Hybognathus amarus) and longnose dace (Rhinichthys cataractae). In contrast, the red shiner alone dominated the Belen Valley, nonnative fishes were less dominant, and aside from the Rio Grande silvery minnow and longnos...

We report the diagnosis and outcome of a fetus with an unusual left ventricular wall defect. A 34-week fetus presented for echocardiographic evaluation because of an irregular cardiac rhythm. Fetal echocardiography revealed frequent ventricular ectopy and an “accessory” ventricular chamber diagnosed as a left ventricular diverticulum (LVD). The ectopy resolved in utero but recurred after delivery. Angiography revealed a “bifid” LVD. Inderal therapy suppressed the ventricular ectopy. The association between ventricular ectopy and LVD is unusual, but the prognosis of LVD even with arrhythmia is excellent.

Linear α-olefins (LAOs) find industrial use as high-value chemical intermediates. Most of the LAO production is based on ethylene oligomerization and does not yield a market-related product distribution. Various non-ethylene-based LAO production routes have been evaluated and it was found that a process based on boron chemistry was the most likely to be successfully commercialized. Process flow diagrams for a low-temperature (150−200 °C) continuous boron-based process to produce LAOs from linear internal olefins are presented, showing that it can be designed with or without a solvent in the boron cycle. Experimental data are presented to illustrate progress made in understanding the chemistry associated with such a process. It is shown that (a) solvent exchange competes with hydroboration and is rate-controlling by regulating borane availability, (b) reactivity of substituted boranes is determined by the availability of the empty pz orbital of boron, (c) steric effects influence the rate of hydroboration ...

As a poet, novelist, and playwright, Sebastian Barry has established his reputation, in recent years, as one of Ireland's young literary stars. Particularly through his efforts for the stage and through his 1995 breakout play, The Steward of Christendom, Barry finds himself today compared to and associated with that host of Irish playwrights — including Brian Friel, Fr;nk McGUinness, Tom Murphy, Marina Carr, and Martin McDonagh — who have revitalized Irish theatre in the last few decades. Barry also shares a common goal with these playwrights: restaging Ireland.

Despite the critical role that shear is hypothesized to play in the damage modes that limit the performance of total hip and knee replacements, the shear behavior of ultra-high molecular weight polyethylene (UHMWPE) remains poorly understood, especially after oxidative degradation or radiation crosslinking. In the present study, we developed the miniature specimen (0.5 mm thickness×6.4 mm diameter) shear punch test to evaluate the shear behavior of UHMWPE used in total joint replacement components. We investigated the shear punch behavior of virgin and crosslinked stock materials, as well as of UHMWPE from tibial implants that were gamma-irradiated in air and shelf aged for up to 8.5 years. Finite element analysis, scanning electron microscopy, and interrupted testing were conducted to aid in the interpretation of the shear punch load–displacement curves. The shear punch load–displacement curves exhibited similar distinctive features. Following toe-in, the load–displacement curves were typically bilinear, and characterized by an initial stiffness, a transition load, a hardening stiffness, and a peak load. The finite element analysis established that the initial stiffness was proportional to the elastic modulus of the UHMWPE, and the transition load of the bilinear curve reflected the development of a plastically deforming zone traversing through the thickness of the sample. Based on our observations, we propose two interpretations of the peak load during the shear punch test: one theory is based on the initiation of crystalline plasticity, the other based on the transition from shear to tension during the tests. Due to the miniature specimen size, the shear punch test offers several potential advantages over bulk test methods, including the capability to directly measure shear behavior, and quite possibly infer ultimate uniaxial behavior as well, from shelf aged and retrieved UHMWPE components. Thus, the shear punch test represents an effective and complementary new tool in the armamentarium of miniature specimen mechanical testing methods for UHMWPE used in total joint replacement components.

This case study describes a bilobed or bipartite placenta followed by serial ultrasound. Incidence of occurrence is reported by Fujikura et al as 4.2% in a study of 8505 deliveries,or approximately 1 in 357 deliveries. The diagnosis of an anomalous placenta is important for patient management at time of delivery. Specifically,the bilobed placenta can be associated with first-trimester bleeding,polyhydramnios,abruption,and retained placenta. Care ful attention to the cord insertion is also required for optimal fetal management. The authors describe the sonographic features and evolution of a bilobed placenta and its relationship to the pregnancy outcome.

Recent, brittle fracture in Grade 23 power plant components at relatively low temperatures has increased the need to assess the cracking behavior of this material. Time-dependent cracking in the heat-affected zone of Grade 23 weldments was assessed using crack growth testing of subsize compact tension specimens at a temperature (482°C, 900°F) characteristic of the upper portion of a furnace wall in supercritical boilers. Results of additional testing at a higher, typical design temperature (566°C, 1050°F) for superheater and reheater tubing and headers will be reported later. Post-test metallurgical evaluation of the cracking morphology was conducted using traditional light microscopy and laser microscopy. Although large-scale creep deformation is absent under these lower test temperature conditions, significant weldment heat-affected zone intergranular cracking was documented. An example of application of the data to the inservice integrity and life assessment of a furnace tube is also described, providing preliminary perspective on the factors controlling lifetime and manageability of integrity. Paper published with permission.

The small punch test was developed to investigate the mechanical behavior of polyethylene using miniature specimens (< 14 mg) measuring 0.5 mm in thickness and 6.4 mm in diameter. The objective of this study was to demonstrate the feasibility and reproducibility of the small punch test when applied to clinically relevant polyethylenes. Mechanical behavior was characterized during 66 tests performed on GUR4150HP and GUR4120 specimens following alternate sterilization methods and 4 weeks of accelerated aging at 80 degrees C. The small punch test was found to be highly reproducible with regard to characterizing the ductility, ultimate strength, and fracture resistance of sterilized and aged polyethylene. In the future, the small punch test can be used to directly measure mechanical properties near the articulating surface of retrieved components.

For over three decades, the long seam-welded low alloy steel, Grades 11 and 22, high energy piping in fossil power plants has been considered at risk of premature damage and failure. The experience with piping damage and failures has been documented and extensively studied, but there remains a lack of perspective on how the overall experience with such piping, including that of the large “survivor” population, compares with what one may expect with the design rules used in their construction. Such a perspective can be useful in helping decide on suitable design rules for this class of piping. This paper focuses on an aggregate, global, semi-quantitative evaluation of the damage and failure experience in fossil plant low alloy steel long seam-welded piping in terms of a rate of failure measured against the performance of the overall population. A key aspect of the evaluation is the consideration of the survivor population, particularly important since the documented cases of failure and damage represent a very small fraction of the population of relevant components. The damage and failure rates have been derived from the Electric Power Research Institute database, using an exposure parameter represented by the product of operating time and length of piping. The rates are viewed against the backdrop of the statistical scatter band of base metal stress rupture data used in development of the ASME Code design allowable stresses and against the weld strength reduction factors recently adopted by the ASME Boiler Pressure Vessel Code, Section I and the Power Piping Code, B31.1.Copyright © 2011 by ASME

The small punch (miniature disk bend) test was used to estimate conventional tensile and fracture properties of the reactor pressure vessel A 533B plate steel provided by ASTM for its Cross-Comparison Exercise on Determination of Material Properties Through the Use of Miniature Mechanical Testing Techniques. The test procedures followed those developed over the last six years mainly through support of the Electric Power Research Institute. The small punch, disk-shaped specimen of 6.35 mm (0.25 in.) diameter and 0.5 mm (0.020 in.) thickness is loaded by a 2.54 mm (0.1 in.) diameter hemispherical head punch at a constant displacement rate of typically 0.25 mm (0.01 in.) per minute. The room-temperature material fracture toughness (K I c ) and uniaxial tensile stress-strain curve and properties estimated from three separate small punch tests at room temperature show good reproducibility and agreement with the conventionally-measured, large specimen values. A series of small punch tests exhibited well-defined temperature-dependent energy transition behavior and potential for estimation of standard Chatpy transition temperatures from such data.

Short hairpin RNAs (shRNAs) and short interfering RNAs (siRNAs) probably enter different stages of the microRNA (miRNA) pathway for depletion of mRNA and suppression of protein translation. Primary and secondary structural characteristics that are shared between endogenous primary miRNA transcripts (pri-miRNAs) may contribute toward efficient biogenesis and potent silencing. This study investigates known miRNA transcripts for characteristics that are conserved between miRNAs and that distinguish them from random hairpins with similar lengths. The primary structure is conserved, as demonstrated by a significant presence or absence of certain bases at specific positions in the miRNA precursors and their flanking regions. The secondary structure is also conserved between miRNAs, as internal loops and bulges commonly appear in specific positions in the miRNA stem. The conservation of base-pairing continues past the mature duplex and 13 bases into the primary stem, with no detectable conservation of secondary structure beyond this region. Based on these observations, we have designed a hairpin construct that incorporates the most important characteristics present in endogenous miRNAs. Preliminary experiments suggest that this construct may rescue the efficacy of shRNA triggers that cannot be used with a miR-30-based hairpin, and vice versa.

Three identical 85 MW combustion turbines experienced cracking and failure of several first stage compressor stator (S1) blades. The root cause analysis involved the following distinct stages: 1. Examination of failed blades including fractography and analyses of the mechanics of their fracture; 2. Blade vibration analysis to determine the modes of vibration and corresponding resonant frequencies; 3. Inlet plenum flow and acoustical analysis to identify possible sources of excitation. This paper summarizes the methodology and results of the root cause analysis investigation and outlines the convergence of results obtained from the independently conducted mechanical and acoustical analyses.Copyright © 2005 by ASME

The identification of the PWSCC (Primary Water Stress Corrosion Cracking) mechanism responsible for leakage from an Alloy 600 nozzle tube of a PWR RPV (pressurized water reactor reactor pressure vessel) head more than a decade ago led to a significant body of research into understanding the phenomenon and to development of bases for safely managing primary pressure boundary integrity. However, the relatively recent experience at Davis-Besse, wherein penetration leakage resulted in significant vessel head material wastage, led to the heretofore unconsidered issue of vessel failure risk due to head rupture. This paper addresses, in preliminary fashion, one key input to determining the risk associated with head material wastage and potential rupture — the local environmental and fluid conditions associated with a range of leak paths. The results indicate a need for rigorous prediction of fluid conditions for a range of leak situations to help establish criteria for addressing penetration leaks.

Polymethylmethacrylate (PMMA) bone cement is used in total joint replacements to anchor implants to the underlying bone. Establishing and maintaining the integrity of bone cement is thus of critical importance to the long-term outcome of joint replacement surgery. The goal of the present study was to evaluate the suitability of a novel testing technique, the small punch or miniaturized disk bend test, to characterize the elastic modulus and fracture behavior of PMMA. We investigated the hypothesis that the crack initiation behavior of PMMA during the small punch test was sensitive to the test temperature. Miniature disk-shaped specimens, 0.5 mm thick and 6.4 mm in diameter, were prepared from PMMA and Simplex-P bone cement according to manufacturers' instructions. Testing was conducted at ambient and body temperatures, and the effect of test temperature on the elastic modulus and fracture behavior was statistically evaluated using analysis of variance. For both PMMA materials, the test temperature had a significant effect on elastic modulus and crack initiation behavior. At body temperature, the specimens exhibited "ductile" crack initiation, whereas at room temperature "brittle" crack initiation was observed. The small punch test was found to be a sensitive and repeatable test method for evaluating the mechanical behavior of PMMA. In light of the results of this study, future small punch testing should be conducted at body temperature.

The mechanical behavior and evolution of crystalline morphology during large deformation of eight types of virgin and crosslinked ultra high molecular weight polyethylene (UHMWPE) were studied using the small punch test and transmission electron microscopy (TEM). We investigated the hypothesis that both radiation and chemical crosslinking hinder molecular mobility at large deformations, and hence promote strain hardening and molecular alignment during the multiaxial loading of the small punch test. Chemical crosslinking of UHMWPE was performed using 0.25% dicumyl peroxide (GHR 8110, GUR 1020 and 1050), and radiation crosslinking was performed using 150 kGy of electron beam radiation (GUR 1150). Crosslinking increased the ultimate load at failure and decreased the ultimate displacement of the polyethylenes during the small punch test. Crosslinking also increased the near-ultimate hardening behavior of the polyethylenes. Transmission electron microscopy was used to characterize the crystalline morphology of the bulk material, undeformed regions of the small punch test specimens, and deformed regions of the specimens oriented perpendicular and parallel to the punch direction. In contrast with the virgin polyethylenes, which showed only subtle evidence of lamellar alignment, the crosslinked polyethylenes exhibited enhanced crystalline lamellae orientation after the small punch test, predominantly in the direction parallel to the punch direction or deformation axis. Thus, the results of this study support the hypothesis that crosslinking promotes strain hardening during multiaxial loading because of increased resistance to molecular mobility at large deformations effected by molecular alignment. The data also illustrate the sensitivity of large deformation mechanical behavior and crystalline morphology to the method of crosslinking and resin of polyethylene.

The small punch or miniaturized disc bend test has been used successfully to characterize the ductility and fracture resistance of metals and ceramics with specimens measuring 0.5 mm in thickness. This study was performed to demonstrate the feasibility of performing small punch tests on implant grade ultra-high-molecular-weight polyethylene (UHMWPE). Large-deformation finite element simulations were developed and validated to explore the hypothesis that the macroscopic constitutive behaviour of UHMWPE may be inferred from a miniature specimen testing technique which can be used to characterize the ductility and work to failure for UHMWPE. The load-displacement curve was insensitive to cyclic preconditioning of the test specimen and only mildly sensitive to the loading rate. Furthermore, the initial slope of the small punch load-displacement curve was used to determine the elastic modulus of the UHMWPE with the help of the inverse finite element method. The ultimate goal of this research is to develop the capability to perform local measurements of material tensile and static fracture properties in as-manufactured, as-sterilized and as-retrieved UHMWPE components.

Gamma sterilization results in temporally and spatially inhomogeneous density distributions through the thickness of ultra-high molecular weight polyethylene (UHMWPE) components for total joint replacement [1]. Conventional approaches to estimate the through-thickness distribution of mechanical properties in total joint replacement components have relied on empirical correlations between local measurements of density and these properties [2].

Vaelav Havel's recent rise to political power in the now-dissolved Czechoslovak Republic has only confinned some critics' contentions that Havel's dramatic works are all basically political in origin and theme. These critics' beliefs are supported by some striking similarities in many of Havel's plays; the bureaucracies that are. often seen as thinly veiled representations of totalitarian regimes, for example, are present in or alluded to in all of Havel's major works beginning with The Garden Parry (i963) and ending with Temptation (1985). But while the existence of these bureaucratic systems and the protagonists' struggle to retain their personal identity in their dealings with such systems may suggest a political theme, they by no means limit Havel 's plays to political matters. The appeal of Havel's plays in the West especially in the United States, where threats of totalitarianism are distant seems to suggest that these works hold within themselves something beyond their political content, something capable of capturing the attention of a large portion of the Western hemisphere. Martin Esslin offers perhaps a better perspective to Havel 's plays (or at least one that is better able to explain the playwright's international popularity) when he identifies Havel as an absurdist. Esslin's absurdist playwrights strive to express "the senselessness of the human condition and the inadequacy of the rational approach by the open abandonment of rational devices and discursive thought";' and indeed, Havel injects a multitude of contradictions and paradoxes into his plays, seemingly to express this very idea. And alongside these paradoxes and contradictions, Havel's works also mercilessly employ repetitions of words and actions. The end result of these techniques is a world often centered around scientific or business affairs where the human is remote or even alien; and it is in such a world that Havel 's protagonists confront the absurd in the guise of bureaucracy and inner-office power struggles. For Hugo Pludek, Josef Gross, Leopold Net

Following the catastrophic failures of seam-welded reheat piping at two power stations in 1985/86, the industry, with the assistance of the Electric Power Research Institute (EPRI) embarked on an aggressive inspection and evaluation effort to minimize the apparent risk associated with operating seam-welded hot reheat piping. This effort resulted in the EPRI guidelines for the evaluation of seam- welded stream pipes issued in 1987. Since 1987, more data and plant experience relating to seam weld cracking have become available. The data and experience have furthered our understanding of the inservice damaging process, and have helped assess the field effectiveness of the EPRI- recommended procedure for inservice seam-welded pipe inspection. Based on metallurgical evaluation and mechanical tests of weldments, the factors contributing to failures have been identified to be some or all of the following: excess stress and temperature; pre-existing flaws; nonmetallic inclusions; sharp weld cusps and creep strength mismatch; impurity segregation; weld roof-angle; etc. Since exceptions exist in every case, attempts to develop screening criteria for pipes 'at risk' have been less than successful. This paper presents an overview of the current state-of-knowledge with regard to the integrity of hot reheat seam-welded piping in the USA, with summary guidance on quantitative application of this knowledge of the life prediction of inservice piping.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

the decline of the Colorado pikeminnow and other native fish species (McAda, 1983; Pimental et al., 1985). Populations of Colorado pikeminnow remain in the Green, White, Yampa, Colorado, and San Juan rivers (Minckley and Carothers, 1979; Holden and Wick, 1982; Platania et al., 1991; Tyus, 1991; Ryden and Ahlm, 1996). Colorado pikeminnow was listed as endangered by the United States Fish and Wildlife Service in 1974 (Federal Register 39:1175, 1974) and is protected by all states in its historic range (Propst, 1999). Colorado pikeminnow begin to feed on fish at 50 mm total length (TL; Vanicek and Kramer, 1969). Adult Colorado pikeminnow, which can achieve 948 TL in the San Juan River (Ryden and Ahlm, 1996), can take prey 1/3 to 1/2 their body length (Osmundson et al., 1998). Prior to the establishment of nonnative fishes, soft-rayed fishes were the only prey available to Colorado pikeminnow (Holden and Wick, 1982; Pimental et al., 1985). Establishment of nonnative, hardand spiny-rayed fishes, including channel catfish, (Ictalurus punctatus), exposed Colorado pikeminnow to a potential choking hazard which was previously nonexistent. Anecdotal reports of Colorado pikem nnow with channel catfish lodged in their throats (e.g., Vanicek and Kramer, 1969) were undocumented until 1983. McAda (1983) collected an adult Colorado pikeminnow (550 mm TL) from the Green River in 1974 with a channel catfish (120 mm TL) lodged in its throat. Three similar incidents subsequently were reported from the Green River in 1982 and 1983 (Pimental et al., 1985). Our collection of a juvenile Colorado pikeminnow with a channel catfish lodged in its mouth from the San Juan River offers a new perspective on this phenomenon, especially as it relates to recovery efforts for Colorado pikeminnow in the San Juan River. On 1 October 1999, at approximately 1145 h while electrofishing at river kilometer (RK) 138.4, 12.1 km downstream of the bridge at Montezuma Creek, Utah, we collected a subadult Colorado pikeminnow (346 mm TL) with a channel catfish (111 mm TL) firmly lodged in its mouth anterior to the gills. The channel catfish was alive and struggling, with spines extended. The dorsal spine had penetrated the roof of the Colorado pikeminnow's mouth and had entered the right eye socket causing distention and hemorrhagic swelling. Both pectoral spines had penetrated the sides of the Colorado pikeminnow's mouth. The posterior end of the channel catfish, from just anterior to the adipose fin, protruded from the Colorado pikeminnow's mouth. A strip of flesh about 10 mm wide was worn from the body of the channel catfish, where the Colorado pikeminnow's mouth would normally close. We photographed the fishes, then removed the channel catfish from the Colorado pikeminnow's mouth by severing the spines and backing the fish out of the mouth. Both fish were weighed and measured. The channel catfish was removed from the river and the Colorado

Silastic tubing was used as a replacement of the common bile duct in nineteen animals, four of which had experimentally produced total obstruction of the common bile duct. Satisfactory function of the Silastic tubing as a bile conduit was observed in thirteen of the nineteen dogs. Common malfunctions encountered with synthetic replacement material for the common bile duct are discussed with reference to the use of Silastic tubing in this study.

Ca-EDTA- 14 C was administered to rats at three different dose levels, only one of which was capable of inducing vacuolization in proximal convoluted tubular cells within 24 hr. Differential centrifugation indicated that the percentage uptake with all three doses was similar over a period of 30 min to 24 hr. The behaviour of the particles relative to time as well as on sucrose water density gradients suggested that the EDTA- 14 C eventually shares particle space with lysosomal enzymes.

O NE of the outstanding scientific advances of this decade in the field of electro-optics has been the development of the laser beam. The state of the art has progressed so rapidly that laser devices with pulsed powers of 1 billion watts or with continuous wave (CW) power of 1000 watts are available. By focusing the laser beam, power-densities of 10 ~2 W/cm: of pulsed energy and 10 ~ W / c m 2 of CW energy are available for experimentation. Because we need to know the effects of laser energy on biological tissues from the point of view of public health hazard as well as biomedical application, the following studies were carried out. The principles of laser physics and engineering have been described in earlier publications3-S, 12 Following the demonstration by McGuff ~5 and Minton ~6 tha t pulsed laser radiation destroyed cancer tissue, Rosomoff ~7 applied a similar technique to malignant, hunmn brain neoplasms exposed surgically in the operating room. The patients and animals subjected to pulsed laser radiation in their experiments appeared unharmed. On the other hand, Fine, et a l . , 5 found that a laser pulse of 100 joules (J)++ at 694 nanometer (nm)w

THE independent metabolic activities of some of the obligate intracellular bacteria, such as rickettsiae and chlamydiae1, have been extensively investigated2. Such work has rarely included Rickettsia rickettsi, the agent of Rocky Mountain spotted fever, because of the difficulty of obtaining sufficient material of adequate purity and stability. The only data on respiration of R. rickettsi are those given in a preliminary report by Price3, who carried out his experiments with the collection from several thousand infected yolk sacs and tested the micro-organisms immediately after the final step of purification.

This study of the effect of laser radiation on the brain was made to further our understanding of the interaction of light with living matter and to provide a basis for the possible uses of laser energy in biology and medicine. The physics and engineering aspects of lasers are adequately treated elsewhere (1–3). Light produced by lasers differs from that of conventional sources in that it is strongly coherent and emitted in a narrow, collimated monochromatic beam which can be focused to produce high energy and power densities which are destructive to tissues. The ability to produce sharply circumscribed superficial lesions has been demonstrated (4) and suggests the application as an ablative tool in neurosurgery and neurophysiological research. Using equipment similar to ours, Fine et al. (4, 5) found that 75 per cent of mice died within 24 hours when a single 1-millisecond focused or unfocused laser pulse of about 100 joules struck the brain of the mouse through the intact scalp and skull. In earlier experiments we (G) were able to kill nearly every mouse within a few minutes, using only a single 1-millisecond, 20-joule pulse focused within the brain through the scalp and skull. The lethal mechanism was not explained by the small focal lesions. The occurrence of isolated hemorrhages in the base of the brain away from the site of impact had been thought to be an artifact produced during the removal of the brain from the cranium. If laser light had actually penetrated to that depth in sufficient intensity to produce hemorrhage, a continuous lesion would be expected.

Clinical reports and certain experimental studies have indicated that ethylenediaminetetraacetate and diethylenetriaminepentaacetate are nephrotoxic. Since these compounds have a very high order of physiologic and biochemical specificity, studies were performed in the expectation that insights of a mechanistic nature might be obtained. It was found that the tubular vacuolization produced in the rat by intraperitoneal injection of the chelates daily for 10 days was not accompanied by significant elevation of serum creatinine or urea nitrogen. In addition, there was no impairment in renal excretion of the 14C-labeled chelates or in the ability of slices of the renal cortex to accumulate p-aminohippurate. The results with labeled compounds indicated that the vacuoles were not simple repositories of accumulated chelate, and metal analyses of the kidney indicated that vacuolization could occur independent of changes in the metal spectrum. Kidneys with preexisting or evolving damage due to vitamin D2 or lead intoxication did not appear to be more vulnerable to the action of the chelates. Advice to the effect that renal function should be followed in patients receiving these chelates is consistent with good medical practice, but the label “nephrotoxin” is unjustified. There are similarities between the vacuoles produced by these chelates and those observed with sucrose and mannitol. The driving forces in these morphologic events appear to center on the moiety of these materials that gain entrance to the cell rather than on the number of osmotically active particles in the filtrate or urine volume. Observations and thoughts concerning the origin and fate of the vacuoles are discussed.

The renal cortices of rats were examined for changes in lysosomal enzymes 2 and 24 hr after the administration of 1·0 and 2·5 g of calcium disodium ethylene-diaminetetraacetic acid per kg. The enzymes measured were aryl sulfatase, acid phosphatase, and acid ribonuclease. Though vacuolization occurred at both time intervals with both doses, enzymatic changes were observed only at the 24-hr interval. The changes were manifested as a decrease in the concentration of the three enzymes in the nuclear-weight fractions. It is suggested that part of the chelate enters the cell via pinocytosis, resulting in the formation of a vacuole analogous to the phagosome described by previous investigators. A subsequent combination of the vacuoles with lysosomes is proposed.

There has been considerable interest recently in the use of Doppler shifted signal information as a technique for passive acoustic localization. An investigation of this phenomenon using conventional techniques, however, rapidly becomes complicated by the large number of parameters and geometrical configurations that must be considered. In particular, it is especially difficult to determine the sensitivity of the technique to measurement errors. As an alternative, this paper treats the Doppler profile in terms of its inherent information content and indicates how such information may be utilized to obtain both qualitative and quantitative results. By invoking Fourier transform and sampling techniques, the limitations of Doppler localization are viewed in terms of conventional filter bandwidth and aliasing problems. Furthermore, measurement sensitivity is treated as a generalized S/N ratio enhancement problem. Utilizing the methods of this paper, a more generalized and complete understanding of the Doppler phenomena is achieved when compared to the specialized results of conventional methods.

The time waveforms of the underwater acoustic transients under consideration may be described as noise‐corrupted pulses with varying risetimes and fall times, varying durations, and varying levels. In the past, these transients have been experimentally obtained using omnidirectional hydrophones and recorded on analog magnetic tape. The fact that these transients have been properly recorded is aurally verified before any spectral analysis is commenced. In order to perform the preanalysis detection of the transients at a faster rate and at adverse signal‐to‐noise ratios, an effort was initiated to develop an automatic system for the detection of this particular class of underwater acoustic transient. The development program consisted of three phases. First, the general class of transient was studied in detail to determine recognizable and repeatable attributes fo the signal. Using these attributes, a mask of the transient was constructed. A cross‐correlation detector was developed that used the mask in conjunction with a general prupose computer and a specially designed analog system. Finally, the automated detector was used to locate transients which had previously gone undetected by direct aural means. This paper describes the metamorphosis of the development program. Examples of the detector output are also given. [Work supported by ONR.]