cssi/SciSciGPT-SciSciNet huggingface dataset:
The Transfusion Iron Overload Score Is a Potential Predictor of Survival in Stem Cell Transplant Patients.

Abstract Iron overload at the time of bone marrow transplantation has recently been associated with increased mortality. The mechanism by which iron overload negatively impacts survival is unclear. In an effort to better define iron overload and its potential role in the transplant setting, we examined 78 consecutive patients at risk for transfusion-related iron overload (AML, ALL, MDS, and aplastic anemia) undergoing either autologous or allogeneic stem cell transplant at our institution between 1999 and 2004. To estimate transfusion-related iron overload, we devised a novel scoring system based on routinely available laboratory variables obtained prior to transplant. In our scoring system, a single point was awarded for each of the following: 1. number of red cell units transfused prior to transplantation > 25; 2. serum ferritin > 1000 ng/ml; and 3. a semi-quantitative bone marrow iron stain of 6+. The Transfusion Iron Overload Score (range of 0 to 3) predicted for overall survival in our patient sample (Fig. 1, p = 0.0003 by Kaplan-Meier log rank trend) and was more powerful than using serum ferritin alone (p = 0.02). The calculated score retained its significant association with overall survival while controlling for traditional risk factors (age, sex, diagnosis, transplant type, donor relation, and remission status), inflammation (c-reactive protein), and measures of organ damage (transaminases, total bilirubin, INR, and cardiac ejection fraction) (p = 0.04 by Cox proportional-hazards regression). The 27 patients (35%) with a high score (≥ 2) had a dramatically lower median survival of 5.0 months compared to 29.3 months in those with an iron score of less than two (unadjusted hazard ratio of 2.5; 95% CI of 1.6 to 6.3). The observed mortality seen in those with a high score was primarily attributable to treatment-related mortality (p = 0.018) rather than disease-related mortality (p = 0.48). This finding likely accounts for the significant survival impact of iron overload seen in the allogeneic (p = 0.006) but not the autologous (p = 0.48) subgroup. In conclusion, the Transfusion Iron Overload Score served as a strong independent predictor of survival in our stem cell transplant population, identifying patients at significant risk for early treatment-related mortality. Our results lend further support to the notion that iron overload is detrimental in the transplant setting, and for the first time suggest that transfusion-related iron overload increases mortality via a mechanism independent of pre-existing inflammation and end-organ dysfunction. Download : Download high-res image (70KB) Download : Download full-size image Figure 1 . Overall post-transplant survival by the Transfusion Iron Overload Score.
Activation of Nrf2 Translation by a Keap1 Independent Mechanism

Nuclear factor (erythroid-derived 2)-like 2 (nrf2) is the master regulator of the antioxidant response, and its function is tightly regulated at the transcription, translation, and post-translational level. It is well known that Keap1 regulates Nrf2 signaling but the Nrf2 regulation at the translation level and its chemical modulation is less documented. Here, we show a complementary way to promote an increase in the Nrf2 levels by overcoming its basal translational repression thus opening the possibility for the discovery of novel alternatives for promoting cellular protection against oxidative stress. We developed a novel reporter system that allowed for the identification of natural compounds present in the human diet as inducers of Nrf2 translation by a mechanism independent of Keap1-mediated degradation. Apigenin, resveratrol and piceatannol were identified as inducers of Nrf2 translation. More importantly, the newly synthesized Nrf2 overcomes keap1-regulation, translocates to the nuclei and activates the antioxidant response. We conclude that Nrf2 translational control is physiologically relevant and can be regulated by apigenin. Also, targeting this mechanism could provide new insights into prevention and treatment of multiple diseases where oxidative stress plays a major role.
Abnormal Global Longitudinal Strain Predicts Future Deterioration of Left Ventricular Function in Heart Failure Patients With a Recovered Left Ventricular Ejection Fraction.

Background—Patients with recovery of left ventricular ejection fraction (LVEF) remain at risk for future deterioration of LVEF. However, there are no tools to risk stratify these patients. We hypot...
The “Non-viral” Approach for siRNA Delivery in Cancer Treatment: A Special Focus on Micelles and Liposomes

Over the past two decades, small interfering RNA (siRNA) has gained widespread popularity as an efficient tool for cancer therapy. Unfortunately, due to its inherent instability, the progress in the field has yet to hit a benchmark with no marketed siRNA formulations for cancer, yet. siRNA delivery via nonviral carriers have recently generated immense interest and this chapter is an attempt at a comprehensive coverage of liposomes and micelles as non-viral siRNA delivery systems. The myriad of options and recent advancements with respect to these nanocarriers in cancer therapy are discussed here.
Preoperative Evaluation of a Patient for Peritoneal Dialysis Catheter

Preoperative evaluation for placement of a peritoneal dialysis catheter by fluoroscopically or peritoneoscopically guided method entails a detailed history and physical examination to determine anatomic barriers to placement of the catheter and risk factors that could indicate a likelihood of perioperative complications. Recommended pre-procedure tasks are discussed. Complications common to patients with chronic kidney disease undergoing this procedure are addressed. This chapter reviews recommendations of pre-procedure testing.
Measuring Response Rate and Increasing Satisfaction in Innovative Environments: The Impact of Feedback

Engineering productivity has been a popular topic of discussion from both an employee and employer perspective. Through rigorous experimentation and multi-methods approach, alongside subjective responses, we saw significant improvements in our engineering system. This paper reflects over a year of learnings on methods to increase response rates and designing surveys for monitoring and impacting both efficiency and satisfaction for internal developers. Measuring these concepts became important as we were making significant changes to our engineering system. These methods can be applied in other contexts to increase response rates and monitor satisfaction overtime.
The lymphocyte uropod: a specialized surface site for immunologic recognition.

Functional specialization of the cell surface of motile protozoa such as the Paramecium and amoeba are generally recognized (Ambrose and Forrester, 1968; Wolpert and Gin-gell, 1968). Less well appreciated is the existence of differentiated surface membranes on mammalian leukocytes. In this laboratory we have been interested in a modification of the lymphocyte surface called the uropod, an area consisting of microvillus projections of cell membrane adjacent to the golgi-associated cell pole. The cytoplasm contained in the uropod is rich in microtubules, mitochondria, endoplasmic reticulum, and numerous endocytic vesicles, and is quite distinct from the pseudopod region which contains few such subcellular organelles. Moreover, the uropod is not engaged in cell motility as is the pseudopod. The lymphocyte surface membrane functions in immunologic recognition, cell cooperation, and cell-mediated cytotoxicity in an as yet undefined manner. Circumstantial evidence suggests that the uropod may represent the site of such interactions.
The Search for New Chemical Oscillators

Before 1980, the only chemical oscillators of nonbiological origin had been discovered by chance or were variants of the two accidentally discovered systems. Since that time, experimental and theoretical advances have made it possible to systematically design new oscillating chemical reactions.
Tolerability of long-term fluconazole therapy.

BACKGROUND Fluconazole is a commonly prescribed first-generation triazole antifungal. Although the toxicity profile of fluconazole has been evaluated in clinical trials, there are scant data regarding its tolerability with long-term therapy. Treatment guidelines for coccidioidomycosis recommend fluconazole therapy and severe or disseminated infections can require lifelong treatment. OBJECTIVES To assess the prevalence of long-term fluconazole adverse effects, their consequences for antifungal therapy, time to adverse effects and the association between dosing regimen or fluconazole serum level and adverse effect status. METHODS We conducted a single-centre, retrospective study of adult patients (≥18 years) with proven or probable coccidioidomycosis receiving long-term fluconazole therapy for an intended duration of ≥28 days. RESULTS Out of 124 patients included, 64 (51.6%) experienced adverse effects. The most common adverse effects were xerosis (16.9%), alopecia (16.1%) and fatigue (11.3%). Of the 64 patients experiencing adverse effects, 42 (65.6%) required a therapeutic intervention such as dose reduction, discontinuation or switch to a new antifungal. Patients experiencing adverse effects were prescribed higher total daily fluconazole doses (6.7 versus 5.7 mg/kg; P < 0.01). The median therapeutic drug levels did not differ significantly between patients who experienced adverse effects and those who did not (36.1 versus 28.1 mg/L; P = 0.35). CONCLUSIONS A significant number of patients receiving long-term fluconazole therapy for coccidioidomycosis experienced adverse effects. Of these, around two-thirds required a therapeutic change. We believe these findings are representative of the adverse effect profile of long-term fluconazole therapy as it is used in clinical practice for coccidioidomycosis as opposed to use in clinical trials.
Association Between Critical Care Admissions and Cognitive Trajectories in Older Adults.

OBJECTIVES Patients requiring admission to an ICU may subsequently experience cognitive decline. Our objective was to investigate longitudinal cognitive trajectories in older adults hospitalized in ICUs. We hypothesized that individuals hospitalized for critical illness develop greater cognitive decline compared with those who do not require ICU admission. DESIGN A retrospective cohort study using prospectively collected cognitive scores of participants enrolled in the Mayo Clinic Study of Aging and ICU admissions retrospectively ascertained from electronic medical records. A covariate-adjusted linear mixed effects model with random intercepts and slopes assessed the relationship between ICU admissions and the slope of global cognitive z scores and domains scores (memory, attention/executive, visuospatial, and language). SETTING ICU admissions and cognitive scores in the Mayo Clinic Study of Aging from October 1, 2004, to September 11, 2017. PATIENTS Nondemented participants age 50 through 91 at enrollment in the Mayo Clinic Study of Aging with an initial cognitive assessment and at least one follow-up visit. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Of 3,673 participants, 372 had at least one ICU admission with median (25-75th percentile) follow-up after first ICU admission of 2.5 years (1.2-4.4 yr). For global cognitive z score, admission to an ICU was associated with greater decline in scores over time compared with participants not requiring ICU admission (difference in annual slope = -0.028; 95% CI, -0.044 to -0.012; p < 0.001). ICU admission was associated with greater declines in memory (-0.029; 95% CI, -0.047 to -0.011; p = 0.002), attention/executive (-0.020; 95% CI, -0.037 to -0.004; p = 0.016), and visuospatial (-0.013; 95% CI, -0.026 to -0.001; p = 0.041) domains. ICU admissions with delirium were associated with greater declines in memory (interaction p = 0.006) and language (interaction p = 0.002) domains than ICU admissions without delirium. CONCLUSIONS In older adults, ICU admission was associated with greater long-term cognitive decline compared with patients without ICU admission. These findings were more pronounced in those who develop delirium while in the ICU.
My Way: A Computational Autobiography

In this paper, the author recounts his forty-year plus struggle to find a sound basis for understanding the computational fluid dynamics of compressible flow.
From Reproductive Rights to Reproductive Justice

This month the Social Medicine Journal of-fers readers the text of the Annual Harold Wise Memorial Lecture held on June 13, 2017 at the Department of Family and Social Medicine at Montefiore Medical Center. Harold Wise was the founder of the Residency Program in Social Medicine and the award recognizes a faculty member who best represents the values of the Residency Program
Dispersion Engineering With Photonic Inverse Design

Dispersion engineering, such as the design of slow light waveguide systems, is an effective tool for a wide range of photonic applications, but presents a difficult optical design challenge. Most applications require a slow light waveguide design that mitigates group velocity dispersion, and efficient coupling solutions over the slow light operating bandwidth. In this work, we optimize the slow light dispersion relation of a photonic crystal waveguide with three dimensional (3D) inverse design methods. In addition, we design mode couplers for the photonic crystal waveguide. The optimized waveguide supports a slow light mode with a group index of $\mathbf {n_g = 25}$ and a normalized bandwidth group index product of $\mathbf {0.38}$ . A compact mode coupler to a strip waveguide is designed with an average efficiency of 92.7% within the slow light operating bandwidth. Lastly, we design a fully etched grating which couples directly to the slow light mode with a 32.5% average efficiency.
The history of antimalarials.

In the city of Lima, capital of Peru, the wife of the Viceroy, at that time the Count of Cinchon fell sick... Her illness was tertian fever... The rumour of her illness... became known by the peopl...
Two-Player, Two-Strategy Games

While the analysis in this chapter is straightforward, a considerable amount of new information is developed. Thus, a quick preview will help to pull it together.
Auditing research using Chinese data: what’s next?†

During the past decade, there has been a surge in auditing research that exploits Chinese data, much of which is published in top tier journals. China has been an attractive setting for auditing re...
The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation

Abstract Evidence strongly suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain. SARS-CoV-2 enters cells via the S1 subunit of its spike protein, and S1 can be used as a proxy for the uptake patterns and mechanisms used by the whole virus; unlike studies based on productive infection, viral proteins can be used to precisely determine pharmacokinetics and biodistribution. Here, we found that radioiodinated S1 (I-S1) readily crossed the murine blood-brain barrier (BBB). I-S1 from two commercial sources crossed the BBB with unidirectional influx constants of 0.287 ± 0.024 μL/g-min and 0.294 ± 0.032 μL/g-min and was also taken up by lung, spleen, kidney, and liver. I-S1 was uniformly taken up by all regions of the brain and inflammation induced by lipopolysaccharide reduced uptake in the hippocampus and olfactory bulb. I-S1 crossed the BBB completely to enter the parenchymal brain space, with smaller amounts retained by brain endothelial cells and the luminal surface. Studies on the mechanisms of transport indicated that I-S1 crosses the BBB by the mechanism of adsorptive transcytosis and that the murine ACE2 receptor is involved in brain and lung uptake, but not that by kidney, liver, or spleen. I-S1 entered brain after intranasal administration at about 1/10th the amount found after intravenous administration and about 0.66% of the intranasal dose entered blood. ApoE isoform or sex did not affect whole brain uptake, but had variable effects on olfactory bulb, liver, spleen, and kidney uptakes. In summary, I-S1 readily crosses the murine BBB, entering all brain regions and the peripheral tissues studied, likely by the mechanism of adsorptive transcytosis. Graphical Abstract
address to HP/1000 international users group

Publisher Summary This chapter discusses the trends in the computer industry and the way the user groups play a major role. Computer technology is proposed to be one of the three most important factors affecting industries; the other two are agriculture and energy. The chapter discusses that the United States has enjoyed a remarkable position in trade and economic power. It has held a dominant position in technology—particularly electronics and computer technology. The direct result of the relative loss of productivity puts the United States in an overall net import position, particularly in several key industries—automobiles, steel, and consumer electronics. The reasons for the importance of computer are them being key to growth in productivity of labor, to building better products—quality and automation, to better management of resources, and to increase in asset and capital productivity.
MRI-based thermal dosimetry based on single-slice imaging during focused ultrasound thalamotomy.

Transcranial MRI-guided focused ultrasound (MRgFUS) is a noninvasive thermal ablation method approved for the treatment of essential tremor and tremor-dominant Parkinson's disease. This method uses MR temperature imaging (MRTI) to monitor the treatment. Accurately tracking the accumulated thermal dose is important for both safety and efficacy. Currently, MRTI is obtained in a single plane that varies between sonications, preventing direct tracking of the accumulated dose. In this work, we tested a method to estimate this dose during 120 MRgFUS treatments. This method used the MRTI to create simulated thermal images for sonications when the imaging plane was changed. This approach accurately predicted the lesion shapes. The mean Sorensen-Dice similarity coefficient between the lesion segmentations and dose regions at the 17 cumulative min at 43 °C (CEM43) threshold used by the device software was 0.82 but varied among different treatments (range: 0.34-0.95). Tissue swelling appeared to explain when mismatch occurred, although other errors probably contributed. Overall, the mean distance between the lesion segmentations and the 17 CEM43 dose contours was 0.37 ± 0.57 mm. The probability for thermal damage was estimated to be 50% at 13.6 CEM43 and a maximum temperature of 48.6 °C. Due to large thermal gradients, which exceeded 99 CEM43/mm on average, the area where the probability for thermal damage was uncertain was narrow. Overall these results show that the 17 CEM43 threshold is on average a good predictor for thermal lesions, although there will always be a narrow margin where the fate of the tissue is uncertain.
A plea for making brown bandages stick

The act of healing is a uniquely humanizing experience ubiquitously symbolized by the application of a bandage, an action that occurs daily in dermatology and pediatric clinics. The beige bandages we use in clinics are merely a visible symbol and reinforcement of what is considered standard and what is a deviation from the norm. One hundred years ago, Johnson & Johnson was a pioneer in the field when they invented the adhesive bandage. One hundred years ago, they set an industry standard by creating, exporting, and upholding a normative standard for practically all adhesive bandages in medicine, including birth control and nicotine patches to nasal strips. It took one hundred years after its inception and with over 100 billion Band-Aids produced with cartoons and superheroes, and in countless forms, for the inventors of bandages to offer a multitude of skin tones. Can we as healers stick with them? Or, can we implore ourselves to decolonize our clinics with a seemingly insignificant yet powerful symbolic gesture that lets our patients know that they are seen and not deviations from the norm? The conversation of diversity and inclusion in health and healing and institutional racism is obviously much deeper and profound than adhesive bandages. However, we can choose to acknowledge and celebrate diversity and inclusion in our practices as much as we can because it is significant to all of our patients, children, and adults alike.
Diaspora and Social Networks in a World War II Japanese American Incarceration Center

Social network data demonstrates how communities respond to changes in social structures, like those caused by diasporic movements. Network data from the Granada Relocation Center (Amache), a WWII Japanese American incarceration center in Southeastern Colorado demonstrate the social ties fostered by internees through participation in sporting activities. The importance of previous community membership in the development of social ties is seen in a social network analysis of sport team members. Network data is correlated to archaeological evidence of sporting facilities and their role in the development of community membership and social interaction among a diasporic population.
Open the door to the atomic world by single-molecule atomic force microscopy

Summary Single-molecule atomic force microscopy (sm-AFM) is a state-of-the-art AFM involving single-molecule tip functionalization, characterization, and manipulation. The pioneering work of tip functionalization with a CO molecule in 2009 realized an unprecedented atomic resolution, allowing the elucidation of chemical structures in real space with a superior single-molecule sensitivity. Furthermore, as an atomically precise manipulation tool, sm-AFM realizes both lateral and vertical movements of single molecules and even single atoms. Meanwhile, as a compatible on-surface reactor, sm-AFM enables the creation and in situ imaging of novel molecules and radicals that has never been achieved via conventional approaches. Endowed with these extraordinary capabilities, sm-AFM takes us into the atomic world. In this review, we reveal the principle and working condition of sm-AFM, provide up-to-date understanding on characterization, atomic manipulation, and on-surface reactions using sm-AFM, evaluate current methods for image simulation, and further outline the challenges and future perspectives for the development of sm-AFM.
La comparación de los pronombres de segunda persona del singular en el español peninsular y en el euskera: ¿una misión imposible?

espanolEste trabajo toma los pronombres de segunda persona del singular —Pro2s— del espanol centro-norteno —tu y usted— y del euskera —hi y zu— como base, y con ello revisa estudios empiricos ya publicados sobre el espanol peninsular (Pedroviejo Esteruelas, 2006; Sampedro Mella, 2016; Sanroman Vilas, 2010). Por su parte, los datos para el euskera se basan en el analisis de 540 conversaciones de la serie Goenkale. Este estudio concluye que los Pro2s no son equivalentes al existir un pronombre pragmaticamente no marcado en euskera: zu. La unica similitud esta entre usted y zu cuando se usan de forma asimetrica. EnglishThis paper takes the second person singular pronouns of North Peninsular Spanish (tu & usted) and those of Basque (hi & zu) as the point of departure, and reexamines published empirical studies on northern peninsular Spanish pronouns (Pedroviejo Esteruelas, 2006; Sampedro Mella, 2016; Sanroman Vilas, 2010). The data on Basque pronouns comes from the analysis of 540 conversations from the series Goenkale. This study concludes that the pronouns are not equivalent due to the existence of a pragmatically unmarked pronoun in Basque: zu. The only similarity is between ustedand zu when they are used asymmetrically.
Adolescent Ethanol Exposure Alters Cholinergic Function and Apical Dendritic Branching Within the Orbital Frontal Cortex.

Abstract During adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.
“We have to be uncomfortable and creative”: Reflections on the impacts of the COVID-19 pandemic on overdose prevention, harm reduction & homelessness advocacy in Philadelphia

Abstract The COVID-19 pandemic and ensuing service delivery interruptions had serious impacts on people who use drugs (PWUD) and people experiencing homelessness, including instability in the drug supply, decreased access to substance use disorder (SUD) treatment and harm reduction supplies, increased substance use and relapse due to stress and isolation, inability to properly isolate and quarantine without stable housing, and risk of COVID-19 spread in congregate living spaces. At the same time, many have noted a potential opportunity for rapid change in health, housing, and drug policy despite previous stagnation—referred to as a “punctuated equilibrium” by Baumgartner and Jones—in response to the pandemic. The pandemic forced some important policy interventions in the United States at both national and local levels, including eviction moratoriums and loosening of drug policy related to substance use treatment. However, to what extent some of these changes will be sustained past the current COVID-19 crisis is still unclear, as is how drug and housing related policy shifts have impacted the work of frontline overdose prevention, substance use treatment, and homelessness advocacy workers. In this qualitative study, we used semi-structured interviews to assess how Philadelphia’s harm reduction advocates, community organizers, and SUD treatment clinicians have responded to the overdose and homelessness crises during COVID-19, and how they predict the pandemic and ensuing policy changes will impact the future of overdose prevention, harm reduction efforts, and homelessness advocacy. We interviewed 30 eligible participants during July and August 2020. The analysis of these data yielded three themes: 1/“None of it should be new to anybody”: COVID-era issues impacting PWUD and people experiencing homelessness are extensions of existing problems; 2/“An opportunity to actually benefit in some way from this crisis”: Possibility for innovation and improved care for PWUD and people experiencing homelessness; and 3/“Nothing we’ve tried has worked, so we have to be uncomfortable and creative”: The uncertain path forward. Despite the many barriers that participants faced to promoting the health and well-being of marginalized communities during the pandemic, they also believed that the pandemic presented an important opportunity for positive policy change that has the potential to promote drug user health into the future, including a continuation of loosened federal restrictions on substance use disorder treatment, legalization of safe consumption spaces, safe supply of substances, and progressive, creative housing solutions.
Lived Experience and Disability Justice in the Family Regulation System

In the family regulation system, the label of disability is used to strip parents of rights and credibility, and the system itself—along with the actors within it—fails to understand the nature of disability while simultaneously espousing and adopting harmful stereotypes of disability to conclude that disabled parents cannot parent. Those who resist diagnosis with a disability are denigrated as being unable to understand themselves and their children by reason of disability. Those who do have disabilities are penalized for exhibiting behaviors relating to their disabilities. By presenting the lived experience of one parent in the family regulation system who has been labeled as having a psychiatric disability, we expose how regardless of a parents’ disability status, once saddled with a disability label, their experience in family court is irrevocably marred. This Essay explores how the forces of racism and ableism converge to create the ongoing pathology of parents with disabilities and those who have been labeled as disabled in the family regulation system. Specifically, we share one co-author’s experiences of the system as both disabling and inequitable.
Separation and Properties of Three Acid Phosphatases from Human Placenta

Abstract 1. Three chromatographically and enzymatically distinct forms of acid phosphatase have been separated from extracts of human placental villus tissue by gel filtration. 2. These enzymes, termed I, II, and III, have molecular weights of g200,000, 105,000, and 35,000, respectively; and pH optima for p-nitrophenyl phosphate hydrolysis of 5.5, 4, and 5.5. 3. Enzyme II, which is probably of lysosomal origin, is 90% inhibited by 20 mm l-(+)tartrate. Enzyme III is insensitive to tartrate but is completely inhibited by 10 µm p-chloromercuribenzoate, and I displays an intermediate sensitivity to tartrate. Both I and II, but not III, are also inhibited by molybdate and fluoride. 4. Whereas enzymes I and II appear to be typical nonspecific acid phosphohydrolases, enzyme III is atypical in that most of the common phosphate esters are poor substrates. It is further distinguished by a stimulatory response to purines and an apparent allosteric type inhibition by pyridoxine 5-phosphate.
Regulation of ribonucleic acid synthesis in growing bacterial cells. I. Control over the total rate of RNA synthesis.

Abstract It is well known that bacterial cells regulate their rate of RNA accumulation (net RNA synthesis) in strict accord with the potential of a particular medium to support growth at a given rate, and that in shifts from one medium to another there are rapid and seemingly preferential changes in the net rate, while the other parameters of cell growth change more slowly. In this study, in addition to making measurements of net rates of RNA synthesis in steady states and shifts from one medium to another, measurements of the total rate, that is the sum of the rates of synthesis of stable and unstable RNA species, are made. This is done by measuring the early slope of the incorporation of a radioactive precursor ([3H]guanine) into RNA, and correcting for the specific activity of the intracellular precursor ([3H]GTP) at those times. It is found that, in differing steady states of growth, cells vary, not only their total rate of RNA synthesis, but also the fraction of the total given to the formation of unstable species. Expressed as a ratio of stable to unstable RNA's, this latter value is about one to one in minimal-glucose and two to one in medium enriched with amino acids. Moreover, transients between steady states give a stronger indication that the synthesis of stable and unstable RNA species can vary independently. In shift-up for example, while the net rate of accumulation, presumably largely the synthesis of the stable ribosomal and transfer RNA's, increases immediately, giving rise to the striking increase of isotope uptake known to take place, the rate of total synthesis increases only in the course of 5 to 15 minutes, such that at early times the ratio of stable to unstable RNA's made reaches about three to one. These experiments suggest that the mechanism for the control of RNA synthesis involves both a means whereby the total capacity of the cell to make RNA is limited, as well as a mechanism by which the distribution of that capacity between template sites leading to the synthesis of stable and unstable RNA species is regulated.
Quantitation of Microorganisms in Sputum

A method of quantitating microbial cultures of homogenized sputum has been devised. Possible application of this method to the problem of determining the etiologic agent of lower-respiratory-tract infections has been studied to determine its usefulness as a guide in the management of these infections. Specimens were liquefied by using an equal volume of 2% N-acetyl-L-cysteine. The liquefied sputum suspension was serially diluted to 10-1, 10-3, 10-5, and 10-7. These dilutions were plated on appropriate media by using an 0.01-ml calibrated loop; they were incubated and examined by standard diagnostic methods. Quantitation of fresh sputum from patients with pneumonia prior to antimicrobial therapy revealed that probable pathogens were present in populations of 107 organisms/ml or greater. Normal oropharyngeal flora did not occur in these numbers before therapy. Comparison of microbial counts on fresh and aged sputum showed that it is necessary to use only fresh specimens, since multiplication or death alters both quantitative and qualitative findings. Proper collection and quantitative culturing of homogenized sputum provided information more directly applicable to patient management than did qualitative routine methods. Not only was the recognition of the probable pathogenic organism in pneumonia patients improved, but serial quantitative cultures were particularly useful in recognizing the emergence of superinfections and in evaluating the efficacy of antimicrobial therapy.
The Effect of Size Appropriate and Proper Restraint Use on Injury Severity of Children

The United States National Transportation Safety Board examined the effect of not using an age-appropriate restraint system and the effect of not using a restraint system properly on injury severity. The Safety Board found that improperly restrained children in an age-appropriate restraint system sustained a greater proportion of moderate or worse (Abbreviated Injury Scale (AIS) 2-6) injuries than properly restrained children who were in the wrong restraint for their size. This was true particularly for infants and small children who were likely to be in a child restraint system. The study underscores the importance of proper use of restraint systems, and makes recommendations for improvements in restraint system designs for children. (A) For the covering abstract of the conference see IRRD 899572.
Evaluation of the HPC challenge benchmarks in virtualized environments

This paper evaluates the performance of the HPC Challenge benchmarks in several virtual environments, including VMware, KVM and VirtualBox. The HPC Challenge benchmarks consist of a suite of tests that examine the performance of HPC architectures using kernels with memory access patterns more challenging than those of the High Performance LINPACK (HPL) benchmark used in the TOP500 list. The tests include four local (matrix-matrix multiply, STREAM, RandomAccess and FFT) and four global (High Performance Linpack --- HPL, parallel matrix transpose --- PTRANS, RandomAccess and FFT) kernel benchmarks. The purpose of our experiments is to evaluate the overheads of the different virtual environments and investigate how different aspects of the system are affected by virtualization. We ran the benchmarks on an 8-core system with Core i7 processors using Open MPI. We did runs on the bare hardware and in each of the virtual environments for a range of problem sizes. As expected, the HPL results had some overhead in all the virtual environments, with the overhead becoming less significant with larger problem sizes. The RandomAccess results show drastically different behavior and we attempt to explain it with pertinent experiments. We show the cause of variability of performance results as well as major causes of measurement error.
Fractionalization and the Municipal Bond Market

We study the impact of ethnic and religious fractionalization on the U.S. municipal debt market, and find that issuers from more ethnically and religiously fractionalized counties pay higher yields on their municipal debt. A two standard deviation increase in religious fractionalization is associated with a six basis point increase in bond yields, and a two standard deviation increase in ethnic fractionalization is associated with a ten basis point increase. To provide a scale for these results, a four-notch rating change, from AAA to AA-, is associated with an eight basis point increase in yields. Additional analysis suggests that at least some of this effect is not driven by the risk of the bonds, but instead reflects inefficiency in the underwriting process.
An Evaluation of Energy Transfer Pathways in Thermal Transport Across Solid/Solid Interfaces

Thermal transport across solid/solid interfaces has been extensively studied, but heat transfer pathways other than phonon transmission and electron-phonon nonequilibrium in the metal were usually neglected. In this work, we aim to build a general and unified model including both the above transport channels and others such as electron transmission and electron-interface coupling. For a general solid/solid system with electrons and phonons existing on both sides, an analytical solution to the interfacial thermal resistance is obtained. We show that the relative contribution from different transport channels depends on both the local condition at the interface and the bulk properties of each side of the interface. We find that for a metallic thin film deposited on a semiconductor substrate, the contribution of electron transmission to thermal transport is negligible when the semiconductor is not heavily doped even though the electronic interfacial thermal boundary resistance can be lower than the phononic counterpart at high temperatures. In contrast, the electron-interface channel plays an important role in the intrinsic to low-doped regime, where substrate phonons can remove heat efficiently from the interface.Copyright © 2013 by ASME
Requirement for extracellular calcium or magnesium in mitogen‐induced activation of human peripheral blood lymphocytes

The importance of calcium in lymphocyte activation is well recognized, but the levels of extracellular ionized free calcium (Ca++) necessary for lymphocyte proliferation via various pathways have not been investigated in detail. We studied the ability of a lectin mitogen (PHA) and a calcium ionophore (ionomycin) to induce interleukin 2 receptors, interleukin 2 (IL2) production, and proliferation over various concentrations of extracellular Ca++. Reducing the Ca++ levels from the normal 200 microM to 10 microM in PHA-stimulated cultures partially inhibited IL2 receptor expression, IL2 production, and subsequent proliferation. At 1 microM Ca++, both IL2 activity and proliferation were eliminated, but partial IL2 receptor expression was still observed. Ionomycin did not induce any of these events in cultures where the extracellular Ca++ concentration was below 100 microM. Restoring calcium in the medium resulted in normal levels of IL2 receptor expression, IL2 activity, and proliferation when PBL were stimulated with either mitogen. Exogenous magnesium partially restored these events in PHA-stimulated cultures, but had no effect when ionomycin was used as the mitogen. These data indicate that stimulation by ionomycin is much more dependent upon the levels of extracellular Ca++ than is PHA. Extracellular calcium also appears to be necessary subsequent to IL2 receptor acquisition, since the latter was seen without IL2 activity or proliferation at very low extracellular Ca++, and IL2 failed to restore the proliferative response under these conditions. The data also suggest that PHA, but not ionomycin, can activate lymphocytes via a magnesium-dependent pathway, or that PHA has a lower specificity for divalent cation cofactors.
Monoclonal antibodies to phenobarbital-induced rat liver cytochrome P-450

Abstract Somatic cell hybrids were made between mouse myeloma cells and spleen cells derived from BALB/c female mice immunized with purified phenobarbital-induced rat liver cytochrome P-450 (PB-P-450). Hybridomas were selected in HAT medium, and the monoclonal antibodies (MAbs) produced were screened for binding to the PB-P-450 by radioimmunoassay, for immunoprecipitation of the PB-P-450, and for inhibition of PB-P-450-catalyzed enzyme activity. In two experiments, MAbs of the IgM and IgG1 were produced that bound and, in certain cases, precipitated PB-P-450. None of these MAbs, however, inhibited the PB-P-450-dependent aryl hydrocarbon hydroxylase (AHH) activity. In two other experiments, MAbs to PB-P-450 were produced that bound, precipitated and, in several cases, strongly or completely inhibited the AHH and 7-ethoxycoumarin deethylase (ECD) activities of PB-P-450. These MAbs showed no activity toward the purified 3-methylcholanthrene-induced cytochrome P-450 (MC-P-450), β-naphthoflavone-induced cytochrome P-450 (BNF-P-450) or pregnenolone 16-α-carbonitrile-induced cytochrome P-450 (PCN-P-450) in respect to RIA determined binding, immunoprecipitation, or inhibition of AHH activity. One of the monoclonal antibodies, MAb 2-66-3, inhibited the AHH activity of liver microsomes from PB-treated rats by 43% but did not inhibit the AHH activity of liver microsomes from control, BNF-, or MC-treated rats. The MAb 2-66-3 also inhibited ECD in microsomes from PB-treated rats by 22%. The MAb 2-66-3 showed high cross-reactivity for binding, immunoprecipitation and inhibition of enzyme activity of PB-induced cytochrome P-450 from rabbit liver (PB-P-450 LM2 ). Two other MAbs, 4-7-1 and 4-29-5, completely inhibited the AHH of the purified PB-P-450. MAbs to different cytochromes P-450 will be of extraordinary usefulness for a variety of studies including phenotyping of individuals, species, and tissues and for the genetic analysis of P-450s as well as for the direct assay, purification, and structure determination of various cytochromes P-450.
Reliable cache design with on-chip monitoring of NBTI degradation in SRAM cells using BIST

Constant scaling in device dimensions and increasing operating temperatures and vertical electrical fields have all contributed to faster device aging due to NBTI. The problem is further compounded in SRAM cells where the devices are among the smallest for a technology node. Since NBTI degradation is a gradual process, it is proposed that if the threshold voltage increase in PMOS devices of SRAM cells can be monitored, cache arrays with failing cells can be reliably operated after reconfiguration, given available memory redundancy. Using an experimentally verified NBTI model, we study DC noise margins in conventional 6T SRAM cells, as a function of NBTI degradation, in the presence of process variations. An on-chip NBTI monitoring scheme is presented that can be embedded within conventional cache designs without affecting normal device operation, enabling the prediction of cell failure before its occurrence.
Retracing the Roots of Teacher Activism in Urban Schools.

This article explores experiences that led individuals to become teacher leaders advocating for under-served students in urban schools. Cohort members in an urban teacher leadership master’s degree programme engaged in systematic critical reflection about becoming leaders for equity, describing the influences of their families and communities, positive and negative experiences in school, and the importance of leadership opportunities provided within and beyond school. Being marginalized as students influenced their activism and their commitment to teach in their communities. Vignettes or cases show how teachers’ professional identity was powerfully shaped by educational interactions influenced by differences in race, class, gender, and language. These urban teachers take leadership by advocating for marginalized students and their families and are truly activists for social justice.
Neuroimaging studies of the cerebellum: language, learning and memory

During the decade following a functional neuroimaging study of language that showed cerebellar involvement in a cognitive task, PET and fMRI studies have continued to provide evidence that the role of the cerebellum extends beyond that of motor control and that this structure contributes in some way to cognitive operations. In this review, we describe neuroimaging evidence for cerebellar involvement in working memory, implicit and explicit learning and memory, and language, and we discuss some of the problems and limitations faced by researchers who use neuroimaging to investigate cerebellar function. We also raise a set of outstanding questions that need to be addressed through further neuroimaging and behavioral experiments before differing functional accounts of cerebellar involvement in cognition can be resolved.
Named reporting and mandatory partner notification in New York State: the effect on consent for perinatal HIV testing

The impact of the implementation of named reporting and mandatory partner notification on the percentage of patients not accepting prenatal human immuno-deficiency virus (HIV) testing or deferring prenatal care has been examined in only a preliminary fashion. This retrospective, population-based cohort study of 5,007 patients admitted to a tertiary care labor-and-delivery unit in Central New York State between December 15, 1999, and March 14, 2001, is the first study to address the impact of named reporting and mandatory partner notification on prenatal HIV testing and prenatal care seeking. The percentage of patients who did not undergo prenatal HIV testing was significantly increased after the institution of named reporting and mandatory partner notification: 118/4,030 preimplementation, 59/966 postimplementation, with relative risk (RR)=2.09 (1.54<RR<2.83). This remained significant after logistic regression controlled for confounding variables, with odds ratio (OR)=1.5 (1.07<OR<2.10). The percentage of patients who did not receive prenatal care was significantly increased after the institution of named reporting and mandatory partner notification: 14/4,030 preimplementation, 18/966 postimplementation, with RR=5.36 (2.68<RR<10.75). This remained significant after logistic regression controlled for confounding variables. OR=3.77 (1.84<OR<7.72). There is a strong indication that the institution of named reporting and mandatory partner notification has significantly impacted the willingness of pregnant women to undergo HIV testing and prenatal care. Further analysis of the impact in perinatal populations is needed before the continued implementation of this controversial public policy initiative.