cssi/SciSciGPT-SciSciNet huggingface dataset:
Cross-talk among writers, readers, and erasers of m6A regulates cancer growth and progression

The importance of RNA methylation in biological processes is an emerging focus of investigation. We report that altering m6A levels by silencing either N6-adenosine methyltransferase METTL14 (methyltransferase-like 14) or demethylase ALKBH5 (ALKB homolog 5) inhibits cancer growth and invasion. METTL14/ALKBH5 mediate their protumorigenic function by regulating m6A levels of key epithelial-mesenchymal transition and angiogenesis-associated transcripts, including transforming growth factor–β signaling pathway genes. Using MeRIP-seq (methylated RNA immunoprecipitation sequencing) analysis and functional studies, we find that these target genes are particularly sensitive to changes in m6A modifications, as altered m6A status leads to aberrant expression of these genes, resulting in inappropriate cell cycle progression and evasion of apoptosis. Our results reveal that METTL14 and ALKBH5 determine the m6A status of target genes by controlling each other’s expression and by inhibiting m6A reader YTHDF3 (YTH N6-methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. Furthermore, we show that ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor HuR to regulate the stability of target transcripts. We discover that hypoxia alters the level/activity of writers, erasers, and readers, leading to decreased m6A and consequently increased expression of target transcripts in cancer cells. This study unveils a previously undefined role for m6A in cancer and shows that the collaboration among writers-erasers-readers sets up the m6A threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus, such as hypoxia, perturbs that m6A threshold, leading to uncontrolled expression/activity of those genes, resulting in tumor growth, angiogenesis, and progression.
A New Frontier for Pull-Based Graph Processing.

The trade-off between pull-based and push-based graph processing engines is well-understood. On one hand, pull-based engines can achieve higher throughput because their workloads are read-dominant, rather than write-dominant, and can proceed without synchronization between threads. On the other hand, push-based engines are much better able to take advantage of the frontier optimization, which leverages the fact that often only a small subset of the graph needs to be accessed to complete an iteration of a graph processing application. Hybrid engines attempt to overcome this trade-off by dynamically switching between push and pull, but there are two key disadvantages with this approach. First, applications must be implemented twice (once for push and once for pull), and second, processing throughput is reduced for iterations that run with push. We propose a radically different solution: rebuild the frontier optimization entirely such that it is well-suited for a pull-based engine. In doing so, we remove the only advantage that a push-based engine had over a pull-based engine, making it possible to eliminate the push-based engine entirely. We introduce Wedge, a pull-only graph processing framework that transforms the traditional source-oriented vertex-based frontier into a pull-friendly format called the Wedge Frontier. The transformation itself is expensive even when parallelized, so we introduce two key optimizations to make it practical. First, we perform the transformation only when the resulting Wedge Frontier is sufficiently sparse. Second, we coarsen the granularity of the representation of elements in the Wedge Frontier. These optimizations respectively improve Wedge's performance by up to 5x and 2x, enabling it to outperform Grazelle, Ligra, and GraphMat respectively by up to 2.8x, 4.9x, and 185.5x.
Assessment of response to medication in individuals with Parkinson’s disease

Abstract Background and Objective Motor fluctuations between akinetic (medication OFF) and mobile phases (medication ON) states are one of the most prevalent complications of patients with Parkinson’s disease (PD). There is a need for a technology-based system to provide reliable information about the duration in different medication phases that can be used by the treating physician to successfully adjust therapy. Methods Two KinetiSense motion sensors were mounted on the most affected wrist and ankle of 19 PD subjects (age: 42–77, 14 males) and collected movement signals as the participants performed seven daily living activities in their medication OFF and ON phases. A feature selection and a classification algorithm based on support vector machine with fuzzy labeling was developed to detect medication ON/OFF states using gyroscope signals. The algorithm was trained using approximately 15% of the data from four activities and tested on the remaining data. Results The algorithm was able to detect medication ON and OFF states with 90.5% accuracy, 94.2% sensitivity, and 85.4% specificity. It performed equally well for all the activities with an average accuracy of 91.3% for the activities that were used in the training phase and 88.4% for the new activities. Conclusions The developed sensor-based algorithm could provide objective and accurate assessment of medication states that can lead to successful adjustment of the therapy resulting in considerably improved care delivery and quality of life of PD patients.
Memory Changes with Aging

Almost every elderly person can attest to his or her diminishing memory. Similarly, younger persons coming in contact with the elderly can verify a decline in the memory capacity of the elderly. However, a scientific approach to determine the amount or the type of memory deficits in the elderly has not produced definitive results. Contradictory findings abound in the literature.
High Performance Memory Repair

As process technology dimensions shrink, manufacturing defect density is increasing, adversely impacting product yield. Products have typically built redundancy and repair features in SRAM. Register File arrays (RFs) can also benefit from redundancy and repair. There are various types of repair techniques used in SRAMs today which can also be employed on RFs. However all known techniques (column, row, 1-bit, multi-bit) incur a performance loss of at least two gate delays due to the addition of logic either on the memory address path or on the read output path. This paper describes a row repair scheme that incurs virtually no performance penalty. In simulations conducted in recent process nodes, we noted a performance impact of less than half a gate delay
Vaccine Refusal and Pharmaceutical Acquiescence: Parental Control and Ambivalence in Managing Children’s Health:

Parents who confidently reject vaccines and other forms of medical intervention often seek out pediatric care, medical treatments, and prescription medications for their children in ways that seem ...
Extracellular matrix dynamics in tubulogenesis.

Abstract Biological tubes form in a variety of shapes and sizes. Tubular topology of cells and tissues is a widely recognizable histological feature of multicellular life. Fluid secretion, storage, transport, absorption, exchange, and elimination—processes central to metazoans—hinge on the exquisite tubular architectures of cells, tissues, and organs. In general, the apparent structural and functional complexity of tubular tissues and organs parallels the architectural and biophysical properties of their constitution, i.e., cells and the extracellular matrix (ECM). Together, cellular and ECM dynamics determine the developmental trajectory, topological characteristics, and functional efficacy of biological tubes. In this review of tubulogenesis, we highlight the multifarious roles of ECM dynamics—the less recognized and poorly understood morphogenetic counterpart of cellular dynamics. The ECM is a dynamic, tripartite composite spanning the luminal, abluminal, and interstitial space within the tubulogenic realm. The critical role of ECM dynamics in the determination of shape, size, and function of tubes is evinced by developmental studies across multiple levels—from morphological through molecular—in model tubular organs.
Fixed human-specific neuro-regulatory single nucleotide mutations manifest staggering breadth of associations with physiological processes, morphological features, and pathological conditions of Modern Humans

Abstract Despite recent remarkable advances in identification and characterization of human-specific regulatory DNA sequences, their global impact on physiological and pathological phenotypes of Homo sapiens remains poorly understood. Gene set enrichment analyses of 8,405 genes linked with 35,074 human-specific (hs) neuro-regulatory single-nucleotide changes (SNCs) revealed the staggering breadth of significant associations with morphological structures, physiological processes, and pathological conditions of Modern Humans. Significantly enriched traits include more than 1,000 anatomically-distinct regions of the adult human brain, many different types of human cells and tissues, more than 200 common human disorders and more than 1,000 records of rare diseases. Thousands of genes connected with neuro-regulatory hsSNCs have been identified in this contribution, which represent essential genetic elements of the autosomal inheritance and offspring survival phenotypes. A total of 1,494 hsSNCs-linked genes have associated with either autosomal dominant or recessive inheritance and 2,273 hsSNCs-linked genes have been associated with premature death, embryonic lethality, as well as pre-, peri-, neo-, and post-natal lethality phenotypes of both complete and incomplete penetrance. Therefore, thousands of heritable traits and critical genes impacting the offspring survival appear under the human-specific regulatory control in genomes of Modern Humans. Interrogations of the Mouse Genome Informatics (MGI) database revealed readily available mouse models tailored for precise experimental definitions of regulatory effects of neuro-regulatory hsSNCs on genes causally affecting thousands of defined mammalian phenotypes and hundreds of common and rare human disorders. These observations highlight the remarkable translational opportunities afforded by the discovery of genetic regulatory loci harboring hsSNCs that are fixed in humans, distinct from other primates, and located in differentially-accessible (DA) chromatin regions during human brain development.
10.01 – Biotransformation: Introduction and Historical Perspective

In the past 200 years, the science of metabolism has developed from a concept to a detailed process that can be applied not only to chemicals endogenous to the body but also to any compound that a human could conceivably ingest. The field has its origins not only in toxicology per se but also in chemical carcinogenesis and in the metabolism of steroids and biogenic amines. The field of biotransformation has developed with the input of approaches from analytical chemistry, enzymology, genetics, and recombinant DNA technology. Work in the nineteenth century was focused on the identification of urinary metabolites but has now reached the point where we now have many crystal structures of the enzymes, transgenic rodent models, and knowledge of human genetic deficiencies in order to make more intelligent predictions about the toxicity of chemicals.
Outcomes of Urinary Diversion for Late Adverse Effects of Gynecologic Radiotherapy

Abstract Objectives To describe the risks of urinary diversion performed to address adverse effects of gynecologic radiation, with the hypothesis that high grade complications would be more common in sarcopenic women and in those undergoing continent diversion (vs. non-continent) or concomitant cystectomy (vs. bladder-sparing diversion). Methods : A retrospective review was performed of patient records of women who underwent urinary diversion for urinary adverse effects of gynecologic radiotherapy during the period of 2008 - 2018 from three tertiary centers. Skeletal muscle index was calculated to assess for sarcopenia based on preoperative computed tomography scans. Outcomes include high-grade post-operative complications within 90 days of surgery, 30-day readmission rate, and long-term (>90 days) outcomes. Results : Among 34 women who met the inclusion criteria, the majority were white/Caucasian (73.5%). 26/34 (76.5%) underwent non-continent diversion. Seventy nine percent (27/34) (79.4%) of women experienced complications within 90 days; 9/34 (26.5%) experienced high-grade (Clavien grade ≥3) complications. Thirty two percent (11/34) were readmitted within 30 days. Rates of high-grade complications were not significantly impacted by diversion type (p=0.49), concurrent cystectomy (p=0.70), or sarcopenia (p=1.0). Conclusions : Urinary diversion for late adverse effects of gynecologic radiotherapy is associated with high peri-operative risk, even in skilled hands. In this series, neither sarcopenia, nor continent diversion, nor cystectomy were associated with increased complications. Patients and surgeons should consider risks and benefits when deciding to proceed with urinary diversion, however further study is needed to elucidate significant pre-operative markers which may pre-dispose patients to significant complications.
Impact of baseline serum IL-8 on metastatic hormone-sensitive prostate cancer outcomes in the Phase 3 CHAARTED trial (E3805).

Background The immunosuppressive cytokine interleukin- 8 (IL-8), produced by tumor cells and some myeloid cells, promotes inflammation, angiogenesis, and metastasis. In our discovery work, elevated serum IL-8 at androgen deprivation therapy (ADT) initiation portended worse overall survival (OS). Leveraging serum samples from the phase 3 CHAARTED trial of patients treated with ADT +/- docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC), we validated these findings. Methods Two hundred and thirty-three patients had serum samples drawn within 28 days of ADT initiation. The samples were assayed using the same Mesoscale Multiplex ELISA platform employed in the discovery cohort. After adjusting for performance status, disease volume, and de novo/metachronous metastases, multivariable Cox proportional hazards models assessed associations between IL-8 as continuous and binary variables on OS and time to castration-resistant prostate cancer (CRPC). The median IL-8 level (9.3 pg/ml) was the a priori binary cutpoint. Fixed-effects meta-analyses of the discovery and validation sets were performed. Results Higher IL-8 levels were prognostic for shorter OS (continuous: hazard ratio [HR] 2.2, 95% confidence interval [CI]: 1.4-3.6, p = .001; binary >9.3: HR 1.7, 95% CI: 1.2-2.4, p = .007) and time to CRPC (continuous: HR 2.3, 95% CI: 1.6-3.3, p 9.3 pg/ml from patients treated with ADT alone was prognostic for poorer OS (HR 1.8, 95% CI: 1.2-2.7, p = .007) and shorter time to CRPC (HR 1.4, 95% CI: 0.99-1.9, p = .057). Conclusions In the phase 3 CHAARTED study of men with mHSPC at ADT initiation, elevated IL-8 portended worse survival and shorter time to castration-resistant prostate cancer independent of docetaxel administration, metastatic burden, and metachronous versus de novo metastatic presentation. These findings support targeting IL-8 as a strategy to improve mHSPC outcomes.
On the magnetic fields and particle acceleration in Cas A

We investigate the non-thermal X-ray emission from Cas A. For the hard X-ray continuum we test the model proposed by Laming, which invokes bremsstrahlung from electrons accelerated by lower hybrid plasma waves. The justification for this model comes from our determination of a lower limit to the average magnetic field of B > 0.5 mG, which suggest that most of the electron populations are too much affected by synchrotron losses to produce X-ray synchrotron emission. An exception is the X-ray emission from the rim surrounding Cas A, seen in Chandra continuum images. The width of this rim of 1.5" to 4", can be used to infer the magnetic field near the shock front, for which we estimate B = 0.08 - 0.16 mG, and electron energies of about 57 - 40 TeV. This is lower than the average magnetic field, but higher than what may be expected from shocked interstellar medium, suggesting a high pre-shock magnetic field, or rapid, post shock, field amplification. Combining the two magnetic field measurements we have constructed a simple two zone model. Most of the radio emission comes from inside Cas A, where the magnetic field is strong, whereas the inverse Compton emission comes from near the shock front. Only for our lower limit on the magnetic field strength near the shock front is it possible to explain the recent detection of TeV emission by HEGRA with inverse Compton, for which, in addition, we have to assume a rather high far infrared photon density that should be twice as high as our best estimate of roughly 70 cm^{-3}. Pion decay is therefore likely to be the dominant emission from Cas A at TeV energies.
Intrinsic and extrinsic emotion regulation strategies in relation to pathological narcissism

Emotion regulation may play a role in the intrapersonal and interpersonal disturbances associated with pathological narcissism. The purpose of this study was to explore relationships between emotion regulation strategies and pathological narcissism among a large and diverse sample of college students (N = 1301). Narcissistic vulnerability was associated with greater use of intrinsic affect-worsening emotion regulation strategies, while narcissistic grandiosity was associated with greater use of intrinsic affect-worsening, intrinsic affect-improving, and extrinsic affect-improving emotion regulation strategies. Emotion regulation strategies may play a role in the psychological fragility of vulnerable narcissism and the maladaptive compensatory responses of grandiose narcissism.
‘By Dred Things I am Compelled’: China and the Challenge to International Human Rights Law and Policy

The rise of China as a global power has expanded beyond the realm of economic to international human rights law and policy. This contribution examines both the nature and role of Chinese conceptions of international human rights on the evolution of both. It first examines the conceptual premises on the basis of which Chinese approaches to international human rights law and norms are developed. It then considers the effects of such development in those situations where enterprises might be caught between conventional conceptions and those now emerging from China. It ends with a close examination of the character of this “New Era” approach to international human rights through the lens of the successful Chinese effort to gain the adoption, by the UN Human Rights Council, of a resolution A/HRC/37/L.36, which embedded the Chinese conception of mutually advantageous cooperation into the heart of the UN’s human rights discourse. Most enterprises are now caught between the construction of human rights conceptual world orders in which compliance with one standard risks liability for complicity with the other in the realms of societal, legal and normative orders. Such has been the context in which the evolution of contemporary Chinese engagement with international law and norms has emerged.
Mental Health Information Seeking Online: A Google Trends Analysis of ADHD

Health information influences consumer decision making to seek, select, and utilize services. Online searching for mental health information is increasingly common, especially by adolescents and parents. We examined historical trends and factors that may influence population-level patterns in information seeking for attention-deficit/hyperactivity disorder (ADHD). We extracted Google Trends data from January 2004 to February 2020. Keywords included "ADHD," "ADHD treatment," "ADHD medication," and "ADHD therapy." We examined trends (systematic change over time) and seasonality (repeating pattern of change) via time-series analyses and graphics. We also used interrupted time-series analyses to examine the impact of celebrity and pharmaceutical events. Queries of "ADHD medication" increase, while queries for "ADHD therapy" remain relatively low despite a positive linear trend. Searches for "ADHD treatment" displayed a downward trend in more recent years. Analyses on seasonality revealed that holiday breaks coincided with a decrease in search interest, while post-break periods illustrated a rise, and the ADHD Awareness Month (October) coincided with a rise of public interest in all four search terms. Celebrity effects were more prominent in earlier years; the "Own It" pharmaceutical campaign may have increased ADHD awareness and the specificity of searches for "ADHD medication." The anonymous, accessible, and low-cost nature of seeking information online makes search engines like Google important sources of mental health information. Changing search patterns in response to seasonal, advocacy, and media events highlight internet-based opportunities for raising awareness and disseminating empirically supported information.
Place attachment and the historic brewpub: a case study in Greensboro, North Carolina

Over the last couple decades, brewpubs have emerged as a cultural phenomenon uniquely positioned to tie together downtown revitalization, historic preservation, and community connections to local place. A common strategy for the locally-owned brewpub is to incorporate historic place into the business brand while simultaneously inhabiting buildings in historic downtowns. Brewpub owners are therefore making calculated decisions about the physical environment of the pub. This study seeks to understand how the benefits of historic preservation in brewpubs can extend beyond tax incentives to include positive social outcomes. In particular, the work here explores the types of attachments patrons may form to historic brewpub environments with an emphasis on the role of the physical built environment. Attachment to place in this study is understood through the lens of the PPP framework of place that emphasizes a multi-dimensional concept involving person, place, and process (Gifford and Scannell , 2010). This project involves a mixed-methods research design at a single case study site in Greensboro, NC. Natty Greene's Brewing Company is located along the main thoroughfare of historic downtown Greensboro. This brewpub's integral role in downtown revitalization and participation in a Historic Tax Credit-earning rehabilitation project make it a unique exemplar, and especially well-suited for research on place attachment in historic brewpub settings. Data were collected through a structured online survey (n=78) followed by a photography activity (n=7) that was more qualitative in nature. The survey results revealed that attachment to the physical environment along with customer satisfaction were among the strongest predictors of overall place attachment. In addition, some meaningful differences in place attachment based on demographic factors such as gender, age group, frequency of visits, and length of residency in Greensboro were shown to exist. The photography project offered a more in-depth view of patron reactions to the built environment of Natty Greene's. Nine major themes emerged from participant photographs, including: symbolic meanings, satisfaction, openness, diversity of social functions, positive reflection on downtown, location, historic feel, materials and textures, and design features. Taken together, the mixture the methodologies employed in this study indicate that designing a historic physical environment in brewpubs is a promising strategy for engendering attachment to place for visitors. In the end, emotional attachment to place matters because of the responses it may inspire. Person-place bonds can motivate the preservation of buildings, the revitalization of a downtown, or loyalty to a local business.
Ariadne's Provisions: A 'Clue of Thread' to the Intricacies of Procedural Default, Adequate and Independent State Grounds, and Florida's Death Penalty

This Article will attempt to provide a “clue of thread” to state prisoners who wish to return alive from their venture into the habeas corpus corridor of the labyrinth of federalism. This labyrinth’s intricate passageways include the doctrines of procedural default and adequate and independent state grounds. The labyrinth of federalism houses the half-capital punishment and half-states rights creature born from a series of unfortunate circumstances typical of Greek tragedies. Like the minotaur, this creature demands human sacrifices.
A complex magnetic structure in the magnetoresistive La0.82Ba0.18CoO3

The magnetic structure of the perovskite cobaltite La0.82Ba0.18CoO3 was investigated using powder neutron diffraction. Although macroscopically this composition is thought to be in the spin-glass phase from bulk magnetic measurements, the presence of Bragg-like magnetic features in the neutron diffractograms suggests otherwise. At 4 K, two long-range magnetic orders are observed with two propagation wave vectors, k1 = (0,0,0) and k2 = (0,-0.5,0.5), corresponding to ferromagnetic and antiferromagnetic orders, respectively. However, above 100 K, the k2 component almost disappears, while k1 persists.
The Legacy of Geoffrey of Monmouth: Some Studies on Medieval Insular History and Fiction

History on the Edge: Excalibur and the Borders of Britain, 1100–1300. By Michelle R. Warren. University of Minnesota Press. 2000.Sovereign Fantasies: Arthurian Romance and the Making of Britain. By...
Adaptive power and rate control for satellite communications in Ka band

Adaptive power and rate control for efficient use of satellite channels in the Ka band are considered. Fading due to rain is modeled as a log-normally distributed, autoregressive process with known statistics. Adaptation policies based on MMSE channel estimation are designed taking into account the effect of channel estimation errors in an optimal manner so as to satisfy the required outage probability for given fading dynamics. Analytical results show average power savings or average bit rate increase that are available from adaptive techniques. It is demonstrated that a large improvement over a non-adaptive system is available provided an appropriately designed adaptation scheme that makes use of the channel fading statistics. Finally, practical methods based on adaptive modulation level selection in a fixed-bandwidth system are evaluated analytically in terms of average bandwidth efficiency.
Binswanger's Disease (Part II): Pathogenesis of Subcortical Arteriosclerotic Encephalopathy and Its Relation to Other Dementing Processes:

Subcortical arteriosclerotic encephalopathy (SAE) is a common though infrequently recognized dementia of the elderly. The unique vascular anatomy of the subcortical white matter and central brain stem probably predisposes those regions to chronic ischemia and incomplete infarction in the presence of various cardiovascular and hemodynamic insults. Recent studies have begun to define the risk factors for SAE, and others have shown it to be a condition frequently comorbid with the dementias of Alzheimer's disease, the multi-infarct state, and normal pressure hydrocephalus. Recent research into the etiologies of these disorders suggest certain pathogenetic links between them, strongly implying that they are not neatly distinct disease entities, as is commonly believed, and accounting for some of the overlap between these dementing illnesses seen clinically. (J Geriatr Psychiatry Neurol 1989; 2:171-181).
Business process flexibility: a driver for outsourcing

Many organizations have implemented business process management solutions that are enabled by enterprise resource planning (ERP) systems. More recently, organizations have focused their strategies on the additional benefits that are realizable by augmenting ERP with customer and supplier extensions. This paper focuses on the process integration issues that must be addressed when linking customers and suppliers to back‐office systems. Our hypothesis is that flexible process management, as required by modern customer/supplier relationships, are too costly to implement via traditional ERP solutions. Given that modern competitive advantage is measured in terms of business process flexibility, managers are faced with the daunting prospect of changing ERP configurations on a continuous basis. Such rapid process change requirements are beyond the financial capabilities of most companies, who prefer to leave a well‐tested configuration unchanged. How then are companies managing to deploy fast‐paced process change to support their new e‐business models? This paper describes the strategies that are being used to provide and maintain flexible eBusiness solutions.
Specific Response of the Immunoglobulins to Rubella Infection

The teratogenic consequences of rubella infection early in pregnancy are well known. However, experience with the rubella epidemic in 1964 revealed unexpected virologic and serologic consequences of maternal infection. Despite the fact that the rubella syndrome was caused by maternal infection prior to the immunologic maturity of the fetus, serologic immunity rather than tolerance was observed in older children with the syndrome (1, 2). Furthermore, rubella virus was found to persist in the affected infants for many months despite the presence of serum antibodies (3-5). Attempts to equate the presence of rubella antibodies in these infants with an active immune response by means of conventional serology was complicated by the presence of passively acquired maternal antibodies of the IgG variety which persist for several months. Since IgA and IgM do not cross the placental barrier readily, the association of antibody activity within the IgM and/or IgA class of globulins of the infant's serum would indicate...
Historical review of melanoma treatment and outcomes

The surgical and medical management of melanoma has changed dramatically since the first description of melanoma as a disease entity more than 200 years ago. Refinement of surgical techniques, including evaluation of optimal surgical margins, utility of elective lymph node dissection, and incorporation of sentinel lymph node mapping as both a prognostic tool and guide for selective lymphadenectomy have lessened surgical morbidity and improved outcomes for early-stage and locally advanced melanoma. Astute clinical observations of the integrated roles of the immune system and oncogenic mutations have more recently led to improvements in survival and quality of life for advanced melanoma. Herein, we provide an overview of the most significant surgical and medical milestones in the treatment of melanoma over the past 2 centuries.
Comparison of a quadroma and its parent hybridomas in fed batch culture

A quadroma (#22 x 63), formed by the fusion of two hybridomas, and its parent hybridomas (#22 and FMC 63) were each grown in fed batch cultures in order to examine the change in antibody productivity over time of the quadroma compared to its parent hybridomas. The growth rate, glucose uptake rate and lactate production rate of the quadroma were found to be intermediate between those of its parent cells of origin. The specific antibody productivity and internal antibody content of the quadroma followed the same decreasing trends over time as those seen in both parent hybridomas. Losses in specific antibody production rate and antibody content, however, occurred at a faster rate for the quadroma than for either of its parent hybridomas. Although the growth of a non-producing subpopulation is presumed to account for the drop in antibody production, there was no direct correlation between the percentage of high antibody containing cells, as determined by flow cytometry, and the specific antibody production rate.
Changes in longevity and causes of death among persons with hemophilia A

To examine recent changes in longevity and the causes of death among persons with hemophilia A, we evaluated death certificate data for persons who died in the United States from 1968 through 1989 and had hemophilia A or congenital Factor VIII disorder (ICD code 286.0) listed on the death certificate as one of the multiple causes of death. Multiple-cause-of-death mortality data for the United States from 1968 to 1989 were examined to compare death rates by year, focusing on death rates and causes of death for 1979-1981, 1983-1985, and 1987-1989. Gender, age group, race, geographic region, and median age at death of persons with hemophilia A and human immunodeficiency virus (HIV)-related disease listed as a cause of death were compared with those with hemophilia A without HIV-related disease. From 1968 through 1989, 2,792 hemophilia A deaths were reported. The death rate increased from 0.5 to 1.3 per 1,000,000 persons. From 1979-1981 through 1987-1989, mortality increased in all age groups above 9 years of age and age at death shifted markedly to lower ages. Median age at death decreased from 57 years in 1979-1981 to 40 years in 1987-1989. The percentage of deaths due to hemorrhage or diseases of the circulatory system decreased markedly as the result of the increase in deaths associated with HIV infection or infections other than HIV infection. Spread of HIV-1 infection in persons with hemophilia A has disrupted the reduction in mortality seen with factor replacement therapy, implementation of home care, and use of comprehensive hemophilia treatment centers. It is hoped that advances in the care of HIV-infected persons will improve survival in the hemophilia community.
Process Optimization and Properties of Laser Cladding High Speed Steel Coatings on Nodular Cast Iron

Rolls in the steel industry withstand very high loads, thermal cycling leading to thermal fatigue, and severe environmental. How to improve the wear resistance and elongate the service life of rolls matters a lot in reducing the consumption of rolls. In recent years, because of its better red-hardness and wear property, high speed steel (HSS) was used to manufacture the new type composite rolls. As a surface treatment technology, laser cladding can fabricate coating to improve the wear resistance of substrate. In this paper, the substrates for laser cladding were nodular cast iron rolls, Nd:YAG solid pulsed laser and continuous wave CO2 laser were both used to explore the feasibility of preparation HSS coatings. The Nd:YAG laser cladding results that the coated layers combined metallurgically with the substrate with a lot of microcracks. The average microhardness up to 600 HV is about 2 times as high as that of the substrate. The CO2 laser cladding results that: fully dense and crack free clad surfaces of high speed steel with an excellent metallurgical bonding were deposited. The average microhardness up to 900 HV is about 3 times as high as that of the substrate. The high-temperature (500 °C) wear rate is 40% of nodular cast iron’s in 30 min.
Neoadjuvant therapy for advanced squamous cell carcinoma of the cervix: Cisplatin followed by radiation therapy—A pilot study of the gynecologic oncology group

Eleven patients with untreated advanced squamous cell carcinoma of the cervix (FIGO Stage IIIB and IVA, or positive paraaortic nodes) were treated with cisplatin 50 mg/m2 every 3 weeks for six courses prior to irradiation therapy (RT). Six patients completed six courses of cisplatin prior to RT with one complete and two partial responses (PR). Five other patients did not complete cisplatin therapy; two progressed after two and three courses, one had a PR after three courses and refused further therapy, one refused treatment after two courses and one elected to begin RT after one course. Two patients had reversible nephrotoxicity. No other major toxicity was noted. Six patients had stem cell assay prior to treatment and assay results were predictive of cisplatin response in five. Only one patient remains alive at 44+ months. Cisplatin chemotherapy prior to irradiation therapy is feasible and without substantial toxicity but is unlikely to be of benefit in patients with advanced cervical cancer.
Nitrogen Release Rate Differs by Fertilizer Source

Abstract Controlled-release fertilizers allow growers to reduce leachate nitrogen loss and better manage crop nutrition in comparison to water-soluble fertilizers. Nitrogen leaching and plant growth were evaluated in a container production system using a granular water-soluble (GWS) ammonium nitrate fertilizer (34-0-0), a controlled-release fertilizer (CRF) (18N-6P-12K), and a non-fertilized control (NFC). Selected plant species were grown for ten weeks using 1,485 g N per cubic meter (2.5 pounds N per cubic yard) CRF or the GWS fertilizer. Leachate pH was higher (7.0+) for the GWS and NFC treatments than the CRF (6.5 to 7.0). Total soluble salts in the leachates reflected the initial leaching of salts from the substrate, with a continued decrease in soluble salts for the GWS fertilizer and NFC treatments. With the CRF, soluble salts decreased slightly during the first five weeks, but then increased over the next five weeks. The CRF provided acceptable ammonium levels for production purposes throughout th...
The Relation Between Testing Environment and Baseline Performance in Child and Adolescent Concussion Assessment

Background:Previous research has demonstrated differences in cognitive performance when baseline concussion assessment is performed in a group versus an individual setting. Accurate baseline assessment is imperative when such data are used to make clinical decisions regarding cognitive and symptom recovery after concussion.Hypothesis:The use of similar standardized test administration procedures and test conditions across group and individual settings results in no differences in cognitive performance or symptom reporting.Study Design:Cohort study; Level of evidence, 3.Methods:A total of 939 participants (aged 5-18 years), including 313 tested individually and 626 tested in a group setting, matched on age, sex, and attention-deficit/hyperactivity disorder status, were administered concussion baseline assessment using the desktop version of the Immediate Post-Concussion Assessment and Cognitive Testing and a new pediatric measure, the Multimodal Assessment of Cognition & Symptoms for Children. Cognitive pe...
Modeling the Complexity of Post-Treatment Drinking: It’s a Rocky Road to Relapse

The most widely cited road block to successful treatment outcomes for psychological and substance use disorders has been described as the return to the previous behavior, or “relapse.” The operational definition of “relapse” varies from study to study and between clinicians, but in general the term is used to indicate the return to previous levels of symptomatic behavior. One explanation for the variation in the operationalization of relapse is the wide variety of behaviors for which the term is applied, including (but not limited to): depression, substance abuse, schizophrenia, mania, sexual offending, risky sexual behavior, dieting, and the anxiety disorders. A second explanation for the multitude of definitions for relapse is the inherent complexity in the process of behavior change. In this paper we present the most recent treatment outcome research evaluating relapse rates, with a special focus on the substance use disorders. Following this review of the literature we present an argument for the operationalization of relapse as a dynamic process, which can be empirically characterized using dynamical systems theory. We support this argument by presenting results from the analysis of alcohol treatment outcomes using catastrophe modeling techniques. These results demonstrate the utility of catastrophe theory in modeling the alcohol relapse process. The implications of these analyses for the treatment of alcohol use disorders, as well as a discussion of future research incorporating nonlinear dynamical systems theory is provided.
The social worlds of 8‐ and 12‐month‐old infants: Early experiences in two subcultural contexts

In this study, we explored the everyday experiences of 40 infants from families who migrated recently from Central America to the US. Another 42 infants from middle class families of Euro-American background were included to facilitate the evaluation of our methodology and findings. Detailed descriptions of the previous 24 hours were obtained by interviewing the mothers when their infants were 8 and 12 months of age. The infants' experiences and activities were very similar in both groups, and the effects of the mothers', fathers' or others' presence on ongoing activities were similar, too. The groups differed with regard to (1) the circadian distribution of activities, (2) opportunities for interactions with various people, and (3) the differences between weekdays and weekends. Overall, the social worlds of the Central American children were characterized by the simultaneous presence of several people and thus by multiple social partners. The social worlds of the Euro-American children were characterized by more opportunities for dyadic interactions and by exposure to fewer partners.
Interaction of the Essential Drosophila Nuclear Protein YA with P0/AP3 in the Cytoplasm and in Vitro: Implications for Developmental Regulation of YA's Subcellular Location

Abstract The Drosophila nuclear lamina protein YA is essential for the transition from female meiosis to embryo mitosis. Its localization and, hence, function is under developmental and cell cycle controls. YA protein is hyperphosphorylated and cytoplasmic in ovaries. Upon egg activation, YA is partially dephosphorylated and acquires the ability to enter nuclei. Its function is first detected at this time. To investigate the cytoplasmic retention machinery that keeps YA from entering nuclei, we used affinity chromatography and blot overlay assays to identify cytoplasmic proteins that associate with YA. Drosophila P0/AP3, a ribosomal protein that is also an apurinic/apyrimidinic endonuclease, binds to YA in ovary and embryo cytoplasms. P0 and YA bind specifically and directly in vitro and are present in a 20S complex in the cytoplasmic extracts. YA protein can be phosphorylated by MAPK, but not by p34Cdc2 kinase, in vitro. This phosphorylation increases YA's binding to P0. We propose that the P0-containing 20S cytoplasmic complex retains hyperphosphorylated ovarian YA in the cytoplasm. In response to egg activation, YA is partially dephosphorylated and its binding to the 20S complex is reduced. Hence, some YA dissociates from the complex and enters nuclei. Consistent with this model, decreasing P0 levels partially suppress a hypomorphic Ya mutant allele.
Collisional incoherence in neutrino line emission

The collisional broadening of neutrino line emission in stellar cores is analyzed. In a Lorentz model for impact broadening the linewidth is determined by the neutrino wavelength and by the thermal velocity and the collision frequency of the emitting nucleus. The general expressions are applied for the /sup 7/Be electron-capture reaction in the Sun. The resulting collisional coherence time of 5 x 10/sup -17/ sec yields an upper limit of 10/sup -7/ eV/sup 2/ on the difference in the neutrino mass squared for observable neutrino oscillations on Earth.
MRPC: a high performance RPC system for MPMD parallel computing

MRPC is an RPC system that is designed and optimized for MPMD parallel computing. Existing systems based on standard RPC incur an unnecessarily high cost when used on high-performance multi-computers, limiting the appeal of RPC-based languages in the parallel computing community. MRPC combines the efficient control and data transfer provided by Active Messages (AM) with a minimal multithreaded runtime system that extends AM with the features required to support MPMD. This approach introduces only the necessary RPC overheads for an MPMD environment. MRPC has been integrated into Compositional C++ (CC++), a parallel extension of C++ that offers an MPMD programming model. Basic performance in MRPC is within a factor of two from those of Split-C, a highly tuned SPMD language, and other messaging layers. CC++ applications perform within a factor of two to six from comparable Split-C versions, which represent an order of magnitude improvement over previous CC++ implementations. Copyright © 1999 John Wiley & Sons, Ltd.
Pediatric neurodevelopment and sports participation: When are children ready to play sports?

A fundamental knowledge of normal child and adolescent development is essential to providing a developmentally appropriate sports experience for the child, and to providing guidance to parents regarding their child's sport participation. This article reviews neurodevelopment, normal child and adolescent development relevant to sport participation, and developmental readiness to participate in sports. Neurodevelopmental maturation is a complex, continuous process. The sense of social comparison is not achieved until after 6 years of age, and the ability to understand the competitive nature of sports is generally not achieved until 9 years of age. By about 12 years of age, most children are mature enough to comprehend the complex tasks of sports and are physically and cognitively ready to participate in competitive sports with appropriate supervision.
Improved corrosion behavior of nanocrystalline zinc produced by pulse-current electrodeposition

Pulse electrodeposition was used to produce nanocrystalline (nc) zinc from zinc chloride electrolyte with polyacrylamide and thiourea as additives. Field emission scanning electron microscopy (FESEM) was used to study the grain size and surface morphology of the deposits and X-ray diffraction was used to examine their preferred orientation. Corrosion behavior of the electrodeposited nc zinc in comparison with electrogalvanized (EG) steel in de-aerated 0.5 N NaOH solution was studied using potentiodynamic polarization and impedance measurements. A scanning electron microscope (SEM) was used to characterize the surface morphology of the EG steel before corrosion testing. Surface morphologies of nc zinc deposits and EG steel were also studied after potentiondynamic polarization by SEM. Nanocrystalline zinc (56 nm) with random orientation was produced. The estimated corrosion rate of nc zinc was found to be about 60% lower than that of EG steel, 90 and 229 lA/cm 2 , respectively. The surface morphology of corroded nc zinc was characterized by discrete etch pits, however, uniform corrosion was obtained after potentiodynamic polarization of EG steel. The passive film formed on the nc zinc surface seems to be a dominating factor for the corrosion behavior observed.
Systematic design of 10-bit 50MS/s pipelined ADC

A systematical design analysis of a 10-bit 50MS/s pipelined ADC is presented. With an opamp-sharing technique, the power consumption is reduced drastically. Simulated in a 130-nm CMOS process, it achieves a 58.9dB signal-to-noise ratio (SNR), a 9.3 effective number of bits (ENOB), 64dB spurious free dynamic range (SFDR) with a sinusoid input of 4.858-MHz 1-Vpp at 50MS/s, and consumes less than 24 mW from a 1.2-V supply.
Near-atomic resolution crystal structure of an A-DNA decamer d(CCCGATCGGG): cobalt hexammine interaction with A-DNA.

The structure of the DNA decamer d(CCCGATCGGG) has been determined at 1.25 A resolution. The decamer crystallized in the tetragonal space group P4(3)2(1)2, with unit-cell parameters a = b = 44.3, c = 24.8 A and one strand in the asymmetric unit. The structure was solved by the molecular-replacement method and refined to R(work) and R(free) values of 16.3 and 18.5%, respectively, for 5969 reflections. The decamer forms the A-form DNA duplex, with the abutting crystal packing typical of A-DNA. The crystal packing interactions seem to distort the local conformation: A5 adopts the trans/trans conformation for the torsion angles alpha and gamma instead of the usual gauche(-)/gauche(+) conformations, yielding G*(G.C) base triplets. The highly hydrated [Co(NH(3))(6)](3+) ion adopts a novel binding mode to the DNA duplex, binding directly to phosphate groups and connecting to N7 and O6 atoms of guanines by water bridges. Analysis of thermal parameters (B factors) shows that the nucleotides involved in abutting crystal packing are thermally more stable than other nucleotides in the duplex.
Antagonism of amphetamine stereotyped behavior by diastereoisomeric dihydrodibenzothiepin neuroleptics

Differences in neuroleptic activity were observed between the diastereoisomers of a dihydrodibenzothiepin derivative, while no potency differences were seen between their respective enantiomorphs.