cssi/SciSciGPT-SciSciNet huggingface dataset:
Acute and chronic effects of single dose memantine after controlled cortical impact injury in adult rats.

Background Altered glutamatergic neurotransmission after traumatic brain injury (TBI) contributes to excitotoxic cell damage and death. Prevention or suppression of such changes is a desirable goal for treatment of TBI. Memantine (3,5-dimethyl-1-adamantanamine), an uncompetitive NMDA receptor antagonist with voltage-dependent open channel blocking kinetics, was reported to be neuroprotective in preclinical models of excitotoxicity, brain ischemia, and in TBI when administered prophylactically, immediately, or within minutes after injury. Methods The current study examined effects of memantine administered by single intraperitoneal injection to adult male rats at a more clinically relevant delay of one hour after moderate-severe controlled cortical impact (CCI) injury or sham surgery. Histopathology was assessed on days 1, 7, 21, and 90, vestibulomotor function (beam balance and beam walk) was assessed on days 1-5 and 71-75, and spatial memory (Morris water maze test, MWM) was assessed on days 14-21 and 83-90 after CCI injury or sham surgery. Results When administered at 10 mg/kg, but not 2.5 or 5 mg/kg, memantine preserved cortical tissue and reduced neuronal degeneration 1 day after injury, and attenuated loss of synaptophysin immunoreactivity in the hippocampus 7 days after injury. No effects of 10 mg/kg memantine were observed on histopathology at 21 and 90 days after CCI injury or sham surgery, or on vestibulomotor function and spatial memory acquisition assessed during any of the testing periods. However, 10 mg/kg memantine resulted in trends for improved search strategy in the MWM memory retention probe trial. Conclusions Administration of memantine at a clinically-relevant delay after moderate-severe CCI injury has beneficial effects on acute outcomes, while more significant improvement on subacute and chronic outcomes may require repeated drug administration or its combination with another therapy.
Genetic associations of perinatal pain and depression

Underlying genetic influences may affect perinatal pain, depression, or both. We investigated the role of 59 single-nucleotide polymorphisms on 20 quantitative traits measured in perinatal women. M...
A bioengineered living cell construct activates metallothionein/zinc/MMP8 and inhibits TGFβ to stimulate remodeling of fibrotic venous leg ulcers

Venous leg ulcers (VLU) represent a major clinical unmet need, impairing quality of life for millions worldwide. The bioengineered bilayered living cell construct (BLCC) is the only FDA-approved therapy demonstrating efficacy in healing chronic VLU, yet its in vivo mechanisms of action are not well understood. Previously, we reported a BLCC-mediated acute wounding response at the ulcer edge; in this study we elucidated the BLCC-specific effects on the epidermis-free ulcer bed. We conducted a randomized controlled clinical trial (ClinicalTrials.gov NCT01327937) enrolling 30 subjects with nonhealing VLUs, and performed genotyping, genomic profiling, and functional analysis on wound bed biopsies obtained at baseline and 1 week after treatment with BLCC plus compression or compression therapy (control). The VLU bed transcriptome featured processes of chronic inflammation and was strikingly enriched for fibrotic/fibrogenic pathways and gene networks. BLCC application decreased expression of profibrotic TGFs1 gene targets and increased levels of TGFs inhibitor decorin. Surprisingly, BLCC upregulated metallothioneins and fibroblast-derived MMP8 collagenase, and promoted endogenous release of MMP-activating zinc to stimulate antifibrotic remodeling, a novel mechanism of cutaneous wound healing. By activating a remodeling program in the quiescent VLU bed, BLCC application shifts nonhealing to healing phenotype. As VLU bed fibrosis correlates with poor clinical healing, findings from this study identify the chronic VLU as a fibrotic skin disease and are first to support the development and application of antifibrotic therapies as a successful treatment approach.
Postoperative Recovery of Left Ventricular Function following Repair of Large Ventricular Septal Defects in Infants.

Introduction Early postoperative left ventricular (LV) dysfunction is observed following repair of large ventricular septal defects (VSDs), but the frequency and rate of recovery of LV function are unknown. This study aims to characterize the incidence and rate of recovery of postoperative LV dysfunction following repair of large VSDs and to improve understanding of LV mechanics before and after VSD repair. Methods Infants who underwent surgical repair of an isolated large VSD were included. Pre- and postoperative echocardiographic images were reviewed, and LV function was assessed by both conventional echocardiography and speckle-tracking strain analyses. Postoperative LV dysfunction was defined as an LV ejection fraction (LVEF) Results Of 104 infants evaluated (median age, 0.31 [0.22, 0.56] years), all had normal preoperative LVEF and 39 (38%) had postoperative LV dysfunction. Follow-up echocardiograms were available in 31 (80%) patients, all of whom had LVEF > 50% within 9 months of surgery. Lower preoperative apical four-chamber longitudinal strain (A4LS) and greater LV end-diastolic volume indexed to body surface area1.38 were independently associated with postoperative LV dysfunction. An absolute preoperative A4LS Conclusions Infants with LV dysfunction following repair of large VSDs recover function within 9 months. Preoperative A4LS can be helpful to detect subclinical LV dysfunction in the setting of a large hemodynamically significant VSD and guide postoperative expectations for providers and families.
Sequence matters: elotuzumab more effective if used before daratumumab

Treatment of an incurable and genetically unstable malignancy such as multiple myeloma (MM) requires a succession of therapeutic regimens to counter an evolving clone. How we sequence these therapi...
Enolate-forming compounds provide protection from platinum neurotoxicity

Cisplatin (CisPt) and other platinum (Pt)-based antineoplastic drugs (e.g., carboplatin, oxaliplatin) are highly effective and widely used in the treatment of solid tumors in both pediatric and adult patients. Although considered to be life-saving as a cancer treatment, Pt-based drugs frequently result in dose-limiting toxicities such as chemotherapy-induced peripheral neuropathies (CIPN). Specifically, irreversible damage to outer hair cells and injury of sensory neurons are linked to profound sensorineural hearing loss (ototoxicity), which complicates tumor management and can lead to a poor clinical prognosis. Given the severity of CIPN, substantial effort has been devoted to the development of neuroprotective compounds, regardless clinical results have been underwhelming. It is noteworthy that Pt is a highly reactive electrophile (electron deficient) that causes toxicity by forming adducts with nucleophilic (electron rich) targets on macromolecules. In this regard, we have discovered a series of carbon-based enol nucleophiles; e.g., N-(4-acetyl-3,5-dihydroxyphenyl)-2-oxocytclopentane-1-carboxamide (Gavinol), that can prevent neurotoxicity by scavenging the platinum ion. The chemistry of enol compounds is well understood and mechanistic research has demonstrated the role of this chemistry in cytoprotection. Our cell-derived data were corroborated by calculations of hard and soft, acids and bases (HSAB) parameters that describe the electronic character of interacting electrophiles and nucleophiles. Together, these observations indicate that the respective mechanisms of Pt neurotoxicity and antitumor activity are separable and can therefore be affected independently.
Surveillance of echinococcosis in Yixing City from 2011 to 2018

OBJECTIVE To analyze the results of echinococcosis surveillance in Yixing City from 2011 to 2018, so as to provide insights into echinococcosis control in the city. METHODS All echinococcosis cases reported in Yixing City since 2007 that were captured from the China National Notifiable Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention received a case study, and serological test and transabdominal B-mode ultrasound screening were performed among permanent residents and mutton market workers in Fangdong and Fangzhuang villages of Yixing City from 2011 to 2018. The cyst, mass and tubercle were detected in the liver and lung of the sheep from the mutton markets, and the Echinococcus coproantigen was detected in the canine stool samples from Fangdong and Fangzhuang villages. In addition, the awareness of echinococcosis prevention and control knowledge was investigated in the two villages using a questionnaire survey from 2011 to 2018. RESULTS A total of 7 cases with echinococcosis had been reported in Yixing City since 2007, with prevalence of 0.56/100 000, and all cases were E. granulosus-infected patients, including 2 cases with a history to travel to echinococcosis-endemic areas and 5 cases with a history of working in local mutton markets or dog contacts. From 2011 to 2018, a total of 1 861 residents received serological tests, with 0.54% seropositivity, and no seropositives were detected since 2016. Among the 1 807 individuals receiving transabdominal B-mode ultrasound screening, suspected cysts were found in 143 individuals (7.91%), and 1.40% (2/143) seropositivity was detected in these individuals. The mean positive rate of the Echinococcus coproantigen was 0.67% (3 /446) in the canine stool samples. Among the 4 010 sheep liver and lung specimens sampled from the mutton markets, 7 specimens (0.17%) were detected with cysts or tubercles. In addition, the mean awareness rate of echinococcosis prevention and control knowledge was 76.95% among the 538 subjects receiving questionnaire surveys from 2011 to 2018, and the overall awareness appeared a tendency towards a rise year after year. CONCLUSIONS Although the prevalence of echinococcosis and the seropositivity of anti-Echinococcus antibodies are low, there is still a risk of transmission of echinococcosis in Yixing City. The surveillance of echinococcosis should continue to be intensified and related control interventions are required.
Mechanistic insights and consequences of intrapore liquids in ethene, propene, and butene dimerization on isolated Ni2+ sites grafted within aluminosilicate mesopores

Abstract The stability, selectivity, and reactivity conferred by intrapore liquids onto Ni2+ species grafted within mesoporous aluminosilicates for the dimerization of C2-C4 alkenes are reported and interpreted by the preferential stabilization of dimer desorption transition states, which inhibit further growth during the surface sojourn that forms these dimers. The marked decrease in deactivation rate constants leads to catalyst half-lives > 600 h for all alkenes and to turnover rates (per Ni) at sub-ambient temperatures (240–260 K) that exceed those at the higher temperatures previously used for Ni-based solid catalysts (350–500 K). These effects appear at the relative pressures required for alkene capillary condensation within Ni-Al-MCM-41 catalysts with different mesopore diameters and are also evident when the intrapore liquids consist of unreactive alkanes, indicative of solvation effects conferred by non-covalent interactions mediated by dispersion forces. For all alkenes, turnover rates (per Ni) are unaffected by Ni content until each acidic proton in the Al-MCM-41 is replaced by one Ni atom, consistent with the involvement of grafted (Ni-OH)+ monomers as active centers and excess Ni leading to inactive NiO species. The stable nature of these catalysts allows accurate mechanistic assessments and a demonstration of the kinetic relevance of the C C coupling elementary steps on essentially bare (Ni-OH)+ centers, leading to rates described by second-order dimerization constants (αn′) and adsorption constants (βn′) for each alkene (Cn); these parameters are influenced only slightly by intrapore liquids, because they reflect free energies of formation of surface-bound species and transition states from gaseous precursors. These αn′ and βn′ parameters increase with alkene size, with the enthalpic component of αn′ increasing from 21 to 46 kJ mol−1 and the activation entropy becoming more negative (−103 to −187 J (mol K)−1), consistent with C C coupling transition states that occur late along the reaction coordinate and resemble its bound dimer product. The low C3n/C2n ratios observed in the presence of intrapore liquids (
Design of Low-Speed Slotted, Natural-Laminar-Flow Airfoil Reproducing Transonic Behaviors

Airfoils tested at low speeds generally produce surface pressure distributions that differ substantially from those measured at transonic conditions, which in turn results in very different boundar...
Endocrine resistance in breast cancer: from molecular mechanisms to therapeutic strategies.

Estrogen receptor-positive (ER +) breast cancer accounts for approximately 75% of all breast cancers. Endocrine therapies, including selective ER modulators (SERMs), aromatase inhibitors (AIs), and selective ER down-regulators (SERDs) provide substantial clinical benefit by reducing the risk of disease recurrence and mortality. However, resistance to endocrine therapies represents a major challenge, limiting the success of ER + breast cancer treatment. Mechanisms of endocrine resistance involve alterations in ER signaling via modulation of ER (e.g., ER downregulation, ESR1 mutations or fusions); alterations in ER coactivators/corepressors, transcription factors (TFs), nuclear receptors and epigenetic modulators; regulation of signaling pathways; modulation of cell cycle regulators; stress signaling; and alterations in tumor microenvironment, nutrient stress, and metabolic regulation. Current therapeutic strategies to improve outcome of endocrine-resistant patients in clinics include inhibitors against mechanistic target of rapamycin (mTOR), cyclin-dependent kinase (CDK) 4/6, and the phosphoinositide 3-kinase (PI3K) subunit, p110α. Preclinical studies reveal novel therapeutic targets, some of which are currently tested in clinical trials as single agents or in combination with endocrine therapies, such as ER partial agonists, ER proteolysis targeting chimeras (PROTACs), next-generation SERDs, AKT inhibitors, epidermal growth factor receptor 1 and 2 (EGFR/HER2) dual inhibitors, HER2 targeting antibody-drug conjugates (ADCs) and histone deacetylase (HDAC) inhibitors. In this review, we summarize the established and emerging mechanisms of endocrine resistance, alterations during metastatic recurrence, and discuss the approved therapies and ongoing clinical trials testing the combination of novel targeted therapies with endocrine therapy in endocrine-resistant ER + breast cancer patients.
Sex and estrous-phase dependent alterations in depression-like behavior following mild traumatic brain injury in adolescent rats.

Following mild traumatic brain injury (TBI), high school and collegiate-aged females tend to report more emotional symptoms than males. Adolescent male and female rats (35 days old) were subjected to mild TBI and evaluated for anxiety- and depression-like behaviors using the elevated plus maze and forced swim test (FST), respectively, and cellular alterations. Injured brains did not exhibit an overt lesion, atrophy of tissue or astrocytic reactivity underneath the impact site at 6-week post-injury, suggestive of the mild nature of trauma. Neither male nor female brain-injured rats exhibited anxiety-like behavior at 2 or 6 weeks, regardless of estrous phase at the time of behavior testing. Brain-injured male rats did not exhibit any alterations in immobility, swimming and climbing times in the FST compared to sham-injured rats at either 2- or 6-week post-injury. Brain-injured female rats did, however, exhibit an increase in immobility (in the absence of changes in swimming and climbing times) in the FST at 6 weeks post-injury only during the estrus phase of the estrous cycle, suggestive of a depression-like phenotype. Combined administration of the estrogen receptor antagonist, tamoxifen, and the progesterone receptor antagonist, mifepristone, during proestrus was able to prevent the depression-like phenotype observed during estrus. Taken together, these data suggest that female rats may be more vulnerable to exhibiting behavioral deficits following mild TBI and that estrous phase may play a role in depression-like behavior.
Sorting the Revolutionary from the Terrorist: The Delicate Application of the Political Offense Exception in U.S. Extradition Cases

* J.D., Stanford Law School, 2006. Law Clerk to the Honorable Barry G. Silverman, U.S. Cour of Appeals for the Ninth Circuit, 2006-2007. I am grateful to Jenny Marti ez and Robert Weisberg for their guida ce, patience, and inspiration. This Note is a tribute to their mentorship. Jameson Jones, Nancy Leo g, Hilary Ley, and Julie Smolinski also provided invaluable suggestio s. A special thank you to the Office of the Federal Public Defender, particularly Michael Nachmanoff and Meghan Skelton, or introducing me to this topic.
Role of Bacterial Chemical Components in Immunofluorescence

Jones, Wallis L. (Communicable Disease Center, Atlanta, Ga.), and Vester J. Lewis. Role of bacterial chemical components in immunofluorescence. J. Bacteriol. 91:1700–1704. 1966.—The problem of heterologous staining of bacteria in pure culture and in clinical specimens by fluorescein-labeled antisera for Corynebacterium diphtheriae was examined by observing the presence of particular cellular components in the bacteria involved. Decreases in the degree of staining of C. diphtheriae, diphtheroids, and cocci by the immunofluorescent reagent were shown to accompany hydrolytic removal from the cells of specific compounds, the identities of which varied from those of the treated organisms.
ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway

The rare diseases ataxia-telangiectasia (AT), caused by mutations in the ATM gene, and Nijmegen breakage syndrome (NBS), with mutations in the p95/nbs1 gene, share a variety of phenotypic abnormalities such as chromosomal instability, radiation sensitivity and defects in cell-cycle checkpoints in response to ionizing radiation1,2,3,4. The ATM gene encodes a protein kinase that is activated by ionizing radiation or radiomimetic drugs5,6, whereas p95/nbs1 is part of a protein complex that is involved in responses to DNA double-strand breaks3,7. Here, because of the similarities between AT and NBS, we evaluated the functional interactions between ATM and p95/nbs1. Activation of the ATM kinase by ionizing radiation and induction of ATM-dependent responses in NBS cells indicated that p95/nbs1 may not be required for signalling to ATM after ionizing radiation. However, p95/nbs1 was phosphorylated on serine 343 in an ATM-dependent manner in vitro and in vivo after ionizing radiation. A p95/nbs1 construct mutated at the ATM phosphorylation site abrogated an S-phase checkpoint induced by ionizing radiation in normal cells and failed to compensate for this functional deficiency in NBS cells. These observations link ATM and p95/nbs1 in a common signalling pathway and provide an explanation for phenotypic similarities in these two diseases.
Dissimilation of Aromatic Compounds by Alcaligenes eutrophus

The range of aromatic compounds that support the growth of Alcaligenes eutrophus has been determined, and the pathways used for the dissimilation of these substrates have been explored, largely by enzymatic analyses. The beta-ketoadipate pathway operates in the dissimilation of benzoate and p-hydroxybenzoate; the genetisate pathway, in the dissimilation of m-hydroxybenzoate; and the meta cleavage pathway, in the dissimilation of phenol and p-cresol. l-Tryptophan is oxidized via anthranilate; but the metabolic fate of anthranilate was not established. The metabolism of the three stereoisomers of muconic acid was also examined.
SBVR Use Cases

Semantics of Business Vocabulary and Rules (SBVR) is a new standard from the OMG that combines aspects of ontologies and of rule systems. This paper summarizes SBVR, reviews some possible use cases for SBVR, and discusses ways that vocabularies and rules given in SBVR could relate to established ontology standards, to rules technologies, and to other IT implementation technologies. It also describes experience with an SBVR prototype that transforms a subset of SBVR rules types to several types of runtime implementations.
Evaluating OpenMP on chip multithreading platforms

Recent computer architectures provide new kinds of on-chip parallelism, including support for multithreading. This trend toward hardware support for multithreading is expected to continue for PC, workstation and high-end architectures. Given the need to find sequences of independent instructions, and the difficulty of achieving this via compiler technology alone, OpenMP could become an excellent means for application developers to describe the parallelism inherent in applications for such architectures. In this paper, we report on several experiments designed to increase our understanding of the behavior of current OpenMP on such architectures. We have tested two different systems: a Sun Fire V490 with Chip Multiprocessor technology and a Dell Precision 450 workstation with Simultaneous MultiThreading technology. OpenMP performance is studied using the EPCC Microbenchmark suite, subsets of the benchmarks in SPEC OMPM2001 and the NAS parallel benchmark 3.0 suites.
Robust sublinear complexity Walsh-Hadamard transform with arbitrary sparse support

In this paper, we propose algorithms for computing Walsh-Hadamard transform with arbitrary K-sparse support. When K is sublinear in the dimension N of the time-domain signal, the algorithms achieve vanishing error probability as K increases without bound and involve sublinear computational complexity. Specifically, under the noiseless setting, an algorithm based on random hashing and successive cancellation is proposed, where O (K log K log N over K) operations on O(K log N over K) samples of the signal suffice. Under the noisy setting, a fast algorithm using the same framework is also proposed, which needs O (K log3 K log N over K) operations and O (K log2 K log N over K) samples. The latter algorithm reduces the complexity from superlinear in existing work to sublinear. The enabling idea is to relate the random hashing design to coding over a binary symmetric channel or a binary-input additive white Gaussian noise channel, whose quality depends on the noise level of the observations. Such inherent connection allows us to leverage well-established capacity-approaching codes to obtain the transform-domain signal with sublinear complexity.
Book Review: Human Rights and the WTO: The Case of Patents and Access to Medicines, by Holger Hestermeyer

Human rights and patent rights have become increasingly intertwined in discussions surrounding access to pharmaceutical drugs by citizens of developing countries. This discussion is a particularly contentious one for reasons of socioeconomics and geography. Drug companies in more developed countries (“MDCs”) tend to own the patent rights covering newer medicines, and justify the monopoly prices they charge as a necessary return on investment for inventing new drugs. Less developed countries (“LDCs”), lacking the purchasing power to pay monopoly prices for patented drugs, tend to argue that monopoly prices for drugs violate human rights of access to medicines. The result is an often shrill debate over the primacy of patent rights or human rights. In his excellent book, HUMAN RIGHTS AND THE WTO: THE CASE OF PATENTS AND ACCESS TO MEDICINES, Holger Hestermeyer has tackled this complex and contentious conflict, disentangled it into its essential constituent parts, including patent law, human rights, and international trade under the World Trade Organisation (“WTO”) regime and its side-agreement on Trade-Related Aspects of Intellectual Property (“TRIPS”), and then artfully reconstructed a clear, cogent, and hopeful model of how to approach a resolution. His research is meticulous, his prose spare yet fluent, and his arguments persuasive and well-supported.
Water–gas shift catalysis over transition metals supported on molybdenum carbide

Abstract We report here that WGS rates per total surface area at 120 °C, 7% CO, 22% H 2 O, 8.5% CO 2 , 37% H 2 for Pt, Au, Pd and Ni supported over Mo 2 C were 4–8 times higher than those of the commercial Cu/ZnO/Al 2 O 3 catalyst. In agreement with previous literature, the WGS rate per total moles of Pt over Pt/Mo 2 C at 120 °C has been shown to be higher than on any Pt/Metal oxide catalyst. We have made use of systematic changes in the apparent kinetic parameters with various admetals (decrease in apparent CO order and apparent activation energy and increase in apparent H 2 O order compared to unpromoted Mo 2 C) to conclude that the function of the rate-promoting admetals is to enhance the relative surface concentration of the adsorbed CO, thereby leading to a promotion in the WGS rate per total surface area of the catalyst. Temperature programmed desorption of CO was used to show that the CO adsorption properties of Mo 2 C were modified by the various admetals by creating new metallic sites. In situ X-ray absorption on Pt and Au and STEM–EELS experiments showed that the supported Au nanoparticles over Mo 2 C decrease in average particle size from ∼9 nm to 3 nm after a 600 °C carburization pretreatment. Pt was also shown to have assumed a stable structure at 600 °C in the form of a Pt–Mo alloy. We suggest that Mo 2 C can be used to synthesize thermally robust supported metal catalysts.
Prejudice in the Lives of Asian Americans

Expressions of prejudice were compared between Asian American and Black, Hispanic, Jewish, and White respondents to social distance and stereotype items on 5 recent nationwide public opinion surveys. There was much prejudice toward Asian Americans. Their prejudice was greatest toward Blacks and Hispanics and least toward Jews and Whites. Among Asian American subgroups, prejudice toward Blacks, Hispanics, and Whites was greatest by Chinese Americans and Japanese Americans; and least by Filipino Americans and Asian Indian Americans. Suggestions are made for further research.
Hydrolysis of lactose in skim milk by immobilized β-galactosidase in a spiral flow reactor

beta-galactosidase from Aspergillus Oryzae immobilized in a spiral flow reactor was used to effect the hydrolysis of the lactose component of skim milk. Residence time distribution measurements were used to assess the amount of longitudinal dispersion occurring as a consequence of the spiral flow pattern and the semiporous nature of the polymeric material used to construct the spiral. It was possible to model the flow conditions as tubular flow with a Peclet number that was a linear function of the reactor space time. Nonlinear regression methods were used to determine the kinetic parameters of three proposed enzymatic rate expressions. The best fit of the data was obtained using a rate expression containing separate terms for competitive inhibition of the reaction by both the a and beta anomers of galactose. This kinetic model also incorporates the kinetics of the mutarotation between these forms. At 30 degrees C and a space time of 7 minutes, 80% of the lactose present in skim milk can be converted to glucose and galactose.
Enhanced Intercellular Retention Activity of Novel pH-sensitive Polymeric Micelles in Wild and Multidrug Resistant MCF-7 Cells

Purpose The purpose of this work was to demonstrate the advantage of using pH-sensitive polymeric mixed micelles (PHSM) composed of poly(l-histidine) (polyHis)/poly(ethylene glycol) (PEG) and poly(l-lactic acid) (pLLA)/PEG block copolymers with folate conjugation to increase drug retention in wild-type and MDR tumor cells.
TEM 00 Mode Ho:YLF Laser

A flashlamp pumped liquid nitrogen cooled Ho:YLF laser was constructed and operated both normal mode and Q-switched. In normal mode operation, the laser produced over 300 mj at 2.9 percent slope efficiency but it operated on several lines. Lasing was restricted to one line and Q-switched operation was achieved up to 150 mj.
Indirect gastrointestinal transit monitoring and absorption of theophylline

The gastrointestinal transit and absorption of a multiparticulate controlled-release theophylline preparation were investigated under fed and fasted conditions. Transit of the theophylline pellets in the gastrointestinal tract was monitored using two marker drugs, namely, paracetamol and sulfasalazine. Food was found to delay the gastric emptying and caecal arrival of the pellets, but had no significant effect on the small intestinal transit time. The delay in gastric emptying was associated with a delay in drug absorption. Under the fasted condition, approximately 13% of the drug was absorbed while the pellets were in the stomach, 57% while in the small intestine and the remaining amount while in the colon. As for the fed mode, the percent absorbed while the pellets were in these regions were 9%, 72%, and 19%, respectively.
Evidence for a role of topoisomerase II in the Ca2+-dependent basal level expression of the rat prolactin gene.

The PRL gene is expressed at a high basal level in rat pituitary tumor GH3 cells, and this basal level enhancement of PRL gene expression is maintained through a Ca2+-calmodulin-dependent mechanism. We have now examined whether the enzyme, DNA topoisomerase II, which has been shown to be phosphorylated by a Ca2+-calmodulin-dependent protein kinase, plays a role in the Ca2+-calmodulin-dependent basal level enhancement of PRL gene expression. The topoisomerase II inhibitor, novobiocin, at concentrations in the range of 35–140 µм, effectively blocked the ability of Ca2+ to increase PRL mRNA levels. Examination of the effects of novobiocin on the levels of protein synthesis, glucose-regulated protein (GRP) 78 mRNA, histone 3 mRNA, and 18S ribosomal RNA indicated that the drug selectivity inhibited PRL gene expression. Two other topoisomerase II inhibitors, m-AMSA and VM26, also diminished the Ca2+-induced levels of PRL mRNA at concentrations (100–400 nm) that did not lower total mRNA levels. We then examined ...
Autologous mixed lymphocyte reaction in lymphoid malignancies. Lack of correlation with disease activity or clinical remission

The proliferative response of T-enriched lymphocytes to autologous antigenic determinants present in cell populations depleted of T lymphocytes (autologous mixed lymphocyte reaction) was investigated in patients with chronic lymphocytic leukemia at different clinical stages and during clinical remission and in patients with hairy cell leukemia and patients with malignant lymphoma in long-term remission (median 35.5 months). An absence of autologous reactivity was found independently of the tumor burden, and no restitution of the autologous response was observed in patients in clinical remission. The response to phytohemagglutinin and to irradiated allogeneic T-depleted lymphocytes from normal individuals was found to be preserved in all patients, but lower than in healthy subjects. These observations suggest a defect of either the responder or stimulator population or a defect in the mechanism(s) regulating the autologous response. The possible pathogenic role of the AMLR in malignant lymphoproliferative disorders is discussed.
Gender differences in the relationship between physical activity and smoking among psychiatrically hospitalized adolescents

Abstract Physical activity has been identified as a protective factor with regard to tobacco use, such that physically active adolescents are less likely to initiate smoking, and smokers are less physically active than non-smokers. These findings, along with the well-documented benefits of exercise on mood and well-being in adults, have stimulated interest in exercise-based smoking cessation interventions. However, little research has explored the relationship between physical activity and smoking characteristics within adolescent smokers. Also, gender differences in adolescents' motives for smoking and exercise may have implications for intervention development, especially in clinical populations. The current study explored the relationship between physical activity and smoking in a sample of adolescent smokers ( N = 191) and non-smokers ( N = 48) receiving inpatient psychiatric treatment (61% female, mean age 15.3 years). Results indicated that smokers were less likely to be physically active than non-smokers. Additionally, there was a consistent pattern of gender differences in the relationship between smoking and physical activity within smokers. Specifically, physically active male smokers were less nicotine dependent and less prone to withdrawal symptoms, and had a trend toward greater motivation to quit, than their non-active counterparts. In contrast, physically active female smokers did not differ in dependence or withdrawal and were less motivated to quit than non-active female smokers. Taken together, these results suggest that within clinical populations of adolescent females, smoking and exercise may be used jointly as weight control strategies. Exercise-based interventions for smoking cessation for adolescent females, especially clinical populations, should address weight and body image concerns.
Essential newborn care in rural settings: The case of Warrap State in South Sudan

Essential newborn care is taking a predominant role in addressing under-five healthcare delivery interventions. There are no current well-established guidelines or common methodologies on how to assess the situation of newborn care in countries with weak health information systems, especially when addressing situational needs in rural settings. The main objective of this study was to test the feasibility of collecting information using a community based approach to assess the level of coverage of essential newborn care, especially for rural settings. Six indicators related to promotion and provision of thermal care, early initiation of exclusive breastfeeding, and hygienic cord care, were measured. A two-stage stratified and weighted random sampling was carried out. Standard sample calculations were used to determine a sample of 511 respondents. Descriptive results from the population survey showed that the prevalence of newborns receiving all recommended elements of essential new born care in the surveyed area was 1%. The most common element completed, with nine out of ten respondents, was wrapping the newborn immediately after birth, but only 1% were not bathed within the first six hours after birth. Survey results confirmed low coverage of systematic application of essential newborn care measures in rural areas of Warrap State in South Sudan.This observational study indicates that the collection of information on health care behaviours around essential newborn care indicators (thermal, cord and eye care, and breastfeeding) can be reliably achieved, especially in hard-to-reach areas, at the community level.
A Simple Method for Accurate Estimation of Apoptotic Cells

A simple, sensitive, and reliable "DNA diffusion" assay for the quantification of apoptosis is described. Human lymphocytes and human lymphoblastoid cells, MOLT-4, were exposed to 0, 12.5, 25, 50, or 100 rad of X-rays. After 24 h of incubation, cells were mixed with agarose, microgels were made, and cells were lysed in high salt and detergents. DNA was precipitated in microgels by ethanol. Staining of DNA was done with an intense fluorescent dye, YOYO-1. Apoptotic cells show a halo of granular DNA with a hazy outer boundary. Necrotic cells, resulting from hyperthermia treatment, on the other hand, show an unusually large homogeneous nucleus with a clearly defined boundary. The number of cells with apoptotic and necrotic appearance can be scored and quantified by using a fluorescent microscope. Results were compared with other methods of apoptosis measurement: morphological estimations of apoptosis and DNA ladder pattern formation in regular agarose gel electrophoresis. Validation of the technique was done using some known inducers of apoptosis and necrosis (hyperthermia, hydrogen peroxide, mitoxantrone, novobiocin, and sodium ascorbate).
Carbon balance in bioregenerative life support systems: some effects of system closure, waste management, and crop harvest index.

In Advanced Life Support (ALS) systems with bioregenerative components, plant photosynthesis would be used to produce O2 and food, while removing CO2. Much of the plant biomass would be inedible and hence must be considered in waste management. This waste could be oxidized (e.g., incinerated or aerobically digested) to resupply CO2 to the plants, but this would not be needed unless the system were highly closed with regard to food. For example, in a partially closed system where some of the food is grown and some is imported, CO2 from oxidized waste when combined with crew and microbial respiration could exceed the CO2 removal capability of the plants. Moreover, it would consume some O2 produced from photosynthesis that could have been used by the crew. For partially closed systems it would be more appropriate to store or find other uses for the inedible biomass and excess carbon, such as generating soils or growing woody plants (e.g., dwarf fruit trees). Regardless of system closure, high harvest crops (i.e., crops with a high edible to total biomass ratio) would increase food production per unit area and O2 yields for systems where waste biomass is oxidized to recycle CO2. Such interlinking effects between the plants and waste treatment strategies point out the importance of oxidizing only that amount of waste needed to optimize system performance. Published by Elsevier Science Ltd on behalf of COSPAR.
Hydrodynamic profiles and constants of motion fromd-Branes

Various hydrodynamic systems, governed by nonlinear differential equations, have a hidden higher-dimensional dynamic Poincare symmetry because the governing equations descend from a Nambu-Goto action. For the same reason, there are also equivalence transformations between different models. We discuss these interconnections and summarize them in a simple diagram.
CELL VOLUME EXPANSION IN SM5 (FE, T)17, T=TI, V, MAGNETIC PHASES

Abstract The formation of binary Sm5Fe17 is reported for the first time. The room-temperature i H c observed was 7 kOe. It is also shown that V and Ti replacements for approximately 10% of the Fe yield a systematic and expected expansion of the unit-cell volume. This is interpreted to mean that the Ti and V are replacing part of the iron in the primary magnetic phase.
The dissociation curve for goose blood.

Abstract The oxyhemoglobin dissociation curves for goose blood were determined at pH values of 7.25, 7.4 and 7.6. Curves were constructed by polarographic analyses of O 2 tension and spectrophotometric determination of Hb saturation. The curves obtained showed a significant displacement to the right in comparison with human dissociation curves. Also, the hemoglobin saturation never exceeded 95 % up to an oxygen tension of 150 mm Hg (pH 7.40). Bohr effect Oxygen dissociation curve T50
Inoculum potential of verticillium—infested potato cultivars

Viable propagules ofVerticillium albo-atrum andV. dahliae were recovered from potato stems before and after burial in the field during 1968–1971. Of 14 cultivars tested: Red Pontiac and Superior ranked highest in numbers of propagules ofV. albo-atrum. Russet Burbank, Kennebec, and Irish Cobbler ranked highest withV. dahliae, respectively.
Joint CT/CBCT deformable registration and CBCT enhancement for cancer radiotherapy

This paper details an algorithm to simultaneously perform registration of computed tomography (CT) and cone-beam computed (CBCT) images, and image enhancement of CBCT. The algorithm employs a viscous fluid model which naturally incorporates two components: a similarity measure for registration and an intensity correction term for image enhancement. Incorporating an intensity correction term improves the registration results. Furthermore, applying the image enhancement term to CBCT imagery leads to an intensity corrected CBCT with better image quality. To achieve minimal processing time, the algorithm is implemented on a graphic processing unit (GPU) platform. The advantage of the simultaneous optimization strategy is quantitatively validated and discussed using a synthetic example. The effectiveness of the proposed algorithm is then illustrated using six patient datasets, three head-and-neck datasets and three prostate datasets.
Quantum mechanical calculation of the carrier distribution and the thickness of the inversion layer of a MOS field-effect transistor

Abstract The carrier distribution in the inversion layer of a MOS-structure at room temperature was calculated assuming a quantization of the allowed energy levels at the surface and a linear electrostatic potential. It was found that for strong inversion the carrier distribution deviates considerably from the one found by using classical statistics but approaches the classical limit for weak inversion when many electric subbands are occupied. A new definition for the channel thickness was introduced based on the integrated charge in the channel and compared to other definitions. Channel thicknesses so defined range from 30 to 400 A for practical devices depending on surface potential. The integrated charge in the channel deviated little from the one found using classical statistics.
Environmental Causes of Cancer of the Lung Other Than Tobacco Smoke

The recognized or strongly suspected environmental causes of cancer of the respiratory system form an important segment of the environmental carcinogenic spectrum. 1. With one exception all so far known exogenous respiratory carcinogens were discovered during the last 25 years (Table I), that is, during the period in which a remarkable and progressive rise in the number and frequency of cancers of the lung was observed in most industrialized countries (Fig. 1). 2. The various respiratory carcinogens are more or less well defined chemical or physical agents and/or are associated with distinct occupational activities engaged in by circumscribed workers groups (Table II). 3. The clinical, epidemiologic, pathologic and experimental observations related to these agents all of which act through the respiratory route
Crosspresentation: Plasmacytoid Dendritic Cells Are in the Business

Crosspriming and crosspresentation are performed by specialized subsets of dendritic cells. In this issue, Hoeffel et al. (2007) show that human plasmacytoid dendritic cells can crosspresent HIV-derived peptides conjugated to a lipopeptide or HIV-infected cells undergoing apoptosis.
Correlation between recombinase activating gene 1 ubiquitin ligase activity and V(D)J recombination

The really interesting new gene (RING) finger ubiquitin ligase domain of the recombinase activating gene 1 (RAG1) V(D)J recombinase protein adopts a standard cross-brace architecture but co-ordinates three zinc ions as opposed to the canonical two. We demonstrated previously that disruption of the conserved zinc co-ordination sites resulted in loss of structural integrity and ubiquitin ligase (E3) activity and interfered with the ability of full-length RAG1 to support recombination. Here we present evidence that amino acids surrounding the third, non-canonical site also contribute to functional interaction with the ubiquitin conjugating (E2) enzyme CDC34, while certain residues on the RING domain's surface important for interaction between other E2-E3 pairs are less critical to the functional RAG1-CDC34 interaction in this assay. Partial reduction of ubiquitin ligase activity was significantly correlated with reduction in the ability of RAG1 to support recombination of extra-chromosomal substrates (r = 0.805, P = 0.009). While poly-ubiquitin chains could be generated, RAG1 did not promote rapid chain extension following mono-ubiquitylation of substrate, regardless of the E2 enzyme used. No single ubiquitin lysine mutant disrupted the ability of CDC34 to form ubiquitin chains on RAG1, and mass spectrometric analysis of the poly-ubiquitylated products indicated ubiquitin chain linkages through lysines 48 and 11. These data suggest that RAG1 promotes a mono-ubiquitylation reaction that is required for optimal levels of V(D)J recombination.
Q measurements for phase X overtones

Linear stacking procedures are used to retrieve the attenuation of 91 modes belonging to the 3rd, 4th and 5th Rayleigh overtones branches in the 80–160 s period range, and contributing to the so-called “PhaseX” wave group. Our data show in general slightly less attenuation than expected from available models. Data space inversion shows that, when combined with previously measured fundamental modeQ's, this new dataset improves resolution significantly in the 1000–2000 km depth range. Based on this remark, we carry out a number of parameter space inversions. Our results suggest a narrow (80–200 km) zone of high attenuation (Qμ=75–90), low attenuation in the intermediate mantle (670–1500 km); (Qμ≈350), and lower values in the deeper mantle (Qμ≈200).
Female–male differences in conversational interaction

This article describes a preliminary experiment looking at possible differences in how females and males interact in conversation. The article analyzes data from an experiment where two females and two males talked to each other in all possible pairs; a total of 60 minutes of conversation (six dyads) was transcribed. The goal was to isolate quantifiable entities related to controlling or directing the conversation. We looked at issues such as who talked how much, how fluently or confidently – and how the two people in the conversation interacted in terms of interruptions and indications of support, agreement, or disagreement. The findings from such a small sample are only relevant to suggest hypotheses for further research. However, we noticed a number of interesting differences: the female speakers used more 1st person pronouns and fewer 3rd person references than the male speakers; the female speakers used mm hmm at a much higher frequency than the male speakers; the female speakers also interrupted each other more; and the female/female conversation seemed more fluent than the other conversations, as measured by number of disfluencies and number of affirmative transitions upon speaker change. All of these differences suggest that this area is a fruitful one for further investigation. (Conversational analysis, gender differences)
Jakes fading model revisited

The Jakes fading model is a deterministic method for simulating time-correlated Rayleigh fading waveforms and is still widely used today. However, since it is difficult to create multiple uncorrelated fading waveforms with this model, the authors propose modifications to the model which solve this problem.< >
Elevated Serum Lipoprotein(a) Is a Risk Factor for Clinical Recurrence After Coronary Balloon Angioplasty

Background Elevated lipoprotein (Lp) (a) concentrations are associated with coronary artery disease and myocardial infarction. Lp(a) is structurally related to proteins involved in lipid transport, fibrinolysis, coagulation, and cellular mitogenesis and is known to have important physiological interactions with the coagulation and fibrinolytic systems. Because these processes may be important to arterial healing after balloon injury, we hypothesized that elevated Lp(a) concentrations may be associated with recurrence of symptoms and restenosis after balloon angioplasty. Methods and Results We assessed 240 consecutive patients undergoing coronary balloon angioplasty with measurements of Lp(a), total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A-I, and apolipoprotein B-100 concentrations from fresh specimens. Patients were evaluated 4 to 6 months after angioplasty for clinical recurrence by repeat angiography if angina had returned or by maximal exercise treadmill testing wi...