cssi/SciSciGPT-SciSciNet huggingface dataset:
Selective ability of S-phase cell extracts to dephosphorylate SV40 large T antigen in vitro.

Simian virus 40 (SV40) large tumor antigen (T) is an oncoprotein whose biological and biochemical functions appear to be modulated by phosphorylation. Recently, SV40 DNA replication in vitro has been shown to be activated by dephosphorylation involving the activity of a serine/threonine phosphoprotein phosphatase belonging to the type 2A class (PP2A) [Virshup, D.M., Kauffman, M.G. & Kelly, T.J. (1989) EMBO J., 8, 3891-3898]. To address the question of how specificity of PP2A activity towards T is regulated, an in vitro assay to study the process of T dephosphorylation was developed. Unlabeled extracts from cells enriched for various stages of the cell cycle were incubated with 32P-labeled, immunocomplexed T. Extracts from a population of cells enriched for S phase demonstrated a selective ability to dephosphorylate this labeled protein when compared with extracts prepared from G1- and M-phase cells. The time course of release from growth arrest demonstrated that this T-specific phosphatase activity occurred at the onset of host-cell DNA synthesis. In contrast, when using 32P-labeled phosphorylase a as the substrate, phosphatase activity appeared to be present throughout the cell cycle. The data presented here are consistent with the notion that PP2A activity towards T is regulated in a cell cycle-dependent manner.
Laser-Controlled Unimolecular and Bimolecular Processes: Field-Dependent Rate “Constants”

The radiation field of a laser has four well-defined parameters: intensity, frequency, polarization and propagation vector. Some of these parameters are continuously tunable. Molecular rate processes induced by the laser field can therefore be controlled directly by varying the field parameters. It is expected that the rate (per molecule per second) y of laser-induced unimolecular process is directly dependent on these field parameters. However most laser-induced bimolecular processes (or commonly called laser- induced chemistry) utilize the laser photons for preparing molecular population in the excited states which then react with their collisfon partners unperturbed by the laser field, presumably due to the relatively weak laser intensity. The new rate constant k for such process is not a function of the laser field parameters. The kind of laser-induced bimolecular processes we consider h9ere have their rate “constants” [or cross sections) directly dependent on the laser intensity I, frequency ω, polarization E and the energy differences Δ and some transition moment(s) μ characteristic of the colliding complex (the quasimolecule), i.e. k(I, ω, e, Δ, μ). The reason for this is that the radiative effects we consider here occur during the collision. To underscore this distinction with the more familiar laser- induced chemistry, we call this kind of process laser-controlled since the rate constants (or cross sections) can be externally varied by changing the laser field parameters.
A Summary of the Theory and Application of the Conics Method in Robot Kinematics

A summary of the conics method is presented. This method provides a new way to analyze the kinematic geometry of fourth order manipulators. A condition is developed that is sufficient for a fourth order solution to reduce to a quadratic. Applying this condition to a 3R regional manipulator yields seven quadratic robot designs. Several of the derived geometries are sufficiently obscure that their discovery is unlikely without such a systematic approach.
Ecoevolutionary Processes Regulating Microbiome Community Assembly in a Changing Global Ecosystem

Owing to tremendous complexity and diversity of microbiome communities, it has been challenging to comprehend and perceive the ecological processes regulating the microbiome community assembly from micro to macro scales. In macroecology, Vellend proposed that the four ecological processes such as selection, drift, dispersal, and mutation/speciation determine the patterns of ecological communities. Recently, there emerged a great interest in understanding the role of these processes in microbiome community ecology. A few studies have suggested that these processes interactively determine the patterns of microbiome diversity across environmental and biogeographic gradients. However, it largely remains untested to partition the relative effect size of these processes on microbiome diversity and functioning from micro- to macro-scales. Meanwhile, a very little know-how about the multifaceted impacts of global land use and climate changes on these processes makes it difficult to perceive their role in the generation and maintenance of microbiome ecological diversity and functioning. There is a pressing demand to develop, test, build, and apply new ecological hypotheses and theories with the help of ecostatistical and robust genomic techniques to understand the relative significance of different ecoevolutionary processes in microbiome functional community ecology in the time of global climate change and microbial diversity loss.
Employing Overlayers To Improve the Performance of Cu2BaSnS4 Thin Film based Photoelectrochemical Water Reduction Devices

Earth−abundant Copper-Barium-Thiostannate Cu2BaSnS4 (CBTS)-based thin films have recently been reported to exhibit the optoelectronic and defect properties suitable as absorbers for photoelectrochemical (PEC) water splitting and the top cell of tandem photovoltaic solar cells. However, the photocurrents of CBTS-based PEC devices are still much lower than the theoretical value, partially due to ineffective charge collection at CBTS/water interface and instability of CBTS in electrolytes. Here, we report on overcoming these issues by employing overlayer engineering. We find that CdS/ZnO/TiO2 overlayers can significant-ly improve the PEC performance, achieving saturated cathodic photocurrents up to 7.8 mA cm−2 at the potential of -0.10 V versus reversible hydrogen electrode (RHE) in a neutral electrolyte solution, which is much higher than the best bare CBTS film attaining a photocurrent of 4.8 mA cm−2 at the potential of -0.2 V versus RHE. Our results suggest a viable approach for improving the performance ...
The principles and practice of human evolution research: Are we asking questions that can be answered?

Abstract The research agenda of paleoanthropology involves many topics and methodologies. Fossil specimens are allocated to species, and those species are assigned to the hominin clade. After that we want to know how they are related to each other, what they ate, how much they weighed, how smart they were, etc. We also want to know about the origin of particular attributes of hominins, such as our delayed growth and development, bipedalism, and language. The data available to answer these complex questions are confounded by fragmentary fossil specimens, small sample sizes, limited opportunities for controlled experimentation, and the inherent limitations of historical data. Also, because many traits are effectively unique to hominins, even observational comparative studies are inevitably limited in what they can tell us, if not impossible to conduct. We explore how these limitations should, but often do not, constrain the questions that paleoanthropologists should attempt to answer.
Near‐Infrared‐Absorbing Metal‐Free Organic, Porphyrin, and Phthalocyanine Sensitizers for Panchromatic Dye‐Sensitized Solar Cells

Dye-sensitized solar cells (DSCs) are a promising source of renewable energy. However, power conversion efficiency (PCE) of devices has been limited largely by the difficulty of producing electricity using photons from the near-infrared (NIR) spectral region. Metal-free organic sensitizers frequently employ strong electron donating or withdrawing moieties to tune the optical band gap to allow the absorption of lower energy wavelengths in charge transfer systems while porphyrins and phthalocyanines use substituents to shift the Soret and Q bands toward lower energy absorption. Very few devices employing precious metal free dyes have been able to achieve panchromatic, NIR photon conversion for electricity generation at wavelengths >750 nm despite a tremendous number of sensitizers published over last 25 years. This minireview seeks to compile a summary of these sensitizers to encourage assimilation, analysis and development of efficient future NIR sensitizers. Herein, we discuss common synthetic strategies, optical properties and electronic properties of the most successful panchromatic organic sensitizers in this regard.
Investigating the candidacy of a capsular polysaccharide-based glycoconjugate as a vaccine to combat Haemophilus influenzae type a disease: A solution for an unmet public health need

After the introduction of the glycoconjugate vaccine based upon the capsular polysaccharide ofHaemophilus influenzaetype b in the mid 1980s there was a remarkable decrease in the number of invasive cases reported for this organism. Since the 1990s several groups have observed the emergence ofHaemophilus influenzaetype a (Hia), especially in indigenous communities in the northern regions of Canada and Alaska, to a stage where a solution is warranted to prevent further unnecessary deaths due to this pathogen. A glycoconjugate vaccine solution based upon the type a capsular polysaccharide (CPS) was investigated pre-clinically in an effort to illustrate the proof of concept for this approach. In this study we describe the growth of Hia and the isolation, purification and conjugation of the CPS to several carrier proteins. The resulting glycoconjugates were immunised in mice and rabbits provoking sera that facilitated bactericidal killing against all type a strains that we tested. This study has illustrated the pre-clinical proof of concept of a glycoconjugate vaccine based on the CPS of Hia asa solution to this emerging disease.
Finite and infinite lossy conductors over a lossy ground plane excited by an electromagnetic pulse

We report a frequency-domain method based on transmission line theory that we name ATLOG — Analytic Transmission Line Over Ground — to model finite or infinite wires interacting with a conducting ground excited by an electromagnetic pulse. This method allows for the treatment of finite or infinite lossy, coated wires above a lossy ground, as well as resting on or buried beneath the ground. Comparisons with full-wave simulations strengthen the validity of the proposed method.
Leadership Roles and Activities Among Alumni Receiving Postdoctoral Fellowship Training in Cancer Prevention.

This study was conducted in 2016–2017 to better understand formal and informal leadership roles and activities of alumni from postdoctoral research training programs in cancer prevention. Data were obtained from surveys of 254 employed scientists who completed cancer prevention postdoctoral training within the National Cancer Institute (NCI) Cancer Prevention Fellowship Program, or at US research institutions through NCI-sponsored National Research Service Award (NRSA) individual postdoctoral fellowship (F32) grants, from 1987 to 2011. Fifteen questions categorized under Organizational Leadership, Research Leadership, Professional Society/Conference Leadership, and Broader Scientific/Health Community Leadership domains were analyzed. About 75% of respondents had at least one organizational leadership role or activity during their careers, and 13–34% reported some type of research, professional society/conference, or broader scientific/health community leadership within the past 5 years. Characteristics independently associated with leadership from regression models were being in earlier postdoctoral cohorts (8 items, range for statistically significant ORs = 2.8 to 10.8) and employment sector (8 items, range for statistically significant ORs = 0.4 to 11.7). Scientists whose race/ethnicity was other than white were less likely to report organizational leadership or management responsibilities (OR = 0.4, 95% CI 0.2–0.9). Here, many alumni from NCI-supported cancer prevention postdoctoral programs were involved in leadership, with postdoctoral cohort and employment sector being the factors most often associated with leadership roles and activities. Currently, there is relatively little research on leadership roles of biomedical scientists in general, or in cancer prevention specifically. This study begins to address this gap and provide a basis for more extensive studies of leadership roles and training of scientists.
Altered ultradian cortisol rhythmicity as a potential neurobiologic substrate for chronic insomnia.

Summary Chronic insomnia is highly prevalent and associated with significant morbidity (i.e., confers risk for multiple psychiatric and medical disorders, such as depression and hypertension). Therefore, it is essential to identify factors that perpetuate this disorder. One candidate factor in the neurobiology of chronic insomnia is hypothalamic-pituitary-adrenal-axis dysregulation, and in particular, alterations in circadian cortisol rhythmicity. Cortisol secretory patterns, however, fluctuate with both a circadian and an ultradian rhythm (i.e., pulses every 60–120 min). Ultradian cortisol pulses are thought to be involved in the maintenance of wakefulness during the day and their relative absence at night may allow for the consolidation of sleep and/or shorter nocturnal awakenings. It is possible that the wakefulness that occurs in chronic insomnia may be associated with the aberrant occurrence of cortisol pulses at night. While cortisol pulses naturally occur with transient awakenings, it may also be the case that cortisol pulsatility becomes a conditioned phenomenon that predisposes one to awaken and/or experience prolonged nocturnal awakenings. The current review summarizes the literature on cortisol rhythmicity in subjects with chronic insomnia, and proffers the suggestion that it may be abnormalities in the ultradian rather than circadian cortisol that is associated with the pathophysiology of insomnia.
Global Consumer Culture and Advertising Research

In the two and a half decades since I officially entered academia, a great deal has changed in terms of internationalization of the advertising field. While studying as a Ph.D. student at Michigan ...
Transmitral Septal Myectomy

In patients undergoing operative intervention for hypertrophic cardiomyopathy (HCM), intrinsic abnormalities of the mitral valve may need to be addressed at the time of septal myectomy. Advantages of a transmitral approach to septal myectomy include a panoramic view of the septum and the exposure necessary to address concomitant mitral valve pathology. Herein, we describe our technique for transmitral septal myectomy in symptomatic patients with HCM. The transmitral approach to septal myectomy should be given consideration as the preferred approach for the surgical treatment of HCM.
Supramolecular Membrane Structure

To this point we have been concerned with the molecular and macromolecular building blocks of membranes. This chapter will focus on how these building blocks are assembled to become functional membranes.
The Culture, Characterization and Triggering of B-Lymphocytes

Normal B-lymphocytes depend greatly on contact with other cells such as T-cells or BM stromal cells, as well as growth factors such as IL-4 and IL-6, for their growth, differentiation, and survival. Although short-term culture of B-lymphocytes is possible using T-cell co-cultures and/or mitogens, long-term culture requires the establishment of an adherent layer of feeder BM stromal cells, use of combinations of growth factors (i.e. CD40L + IL-4), or immortalization (i.e. EBV transformation). Currently, the efficiency of cloning stably transfected normal B-lymphocytes is optimally achieved by using feeder cell layers.
BISCUIT: Building Intelligent System Customer Investment Tools

Abstract Smart buildings as human-cyber-physical systems (h-CPSs) are capable of providing intelligent services, such as indoor positioning, personalized lighting, demand-based heating ventilation and air-conditioning, and automatic fault detection and recovery, just to name a few. However, most buildings nowadays lack the basic components and infrastructure to support such services. The investment decision of intelligent system design and retrofit can be a daunting task, because it involves both hardware (sensors, actuators, servers) and software (operating systems, service algorithms), which have issues of compatibility, functionality constraints, and opportunities of co-design of synergy. This work proposes a user-oriented investment decision toolset aimed at handling the complexity of exploration in the large design space and to enhance cost-effectiveness, energy efficiency, and human-centric values. The toolset is demonstrated in a case study to retrofit a medium-sized building, where it is shown to propose a design that significantly lowers the overall investment cost while achieving user specifications.
High Technology Mass Media as Strengthening Democracy: Immediacy and Community in the Blogosphere – Extremism Plus Increased Citizens’ Involvement

Along with the extremism which the blogs have generated, there is also a heightened political involvement. Young people especially have connected with each other through the blogosphere. This is both dangerous for democracy, and yet exciting too. For, something like the “face-to-face” democracy of the ancient Greek world is recreated in the blogs, such that huge demonstrations and voter turnout can be generated through internet political blog activity.
A Factor Analysis and Test of Longitudinal Measurement Invariance of the Children’s Depression Inventory (CDI) Across Adolescence

Depression increases dramatically during adolescence. This finding has been demonstrated using multiple measures, including the Children's Depression Inventory (CDI). The CDI is one of the most commonly used measures to assess depression in youth. However, there is little agreement on its factor structure, and it is possible that its factor structure changes over time. Yet, no study to date has investigated whether this structure is longitudinally invariant from early- to mid-adolescence. The present study examined the factor structure of the CDI in a sample of 227 adolescents aged approximately 13 at baseline and 16 at follow-up. The analyses revealed that a one-factor structure was a good fit to the data at each assessment. Moreover, tests of measurement invariance supported configural, metric, and scalar invariance across time. These findings suggest that changes in depressive symptoms during adolescence are due to true developmental changes, rather than changes in measurement properties.
Recognized ASCA Model Program (RAMP) and Student Outcomes in Elementary and Middle Schools

This study evaluates the relationship between the Recognized American School Counselor Association Model Program (RAMP) designation and students’ achievement and attendance outcomes in elementary a...
Evaluation of the agreement between a point-of-care lactate meter and a handheld laboratory analyzer in cats treated in emergency practice.

OBJECTIVE: The purpose of this study was to determine if there was agreement between a new point‐of‐care (POC) lactate analyzer and a handheld laboratory analyzer when measuring blood lactate concentration in cats. DESIGN: Prospective observational study. SETTING: University veterinary teaching hospital. ANIMALS: Fifty‐four cats that presented to an emergency service. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Lactate concentrations as measured by the handheld laboratory analyzer ranged from 0.3 to 15.4 mmol/L. Agreement analysis of the handheld laboratory analyzer and the POC lactate meter demonstrated a bias, −0.06 and limits of agreement ranging from −0.87 to 0.99 mmol/L. Regression analysis demonstrated a coefficient of determination (R²) of 0.98. CONCLUSION: Results of the present study indicate that the POC lactate meter provided results that are in agreement with a handheld laboratory analyzer when measuring lactate in clinically ill patients.
Dynamic Analysis of Overflow Decompression Drilling Circuit of Coalbed Methane Drilling Rig

The pressure-relief drilling circuit of CBM drilling rig is studied, and the pressure-flow characteristics of relief valve during the process of relief drilling are analyzed. Combining with the load characteristics of ZMK5530TZJ60 drilling rig, the selection of relief valve and the prevention of parameter matching are put forward. Using AMEsim software dynamic simulation system, pressure and flow characteristics of pressure relief drilling loop are obtained. At the same time, parameter matching is optimized by software simulation. It can be used for reference for matching and optimizing parameters of decompression drilling circuit of CBM drilling rig.
Extremist ideology as a complex contagion: the spread of far-right radicalization in the United States between 2005-2017

Increasing levels of far-right extremist violence have generated public concern about the spread of radicalization in the United States. Previous research suggests that radicalized individuals are destabilized by various environmental (or endemic) factors, exposed to extremist ideology, and subsequently reinforced by members of their community. As such, the spread of radicalization may proceed through a social contagion process, in which extremist ideologies behave like complex contagions that require multiple exposures for adoption. In this study, I applied an epidemiological method called two-component spatio-temporal intensity modeling to data from 416 far-right extremists exposed in the United States between 2005 and 2017. The results indicate that patterns of far-right radicalization in the United States are consistent with a complex contagion process, in which reinforcement is required for transmission. Both social media usage and group membership enhance the spread of extremist ideology, suggesting that online and physical organizing remain primary recruitment tools of the far-right movement. Additionally, I identified several endemic factors, such as poverty, that increase the probability of radicalization in particular regions. Future research should investigate how specific interventions, such as online counter-narratives to battle propaganda, may be effectively implemented to mitigate the spread of far-right extremism in the United States.
Rayleigh and Rayleigh-Debye-Gans light scattering intensities and spetroturbidimetry of dispersions of unilamellar vesicles and multilamellar liposomes.

Abstract Hypothesis: Since the volume fraction of the surfactant bilayer(s), of thickness d b , in a vesicle and liposome is smaller than one, the dependences of the Rayleigh (R) scattering intensity and turbidity on the particle radius a are weaker than those for a homogeneous sphere, which are proportional to a 3 . The dependences of the Rayleigh-Debye-Gans (RDG) scattering intensity and turbidity on a are also weaker. Work done: The dependences of the effective relative refractive index on a , d b , and d w (water layer thickness) were derived. The specific Rayleigh ratio R θ * * and the specific turbidity τ * * for single and independent scattering were derived analytically for R and RDG scattering. Spectroturbidimetry data at 25 ° C for a cationic double-chain surfactant, didodecyldimethylammonium bromide (DDAB) were compared to the turbidity predictions. Findings: For R scattering, R θ * * and τ * * are proportional to a 2 d b for vesicles, and to a 3 d b d w + d b for liposomes. For RDG and particle radii 20–1000 nm, τ * * is proportional to a n , where n is 2 to 0.4 for vesicles and 2 to 1.1 for liposomes. Turbidity data for DDAB vesicles are consistent with the RDG predictions, which are also used to estimate the vesicles’ sizes. RDG applies to liposomes
Research progress of ‘Family-Centered Care' in pediatrics

‘Family- Centered Care' was more and more concerned by medical personnel and the society,this paper mainly introduced the international status of " Family - Centered Care" application in pediatrics to promote the mode widespread application and spreading in China. Key words: Family; Nursing; Pediatric; Progress
Assessing the effectiveness of a narrative-based patient education video for promoting opioid tapering.

Abstract Objective To compare effectiveness of a narrative-based educational video versus an informational pamphlet for increasing patients’ self-efficacy and intention to taper their opioid use. Methods Five thousand participants recruited from MTurk were screened to identify eligible patients. Eligible participants (n = 365, 49.9 % female, mean age = 37 years) were randomized to either watch the narrative video or read the pamphlet. Linear regression models were used for the main analysis. Results Participants’ perceptions of tapering effectiveness were higher in the video group (mean = 4.06) than the pamphlet group (mean = 3.67), adjusted mean difference = 0.34, 95 %CI 0.13 - 0.54,P Conclusion A narrative-based video about opioid tapering enhanced patients’ perceptions of the effectiveness of tapering and their tapering self-efficacy. Practice implications Narrative-based videos may be effective for changing patient attitudes about opioid tapering.
Renal artery dissection as an overuse Injury.

The diagnosis of renal infarction is often convoluted due to its non-specific presentation. It can mimic disease processes as disparate as pyelonephritis, diverticulitis, or nephrolithiasis. This c...
Ketogenic Diet, Inflammation, and Epilepsy

Ketogenic diet is a high-fat, low-carbohydrate metabolic intervention that has been in use for the treatment of epilepsy for almost a hundred years. This metabolic intervention affects epilepsy through multiple mechanisms, which combine to exert potent anti-inflammatory activity. Thereby, ketogenic diet not only affects seizures per se but also has the potential to attenuate or prevent the development of epilepsy and its progression. This chapter will focus on novel disease-modifying properties of ketogenic diet therapy and will discuss therapeutic challenges and opportunities.
Spatiotemporal analysis of out-of-hospital cardiac arrest in the City of Los Angeles, 2011-2019.

Abstract Objective The goal of this analysis is to spatiotemporally identify and categorize areas in a large urban city according to Out-of-Hospital Cardiac Arrest (OHCA) rates and No Bystander CPR (NBCPR) risk levels. Study Area and Participants The study comprised all cardiac arrests within the administrative geographic boundary of the City of Los Angeles. The final sample included 15,904 cases that were geolocated within 985 census tracts. Main Outcomes and Measures The primary outcome was stratification of census tracts into risk levels of OHCA and NBCPR by observed spatiotemporal patterns. Results Of 985 census tracts in the analytical sample, 182 census tracts (18.5%) were identified as having higher risk of OHCA and NBCPR. This assessment resulted in 129 census tracts in Tier 3 (moderate risk), 36 in Tier 2 (moderate-high risk), and 17 in Tier 1 (highest risk). Census tracts in Tiers 2 and 3 had higher amounts incident OHCA, while those in tier 1 had more OHCA events with NBCPR. These areas were largely contiguous and located in the Central and South areas of Los Angeles. Conclusions Using a novel three-tiered neighborhood risk classification tool, specific neighborhoods have been identified in the second largest city in the U.S. with consistently high or accelerating rates of OHCA and low bystander CPR. Further study of bystander response and community-based public health campaigns are needed in these communities.
Social Connectivity During the COVID-19 Pandemic: Disparities among Medicare Beneficiaries.

PurposeSocial connections are essential for health and well-being at all ages and may be especially important for promoting health in later life. Maintaining social connections, however, became inc...
Readmission Rates in Robotic Gynecologic Surgery: A Comparison between Inpatient and Outpatient Surgery in a Large Health System

Study Objective Current literature suggests that same-day discharge (SDD) after minimally invasive gynecologic surgery (MIGS) is feasible and associated with better perioperative outcomes. This study aims to evaluate how rates and reasons for readmission after robotic gynecologic surgery evolved over a four-year period in a large hospital system following an increase in SDD. Design Retrospective cohort study. Setting Health system including 11 academic and community hospitals. Patients or Participants 6,170 patients undergoing robotic gynecologic surgery during 2017-2020. Interventions N/A. Measurements and Main Results In this study, 6,170 patients underwent robotic gynecologic surgery between 2017-2020. 3,316 patients were discharged the same day of surgery (outpatient, OP) and 2,854 were discharged on or after postoperative day 1 (inpatient, IP). 118 total patients were readmitted with a readmission rate of 3.2%. When stratified into IP and OP, the readmission rates were 4.8% and 2.3%, respectively. Over the 4-year period, the rate of SDD as a percentage of total robotic gynecologic surgeries increased by 28.3% with 59% SDD in 2020. We observed the lowest overall rate of readmission during 2020, which was also the year with the highest rate of SDD. When stratified for readmission indications, 2020 also accounted for the lowest incidence of readmission for venous thromboembolism and genitourinary complications compared to prior years. There were no readmissions for wound dehiscence or post-operative pain in this year. The rates of readmission for infection, hemorrhage, and gastrointestinal complications in 2020 were comparable to prior years in which SDD rates were lower. Conclusion As rates of SDD increased between 2017-2020, the readmission rate after robotic gynecologic surgery decreased. When stratified for specific indications, all rates for readmission in 2020 (the highest SDD year) were comparable or lower than previous years. Our study supports the current literature which demonstrates that SDD after MIGS is both safe and feasible.
Programmable large DNA deletion, replacement, integration, and inversion with twin prime editing and site-specific recombinases

The targeted deletion, replacement, integration, or inversion of DNA sequences at specified locations in the genome could be used to study or treat many human genetic diseases. Here, we describe twin prime editing (twinPE), a method for the programmable replacement or excision of DNA sequence at endogenous human genomic sites without requiring double-strand DNA breaks. TwinPE uses a prime editor (PE) protein and two prime editing guide RNAs (pegRNAs) that template the synthesis of complementary DNA flaps on opposing strands of genomic DNA, resulting in the replacement of endogenous DNA sequence between the PE-induced nick sites with pegRNA-encoded sequences. We show that twinPE in human cells can perform precise deletions of at least 780 bp and precise replacements of genomic DNA sequence with new sequences of at least 108 bp. By combining single or multiplexed twinPE with site-specific serine recombinases either in separate steps or in a single step, we demonstrate targeted integration of gene-sized DNA plasmids (>5,000 bp) into safe-harbor loci including AAVS1, CCR5, and ALB in human cells. To our knowledge, these results represent the first RNA-programmable insertion of gene-sized DNA sequences into targeted genomic sites of unmodified human cells without requiring double-strand breaks or homology-directed repair. Twin PE combined with recombinases also mediated a 40,167-bp inversion at IDS that corrects a common Hunter syndrome allele. TwinPE expands the capabilities of precision gene editing without requiring double-strand DNA breaks and synergizes with other tools to enable the correction or complementation of large or complex pathogenic alleles in human cells.
Pharmacological Interference with DNA Repair

Many carcinogens and antineoplastic agents act primarily by damaging DNA. A very large portion of this damage is repaired by normal cells. Defects in these repair processes have serious consequences, as shown by xeroderma pigmentosum, ataxia telangiectasia and other cancer-prone genetic diseases. Drugs can also interfere with DNA repair pathways. They, like the genetic defects, increase the lethality of DNA damaging agents. Unlike these diseases, however, some drugs have been shown to decrease carcinogenicity. The basis for this paradoxical effect may be the ability of DNA repair inhibitors to convert normally sublethal misrepaired lesions into lethal ones. Drugs that interfere with DNA repair thus have promise not only for increasing the efficacy of chemotherapy, but also for decreasing carcinogenicity.
Making the Property Tax Work

As with any reform, making the property tax work requires visionary leadership, an appropriate policy framework, strong administrative capacity, and appropriate incentives to mobilize the political, administrative and popular support needed to enhance property tax revenues, equity and efficiency. This paper focuses on these requirements for successful property tax reform, identifying the key policy and administrative components and possible strategies needed to make the property tax work. Part 1 outlines the broader public sector reform environment needed to facilitate and support sustainable property tax reform. Part 2 identifies the policy and administration determinants affecting the realization of property tax revenue, equity and efficiency outcomes. Part 3 focuses on the ingredients needed to design a successful reform implementation strategy, while Part 4 summarizes the key recommendations for making the property tax work, especially in transitional and developing countries.
With the Illinois Brick Wall Down, What's Left?: Determining Antitrust Standing Under State Law

This Article deals with a problem which has repeatedly arisen in state and federal courts, resulting in a number of splintered opinions. In 1977, the Supreme Court ruled that only direct purchasers of a price-fixed product may sue under the Sherman Act. Thus, under the “Illinois Brick rule,” consumers who buy a price-fixed product from a middle-man may not sue. Many states responded by passing “Illinois Brick repealers” which aimed to allow such suits. This Article addresses two questions which have divided the state and federal courts: Did the Illinois Brick repealers grant automatic standing to any indirect purchaser of a price-fixed product, or did they simply repeal the per se rule that J.D., Yale Law School, 2009; B.A., Gettysburg College, 2006. The author would like to thank George Priest for providing valuable feedback and being an all-around great guy. 256 BUSINESS, ENTREPRENEURSHIP, & THE LAW Vol. III:II indirect purchasers can never sue, leaving the question of which indirect purchasers may sue to a traditional “antitrust standing” analysis? If the latter, to what extent must the traditional antitrust standing doctrine be modified to render it consistent with the policies of the Illinois Brick repealers? Although no academic piece has considered these questions, twenty state and federal courts have—all within the last ten years. This Article summarizes the approaches the courts have taken to both of these questions, criticizes those that have gone wrong in its view, and offers a modified test that is both practical and faithful to the policy choices embodied in the repealers.
AP-4, a Novel Protein Complex Related to Clathrin Adaptors *

Here we report the identification and characterization of AP-4, a novel protein complex related to the heterotetrameric AP-1, AP-2, and AP-3 adaptors that mediate protein sorting in the endocytic and late secretory pathways. The key to the identification of this complex was the cloning and sequencing of two widely expressed, mammalian cDNAs encoding new homologs of the adaptor β and ς subunits named β4 and ς4, respectively. An antibody to β4 recognized in human cells an ∼83-kDa polypeptide that exists in both soluble and membrane-associated forms. Gel filtration, sedimentation velocity, and immunoprecipitation experiments revealed that β4 is a component of a multisubunit complex (AP-4) that also contains the ς4 polypeptide and two additional adaptor subunit homologs named μ4 (μ-ARP2) and e. Immunofluorescence analyses showed that AP-4 is associated with the trans-Golgi network or an adjacent structure and that this association is sensitive to the drug brefeldin A. We propose that, like the related AP-1, AP-2, and AP-3 complexes, AP-4 plays a role in signal-mediated trafficking of integral membrane proteins in mammalian cells.
Culture, Gender, And Suicidal Behavior In Sri Lanka

In less than 50 years, the rate of suicide among Sri Lankans has risen from a modest level to one of the highest in the world. This article describes the current pattern of suicides, including sex differences and similarities, and reviews some of the institutional practices, material conditions, and social norms that may figure in the increases. A study is reported, which asked how ordinary Sri Lankans account for suicidal behavior and what practices they recommend for assisting suicidal individuals. Gender inflected these accounts, with essentialist accounts associated with women's suicides and contextual accounts associated with men's suicides.
Defective interfering particles of Sindbis virus. III. Intracellular viral RNA species in chick embryo cell cultures.

Abstract Serial undiluted passage of wild-type Sindbis virus (SV-W) in primary chick embryo cell cultures resulted in a cyclic variation in the yield of infectious virus. Cells infected with virus stocks (SV-CP) derived from such passage series directed significantly less viral RNA synthesis than cells infected with SV-W at the same multiplicity of infection (MOI) and produced particles (ϱ = 1.20 g/cc) capable of homologous interference. Cells infected with SV-CP stocks of increasing passage number contained, in addition to 22S dsRNA (found in SV-W infected cells), species of virus-specific dsRNA of decreasing molecular size. The rate of evolution to the smaller dsRNA species was considerably faster during serial undiluted passage of SV-W in BHK-21 cells than in chick cells. Cells infected with SV-CP stocks also contained a new species of ssRNA for each additional species of dsRNA produced suggesting that the two are functionally related.
A Novel and Efficient Model of Coronary Artery Ligation in the Mouse

Coronary artery ligation to induce myocardial infarction (MI) and ischemia/reperfusion (I/R) injury in mice is typically performed by an invasive and time-consuming approach that requires ventilation and a full thoracotomy (classical method), often resulting in extensive tissue damage and high mortality. Here, we describe a novel and rapid surgical method to induce MI that does not require ventilation. This method is much more efficient and safer than the classical method of MI and I/R injury.
Factors Influencing Levels of 17-Hydroxyprogesterone in Very Low Birth Weight Infants and the Relationship to Death and IVH

Factors Influencing Levels of 17-Hydroxyprogesterone in Very Low Birth Weight Infants and the Relationship to Death and IVH
The subcellular distribution of carbonic anhydrase in homogenates of perfused rat brain.

— The distribution of carbonic anhydrase was examined in subcellular fractions of perfused rat brain and compared with those of markers for cytosol (lactic dehydrogenase), mitochondrial matrix (glutamic dehydrogenase), and mitochondrial membranes (succinic dehydrogenase). About half of the total carbonic anhydrase was found in particulate fractions, with the greatest part of this in the crude mitochondrial fraction. This fraction was separated into its components on a discontinuous sucrose gradient either as such or after isotonic mechanical disruption with a French pressure cell, and the resultant fractions were characterized by electron microscopy and by assay of marker enzymes. Carbonic anhydrase was solubilized by mechanical disruption, but not to the same extent as lactic dehydrogenase. The highest specific activity for carbonic anhydrase was found in the myelin fraction of the gradient. A mitochondrial locus for carbonic anhydrase is unlikely, but the presence of the enzyme in synaptosomes remains in question. Addition of soluble carbonic anhydrase did not significantly increase the activity of particulate fractions. Treatment of particulate fractions with detergent was necessary to reveal latent activity; this procedure resulted in a more than ten-fold increase in the measurable carbonic anhydrase activity of myelin fragments.
Electro-Optically Tunable Folded Arrayed Waveguide Grating Multiplexer

Quadratic electro-optic shift of central wavelength in boron-phosphorous-doped folded Arrayed Waveguide Grating (AWG) multiplexer has been demonstrated. A spectral shift of ~1-GHz/KV was obtained with virtually zero power consumption.
USING A TRAINABLE PATTERN‐DIRECTED COMPUTER PROGRAM TO SCORE NATURAL LANGUAGE ITEM RESPONSES

In this study we investigated a computer scoring procedure for constructed-response items whose responses consist of natural language phrases or sentences. The costs for scoring such items either manually or by a traditional natural language computer processing approach is typically expensive. The purpose of this study was to investigate the feasibility of an alternate method to the traditional natural language processing approach. The two main goals of the study were to create a prototype scoring program based on an appropriate methodology and to carry out a preliminary comparison of the results of the scoring methodology to the scores of human raters. Our approach to scoring is based on the assumption that a set of responses can be described as a small language. From this language we can construct a grammar that describes the language. The grammar can then be used as a tool for recognizing sentences in the language. With respect to the task of scoring, this means creating a grammar from a sample of responses that have been scored correct or incorrect. This grammar is then used by a program to classify responses that were not used to create the grammar. The program automatically classifies a response as correct (or incorrect). The computer program was used to score sets of responses from three items. Two sets of data consisted of short responses (3 to 5 words). The third set of data consisted of longer responses (12 to 15 words). The scoring program rating agreed perfectly with those of human raters for the first two data sets and achieved a maximum agreement of 90% for the third data set. We conclude from these preliminary results that a trainable pattern-directed computer scoring program may be a viable, cost-effective approach to scoring short natural language responses. Longer responses present a number of problems that require further investigation. We suggest a number of ways that the prototype program can be extended to compensate for these more complex responses.
A Markov analysis of interview communication

This study focused on patterns of verbal behavior embedded in the interview process rather than on externalfactors as predictors of outcome. A Markov model was used to map the relationships between interviewer styles, time, and patterns of communication. Each interview was conceptualized as a system, and the categories of verbal behavior were treated as the finite number of states the system could ocupy. Thirteen‐state and three‐state models of the interview systems were constructed which displayed both state probabilities and transition probabilities of the system's states. The basic finding was that although each interview system had different probability structures, the structure of any one system was quite stable over time.
Comparison of resistance to sliding between different self-ligating brackets with second-order angulation in the dry and saliva states

Resistance to sliding was investigated for 3 self-ligating brackets having passive slides and 3 self-ligating brackets having active clips. Four of these products are currently marketed, and 2 are of historic interest. For all cases, an 0.018 x 0.025-in stainless steel archwire was drawn through each bracket at a rate of 10 mm/min over a distance of 2.5 mm. For each bracket, the resistances to sliding were measured at 14 second-order angulations, which ranged from -9 degrees to +9 degrees. Both the dry and the wet (human saliva) states were evaluated at 34 degrees C. From dimensional measurements, the critical contact angles for binding were determined for all products and ranged from 3 degrees to 5 degrees. Below each characteristic critical angle, brackets with passive slides exhibited negligible friction; brackets with active clips exhibited frictional forces as great as 50 cN (50 g). Above each critical angle, all brackets had elastic binding forces that increased at similar rates as angulation increased and were independent of bracket design. Generally speaking, at second-order angulations that exceeded the critical angle, brackets with active clips that had a low critical angle had more resistance to sliding than did brackets with active clips that had a higher critical angle. Brackets with passive slides that had a high critical angle exhibited the lowest resistance to sliding, but could do so at a cost of some loss of control. Nonetheless, self-ligating brackets represent a compromise between friction and control; ie, self-ligating brackets produce frictional forces that are more reproducible than do conventionally ligated stainless steel brackets but without the potential control problems associated with Begg-style brackets.
Multiscale, dictionary-based speckle denoising

We propose a multiscale, dictionary-based, data-adaptive estimation method to recover intensities from multiplicative, speckle data. The proposed method preserves the edges and textures in the underlying image while smoothing intensities in homogenous regions.
Reversible inhibition of endocytosis in cultured neurons from the Drosophila temperature-sensitive mutant shibirets1.

The Drosophila mutant, shibirets1 (shits1), is paralyzed at restrictive temperatures (> 29oC) by a reversible block in synaptic transmission. Heat pulses deplete synaptic vesicles in nerve terminals and inhibit endocytic internalization of plasma membrane in garland cells and oocytes. In dissociated cultures of larval central nervous system (CNS), a temperature-sensitive defect is also expressed in shits1 neurons: at 30oC, growth cone formation is retarded and neurite outgrowth is arrested.We now report that we have examined constitutive endocytosis in Drosophila CNS culture and have demonstrated directly an endocytic defect in shits1 neurons. At the permissive temperature, 20-22oC, both shits1and wild-type neurons actively endocytosed fluorescein-labelled dextran (40KD, 5%) or horseradish peroxidase (HRP, 1%). Within 5 min, HRP was seen in vesicles, cup-shaped bodies, tubules and multivesicular bodies in neurites and cell bodies. In contrast, endocytosis was inhibited in cultures derived from the tempera...