cssi/SciSciGPT-SciSciNet huggingface dataset:
Transitioning to intravitreal aflibercept following a previous treat-and-extend dosing regimen in neovascular age-related macular degeneration: 24-month results

To evaluate frequency of injections, visual and anatomical outcomes of neovascular age-related macular degeneration (nAMD) patients transitioned to intravitreal aflibercept after failure to extend treatment interval beyond 8 weeks with prior intravitreal bevacizumab or ranibizumab. Retrospective review of patients with nAMD switched to aflibercept following ≥6 prior intravitreal ranibizumab or bevacizumab injections at 4–8-week intervals. Three monthly aflibercept injections were given followed by a treat-and-extend dosing regimen. Twenty-one eyes of 18 patients who had received a mean of 23.8±18.8 (mean±SD; range 6–62) prior ranibizumab or bevacizumab injections were included. Over a mean follow-up of 24 months after the transition, 9.2±2.9 (range 4–21) aflibercept injections were required. Interval between aflibercept injections increased to 57.3 days (range 35–133 days), as compared with 37±6.1 days (range 29–54 days) with the prior agents (P=0.01). Mean best-corrected visual acuity was preserved (0.42±0.31 vs 0.42±0.23 logMAR; P=0.2). Mean OCT central subfoveal thickness (292.1±83.2 μm to 283.6±78.6 μm; P=0.4) and mean macular volume (7.9±0.95 mm3 to 7.67±0.94 mm3; P=0.16) remained stable. Patients requiring treatment more frequently than every 8 weeks with ranibizumab and bevacizumab were transitioned to >8-week treatment interval with aflibercept while maintaining the anatomic and visual gains.
m 6 A RNA methylation: from mechanisms to therapeutic potential

RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N6 -methyladenosine (m6 A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m6 A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre-mRNA processing, nuclear export, decay, and translation. The importance of m6 A methylation as a mode of post-transcriptional gene expression regulation is evident in the crucial roles m6 A-mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m6 A exerts its functions and discuss recent advances that underscore the multifaceted role of m6 A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m6 A deposition on mRNA and its context-dependent effects on mRNA decay and translation, the role of m6 A methylation of non-coding chromosomal-associated RNA species in regulating transcription, and the activities of the RNA demethylase FTO on diverse substrates. We also discuss emerging evidence for the therapeutic potential of targeting m6 A regulators in disease.
Sensory Innervation of the Larynx and the Search for Mucosal Mechanoreceptors

Purpose The larynx is a uniquely situated organ, juxtaposed between the gastrointestinal and respiratory tracts, and endures considerable immunological challenges while providing reflexogenic responses via putative mucosal mechanoreceptor afferents. Laryngeal afferents mediate precise monitoring of sensory events by relay to the internal branch of the superior laryngeal nerve (iSLN). Exposure to a variety of stimuli (e.g., mechanical, chemical, thermal) at the mucosa-airway interface has likely evolved a diverse array of specialized sensory afferents for rapid laryngeal control. Accordingly, mucosal mechanoreceptors in demarcated laryngeal territories have been hypothesized as primary sources of sensory input. The purpose of this article is to provide a tutorial on current evidence for laryngeal afferent receptors in mucosa, the role of mechano-gated ion channels within airway epithelia and mechanisms for mechanoreceptors implicated in laryngeal health and disease. Method An overview was conducted on the distribution and identity of iSLN-mediated afferent receptors in the larynx, with specific focus on mechanoreceptors and their functional roles in airway mucosa. Results/Conclusions Laryngeal somatosensation at the cell and molecular level is still largely unexplored. This tutorial consolidates various animal and human researches, with translational emphasis provided for the importance of mucosal mechanoreceptors to normal and abnormal laryngeal function. Information presented in this tutorial has relevance to both clinical and research arenas. Improved understanding of iSLN innervation and corresponding mechanotransduction events will help shed light upon a variety of pathological reflex responses, including persistent cough, dysphonia, and laryngospasm.
Reparations and the Right to Return

American slavery was a system of theft – theft of life, of human dignity, of family, of safety, of identity, of property, and of home. After the abolition of slavery, that theft continued through Jim Crow and state-sponsored racial terror. As Black families acquired land and other property despite that institutionalized terror, they commonly had their property stolen. One result of this legacy of theft is America’s profound racial segregation and wealth inequality. As America responds to the renewed momentum in the fight for Black reparations, the country must grapple with how to address the full legacy of the land theft and displacement born from slavery. The right to return has long been used internationally as a legal and conceptual framework to protect ethnic minorities who were the victims of ethnic cleansing. It is a demand for people who have been displaced from their country, community, or home to return with safety, dignity, and support. This essay explores how the right to return framework can be used to advance reparations for slavery, Jim Crow, and the decades of racial violence that forced Black people out of their homes, businesses, and communities. Reparations grounded in this right would acknowledge the centuries of harm to Black people who were driven from their homes through America’s ethnic cleansing and endeavor to bring those people, their descendants, and members of the community home, assist them in rebuilding their lives, or compensate them for their loss.
Platelet proteome dynamics in hibernating 13-lined ground squirrels.

Hibernating mammals undergo a dramatic drop in temperature and blood flow during torpor, yet avoid stasis blood clotting through mechanisms that remain unspecified. The effects of hibernation on he...
Conflict in the Health Care Workplace

Managing conflict in the workplace is a time-consuming but necessary task for the physician leader. Conflicts may exist between physicians, between physicians and staff, and between the staff or the health care team and the patient or patient’s family. The conflicts may range from disagreements to major controversies that may lead to litigation or violence. Conflicts have an adverse effect on productivity, morale, and patient care. They may result in high employee turnover and certainly limit staff contributions and impede efficiency. Litigation is now readily available for those who feel that they are working in a hostile work environment. The hostile environment may be the result of abusive behavior by other employees, supervisors, or physicians. The abuse may take the form of a demeaning attitude, ridicule, off-color jokes, sexual harassment, or even physical violence. Societies have significantly decreased their tolerance of disruptive behavior. A group or organization can now hold vicarious liability for condoning a hostile work environment if it fails to act when a complaint is made.
Congenital and neonatal thrombocytopenic purpura: a review.

Summary Thrombocytopenia should always beconsidered in the clinical evaluation of hemorrhage in the newborn and young infant. Often recognizable with no more difficulty than the careful perusal of a peripheral blood film, the presence of low platelets should initiate efforts to establish the responsible mechanism. The onset and duration of bleeding and the presence or lack of accompanying illness or anomalies contribute direction to these efforts. In the newborn period, mild thrombocytopenic purura in an infant without other disturbances suggests immunothrombocytopenia and the passive transferral of maternal antibody. This suspicion may be supported by deliberate examination of the mother with emphasis on inspection for purpura, blood examination for thrombocytopenia, and taking a careful history for evidence of a bleeding tendency, recent suspicious drug exposure, or previous births resulting in transient neonatal purpura. Persistence of thrombocytopenia beyond the immediate neonatal period might still reflect a maternal influence. More likely, however, is the possibility of primary illness in the infant, whether congenital or acquired. The presence of other congenital anomalies suggests underlying megakaryocyte hypoplasia, whereas the presence of signs of illness, such as anemia, icterus, visceromegaly, skin rash, and failure to thrive, might indicate one of many serious disease states, such as infection, leukemia, or reticuloendotheliosis. Management of the thrombocytopenic state in a newborn infant requires judicious watching since the disorder is so frequently benign and self-limited. The attending physician bears considerable responsibility, however, in estimating the imminence of intracranial hemorrhage and in initiating proper therapeutic measures. When thrombocytopenia is chronic, the management is directed at the underlying cause, if possible, and toward attempts to prevent serious bleeding by supporting vascular hemostasis, when necessary, with steroid hormones, splenectomy, or platelet transfusions.
On Creativity in Sporting Activity: With Some Consequences for Education

This paper proposes a definition of sporting creativity that is based on a phenomenological account of sporting experience. Taking philosophical cues from the thought of Charles Sanders Peirce, it argues that creativity in sporting activity is the ability to respond to the physical challenges encountered in the practice of sport in spontaneous and imaginative ways on the basis of carefully cultivated physical and mental—or bodyminded—habits. This definition involves several key Peircean notions such as imagination, spontaneity, habit, and the continuity of body and mind, which are expounded one by one (section I). Some examples then illustrate the proposed definition (section II). This is followed by a more detailed discussion of the relationship between imagination, bodyminded skill, practice, experience, and the conception of possibilities in order to enrich the phenomenological description of creative sporting activity (section III). The paper then turns to consider some reasons why sporting creativity is of philosophical interest to sporting communities and, especially, for the integral education of the bodyminded person (section IV). These reasons are finally recast in terms of possibilities for creative self-realization in sport, highlighting the upshot of an education for creativity (section V).
Trust and commitment: Indicators of successful learning in international joint ventures (IJVs)

This study focused on the importance of trust and commitment to International Joint Ventures (IJVs). According to Kogut (1988), joint ventures are formed for various reasons, one of important reasons being learning between the partners. This article proposes that trust and commitment are positively related to learning between IJV partners. An empirical analysis was conducted by surveying 1000 CEOs of IJVs in India. The study does show that there is a positive relationship between learning and trust and commitment. The study also proves that IJVs with better trust mechanisms tend to learn more from their partners.
Recent advances in nanotechnology: key issues & potential problem areas

Recent developments in nanosciences and nanotechnology have created tremendous enthusiasm among researchers and scientists across the globe. The rapidly increasing interest among various engineering disciplines toward research and development needs of nano-domain have spurred the growth in areas such as nanoelectronics, biotechnology & health delivery system and commerce in general. In this paper, a state-of-the-art encompassing the recent developments and the key problems in nanomanufacturing that relate to the domain are presented. Furthermore, contribution in this field from the researchers in different parts of the world are included and compared to monitor the present progress. With the down sizing of present silicon, IC technology, validity of Moore's law has become seemingly limited. However, it is strongly believed that the novel materials will provide the answer for further scaling of device density and performance. For example, most recent attention has been paid on carbon nanotubes, which can be used in nanosize electronic devices. It is still a question whether nanotube based technology will actually contribute to the existing CMOS technology or it is a totally new device architecture from CMOS technology. Besides, it is unclear whether this material will meet scalability, durability and existing performance. Modelling and simulation is a vital element for gaining insight to the behaviour of these materials and also to the characterization process. A part of this paper will be devoted to fully analyze the current trends in nanoelectronics based on nanostructured materials other than silicon.
Efficient method for computing the maximum-likelihood quantum state from measurements with additive Gaussian noise.

We provide an efficient method for computing the maximum-likelihood mixed quantum state (with density matrix $\ensuremath{\rho}$) given a set of measurement outcomes in a complete orthonormal operator basis subject to Gaussian noise. Our method works by first changing basis yielding a candidate density matrix $\ensuremath{\mu}$ which may have nonphysical (negative) eigenvalues, and then finding the nearest physical state under the 2-norm. Our algorithm takes at worst $O({d}^{4})$ for the basis change plus $O({d}^{3})$ for finding $\ensuremath{\rho}$ where $d$ is the dimension of the quantum state. In the special case where the measurement basis is strings of Pauli operators, the basis change takes only $O({d}^{3})$ as well. The workhorse of the algorithm is a new linear-time method for finding the closest probability distribution (in Euclidean distance) to a set of real numbers summing to one.
Handwriting Without Tears®: General Education Effectiveness Through a Consultative Approach

OBJECTIVE This study explores the effectiveness of the Handwriting Without Tears(®) (HWT) kindergarten printing curriculum in general education through a consultative approach with occupational therapy. METHOD One cohort of students was the control (n = 19), whereas two other cohorts were experimental groups learning printing through the HWT curriculum (n = 20 each). The Test of Handwriting Skills-Revised (THS-R) was used to collect end-of-year legibility scores for all cohorts. RESULTS Both experimental groups individually and both experimental groups combined into one group outperformed the control group on all 10 of the THS-R subtests-scoring significantly higher (p < .05 using analysis of covariance controlling for age and gender) on 6 of the subtests for the former and 7 for the latter-and on overall score. Large treatment effects were found for the standard score for each experimental group (d = 0.81, 1.03, and 1.00). CONCLUSION This study supports the consultative role of occupational therapy with teachers in general education for handwriting curriculum implementation and the success of HWT for printing instruction.
SNM-aware power reduction and reliability improvement in 45nm SRAMs

Read stability and write ability are important factors in SRAM design. However, read stability and write ability of the 6T-cell are conflicting design requirements. It is increasingly more difficult to balance these requirements with conventional transistor sizing and V th optimization as technology scales. In this paper, we present a method to help reduce SRAM power consumption by deciding the optimal pull-up transistor size in 6T SRAM cell. Our experiments show that the proposed method can reduce the supply voltage as much as 7–8%. Furthermore, our method has an average 7.76% power reduction in both active and standby mode at 25°C, a 35% V th variation reduction, 7.78% SNM variation reduction and 11.3% NBTI degradation reduction with at most 1.95% area overhead.
Surgical unit time utilization review: resource utilization and management implications

As health care providers seek ways to reduce the cost of health care services, hospital operating rooms (ORs) have been identified as potential areas for cost reduction efforts. Cost containment efforts which have shifted significant portions of the inpatient population to ambulatory areas have resulted in an inpatient population which is sicker and more procedure-intensive. Efficient management of operating rooms has assumed even greater importance in this environment. Inefficient or inaccurate scheduling of OR time often results in delays of surgery or cancellations of procedures, which are costly to the patient and the hospital. Approaches to efficient use of ORs include computerized scheduling, utilization monitoring, and refinement of scheduling policies and procedures. In the absence of commercially avaiable software to meet operating room management information needs, Johns Hopkins developed its own system in 1983. This software provides detailed information for daily OR management and long-term planning. The computerized operating room scheduling and monitoring system is described in this article and an operational measure of scheduling accuracy is proposed. Suggestions are made for incorporating this measure into planning and allocation decisions.
Sensitivity of the Amundsen Sea Low to Stratospheric Ozone Depletion

AbstractDramatic sea ice loss in the Amundsen and Bellingshausen Seas and regional warming in West Antarctica and the Antarctica Peninsula have been observed over the last few decades. Both of these changes are strongly influenced by the presence of the Amundsen Sea low (ASL), a climatological region of low pressure in the Amundsen Sea. Studies have demonstrated a deepening of the ASL, particularly in austral spring and to a lesser extent autumn, the former related to decreases in the underlying cyclone central pressures and the latter previously suggested to be due to stratospheric ozone depletion.This study further investigates the sensitivity of the ASL to stratospheric ozone depletion using geopotential height from a suite of chemistry–climate models (CCMs) as well as historical simulations from phase 5 of the Coupled Model Intercomparison Project (CMIP5). Overall, both model types capture the mean characteristics of the ASL, although they have notable positive height biases at 850 hPa and a subdued s...
Searching for direction: Courts, social science, and the adjudication of racial profiling claims

As an issue of contemporary legal and social concern, racial profiling has become part of the national discourse. As claims of racial profiling proliferate, courts are struggling to adjudicate them without sound social science research on law enforcement stop practices. This article reviews the methodological and analytical weaknesses inherent in most of the research on racial profiling and illustrates how these weaknesses have caused problems for courts in deciding racial profiling claims. It also presents a methodological strategy for curing many of the defects in previous racial profiling studies, thereby providing courts with a sound basis for deciding equal protection-based claims that often rely on statistical evidence.
Vitamin E inhibits cyclosporin A and H2O2 promoted Epstein-Barr virus (EBV) transformation of human B cells as assayed by EBV oncogene LMP1 expression.

Abstract Background We have previously shown that oxidative stress induced by H 2 O 2 or cyclosporin A (CsA) can promote Epstein–Barr virus (EBV) transformation of human B cells as analyzed by colony formation, cell number, and by 3 H-thymidine incorporation. In this report, we used EBV oncogene LMP1 as a marker to analyze H 2 O 2 or CsA promotion of EBV transformation of human B cells and to test whether antioxidant vitamin E could inhibit H 2 O 2 or CsA promoted LMP1 expression in the EBV-infected cells. Materials and methods Human splenocytes were prepared by centrifugation and plating technique to provide a greater than 80% pure preparation of B cells and were used for EBV infection. The EBV infected cells were treated with H 2 O 2 (0.1 m m , 10 min), or with CsA (500 ng/ml) with or with out vitamin E (40 μ m ). The cells were cultured for up to 4 weeks. Samples were taken every week and were stained with phycoerythrin-conjugated mouse anti-LMP1 monoclonal antibody to assay LMP1 positive population by flow cytometry. Results In EBV-infected cells, the LMP1-positive cell population reached 14% after 4 weeks of culture. CsA or H 2 O 2 treatment promoted LMP1 positive population to 43% and 41% after 4 weeks of culture. Vitamin E (40 μ m ) completely inhibited LMP1 expression in EBV-infected cells and in CsA- or H 2 O 2 -treated cells. Conclusion In agreement with our previous observation, CsA or H 2 O 2 can promote EBV transformation of human B cells. This oxidative stress induced promotion of EBV transformation can be blocked by antioxidant Vitamin E. This finding may have future therapeutic implications for post-transplant lymphoproliferative disorder.
Effect of mechanical processing on the stability of metastable icosahedral quasicrystalline nanoparticles in zirconium and hafnium based metallic glasses

Abstract Metastable icosahedral quasicrystalline nanoparticles precipitate in the initial crystallization processes of some selected zirconium and hafnium based metallic glasses. All such particles reported so far are embedded in residual glassy matrix. It is predicted that, if these are separated as free standing particles, they can be applied in a variety of fields. Breaking the suitably annealed metallic glasses to small pieces by mechanical approaches is considered to be the first step toward this goal. The result of such an attempt is reported here. Several previously reported metallic glasses such as Zr 70 Cu 27.5 Rh 2.5 and Hf 69.5 Al 7.5 Ni 11 Cu 12 have been abraded by using regular sandpapers and diamond papers, scraped with diamond scratchers, and sliced by using microtome. Thus obtained small pieces have been examined by Scanning Electron Microscope, Transmission Electron Microscope, and Energy Dispersive X-ray Spectroscopy. It has been revealed that the mechanical breaking processes cause an undesired phase transformation of the quasicrystalline nanoparticles to the crystalline phases. The reason for this undesired phase transformation was analyzed and the appropriate procedures to avoid this negative effect for future work were suggested.
The Ford Cargo

During 1981 and 1982 the fifteen year old Ford ‘D’ Series was replaced by the distinctively designed Cargo range. This is intended to meet road transport needs in the 1980s and beyond for vehicles from 6 to 32.5 tonnes gross mass and up to 150 kW. This segment covers about 50 per cent of the total Western European market for commercial vehicles above 3.5 tonnes.This paper gives a glimpse of how the objectives for such a programme were defined and how they were met by careful attention to planning, initial design, development and testing with the close co-operation of manufacturing engineers at all stages.
Riemannian submersions and the regular interval theorem of Morse theory

A generalized version of the regular interval theorem of Morse theory is proven using techniques from the theory of Riemannian submersions and conformal deformations. This approach provides an interesting link between Riemannian submersions (for real valued functions) and Morse theory.
Using the game of life to introduce freshman students to the power and elegance of design patterns

In this paper, we describe two programming assignments based on a refactoring of the classic Game of Life application. In particular, we use the Game of Life to help teach freshman students two important and widely applicable design patterns - Command and Visitor.
Concentrative uptake of melphalan, a cancer chemotherapeutic agent which is transported by the leucine-preferring carrier system.

Abstract The transport of melphalan, L -phenylalamine mustard, proceeded uphill against a concentration gradient and resulted in a distribution ratio of approximately 10. Concentrative uptake was temperature sensitive and was inhibited by the metabolic inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and L -leucine, a natural substrate of the transport carriers. These results indicate that melphalan transport is an energy requiring process and that naturally occurring competitive substrates such as leucine markedly reduce concentrative uptake of the drug.
Seismic Performance of Steel Girder Bridges with Ductile Cross Frames Using Buckling-Restrained Braces

Ductile end cross frames have been proposed in the past for seismic design of steel plate girder bridges. In this paper buckling-restrained braces (BRBs) are investigated as ductile end cross frames and compared against the performance of yielding X braces. Component experiments on the BRBs showed that these braces dissipated energy very efficiently and have stable hysteretic behavior. Shake-table experiments on a large scale bridge model investigated the performance of braces with both pin-ended connections and fixed-end connections. Despite slippage, the pin-ended connections are considered more effective as flexural action in the relatively short braces is prevented. The base shear in the bridge model in response to 2.0 times the El Centro earthquake was 69% of the elastic base shear at an average drift of 2.5% during experiments. The relatively large deformation capacity of the BRBs, although not as great as the X braces, is necessary to achieve a significant reduction in base shear. The maximum cross frame displacements with the BRBs are consistently smaller than those in X braces at the same level of base shear.
High rate premetallization sputter etching of submicron vias using a high-density dual-frequency plasma source

This paper reports on the results of the optimization of a high throughput sputter etch process prior to interconnect deposition with no device damage, performed on the Endura HP PVD system. The second level metallization for a 2-level metal interconnect scheme requires a pre- metallization sputter etch of the vias in order to remove the native oxide and the fluoro-carbon residues left after the ILD oxide etch. For high throughput processing, high etch rates are required along with the essential prerequisites of plasma processing, namely, good process uniformity and no electrical device damage. A high density dual-frequency system with independent control of plasma and bias powers was used to optimize the pre-metallization etch using the second level of a 256 K SRAM device test structure fabricated in a 150 mm wafer production line. Response surface methodology (RSM) was used to explore the parameter space of the sputter etch process. The rf plasma power, rf bias power and the SiO2 thickness etched were chosen as the 3 independent variables. The SiO2 etch rate, SiO2 etch uniformity, via resistance & uniformity and threshold voltage & uniformity were measured and modeled as the response variables. SiO2 etch rates from 214 A/min to 926 A/min, SiO2 etch uniformities from 1.88 to 7.27% 1-sigma, via resistances from 0.32 to 0.42 Ohms, and threshold voltages from 0.74 V were obtained. A suitably wide process window was established with the excellent process/device results and a 40% reduction in process time.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Semistable Bundles over an Elliptic Curve

Abstract We identify the moduli space M n, d of semistable bundles of rank n and degree d on an elliptic curve C as a symmetric product of the curve, its dimension being the greatest common divisor of n and d. Under this identification the determinant map det: M n, d corresponds to the Abel-Jacobi map α: ShC → Jh, so that the fixed-determinant moduli space is identified with a projective space. We then describe the Brill-Noether loci, theta divisors, and Picard groups and compute the space of theta functions for both the full moduli space and the fixed-determinant moduli space of any rank and any degree. We extend to elliptic curves a theorem of Drezet and Narasimhan on the Picard group of moduli spaces, as well as two formuulas of Beauville, Narasimhan, and Ramanan on theta functions of level one. Our results verify in particular for an elliptic curve a formula of E. Verlinde, and an equality first noticed by Bott and Szenes relating theta functions over the full moduli space and over the fixed-determinant moduli space.
Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels

Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1–KCNEx complexes. Mutations in either KCNQ1 or KCNE1 genes result in diseases in brain, heart, and the respiratory system. In addition to complexities arising from existence of five KCNE subunits, KCNE1 to KCNE5, recent studies in heterologous systems suggest unorthodox stoichiometric dynamics in subunit assembly is dependent on KCNE expression levels. The resultant KCNQ1–KCNE channel complexes may have a range of zero to two or even up to four KCNE subunits coassembling per KCNQ1 tetramer. These findings underscore the need to assess the selectivity of small-molecule KCNQ1 modulators on these different assemblies. Here we report a unique small-molecule gating modulator, ML277, that potentiates both homomultimeric KCNQ1 channels and unsaturated heteromultimeric (KCNQ1)4(KCNE1)n (n < 4) channels. Progressive increase of KCNE1 or KCNE3 expression reduces efficacy of ML277 and eventually abolishes ML277-mediated augmentation. In cardiomyocytes, the slowly activating delayed rectifier potassium current, or IKs, is believed to be a heteromultimeric combination of KCNQ1 and KCNE1, but it is not entirely clear whether IKs is mediated by KCNE-saturated KCNQ1 channels or by channels with intermediate stoichiometries. We found ML277 effectively augments IKs current of cultured human cardiomyocytes and shortens action potential duration. These data indicate that unsaturated heteromultimeric (KCNQ1)4(KCNE1)n channels are present as components of IKs and are pharmacologically distinct from KCNE-saturated KCNQ1–KCNE1 channels.
Protein metabolism in SV40-infected cells.

Abstract Simian virus 40-induced alterations in protein metabolism were investigated in confluent monolayers of BS-C-1 monkey kidney cells. Viral-induced changes were observed which were specific for both the prereplicative and the replicative phases of infection. The prereplicative phase is that period of the infection prior to the onset of viral DNA synthesis, which begins at 19–20 hr. A viral-induced stimulation of protein synthesis is first observable at about 10–12 hr, and by 20 hr after infection the rate of protein synthesis has increased to more than 20% above that of mock-infected cells. Gel electrophoresis of the proteins synthesized during the prereplicative period did not reveal any differences from control cells in any cell fraction except the cytosol, i.e., the nonparticulate portion of the cytoplasm. In this fraction several new species were observed, but together they did not constitute more than 1% of the overall rate of protein synthesis. An inhibition of labeling of one, and possibly two, host proteins was also discerned in the cytosol. Each of the polypeptide changes just described was also observed in infected cells which had been treated with cytosine arabinoside. This confirms the assignment of these effects to the early phase of infection, as it has been well-established that cytosine arabinoside blocks viral DNA synthesis and all late viral functions, but has little effect on early events. During the replicative period the rate of protein synthesis continues to increase to more than 50% above that of mock-infected cells. Starting at 20 hr postinfection, proteins destined for the nucleus are synthesized at higher relative rates than those of cytoplasmic fractions. As a consequence, a very large progressive accumulation of protein in the nucleus begins at about 40 hr after infection. Much of this increased nuclear mass could be accounted for as progeny virus particles found in the membranous fraction of sonicated nuclei. Gel electrophoresis of newly-made proteins late in infection showed that the two major viral structural proteins constituted about 20% of cellular protein synthesis. There was an additional viral-induced nonstructural polypeptide in the cytosol which constituted less than 1% of the newly-made proteins. As expected, these three new proteins were not synthesized in infected cells which had been treated with cytosine arabinoside. It was also observed that the labeling of the major host protein in the nuclear membrane was inhibited during the late phase of infection.
Kainate receptor activation potentiates GABAergic synaptic transmission in the nucleus accumbens core

Inhibitory synaptic transmission plays an important role in regulating the activity of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc). The kainate (KA) subtype of ionotropic glutamate receptor has been shown to potently modulate GABAergic synaptic transmission in several brain regions. Although KA receptor subunits are expressed in the NAcc, KA receptor modulation of GABAergic synaptic transmission in this brain region has not been previously examined. In the current study, we sought to determine if KA receptor activation could alter inhibitory synaptic transmission in the NAcc as it has been shown to do in other brain regions. Using the whole cell patch-clamp technique, we demonstrate that KA receptor activation potentiates evoked GABAergic synaptic transmission and increases the frequency of spontaneous, but not miniature, GABAA-receptor-mediated IPSCs in the NAcc. In contrast, KA has no effect on currents evoked by exogenous application of GABA onto MSNs. Taken together, these data suggest that activation of KA receptors in the NAcc core potently facilitates action-potential-dependent GABAergic synaptic transmission, likely via an excitation of presynaptic GABAergic interneurons.
Experiments in control of flexible structures with noncolocated sensors and actuators

While the stable control of such flexible structures as limber spacecraft is easily achieved through the colocation of control actuators with sensors, noncolocation renders this extremely difficult. The most difficult case in point is that in which structural damping is low and spacecraft stiffness and inertia values are uncertain and changing. Attention is presently given to an apparatus in which each basic sensor/actuator noncolocation configuration is available, and inertias can be abruptly halved or doubled during control maneuvers. This feature can impose a sudden reversal in the plant's pole-zero sequence, which is a very difficult condition for the controller. Test results obtained to date demonstrate the inherent difficulty of achieving robustness in the case of noncolocation. It is noted that there may be very simple configurations in which there is no alternative to adaptive control.
Endogenous Skin Fluorescence is a Good Marker for Objective Evaluation of Comedolysis

Objective evaluation of comedone lesions, especially in vivo, remains a challenge. We have used the rhino mouse model in combination with topical application of all-trans retinoic acid as a comedolytic agent, to investigate the potential of fluorescence spectroscopy as a noninvasive technique in the assessment of noninflammatory acne. The results indicate that there is a strong correlation between the fluorescence excitation spectral features assessed in vivo, and the histologic changes identified, particularly the size of the utriculi as well as the dermal and epidermal thickness. We conclude that fluorescence excitation spectroscopy represents a promising novel and useful tool in the quantitative evaluation of the pseudocomedones and could also be used for the rapid and noninvasive assessment of comedolysis induced by the application of pharmacologic agents such as retinoids.
Einstein and Oppenheimer: Scientists’ Lives in the Currents of History

Einstein's Nobel Prize: A Glimpse Behind Closed Doors, by Aant Elzinga, Sagamore Beach: Science History Publications, 2006. Einstein and Oppenheimer: The Meaning of Genius, by Silvan S. Schweber, C...
Claudication secondary to Perclose use after percutaneous procedures

The use of suture-mediated arterial closure devices has dramatically increased with the increased number of percutaneous procedures being performed. Complications from suture-mediated closure devices have been underreported. Specifically, arterial stenosis resulting in claudication has not been previously described in detail. We present nine patients who presented with various leg symptoms after Perclose was used to achieve arterial hemostasis following percutaneous procedures. All cases were found to have significant arterial stenoses from the Perclose sutures. Once diagnosis was correctly made, the patients either underwent surgical repair or percutaneous balloon angioplasty and in all cases the symptoms abated.
An iterative method for the solution of the initial boundary-value problem of propagation of elastic disturbances in an inhomogeneously strained body

We propose an iterative method for the solution of initial boundary-value problem for a hyperbolic equation, which models the sounding of an inhomogeneously strained body of finite sizes with elastic disturbances.
Calculation of T=2 → T=1 → T =0 M1 decays in A =20 and A =32 nuclei

Abstract Absolute strenghts and branching ratios are calculated for M1 transitions between states of different isospin in two A = 4 n nuclei of the sd-shell.
Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer

Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs. They are neither conventional cytotoxic agents, nor are they monofunctional drugs that uniquely target single steps in signal transduction pathways. Synthetic oleanane triterpenoids have profound effects on inflammation and the redox state of cells and tissues, as well as being potent anti-proliferative and pro-apoptotic agents. Rexinoids are ligands for the nuclear receptor transcription factors known as retinoid X receptors. Both classes of agents can prevent and treat cancer in experimental animals. These drugs have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments.
Three-dimensional reconstruction of active muscle cell segment volume from two-dimensional optical sections

An ultramicroscope coupled to a square-aspect-ratio sensor was used to image the dynamic geometry of live muscle cells. Skeletal muscle cells, dissected from frogs, were suspended in the optical axis and illuminated from one side by a focused slit of white light. The sensor detected light scattered at 90 degrees to the incident beam. Serial cross-sections were acquired as a motorized stage moved the cell through the slit of light. The axial force at right angles to the cross- sections was recorded simultaneously. Cross-sections were aligned by a least-squares fit of their centroids to a straight line, to correct for misalignments between the axes of the microscope, the stage, and the sensor. Three- dimensional volumes were reconstructed from each series and viewed from all directions to locate regions that remained at matching axial positions. The angle of the principal axis and the cross-sectional area were calculated and associated with force recorded concurrently. The cells adjusted their profile and volume to remain stable against turning as contractile force rose and fell, as predicted by the law of conservation of angular momentum.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure.

Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system.
What is “Normative” for Fish Pathogens? A Perspective on the Controversy over Interactions between Wild and Cultured Fish

Abstract In its report, Return to the River, the Independent Scientific Group (now called the Independent Scientific Advisory Board—the scientific peer review arm of the Northwest Power Planning Council) advanced the notion of a “normative river ecosystem” as a new conceptual foundation for salmonid recovery in the Columbia River basin. With this perspective, the sum of the best scientific understanding of how organisms and aquatic ecosystems naturally function should be the norm or standard of measure for how we judge the effects of human activities on aquatic systems. For the best likelihood of recovery, key aspects of altered systems should be brought back toward normative (although not necessarily fully back to the historical or pristine state); new alterations should be judged by how much they move key functions away from normative or what might be considered as normal. In this paper, I ask what “normative” is for fish pathogens and how this concept could help resolve the long-standing disputes betwe...
Quantitative dependence of mitochondrial oxidative phosphorylation on oxygen concentration: a mathematical model.

Abstract The model of Wilson and co-workers ( 2. , 3. , Arch. Biochem. Biophys. 182, 749–762) for the regulation of mitochondrial oxidative phosphorylation has been extended to include the dependence on oxygen tension. The derived rate expression correctly describes the observed dependence of cellular energy metabolism on oxygen tension, including the oxygen dependence at “normoxic” physiological values. Experimental evidence is presented that oxidative phosphorylation by suspensions of isolated rat liver mitochondria is also dependent on oxygen concentration up to values of at least 100 μ M .
Scaling in steady-state cluster-cluster aggregation.

The diffusion-limited cluster-cluster aggregation model is investigated under conditions which for long times lead to steady-state coagulation. Single particles are added to the system at a constant rate and the larger clusters appearing as a result of the aggregation process are removed according to various rules. Our results show that the dependence of the number of clusters, N(t), on the feed rate \ensuremath{\kappa} in a unit volume and the time t can be well represented by a scaling form N(t)\ensuremath{\sim}${\ensuremath{\kappa}}^{\ensuremath{\alpha}}$f(${\ensuremath{\kappa}}^{\ensuremath{\beta}}$t) with a scaling function f(x)\ensuremath{\sim}x for x\ensuremath{\ll}1 and f(x)=1 for x\ensuremath{\gg}1. The exponents \ensuremath{\alpha} and \ensuremath{\beta} are found to depend on the spatial dimension d, of the system, but within the statistical errors they always satisfy the relation \ensuremath{\alpha}+\ensuremath{\beta}=1 in accordance with the prediction of a generalized rate equation discussed by R\'acz (see the companion paper). The values we have obtained for \ensuremath{\alpha} and \ensuremath{\beta} are consistent in two and three dimensions with the corresponding results of the Smoluchowski equation approach but inconsistent in one dimension. This can be considered as an indication of the fact that the upper critical dimension for the kinetics of the diffusion-limited cluster-cluster aggregation model is 2.
Remote Sensing Evaluation of CLM4 GPP for the Period 2000–09*

AbstractRemote sensing can provide long-term and large-scale products helpful for ecosystem model evaluation. The authors compare monthly gross primary production (GPP) simulated by the Community Land Model, version 4 (CLM4) at a half-degree resolution with satellite estimates of GPP from the Moderate Resolution Imaging Spectroradiometer (MODIS) GPP product (MOD17) for the 10-yr period January 2000–December 2009. The assessment is presented in terms of long-term mean carbon assimilation, seasonal mean distributions, amplitude and phase of the annual cycle, and intraannual and interannual GPP variability and their responses to climate variables. For the long-term annual and seasonal means, major GPP patterns are clearly demonstrated by both products. Compared to the MODIS product, CLM4 overestimates the magnitude of GPP for tropical evergreen forests. CLM4 has a longer carbon uptake period than MODIS for most plant functional types (PFTs) with an earlier onset of GPP in spring and a later decline of GPP in...
Aestheticized Politics,1 or the Long Shadow of Ernst Jünger's “Old Testament?”

In his “Old Testament,” inasmuch as its legacy crystallizes in the essay The Worker (1932), Junger conceives of an anti-bourgeois, technological society whose signature is the rule of soldier cum technocrat. Without renouncing its theories, the author appears to reverse himself in his subsequent writings, notably in the fictitious works On the Marble Cliffs (1939) and Heliopolis (1949). However, the aestheticism of the essay also informs his later fiction, both casting doubt on the nature of the reversal and handicapping a proper appreciation of the author's politics. It will be argued that, while Junger's aesthetic perception of reality has evolved intact from his “Old Testament,” there is sufficient evidence in both his writing and conduct to contradict the captivating notion that aestheticized politics equals fascism.