cssi/SciSciGPT-SciSciNet huggingface dataset:
The ubiquitin-proteasome system regulates lung inflammation by targeting IL-33 receptor ST2L stability

A lung injury is characterized as acute respiratory failure resulting from acute pulmonary inflammation. Cytokine release and cytokine-mediated signaling contribute to pathogenesis of lung inflammatory diseases. Ubiquitin-proteasome system regulates turnover of majority of intracellular proteins. Here, we show a new orphan protein that exhibits the prototypical behavior of a SCF E3 ligase subunit; termed FBXL19 (F-box protein 19, SCFFBXL19) regulates lung inflammation and injury. ST2L, a receptor of IL-33, is instable in response to IL-33 treatment. IL-33 induces ST2L ubiquitination and degradation in the proteasome system. FBXL19 targets ST2L and mediates ST2L ubiquitination and turn over. Lysine 326 within ST2L is an ubiquitin acceptor site and lysine 326 mutant of ST2L enhances its stability. IL-33-ST2L pathway plays a critical role in LPS-induced lung injury. To investigate the effect of FBXL19 in LPS-induced lung injury, we expressed a FBXL19-tdTomato fluorescence fusion protein or a lenti-control-tdTomato in mice and in vivo expression of these constructs in lung tissue was analyzed by fluorescence scanning. TUNEL assays show that FBXL19 over-expression in mice blocked LPS intratracheal challenge-induced cell death. Further, FBXL19 administration effectively attenuated LPS-induced pulmonary inflammation histologically, alveolar protein leak, and reduced IL-6 and TNFα levels in BAL fluid. These results suggest that FBXL19 exhibits an anti-inflammatory property and protects against LPS-induced lung inflammation and injury via targeting IL-33-ST2L pathway.
Privacy-Preserving Tabu Search for Distributed Graph Coloring

Combinatorial optimization is a fundamental problem found in many fields. In many real life situations, the constraints and the objective function forming the optimization problem are naturally distributed amongst different sites in some fashion. The typical approach is to collect all of this information together and centrally solve the problem. However, this requires all parties to completely share their information, which may lead to serious privacy issues. Privacy-preserving techniques need to be developed to enable distributed optimization with limited information disclosure. A further complicating factor is that combinatorial optimization problems are typically NP-hard, requiring approximation algorithms or heuristics to provide a practical solution. In this paper, we focus on a very well known hard problem -- the distributed graph coloring problem, which has been utilized to model many practical problems in scheduling and resource allocation. We propose an efficient protocol that securely solves this problem based on the tabu search metaheuristic. Specifically, our solution uses a distributed local search algorithm to find a good solution. We analyze the security of our approach and experimentally demonstrate the effectiveness of our approach.
Noncollinear wave mixing of attosecond XUV and few-cycle optical laser pulses in gas-phase atoms: Toward multidimensional spectroscopy involving XUV excitations

A method to realize table-top attosecond spectroscopy is demonstrated in which a link is provided between background-free nonlinear signals and the time evolution of individual quantum pathways.
Japanese Votive Paintings and Issues of Display

Buddhist temples and Shinto shrines throughout Japan are dotted with a variety of paintings made to serve votive purposes. They are part of a long tradition dating back to the seventh century. Earl...
The İnönü era translation movement: classics in the service of Turkish nationalism

ABSTRACTIn 1939, a comprehensive and systematic translation movement began in Turkey under the supervision of ‘Turkish humanists’ who believed in the survival of the traces of ancient Greek culture within the daily lives and literary traditions of Anatolian peoples. This article, which is based on the premise that translations should be discussed as records of cultural contestation and ideological struggles rather than as simple linguistic transpositions, examines this state-sanctified movement vis-a-vis the nationalist project. The Turkish humanists’ belief in a geography-based nationalism was promoted by the state insofar as their attempt to influence the direction of the development of ‘nascent’ Turkish identity and literature coincided with the aims of the state. Ostensibly initiated to introduce the Turkish reading public to Western classics, the translated texts were used, I argue, as a means in fashioning and controlling the emergent national identity during the first decade of the Inonu era.
Educational Attainment, Citizenship, and Black American Women in Elected and Appointed National Leadership Positions

This article examines the issue of American citizenship and how it is related to Black Americans, especially from the perspectives of educational attainment and national political leadership positions (focusing on the U.S. Senate, office of governor, and the U.S. Supreme Court). The article presents seven interrelated conceptual or theoretical perspectives of American citizenship (Three Citizenships; Gender; Equality; Race; Belonging; Military Service; and Protestant Christianity), and where Black Americans (especially Black women) fit in them. The article claims that while Black American women have made substantial progress in college degree attainment, they have done so at a very high financial cost. The article claims that compared with other groups in the society, the gains in educational attainment made by Black American women have not resulted in them being elected or selected to these national leadership positions. Among the factors presented for this exclusion of Black women are: lack of strong support from Black American male leaders and institutional support; ambition; first occupy public office within the states of the Union; they must become moderate politicians; perception that Black women have more privileges in the society than Black men and other groups; and negative media portrayal of Black female candidates. The article claims that despite being one of the oldest and most native groups in the United States, with over nine out of every 10 of them being native-born citizens, Black American women in particular tend to have the characteristics of non-citizens.
Antibody blockade of semaphorin 4D promotes infiltration of activated tumor infiltrating leukocytes and inhibits tumor growth. (TUM7P.1030)

Semaphorin 4D (SEMA4D, CD100) and its receptor plexin-B1 are broadly expressed in cancer and expression correlates with invasive disease. A novel function of SEMA4D, regulating immune cell infiltration and activity in the tumor microenvironment (TME), is described. Antibody neutralization of SEMA4D enhances recruitment of activated antigen presenting cells and lymphocytes into the TME, shifting the balance of cells and cytokines toward increased Th1 and reduced immunosuppression. This orchestrated change in the tumor architecture was associated with durable tumor rejection and immunologic memory in several syngeneic tumor models. The immunomodulatory activity can be enhanced by combination with other immunotherapies. Strikingly, in some models, the combination of anti-SEMA4D antibody with immune checkpoint blockade acts synergistically to reverse tumor growth. Inhibition of SEMA4D represents a novel mechanism and therapeutic strategy to promote functional immune infiltration into the tumor and inhibit tumor progression. A humanized antibody, VX15/2503, has completed a Phase I prospective multiple ascending dose trial in 42 adult patients with advanced refractory solid tumors, in which the highest doses were well tolerated. Patients with the longest duration of treatment, 48-55 weeks, included colorectal, breast, and a papillary thyroid patient, who had a partial response by RECIST. A phase 1b/2a trial of combination therapy is planned.
Hurthle Cell Lesions

Thyroid tumors composed predominantly of Hurthle cells are a group of uncommon tumors recognized by the WHO as an oncocytic subset of follicular neoplasms. For this reason, Hurthle cell neoplasms can also be called “follicular neoplasms with oncocytic features.” Although the name was coined by Ewing in 1928, the Hurthle cell was originally described by Azkanazy in 1898 as a polygonal cell with abundant granular cytoplasm, the latter reflecting the abundance of mitochondria present in the cytoplasm. Hurthle cells have an enlarged round to oval nucleus with a prominent nucleolus. Other names for this cell have included Azkanazy cells, oxyphilic cells, and oncocytes. Hurthle cells are essentially nonfunctional, and Hurthle cell nodules are almost always cold nodules using radionuclide scans.
Human and Animal Retroviruses: HIV-1 Infection Is a Risk Factor for Malignancy

Three malignancies are prognostic indicators of acquired immunodeficiency syndrome due to human immunodeficiency virus type 1 (HIV-1) infection: Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and invasive cervical carcinoma. Each is associated with a slowly transforming oncogenic viral coinfection: human herpesvirus 8, Epstein–Barr virus, and human papillomaviruses, respectively. Five other malignancies occur at increased frequencies among those infected with HIV-1. Anti-HIV-1 treatment in synch with management of chemotherapeutic regiment significantly improves clinical outcomes in cancer patients infected with HIV-1. HIV-1 immunodepletion, cytokine stimulation, and paracrine activity of Tat are the key pathophysiological drivers of HIV-1-associated cancer. These activities stand in contrast to the activation of cellular proto-oncogenes by avian and murine retroviruses, and cell transformation by the viral oncoprotein of human leukemia virus type 1. Remarkably, HIV-1 does neither. Instead, HIV-1 stands as a natural model system to view the fundamental connection between the human immune response and neoplastic progression that are manifest of coinfection or lifestyle behaviors. The connections are wired between and among cell lineages by cytokine signaling, paracrine interactions, and secondary effects of immune disbalance. The next frontiers of exploration are to understand the interrelationship between the innate response to HIV-1 and other chronic virus infections and to define the microRNA signatures that modulate these biological processes. The outcomes are likely to converge and build new bridges from the bench to the bedside.
A Pragmatic Evaluation of Three Models of Disability in Special Education

This paper explains and utilizes the philosophy of pragmatism in the evaluation of three models of disability used in disability research and services. The three models are (1) the functional limitations model, (2) the minority group model, and (3) the social construction model. Pragmatism emphasizes the moral and political utility of ideas, the ways that a person, group, or culture can use a concept or belief to guide action in service to a democracy that values diversity, individuality, and equality. This analysis evaluates the practical usefulness of these three models in light of these democratic priorities.
Adjusting subjectively rated scores

In the context of educational testing, estimation of the variance components and of the reliability coefficients is at best of secondary importance to the pivotal task — assigning scores to the essays (performances, problem solutions, or the like) in a way that reflects their quality as faithfully as possible. In ideal circumstances, this would correspond to reconstructing the true score α i for each essay. A more realistic target is to get as close to α i as possible. This chapter discusses improvements on the trivial estimator of the true score, the mean score over the K sessions, \({y_{i,.}} = ({y_{i,{j_{i1}}}} + \ldots + {y_{i,{j_{iK}}}})/K,\) by means of several adjustment schemes. The variance components, σ a 2 and σ b 2 and σ e 2 play an important role in these schemes. To motivate them, consider the following extreme cases: when everybody has the same true score, σ a 2 = 0, each examinee should be given the same score, irrespective of the grades given by the raters. Similarly, when the raters vary a great deal in their severities (large σ b 2 ), or the rating is very inconsistent (large σ a 2 ), an extreme score (say, 0 or 9 on the scale 0–9) is not a strong evidence of very poor or very high quality of the essay. On average, it may be prudent to ‘pull’ the extreme scores closer to the mean, so as to hedge our bets against the largest possible errors.
Two Forms of Synaptic Depression Produced by Differential Neuromodulation of Presynaptic Calcium Channels.

Summary Neuromodulators are important regulators of synaptic transmission throughout the brain. At the presynaptic terminal, neuromodulation of calcium channels (CaVs) can affect transmission not only by changing neurotransmitter release probability, but also by shaping short-term plasticity (STP). Indeed, changes in STP are often considered a requirement for defining a presynaptic site of action. Nevertheless, some synapses exhibit non-canonical forms of neuromodulation, where release probability is altered without a corresponding change in STP. Here, we identify biophysical mechanisms whereby both canonical and non-canonical presynaptic neuromodulation can occur at the same synapse. At a subset of glutamatergic terminals in prefrontal cortex, GABAB and D1/D5 dopamine receptors suppress release probability with and without canonical increases in short-term facilitation by modulating different aspects of presynaptic CaV function. These findings establish a framework whereby signaling from multiple neuromodulators can converge on presynaptic CaVs to differentially tune release dynamics at the same synapse.
Recent Results from Evaluation of Soft Wearable Robots in Clinical Populations

We have been on developing new approaches to design, manufacture, and control soft wearable robotic devices and characterizing their performance through biomechanical and physiological studies so as to further the scientific understanding of how humans interact with such machines. Example application areas include enhancing the mobility of healthy individuals such as soldiers walking with a heavy load, restoring the mobility of patients with gait deficits such as those poststroke, and assisting those with upper extremity weakness to perform activities of daily living such as patients with a spinal cord injury. This abstract summarizes recent results from evaluation of these devices in clinical populations.
Resident autonomy in the operating room: Does gender matter?

Abstract Introduction Previous data examining the effect of gender on surgical trainee autonomy is lacking. We hypothesized that female general surgery residents have less autonomy than males during laparoscopic cases. Methods We retrospectively reviewed factors associated with level of guidance needed during laparoscopic procedures as reported on intraoperative procedure feedback forms and on FLS tasks from one institution from 2013 to 2016. Data collected included resident and attending gender, level of guidance needed, PGY level, case characteristics, resident intraoperative performance, and skills lab FLS performance. Univariate and multivariate analyses were performed using a mixed-effects regression model. Results We analyzed data from 106 PGY1-PGY5 residents (51% Female) and 104 attendings (26% Female). Female resident gender was associated with more intraoperative guidance in univariate (p = 0.019) and multivariate analysis (p = 0.034). Technical performance between genders was similar. Conclusions This study demonstrated gender-based inequality in intraoperative autonomy even after controlling for technical performance, PGY level, and case factors.
Smart PCA

PCA can be smarter and makes more sensible projections. In this paper, we propose smart PCA, an extension to standard PCA to regularize and incorporate external knowledge into model estimation. Based on the probabilistic interpretation of PCA, the inverse Wishart distribution can be used as the informative conjugate prior for the population covariance, and useful knowledge is carried by the prior hyperparameters. We design the hyperparameters to smoothly combine the information from both the domain knowledge and the data itself. The Bayesian point estimation of principal components is in closed form. In empirical studies, smart PCA shows clear improvement on three different criteria: image reconstruction errors, the perceptual quality of the reconstructed images, and the pattern recognition performance.
Celebrating the Birthday Problem.

What makes the problem so amazing is that the actual probabilities don't correspond with one's intuition. For example, with = 30, a person might intuitively reason as fol lows: If there are 30 people with birthdays randomly distributed throughout the year, then the probability of two or more birth days falling on the same date must be 30 out of 365, or roughly one in twelve. Some people, allowing for some error in their calculations and intuition, would not be surprised at 20 percent probability. But the actual probability is about 71 percent, as seen in table 1. With = 60 people, the probability is 99 percent?a virtual cer tainty. The paradox results from an error in the intuitive approach. The results cited in table 1 are obtained by calculating the probability of matching someone's birth day in the gathering to a date selected at random from the calendar (assuming that everyone has a different birthday). The paradoxical nature and the useful ness of the birthday problem can be better explored by changing its emphasis to some TABLE l The Probability That Among People at Least Two Will Have the Same Birthday
Nutrients influence the multi-trophic impacts of an invasive species unaffected by native competitors or predators

Abstract Non-native species often lead to undesirable ecological and environmental impacts. Two hypotheses that predict establishment of non-native species are enemy release and biotic resistance. Support for these hypotheses in freshwater invasions is mixed. Experiments combined with field observations provide a complementary approach to understanding how interactions between native and non-native species lead to enemy release or biotic resistance. We tested experimentally whether these hypotheses provided insights into the invasion of the banded mystery snail (Viviparus georgianus), which has invaded the Great Lakes region and northeastern Unites States (US) from the southeastern US. Because freshwater systems vary widely in their nutrient concentrations due to natural and anthropogenic processes, we tested whether nutrient additions altered competitive and predatory interactions that regulate mechanisms of enemy release or biotic resistance. We evaluated the status of the mystery snail invasion in a 3-year field survey of Lake George (NY, US) to identify if field observations supported any experimental conclusions. The presence of the banded mystery snail led to a 14% and 27% reduction in biomass of a native competitor under low- and high-nutrient concentrations, respectively. The mystery snail also triggered a 29% biomass loss of a native snail predator, but only in low-nutrient concentrations. Field surveys indicated that the mystery snail dominated the snail community; of seven snail species, it comprised 77% of all snails. Results from the field surveys combined with experimental results indicate that neither competitors nor predators have likely suppressed the invasion of the banded mystery snail. This conclusion is consistent with competitive- and predatory-enemy release as we found no indication of biotic resistance via competition or predation from native species. Our results further highlight that the post-establishment impacts of invasive species are altered by the trophic state of freshwater ecosystems.
Vastly extended drug release from poly(pro-17β-estradiol) materials facilitates in vitro neurotrophism and neuroprotection

Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17β-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vastly prolonged E2 release, we report first-generation poly(pro-E2) biomaterial scaffolds that release E2 at nanomolar concentrations over the course of 1-10 years via slow hydrolysis in vitro. As a result of their finely tuned properties, these scaffolds demonstrate the ability to promote and guide neurite extension ex vivo and protect neurons from oxidative stress in vitro. The design and testing of these materials reported herein demonstrate the first step towards next-generation implantable biomaterials with prolonged release and excellent regenerative potential.
Optical films of glassy cholesteric liquid crystal for simultaneous selective wavelength reflection and circular dichroism (Conference Presentation)

Cholesteric glassy liquid crystal films (Ch-GLCs) are solid-state materials with unique optical properties derived from embedded supramolecular structure. Owing to their ability to be processed into thin films combined with their remarkable durability, Ch-GLCs are increasingly attractive for variety of optical operations including single element circular polarization, notch filtering, and polarized luminescence. Ch-GLCs are most frequently processed into monodomain thin films to exhibit a helical stack of in-plane chiral mesogens with orientation that varies periodically through the thickness of the film. Two distinct optical phenomena emerge from this kinetically frozen supramolecular order: (i) selective reflection and transmission of right and left handed circular polarized light owing to the periodic structure defined by the optical pitch-length and (ii) circular dichroism arising from light-absorbing chiral constituents. In our current experiments, we are modulating the spectral range of the stopband through thin film processing, and we are doping GLC films with absorbing dyes to achieve circular dichroism over different spectral ranges. Our objective is to understand the overlap between stop-band behavior and circular dichoism to enable polarization into the SWIR range as well as optical isolation of incident light. The effort is part of a new center, Advanced Materials for Powerful Lasers (AMPL), based at the University of Rochester.
Covariance Regression Models for Studying Treatment Effect Heterogeneity across One or More Outcomes: Understanding How Treatments Shape Inequality.

Causal analyses typically focus on average treatment effects. Yet for substantive research on topics like inequality, interest extends to treatments’ distributional consequences. When individuals d...
Crystal structure of (R,S)-2-hy­droxy-4-(methyl­sulfan­yl)butanoic acid

The title compound, a major animal feed supplement, abbreviated as HMTBA and alternatively called dl-me­thio­nine hy­droxy analogue, C5H10O3S, (I), was isolated in pure anhydrous monomeric form. The melting point is 302.5 K and the compound crystallizes in the monoclinic space group P21/c, with two conformationally non-equivalent mol­ecules [(IA) and (IB)] in the asymmetric unit. The crystal structure is formed by alternating polar and non-polar layers running along the bc plane and features an extensive hydrogen-bonding network within the polar layers. The Hirshfeld surface analysis revealed a significant contribution of non-polar H⋯H and H⋯S inter­actions to the packing forces for both mol­ecules.
Changes in racial and ethnic disparities in lumbar spinal surgery associated with the passage of the Affordable Care Act, 2006-2014.

Abstract BACKGROUND CONTEXT Since implementation of the Patient Protection and Affordable Care Act (ACA) in 2010, more Americans have health insurance, and many racial/ethnic disparities in healthcare have improved. We previously reported that Black and Hispanic patients undergo surgery for spinal stenosis at lower rates than do white patients. PURPOSE To assess changes in racial/ethnic disparities in rates of lumbar spinal surgery after passage of the ACA. STUDY DESIGN Retrospective analysis. PATIENT SAMPLE Approximately 3.2 million adults who underwent lumbar spinal surgery in the US from 2006 through 2014. OUTCOME MEASURES Racial disparities in discharge rates before versus after ACA passage. METHODS Using the Nationwide Inpatient Sample, the U.S. Census Bureau Current Population Survey Supplement, and International Classification of Diseases, Ninth Revision, Clinical Modification, criteria for definite lumbar spinal surgery, we calculated rates of lumbar spinal surgery as the number of hospital discharges divided by population estimates and stratified patients by race/ethnicity after controlling for sociodemographic characteristics. Calendar years were stratified as before ACA passage (2006–2010) or after ACA passage (2011–2014). Poisson regression was used to model hospital discharge rates as a function of race/ethnicity before and after ACA passage after adjustment for potential confounders. RESULTS All rates are expressed per 1,000 persons. The overall median discharge rate decreased from 1.9 before ACA passage to 1.6 after ACA passage (p CONCLUSION Small but significant decreases occurred in racial/ethnic disparities in hospital discharge rates for lumbar spinal surgery after ACA passage.
Agriculture: A Brief History

An introduction to pesticides in agriculture with emphasis on weed science, herbicides, and their dominance of developed country agriculture and much of the world. It ends with the paradox of pesticide use in agriculture a problem that illustrates the complexity of agriculture’s moral dilemmas.
Sensitivities of Cucurbit Powdery Mildew Fungus (Podosphaera xanthii) to Fungicides

This study was conducted to evaluate the sensitivity of cucurbit powdery mildew fungus (Podosphaera xanthii) to major fungicides used for managing this pathogen in the Midwestern United States. Fun...
Necrosis-Released HMGB1 (High Mobility Group Box 1) in the Progressive Pulmonary Arterial Hypertension Associated With Male Sex.

Damage-associated molecular patterns, such as HMGB1 (high mobility group box 1), play a well-recognized role in the development of pulmonary arterial hypertension (PAH), a progressive fatal disease...
Association of Race, Socioeconomic Factors, and Treatment Characteristics With Overall Survival in Patients With Limited-Stage Small Cell Lung Cancer.

Importance It has been established that disparities in race and socioeconomic status are associated with outcomes of non–small cell lung cancer. However, it remains unknown whether this extends to stage I, II, or III small cell lung cancer (SCLC), or limited-stage SCLC (L-SCLC). Objective To investigate the associations of race, socioeconomic factors, and treatment characteristics with survival among patients with L-SCLC. Design, Setting, and Participants Demographic information for patients with L-SCLC diagnosed between 2004 and 2014 was obtained from the National Cancer Database. The follow-up end point is death or last follow-up (date of last contact). Patients were divided into 5 mutually exclusive cohorts by race. Data analysis was performed in October 2019. Main Outcomes and Measures Cox proportional hazards models were used to calculate univariable and multivariable models. Multivariable analyses were conducted to assess the associations of race and socioeconomic factors with risk-adjusted outcomes. Overall survival between groups was depicted by Kaplan-Meier curves. Results Of 72 409 patients analyzed (median [range] age, 67.0 [23.0-90.0] years), 40 289 (55.6%) were women. The distribution of disease stage was 10 619 patients (14.7%) with stage I disease, 7689 patients (10.6%) with stage II disease, and 54 101 patients (74.7%) with stage III disease. The median (range) duration of follow-up was 8.2 (2.4-15.8) months. Compared with White patients, the hazard of death decreased to 0.92 (95% CI, 0.89-0.95;P Conclusions and Relevance This analysis highlights disparities in race and socioeconomic factors associated with outcomes of L-SCLC. Racial minorities, including African American and Asian patients, have better survival than White patients for L-SCLC after adjustment for sociodemographic factors.
Survey of One Health programs in U.S. medical schools and development of a novel one health elective for medical students

Abstract Lessons learned from recent pandemics, such as SARS-CoV-2 have illustrated that education and training in a One Health approach, which recognizes the interdependency of the health of people, animals and the environment, are essential in improving preparations for and responses to disease outbreaks. For this reason and others, there is a critical need to provide One Health (OH) training to medical professionals early in their careers. 133 U.S. medical schools were surveyed for the incorporation of OH learning activities. Results showed that 56% of surveyed programs included OH-related subject matter, primarily in the context of preclinical classroom learning. This supports previous findings that OH education efforts in medical schools lag behind veterinary schools, with many veterinary schools already including OH as a central part of their curricula. A two week OH elective course for third year medical students was developed and implemented at Georgetown University School of Medicine. Topics such as emerging infectious diseases, zoonoses, vector-borne diseases, epidemiology, emergency preparedness, the human-animal bond, and effects of climate change on public health were discussed. The 21 participants were surveyed before and after the course regarding their knowledge and understanding of OH. Participation in the course enhanced the students' knowledge of OH and furthermore, the students' perception of the importance of incorporating OH within the curriculum and in their future careers changed significantly. This study provides clear evidence that successful integration of OH material is achievable at low cost through interdepartmental and interdisciplinary collaboration. A more holistic approach to health care that takes into consideration environmental, wildlife, and domestic animal factors, and introduction of concepts such as OH into the medical school curriculum, can help close the educational gaps identified in the surveys.
Could Harnessing Natural Killer Cell Activity Be a Promising Therapy for Prostate Cancer

Harnessing natural killer (NK) cell activity, either endogenous NK or NK-cell-based therapy, is in the forefront development for many tumor types. There are compelling clinical evidence demonstrating the significant relevance of loss of NK cell activity with prostate cancer (PCa) disease progression to the lethal phenotype, metastatic castration-resistant PCa (mCRPC). Given that mCRPC is generally regarded as a "cold" tumor and has only elicited marginal response to immune checkpoint blockade therapy to revive CD8 T cell activity, NK cell targeted therapy may present a viable opportunity not only to directly target mCRPC and also to "fire up" the cold mCRPC tumor. However, current efforts on harnessing NK cell activity for treating mCRPC is very limited with only one open NK-cell-based clinical trial. This minireview will present the clinical significance of NK cell activity in controlling metastatic PCa and provide perspectives on harnessing NK cell activity for treating mCRPC.
Quantitative Analyses of Feliform Humeri Reveal the Existence of a Very Large Cat in North America During the Miocene

Felids are keystone predators in modern ecosystems and likely played a similar role in shaping ecosystems through the Cenozoic. Unfortunately, understanding the paleoecological impact of felids has been hampered by taxonomic confusion and uncertainty in big cat diversity through time. This stems, in part, from the importance of dentition in differentiating feliform taxa combined with the abundance of postcrania in the fossil record. This dilemma is best illustrated by the humeri of a very large felid uncovered from a number of Hemphillian-aged localities in North America that, in the absence of craniodental remains, have not previously been definitively identified. We present the results of an analysis of the potential of isolated distal humeri to identify feliform taxa. We compared the form and size of distal humeri across feliforms using geometric morphometric analysis and used linear measurements to reconstruct body mass and estimate prey size. Our results suggest that distal humeri are useful tools for differentiating feliform families, genera, and species. Further, along with a specimen from Idaho with associated dentition, they suggest that the large Hemphillian-aged felid is a new species of Machairodus. Future phylogenetic analyses will be necessary to reconstruct the evolutionary history of North American Machairodontinae, but this new taxon provides evidence for a diverse predator fauna during the late Miocene of North America that included some of the largest felids in Earth history.
Race-Based Medicine: An Unscientific Proxy That Persists Racial Bias

Systems of racial classification have inherent incoherencies which have caused a misconstrued concept of race that requires amelioration in present-day society and medicine. Races like White and Black incorrectly generalize people based on arbitrary criteria that inevitably result in racial bias. Biological differences between people of different races do exist, however these differences do not constitute race per se, but localized interbreeding over time between people of a geographic location leading to traits becoming predominant in those respective populations. That is, biological differences arise due to evolutionary genetics, not inherent categories of mankind. Characteristics like skin color and hair texture are no more meaningful than other features that vary among human appearance, such as hair color, eye color, and height, since genetic difference is found in most biological aspects of the body with no regard to the arbitrary physiognomic and other visual differences that human culture perceives. The societal construction of race becomes further evident when evaluated for the mixing of races in which racial categories effectively dissolve. All humans correspond to the same species and share all the physiology and genetics that make us human. Fine-scale genetic variation of about 0.1% exists between populations and individuals, but society picks and chooses the phenotypes that it wishes to portray as distinctive groups of people. Medicine should include the genetics of difference when making clinical decisions without mistakenly reinforcing race due to its stigmatizing, prejudicing connotations and persistence of harmful racial bias. Many claimed racial biological differences, such as hypertension in African-Americans, are attributed more so to environmental conditions than to genetic factors. Medical differences can arise from inherited deleterious mutations of ancestral origin that were retained in certain areas and populations due to persistent, relatively isolated breeding. But to simply attribute observed differences in health to mere racial categories despite the biological inconsistency of race is to deny patients of their individuality and right to beneficence and justice. Instead, race-based medicine must be salvaged for more scientific practices that do not presuppose unethical racial difference but examine genetic difference in patients as individuals to alleviate racial health disparities.
Economic liberalisation policies and (non-Islamic) market coalition in Egypt

ABSTRACTThis article analyses the implementation of Egyptian economic liberalisation and examines its impact on the formation of a non-Islamic market coalition in Egypt. It argues that the way the Egyptian state implemented economic opening – characterised by political corruption and lack of transparency – worked against the integration of micro-, small, and medium-sized Islamic business groups with the market in the peripheral quarters during the Mubarak era. In the absence of the integration between Islamic business groups and the market reforms, economic liberalisation policies sharpened class struggles which had empowered ideological rigidity in favour of state-centric economic policies within political Islam in Egypt.
Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy.

Animal models have expanded our understanding of temporal lobe epilepsy (TLE). However, translating these to cell-specific druggable hypotheses is not explored. Herein, we conducted an integrative insilico-analysis of an available transcriptomics dataset obtained from animals with pilocarpine-induced-TLE. A set of 119 genes with subtle-to-moderate impact predicted most forms of epilepsy with ~ 97% accuracy and characteristically mapped to upregulated homeostatic and downregulated synaptic pathways. The deconvolution of cellular proportions revealed opposing changes in diverse cell types. The proportion of nonneuronal cells increased whereas that of interneurons, except for those expressing vasoactive intestinal peptide (Vip), decreased, and pyramidal neurons of the cornu-ammonis (CA) subfields showed the highest variation in proportion. A probabilistic Bayesian-network demonstrated an aberrant and oscillating physiological interaction between nonneuronal cells involved in the blood-brain-barrier and Vip interneurons in driving seizures, and their role was evaluated insilico using transcriptomic changes induced by valproic-acid, which showed opposing effects in the two cell-types. Additionally, we revealed novel epileptic and antiepileptic mechanisms and predicted drugs using causal inference, outperforming the present drug repurposing approaches. These well-powered findings not only expand the understanding of TLE and seizure oscillation, but also provide predictive biomarkers of epilepsy, cellular and causal micro-circuitry changes associated with it, and a drug-discovery method focusing on these events.
Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1.

Phospholipid scramblase 1 (PLSCR1) is an IFN-inducible, endofacial plasma membrane protein that has been proposed to mediate accelerated transbilayer movement of plasma membrane phospholipids in cells exposed to elevated cytoplasmic [Ca 2+]. The marked transcriptional up-regulation of this gene by IFN in a wide variety of cell types suggested that PLSCR1 might also contribute to biological effects associated with IFN. To study the potential contribution of cellular PLSCR1 to the antiproliferative and tumor-suppressive activities of IFN, PLSCR1 cDNA was stably expressed in the human ovarian cancer cell line HEY1B, and the growth of these cells was compared with matched vector transfected controls both in vitro and in vivo . Whereas we detected no difference in either growth rate or morphology between PLSCR1 -transfected cells and vector controls during in vitro culture in serum, when these cells were implanted s.c. into athymic nude mice, we observed a marked suppression of tumor development from cells transfected to express elevated levels of PLSCR1. Tumors from the PLSCR1 -transfected cells were greatly reduced in size, showed increased infiltration of leukocytes and macrophages, and appeared to undergo differentiation to a more uniform and spindle-shaped morphology that markedly contrasted the highly undifferentiated and pleiomorphic cell shape normally observed for HEY1B cells in vitro or for vector-transfected control HEY1B cells both in vitro and in vivo . These data suggest that the up-regulation of PLSCR1 expression in tumor cells exposed to IFN may contribute to the observed tumor-suppressive action of this cytokine.
The DARPA Advanced Logistics Project

Logistics deals with the problem of getting the right “stuff” (people, materials, supplies) to the right “place” at the right “time”. Major transportation vendors such as Fedex, UPS, Emery Worldwide, require the efficient solution of logistics problems on a minute by minute basis. Major corporate organizations such as Ford and GM, need to keep inventories at optimal levels, while supporting the smooth inflow of production materials, and smooth outflow of finished products. During the last few years, it has been widely recognized that the next generation of logistics products will, in reality, be powerful information systems that manipulate massive, distributed, logistics databases, and enable logisticians to perform a variety of functions such as tracking the status of supplies and materials, planning based on the current status, efficiently tracking status changes as they occur, and replanning as needed in order to accomplish the mission(s) at hand. In 1996, the Defense Advanced Research Projects Agency (DARPA) started an 80 million dollar research effort called the Advanced Logistics Project (ALP) aimed at developing the next generation of logistics systems. In this paper, we will describe the goals of ALP, describe the multi-agent logistics architecture proposed by ALP, and show how this architecture supports the achievement of ALP's goals.
Studies on amino acid racemases. I. Partial purification and properties of the alanine racemase from Lactobacillus fermenti.

Abstract The alanine racemase from Lactobacillus fermenti has been purified 800-fold with a yield of 8%. The enzyme required pyridoxal phosphate as a cofactor, and the dissociation constant was calculated to be 0.15 µm. A sulfhydryl compound was necessary for maximal activity. Either glutathione or 2-mercaptoethanol was effective. The pH optimum was between pH 9.0 and 9.5. The enzyme was stabilized in its most active form by acetate ion. In the presence of acetate the Km for l-alanine was 10 mm; the Km for d-alanine was 7.3 mm, and the enzyme was inhibited by d-cysteine, d-serine, and d-α-amino-n-butyrate but not the corresponding l isomers. In the absence of acetate the enzyme had a lower specific activity, the Km for l-alanine was 16 mm; the Km for d-alanine was 15 mm, and the enzyme was inhibited by d- and l-cysteine, l-serine, and d- and l-α-amino-n-butyrate. A more detailed study of the recemase inhibition by d-cysteine indicated that with l-alanine as substrate, the slopes of the 1/v versus 1/[S]o plots were increased but the 1/v intercepts did not change. With d-alanine as substrate, the slopes and both the 1/v and 1/[S]o intercepts were altered. The only model of enzymatic behavior which predicted this effect was E ⇌ EL ⇌ FD ⇌ F + D E ⇌ F E + I ⇌ EI where E and F are two forms of the enzyme, D is d-alanine, L is l-alanine, and I is the inhibitor.
Estrogen formation in vitro by fetal liver, fetal adrenal gland, and placenta of early human pregnancy

Abstract Fetal liver and adrenal tissue and placental tissue were incubated in the presence of dehydroepiandrosterone-7α- 3 H. Fetal adrenal and liver tissue were also incubated in combination with placental tissue with the same precursor. Free and conjugated estrogens were analyzed in each incubate. Placental tissue alone formed small amounts of estriol from DHA. Fetal adrenal gland was unable to covert DHA to estrogens; however, if placental tissue was added, estriol was formed. Fetal liver was able to synthesize estrogens from DHA. When placental tissue was combined with liver, estrogens, especially estriol, were increased in free and conjugated forms.
Morphologic Evidence of Accelerated Closure of the Ductus Arteriosus in Preterm Infants

In preterm infants, closure of the ductus arteriosus (DA) is often delayed, especially in those with respiratory distress syndrome (RDS). However, it has been suggested that functional closure of the DA may occur as early as 24 hours of age in some preterm infants exposed to intrauterine stress, and this is usually associated with decreased incidence of RDS. This suggests that accelerated maturation of the DA as well as of the lungs occurs in utero. Accordingly, histologic evidence of accelerated maturation of the DA was sought in a prospective autopsy study of 55 preterm infants ranging in gestational age from 19 to 32 weeks. There were four infants with clinically closed DA which showed histologic evidence of closure. The birth weight of these four infants ranged from 750--1,100 gm, the gestational age ranged from 24--32 weeks, and age of death was 39 hours to 6 days. The immediate causes of death were intracerebral hemorrhage or intrapulmonary hemorrhage, or both. Obstetric complications included chronic second trimester vaginal bleeding, abruptio placenta, malnutrition, diabetes, pulmonic stenosis of moderate degree, and chronic hypertension. These findings support the hypothesis that in some preterm infants exposed to chronic intrauterine stress, maturation of the DA is accelerated. This may result clinically in effective postnatal closure of the DA.
History and Anthropology: A Marriage Made in Heaven

Anthropology is a science of inquiries about the origins and continuities of the patterned differentiation of human beings into distinguishable groups. During the last hundred years, most such inquiries in academic anthropology could be organized under four headings, and in the U.S., these headings became the subfields of anthropology: physical anthropology; archaeology; linguistics; and cultural anthropology or ethnography. Each one of these subfields has a historical component. Anthropology is by its nature a historical form of inquiry, and history and anthropology can be mutually helpful in the pursuit of knowledge.
A Latent Class Analysis of Risk Factors for Acquiring HIV Among Men Who Have Sex with Men: Implications for Implementing Pre-Exposure Prophylaxis Programs.

Current Centers for Disease Control and Prevention (CDC) guidelines for prescribing pre-exposure prophylaxis (PrEP) to prevent HIV transmission are broad. In order to better characterize groups who may benefit most from PrEP, we reviewed demographics, behaviors, and clinical outcomes for individuals presenting to a publicly-funded sexually transmitted diseases (STD) clinic in Providence, Rhode Island, from 2012 to 2014. Latent class analysis (LCA) was used to identify subgroups of men who have sex with men (MSM) at highest risk for contracting HIV. A total of 1723 individuals presented for testing (75% male; 31% MSM). MSM were more likely to test HIV positive than heterosexual men or women. Among 538 MSM, we identified four latent classes. Class 1 had the highest rates of incarceration (33%), forced sex (24%), but had no HIV infections. Class 2 had 10 anal sex partners in the previous 12 months (69%), anonymous partners (100%), drug/alcohol use during sex (76%), and prior STDs (40%). Class 4 had similar characteristics and HIV prevalence as Class 2. In this population, MSM who may benefit most from PrEP include those who have >10 sexual partners per year, anonymous partners, drug/alcohol use during sex and prior STDs. LCA is a useful tool for identifying clusters of characteristics that may place individuals at higher risk for HIV infection and who may benefit most from PrEP in clinical practice.
Cable-based transport observations in the Southeastern Caribbean

Summary form only given. Flow through the island passages that separate the southern Caribbean Sea from the Atlantic Ocean feeds the Florida Current and Gulf Stream, forming an important link in both the wind-driven and thermohaline circulations of the North Atlantic. A recorded history of the variability of this flow will contribute to our understanding of ocean circulation and its role in the Earth's climate. With the generous permission of the owners of the Eastern Caribbean Fibre System, a commercial telecommunication system linking the southern islands of the Antilles chain, cable-voltage observations have been initiated across the southernmost island passage between the Atlantic and the Eastern Caribbean, the Grenada Passage between the islands of Grenada and Trinidad. The work is being done by a group of scientists at the Universities of Washington and Miami, and at the U.S. National Oceanic and Atmospheric Administration (NOAA). The installation will be discussed and initial data presented.