cssi/SciSciGPT-SciSciNet huggingface dataset:
Can finger-prick sampling replace venous sampling to determine the pharmacokinetic profile of oral paracetamol?

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT • Finger-prick blood samples are increasingly used for the clinical and biomedical measurement of drugs and endogenous substance concentration. • The use of different sampling sites can give rise to different drug concentration measurements. WHAT THIS STUDY ADDS • During the absorption phase, the paracetamol concentration in finger-prick blood samples is significantly greater than that in venous blood samples, following oral administration. • Finger-prick and venous blood samples will result in equivalent pharmacokinetic parameters of oral paracetamol only after distribution equilibrium is attained. The drive to increase the availability of paediatric pharmacokinetic data with minimum blood loss has led to the development of micro-sampling techniques. However studies have suggested that pharmacokinetic data from venous or capillary blood samples may not be directly comparable. AIM The aim of this study was to determine whether paracetamol demonstrates concentration differences between finger-prick and venous blood samples. METHODS Paired finger-prick and venous blood samples were taken at 0, 15, 30 and 60 min following 1 g oral paracetamol, from 12 male adult subjects. Paracetamol concentration was determined using HPLC and UV detection with a LLOQ of 2200 pg on column. Intra-assay coefficient of variation for paracetamol at the LLOQ was 3%. RESULTS At 15, 30, and 60 min post dose the median finger-prick paracetamol concentration was 349%, 72%, and 9.3% greater than the equivalent venous concentrations, respectively. Regression analysis confirmed a significant relationship between finger-prick and venous paracetamol concentrations at 15 min (r2 = 0.81, P = 0.006), at 30 min (r2 = 0.82, P < 0.0001) and at 60 min (r2 = 0.87, P < 0.0001) post dose. The regression equation for venous and finger-prick blood concentrations at 15, 30 and 60 min post dose were Venous15 = Finger15 − 3.4, Venous30 = Finger30 − 3.4 and Venous60 = 0.68Finger60 + 3.06, respectively. CONCLUSIONS Paracetamol demonstrates an arteriovenous difference in concentration, and the use of finger-prick samples may give rise to results which differ from those obtained with traditional venous sampling especially during the first 1 h following drug ingestion.
Trap Avoidance in Strategic Computer Game Playing with Case Injected Genetic Algorithms

We use case injected genetic algorithms to learn to competently play computer strategy games. Such games are characterized by player decision in anticipation of opponent moves and imperfect knowledge of game state. Within the broad goal of developing effective and general methods of anticipatory play, this paper investigates anticipation in the context of trap avoidance in an immersive, 3D strike planning game. Case injection allows acquiring player knowledge from experience and incorporating acquired knowledge into future game play. Results show that with an appropriate representation case injection is effective at biasing the genetic algorithm toward producing plans that both avoid traps and carry out the mission effectively.
The Verifiacation Problem for Safe Replaceability

This paper addresses the problem of verifying that a sequential digital design is a safe replacement for an existing design without making any assumptions about a known initial state of the design or about its environment. We formulate a safe replacement condition which guarantees that if an original design is replaced by a new design, the interacting environment cannot detect the change by observing the input-output behavior of the new design. Examples are given to show that safe replacement (≤) allows simplification of the state transition diagram of an original design. It is showed that if D1 is a safe replacement for design D0 then every closed strongly connected component of D1 is contained in Do. We present a decision procedure for determining whether a replacement design satisfies our safe replacement condition.
Asiana Airlines Flight 214: Investigating cockpit automation and culture issues in aviation safety.

This article focuses on a major human factors–related issue that includes the undeniable role of cultural factors and cockpit automation and their serious impact on flight crew performance, communication, and aviation safety. The report concentrates on the flight crew performance of the Boeing 777–Asiana Airlines Flight 214 accident, by exploring issues concerning mode confusion and autothrottle systems. It also further reviews the vital role of cultural factors in aviation safety and provides a brief overview of past, related accidents. Automation progressions have been created in an attempt to design an error-free flight deck. However, to do that, the pilot must still thoroughly understand every component of the flight deck – most importantly, the automation. Otherwise, if pilots are not completely competent in terms of their automation, the slightest errors can lead to fatal accidents. As seen in the case of Asiana Flight 214, even though engineering designs and pilot training have greatly evolved over...
1‐(3‐Chloro­phenyl)‐4‐(3‐chloro­propyl)­piperazinium chloride

The title compound, C13H19Cl2N2+·Cl−, exhibits stereochemical features that are deemed necessary for 5-HT1 subtype serotonin receptor interaction. A distance of 5.69 (1) A is observed between the protonated nitro­gen and the centroid of the phenyl ring. The piperazine ring adopts a chair conformation and the protonated nitro­gen is involved in hydrogen bonding to the chloride counter-ion. The chloro­phenyl moiety is disordered, with the major conformer adopting a trans, trans geometry while the minor conformer is trans, gauche.
The Origins of Native Americans: Evidence from Anthropological Genetics

The Origins of Native Americans: Evidence from Anthropological Genetics. Michael H. Crawford. New York: Cambridge University Press, 1998.308pp.
Synthesis and characterization of SiC whiskers

SiC whiskers were synthesized by the carbothermal reduction of silica with an addition of halide (3NaF{center dot}AlF{sub 3} or NaF) as an auxiliary bath. The whiskers were {beta} phase (3C) and grew in the (111) direction. Three distinctive morphologies were observed: (1) Type A: thin and straight; (2) Type B: thick and bamboo-like; and (3) Type C: thick, straight, and smooth. Type A whiskers contained a high density of basal plane (111) stacking faults along their entire length, whereas Type B whiskers showed periodic changes between stacking faults and well-defined single crystals. Type C whiskers showed stacking faults on the other {l brace}111{r brace} planes instead of on the basal (111) plane. Silica formed molten fluorosilicate with halide and SiC grew via a vapor-solid reaction mechanism through gaseous SiO. These reactions can be expressed as (SiO{sub 2})+C(s)=SiO(g)+CO(g) and SiO(g)+3CO(g)=SiC(s)+2CO{sub 2}(g). The effects of processing parameters on the morphology and size of the whiskers were examined and the relationship between the morphological development of the whiskers and the stacking fault energy was determined.
Conquering Process Variability: A Key Enabler for Profitable Manufacturing in Advanced Technology Nodes

Achieving the required time to market with economically acceptable yield levels and maintaining them in volume production has become a very challenging task in the most advanced technology nodes. One of the primary reasons is the relative increase in process variability in each generation. This paper will describe a comprehensive study of the main sources of variability and their effects on active devices, interconnect and ultimately product performance and yield. We will present benchmarking of yield loss components for different product classes. We will then propose several approaches for variability reduction in the design, yield ramp and volume manufacturing phases.
Evaluation of the reliability of clinical staging of T2 N0 esophageal cancer: A review of the Society of Thoracic Surgeons database

Background Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. Methods We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Results Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy ( p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Conclusions Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study demonstrated similar perioperative morbidity and mortality with and without induction therapy, further study is needed to examine the effect of upstaging on long-term survival.
The theoretical detect index of dimensionality and its application to approximate simple structure

In this paper, a theoretical index of dimensionality, called the theoretical DETECT index, is proposed to provide a theoretical foundation for the DETECT procedure. The purpose of DETECT is to assess certain aspects of the latent dimensional structure of a test, important to practitioner and research alike. Under reasonable modeling restrictions referred to as “approximate simple structure”, the theoretical DETECT index is proven to be maximized at thecorrect dimensionality-based partition of a test, where the number of item clusters in this partition corresponds to the number of substantivelyseparate dimensions present in the test and by “correct” is meant that each cluster in this partition contains only items that correspond to the same separate dimension. It is argued that the separation into item clusters achieved by DETECT is appropriate from the applied perspective of desiring a partition into clusters that are interpretable as substantively distinct between clusters and substantively homogeneous within cluster. Moreover, the maximum DETECT index value is a measure of the amount of multidimensionality present. The estimation of the theoretical DETECT index is discussed and a genetic algorithm is developed to effectively execute DETECT. The study of DETECT is facilitated by the recasting of two factor analytic concepts in a multidimensional item response theory setting: a dimensionally homogeneous item cluster and an approximate simple structure test.
Interpretive monitoring in the caudate nucleus

The ability to adapt behavior in a changing environment is a hallmark of intelligent systems. From adjusting our driving speed to match road conditions to responding to a last-minute change of plans, mental flexibility underpins much of our day-to-day functioning. To perform optimally, an animal must continuously monitor its own behavior and adjust it according to circumstances. A region of the brain called the caudate nucleus is thought to contribute to this process by keeping track of the relation between an action and its outcomes, but it is not clear how it monitors cognitive aspects of ongoing behavior. Yanike and Ferrera have clarified this process by recording electrical activity from the caudate nucleus in two monkeys as they categorized visual stimuli. The monkeys viewed a moving stimulus and classified it as ‘fast’ or ‘slow’ relative to a reference speed that varied from trial to trial. The monkeys were trained to use two different references speeds and were told which reference speed to use at the start of each trial. They used an eye movement to indicate their decision. Most neurons within the caudate nucleus responded after the monkey had made a decision, suggesting that these neurons might be involved in evaluating the decision that had just been made. The response of the neurons depended on the stimulus speed, and also on the category (fast or slow) in which the stimulus belonged. This observation indicates that the caudate nucleus tracked the context (reference speed) as well as the stimulus speed. Yanike and Ferrera also showed that the response of the entire population of caudate neurons could be decoded to reveal both the speed of the stimulus and whether the monkey had categorized it as fast or slow. This shows that after a decision has been made, neurons continue to signal both the stimulus and the context in which that stimulus was presented. Such ‘post-decision’ monitoring is important for anticipating the outcome of the decision. Overall the results suggest that the caudate nucleus helps animals to adapt their behavior to rapidly changing circumstances by supporting decision-making that takes context into account.
Kinetics of shear-activated indentation crack initiation in soda-lime glass

The initiation of radial cracks in Vickers indentation of soda-lime glass is found to be strongly rate dependent. For long contact durations the radial cracks pop in during the indentation event, at a reproducible stage of the unloading half-cycle; for short contacts the pop-in occurs after the event, with considerable scatter in delay time. The phenomenon is interpreted in terms of an incubation time to develop a critical nucleus for the ensuing fracture. Increasing either the water content of the environment or the peak contact load diminishes the incubation time. Scanning electron microscopy of the indentation patterns indicates that the sources of the crack nuclei are constrained shear faults within the deformation zone. A qualitative model is developed in terms of a two-step process, precursor faulting followed by crack growth to pop-in instability. Moisture may influence both these steps, in the first by interfacial decohesion and in the second by slow crack growth. No definitive conclusion is reached as to which of the steps is ratecontrolling, although it appears that it is the shear across the fault and not the tension across the crack which is vital in driving the initiation. The implications of these results in connection with the basic mechanical properties of brittle solids, particularly strength, are considered.
Intra-stent tissue evaluation within bare metal and drug-eluting stents > 3 years since implantation in patients with mild to moderate neointimal proliferation using optical coherence tomography and virtual histology intravascular ultrasound

Abstract Objective We aimed to compare neointimal tissue characteristics between bare-metal stents (BMS) and drug-eluting stents (DES) at long-term follow-up using optical coherence tomography (OCT) and virtual histology intravascular ultrasound (VH-IVUS). Background Neoatherosclerosis in neointima has been reported in BMS and in DES. Methods Thirty patients with 36 stented lesions [BMS (n = 17) or DES (n = 19)] > 3 years after implantation were prospectively enrolled. OCT and VH-IVUS were performed and analyzed independently. Stents with ≥ 70% diameter stenosis were excluded. Results The median duration from implantation was 126.0 months in the BMS group and 60.0 months in the DES group (p 3 years to Conclusion At long-term follow-up beyond 3 years after implantation, the intra-stent neointimal tissue characteristics appeared similar for both BMS and DES.
The green tea polyphenol, epigallocatechin-3-gallate inhibits telomerase and induces apoptosis in drug-resistant lung cancer cells.

Abstract Epidemiological studies on humans and investigations in animal models suggest that consumption of green tea has anti-cancer effects. Small-cell lung carcinoma (SCLC) has a poor prognosis, particularly due to the development of drug resistance. We investigated the effects of the green tea polyphenol, epigallocatechin-3-gallate (EGCG) on human SCLC cells. EGCG had similar effects (IC50 of ∼70 μM) on drug-sensitive (H69) and drug-resistant (H69VP) SCLC cells, indicating that it is not part of the drug resistance phenotype expressed in these cells. In both cell lines, incubation in EGCG at 1 x IC50 for 24 h resulted in 50-60% reduced telomerase activity as measured by a PCR-based assay for telomeric repeats. Colorimetric assays of cells treated for 36 h with EGCG demonstrated a reduction in activities of caspases 3 (50%) and 9 (70%) but not caspase 8, indicating initiation of apoptosis. DNA fragmentation as measured by ELISA occurred within cells treated with EGCG and this was confirmed by TUNEL staining. Flow cytometric analysis of SCLC cells incubated for 36 h in EGCG indicated a cell-cycle block in S phase. These data indicate the potential use of EGCG, and possibly green tea, in treating SCLC.
Effect of Altered Auditory Feedback on People Who Stutter During Scripted Telephone Conversations

The effect of altered auditory feedback (AAF) conditions on stuttering during scripted telephone conversations was investigated. Nine adult participants made 15 scripted telephone calls to businesses in New York City. Alterations in the participants' auditory feedback signal were generated by a commercially available digital signal processor (Casa Futura Technologies Desktop Fluency System Model BTD-400) that shifted participants' speech one-half octave down in frequency, produced a 50-ms delay, or produced non-altered auditory feedback. The AAF effects produced by the digital signal processor were not perceived by the recipients of the telephone calls. The proportion of stuttering events per scripted telephone conversations were significantly reduced in the AAF conditions relative to the non-altered auditory feedback condition (p=.0004). Stuttering frequency was reduced by 55% and 60% for the FAF and DAF, respectively. These findings demonstrate the applicability of this technology to situations of daily...
Noninvasive assessment of left ventricular wall stress in chronic congestive heart failure patients.

In 1969, our group first reported that the intravenous administration of phentolamine can improve cardiac performance in patients with heart failure. 1 Positive inotropism and a reduction in afterload were shown to be the mechanisms that led to cardiac improvement. Since that time the literature is replete with articles attesting to the benefits of vasodilator drugs in the treat ment of acute and chronic heart failure.A reduction in impedance or afterload should produce beneficial hemodynamic effects in patients with left ventricular volume overload due to aortic insufficiency or mitral insufficiency. This has been verified using an intravenous infusion of nitroprusside, 2,3 phentolamine4 and hydralazine.5,6The effects of vasodilators on left ventricular wall stress can now be evaluated noninvasively. Recently Wilson and his group7 documented that nitroglycerin can effectively reduce the peak and end systolic wall stress in patients with aortic regurgitation. These authors concluded that the beneficial ac...
Schutz's theory of relevance

In the course of his extensive research into the nature of social reality, human action, and social interaction, Alfred Schutz returned repeatedly to the phenomenon of relevance. Any attempt to analyze Schutz's crucial concepts (e.g., the Life-world, Intersubjectivity, Typification, Meaningful Action, and Ideal Types) or to use those concepts in the course of phenomenolcfgical social-scientific research will similarly call for an understanding of this underlying phenomenon. Ronald Cox's book offers a comprehensive and comprehendable critique of Schutz's analysis, and of the phenomenon itself. The central importance of the phenomenon of relevance is perhaps best indicated by sketching Cox's own portrayal of how other, and perhaps more obvious, aspects of the social world lead to that phenomenon. This portrayal also serves to introduce Cox's own conception of the nature of his project, as well as suggest what I take to be his most problematic criticism. Schutz's investigations were directed upon the everyday, ordinary experiences which comprise what phenomenologists call the "life-world." More precisely, and to some extent in contrast to much of Husserl's work, Schutz was especially concerned with the inter subjective character of those experiences. He found that we experience our environment (both social and natural) in "typified" ways; i.e. as organized in rather standard ways, and as habitually recognized as so organized, by the experiencers themselves. Cox uses one of Schutz's examples to illustrate this situation: we typically experience certain creatures as dogs, rather than cats or birds, on the basis of certain typical features. We can abstractively thematize those typifications as "types," and, thanks to our language, we can retain our typifications in a
Trade Associations and Economic Power: Interest Group Development in the German Iron and Steel and Machine Building Industries, 1900–1933

This study traces the evolution of several large and powerful trade associations in early twentieth-century Germany and seeks to place them in comparative perspective.
Visible light-induced polymerization of monooxiranes and 1,5,7,11-tetraoxaspiro[5.5]undecanes

The visible-light photohomopolymerization reactivities of several monofunctional oxiranes were evaluated using photodifferential scanning calorimetry (PDSC). Two oxiranes, styrene oxide and 1-methoxy-2-methyl propylene oxide, were selected for copolymerization reactivity studies with five substituted 1,5,7,11- tetraoxaspiro[5.5]undecanes (TOSUs). Reaction mixtures contained a diaryliodonium salt photoacid initiator and a β-diketone photosensitizer. Experimentally determined reaction enthalpies were compared with calculated theoretical values to assess percent conversion. Relative reactivities were evaluated by comparing induction and exotherm peak maximum times. Results of AM1 semiempirical quantum mechanical calculations of reaction energetics were compared to experimental findings for selected polymerizations. IR spectral changes were consistent with oxirane and TOSU ring opening. The effect of temperature on the photopolymerization reactivity characteristics of glycidyl methylphenyl ether alone and in combination with unsubstituted TOSU was also studied. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 159–168, 2002
Anxiety treatment improves physical functioning with oblique scoring of the SF-12 Short Form Health Survey☆

article i nfo Objective: No studies have found a positive effect of anxiety treatment on physical functioning, but recent investigations of the 12-item Short Form Health Questionnaire (SF-12), which is frequently used to assess physical functioning, have suggested that orthogonal scoring of the summary measure may distort representations of physical health. The current study reanalyzes whether anxiety treatment improves physical functioning using oblique scoring in the Coordinated Anxiety Learning and Management (CALM) randomized clinical trial for the treatment of anxiety disorders. Replication was tested in reanalysis of data from the earlier Collaborative Care for Anxiety and Panic (CCAP) randomized clinical trial for the treatment of panic disorder. Method: The CALM study included 1004 primary care patients with panic, social anxiety, generalized anxiety or posttraumatic stress disorders. Patients received usual care (UC) or an evidence-based intervention (cognitive behavioral therapy, psychotropic medication or both; ITV). Physical functioning (SF-12v2) was assessed at baseline and at 6, 12 and 18 months. Oblique and orthogonal scoring methods for the physical functioning aggregate measure from SF-12 scale items were compared. Results:InCALM,physicalfunctioningimprovedtoa greaterdegreeinITVthanUCfor obliquebutnotorthogonal scoring. Findings were replicated in the CCAP data. Conclusions: Evidence-based treatment for anxiety disorders in primary care improves physical functioning when measured using oblique scoring of the SF-12. Due to this scoring issue, effects of mental health treatment on physical functioning may have been understated.
Electrostatic Interactions between a Charged Sphere and an Oppositely Charged, Deformable Interface

Abstract Boundary integral methods are used to calculate the electrostatic interactions between a charged sphere and an oppositely charged fluid/fluid interface. Assuming the dominance of electrostatic, interfacial tension, and gravitational forces, we determine the shape of the deformable interface by satisfying the normal component of the interfacial stress balance. Using this computational approach, we evaluate the effect of sphere position, interfacial tension, and interfacial charge density on the interfacial shape. Finally, the relevance of these calculations to a proposed solubilization mechanism for the reversed micellar incorporation of proteins is discussed.
Impact of partial control on policies enacted by partial targets

Abstract Numerous studies have shown that the valuation effects of corporate policies are conditioned on corporate control. A partial acquisition serves as a unique form of corporate control that has not been thoroughly researched as a control mechanism. When firms are partially acquired, the impact of their subsequent corporate policies may be affected by the degree of control imposed by the partial acquirer. Our primary objective is to test this hypothesis by (1) measuring valuation effects of the partial target and partial acquirer in response to policies enacted by the partially acquired firm (after becoming a partial target), and (2) conducting a comprehensive cross-sectional analysis for each policy which incorporate proxies for the degree of control by the partial acquirer. We find that partial targets and partial acquirers experience significant valuation effects in response to some policies enacted by the target. We also find that the valuation effects on a partial target in response to its subsequent policies are commonly conditioned by the degree of the partial acquirer's control.
A Common Sense Approach: Fighting Poverty Among Single‐Parent Families

The author reviews current trends, predictions, and statistics concerning single-parent families living in poverty and provides a common sense approach for support groups and networks.
Mechanical resonators for storage and transfer of electrical and optical quantum states

We study an optomechanical system in which a microwave field and an optical field are coupled to a common mechanical resonator. We explore methods that use these mechanical resonators to store quantum-mechanical states and to transduce states between the electromagnetic resonators from the perspective of the effect of mechanical decoherence. Besides being of fundamental interest, this coherent quantum state transfer could have important practical implications in the field of quantum information science, as it potentially allows one to overcome intrinsic limitations of both microwave and optical platforms. We discuss several state transfer protocols and study their transfer fidelity using a fully quantum-mechanical model that utilizes quantum state diffusion techniques. This work demonstrates that mechanical decoherence should not be an insurmountable obstacle in realizing high-fidelity storage and transduction.
Compete Globally, Bud Locally

How cells generate a single axis of polarity for mating, division, and movement is unknown. In this issue, Howell et al. (2009) use a synthetic biology approach to demonstrate that rapid competition for a soluble signaling component (Bem1) is essential to ensure a unique axis of polarity in budding yeast.
Structure and thermodynamics of vapor condensate in a finite system.

Une analyse de la structure et de la thermodynamique de l'interface spherique liquide-vapeur d'un simple fluide confine dans un volume fini est presentee. Les solutions numeriques de l'equation d'Yvon-Born-Green pour la distribution de densite d'un fluide de type Lennard-Jones sont obtenues, puis sont comparees aux resultats obtenus par la dynamique moleculaire et sont utilisees pour determiner les tensions superficielles et les surfaces de tension
Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis.

Abstract Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a new class of antihyperglycemic agents that block renal sodium and glucose reabsorption and may reduce blood pressure (BP). We assessed the BP lowering ability of these agents using meta-analytic techniques. PubMed, SCOPUS, and Cochrane Central were searched through October 2013. We included fully published randomized controlled trials (RCTs) that evaluated SGLT2 inhibitors in patients with type-2 diabetes mellitus and reported change in systolic and/or diastolic BP. Subgroup analyses were performed for placebo-controlled trials and those with active controls. We also conducted meta-regression to assess for a dose-response effect, and whether baseline BP, changes in body weight, heart rate, and hematocrit were associated with the BP effects. Twenty-seven RCTs (n = 12,960 participants) were included. SGLT2 inhibitors significantly reduced both systolic BP (weighted mean difference, −4.0 mm Hg; 95% confidence interval, −4.4 to −3.5) and diastolic BP (weighted mean difference, −1.6 mm Hg; 95% confidence interval, −1.9 to −1.3) from baseline. Only canagliflozin had a significant dose-response relationship with SBP ( P = .008). Significant reductions in body weight and hematocrit were seen with the SGLTs. SGLTs had no significant effect on the incidence of orthostatic hypotension ( P > .05). SGLT2 inhibitors significantly reduce BP in patients with type 2 diabetes.
Δ-9-Tetrahydrocannabinol: Effect on macromolecular synthesis in human and other mammalian cells

The principal psychoactive component of marihuana is Δ-9-tetrahy-drocannabinol. This compound at 10−5 molar concentration in the medium of human cell cultures appeared to inhibit DNA, RNA, and protein synthesis by 50, 40, and 30% respectively, as measured by incorporation of radioactive precursors into acid-insoluble cell fractions in human diploid fibroblasts, human neuroblastoma cells, and mouse neuroblastoma cells. While Δ-9-tetrahydrocannabinol inhibited semiconservative DNA synthesis, it had no effect on DNA repair synthesis in human cells as assayed by the photolysis of 5-bromodeoxyuridine incorporation into DNA during repair after ultraviolet radiation damage. Δ-9-tetrahydrocannabinol also had no effect on rejoining of DNA single-strand breaks induced by γ-rays. The nonspecificity of the inhibition of macromolecular synthesis by Δ-9-THC suggested a possible interference with uptake of radioactive precursors. However, experimentation has shown that this depression of macromolecular synthesis cannot be accounted for by reduced transport of radioactive precursors into the cell because the rate of transport of these precursors into the cell is essentially the same in the presence or absence of Δ-9-THC. Pool sizes of macromolecular precursors as measured radioisotopically (3Hthymidine, 3H-uridine, 14C-leucine) appear to be reduced about 50%, and this reduced pool size could fully account for the reduced macromolecular synthesis seen in the presence of Δ-9-THC. We do not know what causes this apparent reduction of pool sizes in the presence of Δ-9-THC.
Mg, a new blood group antigen in the MNS system.

Summary (1) A new blood group antigen, Mg, is described. (2) It is a rare antigen, which appears to be allelic to M and N. (3) It is a possible rare cause of false exclusions of paternity. (4) The antibody which identifies the new antigen is abundant and potent. Resume 1. Un nouvel agglutinogene des globules rouges, Mg, est decrit. 2. Il s'agit d'un facteur rare, apparemment un allele de M et de N. 3. Le facteur pourrait causer, en de rares occasions, une fausse exclusion de paternite. 4. L'anticorps qui permet de reconnaitre ce facteur est frequent et fort. Zusammenfassung Ein neues seltenes Bhtgruppenantigen Mg wird beschrieben. Es handelt sich offenbar um ein Allel der Gene M und N. In seltenen Ausnahmefallen konnte das Antigen Mg zu falschen Vaterschafts-ausschlussen Anlas geben. Gesunde Individuen enthalten in ihrem Serum nicht selten den diesem Antigen entsprechenden Antikorper.
Comprehensive polymorphism survey elucidates population structure of Saccharomyces cerevisiae

Comprehensive identification of polymorphisms among individuals within a species is essential both for studying the genetic basis of phenotypic differences and for elucidating the evolutionary history of the species. Large-scale polymorphism surveys have recently been reported for human, mouse and Arabidopsis thaliana. Here we report a nucleotide-level survey of genomic variation in a diverse collection of 63 Saccharomyces cerevisiae strains sampled from different ecological niches (beer, bread, vineyards, immunocompromised individuals, various fermentations and nature) and from locations on different continents. We hybridized genomic DNA from each strain to whole-genome tiling microarrays and detected 1.89 million single nucleotide polymorphisms, which were grouped into 101,343 distinct segregating sites. We also identified 3,985 deletion events of length >200 base pairs among the surveyed strains. We analysed the genome-wide patterns of nucleotide polymorphism and deletion variants, and measured the extent of linkage disequilibrium in S. cerevisiae. These results and the polymorphism resource we have generated lay the foundation for genome-wide association studies in yeast. We also examined the population structure of S. cerevisiae, providing support for multiple domestication events as well as insight into the origins of pathogenic strains.
A Longitudinal Analysis of the Relations Among Stress, Depressive Symptoms, Leisure Satisfaction, and Endothelial Function in Caregivers

OBJECTIVE—Stress and depressive symptoms have been associated with impaired endothelial function as measured by brachial artery flow-mediated dilation (FMD), possibly through repeated and heightened activation of the sympathetic nervous system (SNS). Behavioral correlates of depression, such as satisfaction with leisure activities (i.e., leisure satisfaction), may also be associated with endothelial function via their association with depressive symptoms. This study examined the longitudinal associations between stress, depressive symptoms, leisure satisfaction, and endothelial function as measured by FMD. METHODS—Participants were 116 elderly Alzheimer’s caregivers (mean age = 74.3 ± 8.1; 68% female; 87% Caucasian) who underwent three yearly assessments of FMD, stress, depressive symptoms, and leisure satisfaction. Mixed regression analyses were used to examine longitudinal relationships between constructs of interest. RESULTS—A significant and positive association was found between leisure satisfaction and FMD (p = .050), whereas a negative relationship was found for stress (p = .017). Depressive symptoms were not associated with FMD (p = .432). Time (p < .001) and the number of years caregiving (p = .027) were also significant predictors of FMD, suggesting that FMD decreased over time and was worse the longer a participant had been a caregiver prior to study enrollment. CONCLUSIONS—These results suggest that behavioral correlates of depression (i.e., engagement in pleasurable activities) may be related to endothelial function in caregivers, and behavioral treatments for depression may be particularly useful in improving cardiovascular outcomes in caregivers.
Production of Hydrogen Peroxide by Lactobacillus delbrueckii subsp. lactis as Influenced by Media Used for Propagation of Cells

Cells of Lactobacillus delbrueckii subsp. lactis I were grown in several media to determine the most suitable medium for production of H 2 O 2 during refrigerated storage. H 2 O 2 was detected from cells that were resus- pended in phosphate buffer containing variable amounts of glucose. Cells grown in MRS broth produced more H 2 O 2 during refrigerated storage than those grown in LBS pr PTM. Cells grown in LBS produced more H 2 O 2 then those grown in PTM. For both MRS and LBS, cells inoculated in phosphate buffer containing 0% glucose produced significantly more H 2 O 2 than those containing 1% or 10% glucose. MRS medium appears to be the best medium for growing cells for the production of H 2 O 2 .
Nanosensor aided photoacoustic measurement of pH in vivo

pH plays a critical role in many aspects of cell and tissues physiology. Lower pH is also a typical characteristic of arthritic joints and tumor tissues. These pH anomalies are also exploited in different drug delivery mechanisms. Here we present, a new method of pH sensing in vivo using spectroscopic photoacoustic measurements facilitated by pH sensitive nanosensors. The nanosensors consist of Seminaphtharhodafluor (SNARF), a pH sensitive dye, encapsulated in a specially designed polyacrylamide hydrogel matrix with a hydrophobic core. The photoacoustic intensity ratio between the excitation wavelengths of 585nm and 565nm increases in the pH range from 6.0 to 8.0 and is used to determine the pH of the local environment. These nanosensors are biodegradable, biocompatible, have a long plasma lifetime and can be targeted to any type of cells or tissues by surface modification using proper targeting moieties. The encapsulation of the dye prevents the interaction of the dye with proteins in plasma and also reduces the dye degradation. The SNARF dye in its free form loses 90% of its absorbance in presence of albumin, a protein found in abundance in plasma, and this has severely limited its adaptation to in vivo environments. In comparison, the SNARF nanosensors lose only 16% of their absorbance in the same environment. We employ these nanosensors to demonstrate the feasibility of pH sensing in vivo through photoacoustic measurements on a rat joint model.
Olivine dissolution kinetics at near-surface conditions

Fluidized bed dissolution experiments have been conducted as a function of pH at 25°C with fayalitic olivine (Fo6) in HCl solutions and with forsteritic olivine (Fo91) in solutions containing the organic ligand potassium hydrogen phthalate (KHP). At 25°C the dissolution rate (R) of fayalite as a function of pH is: R(mol cm −2s−))=1.1·10−10aH+0.69 +3.2·10−14+1.2·10−16aH+−0.31 where aH+ is the activity of H+ in solution. The dissolution rate at 25°C of Fo6 at a given pH is a factor of 6 greater than that of forsteritic olivine. The assumption that the rates increase on a molar basis with Fe content allows calculation of dissolution rates of Fe-Mg solid solution olivines of intermediate compositions. Batch-type dissolution experiments were completed with Fo91 at 65°C in solutions at pH 1.8, 6.0 and 9.8. The rate equation obtained from these experiments is: R (mol cm−2s−1)=3.5·10−10aH+0.5+1.0·10−13aH+0.5 When combined with previously published data for Fo91 at 25°C, the 65°C experiments indicate that the activation energy of the olivine dissolution reaction in acidic, organic-free solutions is ∼19 ± 2.5 kcal. mol−1. Dissolution experiments with forsteritic olivine in solutions containing KHP at 25°C demonstrate that the rate of dissolution is increased in these solutions relative to rates measured in KHP-absent HCl-H2O solutions. Apparently, the increase in rate is caused by Mg complexation at the olivine surface. Ligand-promoted dissolution is thought to occur in parallel with proton-promoted dissolution. Therefore, the net rate, Rnet, is the sum of the two rates: Rnet (mol cm−2s−1)=0.8·10−12[LP]0.45+RH+ where [LP] denotes the concentration of KHP; and RH+ denotes the proton-promoted dissolution rate.
Conventional signal processing applications for programmable analog vector-matrix multiplier circuits

analog weights are stored (generally the weights are stored as ananalog voltage on a capacitor or as charge stored on a floatinggate of a EEPROM transistor) at the multiplier sites. An input-vector element, x is applied simultaneously to all multipliers ona column and the outputs of all multipliers on a row are summed togenerate an output—vector element, y1. The vector—matrix multiplyoperations is a general function utilized in the vast majority of
Oscillation of two-dimensional linear second-order differential systems☆

Abstract This article is concerned with the oscillatory behavior at infinity of the solution y:[a, ∞) → R 2 of a system of two second-order differential equations, y″(t) + Q(t) y(t) = 0, tϵ[a, ∞); Q is a continuous matrix-valued function on [a, ∞) whose values are real symmetric matrices of order 2. It is shown that the solution is oscillatory at infinity if the largest eigenvalue of the matrix ∝at Q(s) ds tends to infinity as t → ∞. This proves a conjecture of D. Hinton and R. T. Lewis (Rocky Mountain J. Math. 10 (1980), 751–766) for the two-dimensional case. Furthermore, it is shown that considerably weaker forms of the condition still suffice for oscillatory behavior at infinity.
A voltage-tunable multi-spectral 320x256 InAs/GaAs quantum-dot infrared focal plane array (FPA)

A voltage-tunable multispectral 320×256 infrared imaging focal plane array (FPA) is reported. The multispectral FPA is based on InAs/GaAs quantum dots infrared photodetectors (QDIP) with different capping layers (i.e. GaAs and In 0.20 Ga 0.80 As), corresponding to the extended middle-wave infrared (EMIR, 5-8 μm) and long-wave infrared (LWIR, 8- 12 μm) detection bands, respectively. The FPA shows a sensitivity of 8.2 mV/C a noise equivalent temperature difference of 172 mK at the FPA operating temperature of 67 K. Thermal images were obtained at both the EMIR and the LWIR bands at a low FPA bias of -0.7V. Voltage-tunable multispectral imaging was also achieved. Since each of the detection spectral of the QD FPA can be individually tuned by engineering its QD capping layer, this approach offers greater flexibility in designing detection spectrum of a multispectral FPA.
On non-negative solvability of nonlinear input–output systems

Abstract Sufficient and necessary conditions are given for the existence of unique non-negative solutions of non-linear input-output systems. As special cases linear and differentiable systems are analyzed.
Local scrape-off layer control using biased electrodes in NSTX

An experiment on the National Spherical Torus Experiment (NSTX) was designed to test the theory that biased electrodes can affect the local scrape-off layer (SOL) by creating a strong radial E x B flow (Cohen and Ryutov 1997 Nucl. Fusion 37 621). These electrodes were located near the outer midplane and were biased at up to +/-90V with respect to the local vacuum vessel ground. This biasing caused large changes in the local SOL profiles as measured by an array of Langmuir probes between the electrodes. A theory is presented which at least partially describes the experimental results.
Single-stage repair of distal aortic arch and thoracoabdominal dissecting aneurysms using aortic tailoring and circulatory arrest

The adjuncts of profound hypothermic circulatory arrest and aortic tailoring are combined with standard graft replacement of the noncritical portions of the aorta. This combination permits single-stage replacement of the arch, thoracic, and abdominal aorta in patients with postdissection aneurysm. Reconstruction is begun with repair of the mid to distal aortic arch and Dacron graft replacement of the proximal descending thoracic aorta, usually under profound hypothermic circulatory arrest. The proximal graft is then cannulated and the patient partially warmed while the middle segment is "tailored." Aortic tailoring consists of longitudinal aortotomy and removal of the dissection membrane(s) from the distal third of the descending thoracic aorta to below the renal arteries. The aorta is then closed creating a single channel 2 to 3 cm in diameter and containing the origins of the important intercostal, lumbar, and visceral arteries. A Dacron graft is used to replace the infrarenal segment. Five patients have successfully undergone single-stage, total repair of the aorta including the arch, thoracic, and abdominal segments. All survival without paraplegia or significant visceral ischemia. Follow-up has not shown dilatation of the tailored segment. We believe that reduction in diameter of the tailored aortic segment and thus wall tension, growth of neointima on all luminal aortic surfaces, and active collagen deposition contribute to the success of this procedure.
Cholinergic targets for cognitive enhancement in schizophrenia: focus on cholinesterase inhibitors and muscarinic agonists

Rationale Alterations in the central cholinergic system of patients with schizophrenia such as reduced numbers of muscarinic and nicotinic receptors in the cortex and hippocampus may contribute to the cognitive impairment of schizophrenia. Therefore, pharmacological treatments that enhance central cholinergic function may be useful as cognitive enhancers in schizophrenia.
Terminal cognitive decline: accelerated loss of cognition in the last years of life.

Objective To test the hypothesis that rate of cognitive decline accelerates in the last years of life. Methods Participants are 853 older persons without dementia at study onset. For up to 8 years, they underwent annual clinical evaluations that included a battery of 19 cognitive tests from which previously established composite measures of global cognition and specific cognitive domains were derived. In analyses, we used linear mixed-effects models that allowed rate of cognitive decline to change at a given point before death to estimate the onset of a terminal decline period and rate of cognitive decline before and after that point. In subsequent analyses, we tested potential modifiers of terminal decline. Results There were 115 deaths. Those who died did not differ from survivors in their level of global cognitive function at study onset, but beginning a mean of 42 months before death, their rate of global cognitive decline sharply increased. The duration and rapidity of terminal decline in global cognition differed from person to person. Terminal cognitive decline was not modified by age, sex, education, or the presence of mild cognitive impairment, but it was not present in those with vascular disease (e.g., stroke and heart attack) or in those without at least one copy of the apolipoprotein E epsilon4 allele, suggesting that Alzheimer's disease pathology may contribute to the phenomenon. Conclusions In old age, cognitive decline markedly accelerates during the last 3 to 4 years of life, consistent with the terminal decline hypothesis.