cssi/SciSciGPT-SciSciNet huggingface dataset:
Natural IgM antibodies that bind neoepitopes exposed as a result of spinal cord injury , drive secondary injury by activating complement

Natural IgM antibodies (Abs) function as innate immune sensors of injury via recognition of neoepitopes expressed on damaged cells, although how this recognition systems function following spinal cord injury (SCI) exposes various neoepitopes and their precise nature remains largely unknown. Here, we investigated the role of two natural IgM monoclonal Abs (mAbs), B4 and C2, that recognize post-ischemic neoepitopes following ischemia and reperfusion in other tissues. Identification of post-SCI expressed neoepitopes was examined using previously characterized monoclonal Abs (B4 and C2 mAbs). The role of post-SCI neoepitopes and their recognition by natural IgM Abs in propagating secondary injury was examined in Ab-deficient Rag1−/− or wild type C57BL/6 mice using Ab reconstitution experiments and neoepitope-targeted therapeutic studies, respectively. Administration of B4 or C2 mAb following murine SCI increased lesion size and worsened functional outcome in otherwise protected Ab-deficient Rag1−/− mice. Injury correlated with colocalized deposition of IgM and C3d in injured spinal cords from both mAb reconstituted Rag1−/− mice and untreated wild-type mice. Depletion of peritoneal B1 B cells, a source of natural Abs, reduced circulating levels of IgM with B4 (annexin-IV) and C2 (subset of phospholipids) reactivity, reduced IgM and complement deposition in the spinal cord, and protected against SCI. We therefore investigated whether the B4 neoepitope represents a therapeutic target for complement inhibition. B4-Crry, a fusion protein consisting of a single-chain Ab derived from B4 mAb, linked to the complement inhibitor Crry, significantly protected against SCI. B4-Crry exhibited a dual function in that it inhibited both the binding of pathogenic IgM and blocked complement activation in the spinal cord. This study identifies important neoepitopes expressed within the spinal cord after injury. These neoepitopes are recognized by clonally specific natural IgM Abs that activate complement and drive pathology. We demonstrate that these neoepitopes represent novel targets for the therapeutic delivery of a complement inhibitor, and possibly other payload, to the injured spinal cord.
Anti-Aβ single-chain variable fragment antibodies restore memory acquisition in a Drosophila model of Alzheimer's disease.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder triggered by the accumulation of soluble assemblies of the amyloid-β42 (Aβ42) peptide. Despite remarkable advances in understanding the pathogenesis of AD, the development of palliative therapies is still lacking. Engineered anti-Aβ42 antibodies are a promising strategy to stall the progression of the disease. Single-chain variable fragment (scFv) antibodies increase brain penetration and offer flexible options for delivery while maintaining the epitope targeting of full antibodies. Here, we examined the ability of two anti-Aβ scFv antibodies targeting the N-terminal (scFv9) and C-terminal (scFv42.2) regions of Aβ42 to suppress the progressive memory decline induced by extracellular deposition of Aβ42 in Drosophila. Using olfactory classical conditioning, we observe that both scFv antibodies significantly improve memory performance in flies expressing Aβ42 in the mushroom body neurons, which are intimately involved in the coding and storage of olfactory memories. The scFvs effectively restore memory at all ages, from one-day post-eclosion to thirty-day-old flies, proving their ability to prevent the toxicity of different pathogenic assemblies. These data support the application of this paradigm of Aβ42-induced memory loss in Drosophila to investigate the protective activity of Aβ42–binding agents in an AD-relevant functional assay.
Intelligent Twitter Spam Detection: A Hybrid Approach

Over the years there has been a large upheaval in the social networking arena. Twitter being one of the most widely-used social networks in the world has always been a key target for intruders. Privacy concerns, stealing of important information and leakage of key credentials to spammers has been on the rise. In this paper, we have developed an Intelligent Twitter Spam Detection System which gives the precise details about spam profiles by identifying and detecting twitter spam. The system is a Hybrid approach as opposed to single-tier, single-classifier approaches which takes into account some unique feature sets before analyzing the tweets and also checks the links with Google Safe Browsing API for added security. This in turn leads to better tweet classification and improved as well as intelligent twitter spam detection.
An evaluation of the National Institutes of Health Early Stage Investigator policy: Using existing data to evaluate federal policy

To assist new scientists in the transition to independent research careers, the National Institutes of Health (NIH) implemented an Early Stage Investigator (ESI) policy beginning with applications submitted in 2009. During the review process, the ESI designation segregates applications submitted by investigators who are within 10 years of completing their terminal degree or medical residency from applications submitted by more experienced investigators. Institutes/centers can then give special consideration to ESI applications when making funding decisions. One goal of this policy is to increase the probability of newly emergent investigators receiving research support. Using optimal matching to generate comparable groups pre- and post-policy implementation, generalized linear models were used to evaluate the ESI policy. Due to a lack of control group, existing data from 2004 to 2008 were leveraged to infer causality of the ESI policy effects on the probability of funding applications from 2011 to 2015. This article addresses the statistical necessities of public policy evaluation, finding administrative data can serve as a control group when proper steps are taken to match the samples. Not only did the ESI policy stabilize the proportion of NIH funded newly emergent investigators but also, in the absence of the ESI policy, 54% of newly emergent investigators would not have received funding. This manuscript is important to Research Evaluation as a demonstration of ways in which existing data can be modeled to evaluate new policy, in the absence of a control group, forming a quasi-experimental design to infer causality when evaluating federal policy.
Synthetic Factor Xa Inhibition in Acute Coronary Syndromes

Over the last decade, several advances in the management of patients with acute coronary syndrome have been made. Despite these therapeutic advances, the risk of major adverse cardiovascular events related to acute coronary syndrome remains significant. These findings have led to continued efforts to find more efficacious antiplatelet agents and anticoagulants to help reduce the risk of recurrent ischemic events. This chapter reviews the clinical data pertaining to the novel anticoagulant fondaparinux for the treatment of acute coronary syndrome.
Allegory in the Work of Philippe de Mézières

Peter S. Hawkins and Anne Howland Schotter’s collection of essays on ineffability and “the struggle of language to speak about dimensions of reality which are ineffable, that is, which lie ‘outside’ the powers of speech”, opens with a citation from St. Augustine: “What can anyone say about you, O Lord, and yet woe to him who says nothing”.1 St. Augustine’s question aptly defines the problem facing Philippe de Mezieres (c. 1327–1405) as he urged on fourteenth century society his prescriptions for the reign of the Kingdom of God on the earth; and one of the devices Philippe uses is the “inexpressibility topos”, described by Schotter as a medieval commonplace, employed by mystical poets to express the Divine.2
Two Roads to Skepticism

There are two main roads to skepticism about knowledge of the external world: a low road and a high road. The low road rests on a common but unconvincing philosophical ploy: redefining a key term to gain support for a controversial claim. Many skeptics advance their skepticism by redefining what knowledge is, specifically, by raising the standards for knowledge beyond plausibility. This strategy amounts to a low victory by high redefinition — really no victory at all. And it suffers from all the disadvantages of the fallacy of ignoratio elenchi by redefinition. Notable low-road skeptics include Descartes in the opening Meditations, David Hume, Peter Unger (1975), and Barry Stroud (1984). Part 1 of this paper assesses Stroud’s central argument for skepticism. It shows that the low road is really a dead end, that the low road is altogether ineffective against the nonskeptic.
Rhegmatogenous retinal detachments in children: Risk factors and surgical outcomes

Abstract Purpose To describe the presenting features and surgical outcomes in a series of children with rhegmatogenous retinal detachments. Design Retrospective, noncomparative, interventional case series. Participants Thirty-nine eyes of 34 children 18 years of age or younger undergoing surgery for rhegmatogenous retinal detachment. Methods Patients were identified by chart review at two affiliated tertiary care centers. Risk factors for retinal detachment were classified into four categories: (1) congenital or developmental structural ocular abnormalities, (2) trauma, (3) previous ophthalmologic surgery, and (4) preceding uveitis. Results Median age was 10 years, and 79% of patients were boys. Nine patients (26%) had bilateral retinal detachment at presentation, or experienced a detachment in their second eye before their nineteenth birthday. Every eye had at least one risk factor for retinal detachment, and more than half had risk factors in two or more categories. Structural abnormalities were most common (56%). Fifty-one percent of eyes underwent previous surgery, 36% experienced trauma, and 15% had uveitis. Detachments tended to be complex. Median follow-up was 24 months. Retinal reattachment was achieved in 79% of eyes; however, visual recovery was modest. Median preoperative and postoperative visual acuities were counting fingers and 20/400, respectively. Predictors of a poor visual outcome were: unmeasurable or light perception-only preoperative vision ( P = 0.0001), macula-off retinal detachment ( P = 0.01), the need for vitrectomy surgery ( P = 0.01), the presence of proliferative vitreoretinopathy grade C or worse ( P = 0.02), and the use of silicone oil ( P = 0.02). Conclusions Predisposing factors in pediatric retinal detachments, particularly congenital and developmental structural abnormalities, may be more common than previously reported. Modern vitreoretinal surgical techniques can help achieve retinal reattachment in most cases. Many factors contribute to the limited visual recovery in this patient population. Predictors of visual outcomes are similar to those observed in adults. Inability of the clinician to determine confidently the preoperative visual acuity is a newly identified predictor of poor visual outcomes.
Rhodopsin in immature rod outer segments.

Purpose. To test the hypothesis that rhodopsin concentration is low in immature rat rod outer segments (ROS). Methods. Microspectrophotometry (MSP) was used to assess rhodopsin absorbances in localized regions of isolated ROS from dark-adapted 13-, 19-, and 34-day-old and adult rats. Photopigment was extracted from the retinas of paired eyes in dark-adapted and light-adapted rats. One retina of each pair was treated with 9-cis retinal before extraction of photopigment. Rhodopsin with native 11-cis retinal was extracted from the fellow retina. Results. By MSP, rhodopsin absorbance was low in the short ROS of 13-day-old rats. In 19-day-old rats with ROS lengths approximately equal to those of adults, absorbance was low at the tip, but at the base, it was equal to the high absorbance at both the tip and the base in adults. The 9-cis retinal did not add absorbance to the photopigment extracts of dark-adapted retinas at any age, but it did add absorbance to extracts of the light-adapted retinas at every age. Conclusions. The MSP results show that the accumulation of rhodopsin in developing rat rods depends on increasing concentrations in localized regions. No evidence of apo-opsin is found in immature rat rods. Thus, in immature ROS regions, the low rhodopsin absorbances suggest that the amount of opsin is also low. Greater disk-to-disk spacing in immature ROS regions than in mature regions could account for these findings.
Aperiodic Order in Nanoplasmonics

In this chapter, we review our work on the engineering of aperiodic order for nanoplasmonics device applications. In particular, we discuss the optical response of arrays of metallic nanoparticles with Fourier spectral features that interpolate in a tunable fashion between periodic crystals and disordered random media, referred to as Deterministic Aperiodic Nano Structures (DANS). These plasmonic structures, conceived by designing spatial frequencies in aperiodic Fourier space, give rise to characteristic scattering resonances and localized mode patterns enhancing the intensity of optical near fields over planar surfaces and broad frequency spectra. Moreover, the distinctive interplay between photonic diffraction and near field plasmonic localization in DANS provides novel opportunities to manipulate light-matter interactions on the nanoscale for device applications to optical biosensing, plasmon-enhanced light sources, solar cells, nonlinear frequency generation, and singular optics.
S-glutathionylation of pyruvate kinase M2 is associated with metabolic reprogramming and cytokine production in the development of allergic obese airway disease

Early on-set allergic obese asthma is an important global clinical problem due to the mounting number of patients and their disease severity that is poorly controlled with available therapeutics. Alterations in metabolism and accompanying changes in redox homeostasis are known to contribute to obesity-associated diseases. Protein S-glutathionylation (PSSG) is a redox-based modification of protein cysteines involving the conjugation of glutathione to the reactive thiol group. We have discovered a direct correlation between PSSG chemistry, glycolysis and inflammation in the lungs from mice fed a high fat diet for 15 weeks. Analysis of lung tissue from obese mice identified that the glycolytic enzyme pyruvate kinase M2 (PKM2), known to catalyze the final step in glycolysis, is a target of s-glutathionylation in the lung tissue from obese mice. Furthermore, we have identified that oxidative stress and s-glutathionylation of PKM2 are increased in primary tracheal epithelial cells cultured in high glucose (25 mM) and treated with palmitate compared to MTECs cultured in normal glucose (5.6 mM). The objective of this study was to identify the s-glutathionylated proteome and investigate if s-glutathionylation of PKM2 alters its protein function to enhance inflammation in the lung tissue from mice treated with house dust mite and subjected to diet induced obesity, a model of early on-set allergic obese asthma. Here we show that s-glutathionylation of PKM2 decreases its glycolytic enzyme activity. This correlates with the upregulation of the inflammatory cytokines thymic stromal lymphopoietin (TSLP) and granulocyte-macrophage colony-stimulating factor (GM-CSF), known to contribute to steroid resistance and neutrophil infiltration in the lung during obesity. Treatment of primary mouse tracheal epithelial cells with the PKM2 small molecule activator TEPP46 attenuates mRNA expression and secretion of TSLP and GM-CSF. Overall, these findings suggest that unique redox perturbations and glycolysis may contribute to the enigmatic endotype of allergic obese asthma.
Partnering with the Department of Insurance: Coordinating a clinical and regulatory review of formulary benefit designs

This case report summarizes a partnership between Butler University College of Pharmacy and Health Sciences and the Indiana Department of Insurance. The report outlines the review of qualified health plans sold on the marketplace. Details are provided on how the College responded to requests by the department to provide a more comprehensive review of marketplace formularies. This included the development of clinical appropriateness tools for multiple disease states. The aim of this partnership was to improve prescription coverage for Indiana residents and address formulary design discrimination.
Pharmacist Statin Prescribing Initiative in Diabetic Patients at an Internal Medicine Resident Clinic

Background:Despite general increases in statin use in the United States, statin therapy may be underutilized in diabetic patients and vulnerable populations.Objective:To determine the impact of a c...
An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies.

Human cytomegalovirus (CMV) is a highly prevalent pathogen with ~60%–90% seropositivity in adults. CMV can contribute to organ rejection in transplant recipients and is a major cause of birth defects in newborns. Currently, there are no approved vaccines against CMV. The epitope of a CMV neutralizing monoclonal antibody against a conserved region of the envelope protein gH provided the basis for a new CMV vaccine design. We exploited the influenza A virus as a vaccine platform due to the highly immunogenic head domain of its hemagglutinin envelope protein. Influenza A variants were engineered by reverse genetics to express the epitope of an anti-CMV gH neutralizing antibody that recognizes native gH into the hemagglutinin antigenic Sa site. We determined that the recombinant influenza variants expressing 7, 10, or 13 residues of the anti-gH neutralizing antibody epitope were recognized and neutralized by the anti-gH antibody 10C10. Mice vaccinated with the influenza/CMV chimeric viruses induced CMV-specific antibodies that recognized the native gH protein and inhibited virus infection. In fact, the influenza variants expressing 7–13 gH residues neutralized a CMV infection at ~60% following two immunizations with variants expressing the 13 residue gH peptide produced the highest levels of neutralization. Collectively, our study demonstrates that a variant influenza virus inserted with a gH peptide can generate a humoral response that limits a CMV infection.
High voltage GaN p-n diodes formed by selective area regrowth

GaN p-n diodes were formed by selective area regrowth on freestanding GaN substrates using a dry etch, followed by post-etch surface treatment to reduce etch-induced defects, and subsequent regrowth into wells. Etched-and-regrown diodes with a 150 μm diameter achieved 840 V operation at 0.5 A/cm 2 reverse current leakage and a specific on-resistance of 1.2 mΩ·cm 2 . Etched-and-regrown diodes were compared with planar, regrown diodes without etching on the same wafer. Both types of diodes exhibited similar forward and reverse electrical characteristics, which indicate that etch-induced defectivity of the junction was sufficiently mitigated so as not to be the primary cause for leakage. An area dependence for forward and reverse leakage current density was observed, suggesting that the mesa sidewall provided a leakage path.
Productive Activity Patterns and Functional Health: A Comparison of Urban and Rural Chinese Older Adults:

This study examines the association between productive activity patterns and functional health trajectories of Chinese older adults and whether this association varies by urban/rural residence. Using three waves of the China Health and Retirement Longitudinal Study from a sample of 7,503 older adults, we first performed latent class analysis (LCA) to identify productive activity patterns based on four activities (work, caregiving, informal help, and formal volunteering). Next, multilevel regression analyses were conducted to assess the association between the identified productive activity patterns and functional health trajectories among older adults. Four productive activity patterns are identified from LCA: nonengagers, working-caregivers, workers, and helpers. We find that participation in productive activities is associated with slower functional health decline. The moderation effects of urban/rural differences are prominent across identified groups. Our findings highlight the importance of the urban/rural context in understanding productive aging and its health consequences among Chinese older adults.
Patterns of mosquito and arbovirus community composition and ecological indexes of arboviral risk in the northeast United States.

Background In the northeast United States (U.S.), mosquitoes transmit a number of arboviruses, including eastern equine encephalitis, Jamestown Canyon, and West Nile that pose an annual threat to human and animal health. Local transmission of each arbovirus may be driven by the involvement of multiple mosquito species; however, the specificity of these vector-virus associations has not been fully quantified. Methodology We used long-term surveillance data consistently collected over 18 years to evaluate mosquito and arbovirus community composition in the State of Connecticut (CT) based on land cover classifications and mosquito species-specific natural histories using community ecology approaches available in the R package VEGAN. We then used binomial-error generalized linear mixed effects models to quantify species-specific trends in arbovirus detections. Primary results The composition of mosquito communities throughout CT varied more among sites than among years, with variation in mosquito community composition among sites explained mostly by a forested-to-developed-land-cover gradient. Arboviral communities varied equally among sites and years, and only developed and forested wetland land cover classifications were associated with the composition of arbovirus detections among sites. Overall, the avian host arboviruses, mainly West Nile and eastern equine encephalitis, displayed the most specific associations among mosquito species and sites, while in contrast, the mammalian host arboviruses (including Cache Valley, Jamestown Canyon, and Potosi) associated with a more diverse mix of mosquito species and were widely distributed throughout CT. Conclusions We find that avian arboviruses act as vector specialists infecting a few key mosquito species that associate with discrete habitats, while mammalian arboviruses are largely vector generalists infecting a wide diversity of mosquito species and habitats in the region. These distinctions have important implications for the design and implementation of mosquito and arbovirus surveillance programs as well as mosquito control efforts.
Predictors of Self-Determination and Mental Health Symptoms Among Youth in Juvenile Justice Facilities:

The purpose of this article was to examine the relationships between (a) youth and facility characteristics and (b) youth risk and resilience factors (i.e., mental health, self-determination [SD]) ...
Use of Champions Identified by Social Network Analysis to Reduce Health Care Worker Patient-Assist Injuries

Background Safe patient handling and mobility (SPHM) programs recommend having champions, but have not indicated how to identify them and have confined their role to peer-based activities, limiting their ability to influence control measures. Methods In a pilot program conducted at a community access hospital in Oregon, researchers applied social network analysis (SNA) of safety advice to identify champion candidates. Candidates were invited to complete mobility, communication, and quality improvement (QI) training modules to become champions. Champions’ roles included peer-based instruction and participation in QI quarterly meetings with hospital leaders. The program process was evaluated through weekly e-mail check-ins and documentation of quarterly meetings. Outcomes were evaluated with a pre-post design, observing 12-month changes in self-reported leading indicators and Good Catch reports, as well as trends in patient-assist injuries (2011–2019). Results SNA identified six candidates, four of whom became champions. Champions completed 48 weekly logs. The quarterly meetings concerned unitwide SPHM training, equipment storage, and onboarding. Results showed significant improvements in equipment use, safety participation, and safety compliance, particularly among workers who would seek SPHM advice from champions or recently hired workers. Compared with the prior year, the Good Catch monthly entries increased from 11.69 to 28.81. The average annual incidence rate of patient-assist injuries dropped from 13.01 for the six years before the program to 3.7 per 100 full-time equivalents (FTE) for the two years after. Conclusion A program with SNA–identified and QI–trained champions improved safety outcomes after one year. Better-designed evaluations are needed to establish the replicability and long-term impact of this program.
An ISM-Band Automated Irrigation System for Agriculture IoT

In this paper, an inexpensive and user-friendly agriculture automation system is proposed by networking a collection of sensors and actuators to sense the moisture content of the soil and control the water valves for multiple irrigation zones. Using freely available frequencies in the Industrial, Scientific, and Medical (ISM) bands, multiple sensors and actuators can be networked to communicate with one another without the need to pay for subscriptions to existing cellular networks. Each sensor and actuator connect to a central communication node which connects the end-user to the sensors and actuators through a cloud server. The proposed system can act as a base for large-scale smart agriculture deployments.
Acute-on-chronic liver failure: update on pathogenesis, therapeutic targets, predictive models, and liver transplantation.

Purpose of review Acute-on-chronic liver failure (ACLF) is a clinical syndrome in patients with chronic liver disease that is associated with multiple organ failures and a high short-term mortality. Systemic inflammation is suggested to play a key role in its pathogenesis, although the precise causative mechanism is unknown. The purpose of this review is to present and discuss new findings related to: mechanisms underlying ACLF, therapeutic targets, risk prediction models for developing ACLF, and liver transplantation for ACLF. Recent findings Recent studies of ACLF pathophysiology classified the immunosuppressive phenotype in monocytes. Investigation of therapeutic strategies identified inhibition of toll-like receptor-4 (TLR-4) and glutamine synthetase (GLUL) as potential targets. Recent studies identified novel risk prediction models for developing ACLF and enhanced our understanding of liver transplantation for ACLF to guide clinicians in determining that patients will benefit from transplantation. Summary Improved knowledge on the pathogenesis of ACLF and identification of TLR-4 and GLUL may lead to clinical trials to study the efficacy of these novel therapeutic targets for patients with ACLF. Liver transplantation is the only current treatment for ACLF. Given the limited availability of donor organs, recent studies have identified ACLF patients who may merit the highest waitlist priority.
A Systematic Investigation of Coupling Between Dark and Bright Polaritons for Infrared Sensing Design

An emerging class of materials for nanophotonics, hyperbolic metamaterials (HMM), opens a wide range of potential technologies. From micro to nano scales, engineering the features of these materials as a function of a host geometry illustrates exotic functionalities. Phonon polaritons (PhPs) with a dielectric host and plasmon polaritons (PPs) with a metallic host are the most common results from light-matter interactions. Accurate analysis enables researchers to engineer unique features, like high dispersion, hence tailored device designs. This work builds upon previous works in this field; the first focused on the possible coupling between PhPs (or the dark modes) and PPs (or the bright modes) whereas the second introduces a mature technique for the analysis. This study explores all possible coupling scenarios between a gold (Au) rod and a hexagonal boron nitride (hBN) rod. In fact, these two materials are established in infrared sensing where Au supports plasmons while hBN provides surface and volume phonons. Varying the geometry of the rods reveals the nature, the distribution, and the coupling of possible modes after analysis. Consequently, a novel procedure for optimal design of IR sensing devices is presented. This numerical platform provides insights into the design of IR sensing structures.
Lineage Reprogramming of Effector Regulatory T Cells in Cancer

Regulatory T-cells (Tregs) are important for maintaining self-tolerance and tissue homeostasis. The functional plasticity of Tregs is a key feature of this lineage, as it allows them to adapt to different microenvironments, adopt transcriptional programs reflective of their environments and tailor their suppressive capacity in a context-dependent fashion. Tregs, particularly effector Tregs (eTregs), are abundant in many types of tumors. However, the functional and transcriptional plasticity of eTregs in tumors remain largely to be explored. Although depletion or inhibition of systemic Tregs can enhance anti-tumor responses, autoimmune sequelae have diminished the enthusiasm for such approaches. A more effective approach should specifically target intratumoral Tregs or subvert local Treg-mediated suppression. This mini-review will discuss the reported mechanisms by which the stability and suppressive function of tumoral Tregs are modulated, with the focus on eTregs and a subset of eTregs, follicular regulatory T (TFR) cells, and how to harness this knowledge for the future development of new effective cancer immunotherapies that selectively target the tumor local response while sparing the systemic side effects.
Affective Justice: The International Criminal Court and the Pan-Africanist Pushback

In Affective Justice: The International Criminal Court and the Pan-Africanist Pushback, Kamari Maxine Clarke makes two major points; both are well taken. The first is that Pan-Africanist responses ...
Leveraging the Treg-intrinsic CTLA4-PKCη signaling pathway for cancer immunotherapy.

Background Our previous studies revealed a critical role of a novel CTLA4-protein kinase C-eta (PKCη) signaling axis in mediating the suppressive activity of regulatory T cells (Tregs) in antitumor immunity. These studies have employed adoptive transfer of germline PKCη-deficient (Prkch−/−) Tregs into Prkch+/+ mice prior to tumor implantation. Here, we extended these findings into a biologically and clinically more relevant context. Methods We have analyzed the role of PKCη in antitumor immunity and the tumor microenvironment (TME) in intact tumor-bearing mice with Treg-specific or CD8+ T cell-specific Prkch deletion, including in a therapeutic model of combinatorial treatment. In addition to measuring tumor growth, we analyzed the phenotype and functional attributes of tumor-infiltrating immune cells, particularly Tregs and dendritic cells (DCs). Results Using two models of mouse transplantable cancer and a genetically engineered autochthonous hepatocellular carcinoma (HCC) model, we found, first, that mice with Treg-specific Prkch deletion displayed a significantly reduced growth of B16–F10 melanoma and TRAMP-C1 adenocarcinoma tumors. Tumor growth reduction was associated with a less immunosuppressive TME, indicated by increased numbers and function of tumor-infiltrating CD8+ effector T cells and elevated expression of the costimulatory ligand CD86 on intratumoral DCs. In contrast, CD8+ T cell-specific Prkch deletion had no effect on tumor growth or the abundance and functionality of CD8+ effector T cells, consistent with findings that Prkch−/− CD8+ T cells proliferated normally in response to in vitro polyclonal or specific antigen stimulation. Similar beneficial antitumor effects were found in mice with germline or Treg-specific Prkch deletion that were induced to develop an autochthonous HCC. Lastly, using a therapeutic model, we found that monotherapies consisting of Treg-specific Prkch deletion or vaccination with irradiated Fms-like tyrosine kinase 3 ligand (Flt3L)-expressing B16–F10 tumor cells post-tumor implantation significantly delayed tumor growth. This effect was more pronounced in mice receiving a combination of the two immunotherapies. Conclusion These findings demonstrate the potential utility of PKCη inhibition as a viable clinical approach to treat patients with cancer, especially when combined with adjuvant therapies.
The effect of WAAM process parameters on process conditions and production metrics in the fabrication of single-pass multi-layer wall artifacts

The present work seeks to understand the impact of varying dwell time and input deposition power on part quality and overall production time for wire arc additive manufacturing. In this work, multi-layer wall geometries were deposited under different input power conditions without affecting the material deposition rate by setting traverse speed and wire feed speed constant and varying the contact tip-to-workpiece distance and the deposition power settings. Current and voltage data and optical imaging of the deposition zone were captured in situ, and wall geometry was characterized using laser scanning, so to understand the applicability of these methods for determining part height in situ. The present results demonstrate that alternating dwell times with lower input deposition power can result in significantly reduced overall production time and minimal material underbuilding, despite increased deposition geometry width. Furthermore, it is shown that while elimination of process dwell results in severe underbuilding of the deposition, it also yields the highest production rate for a hybrid-finished (e.g., deposited, machined) wall in terms of mm in build direction per minute and the highest buy-to-fly ratio.
Two kinds of space in psychophysics

Colors can be represented as points in a 3-D space. We have various color spaces and each is a means to specify colors according to a specified principle. We are not necessarily obliged to regard that all aspects of the spatial representation are meaningfully related to perceptual properties of colors. In psycho-physics, we have a space that is not. a means of representation. It is visual space (VS) that one perceives in front of the self. It is a perceptual reality as the final product of a long series of processes starting from retinal image of the physical space (X). In spite of that VS is based on multiple glances, it is stable and structured in accordance with the condition of X. Hence, it is a challenging problem to make explicit its geometrical properties under various conditions of X. Studies of the author on the two above-mentioned spaces will be summarized. Psychophysical scaling and construction of formal models will play fundamental roles.
Low energy dislocation structures due to fatigue softening.

The evolution of dislocation structures in 6% prestrained steel 1018 during fatigue has been studied by TEM. The dislocations are quite movable, the loose cells quickly change to "checkboard" structures, in which the main cell walls lie about{100}. Then, the low energy dislocation structures-dipolar walls and laby- rinth structures are evolved. The characteristic of labyrinth and the orientation of di- polar walls are quite similar to f. c. c. crystal, it indicates the energy state of system and the moving ability of dislocations are important factors affecting softening pro- cess, rather than the slip geometric characters of dislocations and details of disloca- tions. The decreasing in misorientation between adjoining cells and internal stress are discussed.
A review of plutonium releases from the Savannah River Site, subsequent behavior within terrestrial and aquatic environments and resulting dose to humans

Abstract This chapter reviews two decades of research on plutonium in terrestrial and aquatic environments of the Savannah River Site (SRS), a nuclear production facility covering 800 km2 of South Carolina, USA. Sources and quantities of Pu released over the facility's 40 years of operation are summarized. Some 160 GBq of 238Pu and 239Pu were released in isotopic ratios that allowed researchers to distinguish site emissions from global fallout. The ratios also proved to be a powerful tool useful for identifying major pathways through which Pu moved in the environment. Two major lines of research are reviewed; one examining Pu transport through agricultural systems typical of the southeastern United States, the other examining Pu dynamics within lake systems. Regardless of the crop studied, Pu contamination of plants was dominated by the retention of Pu-bearing particles on plant surfaces, from direct deposition and resuspension, rather than root uptake and translocation of Pu within the plant. Large-scale commercial harvesting of contaminated agricultural crops revealed that mechanized harvesting increased Pu contamination of crops. Differences in Pu concentrations among crops were due largely to external plant morphologies that affected soil loading. Studies on Pu transport in aquatic systems showed that over 99% of the Pu inventory was within lake sediments. Persistent and complex annual cycles still exist for Pu within the lake systems studied, some 20 years after the contamination event. Field studies and modeling helped discern the relative importance of anoxic remobilization from the sediments, hydrologic mixing and sedimentation on the Pu cycle within lakes. Remobilization of Pu in the winter appears to contribute more to the seasonal cycle than does the more commonly observed mechanism of remobilization in summer anoxic waters due to associated Fe-Mn redox phenomena. Doses to humans from Pu releases were also reviewed and found to be less than those acquired from naturally occurring radionuclides or from 137Cs releases. Maximum dose equivalents (85 tzSv) to an individual at the site boundary would have occurred in 1955 and the population dose due to releases that occurred from 1954 to 1989 was 7 person-Sv.
Cardiac Output, Indicator Dilution Measurement of

Knowledge of cardiac output is important for determining the hemodynamic status of an individual. A direct measurement of cardiac output is difficult, since to obtain a direct measurement would require collecting and measuring all of the blood pumped from the heart. Therefore it is necessary to develop indirect methods for the measurement of this important parameter. The Fick and other indicator dilution methods are two of the invasive procedures that produce good results. The fundamental equations and theory necessary to understand the indicator dilution methods of measuring cardiac output including the steady-state Fick method, the transient indicator dilution methods with recirculation, and the thermal dilution method are developed and their application is explained. Keywords: cardiac output; indicator dilution; thermal dilution
Conditional Rewriting Logic: Deduction, Models and Concurrency

Term rewriting has so far been understood almost exclusively as a technique for equational reasoning. This paper proposes a much broader interpretation in which term rewriting can be used both as a semantic foundation and as a programming paradigm in areas such as reactive systems, concurrency theory and object-oriented programming that do not fit naturally within the functional world of equational logic. The interpretation proposed views conditional rewriting as a logic in its own right, with its own proof theory and with a very general model theory of wide applicability. The logic is sound and complete and admits initial models. Equational logic appears as a special refinement of the general framework; this supports a natural unification of the functional and concurrent programming paradigms with a purely declarative style. Throughout the paper, the concurrent nature of term rewriting is emphasized; the role of rewriting as a unified model of concurrency is also discussed.
Measurement of holmium Rydberg series through magneto-optical trap depletion spectroscopy

We report measurements of the absolute excitation frequencies of $^{165}\mathrm{Ho}$ $4{f}^{11}6sns$ and $4{f}^{11}6snd$ odd-parity Rydberg series. The states are detected through depletion of a magneto-optical trap via a two-photon excitation scheme. Measurements of 162 Rydberg levels in the range $n=40$--101 yield quantum defects well described by the Rydberg-Ritz formula. We observe a strong perturbation in the $ns$ series around $n=51$ due to an unidentified interloper at 48515.47(4) ${\mathrm{cm}}^{\ensuremath{-}1}$. From the series convergence, we determine the first ionization potential ${E}_{\mathrm{IP}}=48565.910(3)$ ${\mathrm{cm}}^{\ensuremath{-}1}$, which is three orders of magnitude more accurate than previous work. This work is an important step towards using Ho atoms for collective encoding of a quantum register.
Selenosis, Hepatic Selenium Accumulation, and Plasma Glutathione Peroxidase Activity in Chicks as Affected by a Factor in Linseed Meal

Linseed meal has previously been reported to contain an organic factor that reduces toxicity of selenium in animals. The purpose of the studies reported here was to obtain information on the mechanism of action of the linseed meal factor in counteracting selenosis in chicks. Feeding a diet containing 20% linseed meal to chicks partially counteracted the growth depression caused by including high levels of selenium (10-40 ppm) in the diet. In contrast to the rat, chicks fed diets containing selenium did not accumulate significantly more of the element per unit of liver dry matter when the diet contained linseed meal, and at two selenium levels accumulated significantly less. Linseed meal did not interfere with the absorption of an oral dose of 75Se as measured by tissue retention 24 hours later. A methanol extract of linseed meal did not interfere with the normal increase in plasma glutathione peroxidase activity in chicks fed diets supplemented with low levels of selenium even though the extract counteracted the growth depression obtained by adding 20 ppm selenium. Linseed meal contains a factor that interacts with selenium in the tissues in some unknown way to reduce the toxic effects of the element, but does not prevent normal synthesis of glutathione peroxidase.
Phase II trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma

ABSTRACT Background Enhanced phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key adaptive changes accounting for epidermal growth factor receptor (EGFR) inhibitor-resistant growth in head and neck squamous cell carcinoma (HNSCC). We designed a phase II clinical trial of EGFR tyrosine kinase inhibitor (TKI), erlotinib, in association with the mTOR inhibitor, everolimus, based on the hypothesis that the downstream effects of Akt through inhibition of mTOR may enhance the effectiveness of the EGFR-TKI in patients with recurrent/metastatic HNSCC. Patients and methods Patients with histologically or cytologically confirmed platinum-resistant HNSCC received everolimus 5 mg and erlotinib 150 mg daily orally until disease progression, intolerable toxicity, investigator or patient decision. Cytokines and angiogenic factors profile, limited mutation analysis and p16 immunohistochemistry status were included in the biomarker analysis. Results Of the 35 assessable patients, 3 (8%) achieved partial response at 4 weeks, 1 confirmed at 12 weeks; overall response rate at 12 weeks was 2.8%. Twenty-seven (77%) patients achieved disease stabilization at 4 weeks, 11 (31%) confirmed at 12 weeks. Twelve-week progression-free survival (PFS) was 49%, median PFS 11.9 weeks and median overall survival (OS) 10.25 months. High neutrophil gelatinase lipocalin (P = 0.01) and vascular endothelial growth factor (VEGF) (P = 0.04) plasma levels were significantly associated with worse OS. Conclusions The combination of erlotinib and everolimus did not show significant benefit in unselected patients with platinum-resistant metastatic HNSCC despite a manageable toxicity profile. Markers of tumor invasion and hypoxia identify a group of patients with particularly poor prognosis. Clinical trial number NCT00942734.
Protein recovery from bacterial cell debris using crossflow microfiltration with backpulsing

Abstract Protein recovery from a bacterial lysate was accomplished using crossflow microfiltration with rapid backpulsing. The net flux with backpulsing was found to increase with increasing forward and backpulse pressures, increase to a maximum and then decrease with increasing forward filtration time between backpulses (or decreasing backpulse frequency), increase weakly with increasing shear rate, and decrease strongly with increasing concentration in the feed. Variation of the operating conditions for a dilute feed of 0.0025 g cell debris/g suspension on a wet cell mass basis yielded net flux values as high as 4.5×10 −3 cm/s (160 1/m 2 h) with backpulsing, compared to a steady-state value of 4.0×10 −4 cm/s (14 1/m 2 h) for similar conditions without backpulsing. The optimal backpulse frequency was found to be very high, about 2.5 times per second, for the minimum backpulse duration of 0.09 s. However, the performance of the backpulsing operation declined with increasing concentration of cell debris, with no flux improvement achieved for concentrations greater than 0.01 g cell debris/g suspension. Nevertheless, 100% protein transmission with backpulsing was achieved for all conditions investigated, compared to an average value of 60% transmission in the absence of backpulsing. Thus, rapid backpulsing is an effective method for the recovery of protein from dilute cell debris.
Sex-Role Expectations Associated with Specific Household Tasks: Perceived Age and Employment Differences:

Although sex and age appropriate behavior has been examined, little attention has been given to expectations for the redistribution of household tasks. A questionnaire administered to unmarried college students provides data on expectations for 10 household tasks in three age and employment situations and projections for one's own marriage. Neither age nor work status alone was the basis for the ascription of norms involving domestic tasks. But both youth and dual-career marriage were associated with more shared activities. Future research should focus on the relationship between general attitudes toward sex-role behavior and the redistribution of household tasks.