cssi/SciSciGPT-SciSciNet huggingface dataset:
ReCellular Inc: Managing Demand Uncertainty in Closed-Loop Remanufacturing

The modeling-based case study is useful for two purposes: introduce closed-loop supply chains and highlight and model some of its unique aspects that the traditional newsvendor formulation does not...
The Origins of Technology-Skill Complementarity

Current concern with relationships among particular technologies, capital and the wage structure motivates this study of the origins of technology-skill complementarity in manufacturing. We offer evidence of the existence of technology-skill and capital-skill (relative) complementarities from 1909 to 1929 and suggest that they were associated with continuous-process and batch methods and the adoption of electric motors. Industries that used more capital per worker and a greater proportion of their horsepower in the form of purchased electricity employed relatively more educated blue-collar workers in 1940 and paid their blue-collar workers substantially more from 1909 to 1929. We also infer capital-skill complementarity using the wage-bill for non-production workers and find that the relationship was as large from 1909-19 as it has been recently. Finally, we link our findings to those on the high- school movement (1910 to 1940). The rapid increase in the supply of skills from 1910 to 1940 may have prevented rising inequality with technological change.
Single-Cell Profiling Reveals Metabolic Reprogramming as a Resistance Mechanism in BRAF-Mutated Multiple Myeloma.

Purpose: Although remarkably effective in some patients, precision medicine typically induces only transient responses despite initial absence of resistance-conferring mutations. Using BRAF-mutated myeloma as a model for resistance to precision medicine we investigated if BRAF-mutated cancer cells have the ability to ensure their survival by rapidly adapting to BRAF inhibitor treatment. Experimental Design: Full-length single-cell RNA (scRNA) sequencing (scRNA-seq) was conducted on 3 patients with BRAF-mutated myeloma and 1 healthy donor. We sequenced 1,495 cells before, after 1 week, and at clinical relapse to BRAF/MEK inhibitor treatment. We developed an in vitro model of dabrafenib resistance using genetically homogeneous single-cell clones from two cell lines with established BRAF mutations (U266, DP6). Transcriptional and epigenetic adaptation in resistant cells were defined by RNA-seq and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq). Mitochondrial metabolism was characterized by metabolic flux analysis. Results: Profiling by scRNA-seq revealed rapid cellular state changes in response to BRAF/MEK inhibition in patients with myeloma and cell lines. Transcriptional adaptation preceded detectable outgrowth of genetically discernible drug-resistant clones and was associated with widespread enhancer remodeling. As a dominant vulnerability, dependency on oxidative phosphorylation (OxPhos) was induced. In treated individuals, OxPhos was activated at the time of relapse and showed inverse correlation to MAPK activation. Metabolic flux analysis confirmed OxPhos as a preferential energetic resource of drug-persistent myeloma cells. Conclusions: This study demonstrates that cancer cells have the ability to rapidly adapt to precision treatments through transcriptional state changes, epigenetic adaptation, and metabolic rewiring, thus facilitating the development of refractory disease while simultaneously exposing novel vulnerabilities.
Trends in Adolescent Asthma Responsibility Over a 12-Month Study Period.

Abstract Purpose The aim of this study is to assess factors that influence adolescent asthma responsibility and how patient- and parent-reported asthma responsibility changes over a 12-month period. Methods One hundred sixty-four adolescents and their parents completed questionnaires at baseline and 12 months, including the asthma responsibility questionnaire, in which higher scores indicate greater adolescent responsibility. Multiple linear regression was used to assess how baseline asthma responsibility, self-efficacy, outcome expectations, and demographic characteristics were associated with 12-month asthma responsibility. Results Asthma responsibility as reported by both adolescents and parents shifted significantly toward the adolescent over the study period (p Conclusions Asthma responsibility shifted toward adolescents over a 12-month period. Regardless of age and gender, all types of adolescents were able to improve their responsibility level based on adolescent-reported results. Older females, according to parent-reported results, were more likely to improve their responsibility. Providers need to make sure adolescents are learning all the necessary skills to manage asthma independently before they reach adulthood.
Section 338 and Its Foolish Consistency Rules - The Hobgoblin of Little Minds

When Congress adopted Section 338 in 1982, it included two sets of consistency rules to prevent the continued availability of a means of extending the scope of the General Utilities doctrine by permitting a target corporation to select only some of its assets for nonrecognition of income. The principal purpose of those rules was eliminated in 1986 when Congress repudiated virtually all of the General Utilities doctrine. As a consequence, a number of commentators have urged the repeal of the consistency rules. In January, 1992, the Treasury promulgated proposed regulations that would substantially modify the regulatory application of the consistency and related rules so as to eradicate much of their bite and limit the circumstances in which they will apply. In 1994, with a few modifications, the proposed regulations were finalized. The purposes of this article are to examine whether there is any longer a reason for concern because a target corporation can choose selected assets for nonrecognition and to what extent the 1994 regulations properly deal with potentially abusive circumvention of tax goals. Before examining the current status of the consistency requirements, the historical background that led to the adoption of Section 338 and the operation of the section is discussed. The historical background includes: the judicially created Kimbell-Diamond rule, the codification and modification of that rule by the old version of Section 334(b)(2), the operation of the old version of Section 337 that provided nonrecognition for certain liquidating sales of corporate assets, and the replacement of the old version of Section 334(b)(2) by Section 338. The general operation of Section 338 is then sketched, and the special election provided by Section 338(h)(10) is examined. Finally the consistency rules are examined and critiqued.
Making Assessment Decisions: Macro, Mezzo, and Micro Perspectives

This chapter addresses potential barriers to good clinical decision-making, found at all levels of practice. It begins with decision-making at the micro-level—that is, at the level of the individual clinician, who faces a series of decisions with each new case: how to frame problems, what outcomes to pursue, when to stop collecting information, what risks to take, what criteria to use to select practice methods, and how to evaluate progress. The flexible and diverse nature of clinical practice, while allowing for consideration of specific client needs, also leaves room for many kinds of error. These errors can be avoided, or at least minimized, by the use of evidence-informed assessment practices as outlined in the chapter. At the mezzo-level, requirements of the practice setting (such as mission and funding source) can shape and constrain the way assessment takes place; the media, professional literature, and structure of professional training also exert a powerful influence. Macro-level influences include the widespread medicalization of human behavior; the pharmaceutical companies and managed care institutions comprising the “biomedical industrial complex;” and entities such as the National Institute of Mental Health, the American Psychiatric Association, and the welfare and legal systems. The chapter concludes by urging students to consider the biases that may be inherent in the information on which they base their decisions, as well as how the environment they work in may affect their ability to make sound clinical decisions.
Light-Induced Cytochrome Reduction in Neurosporacrassa Membrane Fractions

Neurospora crassa mycelium harvested from liquid culture was homogenized and the homogenate fractionated by differential centrifugation. Particulate fractions enriched for mitochondria, presumptive plasma membrane, and endoplasmic reticulum respectively were obtained. All of the fractions contained a cytochrome system which became reduced on irradiation with blue light, and became reoxidized upon subsequent darkness. The distribution of this activity matched closely that of a sodium-dependent ATPase, a putative plasma membrane marker, but was markedly different from the distribution either of mitochondrial or endoplasmic reticulum marker enzymes. The light reaction could only be observed when samples were partially anaerobic. The light-minus- darkness difference spectrum, dark decay kinetics, and requirement for partial anaerobicity all closely resembled the same three parameters reported in the literature for intact mycelium of Neurospora (1). Preliminary investigations with a mutant thought to be deficient in b-type cytochromes revealed reduced light sensitivity in a test for light-suppression of circadian formation of conidia. It seems possible that a flavin-cytochrome pigment system could serve as the photoreceptor complex for the in vivo photoresponse.
Diel Activity Patterns of Juvenile Late Fall‐run Chinook Salmon with Implications for Operation of a Gated Water Diversion in the Sacramento–San Joaquin River Delta

In the Sacramento–San Joaquin River Delta, California, tidal forces that reverse river flows increase the proportion of water and juvenile late fall-run Chinook salmon diverted into a network of channels that were constructed to support agriculture and human consumption. This area is known as the interior delta, and it has been associated with poor fish survival. Under the rationale that the fish will be diverted in proportion to the amount of water that is diverted, the Delta Cross Channel (DCC) has been prescriptively closed during the winter out-migration to reduce fish entrainment and mortality into the interior delta. The fish are thought to migrate mostly at night, and so daytime operation of the DCC may allow for water diversion that minimizes fish entrainment and mortality. To assess this, the DCC gate was experimentally opened and closed while we released 2983 of the fish with acoustic transmitters upstream of the DCC to monitor their arrival and entrainment into the DCC. We used logistic regression to model night-time arrival and entrainment probabilities with covariates that included the proportion of each diel period with upstream flow, flow, rate of change in flow and water temperature. The proportion of time with upstream flow was the most important driver of night-time arrival probability, yet river flow had the largest effect on fish entrainment into the DCC. Modelling results suggest opening the DCC during daytime while keeping the DCC closed during night-time may allow for water diversion that minimizes fish entrainment into the interior delta. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Statistical, economic and other tools for assessing natural aggregate

Quantitative aggregate resource assessment provides resource estimates useful for explorationists, land managers and those who make decisions about land allocation, which may have long-term implications concerning cost and the availability of aggregate resources. Aggregate assessment needs to be systematic and consistent, yet flexible enough to allow updating without invalidating other parts of the assessment. Evaluators need to use standard or consistent aggregate classification and statistic distributions or, in other words, models with geological, geotechnical and economic variables or interrelationships between these variables. These models can be used with subjective estimates, if needed, to estimate how much aggregate may be present in a region or country using distributions generated by Monte Carlo computer simulations.
The DNA of annexin V-binding apoptotic cells is highly fragmented

Jurkat leukemia cells induced to undergo apoptosis by treatment with an antibody against the Fas receptor have two annexin V (AV)-binding subpopulations: (a) single-positive cells that bind AV but not propidium iodide (PI); and (b) double-positive cells that bind AV and PI. The single-positive population is thought to represent an early stage of apoptosis. We have examined the relationship between AV binding and a classical characteristic of apoptosis, DNA fragmentation. Time course studies with Jurkat cells treated for 1, 2, or 4 h with anti-Fas indicated that the proportion of AV-binding cells was increased after 2 h. A significant increase in DNA fragmentation was observed only at 4 h as measured by the mean tail moment determined with the alkaline single cell gel electrophoresis (comet) assay. This correlation suggests a temporal relationship between the two parameters, but does not provide direct evidence of what happens in individual cells. We developed a method to measure fluorescent markers of cellular structure or function with a laser scanning cytometer and then perform the comet assay on the same cells. Cells in each AV-binding subpopulation were re-examined before and after electrophoresis. Most AV-/PI- cells had no DNA damage, although a few cells showed a pattern of damage characteristic for apoptosis. Double-positive cells all had damaged DNA; approximately half had the apoptotic pattern, and the rest had a pattern typical for necrosis. Nearly all of the single-positive cells had damaged DNA with the apoptotic pattern. Both AV-positive populations contained cells with little or no detectable DNA after electrophoresis, indicating that the DNA was highly fragmented. These results indicate that AV binding is an excellent marker for apoptotic cells, but that these cells already have fragmented DNA.
A Theory of Compulsory Process Clause Discovery Rights

Anyone who has practiced or studied both civil and criminal litigation in the United States' is immediately struck by the relative lack of discovery devices available to the defendant in a criminal prosecution. The sharp divergence does not appear to be supportable and undermines the criminal trial as a truthseeking device. It does, however, compel rethinking the fact-gathering process in criminal litigation and, in particular, the criminal defendant's role in shaping the evidence at trial. This Article examines how the Compulsory Process Clause speaks to these issues. Approximately twenty years ago, Professor Peter Westen suggested that we ground discovery rights in the Compulsory Process Clause.' His approach, while acknowledged by the United States Supreme Court,3 has proven too unwieldy for adoption. This Article revisits the important questions raised by Professor Westen's work, makes the argument that the Compulsory Process Clause is the appropriate source of at least certain criminal discovery rights, and develops a new framework for resolving discovery problems in criminal litigation. Part I describes the core rights protected by the Compulsory Process Clause. Part II explores the outer limits of the Clause and in particular, the Supreme Court's interpretation of the Compulsory Process Clause as a check against the prosecution's presentation of the evidence. Part III demonstrates the necessity, but unavailability, of formal discovery devices to effect the "checking" function of the Clause. Part IV argues that realizing the "checking" function of the Compulsory Process Clause necessarily means grounding certain discovery rights in the Clause. Part IV also delineates the appropriate scope of Compulsory Process Clause discovery rights. The theoretical framework advanced in this Article is important. While Westen advanced a theory which was more sweeping, it would also necessitate a wholesale rewriting of the Supreme Court's criminal discovery jurisprudence; that theory has largely failed. This Article advances a more specific theory and one that is more consonant with case law and weighty policy considerations.
Immediate placement and provisionalization of implant-supported, single-tooth restorations: a retrospective study

Immediate implant placement into extraction sockets has been widely reported in the dental literature, but few studies have evaluated immediate loading of such implants. This retrospective study evaluated 206 implants placed into fresh extraction sites using a flapless technique, followed by immediate provisionalization with nonoccluding single-tooth restorations and definitive restoration within 2 weeks. Cumulative survival and success rates were 98.77% (mean follow-up, 23.1 months). Periodontitis did not influence the outcome adversely. Within the limitations of this study, immediate implant placement and restoration, followed by definitive loading within 2 weeks, achieved outcomes comparable to those historically reported for delayed implants.
Mediated effects of physical risk factors, leader-member exchange and empowerment in predicting perceived injury risk.

In the context of conservation of resources theory, we examine the indirect (mediated) effects of physical risk factors, leader-member exchange (LMX) and empowerment on perceived injury risk in a heterogeneous sample (N = 226) of individuals employed in occupations related to production, construction and installation/maintenance. Positioning work role stressors and upward safety communications as two important mediating variables, as predicted, LMX and empowerment demonstrated significant indirect effects on perceived injury risk. Results from our model also provide preliminary evidence that an asymmetrical dualistic process exists in terms of the effect physical risk factors have on perceived injury risk via depletion of both psychological (i.e. role stressors) and physical resources (i.e. physical symptoms). Theoretical and practical implications based on the results of our model are also discussed. Copyright © 2011 John Wiley & Sons, Ltd. Language: en
Metallo-Biopolymers: Conjugation Strategies and Applications

Metallo-biopolymers are an exciting class of materials that integrate the optical, electronic, magnetic, and chemical properties of metal complexes with the specificity and highly ordered structures of biopolymers. Metal complexes can be incorporated into the biopolymers using a multitude of synthetic methodologies. Developments in the fields of synthetic organic/organometallic chemistry and biological chemistry have enabled new conjugation methods that can expand the diversity and scope of such integrated metallo-biopolymer assemblies. The conjugation of metal complexes and biopolymers leads to new classes of hybrid materials for applications spanning biomaterials, drug delivery, imaging, sensing, photodynamic therapy, catalysis, optoelectronics, and energy conversion. This review article summarizes the synthetic strategies that have been adopted for the conjugation between biopolymers and metal complexes, as well as some of the various applications of these metallo-biopolymers.
NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca2+ Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery

Cochlear blood flow regulation is important to prevent hearing loss caused by ischemia and oxidative stress. Cochlear blood supply is provided by the spiral modiolar artery (SMA). The myogenic tone of the SMA is enhanced by the nitric oxide synthase (NOS) blocker L-NG-Nitro-Arginine (LNNA) in males, but not in females. Here, we investigated whether this gender difference is based on differences in the cytosolic Ca2+ concentration and/or the Ca2+ sensitivity of the myofilaments. Vascular diameter, myogenic tone, cytosolic Ca2+, and Ca2+ sensitivity were evaluated in pressurized SMA segments isolated from male and female gerbils using laser-scanning microscopy and microfluorometry. The gender difference of the LNNA-induced tone was compared, in the same vessel segments, to tone induced by 150 mM K+ and endothelin-1, neither of which showed an apparent gender-difference. Interestingly, LNNA-induced tone in male SMAs was observed in protocols that included changes in intramural pressure, but not when the intramural pressure was held constant. LNNA in male SMAs did not increase the global Ca2+ concentration in smooth muscle cells but increased the Ca2+ sensitivity. This increase in the Ca2+ sensitivity was abolished in the presence of the guanylyl cyclase inhibitor ODQ or by extrinsic application of either the nitric oxide (NO)-donor DEA-NONOate or the cGMP analog 8-pCPT-cGMP. The rho-kinase blocker Y27632 decreased the basal Ca2+ sensitivity and abolished the LNNA-induced increase in Ca2+ sensitivity in male SMAs. Neither LNNA nor Y27632 changed the Ca2+ sensitivity in female SMAs. The data suggest that the gender difference in LNNA-induced tone is based on a gender difference in the regulation of rho-kinase mediated Ca2+ sensitivity. Rho-kinase and NO thus emerge as critical factors in the regulation of cochlear blood flow. The larger role of NO-dependent mechanisms in male SMAs predicts greater restrictions on cochlear blood flow under conditions of impaired endothelial cell function.
Novel implications in the development of endometriosis: biphasic effect of macrophage activation on peritoneal tissue expression of tissue inhibitor of metalloproteinase-1.

PROBLEM: Elevated levels of activated macrophages are associated with endometriosis, but their role in the etiology of the disease is uncertain. The current study was undertaken to examine whether activated macrophages could modulate peritoneal tissue expression of the tissue inhibitor of metalloproteinase- 1 (TIMP-1), which may play a role in the development of endometriosis. METHOD OF STUDY: Female mice were treated with the macrophage activator lipopolysaccharide (LPS), and peritoneum TIMP-I mRNA was examined by Northern blot analysis. RESULTS: LPS induced a dose-dependent increase (P < 0.05) in TIMP-I mRNA expression at levels of I μg (70.0% ± 5.8% greater than the control), 10 μg (83.0% ± 12.0% greater than the control), and 25 μg (100.0% ± 10.0% greater than the control). In contrast, the administration of 50 μg of LPS resulted in a decrease in TIMP-I mRNA expression below baseline levels (18.0% ± 6.0% less than the control values). CONCLUSIONS: Activated macrophages and/or their products modulate peritoneum TIMP-I expression. These data suggest that, in addition to their phagocytotic role in the peritoneal cavity, these immune cells also may play a novel role in influencing the ability of the peritoneum to regulate tissue/cell invasion and in the development of endometriosis through TIMP-I expression.
Doctors within borders: the potential benefit of otolaryngology "medical missions" at home.

OBJECTIVES: Describe the population, Medicaid, uninsured, and otolaryngology practice demographics for seven representative rural southeastern states, and propose academic affiliated outreach clinics as a service to help meet the specialty care needs of an underserved rural population, based on the "medical mission" model employed in international outreach clinics. STUDY DESIGN: Needs assessment. METHODS: Review of medical licensing and practice location data from state medical licensing authorities, together with population, Medicaid, and uninsured data from state health/human services departments and the U.S. Census Bureau. RESULTS: Of the states examined, 38-74% of the population lives outside major state metropolitan areas, and 23-47% reside in a county in which there are no practicing otolaryngologists. These rural areas contain from 43-75% of the states' Medicaid recipients as well as 37-77% of the uninsured residents. CONCLUSIONS: Borrowing design elements from the international outreach clinics which involve many US otolaryngologists, a similar "medical mission" model could be of benefit domestically. There are rural areas of the southeast where visiting outreach clinics could improve access to otolaryngology care, and facilitate effective use of existing "safety net" healthcare resources.
Reactivity of Dioxovanadium(V) Complexes with Hydrogen Peroxide: Implications for Vanadium Haloperoxidase

The dioxovanadium(V) complexes VO2(bpg) (1), [VO2(pmida)]- (2), and [VO2(ada)]- (3) have been synthesized and characterized as models for the vanadium haloperoxidases. These compounds react with hydrogen peroxide in acetonitrile to form the corresponding peroxovanadium(V) complexes that have been previously studied by stopped-flow spectrophotometry. 1H and 51V NMR spectra of the VO2+ complexes in aqueous solution provide a clear picture of the solution structure of each complex. The results of these kinetic studies suggest an associative mechanism in which peroxide binds to a protonated form of the vanadium complex, followed by loss of a bound hydroxide or water molecule in the rate-determining step of the reaction and rapid rearrangement to the final product. The addition of acid to the reaction mixture results in rapid increases in the rate of peroxide binding by vanadium as a result of increased protonation of the complex. As in previous studies of similar reactions in aqueous solution, the reaction is...
Quantitative Nuclear Evaporation Theory and the Nuclear Potential

The energy level densities of nucleons in a diffuse nuclear well are calculated using an Eckart-Bethe (Woods-Saxon) potential and shown to be a more sensitive function of energy than the calculated densities of nucleons in a square well having the same volume. The particle spectra of 16-MeV ($p, n$) reactions and 14-MeV inelastically scattered neutrons are computed including multiple neutron emission. Using realistic values for the effective nucleon mass, the nuclear radius, and the diffuseness parameters we find that the theoretical spectra fit the experimentally observed spectra well within the experimental error. This fit is obtained without the usual experimental parameter fitting of theoretically undetermined constants. Methods of obtaining single-particle emission spectra from experimentally determined particle spectra when multiple-particle emission occurs are discussed. Our work suggests that a careful analysis of precisely measured evaporation spectra will give some information about the dependence of the diffuseness of the nuclear potential on excitation energy.
Diseases: Study neuron networks to tackle Alzheimer's

Researchers have generally looked for signs of Alzheimer's disease in the whole brain or at the single-gene level. The biggest clues will come from monitoring collections of neurons, says Kenneth S. Kosik.
Port of Last Resort: The Diaspora Communities of Shanghai . By Marcia Reynders Ristaino. Stanford: Stanford University Press, 2001. xviii, 369 pp. $60.00 (cloth).

This book examines two large and generally overlooked diaspora communities, one Jewish and the other Slavic, which found refuge in Shanghai during the period 1900-1950. Victims of discrimination and persecution in their own lands-Central and Eastern Europe, Russia, and Ukraine-they chose Shanghai as their destination because no documentation was required to enter the city and settle there. In their struggle to survive and build a life in this Chinese open port, they encountered severe political, social, economic, and cultural challenges. The Jewish diaspora community began forming in the early 1900s and increased to more than 18,000 after the initial triumphs of Nazism. The Slavic community eventually numbered about 30,000 people, escaping revolution and persecution from Bolshevik and fascist forces at home and in north China. This book focuses on how these diverse groups, adhering to various religious and cultural traditions, formed communities, preserved their national and cultural identities, chose their leaders, found gainful employment, coped with the alien Chinese culture, educated and raised their children, and established a considerable presence in this large, cosmopolitan city. The author examines at length the different experiences and responses of the two diaspora groups during World War II under the Japanese occupation of Shanghai. With the Chinese Communist takeover of the city in 1949, both groups found themselves in a renewed struggle to find a home, adding still another chapter to the saga of their diaspora experiences. The book concludes with an account of how the two groups handled this new challenge and where they finally found refuge. Apart from the particulars of the Shanghai experience, the story of the two communities clearly resonates with today's accounts of societies in conflict, dislocated populations, and varied struggles to survive and sustain life under trying conditions.
Recombinant mitochondrial plasmids in Neurospora composed of Varkud and a new multimeric mitochondrial plasmid

A mitochondrial plasmid, V5124, in Neurospora intermedia isolate 5124 has a deletion in its sequence relative to the highly similar Mauriceville and Varkud plasmids. These insertions in the latter plasmids are 28 bp in length and are positioned at sites that correspond to their major transcript 5′ termini. The 28-bp sequence is nearly identical to a putative processing site upstream of the ND4L gene on the mitochondrial genome. The absence of this 28-bp sequence in V5124 apparently results in transcripts whose 5′ termini correspond to an upstream consensus promoter sequence. Two variant forms of V5124 coexist with V5124 and have either of two similar 0.3-kb inserts positioned exactly as is the 28-bp insert in Varkud. These long inserts are chimeric, partly deriving from a newly discovered multimeric plasmid, MP. MP has significant similarity to a short region of the mitochondrial satellite plasmid VS. Another part of the 0.3-kb inserts in V5124 variants derives from the mitochondrial genome, within restriction fragment EcoRI-8. Neurospora mitochondria in many isolates can have several types of mitochondrial plasmids belonging to different homology groups. We propose that a common ancestral plasmid acquired insertions from either the mitochondrial genome or from other plasmids. The V5124 variants are the first instance of a chimeric mitochondrial plasmid in which distinct plasmids have recombined. This recombination proves that different plasmids coexist currently, or else did so at some point in their evolution, within a single mitochondrion.
Efficient semiparametric estimation of multi-valued treatment effects under ignorability ☆

Abstract This paper studies the efficient estimation of a large class of multi-valued treatment effects as implicitly defined by a collection of possibly over-identified non-smooth moment conditions when the treatment assignment is assumed to be ignorable. Two estimators are introduced together with a set of sufficient conditions that ensure their n -consistency, asymptotic normality and efficiency. Under mild assumptions, these conditions are satisfied for the Marginal Mean Treatment Effect and the Marginal Quantile Treatment Effect, estimands of particular importance for empirical applications. Previous results for average and quantile treatments effects are encompassed by the methods proposed here when the treatment is dichotomous. The results are illustrated by an empirical application studying the effect of maternal smoking intensity during pregnancy on birth weight, and a Monte Carlo experiment.
Quantitation of matrix Gla protein mRNA by competitive polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase as an internal control.

Abstract Matrix Gla (ψ-carboxyglutamic acid) protein (MGP) is a vitamin-K-dependent extracellular matrix protein. A method was developed to quantitate MGP mRNA based on competitive polymerase chain reaction following reverse transcription (competitive RT-PCR). The MGP cDNA was coamplified with a mutant MGP cDNA (competitor). The ratio of MGP to competitor after the PCR reaction was compared to standards to determine the amount of MGP mRNA in RT samples. MGP mRNA in as little as 3.125 ng total RNA was accurately quantitated and was far more sensitive than RNA hybridization methods. To control for variations due to sample preparation, a second competitive RT-PCR was developed to measure the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA from the same sample as an internal control. Thus, the amount of MGP is normalized to the amount of the housekeeping gene GAPDH. The accuracy, sensitivity and ease of this new method enables rapid mRNA quantitation without blotting, hybridization or autoradiography. The method is particularly advantageous for MGP mRNA measurement from a small amount of sample. Using this assay, we established that MGP mRNA increases approx, fivefold with co-treatment of retinoic and ascorbic acids
Arithmetic Frequency Synthesis Using A Systolic Array

A systolic clock generator has been designed and built with 320 identical computing elements on a single VLSI chip which can provide a considerable increase in the rate at which an accumulator may be used to produce a variable frequency clock. A single Arithmetic Frequency Synthesizer (AFS) chip (with appropriate external circuitry), having the equivalent of sixteen accumulators, can provide a programmable clock at frequencies sixteen times greater than that obtainable with a single accumulator. By using up to four AFS chips in parallel, a 64 times improvement of the system output clock frequency may be obtained.
Structure of nanocrystalline ZnO up to 85GPa

Abstract The structure of nanocrystalline and bulk polycrystalline ZnO were examined up to 85 GPa and 50 GPa, respectively using synchrotron X-rays and diamond anvil cells at ambient conditions. The transition from the wurtzite to the rock salt phase in the nano-ZnO takes place at 10.5 GPa; this transition pressure is 1.5 GPa higher than in bulk ZnO. A large volume collapse of about 17.5% is observed during the transition in both systems. The rocksalt phase is stable and no structural transitions are observed for both compounds at higher pressures up to the experimental limit. On decompression the rocksalt phase is found to co-exist with the wurtzite phase at ambient conditions for the nano-ZnO.
Treatment selection factors for stereotactic radiosurgery of intracranial metastases

Purpose : To define treatment selection criteria for patients with intracranial metastases treated with stereotactic radiosurgery. Methods and Materials : Between August 1989 and July 1993, 25 patients with intracranial metastases (28 lesions) were treated with stereotactic radiosurgery at the University of Florida. Thirteen patients were treated for progressive intracranial disease after external-beam radiotherapy, and 12 were treated with radiosurgery as an adjunct to initial treatment. Minimum eligibility criteria included histologic verification of primary disease, Karnofsky performance status 50% or greater, three or fewer intracranial metastases, radiographically distinct lesion(s) 4 cm or less in diameter, and reasonably well-controlled primary disease. Univariate and multivariate analyses tested the prognostic significance of Karnofsky performance status, lesion volume, number of lesions, treatment dose (both external beam and stereotactic), histology, site of primary disease, and time interval (less than or greater than 1 year) from primary diagnosis to development of intracranial metastasis or from treatment of intracranial disease to recurrence. Results : Local control was achieved in 84% of 28 lesions treated. The only significant prognostic indicator among the tested variables was the interval to development or recurrence of intracranial metastasis. Conclusion : Although stereotactic radiosurgery improves local control rates and is likely to offer improved palliation for a select cohort of patients, the selection criteria for such patients remain poorly defined. Our data suggest that an interval of greater than 1 year from primary disease diagnosis to development of intracranial metastasis, or from treatment of intracranial metastasis to its recurrence, defines a patient cohort that is more likely to benefit from this treatment technique.
Efficient transplantation of BCR-ABL-induced chronic myelogenous leukemia-like syndrome in mice.

Lethally irradiated mice reconstituted with bone marrow expressing P210 BCR-ABL can develop myeloproliferative syndromes that resemble the initial phase of human chronic myelogenous leukemia (CML). Mice that develop the CML-like syndrome can be segregated into two groups based on the latency with which the granulocytic disease appears--early onset ( 20 weeks). Only cells from mice exhibiting the late-onset CML-like syndrome can efficiently propagate the disease when transplanted into sublethally irradiated syngeneic recipients. Mice engrafted with late-onset murine CML cells develop a range of hematopoietic disorders that originate from multipotent stem cells. The chronic granulocytic hyperplasia can be propagated by serial transplantation into secondary and tertiary recipient mice. The majority of transplanted mice succumb to acute myeloid and B- and T-lymphoid leukemias. These data support the idea that late-onset murine CML originates from a multipotent progenitor cell with a high replicating capacity. The inability to transplant the disease from mice developing the early-onset CML-like syndrome suggests that this disorder may originate from more differentiated progenitor cells with limited replication capacity that have undergone clonal expansion but are not immortalized. Although both early- and late-onset CML-like syndromes exhibit granulocytic hyperplasia, these disorders represent distinct diseases that appear to originate from different hematopoietic cell types. The late-onset CML-like disease and transfer to secondary recipients provides a useful murine model with features of the chronic and acute phases of human CML.
Dna microarray analysis of protozoan parasite gene expression: outcomes correlate with mechanisms of regulation

DNA microarray analysis has been successfully applied to most of the protozoan parasites that cause human disease, but has not made equal progress in all cases. The results for kinetoplastid parasites (Leishmania and Trypanosoma) are primarily at the stage of validation and new gene discovery. By contrast, the results for apicomplexan parasites (Plasmodium and Toxoplasma) have advanced to the analysis of coordinate regulation of clusters of genes. This difference in progress relates to the more complete genome sequence identified for the apicomplexans and, more significantly, to the differences in the regulation of gene expression between these two groups.
Converging science and technology at the nanoscale: opportunities for education and training.

Reversing the pyramid of learning could expedite the development of a US nanotechnology workforce.
Pronounced hepatic free radical formation precedes pathological liver injury in ethanol-fed rats.

Background: The role of free radicals in alcoholic liver injury remains uncertain. These experiments were conducted to measure radical formation in rats that were fed alcohol along with either fish oil or saturated fats, which cause different types of liver pathology. Methods: Liquid diets containing alcohol or isocaloric dextrose were administered to rats by intragastric infusion for 2 weeks. Radical intermediates detected by spin trapping were measured in bile. Results: In rats that were fed alcohol plus fish oil, biliary concentrations of trapped radicals, which most likely originated from lipids, were 6-fold higher than in controls that were fed fish oil plus dextrose. High rates of radical formation persisted 24 hr after alcohol withdrawal, when all alcohol had been metabolized. In contrast, diets containing alcohol and medium chain triglycerides did not stimulate lipid radical formation. Conclusions: High rates of lipid radical formation were observed only in rats that were fed alcohol in combination with a fish oil diet, and a persistent flux of radical formation continued after alcohol withdrawal. These radical phenomena precede serious liver pathology, which develops after longer periods of fish oil plus alcohol diets.
Potential human error in setting stereotactic coordinates for radiosurgery : implications for quality assurance

Abstract Purpose: The error frequency in setting stereotactic coordinates for gamma knife radiosurgery was investigated to determine what quality assurance safeguards are necessary. Methods and Materials: A prospective study of 200 consecutive isocenter settings for gamma knife radiosurgery was analyzed to identify the frequency of spontaneous errors in setting and checking stereotactic coordinates (corrected prior to treatment). An additional 25 coordinate errors were introduced at random among the next 200 consecutive isocenter settings to provide additional data on identification of errors. Results: Stereotactic coordinates required resetting in 12% (24200) of the isocenters treated due to errors of 0.25–0.50 mm (8%) and 1–20 mm (4%). This comprised 2.2% (261200) of the individual coordinate settings. The frequency of these errors was significantly related to the specific directional coordinate set ( p = 0.0004) and experience ( p = 0.016). Errors were identified by 83.5% (91109) of the observers checking the settings (60.0% of 0.25 mm errors, 94.6% of errors ≥ 0.5 mm, p = 0.0000). Verification of stereotactic coordinates by two observers reduces the probability of an undetected error ≥ 0.25 mm to 11,392 and to 1154,712 for errors ≥ 1 mm. Conclusion: Errors in setting stereotactic coordinates are common (12% prior to checking) but are corrected with a high degree of confidence by a quality assurance policy requiring coordinate verification by a minimum of two observers.
Studies on the absorption of choline chloride.

Abstract Two possibilities exist for the metabolism of choline. The present study was undertaken to clarify the manner in which orally ingested choline disappears from the intestine of the rat. It was found that choline disappears from the intestine of the rat at a very constant rate, in a manner suggesting enzymatic absorption. Incubation of choline with intestinal homogenate for the same length of time as reuired for 39 per cent absorption (two hours) did not result in any decrease of choline concentration. When the intestinal bacteria were suppressed by means of antibiotics in the diet, choline disappeared at the same rate as in the non‐treated control rats. It is concluded that choline is absorbed unchanged from the small intestine, and that intestinal bacteria play only a minor role, if any, in its disappearance.
Deregulation of the cell cycle machinery by Epstein–Barr virus nuclear antigen 3C

Epstein–Barr virus (EBV) is a ubiquitous human herpesvirus associated with a large number of lymphoid and epithelial malignancies. As a successful pathogen it has co-evolved with its human host for millions of years. EBV has the unique ability to establish life-long latent infection in primary human B lymphocytes. During latent infection, a small subset of viral proteins is expressed. These proteins are essential for maintenance of the EBV genome as well as the deregulation of various signaling pathways that facilitate the proliferation and survival of the infected cells. Epstein–Barr nuclear antigen (EBNA)3C is one of the latent proteins shown to be essential for transformation of primary human B lymphocytes in vitro. EBNA3C primarily functions as a transcriptional regulator by interacting with a number of well known cellular and viral transcriptional factors. We have recently identified several binding partners for EBNA3C including proteins that regulate cell cycle and chromatin remodeling. We are activ...
Reconceptualizing the Small Business Consulting Course: A Response to the Porter and Mckibbin Criticisms:

Graduate business education has been criticized for its inattention to integration of the curriculum and the development of specific skills in interpersonal relations, leadership, written and verbal communications, and in decision making under conditions of uncertainty. This article outlines a model for an MBA-level course in small business consulting with the potential for effectively addressing these shortcomings. The advantages and limitations of this model are discussed.
The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest

HIV type I (HIV-1) can cause G2 cell cycle arrest and death of CD4+ T lymphocytes in vitro and inexorable depletion of these cells in vivo. However, the molecular mechanism of viral cytopathicity has not been satisfactorily elucidated. Previously, we showed that HIV-1 kills T cells by a necrotic form of cell death that requires high level expression of an integrated provirus but not the env or nef genes. To determine which viral protein(s) are required for cell death, we systematically mutated, alone and in combination, the ORFs of the NL4-3 strain of HIV-1. We found that the elimination of the viral functions encoded by gag-pol and vpu, tat, and rev did not mitigate cytopathicity. However, elimination of the vif and vpr accessory genes together, but not individually, renders the virus incapable of causing cell death and G2 cell cycle blockade. We thus identify vif and vpr as necessary for T cell cytopathic effects induced by HIV-1. These findings may provide an important insight into the molecular mechanism of viral pathogenesis in AIDS.
Electrophysiological evidence for glutamate as a vomeronasal receptor cell neurotransmitter.

Abstract Bipolar receptor cells in the vomeronasal organ send axonal projections to the accessory olfactory bulb where they synapse with mitral cell dendrites. Although the nature of the synapse is thought to be excitatory, the neurotransmitter(s) involved has not yet been identified. Electrophysiological recordings of single neurons in the mitral cell layer of the AOB in response to vomeronasal nerve stimulation were conducted to characterize the synaptic response and the underlying neurotransmitter substance. Extracellular activity was recorded in vivo (whole animal) and in vitro (AOB slice) from female rats. In vivo, the predominant response to stimulation of the VNO was excitation. In many instances in the whole animal preparation, the excitation was followed by an inhibitory response. Attempts to block the excitatory response by ejecting kynurenic acid in close proximity to the mitral cell being recorded were not successful. Since this failure may have been due to inability of the antagonist to reach its presumed site of action at the dendrite, further recordings were carried out in vitro. In the AOB slice preparation, the predominant response to stimulation of the VN nerve endings was excitation. Superfusion of the non-NMDA antagonist, CNQX, into the medium resulted in a reduction of the orthodromic excitation in 5 of 8 cells. The NMDA antagonist, AP-5, was found to blunt orthodromic excitation in 1 of 4 cells. These results suggest that the excitatory response evoked in mitral cells following stimulation of the VN nerve is mediated by glutamate.
Improvement of sensory quality of reduced fat Cheddar cheese by a Lactobacillus adjunct

Abstract A Lactobacillus helveticus adjunct was added to 33% reduced fat Cheddar cheeses at concentrations of 10 2 or 10 3 CFU. Full fat and reduced fat control Cheddar cheeses were also made according to traditional methods. Reduced fat cheeses containing the Lactobacillus helveticus adjunct were significantly less bitter and contained greater oaky/nutty flavor intensity after three and six months aging than control reduced fat cheeses ( P ≤ 0.05). Trained dairy judge flavor scores for the reduced fat cheeses with the adjunct were not significantly different from flavor scores for the full fat Cheddar cheese ( P > 0.05). Acceptance scores after six months aging for reduced fat cheeses containing the adjunct culture were significantly higher than acceptance scores for the full fat Cheddar cheese ( P ≤ 0.05). Reduced fat cheeses containing Lactobacillus helveticus as an adjunct culture exhibited significantly greater rates of proteolysis than control cheeses ( P ≤ 0.05).