cssi/SciSciGPT-SciSciNet huggingface dataset:
Cash Flow Accounting and Liquidity: Cash Flow Potential and Wealth

Abstract The persistence of a minority interest in ‘cash flow accounting’ alongside the dominant financial reporting pattern that gives cash flow statements a distinctly secondary role in the line-up of flow statements suggests that something is missing from the analyses of the interested parties. The major theme of this paper is that users rely on historical cash flow reporting for information relevant to projecting enterprise liquidity in the short run, and on financial statements based on accrual-deferral accounting for information relevant to their interest in wealth and income. An explicit distinction between the two accounting objectives (providing information for use in assessing future enterprise liquidity and providing information for use in assessing enterprise wealth and income and performance against investors' augmentation-of-wealth objective) is recommended as a basis for clarifying the issues. That distinction suggests the value of two quite different, but related, sets of data: historical ...
Endocrine control of ethanol intake by rats or hamsters: relative contributions of the ovaries, adrenals and steroids.

Abstract Alcohol intake and preference by female rats decreases during pregnancy or following ovariectomy (OVX) in accordance with a model derived from the saccharine preference literature. However, the present Experiment 1 revealed that ovariectomized rats only modestly increased 4% ethanol preference following subcutaneous implantation of Silastic implants containing estradiol. In Experiment 2, OVX female hamsters actually had greater alcohol preference compared to controls. This information led to the suggestion that ovarian estradiol in rats might be effecting alcohol intake by influencing adrenal corticosteroid release, something that does not occur in female hamsters. Adrenal glucocorticoids are known to profoundly alter sensitivity to taste, olfactory and auditory stimuli. Therefore, groups of rats were sham operated, OVX, adrenalectomized (ADX) or both OVX and ADX to test for the relative endocrine effects on alcohol preference. The rank ordering of preference deficits produced was SH
An examination of behavioral, immunological and productive traits in four management systems for sows and piglets

Forty-one sows and litters were utilized in a multi-disciplinary evaluation of four common commercial housing systems for sows and piglets: (1) a standard crate (SC); (2) a modified or turnaround crate (TC); (3) a pen with an indoor and outdoor area (OP); (4) a straw-bedded hut on a lot (HL). HL litters had a higher incidence of still-births than OP litters. Litters raised in HL had higher mortality and weaned fewer and lighter pigs. Litters in TC had lower mortality than SC litters. Sow behavior data (such as sow feeding time) paralleled productivity data (number piglets weaned). Sows who spent more time showing oral behaviors towards bars pre-farrowing had larger litter sizes (r = 0.73, P <0.01). Sows who were less active (that is, moved while standing) pre-farrowing weaned more piglets (r=0.55, P<0.05). Sows who spent more time feeding weaned more pigs (r=0.57, P<0.05). Immunological data indicated that piglets in OP had higher white blood cell numbers and piglets in HL had lower antigen-induced blood antibody titers. Since litters in the TC had improved piglet survival compared with SC, a large-scale performance and economic-evaluation trial is in order to further study the system on commercial farms.
Treatment of traumatic pancreatic pseudocysts in children: the role of percutaneous catheter drainage

Six cases of successful percutaneous catheter drainage (PCD) of pancreatic pseudocysts in children ages 3–13 years are presented. All cases involved blunt abdominal trauma and presented with abdominal pain, vomiting, epigastric tenderness without a palpable mass, and elevated serum amylase. Indications for PCD were an enlarging pseudocysts and marked abdominal pain. Catheter placement was accomplished using CT guidance 15.3±1.8 days (mean ± SEM) following injury. Two patients had transgastric PCD. None of the pseudocysts were infected. Catheters were left in place until the drainage ceased, the serum amylase approached normal, the pseudocyst resolved on ultrasound, and the asymptomatic patient tolerated enteral feedings with the catheter clamped. The mean duration of catheter drainage was 18.3±3.7 days. At the time of catheter insertion, the range of serum amylase values was 242–2810 IU/l, while discharge values were 50–147 IU/l (normal: 16–108 IU/l). The mean hospital stay was 36.2±3.8 days and the mean length of total parenteral nutrition was 27.5±4.5 days. All pseudocysts were treated successfully without complication. PCD of traumatic pancreatic pseudocysts in children was performed safely and effectively in our study. Use of this therapeutic modality allowed earlier treatment, decreased the duration of symptoms, and avoided abdominal operation. PCD may prove to be the treatment of choice for pancreatic pseudocysts in children.
Common Location of Determinants in Initiator Transfer RNAs for Initiator-Elongator Discrimination in Bacteria and in Eukaryotes

Initiator tRNAs are used exclusively for initiation of protein synthesis and not for elongation. We show that both Escherichia coli and eukaryotic initiator tRNAs have negative determinants, at the same positions, that block their activity in elongation. The primary negative determinant in E. coliinitiator tRNA is the C1xA72 mismatch at the end of the acceptor stem. The primary negative determinant in eukaryotic initiator tRNAs is located in the TΨC stem, whereas a secondary negative determinant is the A1:U72 base pair at the end of the acceptor stem. Here we show thatE. coli initiator tRNA also has a secondary negative determinant for elongation and that it is the U50·G64 wobble base pair, located at the same position in the TΨC stem as the primary negative determinant in eukaryotic initiator tRNAs. Mutation of the U50·G64 wobble base pair to C50:G64 or U50:A64 base pairs increases the in vivo amber suppressor activity of initiator tRNA mutants that have changes in the acceptor stem and in the anticodon sequence necessary for amber suppressor activity. Binding assays of the mutant aminoacyl-tRNAs carrying the C50 and A64 changes to the elongation factor EF-Tu·GTP show marginally higher affinity of the C50 and A64 mutant tRNAs and increased stability of the EF-Tu·GTP· aminoacyl-tRNA ternary complexes. Other results show a large effect of the amino acid attached to a tRNA, glutamineversus methionine, on the binding affinity toward EF-Tu·GTP and on the stability of the EF-Tu·GTP·aminoacyl-tRNA ternary complex.
Conceptual Processing during the Conscious Resting State: A Functional MRI Study

Localized, task-induced decreases in cerebral blood flow are a frequent finding in functional brain imaging research but remain poorly understood. One account of these phenomena postulates processes ongoing during conscious, resting states that are interrupted or inhibited by task performance. Psychological evidence suggests that conscious humans are engaged almost continuously in adaptive processes involving semantic knowledge retrieval, representation in awareness, and directed manipulation of represented knowledge for organization,problem-solving, and planning. If interruption of such ''conceptual'' processes accounts for task-induced deactivation, tasks that also engage these conceptual processes should not cause deactivation. Furthermore, comparisons between conceptual and nonconceptual tasks should show activation during conceptual tasks of the same brain areas that are ''deactivated'' relative to rest. To test this model, functional magnetic resonance imaging data were acquired during a resting state,a perceptual task,and a semantic retrieval task. A network of left-hemisphere polymodal cortical regions showed higher signal values during the resting state than during the perceptual task but equal values during the resting and semantic conditions. This result is consistent with the proposal that perceptual tasks interrupt processes ongoing during rest that involve many of the same brain areas engaged during semantic retrieval. As further evidence for this model, the same network of brain areas was activated in two direct comparisons between semantic and perceptual processing tasks. This same ''conceptual processing'' network was also identified in several previous studies that contrasted semantic and perceptual tasks or resting and active states. The model proposed here offers a unified account of these findings and may help to explain several unanticipated results from prior studies of semantic processing.
A fast calibration method for 3-D tracking of ultrasound images using a spatial localizer

Abstract We have developed a fast calibration method for computing the position and orientation of 2-D ultrasound (US) images in 3-D space where a position sensor is mounted on the US probe. This calibration is required in the fields of 3-D ultrasound and registration of ultrasound with other imaging modalities. Most of the existing calibration methods require a complex and tedious experimental procedure. Our method is simple and it is based on a custom-built phantom. Thirty N-fiducials (markers in the shape of the letter “N”) embedded in the phantom provide the basis for our calibration procedure. We calibrated a 3.5-MHz sector phased-array probe with a magnetic position sensor, and we studied the accuracy and precision of our method. A typical calibration procedure requires approximately 2 min. We conclude that we can achieve accurate and precise calibration using a single US image, provided that a large number (approximately ten) of N-fiducials are captured within the US image, enabling a representative sampling of the imaging plane. (E-mail: ykim@u.washington.edu)
Heat and Mass Transfer in Parallel Flow Mist Cooling

The lasing gain media (LGM) of the solid-state heat capacity laser (SSHCL) need to be cooled in a short time in between laser operations to increase the duty cycle. Parallel flow mist cooling is an attractive option to accomplish this. However, no general correlations exist to predict parallel flow mist cooling heat transfer for various fluids. In order to obtain such a correlation this study was undertaken. Drop size distribution from different nozzles was characterized by laser Doppler anemometer. A parallel flow mist cooling experimental set-up was designed and fabricated. Data from over 300 experiments with air, air-water mist, air-denatured ethanol mist and air-pure ethanol mist was obtained. The parameter ranges were: flow velocity between 5 and 50 m/s, drop diameters between 18 and 75 μm, mist concentrations as high as 0.2 kg/m3 , heat fluxes up to 170000 W/m2 and hydraulic diameters between 0.003 and 0.008 m. An enhancement of up to a factor of six relative to the heat flux removed by air was obtained. The experiments indicated that there are four regimes in parallel flow mist cooling. These are: 1) Mass transfer, 2) Forced convection 3), Critical Heat Flux and 4) Film boiling. Two general correlations for parallel flow mist cooling are proposed for the first two of these regimes.Copyright © 2003 by ASME
Random Propagation of a Crack in a Thin-walled Beam

Probabilisticmethodology is used for estimating the growth of an existing crack in a thin-walled beamwith a closed cross section. The beam is subjected to stochastic loads. The initial length of the crack is considered to be an uncertain quantity represented by a random variable. The random characteristics of the stress response, needed for crack growth analysis, are obtained by randomvibration analysis of the thin-walled beam. The crack growth rate equation is solved for a large number of randomly generated sample values of the random parameters. The simulated crack growth results are then used to calculate the probability of failure. The failure is defined as occurringwhen the actual crack size exceeds the critical crack size. For demonstration of the methodology, the numerical results for the timedependent probability of failure are obtained for an example problem of a thin-walled beam.
Bringing the body back into theory and methodology

This is a discussion of a book by Kathryn Linn Geurts, Culture and the Senses. Bodily Ways of Knowing in an African Community, Berkeley, CA: University of California Press, 2002; and a book by Judith Farquhar, Appetites. Food and Sex in Post-Socialist China, Durham, NC and London: Duke University Press, 2002.
Video-assisted diaphragm plication in children.

Abstract Background Diaphragm paralysis after cardiac surgery may be secondary to phrenic nerve injury by ice, electrocautery, or dissection. Although most are asymptomatic, some patients, particularly children, have significant respiratory compromise. Video-assisted plication may offer more rapid improvement and recovery than thoracotomy in pediatric patients. Methods We performed five procedures. The diaphragm was elevated, clamped, oversewn, and tacked down into the pleural gutter. The procedure was performed on 2 infants after repair of total anomalous pulmonary venous connection, on 1 child after the Fontan procedure, on 1 child after repair of tetralogy of Fallot, and on 1 child with congenital eventration. Indications included ventilator dependency, post-Fontan protein losing enteropathy with elevated venous pressures and chronic right lower lobe collapse, persistent atelectasis with recurrent pneumonias, and asymptomatic severe eventration. Results Ventilator-dependent patients were extubated after 2 and 3 days. The remaining patients were immediately extubated. One patient was discharged the day of surgery and 2 were discharged at 1 and 3 days postoperatively. The remaining 2 were discharged on postoperative day 30 and 45 after continued issues with feeding and prematurity. The child with the eventration had rapid expansion and growth of the left lung over the next few weeks with a normal chest radiograph 3 weeks later. The child with recurrent pneumonia reexpanded her left lower lobe and remains free of infection. There were no wound infections, lung or vascular injuries, or complications from the procedure. All the patients had successful flattening of the hemidiaphragm as documented by chest radiograph, with successful lung reexpansion. Conclusions Video-assisted plication of paralyzed diaphragms is effective and safe, involves less morbidity, and has quicker recovery times than traditional open techniques.
Heliostat mean wind load reduction

Abstract Reduction of wind loading on heliostats in typical array fields is important to improve the economy of heliostat support structure and drive mechanisms. The method of investigation was wind-tunnel tests in a boundary-layer wind tunnel designed to model atmospheric surface layer winds. The study revealed that the reduction in mean wind load on heliostats in operational positions within the field could be related to the area of upwind blockage of heliostats and fences. Wind-load reductions of 70% from wind loads on an unprotected heliostat are possible with proper field design. Peak dynamic loads are also decreased within the heliostat field.
Sport-related concussion: "How many is too many?"

The long-term effects of multiple sport-related concussions are currently at the center of debate in the popular press and scientific community. The question, "How many concussions are too many," is frequently asked in the competitive sport environment by parents, athletes, and coaches. While research suggests that a history of concussion influences the risk and recovery from subsequent concussion, studies investigating the long-term effects of multiple concussions are less conclusive. This paper reviews the literature on multiple concussions and the potential long-term consequences of these injuries. Furthermore, this paper addresses how concussion history can inform clinical and return-to-play decisions. Recent studies incorporating novel brain imaging and electrophysiological technology for assessing residual impairment from multiple concussions are reviewed and the clinical implications of this work are discussed.
Novel 5- and 6-subtituted benzothiazoles with improved physicochemical properties: Potent S1P1 agonists with in vivo lymphocyte-depleting activity

Abstract An SAR campaign designed to increase polarity in the ‘tail’ region of benzothiazole 1 resulted in two series of structurally novel 5-and 6-substituted S1P1 agonists. Structural optimization for potency ultimately delivered carboxamide (+)-11f, which in addition to possessing improved physicochemical properties relative to starting benzothiazole 1, also displayed good S1P3 selectivity and acceptable in vivo lymphocyte-depleting activity.
Effects of putrescine and inhibitors of putrescine biosynthesis on organogenesis inEuphorbia esula L.

Exogenous putrescine (≤5 mM) had little effect on root or shoot formation in aseptically isolated hypocotyl segments of leafy spurge (Euphorbia esula L.) grown on full-strength B5 medium. Unexpectedly, putrescine inhibited root and shoot formation in hypocotyl segments grown on B5 medium diluted 10-fold. In the full-strength medium, root and shoot formation were inhibited by 0.5 mM concentrations ofdl-α-difluoromethylornithine (DFMO) anddl-α-difluoromethylarginine (DFMA). DFMO and DFMA are inhibitors of the ornithine decarboxylase and arginine decarboxylase pathways, respectively, of putrescine biosynthesis in plants. Exogenous putrescine (0.5 to 5 mM) did not reverse either the DFMO-or DFMA-induced inhibition of shoot formation. However, the DFMA-induced inhibition of root formation was partially reversed by exogenous putrescine. The auxin, indole-3-acetic acid (IAA), reduced the inhibitory effects of DFMO+DFMA (applied together) on both roots and shoots. In the first few days of culture, the endogenous levels of putrescine and spermidine, but not of spermine, increased in the presence of IAA. The levels of putrescine and spermidine in the tissues did not correlate well with either root or shoot production in the later stages of organ formation; especially in tissues treated with IAA. These results show that there were no obvious correlations between polyamine levels and organogenesis in leafy spurge hypocotyl segments, although residual putrescine or spermidine or both in the tissues at the time of excision may be indirectly involved in the early stages of root formation.
Interferon-induced transfer of viral resistance between animal cells

MANY animal cell types exhibit the ability to communicate between themselves, both in vivo and in vitro1. This phenomenon is thought to occur through gap junctions which allow cells to share their metabolites and small control molecules2–6. The overall effect of this cellular communication seems to be a coordinated control of growth and function of different cells and cell types. Interferon is believed to act at the cell membrane in a fashion similar to polypeptide hormones7–9. This membrane interaction in turn leads to de-repression and production of the antiviral protein10,11. If, as is the case with polypeptide hormones12, the induction of the antiviral protein is mediated through secondary molecules, these might influence adjacent cells. The presence of such intermediary molecules during interferon induction of the antiviral protein has been inferred from kinetic studies13,14. The many instances of the species specificity of interferon action15 make this a testable hypothesis. We show here that cells made resistant to virus infection by treatment with their homologous interferon can transfer viral resistance to cells of a heterologous species insensitive to that interferon and also to cells of the homologous species.
A new rationale for returning to the Moon? Protecting civilization with a sanctuary

Abstract A process is well underway in which the scientific, technical and cultural information vital to our society is stored in digital form within a limited number of computer facilities. This practice is vulnerable to a variety of catastrophes which would destroy our knowledge base in addition to the losses they caused to population and structures. The Alliance to Rescue Civilization (ARC) proposes that a staffed data backup facility be constructed in a secure location, with the Moon as the site of choice. If Earth's population were destroyed entirely, the lunar sanctuary could serve to repopulate the planet.
EOQ FORMULA: IS IT VALID UNDER INFLATIONARY CONDITIONS?

The classical analysis of the economic order quantity (EOQ) problem ignores the effect of inflation. When a firm's cost factors are expected to rise at an annual rate of 10 percent or more, what adjustments in order quantities should the firm make to control its lot-size inventory (or cycle stock)? Using a model that includes both inflationary trends and time discounting, it is concluded that inflation brings no incentive either to increase or to decrease order quantities. In addition, order quantities can be computed using the classical EOQ formula under inflationary conditions, provided that the cost of capital invested in inventory is interpreted as an inflation-free cost. This interpretation implies that changes in the inflation rate should not affect the cost of capital that is utilized in the EOQ formula for determining order quantities.
Perioperative changes in serum creatinine after gynecologic surgery.

Abstract Objective: The purpose of this study was to prospectively determine the normal range of postoperative changes in serum creatinine levels when bilateral ureteral patency was confirmed by cystoscopy. Study Design: A total of 187 consecutive patients who had undergone major gynecologic surgery were evaluated prospectively. All patients had undergone perioperative cystoscopy to evaluate for ureteral patency, and creatinine levels had been determined before and 24 hours after surgery. Results: The mean change in serum creatinine level was 0.01 mg/dL, and the changes for the central 95% ranged from −0.2 to 0.3 mg/dL. With a previously defined cutoff value of an increase of >0.2 mg/dL after operation to indicate ureteral obstruction, specificity and negative predictive values (when compared with cystoscopic findings) were 98% and 100%, respectively. Conclusion: Creatinine levels change minimally during the immediate postoperative period in the absence of ureteral compromise. If bilateral ureteral patency was demonstrated after operation in our population, creatinine level elevations were always
The Friction of Cartography: On the Politics of Space and Mobility among Migrant Communities in the Thai–Burma Borderlands

AbstractThe dominant approach to understanding migration in the Thai–Burma borderlands frames migration largely as an economic effect of industrialization in Thailand and economic stagnation in Burma. Drawing on a range of secondary sources and long-term field-based research on the Thai–Burma border, this article pursues a different approach, seeking to situate current migration trends in a historical and political context. James Scott's recent work on Zomia and upland Southeast Asia is instrumental here. Key factors Scott cites as drivers of flight from state space over the longue duree—taxation, forced or corvee labor, and war and rebellion—remain strikingly relevant today. This article examines the applicability of Scott's migration analysis to contemporary mobility patterns in the Thai–Burma borderlands, proposing two concepts that highlight the politics of mobility in this border area: the friction of cartography and migrant counter-topographies. The former evokes the protective quality of the border...
A comparison of the Giardia lamblia trophozoite and cyst transcriptome using microarrays

Compared with many protists, Giardia lamblia has a simple life cycle alternating between cyst and trophozoite. Most research on the molecular biology of Giardia parasites has focused on trophozoites and the processes of excystation and encystation, whereas cysts have attracted less interest. The striking morphological differences between the dormant cyst and the rapidly dividing and motile trophozoite implies profound changes in the metabolism as the parasite encysts in the host's intestine and excysts upon ingestion by a new host. To investigate the magnitude of the transcriptional changes occurring during the G. lamblia life cycle we compared the transcriptome of G. lamblia trophozoites and cysts using single-color oligonucleotide microarrays. Cysts were found to possess a much smaller transcriptome, both in terms of mRNA diversity and abundance. Genes encoding proteins related to ribosomal functions are highly over-represented. The comparison of the transcriptome of cysts generated in culture or extracted from feces revealed little overlap, raising the possibility of significant biological differences between the two types of cysts. The comparison of the G. lamblia cyst and trophozoite transcriptome showed that transcripts of most genes are present at a lower level in cysts. This global view of the cyst and trophozoite transcriptome complements studies focused on the expression of selected genes during trophozoite multiplication, encystation and excystation.
Identification of Nonuniform Differential Item Functioning Using a Variation of the Mantel-Haenszel Procedure.

The Mantel-Haenszel (MH) procedure has become one of the most popular procedures for detecting differential item functioning (DIF). One of the most troublesome criticisms of this procedure is that whereas detection rates for uniform DIF are very good, the procedure is not sensitive to nonuniform DIF. In this study, examinee responses were generated to simulate both uniform and nonuniform DIF. A standard MH procedure was used first. Then, examinees were split into two samples by breaking the full sample at approximately the middle of the test score distribution. The tests were then reanalyzed, first with the low-performing sample and then with the high-performing sample. This variation improved detection rates of nonuniform DIF considerably over the total sample procedure without increasing the Type I error rate. Items with the largest differences in discrimination and difficulty parameters were most likely to be identified.
Differences in monoamine oxidase activity between cultured noradrenergic and cholinergic sympathetic neurons

Two types of monoamine oxidase activity (MAO-A and MAO-B) help regulate the levels of biogenic amines such as catecholamines and serotonin. Although MAO-A has greater activity toward most catecholamines than MAO-B, no direct experiments have determined the types and levels of MAO activity that are normally expressed in noradrenergic neurons. Noradrenergic neurons from neonatal rat superior cervical ganglia were isolated and cultured under conditions that permit either continued expression of the noradrenergic phenotype or promote a transition to a predominately cholinergic phenotype. After 14–21 days in vitro, neurons from both types of cultures were assayed for the type and amount of monoamine oxidase activity using tryptamine, a common substrate for both MAO-A and MAO-B. Neurons cultured under noradrenergic conditions expressed sevenfold greater MAO activity than neurons cultured under cholinergic conditions. Essentially all MAO activity in the noradrenergic cultures was inhibited by preincubation with 10^(−8–)10^(−9) M clorgyline, which indicated that this activity was primarily MAO-A. Cultures grown under cholinergic conditions exhibited 6- to 10-fold lower MAO-A activity and an 8- to 10-fold lower level of catecholamine synthesis from labeled precursors compared to neurons grown under noradrenergic conditions. These results directly demonstrate that high MAO-A activity is expressed in noradrenergic neurons in vitro. The corresponding decreases in both MAO-A specific activity and catecholamine synthesis as neurons become cholinergic in vitro suggest that the expression of the noradrenergic phenotype involves the coordinate regulation of degradative as well as synthetic enzymes involved in catecholamine metabolism.
A theoretical comparison of cationic and anionic homoaromaticity: Reinforcement of cationic homoaromaticity by σ‐nonclassical effects

A MINDO/3 study of homoaromaticity in the 3-cyclobutenyl cation and the Mobius 3-cyclobutenyl anion has been used to evaluate cationic and anionic homoaromaticity quantitatively. π Homodelocalization energies of the two are found equal in isostructural planar comparisons. In planar optimized structures, the homodelocalization energy of the cation is slightly (about 4 kcal) greater than that of the anion, a consequence of the greater 1,3 distance in the latter. Full optimization produces a highly puckered and further stabilized cation, but engenders no change in the Mobius anion. The total stabilization of the cation relative to the anion is 13 kcal, in accord with the generalization that cationic homoaromaticity is more potent than the anionic variety. The fully optimized cation is revealed to actually have a much smaller π homodelocalization energy than the optimized anion, in contrast to the order of overall stabilities. σ-Nonclassical effects, which are stabilizing in the cation but destabilizing in the Mobius anion, provide the rationale for the above.
Polarized Fluorescence of Guests in MBBA

Abstract Polarized fluorescence of organic molecules were studied utilizing a homogeneously aligned nematic liquid crystal as an orienting matrix. The polarized fluorescence ratios were largest for those guests which were the most linear and, therefore, could be aligned to the greatest extent by the matrix. The polarization of the electronic transitions of the fluorescent guests were determined.
A Review of the Clinical and Research Use of the Bender-Gestalt Test:

The Bender Visual-motor Gestalt test has been an integral part of the standard test battery for the past 50 years. However, the test has been extensively critiqued on issues of inappropriate administration, scoring schemes, and clinical interpretation. In an analysis of recent surveys on test use, the Bender-Gestalt remains quite popular in a variety of clinical settings across all age groups. Secondly, the test has a respectable level of research interest, based on a citation analysis of the Psychological Abstracts database.
Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors

The inhibition of cysteine proteases is being studied as a strategy to combat parasitic diseases such as Chagas' disease, leishmaniasis, and malaria. Cruzain is the major cysteine protease of Trypanosoma cruzi, the etiologic agent of Chagas' disease. A crystal structure of cruzain, covalently inactivated by fluoromethyl ketone inhibitor 1 (Cbz-Phe-Ala-FMK), was used as a template to design potential inhibitors. Conformationally constrained gamma-lactams containing electrophilic aldehyde (12, 17, 18, 25, 26, and 29) or vinyl sulfone (43, 44, and 46) units were synthesized. Constrained lactam 26 had IC50 values of ca. 20 nM against the Leishmania major protease and ca. 50 nM versus falcipain, an important cysteine protease isolated from Plasmodium falciparum. However, all of the conformationally constrained inhibitors were weak inhibitors of cruzain, compared to unconstrained peptide aldehyde (e.g. 5 ) and vinyl sulfone inhibitors (e.g. 48, which proved to be an excellent inhibitor of cruzain with an apparent second order inhibition rate constant (k(inact)/Ki) of 634,000s(-1)M(-1). A significant reduction in activity was also observed with acyclic inhibitors 30 and 51 containing alpha-methyl phenylalanine residues at the P2 position. These data indicate that the pyrrolidinone ring, especially the quarternary center at P2, interferes with the normal substrate binding mode with cruzain, but not with falcipain or the leishmania protease.
The Role of Inward Mixing in the Dissipation of Fog and Stratus

Abstract Satellite imagery shows that extensive areas of radiation fog and stratus dissipate from their outer edges inward. It is proposed that an inward mixing process is at least partially responsible for this inward erosion. The temperature gradient along the fog boundary, which is produced by differential surface heating, should set up a circulation similar to that of a sea breeze. This circulation erodes the fog along the edges as warmer, drier air sinks and mixes into the fog.
Free volume in glassy poly(arylene ether ketone)s

Amorphous polyarylene ether ketones were examined in the glassy state by positron annihilation lifetime spectroscopy (PALS) and in the melt by standard rheological techniques. Specimens were well-characterized fractions of two isomeric structures. PALS clearly shows that the polymer with meta linkages in its backbone contains larger voids (> 0.25 nm radius). Thus despite their similar bulk densities, the two materials must pack very differently on a local scale. On the other hand, the free volumes inferred from the WLF treatment of melt viscosity data are practically identical in both materials ca. 4% at Tg. The comparison between techniques sheds some light on the distribution of free volume. © 1992 John Wiley & Sons, Inc.
A Characterization for reproducing kernel Hilbert spaces

Abstract Let G(t, s) be the Green's functions associated with N, a differential operator restricted to certain boundary conditions. Define (u, v)N = (Nu, v)L2. It is shown that the reproducing kernel Hilbert space generated by G is the same as the Hilbert-space completion with respect to ∥ · ∥N of the set of real valued functions which are in C2n and satisfy the boundary conditions. The concept of Sobolev spaces is used in the proof and examples are given.
Functional assessment following intrathecal baclofen therapy in children with spastic cerebral palsy

The purpose of this article is to describe outcomes of intrathecal baclofen therapy for 29 patients with cerebral palsy, focusing on impairments, functional limitations, and disability. Patients received individualized rehabilitation and were followed up to 24 months. The primary outcome measures were the Ashworth Scale and the functional skills and caregiver assistance scales of the Pediatric Evaluation of Disability Inventory (PEDI). Ashworth Scale scores were significantly reduced (P < or = .0005). All areas of functional skills and caregiver assistance improved. Comparing groups of adults and patients less than 18 years, there were no significant differences, but there was a relationship between age and dose. Comparing groups of patients in high and low levels of independent functional mobility, no significant differences were found. These results provide suggestive evidence that the combination of intrathecal baclofen therapy and rehabilitation has positive effects across the dimensions of disablement. This study serves as a basis for high-level scientific studies of these effects.
Kinetics of the reaction Cl + NO2 + M

Using atomic chlorine resonance fluorescence at 140 nm to detect the decay of atomic chlorine in the presence of an excess of NO2, the rate constant for the reaction Cl + NO2 + M, where M is the total gas concentration, is measured over the temperature range 264 to 417 K and at a pressure 1 to 7 torr in a discharge flow system. The rate constants for M= He and M= N2 are measured and the results are summarized in a table. The systematic error of the rate constants is estimated to be about 15 percent. A static photolysis system coupled with an FTIR spectrophotometer is used to determine the branching ratio for the formation of two possible isomers. The ratio is concluded to be ClONO (greater than or equal 75 percent) and ClNO2 (less than or equal 25 percent) which is in agreement with the results of Niki et al. (1978).
Scandium Clusters in Fullerene Cages

The production and spectroscopic characterization of fullerene-encapsulated metal-atom clusters is reported. In particular, both solution and solid-state electron paramagnetic resonance (EPR) spectra of Sc3C82 have been obtained. ScC82 also gives an EPR spectrum, but Sc2Cn species—the most abundant metallofullerenes in the mass spectrum—are EPR-silent even though Sc2 is EPR-active in a rare-gas matrix at 4.2 K. The results suggest that the three scandium atoms in Sc3C82 form an equilateral triangle—as was previously suggested for Sc3 molecules isolated in a cryogenic rare-gas matrix. The spectrum of ScC82 has features similar to those found earlier for LaC82 and YC82, suggesting that it can also be described as a +3 metal cation within a -3 fullerene radical anion. An implication of this work is that production of macroscopic quantities of clustercontaining fullerenes may make possible the fabrication of exotic new structures with regular arrays of metal-atom clusters isolated in fullerene molecules, resulting in a new type of host/guest nanostructured material.
2'-Substituted analogs of cocaine: synthesis and dopamine transporter binding potencies

A series of 2β-substituted analogues of 4‘-iodococaine (3) was synthesized and evaluated in an in vitro dopamine transporter (DAT) binding assay. Selective hydrolysis at the 2β-position of 3 gave the carboxylic acid 15 that served as the intermediate for the synthesis of compounds 4, 5, and 6−11. The 2β-alkyl derivatives were obtained from ecgonine methyl ester (17) through a series of reactions leading to the aldehyde 20. Wittig reaction of 20 with methyltriphenylphosphorane followed by hydrogenation and benzoylation gave the products 12 and 13. The binding affinity of 4‘-iodococaine (3) was 10-fold less than that of cocaine. The hydroxymethane, acetate, amide, benzyl ester, oxidazole, and ethane derivatives of 3 exhibited decreased binding while the vinyl, phenyl, and ethyl esters showed a moderate increase in binding affinity. Only the isopropyl derivative 8 exhibited a 2-fold increase in binding affinity compared with 4‘-iodococaine (3). Hydroxylation of 8 at the 2‘-position gave 14 which enhanced not...
Transplantation of neural tissue in polymer capsules.

Abstract Neural tissue reaction to permselective polymer capsules and the feasibility of encapsulated neural tissue transplantation were evaluated in a rat model for a period of 1–12 weeks. Polymer implants in the central nervous system were generally well tolerated. The brain reaction to the synthetic material was minimal and did not disturb normal brain architectonics. Embryonic mouse mesencephalon enclosed in a polymer capsule remained morphologically intact for at least 12 weeks in the parietal cortex of rats. We conclude that the immunoprotection provided by a permselective polymer membrane encapsulating neural tissue is compatible with diffusional exchange of nutrients and metabolites. Polymer encapsulation may provide an alternative for the problem of immunorejection in transplantation of neural tissues.
Effect of Testosterone and Oxandrolone on Thrombocyte Aggregation and Synthesis of Prostaglandins in Thrombocytes and Aorta of Atherosclerosis‐susceptible Pigeons*

Effect of intramuscular administration (10 mg/kg/week) of testosterone and oxandrolone on a) thrombocyte aggregation and b) synthesis of prostaglandins from [14C]-arachidonic acid in thrombocytes and aorta of atherosclerosis-susceptible White Carneau pigeon was examined. Neither testosterone nor oxandrolone influenced collagen, ADP and arachidonic acid induced aggregation or the synthesis of prostaglandins in thrombocytes. However, both testosterone and oxandrolone stimulated (p less than 0.05) the synthesis of 6-keto-PGF1 alpha (stable product of prostacyclin) und PGE2 in aorta.
Effects of Trace Layers and Joule Heating on the Temperature Distribution of Printed Circuit Boards: A Computational Study

A printed circuit board (PCB) is generally a multilayered board made of dielectric material and several layers of traces and vias. Performing detailed system-level computational fluid dynamics (CFD) simulations of PCBs including meshed trace and via geometries for each of the layers is impractical. In the present approach, the effects of the trace and via geometry are accurately modeled in the physical model by importing electronics computer aided-design data consisting of the trace and via layout of the board and computing locally varying orthotropic conductivity (k x , k y , and k z ) on the printed circuit board using a background mesh. The spatially varying orthotropic conductivity is then mapped from the background mesh to the CFD mesh and used in a system-level simulation of the PCB with a minimal increase in the overall computational cost. On the other hand, as PCB component densities increase, the current densities increase thereby leading to regions of hot spots due to Joule heating. Hence, it is essential that the computational heat transfer simulations account for the heating due to the high current carrying traces. In order to accurately model the Joule heating of traces and vias, it is of essence to solve for the conservation of current in each of these traces. In this study, the effects of both trace layer nonhomogeneity and Joule heating are examined on a sample PCB with several components attached to it. The results are then compared with those from the conventional modeling techniques. It is demonstrated that there is considerable difference in the location of the hot spots and temperature values between two different methods.
Growth phase mediated regulation of the Actinobacillus pleuropneumoniae ApxI and ApxII toxins.

Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia, a highly contagious and often fatal respiratory tract disease of pigs. The Apx toxins are primary virulence factors of this pathogen, with ApxI and ApxII being produced by all highly virulent strains in North America. Further characterization of these hemolytic toxins is needed to fully understand their role in disease and elucidate the environmental signals and genes that affect their production during infection. Many bacteria regulate genes in response to growth phase, and in this report we examined the effect of growth phase on ApxI and ApxII gene expression. Batch cultures of ApxI- and ApxII-producing strains were grown in heart infusion broth supplemented with β-NAD, and samples were prepared throughout the growth curve. Maximal gene expression occurred in late exponential or early stationary phase, as indicated by a peak in apx mRNA concentration in Northern blot analysis. The amount of accumulated Apx protein and Apx hemolytic activity confirmed this increase in gene expression. These findings suggest a novel transcriptional regulatory mechanism that enhances Apx gene expression under in vitro conditions of high cell density and/or slow growth rate.
Inhibition of Cytochrome P450 6D1 by Alkynylarenes, Methylenedioxyarenes, and Other Substituted Aromatics

Abstract We evaluated 33 compounds, comprising five different structural groups (alkynylpyrenes, alkynylphenanthrenes, methylenedioxyarenes, flavones, and miscellaneous), as inhibitors of house fly P450 6D1 (CYP6D1). In general, alkynylpyrenes were the most potent group of inhibitors, with maximum effectiveness noted when the substituent was in the 4 position. Substituted phenanthrenes were reasonable CYP6D1 inhibitors with the lowest IC 50 observed for the analogue with the methylenedioxy substituent between the 9 and 10 positions. The 10 methylenedioxyarenes varied considerably in their ability to inhibit CYP6D1. Piperonyl butoxide was the most potent inhibitor with increasing length of the alkyl substituent resulting in decreasing inhibition. Karanjin had the lowest IC 50 of the 4 flavones that were tested. Overall, the most potent CYP6D1 inhibitors were large planar compounds. Four inhibitors were evaluated as permethrin synergists in the LPR strain of house fly (permethrin is detoxified via CYP6D1 in this strain) and they increased permethrin toxicity by 16- to 83-fold. The effect of structure on inhibition potency, as well as the mechanism of inhibition for seven representative inhibitors, is discussed.
Identification of Mouse Hepatitis Virus Papain-Like Proteinase 2 Activity

Mouse hepatitis virus (MHV) is a 31-kb positive-strand RNA virus that is replicated in the cytoplasm of infected cells by a viral RNA-dependent RNA polymerase, termed the replicase. The replicase is encoded in the 5′-most 22 kb of the genomic RNA, which is translated to produce a polyprotein of >800 kDa. The replicase polyprotein is extensively processed by viral and perhaps cellular proteinases to give rise to a functional replicase complex. To date, two of the MHV replicase-encoded proteinases, papain-like proteinase 1 (PLP1) and the poliovirus 3C-like proteinase (3CLpro), have been shown to process the replicase polyprotein. In this report, we describe the cloning, expression, and activity of the third MHV proteinase domain, PLP2. We show that PLP2 cleaves a substrate encoding the first predicted membrane-spanning domain (MP1) of the replicase polyprotein. Cleavage of MP1 and release of a 150-kDa intermediate, p150, are likely to be important for embedding the replicase complex in cellular membranes. Using an antiserum (anti-D11) directed against the C terminus of the MP1 domain, we verified that p150 encompasses the MP1 domain and identified a 44-kDa protein (p44) as a processed product of p150. Pulse-chase experiments showed that p150 is rapidly generated in MHV-infected cells and that p44 is processed from the p150 precursor. Protease inhibitor studies revealed that unlike 3CLpro activity, PLP2 activity is not sensitive to cysteine protease inhibitor E64d. Furthermore, coexpression studies using the PLP2 domain and a substrate encoding the MP1 cleavage site showed that PLP2 acts efficiently in trans. Site-directed mutagenesis studies confirmed the identification of cysteine 1715 as a catalytic residue of PLP2. This study is the first to report enzymatic activity of the PLP2 domain and to demonstrate that three distinct viral proteinase activities process the MHV replicase polyprotein.
Positive charges of the initial C-terminus domain of Cx32 inhibit gap junction gating sensitivity to CO2.

Gap junction channels close with CO2 exposure. To determine whether the carboxy-terminus (CT) of connexin32 (Cx32) participates in gating, the CO2 sensitivity of channels made of Cx32 or Cx32 mutants was studied by double voltage clamp. In Xanopus laevis oocytes expressing Cx32, junctional conductance (Gj) dropped to 85% and 47% of controls with 3- and 15-min CO2 exposures, respectively. In response to the 15-min exposure to CO2, pHi dropped to approximately 6.4 in 5–7 min and did not decrease further, even with 30-min exposures. CT deletion by 84% did not affect CO2 sensitivity, but replacement of five arginines (R215, R219, R220, R223, and R224) with asparagines (N) or threonines at the beginning of CT (CT1) in Cx32 or Cx32 deleted beyond residue 225 greatly enhanced CO2 sensitivity (with 3-min CO2 Gj dropped to approximately 8%). Partial R/N replacement resulted in intermediate CO2 sensitivity enhancement. R215 is a stronger inhibitor than R219–220, whereas R223–224 may diminish the inhibitory efficiency of R215 and R219–220. Therefore, positive charges of CT1 reduce the CO2 sensitivity of Cx32, whereas the rest (> 80%) of CT seems to play no role in CO2-induced gating. The role of presumed electrostatic interactions among Cx32 domains in CO2-induced gating is discussed.