Showing papers by "Yale University published in 1981"

Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis

Abstract: We describe the use of gel electrophoresis in studies of equilibrium binding, site distribution, and kinetics of protein-DNA interactions. The method, which we call protein distribution analysis, is simple, sensitive and yields thermodynamically rigorous results. It is particularly well suited to studies of simultaneous binding of several proteins to a single nucleic acid. In studies of the lac repressor-operator interaction, we found that binding to the so-called third operator site (03) is 15-18 fold weaker than operator binding, and that the binding reactions with the first and third operators are uncoupled, implying that there is no communication between the sites. Pseudo-first order dissociation kinetics of the repressor-203 bp operator complex were found to be temperature sensitive, with delta E of 80 kcal mol-1 above 29 degrees C and 26 kcal mol-1 below. The half life of the complex (5 min at 21 degrees C) is shorter than that reported for very high molecular weight operator-containing DNAs, but longer than values reported for much shorter fragments. The binding of lac repressor core to DNA could not be detected by this technique: the maximum binding constant consistent with this finding is 10(5) M-1.

Organizational innovation: the influence of individual, organizational, and contextual factors on hospital adoption of technological and administrative innovations.

Abstract: Individual, organizational, and contextual variables were found to be much better predictors of hospital adoption of technological innovations than of administrative innovations. The two different ...

QCD and instantons at finite temperature

Abstract: The current understanding of the behavior of quantum chromodynamics at finite temperature is presented. Perturbative methods are used to explore the high-temperature dynamics. At sufficiently high temperatures the plasma of thermal excitations screens all color electric fields and quarks are unconfined. It is believed that the high-temperature theory develops a dynamical mass gap. However in perturbation theory the infrared behavior of magnetic fluctuations is so singular that beyond some order the perturbative expansion breaks down. The topological classification of finite-energy, periodic fields is presented and the classical solutions which minimize the action in each topological sector are examined. These include periodic instantons and magnetic monopoles. At sufficiently high temperature only fields with integral topological charge can contribute to the functional integral. Electric screening completely suppresses the contribution of fields with nonintegral topological charge. Consequently the $\ensuremath{\theta}$ dependence of the free energy at high temperature is dominated by the contribution of instantons. The complete temperature dependence of the instanton density is explicitly computed and large-scale instantons are found to be suppressed. Therefore the effects of instantons may be reliably calculated at sufficiently high temperature. The behavior of the theory in the vicinity of the transition from the high-temperature quark phase to the low-temperature hadronic phase cannot be accurately computed. However, at least in the absence of light quarks, semiclassical techniques and lattice methods may be combined to yield a simple picture of the dynamics valid for both high and low temperature, and to estimate the transition temperature.

Prejudice and politics: Symbolic racism versus racial threats to the good life.

Abstract: Although theories of prejudice have been extensively catalogued, empirical confrontations between competing theories are surprisingly rare. The primary goal of the present research was to test two major theoretical approaches to prejudice by whites against blacks: realistic group conflict theory, which emphasizes the tangible threats blacks might pose to whites' private lives; and a sociocultural theory of prejudice termed symbolic racism, which emphasizes abstract, moralistic resentments of blacks, presumably traceable to preadult socialization. The main dependent variable in our analysis is suburban whites' voting behavior in two mayoral elections in Los Angeles, both strongly influenced by racial issues, that matched the same two candidates, one black and one white. In both elections, symbolic racism (sociocultural prejudice) was the major determinant of voting against the black candidate for people removed from possible personal threats posed by blacks as well as for those at risk. Direct racial threats to whites' private lives (to their jobs, their neighborhoods, their children's schooling, their families' safety) had little effect on either antiblack voting behavior or symbolic racism. The article closes by developing the implications of these results for theories of prejudice and, more speculatively, for interpretations of the effects of voters' private lives on their political behavior. Theories of racial prejudice suffer from benign neglect. Although the theories themselves have been extensively and ably catalogued (most notably, by Allport, 1954; Ashmore & DelBoca, 1976; LeVine & Campbell, 1972), empirical confrontations between alternative theories occupy surprisingly little

Psychological status of the script concept.

Abstract: Suggests that there has been growing interest within several subfields of psychology in the schematic nature of mental representations of real-world objects and events. One simple form of schema is the “script,” embodying knowledge of stereotyped event sequences. The present author traces applicatio

Sexual differentiation of the central nervous system

Abstract: Sexual differentiation of reproductive and behavior patterns is largely effected by hormones produced by the gonads. In many higher vertebrates, an integral part of this process is the induction of permanent and essentially irreversible sex differences in central nervous function, in response to gonadal hormones secreted early in development.

Trace Scheduling: A Technique for Global Microcode Compaction

Abstract: Microcode compaction is the conversion of sequential microcode into efficient parallel (horizontal) microcode. Local compaction techniques are those whose domain is basic blocks of code, while global methods attack code with a general flow control. Compilation of high-level microcode languages into efficient horizontal microcode and good hand coding probably both require effective global compaction techniques.

Sociotropic Politics: The American Case

Abstract: American elections depend substantially on the vitality of the national economy. Prosperity benefits candidates for the House of Representatives from the incumbent party (defined as the party that controls the presidency at the time of the election), whereas economic downturns enhance the electoral fortunes of opposition candidates. Short-term fluctuations in economic conditions also appear to affect the electorate's presidential choice, as well as the level of public approval conferred upon the president during his term. By this evidence, the political consequences of macroeconomic conditions are both pervasive and powerful. But just how do citizens know whether the incumbent party has succeeded or failed? What kinds of economic evidence do people weigh in their political appraisals? The purpose of our paper is to examine two contrasting depictions of individual citizens – one emphasizing the political significance of citizens' own economic predicaments, the other stressing the political importance of citizens' assessments of the nation's economic predicament - that might underlie the aggregate entwining of economics and politics. Ours is an inquiry into the political economy of individual citizens.

Clinical biostatistics: LIV. The biostatistics of concordance

Abstract: Clinical Pharmacology and Therapeutics (1981) 29, 111–123; doi:10.1038/clpt.1981.18

Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5‐fluorouracil), and high dose radiation + 5‐fluorouracil. The gastrointestinal tumor study group

Abstract: One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

A New Geochemical Classification of Sedimentary Environments

Abstract: Because of the relative constancy of pH in most subaqueous sediments and the general lack of measurability of Eh, these parameters are not practically useful for classifying sedimentary environments. In their place a new classification is offered which, derived from studies of modern sediments, is based on the presence or absence of dissolved oxygen and dissolved sulfide in the sediments at the time of authigenic mineral formation. Sedimentary environments are first of all divided into oxic and anoxic depending upon the presence or absence of measurable dissolved oxygen. Anoxic environments, in turn, are divided into sulfidic and non-sulfidic depending upon the presence of measurable dissolved sulfide. Anoxic-nonsulfidic environments are further divided into postoxic, or resulting from oxygen removal without sulfate reduction (weakly reducing), and methanic , or resulting from complete sulfate reduction with consequent methane formation (strongly reducing). The environments are shown to succeed one another during early diagenesis in the order: oxic, post-oxic, sulfidic, methanic. Iron and manganese minerals characteristic and stable in each environment are listed and discussed so that they may be used to distinguish the environments when studying the ancient geological record.

A Network Model for the Organization of Type IV Collagen Molecules in Basement Membranes

Abstract: Type IV collagen was solubilized from a tumor basement membrane either by acid extraction or by limited digestion with pepsin. The two forms were similar in composition and the size of the constituent chains but differed when examined by electron microscopy and in the fragment pattern produced by bacterial collagenase. The acid-soluble form showed after rotary shadowing strands mainly of a length of 320 nm which terminated in a globule, or two strands connected by a similar globule. The globule was identified as a non-collagenous domain (NC1) which under dissociating conditions could be separated into two peptides showing a monomer-dimer relationship. Higher aggregates of NC1 were visualized under non-dissociating conditions. Some of the acid-extracted molecules have retained the previously 7-S collagen domain. The pepsin-solubilized form lacked domain NC1 and consisted mainly of four triple-helical strands (length 356 nm) joined together at the 7-S domain (length 30 nm). Common to both forms of type IV collagen was a small collagenase-resistant domain NC2 which was composed of collagenous and non-collagenous elements and located between the 7-S domain and the major triple helix. These data indicate that the collagenous matrix of basement membranes consists of a regular network of type IV collagen molecules which is generated by two different interacting sites located at opposite ends of each molecule. The 7-S collagen domain connects four molecules while the NC1 domain connects two molecules. The maximal distance between identical cross-linking sites (7-S or NC1) was estimated to be about 800 nm comprising the length of two molecules.

People's conceptions of intelligence.

Abstract: : Three experiments are reported investigating experts' and laypersons' conceptions of intelligence. In the first experiment, persons studying in a college library, entering a supermarket, and waiting for trains in a railroad station were asked to list behaviors characteristic of either 'intelligence,' 'academic intelligence,' 'everyday intelligence,' or 'unintelligence,' and to rate themselves on each of the three kinds of intelligence. In the second experiment, experts and laypersons (excluding students) were asked to rate various properties of the behaviors listed in Experiment 1; the laypersons also rated themselves on the three kinds of intelligence and took an IQ test. In the third experiment, laypersons received written descriptions of behaviors characterizing fictitious people, and were asked to rate these people's intelligence. We found that people have well-formed prototypes corresponding to the various kinds of intelligence, that these prototypes are quite similar for experts and laypersons, that the prototypes are closely related to certain psychological theories of intelligence, and that the prototypes are used in the evaluation of one's own and others' intelligence. Moreover, proximity of one's behavioral self-characterizations to an ideal prototype is quite strongly related to intelligence as measured by an IQ test. (Author)

Inward current channels activated by intracellular Ca in cultured cardiac cells.

Abstract: Present concepts of excitable membrane function are based primarily on knowledge of two classes of channels: those activated by neurotransmitters1 and those activated by membrane potential2. Recent evidence suggests that these notions may have to be modified to include other channel types, such as special ion channels activated by membrane potential but regulated by ligands3–5. We report here studies on single channel currents recorded from heart muscle cells, in which we have found a channel, abundant in cardiac membrane, which does not seem to belong in any of the familiar categories. This channel shows little selectivity between cations, but excludes anions. It is activated by intracellular Ca ions but is not appreciably affected by membrane potential.

Hurricane Allen's Impact on Jamaican Coral Reefs

Abstract: Coral reefs of north Jamaica, normally sheltered, were severely damaged by Hurricane Allen, the strongest Caribbean hurricane of this century. Immediate studies were made at Discovery Bay, where reef populations were already known in some detail. Data are presented to show how damage varied with the position and orientation of the substraturn and with the shape, size, and mechanical properties of exposed organisms. Data collected over succeeding weeks showed striking differences in the ability of organisms to heal and survive.

The effect of insulin on renal sodium metabolism. A review with clinical implications.

Abstract: Data are discussed which demonstrate that insulin plays an important role in sodium metabolism. The primary action of insulin on sodium balance is exerted on the kidney. Increases in plasma insulin concentration within the physiological range stimulate sodium reabsorption by the distal nephron segments and this effect is independent of changes in circulating metabolites or other hormones. Several clinical situations are reviewed: sodium wasting in poorly controlled diabetics, natriuresis of starvation, anti-natriuresis of refeeding and hypertension of obesity, in which insulin-mediated changes in sodium balance have been shown to play an important pathophysiological role.

Structure of catabolite gene activator protein at 2.9 Å resolution suggests binding to left-handed B-DNA

Abstract: The 2.9 A resolution crystal structure of Escherichia coli catabolite gene activator protein (CAP) complexed with cyclic AMP reveals two distinct structural domains separated by a cleft. The smaller carboxy-terminal domain is presumed to bind DNA while the amino-terminal domain is seen to bind cyclic AMP. Model building studies suggest that CAP binds to left-handed B-type DNA, contracting its major groove via two alpha-helices. It is possible that the CAP conversion of right- to left-handed DNA in a closed supercoil, is what activates transcription by RNA polymerase.

Insulin resistance in uremia.

Abstract: Tissue sensitivity to insulin was examined with the euglycemic insulin clamp technique in 17 chronically uremic and 36 control subjects. The plasma insulin concentration was raised by approximately 100 microU/ml and the plasma glucose concentration was maintained at the basal level with a variable glucose infusion. Under these steady-state conditions of euglycemia, the glucose infusion rate is a measure of the amount of glucose taken up by the entire body. In uremic subjects insulin-mediated glucose metabolism was reduced by 47% compared with controls (3.71 +/- 0.20 vs. 7.38 +/- 0.26 mg/kg . min; P less than 0.001). Basal hepatic glucose production (measured with [3H]-3-glucose) was normal in uremic subjects (2.17 +/- 0.04 mg/kg . min) and suppressed normally by 94 +/- 2% following insulin administration. In six uremic and six control subjects, net splanchnic glucose balance was also measured directly by the hepatic venous catheterization technique. In the postabsorptive state splanchnic glucose production was similar in uremics (1.57 +/- 0.03 mg/kg . min) and controls (1.79 +/- 0.20 mg/kg . min). After 90 min of sustained hyperinsulinemia, splanchnic glucose balance reverted to a net uptake which was similar in uremics (0.42 +/- 0.11 mg/kg . min) and controls (0.53 +/- 0.12 mg/kg . min). In contrast, glucose uptake by the leg was reduced by 60% in the uremic group (21 +/- 1 vs. 52 +/- 8 mumol/min . kg of leg wt; P less than 0.005) and this decrease closely paralleled the decrease in total glucose metabolism by the entire body. These results indicate that: (a) suppression of hepatic glucose production by physiologic hyperinsulinemia is not impaired by uremia, (b) insulin-mediated glucose uptake by the liver is normal in uremic subjects, and (c) tissue insensitivity to insulin is the primary cause of insulin resistance in uremia.

Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus.

Abstract: The RNP and Sm antigens recognized by lupus erythematosus antibodies are located on discrete particles containing single small nuclear RNA's complexed with proteins. The antigens Ro and La are also on ribonucleoproteins. The small RNA's in ribonucleoproteins with Ro are discrete, like those associated with RNP and Sm; in contrast, ribonucleoproteins with La contain a striking highly banded spectrum of small RNA's from uninfected cells as well as virus-associated RNA from adenovirus-infected cells.

High-temperature Yang-Mills theories and three-dimensional quantum chromodynamics

Abstract: We demonstrate that for sufficiently high temperature $T$ the behavior of any four-dimensional gauge theory with small coupling constant $\ensuremath{\alpha}$, at distances beyond the electrical Debye screening length ${\ensuremath{\xi}}_{D}\ensuremath{\sim}\frac{1}{\sqrt{\ensuremath{\alpha}}T}$, is determined precisely by the corresponding three-dimensional theory. This is the magnetic sector of the original theory, and in the non-Abelian case it is a Yang-Mills theory like three-dimensional quantum chromodynamics (QC${\mathrm{D}}_{3}$). We study QC${\mathrm{D}}_{3}$ in the loop expansion, which is only valid for distances $\ensuremath{\ll}\frac{1}{\ensuremath{\alpha}T}$, in both covariant and Coulomb gauges. At a finite order in the loop expansion, the presence of logarithmic infrared divergences signals the appearance of new operators in the operator-product expansion. For example, in a covariant gauge, the gauge self-energy develops infrared divergences at two-loop order associated with the operator ${\overline{A}}^{2}$. Infrared divergences in the Wilson loop are also considered and shown to cancel below the order at which gauge-invariant local operators can appear in the operator-product expansion. The infrared structure of QC${\mathrm{D}}_{3}$ at distances $\ensuremath{\gtrsim}\frac{1}{\ensuremath{\alpha}T}$ cannot be directly probed in the loop expansion, however. We present a simpler model which is calculable in this infrared limit, and which might serve as a prototype for QC${\mathrm{D}}_{3}$. The model is massless scalar QE${\mathrm{D}}_{3}$, which with $N$ charged scalars is soluble in a $\frac{1}{N}$ expansion as $N\ensuremath{\rightarrow}\ensuremath{\infty}$. Using the $\frac{1}{N}$ expansion, we demonstrate that infrared softening occurs: the long-range behavior of the photon propagator in massless scalar QE${\mathrm{D}}_{3}$ is less singular than that of free fields. Infrared softening might also occur in QC${\mathrm{D}}_{3}$, although it cannot be demonstrated to finite order in the loop expansion. The implications of an assumed infrared softening in QC${\mathrm{D}}_{3}$ for the magnetic sector of Yang-Mills theories at high temperatures are also discussed. In particular, we consider the possibility that, if the softening is sufficiently great, there is screening of hot non-Abelian magnetic fields and possible confinement of primordial magnetic monopoles.

Direct and indirect pathways from the amygdala to the frontal lobe in rhesus monkeys

Abstract: To elucidate the anatomical relationships between the frontal association cortex and the limbic system in primates, projections from the amygdala to frontal cortex were studied in the rhesus monkey using retrograde and anterograde tracing methods. Following injections of horseradish peroxidase (HRP) into the orbital prefrontal cortex, the gyrus rectus, the superior frontal gyrus, and the anterior cingulate gyrus of the frontal lobe, labeled neurons were found in the basolateral, basomedial, or basal accessory nuclei of the amygdala. None of these nuclei contained labeled neurons following HRP injections into the principal sulcus or the lateral inferior convexity of the frontal lobe. This selective distribution of amygdala connections was confirmed by injecting tritiated amino acids into the amygdala. Silver grains were present only over the orbital cortex and gyrus rectus on the ventral surface of the frontal lobe and over the superior prefrontal gyrus and anterior cingulate gyrus on the medial wall of the hemisphere, while the dorsolateral prefrontal cortex was free of radioactivity. The isotope injection of the amygdala also revealed a projection to the magnocellular moeity of the mediodorsal nucleus (MDmc) which is known to innervate the same ventromedial regions of the frontal lobe that receive direct connections from the amygdala. Although MDmc and amygdala project to the same cortical regions, their terminal fields are different. The direct amygdala input terminates in layer 1 in orbital cortex and gyrus rectus and layer 2 in the dorsomedial cortex and cingulate gyrus, while the thalamic input is primarily to layer 3 and, in some areas, also to the superficial half of layer 1. These findings indicate that the frontal lobe of rhesus monkeys can be subdivided into two separable cortical regions:(1) A ventromedial region including the anterior cingulate gyrus which receives both direct (amygdalo-cortical) and indirect (amygdalo-thalamo-cortical) input from the amygdala; and (2) a dorsolateral frontal region which is essentially devoid of either direct or indirect amygdalofugal axons. On the basis of its selective relationship with the amygdala, the ventromedial region may be considered the “limbic” portion of the frontal association cortex.

Cardiovascular Differentiation of Happiness, Sadness, Anger, and Fear Following Imagery and Exercise

Abstract: This study examined cardiovascular patterns following happiness, sadness, anger, fear, relaxation, and control imagery in 32 subjects while they were seated and while they exercised. Affective imagery was an effective strategy for inducing reliable patterns of systolic and diastolic blood pressure and heart rate associated with particular emotional states. Anger, rather than fear, produced the greatest overall increases in cardiovascular measures and was distinctly opposite from relaxation. Anger differed from fear and all other conditions in terms of greater increases in diastolic pressure following imagery and greater increases in heart rate and slower recovery of systolic pressure following exercise. Sadness was unique in that systolic pressure and heart rate were virtually as high when subjects were still as when they were actually moving. Furthermore, sadness was the one emotional state that seemed to interfere with the cardiovascular adjustments normally associated with exercise. Implications of these findings for current biobehavioral models of emotion, including the role that specific emotions may play in the pathogenesis and treatment of cardiovascular disease, are considered.

Synergistic interaction between exercise and insulin on peripheral glucose uptake.

Abstract: The interaction of exercise and insulin on glucose metabolism was examined in 10 healthy volunteers. Four study protocols were used: study 1: plasma insulin was raised by approximately 100 microunits/ml while plasma glucose was maintained at basal levels for 2 h (insulin clamp). Study 2: subjects performed 30 min of bicycle exercise at 40% of VO2 max. Study 3: an insulin clamp was performed as per study 1. Following 60 min of sustained hyperinsulinemia, however, subjects exercised for 30 min as per study 2. Study 4: subjects were studied as per study 3 except that catheters were inserted into the femoral artery and vein to quantitate leg glucose uptake. During the 60-90 min period of hyperinsulinemia (study 1), glucose uptake averaged 8.73 +/- 0.10 mg/kg per min. With exercise alone (study 2), the increment in peripheral glucose uptake was 1.43 +/- 0.30 mg/kg per min. When hyperinsulinemia and exercise were combined (study 3), glucose uptake averaged 15.06 +/- 0.98 mg/kg per min (P less than 0.01) and this was significantly (P less than 0.001) greater than the sum of glucose uptake when exercise and the insulin clamp were performed separately. The magnitude of rise in glucose uptake correlated closely with the increase in leg blood flow (r = 0.935, P less than 0.001), suggesting that the synergism is the result of increased blood flow and increased capillary surface area to exercising muscle. More than 85% of total body glucose metabolism during studies 1 and 3 was accounted for by skeletal muscle uptake. These results demonstrate that (a) insulin and exercise act synergistically to enhance glucose disposal in man, and (b) muscle is the primary tissue responsible for the increase in glucose metabolism following hyperinsulinemia and exercise.