cssi/SciSciGPT-SciSciNet huggingface dataset:
A Pharmacoepidemiologic Approach to Evaluate Real-world Effectiveness of Hormonal Contraceptives in the Presence of Drug-drug Interactions

Background Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates. Methods We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC's effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12-48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting. Results We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person-years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2). Conclusions OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug-drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.
Kreuzbandläsionen Eine medizinisch-statistische Analyse

Die Zahl von Kreuzbandverletzungen hat in der Statistik der Schweizerischen Unfallversicherungsanstalt in den Jahren 1970 bis 1979 deutlich zugenommen. Auf neue und differenzierte diagnostische und therapeutische Moglichkeiten wird hingewiesen. Ein Absinken der Invaliditatsquote als Folge verbesserter diagnostischer und therapeutischer Massnahmen kann erst tendenziell beobachtet werden. Praventive Massnahmen mussen vor allem im Sport zur Anwendung kommen, der mit zunehmender Haufigkeit als Ursache von Kreuzbandverletzungen in Erscheinung tritt.
Tiered intake assessment for low- and no-calorie sweeteners in beverages.

A tiered intake assessment approach is presented and applied to derive the maximum potential global low- and no-calorie sweeteners (LNCS) intake estimates. The US and Uk markets served as represent...
Joint Calibration and Synchronization of Two Arrays of Microphones and Loudspeakers Using Particle Swarm Optimization

This work presents a methodology for the joint calibration and synchronization of two arrays of microphones and loudspeakers. The problem is modeled as estimation of the rigid motion of one array with respect to the other, as well as estimation of the synchronization mismatch between the two. The proposed method uses dedicated signals emitted by the loudspeakers of the two arrays to compute a set of time of arrival (TOA) estimates. Through a simple transformation, estimated TOAs are converted into a set of linearly independent time difference of arrival (TDOA) measurements, which are modeled by a system of nonlinear equations in the unknown parameters of interest. A maximum likelihood estimate is then given as the solution to a nonlinear weighted least squares (NWLS) problem, which is optimized applying a parallelizable variant of Particle Swarm Optimization (PSO). In this paper, we also derive the Cramer-Rao lower bound (CRLB), and benchmark it against the proposed method in a series of Monte Carlo (MC) simulations. Results show that the proposed method attains high-performance comparable to the CRLB.
Audiology findings in patients with teprotumumab associated otologic symptoms.

Abstract Purpose To report a case series of subjective and objective hearing function changes associated with teprotumumab treatment for thyroid eye disease. Observations A 74-year-old female with a history of Graves' disease with thyroid eye disease was treated with teprotumumab. She had a history of bilateral tinnitus and noticed a subjective improvement in her tinnitus after the second infusion. Audiology testing obtained before, during, and after completion of infusions showed symmetric and rapidly progressive worsening of the patient's sensorineural hearing loss. In contrast, a 42-year-old male with a history of Grave's disease endorsed worsening intermittent tinnitus and low-pitched hearing loss after initiation of teprotumumab. Audiology testing before, during, and after completion of infusions showed stable and normal hearing function bilaterally. Conclusion and importance This case series highlights the importance of objective testing in patients prior to and after teprotumumab initiation as subjective hearing changes may not accurately reflect objective hearing function. In addition, this report suggests that teprotumumab may play a role in potentiating sensorineural hearing loss.
Activated eosinophils are the major source of Th2-associated cytokines in the schistosome granuloma.

Eosinophils are a numerically dominant cell population within the schistosome granuloma. These granuloma eosinophils can produce a variety of cytokines, including IL-2, IL-4, IL-5, and IFN-gamma. Therefore, eosinophils may play a key role in the determination of the unique cytokine microenvironment within the granuloma milieu. These studies investigated the potential role of eosinophils in the regulation of granuloma immunopathology. We have characterized spleen- and granuloma-derived eosinophils based on cellular activation and cytokine production during the development of murine schistosomiasis. Based on the criteria of hypodensity and CD69 expression, granuloma eosinophils were highly activated and very homogeneous at 7 and 11 wk postinfection. Splenic eosinophils were also activated at 7 wk postinfection, but were much more heterogeneous than their granuloma counterparts. By 11 wk postinfection, few hypodense splenic eosinophils were observed. Eosinophils represented the majority of cytokine-producing cells in the granuloma and were a dominant source of IL-4. Eosinophils also produced IL-2, IL-5, and IFN-gamma, using the criteria of mRNA in situ hybridization and intracellular cytokine staining by FACS. Granuloma eosinophil activation and cytokine production were greatest at the time of maximum granuloma formation, i.e., 10-12 wk after initial cercarial exposure. Therefore, locally activated eosinophils, not Th2 lymphocytes, produce the majority of Th2 cytokines in the granuloma milieu and may be important determinators of immunopathology in schistosomiasis.
Taking Distribution Seriously

It is common for legal theorists and policy analysts to think and communicate mainly in maximizing terms. What is less common is for them to notice that each time we speak explicitly of socially maximizing one thing, we speak implicitly of distributing another thing and equalizing yet another thing. We also, moreover, effectively define ourselves and our fellow citizens by reference to that which we equalize; for it is in virtue of the latter that our social welfare formulations treat us as "counting" for purposes of socially aggregating and maximizing. To attend systematically to the inter-translatability of maximization language on the one hand, equalization and identification language on the other, is to "take distribution seriously." It is to recognize explicitly, and to trace the important normative consequences that stem from, the fact that all law and policy are as distributive and citizen-defining as they are aggregative. It is also to recognize therefore that all law and policy treat us as equals in some respects - respects in terms of which they identify and "count" us as politically relevant - and as non-equals in other respects. Attending explicitly to these "respects" brings transparency about the degrees to which our laws and policies identify, "count," and treat us as equals in the right respects. This Article accordingly seeks to lay out with care how to take distribution seriously in legal and policy analysis. It does so by two means, keyed to the principal guises in which distribution is typically implicated in legal and policy analysis: First, by careful attention to the internal structures of the social welfare functions favored by most present-day legal theorists and policy analysts. And second, by systematic reference to what linguists call the "cognitive grammar" of non-formal distributive language, a structure that mirrors the structure of distribution itself. The payoffs include both a workable method by which systematically to test proposed maximization norms for their normative propriety, and an attractive distributive ethic that can serve as an ethically intelligible normative touchstone for legal and policy analysis.
Re-evaluating the generation of a "proteasome-independent" MHC class I-restricted CD8 T cell epitope.

The proteasome is primarily responsible for the generation of MHC class I-restricted CTL epitopes. However, some epitopes, such as NP147–155 of the influenza nucleoprotein (NP), are presented efficiently in the presence of proteasome inhibitors. The pathways used to generate such apparently “proteasome-independent” epitopes remain poorly defined. We have examined the generation of NP147–155 and a second proteasome-dependent NP epitope, NP50–57, using cells adapted to growth in the presence of proteasome inhibitors and also through protease overexpression. We observed that: 1) Ag processing and presentation proceeds in proteasome-inhibitor adapted cells but may become more dependent, at least in part, on nonproteasomal protease(s), 2) tripeptidyl peptidase II does not substitute for the proteasome in the generation of NP147–155, 3) overexpression of leucine aminopeptidase, thymet oligopeptidase, puromycin-sensitive aminopeptidase, and bleomycin hydrolase, has little impact on the processing and presentation of NP50–57 or NP147–155, and 4) proteasome-inhibitor treatment altered the specificity of substrate cleavage by the proteasome using cell-free digests favoring NP147–155 epitope preservation. Based on these results, we propose a central role for the proteasome in epitope generation even in the presence of proteasome inhibitors, although such inhibitors will likely alter cleavage patterns and may increase the dependence of the processing pathway on postproteasomal enzymes.
Landmark United States biomedical ethics cases: a selected bibliography.

ABSTRACT The past thirty years have demonstrated a dramatic shift in the traditional physician-patient relationship, from one that has traditionally been paternalistic, or physician-focused, to one that recognizes patient autonomy and is predominately patient-centered. This evolution of patient autonomy has revolutionized the field of medical-legal ethics, as evidenced by the numerous landmark court cases described in this paper. Patients have demanded, and received, the right to make their own decisions about a variety of issues, many of them end-of-life decisions, including withholding treatment, withdrawing treatment, refusing treatment, whether or not to be resuscitated, and their right to die with dignity. Technological advances in the areas of human experimentation, resuscitation, organ transplantation, and assisted reproduction have contributed to the ethical dilemmas faced by patients, physicians, ethicists, and the courts. Due in large part to this shift in attitude and behavior from paternalism ...
Reducing Test Inputs Using Information Partitions

Automatic symbolic techniques to generate test inputs, for example, through concolic execution, suffer from path explosion : the number of paths to be symbolically solved for grows exponentially with the number of inputs. In many applications though, the inputs can be partitioned into "non-interfering" blocks such that symbolically solving for each input block while keeping all other blocks fixed to concrete values can find the same set of assertion violations as symbolically solving for the entire input. This can greatly reduce the number of paths to be solved (in the best case, from exponentially many to linearly many in the number of inputs). We present an algorithm that combines test input generation by concolic execution with dynamic computation and maintenance of information flow between inputs. Our algorithm iteratively constructs a partition of the inputs, starting with the finest (all inputs separate) and merging blocks if a dependency is detected between variables in distinct input blocks during test generation. Instead of exploring all paths of the program, our algorithm separately explores paths for each block (while fixing variables in other blocks to random values). In the end, the algorithm outputs an input partition and a set of test inputs such that (a) inputs in different blocks do not have any dependencies between them, and (b) the set of tests provides equivalent coverage with respect to finding assertion violations as full concolic execution. We have implemented our algorithm in the Splat test generation tool. We demonstrate that our reduction is effective by generating tests for four examples in packet processing and operating system code.
On the synthesis and complexity of feedforward networks

A method for synthesis of one hidden layer feedforward neural networks approximating functions of several variables to the desired degree of accuracy is presented. The method fully determines the network architecture including the values of all weights. In the first step, the inverse Radon transform is used to decompose a problem of of approximating a function of several variables into several problems of approximating a function of one variable. In the second step, each of the obtained one-dimensional functions is approximated by a sub-network. Then sub-networks are combined to construct the network approximating the original function. The upper bound of the final approximation error /spl epsi/ and errors at each step are estimated. The complexity of the network, or the number of neurons in the hidden layer, is O/sub /spl epsi//(1//spl epsi//sup n/), where n is the dimension of the space. >
Models and Analysis for Twin-Lift Helicopter Systems

Multiple-lift schemes using two or more helicopters to lift payloads too large for a single helicopter have been tested on several occasions. However, the manual control tasks involved demanded a considerable amount of flying skill and cooperative abilities from the pilots. Initial to the design of automatic control is the development of reasonable models of the twin-lift system, which is discussed. An appropriate analytical model is described.
GAMETOGENESIS IN THE NON-NATIVE GREEN MUSSEL, PERNA VIRIDIS, AND THE NATIVE SCORCHED MUSSEL, BRACHIDONTES EXUSTUS, IN TAMPA BAY, FLORIDA

Abstract Histologic examination of the nonnative green mussel, Perna viridis, and the native scorched mussel, Brachidontes exustus, at three locations in Tampa Bay, Florida, indicated that cycles of gametogenesis and spawning were similar between species. Major spawning periods occurred in the spring (April) in conjunction with increasing water temperature and the fall (September to November) as the water temperature was declining. Over the summer, both species appeared to undergo varying levels of redevelopment, partial spawning and resorption of oocytes. Gametogenesis was limited over the winter. Differences between populations in levels of gametogenic activity and the timing of the fall spawn were most likely related to differences in salinity and available food at the three sites. A higher fecundity (caused by the faster growth rate and greater maximum size of P. viridis) may result in displacement of native bivalves in Tampa Bay, including B. exustus.
Liaison is as Liaison Does

The term Liaison has a number of connotations.1–4 For the purposes of this discussion it means the relationship between individuals, disciplines, events, and illness. It includes a body of research generative of empirical data that identifies and explores these relationships. Its disciplinary derivatives are biological, psychological, and social, including sub-disciplines within these, especially behavioral science, anthropology, and neuroendocrinology. Most recently, ethics has become an important component of the interests and work of the Liaison physicians.5 Liaison expands its parental derivation from psychosomatic medicine, resting for the moment on the term, Biopsychosocial.6 Liaison identifies process knowledge, as well as a substantive body of knowledge derivative of its research studies. The process of liaison stresses includes methods of obtaining information and the application of its use. Interview technique is fundamental to this process.7 Liaison is between people, beginning with the patient-doctor relationship. It is also between patients and nurses, doctors and doctors, and the medical profession and other institutions of society. Thus, Liaison is incorporative of many disciplinary relationships in its attempt to facilitate a definition of the illness experience.
From Hindu Kush to Sri Lanka and the State of the Art

The Hill of Flutes: Life, Love and Poetry in Tribal India. W. G. Archer. Pittsburgh: University of Pittsburgh Press, 1974. Structural Approaches to South India Studies. Harry M. Buck and Glenn E. Yocum, eds. Chambersburg, Pennsylvania: Wilson Books, 1974. Faction and Conversion in a Plural Society: Religious Alignments in the Hindu Kush. Robert Leroy Canfield. Anthropological Papers, Museum of Anthropology, University of Michigan No. 50. 1973. Elite Politics in Rural India: Political Stratification and Alliances in Western Maharashtra. Anthony Carter. Cambridge Studies in Social Anthropology, 9. London: Cambridge University Press, 1974. The Myth of the Lokamanya: Tilak and Mass Politics in Maharashtra. Richard I. Cashman. Berkeley: University of California Press, 1975.
Parameter determination for BPD mediated vascularPDT.

The cell killing mechanism of benzoporphyrin derivative monoacid ring A (BPD) is known to be predominantly apoptotic or vascular, depending on the drug-light interval (DLI). With a 3 hour DLI, necrosis develops secondary to tumor cell damage, while with a 15 minute DLI, necrosis results from treatment-created vascular damage. The purpose of this study is to examine if the different mechanisms of cell death will affect the photochemical parameters for the macroscopic singlet oxygen model. Using the RIF model of murine fibrosarcoma, we determined the four photochemical parameters (see manuscript) and the threshold singlet oxygen dose for BPD-mediated PDT through evaluation of the extent of tumor necrosis as a function of PDT fluence rate and total fluence. Mice were treated with a linear source at fluence rates from 12-150 mW/cm and total fluences from 24-135 J/cm. BPD was administered at 1mg/kg with a 15 minute DLI, followed by light delivery at 690nm. Tumors were excised at 24 hours after PDT and necrosis was analyzed via HE staining. The in-vivo BPD drug concentration is determined to be in the range of 0.05-0.30 μM. The determination of these parameters specific for BPD and the 15 minute DLI provides necessary data for predicting treatment outcome in clinical BPD-mediated PDT. Photochemical parameters will be compared between 1mg/kg DLI 3 hours and 1mg/kg DLI 15 minutes.
Karyotypic changes associated with spontaneous acquisition and loss of tumorigenicity in a human transformed bronchial epithelial cell line: Evidence for in vivo selection of transformed clones

In this study, we describe the karyotypic changes associated with the spontaneous acquisition of tumorigenicity in an immortalized tumor bronchial cell line. Neoplastic transformation of the NL20 human bronchial epithelial cell line occurred after 3 yr in culture, and was associated with loss of chromosome 18 together with acquisition of multiple copies of 9q21.2→34. The nontumorigenic NL20 cell line had been established by transfection of human bronchial epithelial cells with the SV40 T antigen, and had retained a relatively stable karyotype after the first 32 passages in vitro. However, when cells from p184 were inoculated into nude mice, a transplantable tumor was obtained that was derived from a minor clone present in this otherwise stable line. Subsequent passaging of the NL20 cells in vitro did not yield further tumors, and the minor clone from which the tumorigenic NL20T cell line derived was no longer evident in NL20 cells by Passage 205. Furthermore, the original tumorigenic NL20T cells lost the neoplastic phenotype after 25 passages in vitro and reverted to the nontumorigenic karyotype observed at p189. In contrast to the loss of the tumorigenic phenotype and karyotype, which occurred with in vitro passaging of the original tumor, when the NL20T cells were passaged in other nude mice, they continued to give rise to tumors with sevenfold amplifications of 9q sequences and loss of chromosome 18, and cells from the secondary tumors (NL20T-A cells) have maintained a stable karyotype and remain tumorigenic even after 64 passages in vitro. A mixture of 10% tumorigenic NL20T-A and 90% nontumorigenic NL20 cells formed tumors in athymic nude mice when cultured in vitro on fibronectin, but not on plastic; cytogenetic analysis demonstrated that the tumors and cell cultures were composed of tumorigenic NL20T-A cells, whereas cytogenetic analysis of cells cultured on plastic were identical to the nontumorigenic NL20 cells. These data support the hypothesis that neoplastic transformation in our original cell line arose from in vivo selection of a small mutant clone, which had arisen in culture and was subsequently selected in vivo but was lost with in vitro culture.
A Study of the Frequency Reading Fundamental Vocal of Young Black Adults

This study investigated the measures of central tendency (mean mode) and dispersion (standard deviations and ranges) of the reading fundamental vocal frequency in young black adults. The subjects w...
A simple single-item rating scale to measure medication adherence: further evidence for convergent validity.

Background: Self-report measures of medication adherence are inexpensive and minimally intrusive. However, the validity of self-reported adherence is compromised by recall errors for missed doses and socially desirable responding. Method: Examined the convergent validity of 2 self-report adherence measures administered by computerized interview: (a) recall of missed doses and (b) a single-item visual analogue rating scale (VAS). Adherence was also monitored using unannounced phone-based pill counts that served as an objective benchmark. Results: The VAS obtained adherence estimates that paralleled unannounced pill counts (UPCs). In contrast, self-reported recall (SR-recall) of missed medications consistently overestimated adherence. Correlations with participant characteristics also suggested that the computer-administered VAS was less influenced by response biases than SR-recall of missed medication doses. Conclusions: A single-item VAS offers an inexpensive and valid method of assessing medication adher...
NMR coils with segments in parallel to achieve higher frequencies or larger sample volumes

Abstract The question of using multisegment coils, connected in parallel, for NMR is investigated. It is shown theoretically and experimentally that such coils offer significant improvements over equivalent single coils in several ways: (1) For a given size, they are usable at much higher frequencies; (2) for a given Larmor frequency, they can be made larger to contain more sample; and (3) the axial component of the rf electric field can be reduced for certain coil geometries.
Coexpression of normal and mutated CD40 ligand with deletion of a putative RNA lariat branchpoint sequence in X-linked hyper-IgM syndrome.

We describe a novel CD40 ligand (CD40L) splicing mutation in a patient with X-linked hyper-IgM syndrome (X-HIM) associated with alternate splicing of exon 3, resulting in the expression of both full-length and exon-3-skipped CD40L mRNA. The mutation is an 8-bp deletion 25 bp upstream of the intron 2/exon 3 junction which overlaps a putative RNA branchpoint, suggesting that it may impair RNA lariat formation. The exon-3-skipped CD40L transcript encodes a truncated protein (CD40LDeltaE3) encompassing the cytoplasmic, transmembrane, and extracellular stalk domains, but lacking the CD40L receptor binding domain. CD40LDeltaE3 protein expression was readily detectable in transfected Cos cells by immunofluorescence. In cells cotransfected with CD40LDeltaE3 and wild-type CD40L, expression of CD40LDeltaE3 did not inhibit the expression of wild-type CD40L monomers, but strongly inhibited staining by the conformationally sensitive anti-CD40L mAb 5c8, suggesting that CD40LDeltaE3 acts in a dominant negative manner to inhibit the assembly of functional CD40L trimers. This mechanism may contribute to the pathophysiology of CD40L deficiency in X-HIM patients with leaky splice site mutations.
CD8αβ Has Two Distinct Binding Modes of Interaction with Peptide-Major Histocompatibility Complex Class I *

Interaction of CD8 (CD8alphaalpha or CD8alphabeta) with the peptide-major histocompatibility complex (MHC) class I (pMHCI) is critical for the development and function of cytolytic T cells. Although the crystal structure of CD8alphaalpha.pMHCI complex revealed that two symmetric CD8alpha subunits interact with pMHCI asymmetrically, with one subunit engaged in more extensive interaction than the other, the details of the interaction between the CD8alphabeta heterodimer and pMHCI remained unknown. The Ig-like domains of mouse CD8alphabeta and CD8alphaalpha are similar in the size, shape, and surface electrostatic potential of their pMHCI-binding regions, suggesting that their interactions with pMHCI could be very similar. Indeed, we found that the CD8alpha variants CD8alpha(R8A) and CD8alpha(E27A), which were functionally inactive as homodimers, could form an active co-receptor with wild-type (WT) CD8beta as a CD8alpha(R8A)beta or CD8alpha(E27A)beta heterodimer. We also identified CD8beta variants that could form active receptors with WT CD8alpha but not with CD8alpha(R8A). This observation is consistent with the notion that the CD8beta subunit may replace either CD8alpha subunit in CD8alphaalpha.pMHCI complex. In addition, we showed that both anti-CD8alpha and anti-CD8beta antibodies were unable to completely block the co-receptor activity of WT CD8alphabeta. We propose that CD8alphabeta binds to pMHCI in at least two distinguishable orientations.
ire-1-dependent Transcriptional Up-regulation of a Lumenal Uridine Diphosphatase from Caenorhabditis elegans

Lumenal ecto-nucleoside tri- and di-phosphohydrolases (ENTPDases) of the secretory pathway of eukaryotes hydrolyze nucleoside diphosphates resulting from glycosyltransferase-mediated reactions, yielding nucleoside monophosphates. The latter are weaker inhibitors of glycosyltransferases than the former and are also antiporters for the transport of nucleotide sugars from the cytosol to the endoplasmic reticulum (ER) and Golgi apparatus (GA) lumen. Here we describe the presence of two cation-dependent nucleotide phosphohydrolase activities in membranes of Caenorhabditis elegans: one, UDA-1, is a UDP/GDPase encoded by the gene uda-1, whereas the other is an apyrase encoded by the gene ntp-1. UDA-1 shares significant amino acid sequence similarity to yeast GA Gda1p and mammalian UDP/GDPases and has a lumenal active site in vesicles displaying an intermediate density between those of the ER and GA when expressed in S. cerevisiae. NTP-1 expressed in COS-7 cells appeared to localize to the GA. The transcript of uda-1 but not those of two other C. elegans ENTPDase mRNAs (ntp-1 and mig-23) was induced up to 3.5-fold by high temperature, tunicamycin, and ethanol. The same effectors triggered the unfolded protein response as shown by the induction of expression of green fluorescent protein under the control of the BiP chaperone promoter and the UDP-glucose:glycoprotein glucosyltransferase. Up-regulation of uda-1 did not occur in ire-1-deficient mutants, demonstrating the role of this ER stress sensor in this event. We hypothesize that up-regulation of uda-1 favors hydrolysis of the glucosyltransferase inhibitory product UDP to UMP, and that the latter product then exits the lumen of the ER or pre-GA compartment in a coupled exchange with the entry of UDP-glucose, thereby further relieving ER stress by favoring protein re-glycosylation.
Base composition of RNA obtained from motor neurons in amyotrophic lateral sclerosis.

The base composition of RNA obtained from the large motor neurons of the cervical and lumbar swelling was examined in amyotrophic lateral sclerosis (ALS) patients and a similar number of age-matched controls. Spinal cords were obtained at autopsy and immediately fixed in buffered formalin. The single cell technique of Edstrom was employed to extract, hydrolyze, and electrophoresis the RNA. The base composition obtained for the controls was 17.47% adenine, 28.88% guanine, 28.50% cytidylic acid, and 25.14% uridylic acid. The cervical intumescence revealed higher levels of uridylic acid than the lumbar, 27.23% in the cervical and 23.31% in the lumbar intumescence. The motor neuron cell bodies isolated from patients having had ALS revealed a lower percentage of adenine in both the cervical (13%) and lumbar (10%) intumescences. When the data for these areas were combined, the percentage of adenine was 15.52, compared to 17.47% in the controls (p less than 0.01). The A/U ratio was also significantly reduced in the ALS group. The composition of the remaining bases in ALS appeared to be similar to the controls. The significant change in adenine, coupled with the quantitative reduction in total neuronal RNA, suggests that a disorder of nucleic acid metabolism may relate to the pathogenesis of ALS.
Personality in computer documentation: A preference study

There is a move in technical writing today toward a personalized, `user-friendly' writing style which is strikingly evident in many computer textbooks and instructional manuals. The author presents the results of a study to determine which style of writing people prefer in a computer tutorial, given the choice between formal, moderately friendly, and extremely friendly texts, and whether their level of computer expertise affects their selection.
In situ device for salinity measurements (chloride detection) of ocean surface

Microbend sodium chloride sensors based on polymer swelling are the latest approach to fiberoptic sodium chloride sensors. We have designed, constructed, and tested a compact microbend fiberoptic sodium chloride sensor that utilizes microbend and polymer swelling effects through the use of modified polymer beads. The design of this sensor is an improvement over previously reported microbend sensors. This sodium chloride sensor has shown feasibility as a practical, stable, inexpensive device with excellent performance and most of the desirable sensor properties including reversibility. Further optimization of the sensor is possible for the various applications we envision.
Phasor measurement unit selection for unobservable electric power data integrity attack detection

Abstract Electric power system operators make critical decisions based on remote measurements. If the measurements are compromised, the decisions made on the basis of the bad measurements could lead to critical consequences. Of particular concern are unobservable attacks where compromised measurements are not flagged as erroneous by bad data detection algorithms. Secure measurement devices, such as phasor measurement units (PMUs), can help to recognize these attacks. This paper presents an algorithm based on integer programming for the optimal placement of PMUs to detect unobservable electric power SCADA data integrity attacks. The algorithm can also be used to identify minimal sets of existing PMUs whose data is needed to detect unobservable bad data attacks. Practical examples drawn from the power engineering literature are used to demonstrate the efficiency of the algorithm.
Normal Serum Free Thyroid Hormone Concentrations in Patients Treated With Phenytoin or Carbamazepine: A Paradox Resolved

Objective. —To address the paradox that phenytoin- and carbamazepine-treated patients have decreased serum free thyroxine (T4) and triiodothyronine (T3) concentrations but appear clinically euthyroid and have normal serum thyroid-stimulating hormone (TSH) concentrations. Design. —In vitro studies comparing measurements of total and free T4and T3by ultrafiltration assay (undiluted serum) and a commercial free T4estimate kit in control serum samples or serum samples containing added therapeutic levels of phenytoin or carbamazepine. These measurements were made in serum samples diluted 1:5 with either identical serum or phosphate buffer, pH 7.4, and in serum samples from patients with seizure disorders who were treated with phenytoin or carbamazepine. Setting. —A 650-bed teaching hospital. Patients. —Selected patients (n=19) who were in good health except for seizure disorder, with stable anticonvulsant drug levels in the upper half of the therapeutic range, and were not taking any other drugs that could affect thyroid parameters. Main Outcome Measure. —Serum concentrations of free T4and free T3in patients taking phenytoin or carbamazepine vs normal controls. Results. —Addition of phenytoin or carbamazepine to normal human serum in vitro resulted in a significant increase in free T4fraction and free T4(P Conclusions. —Therapeutic levels of phenytoin and carbamazepine displace T4and T3from serum binding proteins. When added to serum, the drugs effect an increase in free hormone fractions and free T4and T3. In drug-treated patients, increased free T4and free T3fractions offset the significant decrease in serum T4and T3, resulting in normal free T4and free T3concentrations. Since currently available clinical tests will continue to show decreased free T4concentrations in patients taking phenytoin or carbamazepine, clinicians should rely on serum TSH measurements to confirm the euthyroid status of these patients. (JAMA. 1996;275:1495-1498)
M&A lesson: Beware of empire builders

We must learn some lessons from the last wave of mergers, says the author of this article. Many of the largest deals were colossal failures—because empire-building CEOs were unrestrained by lazy boards of directors. © 2004 Wiley Periodicals, Inc.
Mass spectrometric identification of proteins from silver‐stained polyacrylamide gel: A method for the removal of silver ions to enhance sensitivity

Mass spectrometry is a powerful technique for the identification of proteins at nanogram quantities. However, some degree of sample preparation prior to mass spectrometry is required, and silver-stained protein gel samples are most problematic. Here we report our strategy to obtain peptide mass profiles from silver-stained protein gel samples from one- or two-dimensional gels by destaining prior to enzymatic digestion. This study demonstrates that by using the destaining method, the sensitivity and quality of mass spectra is increased for matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometric analysis, permitting more proteins to be identified by peptide mass database analysis.
Desipramine clearance in children and adolescents: absence of effect of development and gender.

Abstract Objective To examine the influence of development and gender on the pharmacokinetics of desipramine (DMI) in the pediatric population. Method DMI pharmacokinetic parameters were calculated from 407 routinely drawn, dose- and weight-normalized serum concentrations in 173 youths receiving DMI (90 children, 83 adolescents; 29 were female, 144 were male). Results Mean pharmacokinetic parameters for the entire population included dose (3.78 ± 1.51 mg/kg), weight- and dose-normalized serum concentration (45.41 ± 47.39 [μg/L]/[mg/kg]), and DMI clearance (0.68 ± 1.51 [L/kg]/hr). No between-group differences for children and adolescents were detected in dose (child, adolescent) (3.73 ± 1.40 mg/kg, 3.83 ± 1.68 mg/kg), weight-and dose-normalized serum concentrations (44.52 ± 39.6 [μg/L]/[mg/kg], 46.34 ± 34.89 [μg/L]/[mg/kg]; p = .62). and clearance (0.680 ± 0.890 [L/kg]/hr, 0.695 ± 1.05 [L/kg]/hr; p = .103). No between-group gender differences were detected in dose (male, female) (3.83 ± 1.55 mg, 3.39 ± 1.84 mg), weight-and dose-normalized serum concentrations (45.15 ± 37.76 [μg/L]/[mg/kg]. 47.14 ± 34.96 [μg/L]/[mg/kg]; p = .720). and clearance (0.699 ± 0.89 [L/kg]/hr, 0.606 ± 0.535 [L/kg]/hr; p = .390). Conclusions These results suggest that age and gender do not significantly influence DMI clearance or dose-normalized serum concentrations in the pediatric population. J. Am. Acad. Child Adolesc. Psychiatry. 1999, 38(1):79–85.
A Methodological Comment on Page's “Role of Demand Awareness in the Communicator Credibility Effect”

(1972). A Methodological Comment on Page's “Role of Demand Awareness in the Communicator Credibility Effect”. The Journal of Social Psychology: Vol. 88, No. 2, pp. 197-201.
The lipid solubility of fixative, staining and embedding media, and the introduction of LX-112 and Poly/bed-812 as dehydrants for epoxy resin embedment

Abstract The manufacture of Shell, Epon-812 (E-812) resin has recently been discontinued. E-812 and two newly introduced E-812 substitutes, the Ladd-112 (LX-112) and the Polysciences, Poly/bed-812 (PB-812) resins, were studied biochemically and morphologically for their effectiveness as polar dehydrants. Their technical properties as general E-812 replacements were also explored. In the biochemical studies, acetone was more effective in retaining lung phospholipid components than ethanol, and resin dehydration was more effective than either acetone or ethanol. There was no appreciable difference in lipid solubility among the three resins. Acetone and uranyl magnesium acetate each had a loosening effect on previously fixed phospholipids. The PB-812 and E-812 resin dehydrated blocks of dense animal tissues, demonstrated serious technical difficulties during sectioning. The L-112 resin substitute, due to its low viscosity and improved infiltration, was found to be technically as effective a dehydrant as ethanol or acetone. None of the three resins was successful as dehydrating agents for the plant tissue. With organic solvent dehydration, both epoxy resin substitutes demonstrated excellent embedment properties with both animal and plant tissues.
Turning genes off by Ssn6–Tup1: a conserved system of transcriptional repression in eukaryotes

The Ssn6-Tup1 repressor forms one of the largest and most important gene-regulatory circuits in budding yeast. This circuit, which appears conserved in flies, worms and mammals, exemplifies how a 'global' repressor (i.e. a repressor that regulates many genes in the cell) can be highly selective in the genes it represses. It also explains how, given the appropriate signal, specific subsets of these genes can be derepressed. Ssn6-Tup1 seems especially robust, bringing about a high level of repression irrespective of its precise placement on DNA or of specific features of the DNA control regions of its target genes. This high degree of repression probably results from several distinct mechanisms acting together.
Effects of land use on dissolved organic matter biogeochemistry in piedmont headwater streams of the Southeastern United States

We measured dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and dissolved organic phosphorous (DOP) concentrations over the course of a year in 15 headwater streams within a Georgia Piedmont watershed that is a mosaic of areas with intensive animal agriculture, forestry, and residential development. The watershed receives large non-point-source organic waste inputs, mostly from poultry and beef production, with lesser quantities from the rapidly growing human population. The organic wastes from animal agriculture are deposited on nearby pastures and the human wastes are mostly treated with septic systems. We selected the headwater catchments to fall along a gradient of organic waste inputs, and hypothesized that stream dissolved organic matter (DOM) concentrations would increase along this gradient. We used a set of readily obtainable landscape indicators (land use categories, soil carbon content, and soil clay content), factor scores derived from a principal components analysis (PCA) of the landscape indicators, and organic waste input estimates to develop simple empirical models that describe our measured DOM concentrations and elemental ratios (C:N, C:P, and N:P). The models show positive correlations of stream DOC, DON, and DOP concentrations with pasture land cover, and with estimated organic waste inputs, lending support to our hypothesis. Over the entire measurement period, buffer land cover better described mean DOC and DON concentrations [maximum adjusted R 2 (AdjR 2) of 0.86 and 0.90, respectively] whereas the best models for mean DOP concentration and elemental ratios were comprised of both watershed and buffer scale indicators or PCA factor scores (maximum AdjR 2 ranged from 0.54 to 0.64). Organic waste estimates were also useful DOM descriptors (maximum AdjR 2 ranged from 0.23 to 0.55), although they were less effective than the landscape indicators. Landscape indicators and organic waste estimates were useful descriptors of DOC concentration variation (maximum AdjR 2 ranged from 0.22 to 0.77) after grouping the observations by season. Watershed scale indicators were better descriptors during most of the seasons. We conclude that landscape indicators and organic waste input estimates are useful descriptors of DOM concentrations and elemental ratios in watersheds dominated by non-point-source organic matter inputs.
Characteristics of the ventilator pressure-and flow-trigger variables

Pressure- and flow-triggering are available in the Puritan Bennett 7200ae and Siemens SV 300. Using a mechanical lung model, we described the characteristics of the pressure- and flow-triggered continuous positive airway pressure (CPAP) of both ventilators. In the Puritan Bennett 7200ae, the pressure-triggered CPAP is characterized by the relatively insufficient flow delivery after the triggering, resulting in a greater lung pressure-time product (total PTP) than the flow-triggered CPAP. Pressure support of 5 cmH2O results in total PTP less than that with flow-triggered CPAP. In the Siemens SV 300, total PTP with pressure- or flow-triggered CPAP is comparable. Total PTP is less with pressure- or flow-triggered CPAP of the Siemens SV 300 than that of the Puritan Bennett 7200ae, respectively. The application of small pressure-or flow-triggered pressure support in the Puritan Bennett 7200 ae eliminates the difference. The impact of these differences on patient inspiratory muscle work remains to be determined.
Hurst index of functions of long-range-dependent Markov chains

A positive recurrent, aperiodic Markov chain is said to be long-range dependent (LRD) when the indicator function of a particular state is LRD. This happens if and only if the return time distribution for that state has infinite variance. We investigate the question of whether other instantaneous functions of the Markov chain also inherit this property. We provide conditions under which the function has the same degree of long-range dependence as the chain itself. We illustrate our results through three examples in diverse fields: queueing networks, source compression, and finance.
Contact-dependent signaling events that promote thrombus formation

There is increasing evidence that formation of a stable hemostatic plug requires adhesive and signaling events that continue beyond the onset of platelet aggregation. These events are facilitated and, in some cases, made possible, by the persistent close contacts between platelets that can only occur when platelets begin to aggregate. Participants include integrins and other cell adhesion molecules, secreted agonists, receptor tyrosine kinases, and protein fragments that are shed from the surface of activated platelets. Collectively, these molecules promote the continued growth and stability of the hemostatic plug.
Laparoscopic gastric banding resolves the metabolic syndrome and improves lipid profile over five years in obese patients with body mass index 30–40 kg/m2

Abstract Background Obesity, metabolic syndrome (MS) and dyslipidemia are independent risk factors for cardiovascular disease. Bariatric surgery is increasingly recognized as an effective intervention for improving each of these risk factors. There are sparse data on the long-term durability of metabolic changes associated with bariatric surgery, in particular with laparoscopic gastric banding (LGB). Our objective was to evaluate the durability of metabolic changes associated with LGB in nonmorbid obesity. Methods Fifty obese patients (BMI 30–40) with ≥1 obesity-related comorbidity were prospectively followed for five years. At follow-up, subjects underwent fasting blood measures, including lipid NMR spectroscopy and standard lipid profile. Results Forty-seven patients (45 female, mean age 43.8 years) completed four years follow-up (46 completed five years). Baseline BMI was 35.1 ± 2.6. Subjects exhibited mean weight loss of 22.3 ± 7.9 kg (22.9 ± 7.4%) at year one and maintained this (19.8 ± 10.2%) over five years. At baseline, 43% (20/47) of subjects met criteria for MS. This was reduced to 15% (7/47) at year one and remained reduced over five years (13%, 6/46) ( p p p p = 0.02), with a trend toward increased HDL particle size ( p = 0.06) at year five. Changes in triglycerides and HDL-C were more prominent in patients with MS at baseline, but unassociated with weight loss or waist circumference. Changes in HDL particle size and concentration were not associated with MS status, weight loss, waist circumference, or statin use. Conclusions LGB produces significant weight loss, resolution of MS and changes in lipid profile suggestive of beneficial HDL remodeling. These changes persist five years following LGB.
An investigation of preservice teachers’ use of guess and check in solving a semi open-ended mathematics problem

Abstract Open-ended problems have been regarded as powerful tools for teaching mathematics. This study examined the problem solving of eight mathematics/science middle-school teachers. A semi-structured interview was conducted with (PTs) after completing an open-ended triangle task with four unique solutions. Of particular emphasis was how the PTs used a specific heuristic strategy. The results showed that the primary strategy PTs employed in attempting to solve the triangle problem task was guess and check; however, from the PTs’ reflections, we found there existed misapplications of guess and check as a systematic problem-solving strategy. In order to prepare prospective teachers to effectively teach, teacher educators should pay more attention to the mathematical proficiency of PTs, particularly their abilities to systematically and efficiently use guess and check while solving problems and explain their solutions and reasoning to middle-school students.