cssi/SciSciGPT-SciSciNet huggingface dataset:
Multiple Autoantibody-Related Paraneoplastic Limbic Encephalitis with Complete Neurologic Recovery (P3.423)

Objective: Outline the clinical course of a patient with multiple autoantibody-related paraneoplastic limbic encephalitis with complete neurologic recovery after treatment. Background: AMPA-Rc, GABA-B-Rc, and CRMP-5 antibodies have been associated with paraneoplastic limbic encephalitis. The presence of concurrent cell-surface and onconeuronal antibodies is associated with poor prognosis. To our knowledge, no reports describe a similar profile of autoantibodies with a favorable outcome as our patient. Design/Methods: Case Report Results: A 39-year-old woman presented with two weeks of behavioral change and amnesia progressing to coma requiring intubation. A mediastinal mass was found on imaging with pathology consistent with thymoma. Further testing showed multiple positive serum autoantibodies against AMPA-Rc (CBA positive;IF titer 1:7680), GABA-B-Rc (CBA positive; 1:7680), CRMP-5 (Western blot Positive), AchR binding (2.11nmol/L), AchR modulating Ab (93%), and N-Type Calcium (0.05nmol/L). CSF revealed anti-AMPA-Rc antibodies. Tumor location delayed surgery and she underwent emergent treatment with PLEX in tandem with neoadjuvant chemotherapy. Her mental status improved and she was discharged home and subsequently underwent thymoma resection and post-operative radiotherapy due to positive resection margins. At 1 year follow-up she has had a continued favorable outcome with return to premorbid baseline. Conclusions: The case presented is unique from previously described cases of autoimmune encephalitis due to it’s impressive autoantibody profile and complete recovery after treatment. It is unclear if the encephalitis was driven from a single autoantibody or an additive effect of multiple autoantibodies. Although, it is possible that the AMPA-Rc antibody was the main driving force of her encephalitis given the presence of high serum titer and presence in spinal fluid. While definitive treatment with surgical resection was delayed, she responded dramatically to plasma exchange which allowed her to be discharged home to complete her therapy. This is notable due to the generally poor prognosis associated with multiple autoantibody-related limbic encephalitis. Disclosure: Dr. Shoemaker has nothing to disclose. Dr. Newsome has nothing to disclose.
Swift heat transfer by fast-forward driving in open quantum systems

Typically, time-dependent thermodynamic protocols need to run asymptotically slowly in order to avoid dissipative losses. By adapting ideas from counterdiabatic driving and Floquet engineering to open systems, we develop fast-forward protocols for swiftly thermalizing a system oscillator locally coupled to an optical phonon bath. These protocols control the system frequency and the system-bath coupling to induce a resonant state exchange between the system and the bath. We apply the fast-forward protocols to realize a fast approximate Otto engine operating at high power near the Carnot efficiency. Our results suggest design principles for swift cooling protocols in coupled many-body systems.
All This Is from God: Augsburger, Lederach, Barth, and Coutts on Forgiveness:

What is forgiveness and why should we forgive? What does it accomplish? Why does it falter? Are there wrong ways or wrong times to forgive? How can we forgive our brothers and sisters from the hear...
Ending Sexual Harassment: Protecting the Progress of #MeToo

How can we best protect and safeguard the progress of the #MeToo movement? This article presents 11 reforms designed to ensure the movement’s drive toward justice. These fall into three areas. The first concern process reforms designed to (a) protect all those involved—accusers and the accused—in investigations of sexual harassment, (b) end differential treatment of those found guilty, and (c) ensure punishments are commensurate with the crime and proportional in terms of other transgressors. The second set of reforms focus on transparency of the process, including clarifying (a) how to file charges, (b) who makes decisions, (c) relevant public information on how charges and procedures are followed, (d) what transgressions result in which punishments, and (e) how complaints are investigated to protect the rights and privacy of all. Finally, I address cultural issues that address (a) our portrayal of women, (b) our societal attempts to prepare young people so they can better protect themselves, and...
Does Implant Choice Affect the Episode Cost of Pertrochanteric Hip Fracture for US Veterans

OBJECTIVE To investigate an association between a surgeon's choice of a cephalomedullary nail (CMN) or sliding hip screw (SHS) with the cost of treating a pertrochanteric hip fracture. DESIGN Multicenter retrospective cohort study. SETTING US Veterans Health Administration Sierra Pacific Network. PATIENTS/PARTICIPANTS Two hundred ninety-four consecutive US veterans admitted for a principal diagnosis of an OTA/AO 31A-type pertrochanteric hip fracture of a native hip from 2000 to 2015. INTERVENTION Internal fixation using a CMN or an SHS. MAIN OUTCOME MEASUREMENTS Veterans Administration Health Economic Resource Center average national cost estimate of combined acute and postacute care episode cost, excluding implant cost, normalized to 2015 US dollars by the Consumer Price Index. RESULTS Median episode cost was $8223 lower with a CMN than an SHS (95% confidence interval, $5700-$10,746, P < 0.001) after matching on a propensity score for treatment with a CMN based on age, sex, body mass index, Charlson Comorbidity Index, fracture characteristics, study site, and admission year. A subgroup propensity-matched analysis excluding reverse obliquity pertrochanteric fractures was not sufficiently powered to detect a difference in episode cost (β = 0.76, P = 0.311). CONCLUSIONS Implant choice significantly affected the episode cost of care of hip fracture at Veterans Health Administration facilities. LEVEL OF EVIDENCE Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The design and implementation of the wolfram language compiler

The popularity of data- and scientific-oriented applications, abundance of on-demand compute resources, and scarcity of domain expert programmers have given rise to high-level scripting languages. These high-level scripting languages offer a fast way to translate ideas into code, but tend to pay a heavy performance overhead. In order to alleviate the performance penalty, each implementation of these languages often offers a compilation path to a subset of the language. In this paper we present the design and implementation of the Wolfram Language compiler, the production compiler for the Wolfram Language. We show how popular language features and runtime behavior, expected by Wolfram Language developers, are efficiently implemented within the compiler. We then show how the compiler provides a friction-less path to migrate programs from the interpreter to the compiler. We evaluate the compiler and show that compiled code matches the performance of highly tuned hand-written C code. The compiler has been released as a prominent feature of Wolfram Engine v1212 and is readily available to developers.
A Dynamical Perspective on Point Cloud Registration

We provide a dynamical perspective on the classical problem of 3D point cloud registration with correspondences. A point cloud is considered as a rigid body consisting of particles. The problem of registering two point clouds is formulated as a dynamical system, where the dynamic model point cloud translates and rotates in a viscous environment towards the static scene point cloud, under forces and torques induced by virtual springs placed between each pair of corresponding points. We first show that the potential energy of the system recovers the objective function of the maximum likelihood estimation. We then adopt Lyapunov analysis, particularly the invariant set theorem, to analyze the rigid body dynamics and show that the system globally asymptotically tends towards the set of equilibrium points, where the globally optimal registration solution lies in. We conjecture that, besides the globally optimal equilibrium point, the system has either three or infinite "spurious" equilibrium points, and these spurious equilibria are all locally unstable. The case of three spurious equilibria corresponds to generic shape of the point cloud, while the case of infinite spurious equilibria happens when the point cloud exhibits symmetry. Therefore, simulating the dynamics with random perturbations guarantees to obtain the globally optimal registration solution. Numerical experiments support our analysis and conjecture.
Defining Appraisal Fair Value

Appraisal is a statutory mechanism that entitles dissenting stockholders of Delaware merger targets to receive a judicially determined valuation of their shares. During a decade when Delaware courts significantly constrained other legal avenues of merger dissent, appraisal petitions increased dramatically, with individual cases potentially implicating billions of dollars of stockholder value. Recent appraisal case law has sparked considerable controversy over the role of market prices in courts’ appraisal valuations. Courts and commentators have struggled to articulate exactly when market prices are the best evidence of fair value, as well as what types of market prices are most relevant to appraisal fair value. This Note presents a revised conception of appraisal fair value that is informed by economic theory and rooted in Delaware corporate law’s longstanding goals of facilitating capital formation and maximizing stockholder value. This Note proposes two changes to existing conceptions of merger deal prices in appraisal cases. First, the appraisal statute should be understood to exclude the value of reduced agency costs from appraisal awards. Second, when material nonpublic information is disclosed to the buyer but withheld from the market, both the appraisal statute and basic notions of market efficiency demand that courts take cognizance of it. The best way to operationalize these conceptual modifications is to presume that the target’s unaffected stock price equals fair value unless the petitioner establishes that material information was withheld from the market. This approach adds needed clarity to the Delaware Supreme Court’s salutary recent embrace of the efficient capital markets hypothesis in the appraisal context. Adopting it would increase stockholder value, encourage efficient change-of-control transactions, and simplify appraisal proceedings. It preserves appraisal’s foundational role as a safeguard against the exploitation of minority stockholders by compensating them when the deal price omits suppressed material information.
Maladaptive response of arterial myocytes to chronic exposure to Ca2+ channel blockers.

> “The tragedies in life are largely arterial.” > > – Sir William Osler, 1908 (1) Hypertension is a debilitating cardiovascular disease characterized by the narrowing of arteries and arterioles which increases resistance to blood flow. This decrease in intraluminal diameter of arteries/arterioles is due to multiple factors, including arterial smooth muscle hypertrophy and hyperplasia as well as increased myogenic tone. Up-regulation of L-type Ca2+ channel activity is a major contributor to enhanced arterial smooth muscle contractility during hypertension (2, 3). Accordingly, current pharmacological guidelines for the treatment of hypertension include the use of L-type Ca2+ channel blockers such as nifedipine or amlodipine (4). In PNAS, Johnson et al. (5) report that chronic exposure to a broad range of these drugs promotes arterial smooth muscle to transition from a contractile to a proliferative phenotype by activating stromal-interacting molecule (STIM)/ORAI store-operated Ca2+ entry (SOCE) (Fig. 1). These findings have profound implications for our understanding of how L-type Ca2+ channel blockers affect vascular function during hypertension and may lead to changes on treatment of the pathology. Fig. 1. Response of contractile and synthetic smooth muscle to hypertension and L-type Ca2+ blockers. ( A ) During hypertension, contractile myocytes shorten in response to increased CaV1.2 channel activity, whereas synthetic myocytes experience a reduction in contractile proteins and increase in SOCE machinery. L-type Ca2+ blockers elicit a decrease in CaV1.2 influx, promoting relaxation and vasodilation. Synthetic myocytes see an increase in SOCE, proliferation, and migration, resulting in hyperplasia and increased incidence of heart failure. ( B ) L-type Ca2+ channel blockers stimulate the assembly of the STIM1/ORAI complexes via an unknown mechanism. The STIM1/ORAI complex promotes SOCE independent of S/ER Ca2+ content or CaV1.2 function. SOCE increases [Ca2+]i and promotes proliferation and migration of … [↵][1]1To whom correspondence may be addressed. Email: lfsantana{at}ucdavis.edu. [1]: #xref-corresp-1-1
Influence of State-Level Emergency Planning Policy Requirements on Secondary School Adoption

Context Emergency action plans (EAPs) are a critical component in the management of catastrophic sport-related injury. Some state high school athletics associations and state legislation have required that schools develop EAPs, but little research exists on the influence of a statewide policy requirement on local adoption of these policies. Objective To examine the efficacy of a statewide policy requirement on local adoption of an EAP. Design Cross-sectional study. Setting Online questionnaire. Patients or other participants Secondary school athletic trainers were invited to complete a survey (n = 9642); 1136 completed the survey, yielding an 11.7% response rate. Main outcome measure(s) Survey responses on the adoption of EAPs along with cardiopulmonary resuscitation and automated external defibrillator (CPR/AED) requirements were cross-referenced with published statewide policies to determine the prevalence of EAP adoption. We evaluated the adoption of emergency action plan components based on the National Athletic Trainers' Association's emergency planning position statement along with CPR/AED requirements to determine component-specific prevalence. We compared the prevalence of EAP and component adoption between states that required EAPs and specific components of EAPs and states without such requirements. Results Athletic trainers in states that required adoption of an EAP reported including more components of the emergency planning position statement (mean = 8 ± 4, median = 9) than in states without a requirement (mean = 7 ± 4, median = 8). The adoption of EAP components did not differ between states that required specific components of the EAP versus development of the EAP only. However, schools in states with both EAP and CPR/AED training requirements reported higher rates of CPR/AED training implementation (95.5%) than states that only required CPR/AED training (81.6%, prevalence ratio = 1.10, 95% confidence interval = 1.01, 1.20). Conclusions Based on these data, statewide policy requirements for the development of an EAP may be associated with increasing adoption of EAPs.
Evidence That VirS Is a Receptor for the Signaling Peptide of the Clostridium perfringens Agr-like Quorum Sensing System

ABSTRACT Since both the Agr (accessory gene regulator)-like quorum sensing (QS) system and VirS/VirR (VirS/R) two-component regulatory system of Clostridium perfringens positively regulate production of several toxins, including C. perfringens beta toxin (CPB), it has been hypothesized the VirS membrane sensor protein is an Agr-like QS signaling peptide (SP) receptor. To begin evaluating whether VirS is an SP receptor, this study sequenced the virS gene in C. perfringens strains CN3685 and CN1795 because it was reported that agrB mutants of both strains increase CPB production in response to the pentapeptide 5R, likely the natural SP, but only the CN3685 agrB mutant responds to 8R, which is 5R plus a 3-amino-acid tail. This sequencing identified differences between the predicted VirS extracellular loop 2 (ECL2) of CN3685 versus that of CN1795. To explore if those ECL2 differences explain strain-related variations in SP sensitivity and support VirS as an SP receptor, virS agrB double-null mutants of each strain were complemented to swap which VirS protein they produce. CPB Western blotting showed that this complementation changed the natural responsiveness of each strain to 8R. A pulldown experiment using biotin-5R demonstrated that VirS can bind SP. To further support VirS:SP binding and to identify a VirS binding site for SP, a 14-mer peptide corresponding to VirS ECL2 was synthesized. This ECL2 peptide inhibited 5R signaling to agrB mutant and wild-type strains. This inhibition was specific, since a single N to D substitution in the ECL2 peptide abrogated these effects. Collectively, these results support VirS as an important SP receptor and may assist development of therapeutics. IMPORTANCEC. perfringens beta toxin (CPB) is essential for the virulence of type C strains, a common cause of fatal necrotizing enteritis and enterotoxemia in humans and domestic animals. Production of CPB, as well as several other C. perfringens toxins, is positively regulated by both the Agr-like QS system and the VirS/R two-component regulatory system. This study presents evidence that the VirS membrane sensor protein is a receptor for the AgrD-derived SP and that the second extracellular loop of VirS is important for SP binding. Understanding interactions between SP and VirS improves knowledge of C. perfringens pathogenicity and may provide insights for designing novel strategies to reduce C. perfringens toxin production during infections.
Prediction of Work Impact in Axial Spondylarthritis by the Work Instability Scale: A Prospective Cohort Study Of 101 Patients

Objective Axial spondyloarthritis (axSpA) may have an impact on work. The Ankylosing Spondylitis Work Instability Scale (AS-WIS) assesses difficulties at work. The objective of this study was to evaluate the predictive value of the AS WIS on work impact. Methods Prospective cohort study with two timepoints (at baseline and after 1.5 years) including patients with axSpA and a paid professional activity. Patients completed the AS-WIS at baseline and work instability was scored as moderate/high if ≥11 (0-20 scale). At follow up, adverse work outcomes (AWO) were defined as short-term sick leave or severe AWO (long-term sick leave, disability, unemployment). Univariable and multivariable logistic regression analyses were performed to explain AWO. Results Of 101 patients, mean age 45 (standard deviation (SD) 9) years, 52% male, disease duration was 14 (SD 8) years. The BASDAI and the BASFI were respectively 34 (SD 21) and 23 (SD 23), 69 (68%) received a TNF-inhibitor. At baseline, 46 (46%) patients had moderate/high AS-WIS. At 1.5 years of follow-up, 37 patients (36%) had AWO: 25 patients (25%) a short-term sick leave, and 12 patients (12%, 7/100 patient years) a severe AWO. Independent baseline factors associated with AWO were a moderate/high AS-WIS score (odds ratio 2.71 [95% confidence interval 1.04-7.22]) and shorter disease duration (0.94 [0.89-0.99]). Conclusion In patients with axSpA, a moderate/high AS-WIS score was predictive of AWO in this population with well-controlled axSpA. This short questionnaire can be helpful to screen for future difficulties at work.
Have Racial and Ethnic Disparities in Juvenile Justice Declined Over Time? An Empirical Assessment of the DMC Mandate:

The present study examines whether racial and ethnic disparities in juvenile justice declined significantly in a state that has made substantial reform efforts in compliance with the Disproportiona...
Free Radical Scavenging and In vitro Cytotoxic Activity of Bugnay (Antidesma bunius) Leaves Extract against A549 Human Lung Adenocarcinoma and HCT-116 Human Colorectal Cancer Cell Lines

Cancer is one of the significant causes of mortality worldwide. Studies on antineoplastic drugs focused on natural products have revealed several mechanisms to inhibit cancer cells. Bugnay (Antidesma bunius) leaves showed potentials due to its activity observed against brine shrimp and breast cancer cells. However, there is still limited knowledge about its activity against other human cancer cells. This study focused on determining the phytochemical compounds in A. bunius leaves extract, the free radical scavenging activity of the extract using the Diphenylpicrylhydrazyl (DPPH) method, and in vitro cytotoxic activity against two cancer cell lines, namely HCT-116 human colorectal and A549 human lung adenocarcinoma cancer cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The phytochemicals identified were unsaturated lactones, flavonoids, phenolics, diterpenes, saponins, tannins, carbohydrates, and reducing sugars. The extract showed significant free radical scavenging activity and a direct correlation of activity with concentration levels. It also exhibited cytotoxic activity against HCT-116 human colorectal and A549 human lung adenocarcinoma. Hence, A. bunius leaves have the potential to be a source of antioxidant and antineoplastic compounds. This warrant further isolation of the compounds for chemotherapeutic purposes. Keywords: Antidesma bunius, Bugnay, Cancer, Cytotoxicity, Radical
Delta Shock Index Predicts Outcomes in Pediatric Trauma Patients Regardless of Age.

Abstract Introduction Changes in the shock index (ΔSI) can be a predictive tool but is not established among pediatric trauma patients. The aim of our study was to assess the impact of ΔSI on mortality in pediatric trauma patients. Methods We performed a 2017 analysis of all pediatric trauma patients (age 0-16 y) from the ACS-TQIP. SI was defined as heart rate(HR)/systolic blood pressure(SBP). We abstracted the SI in the field (EMS), SI in the emergency department (ED) and calculated the change in SI (ΔSI = ED SI–EMS SI). Patients were divided into four age groups: 0-3 y, 4-6 y, 7-12 y, and 13-16 y and substratified into two groups based on the value of the age-group-specific ΔSI cutoff obtained with receiver operating characteristic ROC analysis; +ΔSI and –ΔSI. Our outcome measure was mortality. Multivariable logistic and Cox regression analyses were performed. Results We included 31,490 patients. Mean age was 10.6 ± 4.6 y, and 65.8% were male. The overall mortality rate was 1.4%. In the age group 0-3 y the cutoff point for ΔSI was 0.29 with an area under the curve (AUC) 0.70 [0.62-0.79], ΔSI cutoff 4-6 y was 0.41 AUC 0.81 [0.70-0.92], ΔSI cutoff 7-12 y was 0.05 AUC 0.83 [0.76-0.90], and ΔSI cutoff 13-16 y was 0.13 AUC 0.75 [0.69-0.81]. On the Cox regression analysis, +ΔSI was independently associated with increased in-hospital mortality and 24-h mortality (P ≤ 0.01). Conclusions Vital signs vary by age group in children, but ΔSI inherently accounts for this variation. ΔSI predicts mortality and may be utilized as a predictor to help guide triage of pediatric trauma patients. Level of Evidence Level III Prognostic.
Bayesian Hierarchical Modeling: Application Towards Production Results in the Eagle Ford Shale of South Texas

Recently, the petroleum industry has faced the era of data explosion, and many oil and gas companies resort to data-driven approaches for unconventional field development planning. The objective of this paper is to analyze shale oil wells in a shale reservoir and develop a statistical model useful for upstream. Shale oil wells dataset comprises three aspects of information: oil production rate time series data; well completion data; and well location data. However, traditional decline curve analysis only utilizes the temporal trajectory of the production rates. Motivated by this, we propose a Bayesian hierarchical model that exploits the full aspects of the shale oil wells data. The proposed model provides the following three functionalities: first, estimations of a production decline curve at an individual well and entire reservoir levels; second, identification of significant completion predictors explaining a well productivity; and third, spatial predictions for the oil production rate trajectory of a new well provided completion predictors. As a fully Bayesian approach has been adopted, the functionalities are endowed with uncertainty quantification which is a crucial task in investigating unconventional reservoirs. The data for this study come from 360 shale oil wells completed in the Eagle Ford Shale of South Texas.
Subjective memory in adults over 50 years of age: associations with affective and physiological markers of emotion regulation.

To examine associations among subjective memory reports, psychophysiological markers of emotion regulation, and cognitive performance in healthy adults over 50 years of age.A cross-sectional labora...
Poetics and the Transformations of Semantic Structures in Shawqi Bezai's Poem "Dust Elegy"

The study aims to reveal poetic transformations by monitoring the variables of the structures functioning in the poem (Dust Legacy) by Shawki Bazai', meaning that one of the temptations of textual aesthetic research is to pursue stylistic variables and move the structures of the poem at the artistic and aesthetic level, and for this the poem has taken important motivational paths in highlighting its aesthetic output, according to its stylistic textual variables that aim to discover the creative energy on which the poem works in stimulating the recipient, and its intensity to its creative textual circle. According to this perception, our disclosure of poetry and the transformations of the text structure will be based on the structure of the poem itself without relation to what is outside the text, so the study will be focused on aesthetic values and apocalyptic indicators transmitted by the structures of the poem at the level of its aesthetic sense and textual structure. Focused through its active apocalyptic visions and its open connotations with its values and active textual variables on which its poetry is based in its transformation from one poetic pattern to another within a textual transformational process that confirms the movement of artistically functioning structures, and its poetic arousal through the movement of structures and their variables Stylistic in poetic style.
Reflexive Structures: An Introduction to Computability Theory

1 Functions and Predicates.- 1. Definitions.- 2. Numerical Functions.- 3. Finitary Rules.- 4. Closure Properties.- 5. Minimal Closure.- 6. More Elementary Functions and Predicates.- 2 Recursive Functions.- 1. Primitive Recursion.- 2. Functional Transformations.- 3. Recursive Specifications.- 4. Recursive Evaluation.- 5. Church's Thesis.- 3 Enumeration.- 1. Predicate Classes.- 2. Enumeration Properties.- 3. Induction.- 4. Nondeterministic Computability.- 4 Reflexive Structures.- 1. Interpreters.- 2. A Universal Interpreter.- 3. Two Constructions.- 4. The Recursion Theorem.- 5. Relational Structures.- 6. Uniform Structures.- 5 Hyperenumeration.- 1. Function Quantification.- 2. Nonfinitary Induction.- 3. Functional Induction.- 4. Ordinal Notations.- 5. Reflexive Systems.- 6. Hyperhyperenumeration.- References.
Rb function in cell-cycle regulation and apoptosis

Loss of cell-cycle control is a hallmark of neoplastic cells. One regulator of the critical G1 to S-phase transition in the cell cycle is the retinoblastoma tumour suppressor protein Rb, which interacts with the E2F family of cell-cycle transcription factors to repress gene transcription required for this transition. Through its interaction with E2F, Rb also regulates genes that control apoptosis. Here we review the roles of Rb in regulating the cell cycle and apoptosis and discuss recent results linking these Rb functions to chromatin-remodelling enzymes.
Exception handling in agent-oriented systems

Agent-oriented programming may be the next generation paradigm to try and tame the software complexity beast. Agents are active objects capable of autonomous behavior. Mobility can be one of the attributes of agents in open systems. A software system could be structured as a dynamic, and possibly evolving, ensemble of cooperating agents. However, there is very little in the literature on how to effectively handle exceptions in agent-oriented software systems. Agent-oriented systems have all the exception handling concerns of sequential and concurrent systems, as well as some new issues that arise due to mobility and security in open systems. This paper develops an exception handling model whose salient feature is the separation and encapsulation of exception handling for an agent environment in a special agent called a guardian. The model presented here builds upon the notions of events, exceptions, notifications, and commands in an agent ensemble, and presents a number of exception handling patterns that can be used by a guardian. The model presented here is being investigated in the context of the Ajanta mobile agent programming system.
Identification, purification, and characterization of a calcium-dependent endonuclease (NUC18) from apoptotic rat thymocytes. NUC18 is not histone H2B.

Glucocorticoids stimulate apoptosis in rat thymocytes that is characterized by internucleosomal DNA degradation. We have previously identified an 18-kDa calcium-dependent nuclease whose activity is associated with this DNA degradation. The existence of this nuclease has been challenged by Alnemri and Litwack (1989) J. Biol. Chem. 264, 4104-4111, who suggest that the nuclease we observed was histone H2B. We report here a modified nuclease assay which uses [32P] DNA as a substrate that has enabled the purification and characterization of the 18-kDa nuclease (NUC18). Using Bio-Rex 70 chromatography in conjunction with this assay, we show that NUC18 can be separated from histone H2B. Enzymatically active NUC18, purified to apparent homogeneity, failed to react with two different anti-histone H2B antibodies. NUC18 was inactive in the absence of calcium and known inhibitors of apoptosis, i.e. zinc and aurintricarboxylic acid inhibit its activity. Although NUC18 activity was detected in nuclear extracts of thymocytes of both control and glucocorticoid-treated thymocytes, these activities were distinct. Gel filtration analysis revealed that NUC18 was present as a high molecular weight complex (greater than 100 kDa) in both groups of cells, whereas it also existed as a low molecular weight form in glucocorticoid-treated cells. Thus, NUC18 remains a candidate for the endonuclease responsible for the DNA degradation component of the apoptotic process.
Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma

Introduction We previously reported a contemporaneous onset of cancer and scleroderma in patients with RNA polymerase III (pol) antibodies and identified a biological link between cancer and scleroderma. This investigation was designed to further evaluate whether autoantibody status and other characteristics associate with cancer and a clustering of cancer with scleroderma onset.
Properties of the high-conductance Ca2+-activated K+ (BK) channel in pulmonary arterial smooth muscle cells (847.3)

We reported an upregulation of an oxygen-insensitive splice variant of the high-conductance Ca2+-activated K+ (BK) channel in pulmonary arteries (PA) from rats with chronic hypoxia (CH)-induced pul...
Theoretical comparison for biases of MUSIC-like DOA estimators

Many MUSIC-like DOA estimators, such as min-norm, beamspace MUSIC, likelihood MUSIC, FINE and FINES, have been proposed to improve the performance of MUSIC. Since in the difficult estimation situations the large-sample bias of MUSIC may become the dominant estimation error, comparative study of biases of MUSIC-like estimators in these cases is necessary for their performance evaluation. This paper first identifies the dominant part of the bias of MUSIC for two closely-spaced sources. Then it presents a theoretical analysis of a hierarchy of the performances of these MUSIC-like estimators based on their abilities at reducing this major part of the bias and maintaining the asymptotic variance of MUSIC. The theoretical results explain analytically many previous observations resulting from simulations and numerical computations and may be useful for developing new MUSIC-like algorithms with reduced resolution threshold over that of MUSIC.
New Chronic Kidney Disease and Overall Survival After Nephrectomy for Small Renal Cortical Tumors.

Objective To evaluate kidney functional and overall survival (OS) outcomes in a cohort of patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) for tumors ≤4 cm. Materials and Methods We performed a retrospective study on 2110 patients who underwent PN or RN with normal contralateral kidneys and normal serum creatinine from 1989 through 2012. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Primary end points were baseline incidence of CKD, OS, and new onset of eGFR ≤60 and ≤45 mL/min/1.73 m 2 . Results Preoperatively, 30% and 8% of the cohort had eGFR ≤60 and ≤45 mL/min/1.73 m 2 , respectively. Five-year freedom from eGFR ≤60 mL/min/1.73 m 2 was 24% (95% confidence interval [CI], 19%-30%) and 76% (95% CI, 72%-78%) for RN and PN, respectively, and 5-year freedom from eGFR ≤45 mL/min/1.73 m 2 was 51% (95% CI, 45%-56%) and 91% (95% CI, 89%-93%) for RN and PN, respectively. On multivariable analysis, hazard ratio for RN vs PN was 4.98 (95% CI, 4.11-6.04, P 2 and 9.28 (95% CI, 7.26-11.86, P 2 . The RN group had a higher rate of death per year than the partial group (hazard ratio = 1.61, 95% CI, 1.24-2.08, P = .0003). Conclusion The present study confirms published works demonstrating that a significant proportion of patients have pre-existing CKD. In patients with normal kidney function, RN is associated with a significantly higher risk for developing CKD and worse OS than PN.
WE-D-BRD-02: Tracking Coils for Brachy MR Guidance

The advantages that make MR highly desirable for in-room treatment guidance, i.e. soft-tissue visualization and physiological assessment of healthy/tumor tissues, are largely recognized in the research community. However, the MR absorption in practical clinical workflows is still hindered by lack of sufficient technological infrastructure. Recent advances have been made towards filling that gap such as the development of integrated therapy systems relying on an MR scanner and a radiation source (linac, Co-60) and/or brachytherapy. The session is intended to present new efforts and methods aimed at facilitating the adoption of MR guidance for treatment delivery. Specifically, the discussion will focus on a) linac designs for reduced footprint and seamless integration with MR/linac systems, b) tracking coils for brachytherapy applications, and c) procedures for the commissioning and monitoring of MR and MR/linac performance. Learning Objectives: 1. Understand limitations and proposed solutions for linac designs and associated integration with MR/linac systems; 2. Understand current issues with MR-guided brachytherapy procedures 3. Understand the issues and needs for new MR commissioning and QC. License agreement with Modus Medical Devices to develop a phantom for the quantification of MR image distortions.
Sublethal Staphylococcal Enterotoxin B Challenge Model in Pigs To Evaluate Protection following Immunization with a Soybean-Derived Vaccine

In an effort to develop a sustainable platform for manufacturing protein-based vaccine candidates, we expressed a triple mutant of staphylococcal enterotoxin B carrying the L45R, Y89A, and Y94A modifications in transgenic soybean seeds (soy-mSEB). Soy-mSEB possessed no detectable superantigen activity in vitro. We found that this soybean-derived, nontoxic mutant of SEB could be stably expressed, stored in seeds for extended periods at room temperature without degradation, and easily purified from contaminating soy proteins. Vaccination of pigs with purified soy-mSEB, or the identical triple mutant expressed in Escherichia coli (E. coli-mSEB), resulted in high antibody titers against the native toxin in immunized animals. In fact, titers were indistinguishable regardless of the immunogen used, demonstrating the equivalence of soy-mSEB and E. coli-mSEB vaccinations. Antisera from either immunized group were able to block native SEB superantigen activity in an in vitro neutralization assay. Similar results were obtained when immunized animals were challenged with a sublethal dose of native toxin. Significant reductions in toxin-induced serum cytokine levels were observed in soy-mSEB- and E. coli-mSEB-immunized pigs compared to control animals. The reductions in SEB-induced cytokine responses were similar regardless of the immunogen used for vaccination. Surprisingly, however, some clinical symptoms, such as prostration, lethargy, emesis, and/or diarrhea, were still observed in all immunized animals. These studies demonstrate the potential for soybean-derived proteins as a platform technology for sustainable vaccine manufacturing and the usefulness of a sublethal challenge model in pigs for evaluating the efficacy of potential SEB vaccine candidates.
Fire spread phenomena: the role of observation in experiment

Abstract Summarized are recent experimental findings of fire spread phenomena. This review covers flame spread over solids (including melting solids and metals), large-scale spread through discrete fuels (such as fire brands and fire whirls), and scale modeling techniques applied to flame spread study. Emphasis is placed on the importance of observation in experiments which is the source of imagination and successful modeling.
Simulation study of high injection effects and parasitic barrier formation in SiGe HBTs operating at high current densities

Abstract The effects of high carrier densities near the base–collector (B–C) heterojunction in npn SiGe heterojunction bipolar transistors during device operation at high current densities has been investigated using a commercial numerical device simulator. Due to electron velocity saturation in the B–C space charge region and the presence of the valence band discontinuity at the B–C junction, hole accumulation occurs at the collector end of the base at the onset of base pushout at high current densities. Formation of a parasitic barrier to electron flow in the conduction band occurs at the collector junction which increases recombination in the base and the base current and produces saturation in the collector current. Together, these effects produce an abrupt degradation in the transistor’s current gain and cutoff frequency with increasing emitter junction bias. In this paper, we investigate the onset and relationship of parasitic barrier formation and base pushout, and their dependence on device structure and biasing.
In vitro Transcription and Capping of Gaussia Luciferase mRNA Followed by HeLa Cell Transfection

In vitro transcription is the synthesis of RNA transcripts by RNA polymerase from a linear DNA template containing the corresponding promoter sequence (T7, T3, SP6) and the gene to be transcribed (Figure 1A). A typical transcription reaction consists of the template DNA, RNA polymerase, ribonucleotide triphosphates, RNase inhibitor and buffer containing Mg2+ ions. Large amounts of high quality RNA are often required for a variety of applications. Use of in vitro transcription has been reported for RNA structure and function studies such as splicing1, RNAi experiments in mammalian cells2, antisense RNA amplification by the "Eberwine method"3, microarray analysis4 and for RNA vaccine studies5. The technique can also be used for producing radiolabeled and dye labeled probes6. Warren, et al. recently reported reprogramming of human cells by transfection with in vitro transcribed capped RNA7. The T7 High Yield RNA Synthesis Kit from New England Biolabs has been designed to synthesize up to 180 μg RNA per 20 μl reaction. RNA of length up to 10kb has been successfully transcribed using this kit. Linearized plasmid DNA, PCR products and synthetic DNA oligonucleotides can be used as templates for transcription as long as they have the T7 promoter sequence upstream of the gene to be transcribed. Addition of a 5' end cap structure to the RNA is an important process in eukaryotes. It is essential for RNA stability8, efficient translation9, nuclear transport10 and splicing11. The process involves addition of a 7-methylguanosine cap at the 5' triphosphate end of the RNA. RNA capping can be carried out post-transcriptionally using capping enzymes or co-transcriptionally using cap analogs. In the enzymatic method, the mRNA is capped using the Vaccinia virus capping enzyme12,13. The enzyme adds on a 7-methylguanosine cap at the 5' end of the RNA using GTP and S-adenosyl methionine as donors (cap 0 structure). Both methods yield functionally active capped RNA suitable for transfection or other applications14 such as generating viral genomic RNA for reverse-genetic systems15 and crystallographic studies of cap binding proteins such as eIF4E16. In the method described below, the T7 High Yield RNA Synthesis Kit from NEB is used to synthesize capped and uncapped RNA transcripts of Gaussia luciferase (GLuc) and Cypridina luciferase (CLuc). A portion of the uncapped GLuc RNA is capped using the Vaccinia Capping System (NEB). A linearized plasmid containing the GLuc or CLuc gene and T7 promoter is used as the template DNA. The transcribed RNA is transfected into HeLa cells and cell culture supernatants are assayed for luciferase activity. Capped CLuc RNA is used as the internal control to normalize GLuc expression.
Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-l-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene

Abstract N-Acetyl-S-(1,2-dichlorovinyl)- l -cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)- l -cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)- l -cysteine (DCVC) or S-(1,2-dichlorovinyl)- l -cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague–Dawley rats were dosed (i.p.) with 230 μmol/kg b.w. NA-DCVCS or its potential precursors, DCVCS or NA-DCVC. At 24 h post treatment, rats given NA-DCVC or NA-DCVCS exhibited kidney lesions and effects on renal function distinct from those caused by DCVCS. NA-DCVC and NA-DCVCS primarily affected the cortico-medullary proximal tubules (S2–S3 segments) while DCVCS primarily affected the outer cortical proximal tubules (S1–S2 segments). When NA-DCVCS or DCVCS was incubated with GSH in phosphate buffer pH 7.4 at 37 °C, the corresponding glutathione conjugates were detected, but NA-DCVC was not reactive with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a significant role in DCVC, NA-DCVC, and trichloroethylene nephrotoxicity. They also suggest a role for hepatic metabolism in the mechanism of NA-DCVC nephrotoxicity.
Brain-derived neurotrophic factor (BDNF) Val66Met and adulthood chronic stress interact to affect depressive symptoms

Background BDNF Val66Met by chronic stress interaction has been studied using childhood stress as a moderator, but has not been widely studied using chronic stress in adulthood.
Chemical compositions of the hyphal walls of three chromomycosis agents.

Chemical analyses demonstrated the similar compositions of hyphal walls isolated from the chromomycosis agents Phialophora verrucosa, P. pedrosoi and Cladosporium carrionii. Unfractionated walls of each species consisted of large amounts of glucose (17–31%) and protein components (29–42%) and smaller amounts of mannose (8–14%) and glucosamine (6–8%). Alkali-soluble wall fractions consisted predominantly of glucose and mannose, while alkali-insoluble wall fractions consisted predominately of glucosamine and protein components. Chitin was identified as a wall component by release of N-acetylglucosamine during enzymatic digestions of the walls with Streptomyces griseus chitinase. The presence of chitin in the walls and alkali-insoluble residues was confirmed by X-ray powder analysis. The suggestion is made that the hyphal forms of human pathogenic fungi have wall compositions intermediate between those of euascomycetes and hemiascomycetes.
Cellulose biosynthesis: A model for understanding the assembly of biopolymers

This study provides an updated review of the current status on cellulose biosynthesis. The centerpiece of this work is the presentation of a new model of cellulose biogenesis. This model and its parts are presented to better understand the mechanisms of polymerization and crystallization leading to biopolymer formation. The new information has been derived largely from sequence analysis, biochemistry and ultrastructural data relating to cellulose, Nature's most abundant macromolecule.
On the dimensional reduction of D=10, N=2 supergravities

Abstract We list the four-dimensional supergravities that are derived from the N = 2, ten-dimensional supergravities using the method of coset-space dimensional reduction. The spectrum of each four-dimensional theory consists of those super-multiplets that are invariant under the symmetry transformations of the coset space.
Synthesis, structure, and mesomorphic properties of main-chain liquid-crystalline ionomers containing sulfonate groups

The mesogenic monomer M and a series of main-chain liquid crystalline ionomers (LCIs) containing sulfonate groups were synthesized. The LCIs were prepared by an interfacial condensation reaction of mesogenic monomer 1,4-phenylene-dicarbonic acid bis (4-carboxyl phenyl) ester, brittle yellow (BY), 1,10-sebacoyl dihydroxy, and 1,12-dodecanedioyl dihydroxy. The sulfonate groups introduced to the main-chain backbone were confirmed by ultraviolet spectroscopy. The mesomorphic properties were investigated by differential scanning calorimetry (DSC), thermo gravimetric (TG), and polarizing optical microscopy (POM). Experimental results demonstrated that the glass-transition temperatures increased slightly, melting temperature decreased, and the mesophase temperature ranges increased first and then decreased with increasing content of sulfonate group. All of the polymers were thermally stable up to 320 °C. The LCIns exhibited typical nematic schlieren textures.
Diversity: A Philosophical Perspective

In recent years, diversity, whether it be ecological, biological, cultural, or linguistic diversity, has emerged as a major cultural value. This paper analyzes whether a single concept of diversity can underwrite discussions of diversity in different disciplines. More importantly, it analyzes the normative justification for the endorsement of diversity as a goal in all contexts. It concludes that no more than a relatively trivial concept of diversity as richness is common to all contexts. Moreover, there is no universal justification for the endorsement of diversity. Arguments to justify the protection of diversity must be tailored to individual contexts.