cssi/SciSciGPT-SciSciNet huggingface dataset:
Methionine Transfer Ribonucleic Acid from Folate-sufficient and Folate-deficient Streptococcus faecalis R

Abstract The formation of aminoacyl transfer ribonucleic acid derivatives containing a blocked α-amino group such as the formylmethionyl ester of methionine transfer ribonucleic acid (fMet-tRNAfmet) was studied in Streptococcus faecalis R. This bacterium cannot synthesize folate, and its growth is dependent upon the presence of either added folic acid or a mixture of products of biosynthetic reactions requiring the participation of tetrahydrofolate: serine, methionine, a purine, and thymine. Only extracts prepared from S. faecalis R cells grown on medium containing folic acid catalyzed the formation of an amino acid derivative esterified to tRNA which lacked a free α-amino group; of the amino acids tested, only methionine was a substrate for the formation of such an aminoacyl-tRNA derivative containing a blocked α-amino group. The methionyl-tRNA derivative was identified as N-formylmethionyl-tRNA. Extracts prepared from S. faecalis R cells grown on folate-free medium supplemented with serine, methionine, a purine, and thymine could not catalyze the formation of any detectable aminoacyl-tRNA species containing a modified α-amino group. The in vivo level of charged tRNAmet of exponentially grown S. faecalis R was estimated to be near 100% for both folate-sufficient and folate-deficient grown cells, and the total amount of tRNAfmet was the same under both culture conditions. However, methionyl-tRNAfmet was only formylated in cells grown in the presence of folic acid. Approximately 82 to 85% of the tRNAfmet of S. faecalis R in exponential growth stage in folate-containing medium was blocked to further formylation using 10-[14C]formyltetrahydrofolate as the formyl donor, whereas none of the tRNAfmet prepared from cells grown in the absence of folic acid was blocked to formylation. These results indicate that methionyl-tRNA in S. faecalis R grown in the absence of folic acid but in the presence of the supplements is neither formylated nor contains a blocked α-amino group and provide further evidence that formylation of methionyl-tRNAfmet is not required for the initiation of protein synthesis in S. faecalis R under certain defined conditions of culture.
Cortical stimulation in the definition of eloquent cortical areas

Publisher Summary This chapter provides an overview of “eloquent cortex” and discusses the different aspects of cortical mapping. The important variables that ensure a safe and meaningful study of cortical function include the selection of electrodes, electrode placement, and electrical stimulus that can be reliably delivered to a discrete focal cortical area, and careful and objective recording of responses with clearly specified guidelines. Several mechanisms that could give rise to speech arrest during a stimulation study include stimulation of a positive area, stimulation of a negative motor area, stimulation of the cortex that elicits other distracting symptoms, alteration of consciousness, and stimulation of a language area. Electrical stimulation of the Broca's area may result in the impairment of speech output manifested as speech arrest, slowing of speech, alexia, agraphia, anomia, or paraphasia. These effects can be observed in isolation or in combination from one or more electrodes within the area. Electrical stimulation of Wernicke's area leads to comprehension deficits for auditory and visual stimuli. There are no associated negative motor responses in this area, thus suggesting that Wernicke's area appears to be an exclusive language center and that it is not involved in the organization of voluntary movement.
Studying p53-dependent cell death in vitro and in vivo.

Publisher Summary Essentially, studying p53-dependent cell death is comparing the apoptotic response between p53 wild-type cells or tissues to that of p53 null or mutants. Basically, there are two ways to study how this depends on p53 in vitro. One is to introduce wild-type p53 in p53-null or mutant cells, and the other is to silence p53 in the wild-type cells. There are benefits and disadvantages regarding both methods. It is an advantage of introducing wild-type p53 into the null or mutant cells that direct effects of p53 can be studied. However, because of the growth suppressive effect of p53, the response could not be followed up for a long time. Creating a stable cell line in which the p53 gene is silenced by a short interfering RNA technique solves the problem. However, efficiency of the gene silencing is usually incomplete, and activating the p53 pathway requires additional stimuli, such as cytotoxic drugs, that usually activate the p53 pathway, as well as the other pathways simultaneously. p53-knockout mice were first generated in 1992 and have been extensively used for cancer studies, because they, in a homozygous state, develop lymphomas and soft tissue sarcomas within 3 to 5 months of age. However, use of the p53-deficient model has not been restricted to cancer studies. Important insights have been achieved into p53 function in cell-cycle control, response to DNA damage, apoptosis, hypoxia, oncogenic stimuli, embryonic development, and immunity.
A strong law of large numbers related to multiple testing normal means

Abstract We prove a strong law of large numbers for simultaneously testing whether the means of a set of dependent normal random variables are zero. Our result can be used to check whether the widely-used “weak dependence” assumption holds.
A new Approach to Policy-Based Routing in the Internet

The current Internet routing architecture is based on a distributed, address-based, hop-by-hop routing model. In contrast, current proposals for policy-based routing are based on an on-demand, source-specified routing model. The benefits of the Internet model are that it is very robust, efficient, and responsive. However, it only supports a single forwarding class per destination. As a result, the Internet does not efficiently support quality-of-service (QoS) or traffic engineering, which are critical capabilities for the future of the Internet. In this chapter we review these previous solutions, review their limitations, and propose a new distributed policy routing model which we call distributed label-swap routing.
Decreased respiratory symptoms in cannabis users who vaporize

Cannabis smoking can create respiratory problems. Vaporizers heat cannabis to release active cannabinoids, but remain cool enough to avoid the smoke and toxins associated with combustion. Vaporized cannabis should create fewer respiratory symptoms than smoked cannabis. We examined self-reported respiratory symptoms in participants who ranged in cigarette and cannabis use. Data from a large Internet sample revealed that the use of a vaporizer predicted fewer respiratory symptoms even when age, sex, cigarette smoking, and amount of cannabis used were taken into account. Age, sex, cigarettes, and amount of cannabis also had significant effects. The number of cigarettes smoked and amount of cannabis used interacted to create worse respiratory problems. A significant interaction revealed that the impact of a vaporizer was larger as the amount of cannabis used increased. These data suggest that the safety of cannabis can increase with the use of a vaporizer. Regular users of joints, blunts, pipes, and water pipes might decrease respiratory symptoms by switching to a vaporizer
Induction and suppression of hepatic and extrahepatic microsomal foreign-compound-metabolizing enzyme systems by 2,3,7,8-tetrachlorodibenzo-p-dioxin☆

Abstract The effects of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) on a number of hepatic and extrahepatic foreign-compound-metabolizing enzyme systems in microsomes from rats, rabbits and guinea pigs were investigated. Following TCDD treatment, the N -demethylation of benzphetamine, aminopyrine and ethylmorphine was suppressed in hepatic microsomes from male but not from female rats. However, both cytochrome P-450 and benzpyrene hydroxylase were significantly stimulated in hepatic microsomes from both male and female rate at doses as small as 1 μg TCDD/kg body weight. The inductive effect on rat hepatic microsomal enzymes was considerably more persistent than the suppressive effect. Following a single oral dose of 25 μg TCDD/kg body weight, benzpyrene hydroxylase of male rat liver microsomes remained significantly elevated for 73 days but the suppression of benzphetamine N -demethylase had gone after 35 days. The induction of benzpyrene hydroxylase in male rat liver microsomes by TCDD was independent of the age of the rat and the levels to which this enzyme was increased was similar in male rats of all ages. However, the suppression of benzphetamine N -demethylase in male rat liver microsomes was age related: the suppression was seen only in adult animals and in the very young (10 days old) the enzyme was actually induced by TCDD. Inductive effects appeared in both smooth and rough-surfaced hepatic microsomes from male rats but the suppression of N -demethylidon occurred perhaps the derepression arises through the interaction of TCDD or metabolite of TCDD, with the operator gene itself.
Photodissociation spectroscopy of Mg+H2O

Mg+H2O ion—molecule complexes are produced in a pulsed supersonic nozzle cluster source. These weakly bound complexes are mass selected and studied with laser photodissociation spectroscopy in a reflectron time-of-flight mass spectrometer system. An electronic transition assigned as 2B2→X2A1 is observed with an origin at 28399 cm−1 (vac). The spectrum has a prominent progression in the metal—H2O stretching mode with a frequency (ω′e) of 517.1 cm−1. An extrapolation of this progression fixes the excited state dissociation energy (D′0) at 16008 cm−1. The corresponding ground state value (D″0) is 8732 cm−1 (25.0 kcal/mol). The solvated bending mode and asymmetric stretching mode of water are also active in the complex. A second electronic transition assigned as 2B1←X 2A1 is observed with an origin at 30386 cm−1 and a metal stretch frequency of 483.4 cm−1. This study was guided by ab initio calculations by Bauschlicher and co-workers, which provide accurate predictions of the electronic transition energies, vibrational constants and dissociation energies.
Transformations of solutions for equations and hierarchies of pseudo-spherical type

It is known that if an equation describes non-trivial one-parameter families of pseudo-spherical surfaces, its conservation laws, (generalized, nonlocal) symmetries and Backlund transformations can be studied by geometrical means [4, 10]. In this letter it is pointed out that there exist correspondences, or 'generalized Backlund transformations', between arbitrary solutions (satisfying some genericity conditions) of any two single equations describing pseudo-spherical surfaces. Then, the notion of a hierarchy of equations of pseudo-spherical type is introduced, and a theorem stating that there also exist correspondences between arbitrary solutions of any two such hierarchies is presented. A full account of these results appears elsewhere [12, 13].
Phase II study of VP16-213 (Etoposide) in refractory metastatic breast carcinoma

VP16-213 is a semi-synthetic derivative of podophyllotoxin. Preclinical trials have indicated a marked schedule dependency in the L1210 system suggestive of an advantage to short-cycle times and divided dose regimens. Seventy-seven patients with advanced breast carcinoma were studied. All patients had failed conventional combination chemotherapy (median prior chemotherapy: 23 months). All had prior Adriamycin and more than half had prior exposure to vinca alkaloids. The patients were randomly allocated to either: 1) intermittent bolus —50–70 mg/m2/day over 1 h daily for 5 days (39 patients), or 2) infusion — 50–70 mg/m2/day as a continuous infusion for 5 days (38 patients). In the intermittent group, three patients were inevaluable (early death) and one was lost to follow-up. In the infusion group, four patients were inevaluable (early death), two were lost to follow-up and one refused further treatment. In the intermittent group of 35 evaluable patients, five (14%) achieved partial remission, three (9%) had responses less than partial, six (17%) had stable disease, and 21 (60%) had progressive disease. In the infusion group of 31 evaluable patients, one (3%) achieved complete remission, three (10%) achieved partial remission, three (10%) had responses less than partial, five (16%) had stable disease and 19 (61%) had progressive disease. Principle toxicity observed was myelosuppression, which was severe (granulocytes <1,000) in approximately 50% with nadirs occuring at about day 12. Recovery was rarely prolonged beyond day 20. Nausea and vomiting were moderate with the intermittent schedule and almost absent with the infusion schedule. One patient in the intermittent group developed an anaphylactoid reaction requiring discontinuation of the drug. Congestive heart failure was precipitated by the fluid load in five patients on the infusion schedule. VP16-213 has significant antitumor activity in refractory breastcarcinoma and merits further evaluation. The infusion schedule showed no advantage over the intermittent schedule of this study.
Identification of S-(n-butylcarbamoyl)glutathione, a reactive carbamoylating metabolite of tolbutamide in the rat, and evaluation of its inhibitory effects on glutathione reductase in vitro.

Tolbutamide (TOLB), a widely used hypoglycemic agent in the therapy of non-insulin-dependent diabetes mellitus, has been reported to be teratogenic and/or embryotoxic in several animal species and humans. It has been proposed that the teratogenic effects of TOLB are linked to drug-mediated depletion of glutathione (GSH) through inhibition of the enzyme glutathione reductase (GR), although the mechanism by which this inhibition occurs remains unknown. In the study presented here, rats were injected with TOLB (200 mg/kg ip), and bile was collected for analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS). This led to the identification of S-(n-butylcarbamoyl)glutathione (SBuG), a reactive GSH conjugate derived from n-butyl isocyanate, as a minor metabolite of TOLB in bile. Upon incubation of SBuG (0.25−1.0 mM) with GR from either yeast or bovine intestinal mucosa in the presence of NADPH (0.20 mM), enzyme activity was lost in a time- and concentration-dependent manner. No inhibition was obse...
Mortality among prematurely born infants

Summary Reduction of mortality among prematurely born infants constitutesa large part of the infant mortality problem in the United States today. Since in a large proportion of cases the causes of premature birth are reported as “unknown,” further efforts should be made to determine these causes. Moreover, information now available as to the causes of premature birth should be more generally applied in efforts to prolong pregnancy until the infant is mature enough to survive. The causes of death of prematurely born infants are in at least half the cases reported as “unknown.” Further investigations should be made, since the causes must be understood before attempts to lower mortality can be intelligently made. The methods of care and treatment of prematurely born infants nowin use should be evaluated on the basis of morbidity and mortality studies, and the methods found to be of value should be more widely applied. Since it is among infants of low birth weight that mortality is highest, further efforts should be made to develop special methods of caring for this group of infants. It is only when the medical profession and the public become betteraware of the problem of the prematurely born infant, and when they make concerted efforts to solve it, that mortality among these infants will be reduced to any great extent.
Brachiocephalic reconstruction II: operative and endovascular management of single-vessel disease.

Objective Although the surgical management of brachiocephalic disease is well established, evolving endovascular techniques present new options for treatment. We explored the potential benefits and drawbacks of these interventions in terms of outcome. Methods From 1966 to 2004, 391 consecutive patients (43.7% male; mean age, 61.9 years) with single-vessel brachiocephalic disease were treated with either operative bypass (group A; n=229) or percutaneous transluminal angioplasty and stenting (group B; n=162). Results All patients were asymptomatic after surgery or endovascular intervention. Group A and group B had similar operative mortality (0.9% vs 0.6%) and stroke (1.3% vs 0%) rates. However, 5 years after the procedure, group A had significantly better freedom from graft or intervention failure (92.7% ± 2.1%) than did group B (83.9% ± 3.7%; P = .03, Kaplan-Meier analysis; P = .001, Cox regression analysis). At 10 years, group A had the following rates of actuarial freedom from specific events: death, 73.7% ± 4.6%; myocardial infarction, 84.2% ± 3.6%; stroke, 91.4% ± 3.4%; graft failure, 88.1% ± 3.3%; coronary revascularization, 69.8% ± 5.1%; and other vascular operation, 70.7% ± 4.6%. Endovascular intervention involved less initial cost (mean savings, $8787 per procedure), was less invasive, and did not necessitate general anesthesia. On satisfaction questionnaires, 96.5% of patients receiving an endovascular intervention and 95.1% of patients receiving operative bypass for single-vessel brachiocephalic disease subjectively rated their treatment as "good" or "very good." Conclusions Operative bypass and endovascular intervention for single-vessel brachiocephalic disease are both associated with acceptably low operative morbidity and mortality. Operative bypass produces significantly better mid-term freedom from graft or intervention failure than endovascular intervention and produces excellent long-term freedom from failure. Endovascular intervention offers tangible benefits regarding cost, level of invasiveness, and subjective patient satisfaction. Undetermined are the differences between the procedures regarding long-term durability, patterns of failure, efficacy as an adjunct to coronary artery bypass grafting, need for anticoagulation, efficacy as treatment for complex (multivessel) disease, and long-term cost.
Response of alfalfa to fertilization with P and Mg in the greenhouse

Abstract Alfalfa (Medicago sativa L.) needs a considerable amount of P and Mg for maximum growth and production. ‘Lew’ alfalfa was grown in a greenhouse‐pot trial in Mohave sandy loam soil with several rates of P and Mg applied singly and in combination. There was a positive response to P applied alone, but Mg applied alone reduced plant growth even though herbage‐Mg concentration was increased (from 0.22% to 0.40% with the highest rate of 400 kgMg/ha). However, fertilization with both Mg and P resulted in a significant yield response and a higher herbage‐P concentration than when only P was applied. Within the conditions of this experiment, a response to fertilization with Mg is likely to occur only when the level of the P in the plants is adequate.
Spectral analysis of the visually evoked occipitogram in man.

Abstract The visually evoked occipitogram was studied in two color-normal observers over the visible spectrum (380–700 nm) in 16 steps at matched intensities. Confirming earlier reports, the waveform of the responses varies as a function of wavelength. A Fourier analysis indicates that this chromatic coding is confined primarily to the 4–8 c/s components in the waveforms. However, uncoded responses are also reported for other color-normal observers, which introduces a note of caution into our interpretation of these findings. These individual differences persist for on-off , on and off evocation. The VEOG responses in several color-deficient observers are also reported, indicating that an amplitude depression exists in the deuten group.
Does Dementia Associated with Vitamin B12 Deficiency Respond to Treatment? (P02.057)

Objective: To assess the reversibility of the dementia associated with vitamin B12 deficiency. Background The determination of B12 levels in patients with dementia is a routine practice to identify a reversible cause of dementia. However, conflicting evidence exists regarding the effects of B12 replacement on the dementia. Design/Methods: We reviewed the clinical courses of patients who had presented to our dementia clinic and were found to have a B12 deficiency, defined as a low B12 level and elevated methylmalonic acid (MMA) and homocysteine levels. A comparison group of patients with probable Alzheimer9s disease, matched for age, sex and baseline Mini-Mental State Examination (MMSE) score were also identified. Chi-square and Mann-Whitney U test were used for comparison of variables. Results: From a cohort of 1548 consecutive patients, 33 with B12 deficiency were identified. Mean age was 78.8±8.8 years; mean MMSE 21.6±4.8; mean B12 level 153.3 ±33.3 pg/ml. They were treated with B12 and followed for a mean duration of 26.6 months. There was no significant difference in baseline characteristics between the B12 deficiency group and the Alzheimer9s group except for initial vitamin B12 levels. Between the two groups, there was no difference in the rate of decline of the MMSE score (-0.19±0.37 vs -0.12±0.16, p=0.45), absolute change in MMSE score (-4.3±4.8 vs -6±7.8, p=0.17), or the number whose MMSE scores were stable or improved (30% vs 27%, p=0.78). None experienced a dramatic clinical reversal of their dementia with B12 replacement. Conclusions: Compared to patients with Alzheimer9s disease, our results showed no evidence of reversibility, stabilization, or retardation of progression of their dementia with B12 replacement. We acknowledge our patients with B12 deficiency may also have had Alzheimer9s. Considering our patient population, the dementia associated with B12 deficiency appears unlikely to reverse. Disclosure: Dr. Bhargava has nothing to disclose. Dr. Ala has received personal compensation for activities with The Dunn Group, MEDA Corp, The Council of Advisors, and the Gerson Lehrman Group as a consultant. Dr. Ala has received research support from Teva Pharmaceutical Industries, Neurochem, Ono Pharmaceutical Company, and Elan Pharmaceuticals.
Natural history of brainstem cavernous malformations.

Objective To review the natural history and determine the rates of intra- and extralesional hemorrhaging of brainstem cavernous malformations (cavernomas) monitored by one neuro-ophthalmology service. Methods A record review of all patients with brainstem cavernomas who were evaluated by a neuroophthalmology service between 1987 and 1999 was performed. We recorded the clinical symptoms and Rankin disability grade at presentation, during the worst clinical episode, and at the last follow-up examination. Magnetic resonance imaging scans were reviewed for evidence of intralesional hemorrhage (a bleeding episode), edema, or venous anomalies, and the cavernoma size was assessed. Results Thirty-seven patients (age range, 6-73 yr; mean age at presentation, 37.5 yr) underwent a mean of 4.9 years of follow-up monitoring. At presentation, there were 27 bleeding events and 8 nonhemorrhagic events; 2 patients did not exhibit symptoms. Patients who were at least 35 years of age exhibited a lower risk of bleeding episodes (odds ratio, 0.15; 95% confidence interval, 0.1-0.4). Cavernomas of at least 10 mm were associated with a higher risk of bleeding episodes (odds ratio, 3.48; 95% confidence interval, 1.3-9.4). Thirty-nine bleeding episodes occurred in 31 patients, yielding a bleeding rate of 2.46%/yr. There were eight rebleeding episodes, yielding a rebleeding rate of 5.1%/yr. Three patients experienced extralesional bleeding episodes; all of these patients experienced rebleeding. Of the 39 follow-up magnetic resonance imaging scans, the cavernoma size was unchanged in 66.7%, smaller in 18%, and larger in 15%. At the last follow-up examination, the mean Rankin grade was 1.0 for all patients, 0.6 for the 25 nonsurgically treated patients, and 1.4 for the 12 surgically treated patients. Conclusion Rebleeding is not more common among patients who first present with bleeding, and it often has little effect on the neurological status of patients. Significant morbidity attributable to a brainstem cavernoma occurred in 8% of patients during follow-up monitoring of medium duration.
Biological heterogeneity and radiation sensitivity of in vitro propagated lung metastatic lines originated from a transplantable squamous cell carcinoma of BALB/C mouse

Seven cell lines established from a diethylnitrosamine (DEN)-induced forestomach carcinoma (DEN3) of a BALB/c mouse and its six pulmonary metastatic foci were used to study the biological and functional diversity of tumor cells. DEN3 is a highly tumorigenic line capable of forming lung metastases readily. Six metastatic nodules were isolated from the lungs of syngeneic mice and six cell lines were established. The cell lines differed in characteristics such as tumorigenicity, metastatic capability, and in vivo and in vitro growth properties. Radiation sensitivity of these cell lines was examined by exposure, at ner confluency stage of in vitro growth, to doses of 2.5 to 50 Gray (Gy) X-rays (1 Gy=100 rads). Shortly after exposure (approximately 5 min), the cells were harvested and 105 cells were cultured or inoculated into syngeneic mice, or both. Growth of three of the six cell lines tested was prohibited by 5 Gy. However, some populations from the other cell lines were able to survive 5 or 10 Gy. Progenies of the cells that survived primary radiation exposure after several in vitro passages were able to withstand another exposure of the same magnitude but not a higher dose. The X-rayed survivor cells also maintained their tumorigenic potential.
Toward Adding Complexity in Single Molecule FRET Studies of DNA Mismatch Repair

Mistakes made during DNA replication are targeted for post-replicative repair by the DNA mismatch repair system. Purified reconstitutions of DNA mismatch repair require multiple protein interactions, and in vivo studies of DNA mismatch repair function have identified layers of spatial and temporal regulation. We have previously developed single molecule FRET experiments for studies of purified in vitro studies of DNA mismatch interactions from Thermus Aquaticus MutS and MutL. In this poster we present our recent progress developing single molecule FRET assays for more complex studies of DNA repair. In particular, we highlight our work using unnatural amino acid engineering and other methods for site-specific labeling of yeast repair proteins, detailed analysis of kinetics to reveal nucleotide regulation of protein conformations, and steps toward studies in live cells.
Mechanism of action of the Escherichia coli UvrABC nuclease: Clues to the damage recognition problem

During the process of E. coli nucleotide excision repair, DNA damage recognition and processing are achieved by the action of the uvrA, uvrB, and uvrC gene products. The availability of highly purified proteins has lead to a detailed molecular description of E. coli nucleotide excision repair that serves as a model for similar processes in eukaryotes. An interesting aspect of this repair system is the protein complex's ability to work on a vast array of DNA lesions that differ widely in their chemical composition and molecular architecture. Here we propose a model for damage recognition in which the UvrB protein serves as the component that confers enhanced specificity to a preincision complex. We hypothesize that one major determinant for the formation of a stable preincision complex appears to be the disruption of base stacking interactions by DNA lesions.
Are External Reasons Impossible

It is clear that our desires and aims provide us with some reasons for action. Are there also reasons for action that are not contingent upon what desires or aims we have? In his article "Internal and External Reasons,"' Bernard Williams answers a version of this question in the negative. He offers an argument intended to show that there are no reasons to perform actions that would not satisfy the agent's desires, aims, or other "motives." I shall try to bring into sharp focus what I take to be the weaknesses in this argument. But I also wish to show that, although the argument is unsuccessful, Williams does successfully identify the main hurdle that his opponents must surmount if they are to prove that desire-independent reasons are possible. According to Williams there are two mutually incompatible ways to interpret a sentence of the form "P has a reason to A" or "There is a reason for P to A."2 On the first or internal reading, it is a necessary condition for the truth of the sentence that P have some motive or aim which will be served or furthered by his A-ing, so that if he has none, it is not the case that he has a reason to A. On the second or external reading, the reason sentence does not imply that the agent has any such motive or aim and so "will not be falsified by the absence of an appropriate motive" (p. 17). More explicitly, "any model for the internal interpretation must display a relativity of the reason statement to the agent's subjective motivational set, which I shall call the agent's S.... An internal reason statement [a statement interpreted in the internal way] is falsified by the absence of some appropriate element from S" (p. 18). Although no precise definition of a subjective motivational set is given, Williams says that S contains desires, and "such things as dispositions of evaluation, patterns of emotional reaction, personal loyalties, and various projects . .. em-
A Double-Vented Tetraphasic Continuous Column Approach to MuDPIT Analysis on Long Capillary Columns Demonstrates Superior Proteomic Coverage

A double-vented serial tetraphasic capillary column approach is applied to proteomic MuDPIT-type analysis using extended length capillary reverse-phase columns. The heart of the tetraphasic device consists of a triphasic MuDPIT trap located upstream of a venting tee. The trap is followed by a 60 cm high-resolution capillary column. A conventional high-flow HPLC is used to develop gradients at standard flow rates and pressures. The double-vented triphasic MuDPIT trapping device relieves the capillary separation column from the salt burden during the on-line cation-exchange portion of the analysis. Two configurations are presented, a double-vented continuous column model and a discontinuous model in which the triphasic MuDPIT trap is installed on a six-port valve; both configurations were tested with 60 and 10 cm capillary columns. All four systems were challenged with a trypsin digest of undepleted human serum, and a matrix of proteomic results for the different models and column lengths are compared. Keyw...
The effect of Ca2+ channel antagonists (cadmium, ω-conotoxin GIVA, and nitrendipine) on the release of angiotensin II from fetal rat brain in vitro

Abstract We have shown previously that K + stimulation of dissociated cell cultures of fetal rat brain results in a graded release of angiotensin II (ANG II) that is dependent on the availability of extracellular Ca 2+ . In this study, using dissociated cell cultures of fetal rat hypothalamus, thalamus, septum, and midbrain (HTSM), we further examined the role of calcium channels on ANG II release using specific channel blockers (cadmium, ω-conotoxin, and nitrendipine) and a calcium ionophore (A23187). Levels of ANG II release were quantitated by radioimmunoassay and HPLC. For control levels of ANG II release, cells were incubated in a stock buffer containing 89 mM choline chloride/58 mM KCl/2 mM CaCl 2 . Pretreatment of the cells with either 100 μM Cd 2+ (to block N-, L-, and T-type calcium channels), 100 nM ω-conotoxin (to block N- and L-type calcium channels), or 500 nM nitrendipine (to block L-type calcium channels) decreased ANG II release by approximately 71%, 71%, and 22%, respectively, when compared to control levels. In contrast, pretreatment of the cells with 1.6 μM A23187 (a calcium ionophore) increased ANG II release by approximately 90% over control levels. These findings suggest that angiotensin release is dependent on the intracellular entry of Ca 2+ ions through primarily N-type channels, and to a lesser extent, L-type channels.
Equity Private Placements, Liquid Assets, and Firm Value

This paper finds wealth enhancement from equity private placement issuances where liquid assets are provided to slack-poor companies. This result runs counter to the expected Jensen's (1986) excess free-cash-flow problem, where the predominant findings of numerous studies include negative wealth effects from externally financed liquidity enhancements. We also find greater announcement-period returns for smaller firms and firms with better recent performance. Investors appear to view either of these factors, together with the private investor’s willingness to provide additional liquidity, as an asymmetric information release on the firm’s viability and likelihood of improved performance.
The POT1-TPP1 telomere complex is a telomerase processivity factor

Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 (protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.
Genetics of Fungi Pathogenic for Man

AbstractGreat strides have been made in research on fungi pathogenic to man and animal during the last three decades, but little progress has been made in the genetics of these microorganisms. The principal reason for such a delay in genetic research is that mechanisms for genetic recombination were not known to exist in most of the pathogens.1 It was not until the early part of the last decade that the parasexual cycle in Aspergillus fumigatus2 and heterothallism in several ringworm fungi were discovered.3-8 The reports of heterothallism in dermatophytes stimulated medical mycologists to search for the perfect state in systemic pathogens. Within the last 5 years, heterothallism has been discovered in Blastomyces dermatitidis, Histo-plasma capsulatum, and Geotrichum candidum.9-11 Although for the last 10 years steady progress has been made employing these fungi as genetic tools, our knowledge of the genetics of human pathogenic fungi is fragmentary compared with what is known about the saprophytes and pla...
Congenital Myasthenic Syndromes: Multiple Molecular Targets at the Neuromuscular Junction

Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis. Defects in ACh resynthesis have now been traced to mutations in choline acetyltransferase. A synaptic CMS is caused by mutations in the collagenic tail subunit (ColQ) of the endplate species of acetylcholinesterase that prevent the tail subunit from associating with catalytic subunits or from becoming inserted into the synaptic basal lamina. Most postsynaptic CMS are caused by mutations in subunits of the acetylcholine receptor (AChR) that alter the kinetic properties or decrease the expression of AChR. The kinetic mutations increase or decrease the synaptic response to ACh and result in slow- and fast-channel syndromes, respectively. Most low-expressor mutations reside in the AChR epsilon subunit and are partially compensated by residual expression of the fetal-type gamma subunit. In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane.
Lithium?metal infused trenches (LiMIT) for heat removal in fusion devices

Observation of liquid lithium flow in metal trenches has been made using a lithium–metal infused trench (LiMIT) tile and is reported here. The flow is self-pumping and uses thermoelectric magnetohydrodynamics to remove heated lithium and replenish it at a lower temperature. Flow velocities have been measured and compared with theoretical predictions.
Curing Dental Resins and Composites by Photopolymerization

The development and continued evolution of photopolymerizable dental materials, particularly dental composite restoratives, represent a significant, practical advance for dentistry. The highly successful integration of the light-activated curing process for dental applications is described in this review. The basic mechanisms by which the photoinitiators efficiently convert monomers into polymers are discussed along with the variety of factors that influence the photopolymerization process. The conventional camphorquinone-amine visible light photoinitiator system used in most dental restorative materials is illustrated in addition to some alternative initiator systems that have been studied for dental materials applications. CLINICAL SIGNIFICANCE Photopolymerization has become an integral component of the practice of dentistry. A better appreciation of the photopolymerization process as well as its potential and limitations may aid the dentist in the delivery of both esthetic and restorative dental care.
Newtonian viscosity measured by impression test

Abstract The problem of viscous flow beneath a flat-end planar as well as a cylindrical punch was analyzed when the punch was pressed onto the surface of a semi-infinite Newtonian fluid by a small load. The steady state penetration velocity of the punch was found directly proportional to both the punching stress and the size of the punch and inversely proportional to the viscosity. The relation among these parameters was not affected by the slip or stick boundary condition at the punch/liquid interface. So this ‘impression test’ should be a good way of measuring viscosity.
Th1 and Th2 Cytokines and IgE Levels in Identical Twins with Varying Levels of Cigarette Consumption

Some have suggested that tobacco smoke may skew the immune system toward a Th2 pattern, however the effects of genetics or childhood exposures could explain these results. We compared PMBC supernatant or serum Th1 (INF-γ) and Th2 (IL-4, IL-5, and IL-13) cytokine and IgE levels in members of 45 pairs of nonasthmatic monozygotic twins with varying levels of current cigarette consumption to determine if smoking was associated with Th1/Th2 function after accounting for genetic factors. A statistically significant dose-response was observed between levels of smoking and IL-13 (p=0.05). Mean IL-13 level among heavy smokers (20+ cigarettes/day) was 146% higher than that among nonsmokers (+26.2 pg/mL; p=0.04). The mean IL-5 level among heavy smokers was 166% higher than that among light (<20 cigarettes/day) smokers (+3.4 pg/mL; p=0.03). No statistically significant differences in INF-γ, IL-4, or IgE levels were observed. Smoking appears to be associated with increased levels of IL-13.
Secure sensor network routing: a clean-slate approach

The deployment of sensor networks in security- and safety-critical environments requires secure communication primitives. In this paper, we design, implement, and evaluate a new secure routing protocol for sensor networks. Our protocol requires no special hardware and provides message delivery even in an environment with active adversaries. We adopt a clean-slate approach and design a new sensor network routing protocol with security and efficiency as central design parameters. Our protocol is efficient yet highly resilient to active attacks. We demonstrate the performance of our algorithms with simulation results as well as an implementation on Telos sensor nodes.
Two-photon excitation spectrum of K2PtCl6

Abstract Two-photon excitation spectra of a transition metal complex dd transition have been measured for the first time. Data for a single crystal of K 2 PtCl 6 at 2 K is reported using laser excitation in the range 680–950 nm. Results suggest an alternate assignment of previous one-photon results.
Hippocampal involvement in detection of deviant auditory and visual stimuli

Recent models of hippocampal function have emphasized its role in processing sequences of events. In this study, we used an oddball task to investigate hippocampal responses to the detection of deviant “target” stimuli that were embedded in a sequence of repetitive “standard” stimuli. Evidence from intracranial event-related potential studies has suggested a critical role for the hippocampus in oddball tasks. However, functional neuroimaging experiments have failed to detect activation in the hippocampus in response to deviant stimuli. Our study aimed to resolve this discrepancy by using a novel functional magnetic resonance imaging (fMRI) technique that drastically improves signal detection in the hippocampus. Significant hippocampal activation was observed during both auditory and visual oddball tasks. Although there was no difference in the overall level of hippocampal activation in the two modalities, significant modality differences in the profile of activation along the long axis of the hippocampus were observed. In both left and right hippocampi, an anterior-to-posterior gradient in the activation (anterior to posterior) was observed during the auditory oddball task, whereas a posterior-to-anterior gradient (posterior to anterior) was observed during the visual oddball task. These results indicate that the hippocampus is involved in the detection of deviant stimuli regardless of stimulus modality, and that there are prominent modality differences along the long axis of the hippocampus. The implications of our findings for understanding hippocampal involvement in processing sequences of events are discussed. © 2004 Wiley-Liss, Inc.
Comparison of the effects on secretion in chromaffin and PC12 cells of Rab3 family members and mutants. Evidence that inhibitory effects are independent of direct interaction with Rabphilin3.

Abstract The Rab class of low molecular weight GTPases has been implicated in the regulation of vesicular trafficking between membrane compartments in eukaryotic cells. The Rab3 family consisting of four highly homologous isoforms is associated with secretory granules and synaptic vesicles. Many different types of experiments indicate that Rab3a is a negative regulator of exocytosis and that its GTP-bound form interacts with Rabphilin3, a possible effector. Overexpression of Rabphilin3 in chromaffin cells enhances secretion. We have investigated the expression, localization, and effects on secretion of the various members of the Rab3 family in bovine chromaffin and PC12 cells. We found that Rab3a, Rab3b, Rab3c, and Rab3d are expressed to varying degrees in PC12 cells and in a fraction enriched in chromaffin granule membranes from the adrenal medulla. Immunocytochemistry revealed that all members of the family when overexpressed in PC12 cells localize to secretory granules. Binding constants for the interaction of the GTP-bound forms of Rab3a, Rab3b, Rab3c, and Rab3d with Rabphilin3 were comparable (K d = 10–20 nm). Overexpression of each of the four members of the Rab3 family inhibited secretion. Mutations in Rab3a were identified that strongly impaired the ability of the GTP-bound form to interact with Rabphilin3. The mutated proteins inhibited secretion similarly to wild type Rab3a. Although Rab3a and Rabphilin3 are located on the same secretory granule or secretory vesicle and interact both in vitro and in situ,it is concluded that the inhibition of secretion by overexpression of Rab3a is unrelated to its ability to interact with Rabphilin3.
Field and Laboratory Investigation of Permeable Asphalt Mixes on Georgia Highways

The Georgia Department of Transportation (GDOT) investigated possible high permeability in asphalt mixes statewide in response to reports of prolonged wetness on pavements around the state after rainfall. In these locations, high permeability manifested itself as wet areas on pavement surfaces where wetness remained after natural conditions should have removed all moisture from the surfaces. Sixteen project sites were inspected for problem areas statewide, and core specimens were taken from six of the sites. Specimens were taken from areas considered representative of the problem areas in each project. The specimens were tested to determine the permeability, bulk specific gravity, maximum theoretical specific gravity, percentage of air voids, percentage of asphalt cement, and gradation of the mix. According to the findings of this investigation, some Superpaver; mixes that were designed in accordance with GDOT specifications exhibited undesirable permeability. The investigation determined that both mix de...
Reply to the Commentary on "Granular discharge rate for submerged hoppers"

A Reply to the Commentary by L. Staron [Pap. Phys. 6, 060010 (20014)]. Received: 16 October 2014, Accepted: 16 October 2014; Edited by: L. A. Pugnaloni; DOI: http://dx.doi.org/10.4279/PIP.060011 Cite as: T J Wilson, C R Pfeifer, N Meysingier, D J Durian, Papers in Physics 6, 060011 (2014)
Formation and characterization of cellulose films from a liquid crystalline solution of cellulose in ammonia/ammonium thiocyanate

Films were cast from liquid crystalline solutions of cellulose in an ammonia (NH3)/ammonium thiocyanate (NH4SCN) solvent. Microscopic examination of the cellulose liquid crystalline solutions used for the film formation exhibited the so-called conjugated phase. It displayed a fingerprint and a uniformly dispersed highly birefringent pattern. Without additives, the films made from these liquid crystalline solutions are clear, flexible, and have high strength comparable to commercial Cellophone® films. The infrared crystallinity index of the film was somewhat higher than that of other cellulose II materials.
Acral keratosis with eosinophilic dermal deposits: a distinctive clinicopatholgic entity or colloid milium redux?

Aims: The differential diagnosis of acral keratoses is broad. Encompassing a variety of infectious, heritable and degenerative disorders, emphasis upon the clinical setting and histologic subtlety are often required to arrive at the correct diagnosis. Herein, we report on a series of adult patients who presented with agminated or solitary papules of the distal finger found on histologic examination to contain amorphous eosinophilic deposits. Results: The eosinophilic deposits were found in close proximity to the overlying epithelium and devoid of apoptotic keratinocytes, plasma cells, or vascular thickening reminiscent of amyloidosis or hyalinosis cutis. Special and immunostains yielded eosinophilic material that was elastin and Protein P negative. Despite a similar histomorphologic appearance to colloid milium, typical clinical features of this entity were not present. Conclusion: The etiologic significance of this condition is unknown. Potential sources of the material and a discussion of the differential diagnosis follow.
Klinische und hirnelektrische Befunde bei 120 anfallsfrei gewordenen Epileptikern

Aus 120 Epileptikern, die seit 1–37 Jahren anfallsfrei waren, wurden 100 Patienten ausgewahlt, bei denen Anfalle in der Anstalt beobachtet worden waren; die Kranken waren, nachdem sie keine Anfalle mehr qatten, weiter in der Anstalt geblieben. Die klinischen Befunde, die an diesen 100 anfallsfrei gewordenen Epileptikern erhohen wurden, stellten wir den Ergehnissen einer gleichen Untersuchung an 300 noch an Anfallen leidenden Anstaltspatienten gegenuber.