Showing papers by "Yale University published in 1982"

Single-Case Research Designs: Methods for Clinical and Applied Settings

Abstract: Single-case research has played an important role in developing and evaluating interventions that are designed to alter a particular facet of human functioning. Now thoroughly updated in its second edition, acclaimed author Alan E. Kazdin's Single-Case Research Designs provides a notable contrast to the quantitative methodology approach that pervades the biological and social sciences. While focusing on widely applicable methodologies for evaluating interventions--such as treatment or psychotherapy using applied behavior analysis--this revised edition also encompasses a broader range of research areas that utilize single-case designs, demonstrating the pertinence of this methodology in various disciplines, from psychology and medicine to business and industry. This well-written, clear, and thoroughly updated text is ideal for practitioners, instructors, and students alike. Features: * Offers new options in experimental design, presenting combinations of designs that increase the range of questions that can be asked about alternative interventions * Details the underlying rationale and methods of evaluating intervention effects through visual inspection in the area of data evaluation * Provides an expanded description of methods (e.g., assessment) and a greater range of examples * Includes an appendix at the end of the book to encourage discussion of the challenges, advances, and dilemmas of data evaluation in the design

A catalogue of splice junction sequences

Abstract: Splice junction sequences from a large number of nuclear and viral genes encoding protein have been collected. The sequence CAAG/GTAGAGT was found to be a consensus of 139 exon-intron boundaries (or donor sequences) and (TC)nNCTAG/G was found to be a consensus of 130 intron-exon boundaries (or acceptor sequences). The possible role of splice junction sequences as signals for processing is discussed.

Communication and Persuasion: Psychological Studies of Opinion Change

Abstract: This is a report of a program of coordinated systematic research on variables determining the effects of persuasive communication.

Best estimate of lifetime psychiatric diagnosis: a methodological study.

Abstract: It is important for genetic, epidemiologic, and nosological studies to determine accurate rates of lifetime psychiatric diagnoses in patient and nonpatient populations. As part of a case-control family study of major depression, lifetime psychiatric diagnoses were made for 1,878 individuals. Sources of information used in making diagnostic estimates included direct interview, medical records, and family history data systematically obtained from relatives. Diagnostic estimates were made by trained interviewers, experienced clinicians, and by computer program. The results indicate that it is possible to make lifetime best estimate diagnoses reliably among both interviewed and noninterviewed individuals for most diagnostic categories and that diagnoses based on interview data alone are an adequate substitute for best estimate diagnoses based on all available information in a limited number of diagnostic categories.

A Family Study of Schizoaffective, Bipolar I, Bipolar II, Unipolar, and Normal Control Probands

Abstract: • In a family study of 1,254 adult relatives of patients and controls, lifetime prevalences of major affective disorder (including schizoaffective) were 37%, 24%, 25%, 20% and 7% in relatives of probands with schizoaffective, bipolar I, bipolar II, and unipolar disease, and normal controls. These data were compatible with the different affective disorders representing thresholds on a continuum of underlying multifactorial vulnerability. In this model, schizoaffective illness represents greatest vulnerability, followed by bipolar I and bipolar II, then unipolar illnesses. Alcoholism, drug abuse, and sociopathy were not more frequent in relatives of patients v relatives of controls. Sex-related transmission of morbid risk was not present. Morbid risk was 74% to offspring of two ill parents, and 27% to offspring of one ill parent. Nationality and age at time of interview seem to be nongenetic factors that affect frequency of diagnosis.

Analysis of Polyamines in Higher Plants by High Performance Liquid Chromatography

Abstract: A sensitive (0.01-1 nmol) method has been developed for the analysis of polyamines in higher plant extracts based on high performance liquid chromatography (HPLC) of their benzoyl derivatives (Redmond, Tseng 1979 J Chromatogr 170: 479-481). Putrescine, cadaverine, agmatine, spermidine, spermine, and the less common polyamines nor-spermidine and homospermidine can be completely resolved by reverse phase HPLC, isocratic elution with methanol:water (64%, v/v) through a 5-mum C(18) column, and detection at 254 nm. The method can be directly applied to crude plant extracts, and it is not subject to interference by carbohydrates and phenolics. A good quantitative correlation was found between HPLC analysis of benzoylpolyamines and thin layer chromatography of their dansyl derivatives. With the HPLC method, polyamine titers have been reproducibly estimated for various organs of amaranth, Lemna, oat, pea, Pharbitis, and potato. The analyses correlate well with results of thin layer chromatography determinations.

A Voltage-Gated Ion Channel Model Inferred from the Crystal Structure of Alamethicin at 1.5-A Resolution.

Abstract: The crystal structure of alamethicin in nonaqueous solvent has been determined, and refined at 1.5-A resolution. The molecular conformation of the three crystallographically independent molecules is largely alpha-helical with a bend in the helix axis at an internal proline residue. The helix structure is highly amphipathic as most of the solvent-accessible polar atoms lie on a narrow strip of surface parallel to the helix axis. Molecular models for the voltage-gated ion channel, with n-fold symmetry and based on the molecular conformations observed in the crystal, are characterized by strong surface complementarity, a hydrophilic interior and a hydrophobic exterior. The channel structures are stabilized by a hydrated annulus of hydrogen-bonded glutamine residues which produce the greatest restriction in the channel diameter.

Modifier role of internal H + in activating the Na + –H + exchanger in renal microvillus membrane vesicles

Abstract: The intracellular pH in animal cells is generally maintained at a higher level than would be expected if H+ were passively distributed across the plasma membrane1. In a wide variety of cells including sea urchin eggs2, skeletal muscle3, renal and intestinal epithelial cells4–6, and neuroblastoma cells7, plasma membrane Na+–H+ exchangers mediate the uphill extrusion of H+ coupled to, and thus energized by, the downhill entry of Na+. Plasma membrane vesicles isolated from the luminal (microvillus, brush border) surface of renal proximal tubular cells possess a Na+–H+ exchanger4,5 that seems to be representative of the Na+–H+ exchangers found in other tissues. For example, the renal microvillus membrane Na+–H+ exchanger, like other N+–H+ exchangers, mediates electroneutral cation exchange4,5, is sensitive to inhibition by the diuretic drug amiloride5,8, and has affinity for Li+ in addition to Na+ and H+ (refs 5, 9). Here we have examined the effect of internal H+ on the activity of the Na+–H+ exchanger in renal microvillus membrane vesicles. Our results suggest that internal H+, independent of its role as a substrate for exchange with external Na+, has an important modifier role as an allosteric activator of the Na+–H+ exchanger. Allosteric behaviour with respect to internal H+ is a property that would enhance the ability of plasma membrane Na+–H+ exchangers to extrude intracellular acid loads and thereby contribute to the regulation of intracellular pH.

Experimental Demonstrations of the “Not-So-Minimal” Consequences of Television News Programs

Abstract: Two experiments sustain Lippmann's suspicion, advanced a half century ago, that media provide compelling descriptions of a public world that people cannot directly experience. More precisely, the experiments show that television news programs profoundly affect which problems viewers take to be important. The experiments also demonstrate that those problems promimently positioned in the evening news are accorded greater weight in viewers' evaluations of presidential performance. We note the political implications of these results, suggest their psychological foundations, and argue for a revival of experimentation in the study of political communication.

Adaptive significance of the age polyethism schedule in honeybee colonies

Abstract: The adaptive origins of the honeybee's age polyethism schedule were studied by testing whether the schedule for labor inside the nest reflects a compromise between efficiency in locating tasks and efficiency in performing tasks. I checked two predictions of this hypothesis: (1) at each age a worker handles a set of tasks (rather than one task), and (2) the elements of each age's task-set co-occur spatially in the nest (rather than being spatially segregated). Most observations match these predictions, once workers reach the age of 2 days. The unpredicted specialization of 0 to 2-day-old workers on the single task of cell cleaning may reflect an unusual ease in locating work sites for this particular task. There are 5 female castes in honeybee colonies: the queen (reproductive caste), plus 4 age subcastes among the workers (cell cleaning caste, broodnest caste, food storage caste, and forager caste).

Modified nucleotides and methods of preparing and using same

Abstract: Compounds having the structure: ##STR1## wherein B represents a purine, 7-deazapurine, or pyrimidine moiety covalently bonded to the C 1' -position of the sugar moiety, provided that when B is purine or 7-deazapurine, it is attached at the N 9 -position of the purine or 7-deazapurine and when B is pyrimidine, it is attached at the N 1 -position; wherein A represents a moiety consisting of at least three carbon atoms which is capable of forming a detectable complex with a polypeptide when the compound is incorporated into a double-stranded ribonucleic acid, deoxyribonucleic acid duplex, or DNA-RNA hybrid; wherein the dotted line represents a chemical linkage joining B and A, provided that if B is purine, the linkage is attached to the 8-position of the purine, if B is 7-deazapurine, the linkage is attached to the 7-position of the deazapurine, and if B is pyrimidine, the linkage is attached to the 5-position of the pyrimidine and wherein each of x, y and z represents ##STR2## either directly, or when incorporated into oligo- and polynucleotides, provide probes which are widely useful. Applications include detection and localization of polynucleotide sequences in chromosomes, fixed cells, tissue sections, and cell extracts. Specific applications include chromosomal karyotyping, clinical diagnosis of nucleic acid-containing etiological agents, e.g. bacteria, viruses, or fungi, and diagnosis of genetic disorders.

The anticancer agent adriamycin can be actively cytotoxic without entering cells

Abstract: The antineoplastic agent adriamycin was coupled to an insoluble agarose support This material was actively cytotoxic to L1210 cells in culture under conditions in which no free adriamycin could enter the cell It is concluded that an agent whose principal target was previously thought to be DNA can exert its cytotoxic action solely by interaction at the cell surface

Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus.

Abstract: Hepatic glucose production (3H-glucose technique) and insulin-mediated glucose uptake (insulin clamp technique) were measured in 38 Type 2 (non-insulin-dependent) and 11 Type 1 (insulin-dependent) diabetic patients. Fasting plasma glucose concentration was 8.3 +/- 0.5 mmol/l in the former, and 9.6 +/- 1.3 mmol/l in the latter group; the respective fasting plasma insulin levels were 19 +/- 2 mU/l (p less than 0.005 versus 13 +/- 1 mU/l in 33 age-matched control subjects), and 9 +/- mU/l (p less than 0.01 versus 14 +/- 1 mU/l in 36 younger control subjects). In the fasting state, hepatic glucose production was slightly increased (15%, 0.1 greater than p greater than 0.05) in the Type 2 diabetic patients and markedly elevated (65%, p less than 0.001) in the Type 1 patients compared with their respective control groups. In both groups of diabetic subjects, the rates of hepatic glucose production were inappropriately high for the prevailing plasma glucose and insulin levels, indicating the presence of hepatic resistance to insulin. Basal plasma glucose clearance was also significantly reduced in both the Type 2 (34%) and the Type 1 (14%) diabetic subjects. The fasting plasma glucose concentration correlated directly with hepatic glucose production, and inversely with plasma glucose clearance. During the insulin clamp, plasma insulin was maintained at approximately 100 mU/l in all groups, while plasma glucose was maintained constant at the respective fasting levels. Total glucose uptake was reduced in both the Type 2 (4.57 +/- 0.31 versus 6.39 +/- 0.25 mg . min -1 . kg -1 in the control subjects, p less than 0.01) and the Type 1 (4.77 +/- 0.48 versus 7.03 +/- 0.22 mg . min -1 . kg -1, p less than 0.01)diabetic patients. Insulin-stimulated glucose clearance was reduced to a similar extent in Type 2 (54%) and Type 1 (61%) diabetic subjects, and correlated directly with fasting glucose clearance. These results show that insulin resistance is a common feature of both types of diabetes and can be demonstrated in the basal as well as the insulin-stimulated state. Both hepatic and peripheral resistance to the action of insulin contribute to diabetic hyperglycaemia.

Inference of Reversible Languages

Abstract: A famdy of efficient algorithms for referring certain subclasses of the regular languages from fmtte posttwe samples is presented These subclasses are the k-reversible languages, for k = 0, 1, 2, . . . . For each k there is an algorithm for finding the smallest k-reversible language containing any fimte posluve sample. It ts shown how to use this algorithm to do correct identification m the ILmlt of the kreversible languages from posmve data A reversible language is one that Is k-reverstble for some k __ 0. An efficient algonthrn is presented for mfernng reversible languages from posmve and negative examples, and it is shown that it leads to correct identification m the hmlt of the class of reversible languages. Numerous examples are gtven to dlustrate the algorithms and their behawor

Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin

Abstract: The biosynthesis of melanin is initiated by the catalytic oxidation of tyrosine to dopa by tyrosinase in a reaction that requires dopa as a cofactor. Tyrosine then catalyzes the dehydrogenation of dopa to dopaquinone. The subsequent reactions can proceed spontaneously in vitro. Tyrosinase, purified from murine melanomas and the skins of brown mice, has now been shown to catalyze a third reaction in mammalian melanogenesis, namely the conversion of 5,6-dihydroxyindile to melanochrome. This reaction requires dopa as a cofactor and is inhibited by tyrosine. Conversely, 5,6-dihydroxyindole inhibits the oxidation of tyrosine to dopa, so that the relative concentrations of tyrosine and 5,6-dihydroxyindole within the mammalian pigment cell are capable of regulating melanogenesis in a previously unrecognized fashion. Tyrosinase has the unusual property of catalyzing three distinct reactions within a single biochemical pathway: the hydroxylation of a monophenol, the dehydrogenation of a catechol, and the dehydrogenation of a dihydroxyindole. The first and third of these reactions require dopa as a cofactor; in the second reaction, dopa is a substrate.

A computer-derived protocol to aid in the diagnosis of emergency room patients with acute chest pain.

Abstract: To determine whether data available to physicians in the emergency room can accurately identify which patients with acute chest pain are having myocardial infarctions, we analyzed 482 patients at one hospital. Using recursive partitioning analysis, we constructed a decision protocol in the format of a simple flow chart to identify infarction on the basis of nine clinical factors. In prospective testing on 468 other patients at a second hospital, the protocol performed as well as the physicians. Moreover, an integration of the protocol with the physicians' judgments resulted in a classification system that preserved sensitivity for detecting infarctions, significantly improved the specificity (from 67 per cent to 77 per cent, P<0.01) and positive predictive value (from 34 per cent to 42 per cent, P = 0.016) of admission to an intensive-care area. The protocol identified a subgroup of 107 patients among whom only 5 per cent had infarctions and for whom admission to non-intensive-care areas might be...

Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons

Abstract: An antiserum to monoamine oxidase B (MAO-B) was used to define the distribution of this metabolic enzyme in the adult rat brain immunocytochemically. MAO-B is specifically located in two major central nervous system cell classes, astrocytes and serotonin-containing neurons. Double-immunofluorescence experiments using antisera to glial fibrillary acidic protein and MAO-B showed that both protoplasmic and fibrillary astrocytes throughout the brain contain MAO-B, whereas oligodendrocytes do not contain the enzyme. Areas lacking a blood-brain barrier, such as the specialized circumventricular organs, also contain MAO-B-positive cells. A double-immunofluorescence experiment using antisera to serotonin and MAO-B enabled the positive identification of neurons containing both molecules. The catecholamine-containing neurons of the brain did not contain detectable amounts of MAO-B. The specific distribution of MAO-B in the adult central nervous system indicates that the role of MAO-B in monoamine metabolism may be more specifically defined than previously believed.

The Role of Knowledge in R&D Efficiency

Abstract: Past research has recognized that both demand and capability influence the allocation of R&D resources. Scholars have had an easier time getting a grip on demand than on capability. While it has been recognized that knowledge is an important part of capability, to date, formalization of knowledge and its role in R&D activity has been unsatisfactory. This paper models the role of knowledge in R&D. Various sources of such knowledge are considered. The model throws a different light on analyses that employ a “knowledge capital stock,†and also illuminates the dual private and public nature of technological knowledge.

The Effect of Graded Doses of Insulin on Total Glucose Uptake, Glucose Oxidation, and Glucose Storage in Man

Abstract: The dose-response relationship between plasma insulin concentration and total glucose uptake, glucose oxidation, and glucose storage was examined in 22 healthy young volunteers by employing the euglycemic insulin clamp technique in combination with indirect calorimetry. Insulin was infused at five rates to achieve steady-state hyperinsulinemic plateaus of 62 ± 4, 103 ± 5, 170 ± 10, 423 ± 16, and 1132 ± 47 μU/ml. With increasing plasma insulin concentrations within the physiologic range, there was a linear increase in glucose uptake with a half maximally effective insulin concentration of 72 μU/ml. Glucose uptake by all tissues of the body reached 80% of its maximum value (12.6 mg/kg · min) at a plasma insulin concentration of ∼200 μU/ml. In contrast to total glucose uptake, glucose oxidation plateaued more quickly, achieved a maximum rate of only 4.0 mg/kg · min, and displayed a lower half maximally effective insulin concentration of 40 μU/ml. The increase in glucose uptake with progressively increasing plasma insulin levels was primarily the result of an increase in glucose storage, with a half maximally effective insulin concentration of 105 μU/ml and maximum rate of 8.7 mg/kg · min. Glucose storage represented over 60–70% of total glucose uptake at all insulin concentrations. After achieving maximum rates of insulin-mediated glucose uptake (plasma insulin concentration = 1132 μU/ml), hyperglycemia (+125 mg/dl) was superimposed on hyperinsulinemia to further enhance glucose transport. Under these conditions, total glucose uptake (32.5 mg/kg · min, P

Single Ca2+-activated nonselective cation channels in neuroblastoma.

Abstract: Recent work suggests an important role for intracellular agents in controlling ion channels in the membranes of nerve cells and other excitable tissues. Calcium ions1,2, cyclic nucleotides3 and protein kinases4,5 can all act on the inner surface of the membrane to influence ion channel activity. Earlier studies of these effects on intact cells could not, however, effectively control or measure conditions on the inner membrane surface. The technique of recording from detached membrane patches6,7permits free access to the intracellular face of ion channels and makes it possible to study them in isolation from the many components of the cytoplasm. With this technique, I have studied the response of membrane patches from neuroblastoma cells to intracellular Ca2+ ions, and have found a class of nonselective cation channels activated by micromolar concentrations of Ca2+ on the intracellular face of the membrane. These channels are almost equally permeable to Na+, K+, Li+ and Cs+ ions, but are practically impermeable to Ca2+ ions. Similar channels were first found recently in cultured heart cells8, where they probably account for the previously reported ‘transient inward’ current9. Their discovery in neuronal cells as well as heart cells suggests that this hitherto scarcely recognized channel species may be more widely distributed than previously supposed.

Nonmonotonic Logic II: Nonmonotonic Modal Theories

Abstract: Tradmonal logics suffer from the "monotomclty problem"' new axioms never mvahdate old theorems One way to get nd of this problem ts to extend traditional modal logic in the following way The operator M (usually read "possible") is extended so that Mp is true whenever p is consistent with the theory Then any theorem of this form may be mvahdated if ~p ~s added as an axiom This extension results m nonmonotomc versions of the systems T, $4, and $5 These systems are complete in that a theorem is provable in a theory based on one of them just if it is true m all "noncommittal" models of that theory, where a noncommittal model ts one m which as many thmgs are possible as possible Nonmonotomc $4 is probably the most interesting of the three, since it is stronger than ordinary $4 but has all the usual inferential machinery of $4 There is a straightforward proof procedure for the sententlal subset of nonmonotomc $4. This approach to nonmonotonlc logic may be applied to several problems in knowledge representation for arUficml mtelhgence Its main advantages over competmg approaches are that tt factors out problems of resource hmltattons and allows the symbol M to appear m any context, since M is a meaningful part of the language

Alpha 2-adrenoceptor-mediated Hyperpolarization of Locus Coeruleus Neurons: Intracellular Studies in Vivo

Abstract: Intracellular recordings in vivo from noradrenergic neurons in the rat locus coeruleus showed that membrane potential was hyperpolarized by the administration of clonidine (an alpha 2-adrenoceptor agonist) or after a burst of spikes evoked by intracellular pulses; both types of hyperpolarization were associated with a decrease in membrane input resistance, and both could be blocked by the alpha 2-adrenoceptor antagonist piperoxane. These results suggest that a hyperpolarization of membrane potential mediated by an alpha 2-adrenoceptor underlies both clonidine- and activation-induced inhibition of locus coeruleus cell firing.