cssi/SciSciGPT-SciSciNet huggingface dataset:
Sodium-hydrogen exchanger regulatory factor-1 (NHERF1) confers salt sensitivity in both male and female models of hypertension in aging.

Abstract Hypertension is a risk factor for premature death and roughly 50% of hypertensive patients are salt-sensitive. The incidence of salt-sensitive hypertension increases with age. However, the mechanisms of salt-sensitive hypertension are not well understood. We had demonstrated decreased renal sodium‑hydrogen exchanger regulatory factor 1 (NHERF1) expression in old salt-resistant F344 rats. Based on those studies we hypothesized that NHERF1 expression is required for the development of some forms of salt-sensitive hypertension. To address this hypothesis, we measured blood pressure in NHERF1 expressing salt-sensitive 4-mo and 24-mo-old male and female Fischer Brown Norway (FBN) rats male and female 18-mo-old NHERF1 knock-out (NHERF1−/−) mice and wild-type (WT) littermates on C57BL/6J background after feeding high salt (8% NaCl) diet for 7 days. Our data demonstrate that 8% salt diet increased blood pressure in both male and female 24-mo-old FBN rats but not in 4-mo-old FBN rats and in 18-mo-old male and female WT mice but not in NHERF1−/− mice. Renal dopamine 1 receptor (D1R) expression was decreased in 24-mo-old rats, compared with 4-mo-old FBN rats. However, sodium chloride cotransporter (NCC) expression increased in 24-mo-old FBN rats. In FBN rats, age had no effect on Na K ATPase α1 and NKCC2 expression. By contrast, high salt diet increased the renal expressions of NKCC2, and NCC in 24-mo-old FBN rats. High salt diet also increased NKCC2 and NCC expression in WT mice but not NHERF1−/− mice. Our data suggest that renal NHERF1 expression confers salt sensitivity with aging, associated with increased expression of sodium transporters.
DNA metabarcoding reveals organisms contributing to particulate matter flux to abyssal depths in the North East Pacific ocean

Abstract The sequestration of carbon in the deep ocean relies on the export of sinking particulate organic matter (POM) originating in the surface waters and its attenuation by organisms that reprocess and repackage it. Despite decades of research, predicting the variability of POM to the deep ocean remains difficult as there is still a gap in the knowledge as to which and how organisms control or influence POM export. Here, we used DNA metabarcoding of the 16S and 18S rRNA genes to investigate the community in sinking particulates collected over 9-months (November 2016–July 2017) at Station M, located within the California Current ecosystem. Particle-associated communities were collected in sediment traps (3900 m and 3950 m), in aggregates that settled on the sea floor (4000 m), and in seawater from the overlying water column. For a majority of the deployment, particulate organic carbon (POC) fluxes were within the Station M long-term time series mean ± σ (8.3 ± 7.9 mg C m−2 d−1). In late June, a high flux event (>long-term POC mean+2σ) was captured, accounting for 44% of the POC collected during the study. The rRNA genes within the sinking particles indicated highly variable eukaryal communities over time, including the export of oligotrophic autotrophs likely by various metazoan taxa during winter, the sporadic and dominant presence of diverse radiolarian orders, and the important role of coastal diatoms during seasonal increases in POC flux. Specifically, the onset of the high POC flux event in June was attributed to the export of a single coastal diatom species. A coincident increase in the relative abundance of metazoan sequences suggests that zooplankton grazing on the diatom community played a role in rapid transport of large quantities of POC to the deep sea. Analysis of the 16S rRNA gene community supported the presence of highly processed POM during winter due to the high relative abundance of deep sea Gammaproteobacteria, that transitioned to fresher, more labile POM with the arrival of a diatom bloom community. These observations support long standing paradigms of particulate export to the deep sea, including its origin and mechanisms of export mediated by a diverse community of organisms, and implicate rapidly exported diatom blooms as at least one source of the increasingly frequent episodic flux events that account for most POC sequestered in the deep ocean at Station M.
Knowing when to stick: touch receptors found in the remora adhesive disc

Remoras are fishes that piggyback onto larger marine fauna via an adhesive disc to increase locomotor efficiency, likelihood of finding mates and access to prey. Attaching rapidly to a large, fast-moving host is no easy task, and while research to date has focused on how the disc supports adhesion, no attention has been paid to how or if remoras are able to sense attachment. We identified push-rod-like mechanoreceptor complexes embedded in the soft lip of the remora adhesive disc that are known in other organisms to respond to touch and shear forces. This is, to our knowledge, the first time such mechanoreceptor complexes are described in fishes as they were only known previously in monotremes. The presence of push-rod-like mechanoreceptor complexes suggests not only that fishes may be able to sense their environment in ways not heretofore described but that specialized tactile mechanoreceptor complexes may be a more basal vertebrate feature than previously thought.
Intramuscular Hematoma as a Manifestation of IgA Vasculitis

We describe an atypical pediatric case of immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schonlein purpura, in which formation of spontaneous hematoma of the paraspinal muscles developed. Spontaneous or unprovoked hematomas rarely occur in IgAV. These manifestations have not been described specifically in the pediatric literature as coinciding with IgAV. These findings are alarming for nonaccidental trauma, particularly in a patient without underlying blood dyscrasia. Our objective for this report is to highlight the possible association of muscular hematoma formation with IgAV and to help providers consider this association when trauma and hemophilia has been ruled out.
Planning to Lead

It’s quite possible to succeed in life through luck and happenstance alone; but, for most of us, it’s much better to have a plan.
Room temperature quantum cascade lasers with 22% wall plug efficiency in continuous-wave operation

We report the demonstration of quantum cascade lasers (QCLs) with improved efficiency emitting at a wavelength of 4.9 µm in pulsed and continuous-wave (CW) operation. Based on an established design and guided by simulation, the number of QCL-emitting stages is increased in order to realize a 29.3% wall plug efficiency (WPE) in pulsed operation at room temperature. With proper fabrication and packaging, a 5-mm-long, 8-µm-wide QCL with a buried ridge waveguide is capable of 22% CW WPE and 5.6 W CW output power at room temperature. This corresponds to an extremely high optical density at the output facet of ∼35 MW/cm2, without any damage.
"Hay que seguir en la lucha": An FQHC's Community Health Action Approach to Promoting Latinx Immigrants' Individual and Community Resilience.

Latinx immigrants have poorer access to health care, compared to non-Latinx Whites. Federally-Qualified Health Centers (FQHCs) provide clinical and community programing to address their clients’ he...
Development of the feeding apparatus in decapod crustaceans

The literature describing the larval development and metamorphosis of decapod crustaceans is reviewed for information concerning the feeding apparatus — the external mandibles and the internal gastric mill and filter of the stomach. The Caridea is the only group in which the masticating mandibles of the larvae are retained after metamorphosis and in which the gastric mill may be functionally reduced or absent in all postlarval stages. The Astacidea, Thalassinidea, and Palinura lack grinding mandibles, even in the larval stages. In the Dendrobranchiata, Anomura, and Brachyura, the function of mastication shifts from the mandibles to the stomach at metamorphosis. Anatomical changes in the feeding apparatus correspond to the changes in behavior, habitat, and diet that occur at metamorphosis.
Resilient Data : An Interdisciplinary Approach

Cybersecurity continues the migration toward data-informed solutions and the quality of the data is gaining in importance. Data accuracy is foundational to the trustworthiness required of artificial intelligence solutions. Trustworthy data must be accurate, robust, resistant and resilient to unauthorized modifications, going beyond traditional security solutions that perform data integrity checking. Cyber-physical systems present unique challenges with physical outcomes.Cyber-physical systems present unique challenges in achieving trustworthy data. The combination of security data and safety data is unique. Capturing both sets of data and determining the accuracy of that data requires an interdisciplinary approach. This effort describes the merging of information theory and information security constructs along with physical systems data. Knowledge is needed in control systems engineering, cybersecurity and information theory. As training data that informs decisions and feeds artificial intelligence algorithms accuracy and resilience are important.Resilient data is trustworthy data that represents a research challenge offering an opportunity to apply lessons learned from information disorders into the broader cybersecurity environment including the cyber-physical systems that power much of the US critical infrastructure. Creating resilient data, for use as training data requires data be examined in ways that have not historically been a part of traditional cybersecurity analysis. This effort describes a proposed method of contextually evaluating cyber-physical systems security data in order to determine the accuracy of the data and in the event of tampering, reconstitute the data to the last known trustworthy state.
Do Traditional Real Estate ETFs Increase the Volatility of REITs

We examine the impact of the introduction of traditional, non-U.S., real estate exchange traded funds (ETFs) on the realized volatility of real estate ETFs’ component stocks in a global setting. We...
The psychosocial impact of COVID-19 within the first six months of the pandemic on youth with epilepsy and their caregivers.

Abstract Objectives We assessed the impact of COVID-19 on children with epilepsy and their families, focusing on epilepsy management, family routines, learning, and adherence to Centers for Disease Control and Prevention (CDC) pandemic guidelines (e.g., social distancing, mask wearing) within the first six months of the pandemic. Group differences in COVID-19 impact on families were also examined based on race and ethnicity, being medically and/or geographically underserved, and insurance status. Methods Participants (n = 131) included children with epilepsy and their families from two clinical trials. The Impact of COVID-19 on Pediatric Epilepsy Management (ICPEM) measure was developed and administered to caregivers online from April 2020 to September 2020 across four large pediatric hospitals. Administration of the ICPEM occurred both during routine study assessments and an additional acute time point to obtain information early in the pandemic (e.g., April and May 2020). Descriptive statistics and t-tests were used for analyses. Results Data indicate minor to moderate impact of COVID-19 on pediatric epilepsy management. Caregivers of children with epilepsy reported the most impact on education and social functioning. Adherence to CDC guidelines was reported to be high. Those having public insurance reported greater difficulties obtaining daily anti-seizure medications compared to those with private insurance. Conclusions This study presents important initial data regarding the impact of COVID-19 epilepsy management and daily functioning in children with epilepsy and their families. While the acute impact of COVID-19 restrictions appear to be mild to moderate, it is unclear what the long-term impact of the pandemic will be on families of children with epilepsy.
Bridging the Metabolic Parallels Between Neurological Diseases and Cancer

Despite the many recent breakthroughs in cancer research, oncology has traditionally been seen as a distinct field from other diseases. Recently, more attention has been paid to repurposing established therapeutic strategies and targets of other diseases towards cancer treatment, with some of these attempts generating promising outcomes [1, 2]. Recent studies using advanced metabolomics technologies [3] have shown evidence of close metabolic similarities between cancer and neurological diseases. These studies have unveiled several metabolic characteristics shared by these two categories of diseases, including metabolism of glutamine, gamma-aminobutyric acid (GABA), and N-acetyl-aspartyl-glutamate (NAAG) [4-6]. The striking metabolic overlap between cancer and neurological diseases sheds light on novel therapeutic strategies for cancer treatment. For example, 2-(phosphonomethyl) pentanedioic acid (2-PMPA), one of the glutamate carboxypeptidase II (GCP II) inhibitors that prevent the conversion of NAAG to glutamate, has been shown to suppress cancer growth [6, 7]. These promising results have led to an increased interest in integrating this metabolic overlap between cancer and neurological diseases into the study of cancer metabolism. The advantages of studying this metabolic overlap include not only drug repurposing but also translating existing knowledge from neurological diseases to the field of cancer research. This chapter discusses the specific overlapping metabolic features between cancer and neurological diseases, focusing on glutamine, GABA, and NAAG metabolisms. Understanding the interconnections between cancer and neurological diseases will guide researchers and clinicians to find more effective cancer treatments.
COVID-19 and Seizures

Abstract This chapter illustrates the effect of the coronavirus disease 2019 (COVID-19) infection in relation to seizures. One of the neurological manifestations of COVID-19 infection includes seizures that are commonly described in other various viral infections and could occur secondary to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and seizures in those who have epilepsy. Status epilepticus, focal and generalized seizures, and nonepileptic seizures could occur. In this chapter, predisposition to the occurrence of seizures is discussed, along with electroencephalography (EEG) findings and management of the condition. Lastly, the impact of the COVID-19 pandemic in this patient population and caregivers is reviewed, along with changes required in health-care systems to manage and provide relevant patient care.
Voter Information and Cues in Direct Legislation Settings

In this paper, we model lobbying and the initiative process as a one-shot game between groups of citizens and the legislature. We model voters as random utility maximizers, as in McKelvey and Patty (2000). Our solution concept is Bayes equilibrium in weakly undominated strategies. Modeling the legislature as an agenda setter, as in Romer and Rosenthal (1978, 1979a, 1979b), we find that it can play an important informational role for voters. In equilibrium, voters make inferences about the expected utility of a proposed initiative if the legislature fails to enact it. This inference is strictly decreasing in group size, implying that voters should be more skeptical of initiatives proposed by larger interest groups. In addition, the expected value of an initiative to members of the sponsoring group is negatively correlated with the expected value to nonmembers, leading to an incentive for groups to misrepresent their expected benefits from an initiative. By using only the simple cues of group size and rejection by the legislature, voters make choices closer to those of fully informed voters. The paper includes simulation results to illustrate its predictions.
Effect of Race and Sex on Primary Care Physicians' Diagnosis and Treatment of Late-Life Depression

Objectives: To examine primary care physician (PCP) contributions toward racial and sex differences in the diagnosis and treatment of late-life depression. Design: Survey using a computerized instrument incorporating video interviews and text, with volunteer PCPs randomly assigned to one of four standardized video vignettes of an elderly patient depicting late-life depression. Vignettes differed only in the patient/actor's race (white/African-American) or sex. Setting: American Academy of Family Physicians meeting, San Diego, California, 2002. Participants: One hundred seventy-eight U.S.-practicing postresidency PCPs who were asked to participate in a clinical decision-making study. Measurements: The computerized survey instrument assessed PCPs' diagnoses, first-line treatment and management recommendations, and judgment of personal characteristics/behaviors for the patients in the vignettes. Results: Eighty-five percent of all PCPs correctly diagnosed the elderly patient(s) with major depression. There were no significant differences in the diagnosis of depression, treatment recommendations, or PCP assessment of most patient characteristics by the race or sex of the patient/actor in the vignette, but PCP characteristics, most notably the location of medical school training (U.S. vs international), affected the likelihood of a depression diagnosis and treatment recommendations. Conclusion: Given standardized symptom-pictures, PCPs are just as likely to diagnose and treat depression in African-American as in white older people, suggesting that bias based simply on apparent patient race is not a likely explanation for the lower rates of depression diagnosis and treatment in older African Americans. PCPs who have trained at international medical schools may benefit from targeted training initiatives on the diagnosis and treatment of late-life depression.
Multicenter crossover comparison of the safety and efficacy of Intraglobin-F with Gamimune-N, Sandoglobulin, and Gammagard in patients with primary immunodeficiency diseases.

The safety and clinical efficacy of a liquid, β-propiolactone-stabilized intravenous γ-globulin, Intraglobin-F, was evaluated in a multicenter, double-blind study comparing Intraglobin-F to Gamimune-N, Sandoglobulin, or Gammagard. β-Propiolactone stabilizes the IgG molecule to decrease aggregate formation and is a potent virucidal agent that reduces the risk of viral transmission by intravenous γ-globulin (IVIG) preparations. Twenty-seven patients with primary immunodeficiency diseases were enrolled at three centers. Each patient received 6 months of therapy with either Intraglobin-F or the IVIG preparation that they had received during the preceding 3 months, then crossed over to the other preparation. Twenty-three patients completed the study. One patient withdrew because of an adverse event, generalized urticaria. A second patient withdrew because of fatigue and perceived decreased efficacy. Adverse reactions were comparable and occurred in 8.7% of the infusions of Intraglobin-F and 6% of the infusions with Sandoglobulin. None were severe or life-threatening. There was no discernible difference in efficacy between any of the products. The number of days when patients noted symptoms in their diaries was similar for Intraglobin-F and the comparison preparations, 4158 vs 4143. Similarly, there were no differences in the number of physician visits (33 vs 22), days missed from work or school (405 vs 404), days with fever (41 vs 47), or days of prophylactic antibiotics (675 vs 642). There was an increase in the number of days when antibiotics were given therapeutically (578 vs 451); most of the difference was attributable to one patient. There also was a difference in the number of days of hospitalization (21 vs 0), but 19 of the days were accounted for by two patients. When the patients were asked to score their feeling of well-being on a scale of 1 to 5, with 1 being entirely well, the mean score for the patients on Intraglobin-F was 1.86 (range, 1.0 to 3.0), compared to 1.85 (range, 1.0 to 3.2) for patients while on the comparison preparations. Trough IgG levels were slightly lower during the period when patients were treated with Intraglobin-F compared to the other products. There were no abnormalities in blood chemistries or hematologic parameters. Thus, Intraglobin-F is comparable to three of the marketed IVIG preparations in efficacy and safety, as well as patient acceptability, and offers the additional benefit of an extra virucidal step to reduce further the risk of transmitting viral infections.
Be Skeptical of Rigid ‘In Extremis’ Dogma Beyond COLREGS

In marine collision law, the in extremis doctrine is commonly thought to include three concepts: (1) a definition of the “in extremis situation,” by which is meant a situation where two vessels have approached so closely that collision can no longer be avoided by one ship acting alone; (2) a release from strict compliance with the Collision Regulations when necessary to avoid immediate danger; and (3) the more lenient standard of care applied in the subsequent legal proceedings to an innocent vessel that was confronted with a sudden emergency that did not allow time for a carefully considered decision before taking avoiding action. This paper explores the two theoretical approaches to collision avoidance maneuvers when a vessel finds itself in extremis. The first is the "universal rules" approach developed by Commander Davis Lott, a former naval officer. The second approach rejects the proposition that maneuvers can be determined in advance.
La Longue durée: A Reply to Joseph Nechvatal

Joseph Nechvatal \'La Beaute tragique: Olkowski, Deleuze, and the \'Ruin of Representation\'\' _Film-Philosophy_, Deleuze Special Issue vol. 5 no. 36, November 2001
Risk factors and prevention of proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is the most common complication after repair of a retinal detachment. It is a clinical syndrome characterized by fibrocellular proliferation resulting in the formation of fibrotic epiretinal (i.e., preretinal and subretinal) membranes. Despite improvements in surgical techniques and anatomical outcomes, the treatment of PVR remains a challenge to preserve functional vision. PVR represents a wound healing response and multiple cytokines and growth factors may play a key role in its development. One of the most critical steps in the development of PVR is transformation of retinal pigment epithelium cells into fibroblastic and myofibroblastic phenotypes, which results in proliferation of fibrocellular membranes. Contraction of the membranes causes tractional retinal detachment. Treatment of PVR includes meticulous removal of fibrocellular membranes, relieving traction on all retinal breaks and intraocular tamponade. Several pharmacologic agents have demonstrated effectiv...
A lytic transglycosylase homologue, PleA, is required for the assembly of pili and the flagellum at the Caulobacter crescentus cell pole

Two distinct protein complexes, the flagellum and the pilus biogenesis machinery, are asymmetrically assembled at one pole of the Caulobacter predivisional cell. Cell division yields dissimilar daughter cells: a stalked cell and a swarmer cell that assembles several pili at the flagellated cell pole. Strains bearing mutations in the pleA gene are pililess and non-flagellated. The PleA protein contains a region that is similar to a peptidoglycan-hydrolytic active site, and a point mutation at this site in PleA results in the loss of flagellum and pili biogenesis. PleA was found to be required for the insertion of the outer membrane pilus secretion channel at the cell pole and for the accumulation of the PilA pilin subunit. PleA is also required for the assembly of substructures of the flagellar basal body hook complex that are located in or traverse the peptidoglycan layer. These results argue that PleA facilitates the assembly of envelope-spanning structures at the cell pole. In support of this, PleA was found to be present only during a short interval in the cell cycle that coincides with the assembly of the flagellum and the pilus secretion apparatus.
Nano/micromotors for security/defense applications. A review

The new capabilities of man-made micro/nanomotors open up considerable opportunities for diverse security and defense applications. This review highlights new micromotor-based strategies for enhanced security monitoring and detoxification of chemical and biological warfare agents (CBWA). The movement of receptor-functionalized nanomotors offers great potential for sensing and isolating target bio-threats from complex samples. New mobile reactive materials based on zeolite or activated carbon offer considerable promise for the accelerated removal of chemical warfare agents. A wide range of proof-of-concept motor-based approaches, including the detection and destruction of anthrax spores, 'on-off' nerve-agent detection or effective neutralization of chemical warfare agents have thus been demonstrated. The propulsion of micromotors and their corresponding bubble tails impart significant mixing that greatly accelerates such detoxification processes. These nanomotors will thus empower sensing and destruction where stirring large quantities of decontaminating reagents and controlled mechanical agitation are impossible or undesired. New technological breakthroughs and greater sophistication of micro/nanoscale machines will lead to rapid translation of the micromotor research activity into practical defense applications, addressing the escalating threat of CBWA.
Dietary Copper in the Physiology of the Microcirculation

Dietary copper has long been known to be essential for cardiovascular homeostasis. However, the role of copper and cuproenzymes in the normal control of vascular physiology is not well understood. Most studies in the cardiovascular system have focused on copper deficiency-induced defects in the heart or large vessels. Recently, attention has also focused on the effects of copper deficiency in the microcirculation or the small blood vessels that control blood flow, nutrient and waste exchange, and peripheral vascular resistance. Studies in the microcirculation demonstrate that copper is important in mechanisms of macromolecular leakage, platelet-endothelial interactions and vascular smooth muscle reactivity. There is a significantly greater leakage of proteins from postcapillary venules in copper-deficient rats in response to mast cell-released histamine. This response appears to be the result of increased numbers of mast cells and thereby increased available histamine. Copper deficiency also causes an inhibition of in vivo thrombogenesis, which appears to be related to an inhibition of platelet adhesion. Subsequent studies have demonstrated that this is probably caused by a diminished concentration of the adhesion molecule von Willebrand factor. Nitric oxide (NO)-mediated arteriole vasodilation is also compromised in copper-deficient rats. This functional deficit to NO can be reversed by the addition of Cu, Zn-superoxide dismutase (SOD), suggesting that degradation of NO by superoxide anion occurs during copper deprivation. These observations demonstrate that dietary copper is necessary for several microvascular control mechanisms affecting inflammation, microhemostasis and regulation of peripheral blood flow.
Lateral retinacular release as a function of femoral component rotation in total knee arthroplasty.

A consensus exists in the orthopaedic community that proper rotational placement of components may reduce the need for lateral release. This study compares the rates and results of lateral release before and after femoral component placement was defined by the transepicondylar axis (TEA). Between 1990 and 1991, 104 primary total knee arthroplasties (TKA) were reviewed during which equal amounts of bone from the posterior femoral condyles were removed. In this group, the lateral release incidence was 24% for varus deformities and 33% for valgus deformities. When the femoral component was externally rotated approximating the TEA, a review of 246 primary TKAs performed between 1998 and 1999 showed lateral release rates of 7% in varus deformities and 29% in valgus deformities. This study documents the statistically significant decline in the lateral release rate with external rotation of the femoral component during TKA in varus deformities (P<.0001), and a decreasing trend in valgus knees (P = .09).
Charge States and Charge-Changing Cross Sections of Fast Heavy Ions Penetrating Through Gaseous and Solid Media

This review surveys the experimental and theoretical situation concerning charge states and charge-changing cross sections of heavy ions up to and including uranium, which penetrate through gaseous and solid targets with velocities primarily in the range ${v}_{0}lvlZ{v}_{0}$ (${v}_{0}=\frac{{e}^{2}}{\ensuremath{\hbar}}=2.188\ifmmode\times\else\texttimes\fi{}{10}^{8}$ cm/sec). Particular emphasis is given to ions with atomic numbers in the range $16\ensuremath{\le}Z\ensuremath{\le}92$. The published literature is covered through August 1971. General physical and mathematical relations are outlined which describe the composition of charge states in a heavy-ion beam which passes through matter. Recent experimental techniques and methods of data analysis are summarized. Extensive experimental results on heavy-ion equilibrium charge state distributions, average equilibrium charge states, and cross sections for capture and loss of one or more electrons in single encounters with target atoms are presented and critically examined. The data extend to ions as heavy as uranium and energies up to \ensuremath{\sim}400 MeV. Systematic trends are emphasized and generalizations are discussed which allow interpolations and to some extent extrapolations of the data to be made to ranges which have not been investigated experimentally. Attention is given to the cross sections for multiple-electron loss which are relatively large but which are poorly understood. We deal with effects of residual ion excitation on charge-changing collisions in the light of recent experimental results. It is shown that the average equilibrium charge of heavy ions can be approximated by utilizing both theoretical concepts which originate from the work of Bohr and Lamb, and semiempirical relations which are based on observed regularities of the data. Recent interpretations of phenomena associated with density effects, i.e., with the increase of projectile ionization which is observed for increasing target densities, are scrutinized and refinements of the theory by Bohr and Lindhard are explored.
A validated gas chromatographic-electron impact ionization mass spectrometric method for methamphetamine, methylenedioxymethamphetamine (MDMA), and metabolites in mouse plasma and brain.

A method was developed and fully validated for simultaneous quantification of methamphetamine (MAMP), amphetamine, hydroxy-methamphetamine, methylenedioxymethamphetamine (MDMA, ecstasy), methylenedioxyamphetamine, 3-hydroxy-4-methoxy-methamphetamine, and 3-hydroxy-4-methoxy-amphetamine in 100 μL mouse plasma and 7.5 mg brain. Solid phase extraction and gas chromatography–electron impact ionization mass spectrometry in selected-ion monitoring mode achieved plasma linear ranges of 10–20 to 20,000 ng/mL and 0.1–0.2 to 200 ng/mg in brain. Recoveries were greater than 91%, bias 92.3–110.4%, and imprecision less than 5.3% coefficient of variation. This method was used for measuring MAMP and MDMA and metabolites in plasma and brain during mouse neurotoxicity studies.
Tumor necrosis factor-alpha and its second messenger, ceramide, stimulate apoptosis in cultured ovarian follicles

In the mammalian ovary, only a small fraction of follicles fully mature and ovulate, while most of them die via apoptosis. Multiple factors promoting follicle survival have been identified, but intraovarian mediators of apoptosis are poorly known. Tumor necrosis factor-alpha (TNF alpha) is a cytokine capable of inducing apoptosis in diverse cell types, and the apoptotic effect of TNF alpha is, partially, coupled to the sphingomyelin signaling pathway with ceramide as a second messenger. Because TNF alpha has been localized in the rat ovary, and TNF alpha treatment increases granulosa cell ceramide production, we studied the effect of treatment with TNF alpha and ceramide on follicle apoptosis. Immature rats were implanted with diethylstilbestrol to stimulate the development of early antral follicles. Follicles were isolated and cultured in a serum-free medium for 24 h with or without hormone treatments. During culture, spontaneous follicle apoptosis occurred (10-fold increase in DNA fragmentation), which was partially blocked by 100 ng/ml FSH (60% suppression). The effect of FSH was counteracted by TNF alpha in a dose-dependent manner, with the maximal effect at 100 ng/ml TNF alpha (90% reversal of FSH action). In situ analysis indicated that the granulosa cell is the follicle cell type undergoing DNA fragmentation. A membrane-permeable ceramide analog, C2-ceramide N-acetyl sphingosine, mimicked the effect of TNF alpha and was able to completely abolish the action of FSH at 50 microM. In contrast, another ceramide analog, C2-dihydroceramide N-acetyl dihydrosphingosine, did not alter the effect of FSH, verifying the specificity of ceramide action. To study the mechanism of TNF alpha and ceramide action, the effect of sodium aurathiomalate (ATM), an inhibitor of interleukin-1 beta-converting enzyme/ced-3-related cystine proteases known to be essential in the execution of mammalian cell apoptosis, was studied. Treatment with ATM (1 mM) prevented the apoptosis-inducing effect of both TNF alpha and ceramide, suggesting a role for cysteine proteases in mediating follicle apoptosis. Treatment with either TNF alpha or ceramide increased both basal and FSH-stimulated progesterone production by cultured follicles. Concomitant treatment by ATM did not alter the stimulatory effect of TNF alpha or ceramide on progesterone production, ruling out nonspecific toxic effect of the inhibitor and indicating that the apoptotic and steroidogenic pathways are independent. In summary, treatment with TNF alpha or its second messenger, ceramide, stimulates apoptosis of early antral follicles in culture, suggesting a potential role for TNF alpha as an intraovarian regulator of follicle atresia by acting through the ceramide signaling pathway.
Reactivity of an FAD-dependent oxygenase with free flavins: a new mode of uncoupling in flavoprotein oxygenases.

Abstract Conversion of 2-methyl-3-hydroxypyridine-5-carboxylic acid (Cpd I) to α-(N-acetylaminomethylene)succinic acid (Cpd A) is catalyzed by an FAD protein, Cpd I oxygenase ( Sparrow, et al., J. Biol. Chem. [1969] 244 , 2590–2600 ) according to the equation: Cpd I + O2 + NADH + H+ → Cpd A + NAD+. When free FAD, FMN or riboflavin is added to reaction mixtures, oxidation of NADH remains dependent on presence of oxygenase and Cpd I, but is partially uncoupled from the oxygenation of Cpd I. Under these conditions, free reduced flavins appear in solution, as shown by their ability to reduce cytochrome c. These effects are not due to an increased rate of NADH oxidation. Such uncoupling may lead to appearance of artifactual species of activated oxygen or flavin that play no intermediate role in the oxygenase reaction.
Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature

Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed 'autoimmune thrombotic thrombocytopenic purpura'. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2-3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors.
Photon-insensitive, thermal to fast neutron detector

Abstract Superheated drops of dichloro-difluoro methane at room temperature and atmosphere pressure vaporize when exposed to thermal, intermediate, and fast neutrons. A mechanism for the thermal sensitivity is proposed.
A novel method for accelerated composting of coir pith

Hillocks of coir pith accumulate in the vicinity of coconut coir-fiber extraction units, of which disposal and management remain a major problem. Southern states of India, especially Kerala, Tamil Nadu, Andhra Pradesh, Karnataka, and Orissa, face this problem. A simple technology for accelerated composting of coir pith was developed, and on-site composting of coir pith hillocks was demonstrated. The composting of pith was complete in 21 days. The composted pith was an excellent organic manure, with a reduced C/N ratio of 20:1, pH of about 6.5, and electrical conductivity of 0.23 dS/cm, making it a more desirable soil organic manure. The composted pith did not contain or carry weeds and undesirable pathogens, thus providing a rich soil environment for plant and vegetation growth.
Extension of the continuum model for transport phenomena occurring during metal alloy solidification—I. The conservation equations

Abstract In this study, models for simulating transport phenomena occurring during solidification of a binary metal alloy are reviewed, with emphasis placed on the benefits and shortcomings of existing continuum and two-phase approaches. Linkages between the two approaches are discussed, and volume-averaging procedures inherent in the two-phase model are used to develop an extension of the continuum model which retains its computational convenience, while eliminating its inability to treat important features such as solutal undercooling, nucleation, stereological characteristics of the solid/liquid interface, solid movement in the form of floating or settling crystals, and shrinkage. Two approaches to development of a mixture momentum equation are considered, one involving evolution from the liquid momentum conservation equation and the other involving summation of the liquid and solid momentum equations. Special features of both approaches are discussed. In a companion paper, additional models are developed to account for the transport (floating and settling) of solid crystals in the melt, solutal undercooling, and nucleation.
RNA-catalysed RNA polymerization using nucleoside triphosphates

The hypothesis that certain RNA molecules may be able to catalyse RNA replication is central to current theories of the early evolution of life. In support of this idea, we describe here an RNA that synthesizes RNA using the same reaction as that employed by protein enzymes that catalyse RNA polymerization. In the presence of the appropriate template RNA and nucleoside triphosphates, the ribozyme extends an RNA primer by successive addition of up to six mononucleotides. The added nucleotides are joined to the growing RNA chain by 3',5'-phosphodiester linkages. The ribozyme shows marked template fidelity: extension by nucleotides complementary to the template is up to 1,000 times more efficient than is extension by mismatched nucleotides.
Investigations of self-absorption in a radio-frequency glow discharge device

The self-absorption behavior of a radio-frequency glow discharge atomic emission device has been studied with Fourier transform spectrometry. Using a resonant transition of a major element, it has been shown that for this device the potential for self-absorption is severe, and no analytically useful discharge conditions that significantly reduce that potential were found. In fact, it is unlikely that such conditions can be found, even with a more exhaustive study. Therefore, there is no compelling reason to alter the discharge conditions that would typically be employed for analyses with the device. Based on the potential for self-absorption, it is advisable to use non-resonant, rather than resonant, transitions of major elements for analytical purposes. On the other hand, the use of resonant transitions of minor or trace elements appears to be free from any significant danger of analytical error induced by self-absorption. However, further studies are needed to validate this conclusion over a wider range of analytes, transitions, sample types, and discharge conditions. Owing to the fact that self-absorption is influenced by the subtleties of the design of a glow discharge device, such as the placement of a vacuum port, these results should not be assumed to be wholly applicable to other glow discharge devices.
Primary Substrate Specificity Determinants for the H4-Specific Protease-Activated Protein Phosphotransferase

The specificity of the histone-H4-specific, protease-activated protein kinase (H4-PK) was examined using two series of synthetic peptides corresponding to the phosphorylation sites in histone H4 and pyruvate kinase. Optimum kinetic constants for phosphorylation were observed using the peptide Val-Lys-Arg-Ile-Ser-Gly-Leu. Peptides in which the Lys was replaced by Arg or the Lys-Arg sequence was transposed were phosphorylated with less favorable kinetics. Peptides with either basic residue deleted did not serve as substrates. Only the H4 peptide, containing an Arg-Arg sequence, was phosphorylated by the cyclic-AMP-dependent protein kinase (CA-PK). Distinct specificity determinants for H4-PK and CA-PK were also observed using the pyruvate kinase peptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly). Collectively the data indicated that the primary substrate specificity determinants for H4-PK are Lys-Arg-Xaa-Ser whereas the CA-PK selectively phosphorylates the sequence Arg-Arg-Xaa-Ser.
An analysis of some short-term health effects of air pollution in the Washington, D.C. metropolitan area☆

Abstract This study assesses some of the short-term health effects of air pollution in Washington, D.C. Specifically, regression models are formulated to explain health-care visits to a group practice medical care plan. Primary interest is focused on the effects of mobile-source air pollutants, particularly photo-chemical oxidants. Meteorological conditions, as well as other variables thought to influence the consumption of medical services, are included in the models as explanatory variables. The study found only a small effect of air pollution levels on the health-care visits to the group practice.
Xanthogranulomatous pyelonephritis, the gatekeeper's dilemma : a contemporary look at an old problem

Abstract Objectives To review 12 patients with a clinicopathogenic diagnosis of xanthogranulomatous pyelonephritis (XGP) and to determine if a computed tomography (CT) scan is the imaging procedure of choice for diagnosis. Methods A retrospective review, over the last 12 years, of patients with XGP at our institution. Results Nine of 10 patients (90%) who were evaluated by CT scan had the correct diagnosis made prior to nephrectomy. The most common presenting symptoms and signs were flank pain (64%), leukocytosis (73%), and anemia (82%). Seventy-five percent of the patients had a ureteropelvic junction stone or a staghorn stone in the affected kidney at the time of clinical presentation. Proteus was the most common organism cultured. Conclusions After reviewing the clinical features of these 12 patients, we recommended CT scan to evaluate the patient in whom clinical suspicion of XGP is entertained. CT has proven to be the most accurate imaging study to evaluate this disease.
Evolution of catalytic RNA in the laboratory

We are interested in the biochemistry of existing RNA enzymes and in the development of RNA enzymes with novel catalytic function. The focal point of our research program has been the design and operation of a laboratory system for the controlled evolution of catalytic RNA. This system serves as working model of RNA-based life and can be used to explore the catalytic potential of RNA. Evolution requires the integration of three chemical processes: amplification, mutation, and selection. Amplification results in additional copies of the genetic material. Mutation operates at the level of genotype to introduce variability, this variability in turn being expressed as a range of phenotypes. Selection operates at the level of phenotype to reduce variability by excluding those individuals that do not conform to the prevailing fitness criteria. These three processes must be linked so that only the selected individuals are amplified, subject to mutational error, to produce a progeny distribution of mutant individuals. We devised techniques for the amplification, mutation, and selection of catalytic RNA, all of which can be performed rapidly in vitro within a single reaction vessel. We integrated these techniques in such a way that they can be performed iteratively and routinely. This allowed us to conduct evolution experiments in response to artificially-imposed selection constraints. Our objective was to develop novel RNA enzymes by altering the selection constraints in a controlled manner. In this way we were able to expand the catalytic repertoire of RNA. Our long-range objective is to develop an RNA enzyme with RNA replicase activity. If such an enzyme had the ability to produce additional copies of itself, then RNA evolution would operate autonomously and the origin of life will have been realized in the laboratory.
A Novel Family of Toxoplasma IMC Proteins Displays a Hierarchical Organization and Functions in Coordinating Parasite Division

Apicomplexans employ a peripheral membrane system called the inner membrane complex (IMC) for critical processes such as host cell invasion and daughter cell formation. We have identified a family of proteins that define novel sub-compartments of the Toxoplasma gondii IMC. These IMC Sub-compartment Proteins, ISP1, 2 and 3, are conserved throughout the Apicomplexa, but do not appear to be present outside the phylum. ISP1 localizes to the apical cap portion of the IMC, while ISP2 localizes to a central IMC region and ISP3 localizes to a central plus basal region of the complex. Targeting of all three ISPs is dependent upon N-terminal residues predicted for coordinated myristoylation and palmitoylation. Surprisingly, we show that disruption of ISP1 results in a dramatic relocalization of ISP2 and ISP3 to the apical cap. Although the N-terminal region of ISP1 is necessary and sufficient for apical cap targeting, exclusion of other family members requires the remaining C-terminal region of the protein. This gate-keeping function of ISP1 reveals an unprecedented mechanism of interactive and hierarchical targeting of proteins to establish these unique sub-compartments in the Toxoplasma IMC. Finally, we show that loss of ISP2 results in severe defects in daughter cell formation during endodyogeny, indicating a role for the ISP proteins in coordinating this unique process of Toxoplasma replication.