cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus

Infection with hepatitis C virus (HCV) is a major medical problem with over 170 million people infected worldwide. Substantial morbidity and mortality are associated with hepatic manifestations (cirrhosis and hepatocellular carcinoma), which develop with increasing frequency in people infected with HCV for more than 20 years. Less well known is the burden of HCV disease associated with extrahepatic manifestations (diabetes, B-cell proliferative disorders, depression, cognitive disorders, arthritis and Sjogren's syndrome). For patients infected with genotype 1 HCV, treatment with polyethylene glycol decorated interferon (peginterferon) α and ribavirin (PR) is associated with a low (40-50%) success rate, substantial treatment-limiting side effects and a long (48-week) duration of treatment. In the past 15 years, major scientific advances have enabled the development of new classes of HCV therapy, the direct-acting antiviral agents, also known as specifically targeted antiviral therapy for hepatitis C (STAT-C). In combination with PR, the HCV NS3-4A protease inhibitor telaprevir has recently been approved for treatment of genotype 1 chronic HCV in the United States, Canada, European Union and Japan. Compared with PR, telaprevir combination therapy offers significantly improved viral cure rates and the possibility of shortened treatment duration for diverse patient populations. Developers of innovative drugs have to blaze a new path with few validated sign posts to guide the way. Indeed, telaprevir's development was once put on hold because of its performance in a standard IC(50) assay. Data from new hypotheses and novel experiments were required to justify further investment and reduce risk that the drug might fail in the clinic. In addition, the poor drug-like properties of telaprevir were a formidable hurdle, which the manufacturing and formulation teams had to overcome to make the drug. Finally, novel clinical trial designs were developed to improve efficacy and shorten treatment in parallel instead of sequentially. Lessons learned from the development of telaprevir suggest that makers of innovative medicines cannot rely solely on traditional drug discovery metrics, but must develop innovative, scientifically guided pathways for success.
The effect of Chinese tallow tree ( Sapium sebiferum ) ecotype on soil–plant system carbon and nitrogen processes

The EICA hypothesis predicts that shifts in allocation of invasive plants give rise to higher growth rates and lower herbivore defense levels in their introduced range than conspecifics in their native range. These changes in traits of invasive plants may also affect ecosystem processes. We conducted an outdoor pot experiment with Chinese tallow tree (Sapium sebiferum, Euphorbiaceae) seedlings from its native (Jiangsu, China, native ecotype) and introduced ranges (Texas, USA, invasive ecotype) to compare their relative performances in its native range and to examine ecotype effects on soil processes with and without fertilization. Consistent with predictions, plant (shoot and root) mass was significantly greater and leaf defoliation tended to be higher, while the root:shoot ratio was lower for the invasive ecotype relative to the native ecotype. Seasonal amounts of soil–plant system CO2 and N2O emissions were higher for the invasive ecotype than for the native ecotype. Soil respiration rates and N2O emission increases from fertilization were also greater for the invasive ecotype than for the native ecotype, while shoot-specific respiration rates (g CO2–C g−1 C day−1) did not differ between ecotypes. Further, soil inorganic N (ammonium and nitrate) was higher, but soil total N was lower for soils with the invasive ecotype than soils with the native ecotype. Compared with native ecotypes, therefore, invasive ecotypes may have developed a competition advantage in accelerating soil processes and promoting more nitrogen uptake through soil–plant direct interaction. The results of this study suggest that soil and ecosystem processes accelerated by variation in traits of invasive plants may have implications for their invasiveness.
Gabapentinoids Suppress Early Afterdepolarizations by Uncoupling α2δ-1 Subunits from CAV1.2 Channels: Implications for CAV Channel Gating-Modifiers as a New Class of Antiarrhythmics

Under certain pathological conditions, the repolarization phase of the cardiac action potential (AP) is interrupted by membrane potential oscillations called early afterdepolarizations (EADs), well-recognized triggers of deadly cardiac arrhythmias. The reactivation of L-type calcium current (ICa,L) plays a prominent role in EAD formation. In recent studies using the dynamic clamp technique, we have shown that a small depolarizing shift (<5mV) of the CaV1.2 steady-state activation potently suppresses EAD occurrence. Based on this findings, we hypothesized that pharmacological interventions that induce a depolarizing shift of macroscopic ICa,L activation (gating modifiers) can suppress EADs and their arrhythmogenic consequences. Gabapentinoids (gabapentin and pregabalin), drugs that selectively bind to α2δ-1 CaV subunits and are commonly used to treat epilepsy and neuropathic pain, are good candidates as Cav gating modifiers. We found that gabapentin induced a time-dependent depolarizing shift of the voltage-dependent activation of CaV1.2 channels expressed in Xenopus oocytes (α1C β3 α2δ-1; 1mM gabapentin, 2h incubation). Since α2δ-1 facilitates CaV1.2 voltage-dependent activation, these results suggest a functional uncoupling of α2δ-1 from a fraction of channels. Importantly, the maximal macroscopic conductance was unaltered, implying that CaV1.2 channel trafficking was not perturbed, in contrast to the effects shown in other CaV isoforms. We then studied gabapentinoids effect on EAD susceptibility in freshly-dissociated rabbit ventricular myocytes under EAD-promoting conditions (600μM H2O2). Strikingly, 1 mM pregabalin suppressed EAD occurrence and restored AP duration as predicted based on the depolarizing shift in voltage-dependent activation. Taken together, these results support the view that gabapentinoids, and more generally CaV1.2 gating modifiers, show promise in suppressing EAD-mediated arrhythmias and could constitute a novel class of antiarrhythmics.
Chromatographic investigation of purines in normal human urine.

SummaryA method has been developed by which individual variations in urinary excertion of purines may be investigated on a qualitative andsemi-quantitative basis. The method employs an ion exchange step to remove uric acid, and separates by paper chromatography the purines precipitated by silver nitrate. Two normal subjects on purine-free diet excreted a total of more than 30 mg/day of non-uric acid purine derivatives. Those identified, in order of diminishing abundance, are hypoxanthine, xanthine, 7-methylguanine, adenine, 1-methylguanine and guanine.
Dimension-Reduced Incremental Harmonic Balance Method for Multi-span Rubbing Rotor System

The finite element model of multi-span rubbing rotor system has a large number of degrees of freedom,which affects the efficiency of the numerical simulation seriously. To overcome this problem and remain the accuracy of numerical simulation at the same time,a newdimension-reduced incremental harmonic balance method combining the fixed interface component mode synthesis method was presented. Firstly,the degree of freedom was reduced by the fixed interface component mode synthesis method,and then the incremental harmonic balance method was applied to obtain the stable state response of the dimension-reduced system,and at last the response of the original rotor system can be obtained. The method can not only get the stable state solution directly,but also be combined with the arc-length method to obtain the unstable state response. The results showthat a two-span rotor system can reach good accuracy and high efficiency with fewdominant modes.
Digging Pile Blast Hole Wall Rock/soil Dynamic Parameters Detection and Assessment

After being shaped of the blast hole on the pile foundations of the viaducts of Shikongshan, Jiananguan and Jiushaxi of Zhang?Long expressway, the blast hole rock/soil dynamic parameters are detected with elastic wave, and the detected results are compared with those got from the design digging The detection provides scientific basis for modification of the design and improvement of the construction technology, to ensure the rationality of the pile foundation structure and reliability of the quality
Study and application of risk assessment of cockroach infestation in key industries during large-scale events

ObjectiveTo establish a cockroach risk assessment system for key industries during large- scale events by risk recognition and evaluation methods, and to apply the system for the cockroach risk assessment in key industries during the Seventh National Intercity Games in Nanchang, China.MethodsThe probabilities of cockroach infestation were qualitatively or quantitatively defined, and the risk indices for infestation in key industries were determined according to AS/NZS4360:2004 risk assessment matrix.ResultsTen key industries were evaluated for the risk of cockroach infestation. Three industries had grade A probability of infestation, 7 industries had grade B probability, and 1 industry had grade C probability; restaurants had grade 3 outcome of infestation, farmer's markets, teahouses, and night clubs had grade 1 outcome, and the other 6 sectors had grade 2 outcome. According to the risk indices in key industries, restaurants had an extremely high-level risk(E) of infestation, hospital, teahouses, and night clubs had a medium-level risk(M), and the other 7 sectors had a high-level risk(H).ConclusionBy establishing the cockroach risk assessment system for key industries, the biohazards of cockroaches in key industries can be predicted. Not only can this system play a good role in early warning, but it can also help us take specific prevention and control measures in the industries with different risk levels.
Iatrogenic Baastrup's Syndrome: A Potential Complication Following Anterior Interbody Lumbar Spinal Surgery.

Background Baastrup9s Syndrome is a condition that occurs when there is abnormal contact between two adjacent spinous processes resulting in back pain. An alteration in lumbar spinal alignment and/or adjacent segment compensatory motion is thought to be potential causative factors. The objective of this study was to present a case series of what appears to be iatrogenic Baastrup9s Syndrome as a mid-to-late term complication following anterior lumbar interbody surgery. Methods A retrospective chart review was performed of all patients undergoing anterior lumbar surgery for either fusion or disc replacement to determine the prevalence of Baastrup9s Syndrome. Results Over a 12-year period, 855 patients who had undergone an anterior approach for lumbar spine surgery were identified. Of them 8 patients with evidence of Baastrup9s Syndrome were found; this demonstrated a prevalence of 0.9%. Diagnostic injection was a helpful clinical tool in confirming the diagnosis of iatrogenic Baastrup9s Syndrome. The partial removal of the impinging spinous processes resulted in excellent clinical relief. Conclusions Iatrogenic Baastrup9s Syndrome may be an iatrogenic result of anterior lumbar surgery in small group of patients. Spinous process excision is a suggested treatment option. Further studies are necessary to explore the above phenomenon. This study is a Level 3 retrospective case series.
Geovaluator, an Expert System for Resource Appraisal: A Demonstration Prototype for Kaolin in Georgia, U.S.A

GEOVALUATOR is an expert system to help geologists and other specialists provide an estimate of the mineral endowment of large areas for mineral exploration and governmental planning. When completed, GEOVALUATOR will estimate the mineral endowment of the United States by combining estimates from the 621 two-degree quadrangles of the National Topographic Map Series. Developed from the well-known expert system PROSPECTOR (of SRI International), the new system will help geologists use their geological knowledge and available data to evaluate mineral endowment. GEOVALUATOR will prompt geologists to use fully their knowledge of geological principles, processes, and facts, together with available data, published and unpublished. The current version of GEOVALUATOR is a demonstration prototype to evaluate the kaolin resources in part of the kaolin belt of Georgia, U.S.A. The demonstration prototype is written in the muLISP language for an IBM personal computer. Working at the keyboard, the user defines the sizes, categories, and numbers of deposits that may be present for a quadrangle. After the user has evaluated the complete set of quadrangles, GEOVALUATOR provides a summary table and a map to display graphically the estimated kaolin endowment of the trial area.
Methane Leaks from Natural Gas Systems Follow Extreme Distributions.

Future energy systems may rely on natural gas as a low-cost fuel to support variable renewable power. However, leaking natural gas causes climate damage because methane (CH4) has a high global warming potential. In this study, we use extreme-value theory to explore the distribution of natural gas leak sizes. By analyzing ∼15 000 measurements from 18 prior studies, we show that all available natural gas leakage data sets are statistically heavy-tailed, and that gas leaks are more extremely distributed than other natural and social phenomena. A unifying result is that the largest 5% of leaks typically contribute over 50% of the total leakage volume. While prior studies used log-normal model distributions, we show that log-normal functions poorly represent tail behavior. Our results suggest that published uncertainty ranges of CH4 emissions are too narrow, and that larger sample sizes are required in future studies to achieve targeted confidence intervals. Additionally, we find that cross-study aggregation o...
Biomechanics of Bone

Publisher Summary This chapter focuses on the biomechanical properties of bones. Bone is a physiologically dynamic tissue whose primary functions are to provide a mechanical support system for muscular activity, provide for the physical protection of organs and soft tissues, and act as a storage facility for systemic mineral homeostasis. The resulting structure of the skeleton is influenced heavily by mechanical principles, acting both as constraints and as driving forces in its architecture. The mechanical behavior of bone may be studied at two levels, material and structural. The material, or tissue, level properties of bone are evaluated by performing standardized mechanical tests on uniform bone tissue samples. They may also be estimated in vivo by using densitometric projections, but these are less accurate than actual mechanical testing. The assessment of bone mechanical properties can be made using techniques ranging from noninvasive imaging to in vitro mechanical tests of excised specimens or whole bones. Microcomputed tomography (CT), magnetic resonance imaging (MRI), and peripheral qualitative CT (pQCT) methods of imaging, especially in use with finite element models, continue to improve in their accuracy of mechanical property assessment. The strength and rigidity of a bone are typically greater in the direction of customary loading, particularly in cortical bone, where osteons are oriented in a longitudinal direction as indicated by the bone's loading history. Cortical bone is stronger in compression than in tension, and after maturation the tensile strength and the modulus of elasticity of femoral cortical bone decline by approximately 2% per decade. Another important mechanical property exhibited by bone is known as viscoelasticity, which is largely due to its water content, whereas material properties, such as strength and toughness, come from its solid-phase components.
Bullying and the Laws Pertaining to It

This Article describes the climate of anti-gay sentiment and fear that has made it difficult for lesbian, gay, bisexual, and transgender (LGBT) students to come out or to seek support within school communities. The 1970s Miami - Dade Gay Rights Ordinance (the so-called Save Our Children campaign) fostered a climate of silence and invisibility that eventually morphed into overt hostility toward LGBT students across most student populations in the country. The Author cites contemporary data showing dramatically high rates of hostility, including bullying and harassment, toward LBGT students. She summarizes the steps taken by the U.S. Department of Education to address bullying and she suggests several critical steps essential to improving the experience of LGBT students.
A purification of venom phosphodiesterase.

For purposes of analysis of polynucleotides, it is desirable to have a phosphodiesterase, substantially free of 5-nucleotidase or other phosphatase activity. The presence of a phosphodiesterase in a wide variety of snake venoms was demonstrated by Gullan and Jackson (1). These venoms were found also to contain a potent 5-nucleotidase, but were free of alkaline phosphatase activity. Hurst and Butler (2) found that certain samples of Russell's viper venom were nearly free of 5-nucleotidase activity, while retaining potent phosphodiesterase action. By a chromatographic procedure, involving the use of cellulose columns, they were able to reduce the 5-nucleotidase activity of rattlesnake venom, relative to its phosphodiesterase activity, and to obtain fractions nearly comparable to the viper venom.
Genes That Control High Level Developmental Switches

The process of segmentation in the embryos of insects, specifically Drosophila melanogaster, can be considered a model system for analyzing the genetic regulation of development. Segmentation of the embryo results in the basic metameric organization seen in all arthropods. Mutations have been recovered and characterized which affect the polarity of the entire embryo in both the anterior-posterior and dorsalventral axes. Other mutations reveal genes which are important in the specification of the number and polarity of body segments. Finally, there are a number of loci (homoeotic genes) which are required for each segment to achieve the proper identity. Such genes have been identified by mutations that cause or allow one segment or set of segmental derivatives to be transformed into the likeness of another homologous segment. The basic polarity of the embryo is apparently specified in the egg by the maternal genome during oogenesis. During early development this basic plan is elaborated on by the zygotic genome. This elaboration can be envisioned to occur as two genetically controlled, integrated series of events. The embryo is progressively divided into a series of developmental fields that correspond to specific subregions of the embryo. At some time, the fields correspond to regions the width of two adjacent metameres. These fields define the domains of activation of various homoeotic genes which specify segment identity. The identity of a particular segment and its derivatives is dependent on the expression of batteries of genetic information. These batteries are activated or repressed by the products of the homoeotic loci and represent the specific repertoire of active “structural” genes in each segment. The homoeotic and segment patterning loci can be viewed as a set of switches which are necessary for the proper reading and interpretation of positional information in the early embryo. This interpretive function is in turn necessary for the proper patterned response of cells during the ontogenic process.
The Mu2e Solenoid Cold Mass Position Monitor System

The Mu2e experiment at Fermilab is designed to search for charged-lepton flavor violation by looking for muon to electron conversions in the field of the nucleus. The concept of the experiment is to generate a low momentum muon beam, stopping the muons in a target and measuring the momentum of the outgoing electrons. The implementation of this approach utilizes a complex magnetic field composed of graded solenoidal and toroidal fields. Monitoring coil movements of the solenoids during cool down and magnet excitation and cool down is needed. A novel design of a Cold Mass Position Monitor System (CMPS) that will be implemented for the Mu2e experiment has been developed and a prototype CMPS has been built and tested. This paper describes the Mu2e Solenoid System CMPS including the description of the calibration, mounting effort and the CMPS DAQ.
Soundness of removing cancellation identities in protocol analysis under Exclusive-OR

In [Mil03,LM05], Millen-Lynch-Meadows proved that, under some restrictions on messages, including identities for canceling an encryption and a decryption within the same term during analysis will be redundant. i.e., they will not lead to any new attacks that were not found without them. In this paper, we prove that slightly modified restrictions are sufficient to safely remove those identities, even when protocols contain operators such as the notorious Exclusive-OR operator that break the free algebra assumption with their own identities, in addition to the identities considered by Millen-Lynch-Meadows.
Provenance-enabled automatic data publishing

Scientists are increasingly being called upon to publish their data as well as their conclusions. Yet computational science often necessarily occurs in exploratory, unstructured environments. Scientists are as likely to use one-off scripts, legacy programs, and volatile collections of data and parametric assumptions as they are to frame their investigations using easily reproducible workflows. The ES3 system can capture the provenance of such unstructured computations and make it available so that the results of such computations can be evaluated in the overall context of their inputs, implementation, and assumptions. Additionally, we find that such provenance can serve as an automatic "checklist" whereby the suitability of data (or other computational artifacts) for publication can be evaluated. We describe a system that, given the request to publish a particular computational artifact, traverses that artifact's provenance and applies rule-based tests to each of the artifact's computational antecedents to determine whether the artifact's provenance is robust enough to justify its publication. Generically, such tests check for proper curation of the artifacts, which specifically can mean such things as: source code checked into a source control system; data accessible from a well-known repository; etc. Minimally, publish requests yield a report on an object's fitness for publication, although such reports can easily drive an automated cleanup process that remedies many of the identified shortcomings.
The basis for prescribed ability group run speeds and distances in U.S. Army basic combat training.

ABSTRACT During the first few days of Army Basic Combat Training (BCT), recruits take a running test and after completing this test they are ranked from fast to slow. Four roughly equal-sized “ability groups” are established from these rankings and recruits run together in these groups for their physical training during BCT. In the past, there has been no formal guidance regarding how fast or how far these ability groups should run. To fill this void, this study provides guidance for running speeds and distances during BCT. The major considerations included are: (1) minimizing injuries, (2) the initial aerobic fitness level of recruits, (3) historical improvements in run times during BCT, (4) historical running speeds of the slower individuals in each ability group, (5) running speeds that must be achieved to “pass” the 2-mile run in BCT, (6) the gender composition of the ability groups, and (7) recommendations from the trainers and field testing. Three databases were analyzed that contained a total of 16...
Residency Ultrasound Education

Ultrasound in residency education differs by specialty. Emergency medicine has developed one of the most comprehensive curriculum recommendations based on ACEP guidance and ACGME requirements. This chapter discusses the four required assets of successful deployment which includes curriculum, faculty, equipment, and competency assessment. There is also a meaningful comparison to other specialties regarding progress of residency training recommendations.
Student Engagement in Direct Instruction, Undergraduate Microbiology Laboratories

Introductory laboratory courses are a standard component of undergraduate science programmes and historically taught using direct instruction/confirmatory lab models. Previous studies have shown th...
PL Continuation Methods

In previous chapters we assumed that the map H : RN+1 → R N was smooth, that zero was a regular value, and that H−1 (0) was a collection of disjoint smooth curves which could be numerically traced using PC-methods. Now we will discuss piecewise linear (PL) methods which can again be viewed as curve tracing methods, but the map H can now be arbitrary. The map H is approximated by a piecewise linear map H T which affinely interpolates H at the nodes of a triangulation T of RN+1. The PL methods trace the piecewise linear 1-manifold H T −1 (0). A connected component of the piecewise linear 1-manifold consists of a polygonal path which is obtained by successively stepping through certain “transverse” (N + 1)-dimensional simplices of the triangulation. Although the PL method works for arbitrary maps, only under some smoothness assumptions on H can one obtain truncation error estimates in terms of the meshsize of the underlying triangulation. In order to be able to discuss these methods it is necessary to introduce a few combinatorial ideas. The first notions we need are those of a simplex and a triangulation.
GLYPHOSATE AND RELATED CHEMISTRY

Abstract Roundup® herbicide has unique broad spectrum postemergent activity. It is readily translocated in plants, is rapidly inactivated by most soils and is essentially non-toxic to mammals, insects and bacteria.
Biomechanics of the ankle: a kinematic study.

Summary Twenty-six normal ankles were examined by x-ray to determine the tibiotalar range of motion during dorsiflexion and plantar flexion during weight bearing and nonweight bearing. The range of motion was then compared to 14 ankles with some abnormality. The range of motion was found to decrease; the significance of this is discussed. Instant centers of the ankle were examined during normal weight and nonweight bearing motion and their locations discussed. These differed considerably from previous studies of ankle axes. Surface velocities at the points of tibiotalar contact were investigated during weight bearing and nonweight bearing and were found to have a definite pattern. The distribution of instant centers was noted to change in abnormal ankles when compared with normal. Surface velocities in abnormal ankles varied from the normal pattern also. Two normal and two abnormal ankles were examined using cine-roentgenography. The normal study showed instant centers and surface velocities similar to those of the other normal x-ray studies. Weight bearing was shown to stabilize abnormal ankle motion. The etiology of anterior tibiotalar facets is discussed.
Laboratory determination of oil draining CO2 hysteresis effects during multiple floods of a conventional clastic oil reservoir

Abstract Determination of hysteresis in relative permeability data is useful in obtaining more reliable predictions of water alternating gas (WAG) enhanced oil recovery performance and accompanying associated storage of CO2. A laboratory-based evaluation of CO2 draining oil has been conducted on reservoir rocks from a conventional clastic oil reservoir undergoing tertiary CO2 enhanced recovery. Experimentation was conducted at reservoir conditions of 16 MPa (2300 psi) and 43 °C (110 °F). Through this study, a better understanding of the oil production and associated storage of CO2 in a conventional clastic oil reservoir has been obtained. Data generated provide an example of a site-specific field project that is currently undergoing a tertiary CO2-based EOR project demonstrating that associated CO2 storage will occur. Through multiple cycles of CO2 injection, this study has shown the effectiveness of first contact CO2 as it relates to the mobilization of oil from injector to producer. Additionally, in this conventional clastic reservoir, CO2 trapping appears to have taken place during the initial imbibition cycle, as oil production and differential pressures remain consistent during subsequent tests.
The Critical Portions of Carpal Tunnel Release, Ulnar Nerve Transposition, and Open Reduction and Internal Fixation of the Distal Part of the Radius.

Background Overlapping surgery is attracting increased scrutiny. The American College of Surgeons states that the attending surgeon must be present for all critical portions of a surgical procedure; however, critical portions of surgical procedures are not defined. We hypothesized that a Delphi panel process would measure consensus on critical portions of 3 common hand surgical procedures. Methods We used a Delphi process to achieve consensus on the critical portions of carpal tunnel release, ulnar nerve transposition, and open reduction and internal fixation of the distal part of the radius. The panelists were 10 hand surgeons (7 fellowship-trained surgeons and 3 fellows). Following an in-person discussion to finalize steps for each procedure, 2 online rounds were completed to rate steps from 1 (not critical) to 9 (extremely critical). We operationalized consensus as ≥80% of ratings within the same range: 1 to 3 (not critical), 4 to 6 (somewhat critical), and 7 to 9 (critical). Because of a lack of consensus on some steps after round 2, another in-person discussion and a third online round were conducted to rate only steps involving disagreement or somewhat critical ratings using a dichotomous scale (critical or not critical). Results Following the first 2 rounds, there was consensus on 19 of 24 steps (including 3 steps being somewhat critical) and no consensus on 5 of 24 steps. At the end of round 3, there was consensus on all but 2 steps (identification of the medial antebrachial cutaneous nerve in ulnar nerve transposition and clinical assessment of joint stability in open reduction and internal fixation of the distal part of the radius), with moderate disagreement (3 compared with 7) for both. Conclusions The panel reached consensus on the designation of critical or noncritical for all steps of a carpal tunnel release, all but 1 step of an ulnar nerve transposition, and all but 1 step of open reduction and internal fixation of the distal part of the radius. The lack of consensus on whether 2 of the steps are critical leaves this determination at the discretion of the attending surgeon. The findings of our Delphi panel provide guidance to our division on which portions of the surgical procedure are critical and thus require the attending surgeon's presence.
Context-Specific Separable Gesture Selection For Control of a Robotic Manufacturing Assistant

Abstract This work aims to facilitate robotic-assisted limited-access manufacturing, where a mechanic manually performs work in an enclosed space while a robot guides a camera to allow the mechanic to observe visually-occluded operations. Gesture control allows the mechanic to adjust their camera view without requiring contact-based interaction through button presses or manual positioning of the robot, which would require setting down tools or exiting the enclosed space. Because the only input to the robotic platform’s gesture recognition system is a continuously tracked hand, there is potential for confusion between the motions of work and motions intended to communicate control. The main contribution of this article is to develop a separability metric Ψ for systematically selecting a set of control gestures that can be easily distinguished from a given set of work gestures. The context-specific control gesture selection process is implemented on a benchmark dataset to validate the method. The process is then implemented on a hand-following robot, and experimental results show that the proposed metric-based selection of the control gesture set results in the improvement of online gesture recognition across eight subjects even in the presence of application-specific distortions in the gestures.
Toric and mulitifocal lens utilization independent of patient cost and physician remuneration at a single institution

Abstract Purpose To determine if the rates of toric and multifocal intraocular lenses (IOLs) are affected by patient cost or physician reimbursement. Methods At Naval Medical Center San Diego (NMCSD) there is no increased patient cost or physician reimbursement for toric or multifocal IOLs. The medical records of all patients who underwent cataract surgery with IOL implantation at NMCSD between 2013 and September 2016 were reviewed. The type of IOL implanted was identified. The rates of toric and multifocal IOL usage were compared to the rates reported in the 2016 American Society of Cataract and Refractive Surgery (ASCRS) Clinical Survey. Results The inclusion criterion was met for 2585 cataract surgeries. The percentage of toric IOLs at NMCSD in 2016 was 10%. If the patients that received 3 piece or anterior chamber IOLs were excluded, the percentage of single piece IOLs that were toric was 12%. The percentage of multifocal IOLs at NMCSD ranged from 0.8% in 2013 to 0.3% in 2016. The rates of toric and multifocal IOLs reported in the ASCRS clinical survey were 10% and 9%, respectively. Conclusions and Importance: The rate of toric IOLs usage was not significantly affected by patient cost or physician reimbursement. The rate of multifocal IOLs usage was significantly lower at NMCSD.
Investigation of Air Permeability of Handwoven Fabrics

Handwoven fabrics, which made with cotton and silk, have unique characteristics and feel and are being produced in many parts of Thailand for making handicrafts such as pieces of clothing, embellishments, and home furnishings. It should be one of the largest income sources for many Thailand people, especially in rural areas (Fujioka,2002). In general, handwoven fabrics are not woven as tightly and strongly as machine-produced woven fabrics, resulting in fraying and shifting fabric shape easily during the construction process. To solve this weakness, fusible polyester interfacing liner tends to be ironed onto the back of handwoven cotton and silk before cutting and sewing since it makes the handwoven fabric stiffer and keeps its shape. It results producers can cut handwoven cotton and silk easily and sew them with fabricless-distorted. However, it also affects the thickening of the fabric,resulting negatively to breathability and ability to transfer heat and humid between wearer body and an inner layer of clothing. Thailand locates in the tropics, which is hot and humid across the nation. This research began with the question if adding layers, like fusible interfacing liner, is appropriate in a hot and humid climate and why this technique has used for a while in Thailand.Limited studies have examined the thermal comfort of multi-layer fabrics,especially with fusible interfacing liner (Shabaridharan, 2012). Therefore, the purpose of this study to investigate if the use of fusible interfacing liner is appropriate and how it affects the thermal comfort of the wearer by measuring air permeability in handwoven cotton and silk.
CD8+ T Cells Require ITK-Mediated TCR Signaling for Migration to the Intestine

The Tec kinase IL-2-inducible T cell kinase (ITK) regulates the expression of TCR-induced genes. Itk-/- T cell responses are impaired but not absent. ITK inhibition prevented colitis disease progression and impaired T cell migration to the colon in mice. To examine the function of ITK in T cell migration to the intestine, we examined the number of gut T cells in Itk-/- mice and then evaluated their expression of gut-homing receptors. Combined with in vitro murine T cell stimulation and in vivo migration assay using congenic B6 mice, we demonstrated an essential role for ITK in T cell migration to the intestine in mice. Reconstitution of Itk-/- mouse CD8+ T cells with IFN regulatory factor 4 restored gut-homing properties, providing mechanistic insight into the function of ITK-mediated signaling in CD8+ T cell migration to the intestinal mucosa in mice.
Intramolecularly Cross-Linked Polymers: From Structure to Function with Applications as Artificial Antibodies and Artificial Enzymes.

ConspectusCross-linking of polymers significantly alters their physical properties, greatly expanding their everyday utility. Indeed, the polymeric networks resulting from linkages between polymer ...
Trade‐off between fecundity and survival generates stabilizing selection on gall size

Complex interactions within multitrophic communities are fundamental to the evolution of individual species that reside within them. One common outcome of species interactions are fitness trade-offs, where traits adaptive in some circumstances are maladaptive in others. Here, we identify a fitness trade-off between fecundity and survival in the cynipid wasp Callirhytis quercusbatatoides that induces multichambered galls on the stem of its host plant Quercus virginiana. We first quantified this trade-off in natural populations by documenting two relationships: a positive association between the trait gall size and fecundity, as larger galls contain more offspring, and a negative association between gall size and survival, as larger galls are attacked by birds at a higher rate. Next, we performed a field-based experimental evolution study where birds were excluded from the entire canopy of 11 large host trees for five years. As a result of the five-year release from avian predators, we observed a significant shift to larger galls per tree. Overall, our study demonstrates how two opposing forces of selection can generate stabilizing selection on a critical phenotypic trait in wild populations, and how traits can evolve rapidly in the predicted direction when conditions change.
Time-resolved compound repositioning predictions on a text-mined knowledge network

Abstract Background Computational compound repositioning has the potential for identifying new uses for existing drugs, and new algorithms and data source aggregation strategies provide ever-improving results via in silico metrics. However, even with these advances, the number of compounds successfully repositioned via computational screening remains low. New strategies for algorithm evaluation that more accurately reflect the repositioning potential of a compound could provide a better target for future optimizations. Results Using a text-mined database, we applied a previously described network-based computational repositioning algorithm, yielding strong results via cross-validation, averaging 0.95 AUROC on test-set indications. The text-mined data was then used to build networks corresponding to different time-points in biomedical knowledge. Training the algorithm on contemporary indications and testing on future showed a marked reduction in performance, peaking in performance metrics with the 1985 network at an AUROC of .797. Examining performance reductions due to removal of specific types of relationships highlighted the importance of drug-drug and disease-disease similarity metrics. Using data from future timepoints, we demonstrate that further acquisition of these kinds of data may help improve computational results. Conclusions Evaluating a repositioning algorithm using indications unknown to input network better tunes its ability to find emerging drug indications, rather than finding those which have been withheld. Focusing efforts on improving algorithmic performance in a time-resolved paradigm may further improve computational repositioning predictions.
The Microwave Absorption Spectum of ( O 16 ) 2 and O 16 O 17

The theory of the fine structure of ${\mathrm{O}}_{2}$ is made somewhat more complete and fitted to the observed microwave spectrum. This gives ${B}_{0}=43102\ifmmode\pm\else\textpm\fi{}5$ Mc/sec for ${\mathrm{O}}^{16}$${\mathrm{O}}^{16}$. In addition there is evidence for the effect of higher order terms such as centrifugal distortion on the magnetic interaction constants. Magnetic hyperfine structure has been observed in the spectrum of ${\mathrm{O}}^{16}$${\mathrm{O}}^{17}$. The spectrum agrees with that predicted on the basis of a perturbation Hamiltonian $b\mathrm{I}\ifmmode\cdot\else\textperiodcentered\fi{}\mathrm{S}+c{I}_{z}{S}_{z}$, where $b=\ensuremath{-}102$ Mc/sec and $c=140$ Mc/sec. The value of 5/2 for the spin of ${\mathrm{O}}^{17}$ is confirmed.
Validation and demonstration of a new comprehensive model of Alzheimer's disease progression

Introduction Identifying the course of Alzheimer's disease (AD) for individual patients is important for numerous clinical applications. Ideally, prognostic models should provide information about a range of clinical features across the entire disease process. Previously, we published a new comprehensive longitudinal model of AD progression with inputs/outputs covering 11 interconnected clinical measurement domains. Methods Here, we (1) validate the model on an independent cohort; and (2) demonstrate the model's utility in clinical applications by projecting changes in 6 of the 11 domains. Results Survival and prevalence curves for two representative outcomes-mortality and dependency-generated by the model accurately reproduced the observed curves both overall and for patients subdivided according to risk levels using an independent Cox model. Discussion The new model, validated here, effectively reproduces the observed course of AD from an initial visit assessment, allowing users to project coordinated developments for individual patients of multiple disease features.
High-harmonic diffractive lens color compensation.

Large diameter, high-harmonic diffractive lenses could find applications in future space telescopes. Residual chromatic aberrations from these lenses can cause significant blurring. Solutions to reduce chromatic dispersion and other aberrations to diffraction-limited performance are discussed. A design example based on a 240-mm-diameter, 1-m focal length multi-order diffractive engineered lens operating over the astronomical R-Band (589–727 nm) is presented. The design example uses a relay subsystem with four times smaller diameter than the primary. This color corrector includes both refractive and diffractive optical elements and reduces the longitudinal chromatic aberrations by more than a factor of 30 compared to the primary lens alone, while maintaining the effective focal length and numerical aperture of the system.
Cryoablation versus antiarrhythmic therapy for initial treatment of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND Atrial fibrillation is a common cardiac arrhythmia that affects approximately 2% of the overall population. Current guidelines suggest the use of antiarrhythmic agents as initial therapy in patients with symptomatic atrial fibrillation; however, using cryoablation as a first-line therapy might provide increased efficacy. METHODS We conducted a systematic review from inception to March 2021 to find randomized controlled trials (RCT) that directly compared cryoablation therapy versus antiarrhythmic therapy as initial treatment for atrial fibrillation. RESULTS The primary outcome of our meta-analysis was recurrence of atrial arrhythmias. The secondary outcome evaluated serious adverse events of each therapy. Three RCTs involving 724 patients were included in the meta-analysis. The results showed a statistically significant reduction in recurrence of atrial arrhythmias in patients receiving cryoablation compared to antiarrhythmic therapy [RR 0.60, 95% CI (0.50, 0.72), P < 0.00001, I2 = 0%]. There was no significant difference in serious adverse events between patients receiving cryoablation compared to patients receiving antiarrhythmic therapy [RR 0.80, 95% CI (0.57, 1.13), P = 0.21, I2 = 0%]. CONCLUSION Our meta-analysis showed that cryoablation therapy as initial therapy is more efficacious than antiarrhythmic therapy in patients with atrial fibrillation without an increased risk of serious adverse events.
Abstract P112: Decreased α-Myosin Expression is Associated with Left Ventricular Hypertrophy in Hypertensive Caribbean Vervets

Caribbean vervets (Chlorocebus aethiops sabeus) develop hypertension (HT; Systolic Blood Pressure ≥ 140 mmHg) in over 30% (125/345) of the outbred population. Elevated total peripheral resistance i...
Leaves of the Same Tree: Trade and Ethnicity in the Straits of Melaka – By Leonard Y. Andaya

This study examines an unusual aspect of Southeast Asian history—the “role of trade in the process of ethnic formation” along the Straits of Melaka, a vital waterway straddling parts of Malaysia an...
CHAPTER 20 – Gene Therapy for Chronic Myelogenous Leukemia

This chapter discusses the gene therapy for chronic myelogenous leukemia (CML). CML is a malignancy of the hematopoietic stem cell, characterized by a reciprocal translocation between chromosomes 9 and 22 (Philadelphia chromosome [Ph]) resulting in the formation of a hybrid bcr-abl gene on chromosome 22. As CML is caused by p210 bcr-abl , suppression of the expression of p210 bcr-abl or proteins downstream in the bcr-abl signal pathway which are specifically activated by p210 bcr-abl may restore normal, nonleukemic growth of bcr-abl + cells. A large body of work has focused on targeting mRNA to eliminate target gene products. Because p210 bcr-abl is tumor specific and responsible for the development of leukemia, it is an obvious target to treat CML. Anti- bcr-abl therapy is therefore ideally targeted at the bcr-abl breakpoint and not the bcr or abl portions of the oncogene. Alternatively, therapies could be directed at molecules downstream from bcr-abl that are involved in the transformation of hematopoietic cells. This requires that activation of the downstream molecules is bcr-abl specific and is not by processes that govern normal progenitor proliferation and differentiation.
Evaluation of the Hill-Siscoe transpolar potential saturation model during a solar wind dynamic pressure pulse

[1] Theory, observations, and simulations have shown that saturation of the cross-polar-cap potential occurs for high solar wind electric field. One of the parameters that affect the saturation process is the solar wind dynamic pressure. Theoretical arguments predict that higher pressure levels lead to higher transpolar potentials and a slower saturation process. The question arises of how the transpolar potential will respond to sudden enhancements of solar wind pressure in the saturation regime, and if the theoretical model predictions can replicate the observations. We use ionospheric flow data from Defense Meteorological Satellite Program (DMSP) spacecraft to calculate the transpolar potential and compare it with theory before and after a sudden increase in solar wind pressure. We find that the model predictions fall below the observed values for both pressure levels but are particularly lower after the dynamic pressure enhancement. The inclusion of a “viscous” potential, or the introduction of variable ionospheric conductivity, cannot remedy the discrepancy. We suggest that modification of the existing models to include magnetotail processes might be needed to bridge the gap between theory and observations.