Showing papers by "Boston University published in 1983"

New diagnostic criteria for multiple sclerosis: guidelines for research protocols.

Abstract: Several schemes for the diagnosis and clinical classification of multiple sclerosis (MS) have been advanced [l}. The best known is that published by Schumacher et alC31. The criteria for this scheme were established in order to select patients for participation in therapeutic trials, and pertain only to what might be called definite MS. No provision was made for incorporating supportive laboratory data into the diagnostic criteria. As no reliable specific laboratory test for the diagnosis of MS has been discovered, the diagnosis remains a clinical one, and there is still a need for clinical diagnostic criteria. However, several laboratory and clinical procedures have been developed within the last decade which aid greatly in demonstrating neurological dysfunction attributable to lesions, and even the lesions themselves. One problem with the various published diagnostic classifications is their discrepant terminology: what is considered “probable” in one is called “definite” in another. Another problem is that all the proposed schemes require much subjective judgment, a difficulty which cannot be completely overcome but can be diminished by adding to the clinical evaluation the results of laboratory, neuroimaging, neuropsychological, and neurophysiological procedures. Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS. Method and Procedure

Absolute stability of global pattern formation and parallel memory storage by competitive neural networks

Abstract: Systems that are competitive and possess symmetric interactions admit a global Lyapunov function. However, a global Lyapunov function whose equilibrium set can be effectively analyzed has not yet been discovered. It remains an open question whether the Lyapunov function approach, which requires a study of equilibrium points, or an alternative global approach, such as the Lyapunov functional approach, which sidesteps a direct study of equilibrium points will ultimately handle all of the physically important cases.

Phases of the mentor relationship.

Abstract: The mentor relationship can significantly enhance development in early adulthood and also in the midcareer stage of the more experienced individual. A conceptual model derived from an intensive bio...

Sonar tracking of multiple targets using joint probabilistic data association

Abstract: The problem of associating data with targets in a cluttered multi-target environment is discussed and applied to passive sonar tracking. The probabilistic data association (PDA) method, which is based on computing the posterior probability of each candidate measurement found in a validation gate, assumes that only one real target is present and all other measurements are Poisson-distributed clutter. In this paper, a new theoretical result is presented: the joint probabilistic data association (JPDA) algorithm, in which joint posterior association probabilities are computed for multiple targets (or multiple discrete interfering sources) in Poisson clutter. The algorithm is applied to a passive sonar tracking problem with multiple sensors and targets, in which a target is not fully observable from a single sensor. Targets are modeled with four geographic states, two or more acoustic states, and realistic (i.e., low) probabilities of detection at each sample time. A simulation result is presented for two heavily interfering targets illustrating the dramatic tracking improvements obtained by estimating the targets' states using joint association probabilities.

Materialism and qualia: the explanatory gap

Abstract: J n “Naming and Necessity”1 and “Identity and Necessity,”2 Kripke presents a version of the Cartesian argument against mate­ rialism. His argument involves two central claims: first, that all identity state­ ments using rigid designators on both sides of the identity sign are, if true at all, true in all possible worlds where the terms refer; second, that psycho-physical identity statements are conceivably false, and therefore, by the first claim, actually false. My purpose in this paper is to transform Kripke’s argument from a metaphysical one into an epistemological one. My general point is this. Kripke relies upon a particular intuition regarding conscious experience to support his second claim. I find this intuition important, not least because of its stubborn resistance to philosophical dissolution. But I don’t believe this intuition supports the meta­ physical thesis Kripke defends—namely, that pyscho-physical identity statements must be false. Rather, I think it supports a closely related epistemological thesis— namely, that psycho-physical identity statements leave a significant explanatory gap, and, as a corollary, that we don’t have any way of determining exactly which psycho-physical identity statements are true.3 One cannot conclude from my version of the argument that materialism is false, which makes my version a weaker attack than Kripke’s. Nevertheless, it does, if correct, constitute a problem for materialism, and one that I think better captures the uneasiness many philos­ ophers feel regarding that doctrine. I will present this epistemological argument by starting with Kripke’s own argument and extracting the underlying intuition. For brevity’s sake, I am going to assume knowledge of Kripke’s general position concerning necessity and the theory of reference, and concentrate only on the argument against materialism. To begin with, let us assume that we are dealing with a physicalist type-identity theory. That is, our materialist is committed to statements like: (1) Pain is the firing of C-fibers. On Kripke’s general theory, if (1) is true at all it is necessarily true. The same of course, is the case with the following statement: (2) Heat is the motion of molecules. That is, if (2) is true at all it is necessarily true. So far so good.

Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation.

Abstract: We describe a new method for subcellular fractionation of human neutrophils. Neutrophils were disrupted by nitrogen cavitation and the nuclei removed by centrifugation. The postnuclear supernatant was applied on top of a discontinuous Percoll density gradient. Centrifugation for 15 min at 48,000 g resulted in complete separation of plasma membranes, azurophil granules, and specific granules. As determined by ultrastructure and the distribution of biochemical markers of these organelles, approximately 90% of the b-cytochrome in unstimulated cells was recovered from the band containing the specific granules and was shown to be in or tightly associated with the membrane. During stimulation of intact neutrophils with phorbol myristate acetate or the ionophore A23187, we observed translocation of 40-75% of the b-cytochrome to the plasma membrane. The extent of this translocation closely paralleled release of the specific granule marker, vitamin B12-binding protein. These data indicate that the b-cytochrome is in the membrane of the specific granules of unstimulated neutrophils and that stimulus-induced fusion of these granules with the plasma membrane results in a translocation of the cytochrome. Our observations provide a basis for the assembly of the microbicidal oxidase of the human neutrophil.

Bargaining under Incomplete Information

Abstract: This paper presents and analyzes a bargaining model of bilateral monopoly under uncertainty. Under the bargaining rule proposed, the buyer and the seller each submit sealed offers that determine whether the good in question is sold and the transfer price. The Nash equilibrium solution of this bargaining game implies an offer strategy of each party that is monotonic in its own reservation price and depends on its assessment of the opponent's reservation price. Issues of relative bargaining advantage and efficiency are examined for a number of special cases. Finally, we discuss the appropriateness of the Nash solution concept.

Cortical connections between rat cingulate cortex and visual, motor, and postsubicular cortices.

Abstract: The connections of rat cingulate cortex with visual, motor, and postsubicular cortices were investigated with retrograde and anterograde tracing techniques. In addition, connections between visual and the postsubicular (area 48) and parasubicular (area 49) cortices were evaluated with the same techniques. The following conclusions were drawn. Area 29 connections: Afferents to area 29 originate mainly from cingulate areas 24 and 25, visual cortex (primarily area 18b), motor cortex area 8, area 11 of frontal cortex, areas 48 and 49, and the subiculum. Efferent connections of area 29 within cingulate cortex and to visual areas differ for each cytoarchitectural subdivision of area 29. Thus, area 29c has limited projections both within cingulate cortex and to areas 48 and 49, while area 29d projects to these areas as well as to area 8, area 18b, and medial area 17. These visual cortex afferents originate mainly from layer V neurons of areas 29b and 29d, while areas 29a and 29c have virtually no projections to visual cortex. Area 24 connections: Afferents to area 24 originate primary from cingulate areas 25 and 29 and visual area 18b and medial area 17. Efferent projections of area 24a are distributed within cingulate cortex, while area 24b has more extensive projections to posterior cingulate and visual cortices. Area 24b is the cingulate subdivision which is both the primary recipient of visual cortex afferents as well as the source of most of the projections of anterior cingulate cortex to visual areas. Visual cortex has reciprocal connections with parts of the postsubicular and parasubicular cortices. Neurons of the internal pyramidal cell layer of both areas 48 and 49 project to areas 17 and 18b, while layers I and III of these parahippocampal areas receive projections from areas 17 and 8b. In conclusion, areas 29d have particularly extensive interconnections with visual cortex, while area 29d also maintains projections to area 8 of motor cortex. This connection scheme supports the view that cingulate cortex may have a role in feature extraction from the sensory environment, as well as in sensorimotor integration. Finally, the postsubiculum may be classified as a limbic association cortex in which extensive visual and cingulate efferents converge.

The human metabolic response to chronic ketosis without caloric restriction: Preservation of submaximal exercise capability with reduced carbohydrate oxidation☆

Abstract: To study the effect of chronic ketosis on exercise performance in endurance-trained humans, five well-trained cyclists were fed a eucaloric balanced diet (EBD) for one week providing 35-50 kcal/kg/d, 1.75 g protein/kg/d and the remainder of kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD), isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented to meet the recommended daily allowances for vitamins and minerals. Pedal ergometer testing of maximal oxygen uptake (VO2max) was unchanged between the control week (EBD-1) and week 3 of the ketogenic diet (EKD-3). The mean ergometer endurance time for continuous exercise to exhaustion (ENDUR) at 62%-64% of VO2max was 147 minutes at EBD-1 and 151 minutes at EKD-4. The ENDUR steady-state RQ dropped from 0.83 to 0.72 (P less than 0.01) from EBD-1 to EKD-4. In agreement with this were a three-fold drop in glucose oxidation (from 15.1 to 5.1 mg/kg/min, P less than 0.05) and a four-fold reduction in muscle glycogen use (0.61 to 0.13 mmol/kg/min, P less than 0.01). Neither clinical nor biochemical evidence of hypoglycemia was observed during ENDUR at EKD-4. These results indicate that aerobic endurance exercise by well-trained cyclists was not compromised by four weeks of ketosis. This was accomplished by a dramatic physiologic adaptation that conserved limited carbohydrate stores (both glucose and muscle glycogen) and made fat the predominant muscle substrate at this submaximal power level.

Cognitive Loss and Recovery in Long-term Alcohol Abusers

Abstract: • The nature of the memory and visuospatial defects associated with chronic alcoholism, and the recovery of these functions, were investigated in a large group of alcoholic men and well-matched nonalcoholic controls. Both young and old alcoholics displayed significant impairments on tasks requiring the learning of novel associations and the holding of information in memory over longer delay intervals. The recovery of cognitive skills was found to depend on the length of abstinence and the particular behavioral functions examined. Whereas psychomotor skills and short-term memory improved significantly with prolonged abstinence, long-term memory was impaired even after seven years of continuous sobriety. We propose that recovery of short-term memory reflects reestablishment of cortical functioning, while the persistent long-term memory defect indicates more permanent damage to diencephalic structures.

The intrinsic architectonic and connectional organization of the superior temporal region of the rhesus monkey

Abstract: The superior temporal region (STR) in the rhesus monkey includes the circular sulcus (Cis), the supratemporal plane (STP), and the superior temporal gyrus (STG). Rostrally the STR is continuous with the periallocortices of the prepyriform and anterior insular regions; caudally it borders the isocortices of the inferior parietal lobule and the superior temporal sulcus. The STR contains 12 cytoarchitectonic areas: four fields on the Cis, four on the STP, and four on the STG. The sulcal fields (root fields) are adjacent to the insula and resemble it in the possession of a relatively strong layer V; the STP fields (core fields) are characterized by well-developed layer IV; and the STG fields (belt fields) exhibit strong differentiation of layer III. In each line of fields the more rostral ones show relative prominence of the deeper layers, with increasing prominence of the superficial layers occurring caudad in a stepwise fashion. Analysis of the connectional organization of the fields within the STR suggests an assembly of four rostrocaudal stages, each composed of one field from each line--a root, a core, and a belt field. There is a specific arrangement of connections among the fields of a given stage and between fields in adjacent stages. Projections directed caudally from one field to another field in the adjacent stage arise in layers V and VI and terminate in the superficial layers (mainly layer I). Projections directed to a field in a rostrally adjacent stage arise from layer III neurons and terminate in layers III and IV, usually in columns. There is also a laminar specificity between fields lying within a given stage.

I Won the Auction But Don't Want the Prize

Abstract: The "winner's curse" occurs in competitive situations when a successful buyer finds that he or she has paid too much for a commodity of uncertain value. This study provides an experimental demonstration of the winner's curse, and identifies factors that affect the existence and magnitude of this bidding abnormality. In an auction setting, two factors are shown to affect the incidence and magnitude of the winner's curse: (1) the degree of uncertainty concerning the value of the item up for bid and (2) the number of competing bidders. Increasing either factor will increase the range of value estimates and bids, making it more likely that the winning bidder will overestimate the true value of the commodity and thus overbid. A number of researchers have suggested that the winner of a sealedbid auction will often lose-that is, the object acquired will be worth less than the price paid. The winning bidder has fallen prey to the "winner's curse." This idea has been suggested theoretically (Case, 1979; Oren and Williams, 1975; Rothkopf, 1980; Winkler and Brooks, 1980) and has been applied to bidding on oil leases (Capen et al., 1971), stock market investments (Miller, 1977), and baseball players (Cassing and

Risk factors for breast cancer

Abstract: Since 1976, data were collected to evaluate risk factors for breast cancer in a hospital-based case-control study of 1185 women with breast cancer and 3227 controls. The risk of breast cancer increased with increasing age at first birth; this effect was not accounted for by parity. An early age at first birth appeared to reduce the risk relative to no pregnancy, whereas a late age at first birth was associated with a higher risk than not having a full-term pregnancy. High parity was associated with a reduction in the risk that was independent of that of age at first birth: for parity ≧5, compared with parity 1-2, the relative risk estimate was 0.7 (95% confidence Interval, 0.5-1.0). Late age at menarche was associated with a lower risk among premenopausal women but not among postmenopausal women. The relative risk decreased with increasing obesity among premenopausal women. Among postmenopausal women, the risk was higher among those who were obese, but there was no evidence of a trend with increasing body mass index. Risk did not vary materially according to history of abortion when gravidity was controlled. Risk was lower among postmenopausal women than among premenopausal women of the same age and increased with increasing age at menopause; bilateral oophorectomy reduced the risk more than hysterectomy alone. A positive history of benign breast disease, a positive family history of breast cancer, Jewish religion, and 12 or more years of education were each independently associated with an increased risk of breast cancer.

Theory of hydromagnetic waves in the magnetosphere

Abstract: Many of the significant theoretical advances in understanding the origin and behaviour of low frequency hydromagnetic waves originating in the magnetosphere in the last decade are reviewed. Topics covered include wave generation mechanisms, wave damping, effects of inhomogeneity, signal behaviour in the ionosphere and atmosphere.

Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I

Abstract: Several mitogens elicit tyrosine-specific protein kinase activities1–7. Although the physiological significance of this is unclear, the generality of these reactions implies that this may be an inherent feature of growth factor–growth factor receptor interactions. The observed mitogenic properties of the polypeptide insulin-like growth factor I (IGF-I)8,9 indicated that it might also stimulate such activity. We report here that IGF-I stimulates a tyrosine-specific protein kinase in a time- and dose-dependent fashion. The close correspondence between an approximate 50% effective dose (ED50) of phosphorylation and an approximate Kd for IGF-I binding leads us to conclude that a high-affinity IGF-I receptor, not the structurally similar insulin receptor10, is the mediator of IGF-I-stimulated kinase activity. Immunoprecipitation indicates that both the β-subunit of the IGF-I receptor and the β-subunit of the insulin receptor are targets for the IGF-I-stimulated protein kinase.

High-density lipoproteins: Epidemiologic profile and risks of coronary artery disease

Abstract: The lipid-atherogenesis connection has undergone an evolutionary metamorphosis from a focus initially on serum total cholesterol, subsequently on other lipids, then on the lipoproteins that transport them, and now on the distribution of cholesterol in the low-density lipoproteins (LDL), high-density lipoproteins (HDL) and very low density lipoproteins. it is now established that the relation of serum total cholesterol to coronary heart disease (CHD) derives chiefly from the atherogenic LDL component, and that level of HDL cholesterol is inversely related to risk. The protective effect of HDL is at least as strong as the atherogenic effect of LDL and is independent of lipids and other risk factors. Every change of 10 mg/dl in the HDL cholesterol level is associated with a 50 % change in risk. At any level of serum total cholesterol, risk varies widely, depending on the LDL HDL ratio. A serum total cholesterol HDL ratio of 5.0 is associated with average risk; optimal ratios, around 3.5, correspond to half the standard risk. Further refinements in the lipid profile may be possible because there are several HDL and LDL subfractions with different atherogenic potential probably related to their apoprotein makeup. Only weak and inconsistent relationships of stroke and peripheral arterial disease to serum cholesterol and its lipoprotein fractions have been found, although there is the expected inverse relation to HDL cholesterol. An inverse relation of LDL level to stroke in women, and in men a possible excess mortality at very low serum cholesterol values attributed to colon cancer, have been reported.

Manifestations of Coronary Disease Predisposing to Stroke: The Framingham Study

Abstract: The relation of coronary heart disease to development of strokes in general and brain infarction in particular has been examined prospectively over 24 years of follow-up in the Framingham Study cohort. In the course of 24 years of biennial surveillance, there were 169 strokes in men and 175 in women aged 45–84; brain infarctions occurred in 100 men and 107 women, comprising 60% of strokes. Routine ECG’s chest X-rays coronary heart disease and cardiac failure status were ascertained biennially on regular examinations and risk of strokes determined in relation to these. Age and other stroke risk factors (including blood pressure, diabetes cigarettes and lipids were also routinely measured and were taken into account in multivariate analysis of the net and joint effects of CHD manifestations as precursors of strokes. The incidence of stroke was lower and stroke occurred later in life than coronary heart disease. Stroke incidence in men lagged that of myocardial infarction by more than 10 years. In women, the incidence of brain and myocardial infarction was similar. In men the average annual incidence of myocardial infarction (8.5/1000) was three times that for brain infarction (2.7/1000).1

Formation of methylamines from ingested choline and lecithin.

Abstract: Humans ingest substantial amounts of choline and lecithin as part of common foods. Physicians have recently begun administering large doses of these compounds to individuals with neurological diseases. A significant fraction of ingested choline is destroyed by enzymes within gut bacteria, forming trimethylamine (TMA), dimethylamine (DMA) and monomethylamine (MMA). Some of these methylamines are eventually excreted into the urine, presumably after being absorbed and carried to the kidneys via the bloodstream. The methylamines formed after choline is eaten could be substrates for the formation of nitrosamines, which have marked carcinogenic activity. Twenty-seven millimoles of choline chloride, choline stearate or lecithin were administered to healthy human subjects. It was found that these treatments markedly increased the urinary excretion of TMA, DMA and MMA, with choline chloride having the greatest effect. Rats were treated with 2 mmol/kg b.wt. of choline chloride or lecithin, and it was found that these treatments significantly increased urinary TMA excretion and did not alter DMA or MMA excretion. Our choline chloride preparation contained no MMA, DMA or TMA; however, it was found that our choline stearate and all the commercially available lecithins tested were contaminated with methylamines. Prior removal of methylamines from our lecithin preparation minimized the effect of oral administration of this compound on methylamine excretion in urine of rats and humans.

Arachidonic acid metabolism by platelets of differing size

Abstract: The relationship between mean platelet volume (MPV) and platelet arachidonic acid metabolism was examined by studying the ability of human platelets of different size to incorporate and metabolize tritiated arachidonic acid ([3H]AA). Platelet phospholipids were labelled with [3H]AA and the platelets were then fractionated into size-dependent subpopulations by counterflow centrifugation. The incorporation of [3H]AA increased through the fractions proportional to the MPV. After thrombin stimulation the per cent of total 3H-radioactivity released from the platelets decreased as the MPV increased. However, fractionation of the released 3H-radioactivity by HPLC (high performance liquid chromatography) demonstrated that MPV had no significant influence on the per cent of total platelet 3H-radioactivity released as cyclooxygenase products or as HETE (12-hydroxyeicosatetraenoic acid) but that the release of unmetabolized [3H]AA decreased as MPV increased. In separate experiments using unlabelled platelets the absolute release of thromboxane B2 (TXB2) after collagen- and thrombin-induced aggregation was measured by radioimmunoassay and was found to increase in proportion to the MPV. These results demonstrate that the release of arachidonic acid metabolites is qualitatively similar in platelets of different size. However, the absolute ability of platelets to incorporate arachidonic acid, convert it to active metabolites and release them is proportional to their volume. The ability of platelets to release unmetabolized arachidonic acid varies inversely with their MPV.