cssi/SciSciGPT-SciSciNet huggingface dataset:
Experimental evidence of interleukin-2 activity in bone marrow transplantation.

PURPOSE: This article reviews the preclinical and clinical experience with the administration of recombinant interleukin-2 (rIL-2) and rIL-2-activated lymphocytes following allogeneic or autologous bone marrow transplantation in patients with hematologic malignancies and advanced breast cancer. METHODS: Recombinant IL-2 was administered following engraftment of bone marrow or peripheral blood stem cell. (PBSC) transplants to enhance the graft versus tumor effect. Ex vivo incubation of bone marrow or PBSC with rIL-2 was used to activate effector lymphocytes (i.e., T cells and natural killer cells) that may enhance the antitumor effect. RESULTS: We have shown in preclinical models that the incubation of bone marrow or PBSC in rIL-2 generates cytotoxic effector cells that are capable of lysing a wide variety of tumor cells. In those models we have also found that these same rIL-2-activated cells are able to induce a syngeneic graft-versus-host disease (GVHD) that correlates with the antitumor effect. We have now taken this concept into the clinic in patients with hematologic malignancies and advanced breast cancer. We have treated patients with stage II through stage IV breast cancer with PBSC that have been incubated with rIL-2. We have now reached a stable phase II dose of rIL-2 with no adverse effect on engraftment. We have found that cytotoxic cells are generated in the patients' circulation, and that these cells are activated T cells, not natural killer cells. Approximately 50% of the patients seem to have autologous GVHD. Patients with stage II breast cancer seem to generate more cytotoxic cells than patients with stage IV breast cancer. We are in the process of examining whether these patients have an increased disease-free survival. CONCLUSION: We have shown that rIL-2-activated cells seem to generate autologous GVHD and possibly induce a graft-versus-tumor effect. Use of similar approaches in BMT will be important in the future to generate similar types of immune antitumor effects.
Do we need a new levodopa

Idiopathic Parkinson's disease (PD) is classified as a chronic progressive neurodegenerative disease. Various each other complementing, still hypothetical aetiologies describe the predominant dopaminergic neuronal death. They include genetic predisposition, exogenous environmental or endogenous toxin exposure, impaired detoxification, defects of mitochondrial function, microglial activation with chronic inflammation, infection with a still unknown pathogenic substrate, disturbed neurotransmission of biogenic amines and glutamate in particular. The essential final step to neuronal apoptosis is a disturbed balance in favour of free radical generation and antioxidant activity, commonly described as oxidative stress (Przuntek et al., 2004).
Markets And Molecules: A Pharmaceutical Primer From The South

The Indian pharmaceutical industry has historically manufactured low-cost drugs for the global poor. Activist mobilizations at the height of the HIV/AIDS epidemic revealed a vast cost gap between global brands and Indian generics, much to the embarrassment of Euro-American corporations that were in the habit of pricing drugs for only the wealthy or well insured. As new drug access controversies focus on anticancer therapies, they reveal new flows of international capital, emergent genetic technologies, and increasingly coercive trade regimes. Together these favor multinational corporate oligopolies, which imperil the legacy of HIV/AIDS activism and the future availability of essential life-saving drugs for the work of global public health. In this essay, I describe how the future of the right to drug access rests uneasily, and potentially calamitously, on a shifting balance of power between global south interests and Euro-American pharmaceutical capital.
The immunological ménage à trois promotes inflammation in Type 2 diabetes. (54.14)

Type 2 diabetes (T2D) is an inflammatory disease promoted by changes in immune cell function. Monocytes and T cells play roles in T2D inflammation as evidenced, in part, by our demonstration of pro-inflammatory T cell subset skewing in T2D patients. However, the role of cross-talk amongst immune system cells in T2D is poorly unstudied. PBMC depletion studies showed that T2D patient T cells, unlike non-diabetic (ND) donor cells, required monocytes to maintain IL-17 hyper-secretion. In contrast, B cell depletion did not affect T2D Th17 function, but surprisingly, B cell depletion from non-diabetic (ND) mixed cell cultures significantly elevated Th17 function. Based on the role B cell IL-10 plays in inflammation resolution, we tested the hypothesis that IL-10 regulates immune cell cross-talk to block Th17 function. IL-10 addition to B cell-depleted PBMCs decreased IL-17 to “healthy” levels in both ND and T2D samples, indicating that both cell types are physiologically capable of interpreting the anti-inflammatory signals from B cells despite the presence of pro-inflammatory monocytes in T2D samples. Critically, unlike ND B cells, T2D B cells fail to secrete IL-10, thus lack of B cell IL-10 in T2D samples compounds elevated pro-Th17 cytokine production by monocytes. We conclude that IL-10 can block monocyte-mediated increases in Th17 function, and that lack of B cell IL-10 in T2D associates with IL-17-induced inflammation thus metabolic imbalance.
Heavy metal ion removal by thiol functionalized aluminum oxide hydroxide nanowhiskers

Abstract In this study, we developed a cost effective method of using thiol functionalized γ-aluminum oxide hydroxide (γ-AlOOH) filters for removing three key heavy metals from water: mercury, lead, and cadmium under non-concomitant conditions. Compared to non-thiol treated γ-AlOOH filters, the introduction of thiol functional groups greatly improved the heavy metal removal efficiency under both static and dynamic filtration conditions. The adsorption kinetics of thiol functionalized γ-AlOOH were investigated using the Lagergren first order and pseudo-second order kinetics models; whereas the isothermal adsorption behavior of these membranes was revealed through the Langmuir and Freundlich models. Heavy metal concentration was quantified by Inductively Coupled Plasma-Mass Spectroscopy, and the thiol level on γ-AlOOH surface was measured by a colorimetric assay using Ellman's reagent. X-ray photoelectron spectroscopy was used to further address the surface sulfur state on the membranes after heavy metal exposure. Mechanisms for heavy metal adsorption were also discussed.
DERELICT AND ABANDONED VESSELS: A UNIQUE STATE APPROACH TO PREVENTION AND REMOVAL

ABSTRACT # 2017-408 The Texas General Land Office (TGLO) has developed an innovative and cost effective approach to dispose of abandoned vessels along the Texas coast. For years, unscrupulous vesse...
Ischemia-Reperfusion Concepts of Myocardial Preconditioning and Postconditioning

The heart is an organ that requires a significant energy input for its contractile function. Energy reserves being low, it is dependent on blood supply. Myocardial ischemia results from an imbalance between intake and myocardial oxygen requirements.
Calories and Chemical Carcinogenesis

It is generally accepted that diet influences the development of cancer in humans and laboratory animals. The dietary component most thoroughly studied for effects on tumor development is fat (Kritchevsky and Klurfeld, 1981). High fat consumption by humans is correlated with cancers of the digestive system—colon, rectum, pancreas, and gall bladder—and of non-intestinal sites, such as breast, ovary, corpus uterus, and prostate (Modanet al., 1975). In animal studies, both the amount and type of fat significantly affect chemically induced tumor growth. Carroll has summarized much of the work in this area of investigation and expressed the currently accepted working hypothesis that dietary fat provides conditions more favorable for tumor growth (Carroll, 1983). Those conditions may include alterations of target cell membranes, immunologic responses, hormone levels, fecal steroid concentrations, or prostaglandin production.
Genomic divergence in allopatric Northern Cardinals of the North American warm deserts is associated with behavioral differentiation

Biogeographic barriers are thought to be important in initiating speciation through geographic isolation, but they rarely indiscriminately and completely reduce gene flow across the entire community. Understanding which species9 attributes regulate a barrier could help elucidate how speciation is initiated. Here, we investigated the association of behavioral isolation on population differentiation in Northern Cardinals (Cardinalis cardinalis) distributed across the Cochise Filter Barrier, a region of transitional habitat which separates the Sonoran and Chihuahuan deserts. Using genome-wide markers, we modeled demographic history by fitting the data to isolation and isolation-with-migration models. The best-fit model indicated that desert populations diverged in the mid-Pleistocene and there has been historically low, unidirectional gene flow into the Sonoran Desert. We then tested song recognition using reciprocal call-broadcast experiments to compare song recognition between deserts, controlling for song dialect changes within deserts. We found that male Northern Cardinals in both deserts were most aggressive to local songs and failed to recognize across-barrier songs. A correlation of genomic differentiation despite historic introgression and strong song discrimination is consistent with a model where speciation is initiated across a barrier and maintained by behavioral isolation.
Fundamentals of Stapling Devices

Surgical staplers have increased the efficiency and ease of completion of many operations. The development of the surgical stapler started in the early 1900s, and these devices have rapidly undergone major improvements throughout the past century. Surgical staplers are now used in a wide range of operations including procedures involving the esophagus, stomach, gallbladder, liver, pancreas, small bowel, colon, lung, and relative vasculature, among other anatomical structures. Although staplers can be simple to use, certain technical aspects must be taken into account, including tissue thickness, strength and composition, staple height, and duration of compression prior to firing the stapler. Further modifications are ongoing to continue to make these devices more efficient and simple to adapt to complex operative situations.
A 7000-year pollen record from the Amazon lowlands, Ecuador

The longest continuous Amazonian palynological record (ca 7010 yrs B.P. to present) from Lake Ayauchi, Ecuador, reveals species-by-species abundance changes during a period of climatic change. Pollen influx from a wet tropical rain forest was found to be high, 1×104−105 grains cm-2 yr-1, although mature forest taxa were poorly represented. Horizons of laminated sediments and weathered gyttja, dated to ca 4200–3150 B.P., evidence a period of reduced net water availability. During this period Ficus, Alchornea and Palmae pollen representation appears to decline, although there is no evidence of a major forest compositional change. The lake was reduced to a shallow, possibly seasonal, pool. Zea cultivation was recorded between ca 2850 B.P., (the earliest paleoecological record to date in the Amazon basin) and ca 800 B.P. It is suggested that Zea was cultivated on exposed lake sediment within the crater at times of low water levels. The abandonment of Zea cultivation may have been due to rising water levels or social unrest.
Approaches to Perception in Phenomenological Psychology: The Alienation and Recovery of Perception in Modern Culture

Perception is so continually present, close to us, and diverse in its forms that it is one of the most challenging themes for psychological reflection. We are so captivated by what we perceive that the hows and whys remain in the background. In the wilderness of everyday life, perception can easily embarrass the investigator who ceases to take it for granted, for attempts at conceptualization seem alien, in one way too crude and in another too sophisticated in their complexity. Perception, therefore, tends to elude the grasp of knowledge and to remain a great mystery.
Activation of TRPV1 Prevents Salt-Induced Kidney Damage and Hypertension After Renal Ischemia-Reperfusion Injury in Rats.

BACKGROUND/AIMS High-salt intake after recovery from renal ischemia-reperfusion (I/R) injury leads to hypertension with severe renal damage. Transient receptor potential vanilloid type 1 (TRPV1) channels have been involved in the regulation of inflammation and oxidative stress following ischemic organ injury. We tested the hypothesis that activation of TRPV1 conveys preconditioning protection to the kidney subjected to I/R. METHODS TRPV1 was activated or down-regulated by subcutaneous injection of a low (1mg/kg) or high (100mg/kg) dose of capsaicin, respectively, 3 hours before ischemia. Rats were fed a 0.4% NaCl diet for 5 weeks after I/R followed by a 4% NaCl diet for 4 more weeks in 4 groups: sham, I/R, I/R+high-dose capsaicin (HCap), and I/R+low-dose capsaicin (LCap). RESULTS Renal TRPV1 expression was decreased in I/R rats (P< 0.05) and further reduced in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap rats compared with the sham group. Blood pressure were elevated in I/R rats (P< 0.05) and further increased in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap rats compared with sham. Renal function was impaired in I/R rats (P< 0.05) and further deteriorated in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap group. Renal inflammatory responses, oxidative stress, and renal collagen deposition were augmented in I/R rats (all P< 0.05) and further intensified in I/R+HCap group (all P< 0.05) but unchanged in I/R+LCap group. CONCLUSION Activation of TRPV1 plays an anti-inflammatory and anti-oxidative stress role in preventing renal tissue damage and salt-induced hypertension after I/R injury, indicating that TRPV1 conveys preconditioning protection that may have therapeutic implication.
Engaging Major Players in Data Monitoring and Regulation: Cambridge Analytica, the Game Theory and the Nash Theory of Equilibrium (Presentation Slides)

“Perhaps the events which occur in a nation that has become accustomed to the fact that the public sphere is the favorable scenario for the satisfaction of private and sectarian interests, no longer bear the potential or capacity to surprise. However, the news that is broadcast daily by the mass media, with a touch of novelty and sensationalism - based on the need to sell advertising guidelines-, have a transversal history and a fundamental question that has been studied lightly from the academia: history, a country that founded a nation with the precept of being a solid democratic system (to the point of calling itself the Athens of South America); the question; Why has this 'solid system' not permeated local interests in territories where democracy has only served as another instrument for sustaining a system of individual privileges, protected by coercive power and complicity-institutional permissiveness?“ Mass media – as well as social media forums and platforms, have indeed assumed a commanding presence and dominance over the years – as evidenced by their impacts on recent 2016 election outcomes in the United States and the 2016 Brexit Referendum in 2016. This fact has further, been accentuated by recent revelations and allegations surrounding Cambridge Analytica’s use and acquisition of, Facebook data – amidst allegations being made against the company over how it gained access to, as well as acquired, private data of Facebook users as a means of influencing voters in the elections. As well as recent events highlighting the impact of major and even local elections on capital markets, the impacts of uncertainties in these markets – as very clearly demonstrated by Brexit results and outcomes, should not be undermined. Such is the impact of uncertainties – as reflected by the weights attached to the values of data and accounting information for users in financial markets in many capital market economies. This presentation also aims to highlight that the claim that “democracy has only served as another instrument for sustaining a system of individual privileges, protected by coercive power and complicity-institutional permissiveness? “ Has been fueled and bolstered by failures to acknowledge and factor in, the growing significance of new and powerful players in the digital and political economy. The presentation also aims to highlight how and why such players should be monitored and regulated.
A note on minimal additive complements of integers

Abstract Let C , W ⊆ Z . If C + W = Z , then the set C is called an additive complement to W in Z . If no proper subset of C is an additive complement to W , then C is called a minimal additive complement. We provide a partial answer to a question posed by Kiss, Sandor, and Yang regarding the minimal additive complement of sets of the form W = ( A + n N ) ∪ F ∪ G , where | F | ∞ , ( F mod n ) ⊆ ( A mod n ) and ( G mod n ) ∩ ( A mod n ) = 0 . We also introduce the dual problem of characterizing sets that arise as the minimal additive complements of some set of integers, proving the analog of Nathanson’s initial result on existence of minimal additive complements.
Analysis of Absorbable Hemostatic Packing Compared to Physiologic Hemostasis in Functional Endoscopic Sinus Surgery With or Without Septoplasty

BackgroundThere currently are no randomized studies examining if absorbable hemostatic packing (AHP) results in better objective and subjective outcomes than physiologic healing in sinus surgery wi...
Beyond Volumetric Albedo — A Surface Optimization Framework for Non-Line-Of-Sight Imaging

Non-line-of-sight (NLOS) imaging is the problem of reconstructing properties of scenes occluded from a sensor, using measurements of light that indirectly travels from the occluded scene to the sensor through intermediate diffuse reflections. We introduce an analysis-by-synthesis framework that can reconstruct complex shape and reflectance of an NLOS object. Our framework deviates from prior work on NLOS reconstruction, by directly optimizing for a surface representation of the NLOS object, in place of commonly employed volumetric representations. At the core of our framework is a new rendering formulation that efficiently computes derivatives of radiometric measurements with respect to NLOS geometry and reflectance, while accurately modeling the underlying light transport physics. By coupling this with stochastic optimization and geometry processing techniques, we are able to reconstruct NLOS surface at a level of detail significantly exceeding what is possible with previous volumetric reconstruction methods.
Leadership Reflections: It is Not About the Perks

AbstractOur guest columnist is Karl Bridges who has served in a variety of leadership roles in academic libraries. I have gotten to know Karl over the past few years as he was asked to serve in an ...
Role of Ocular Motor Assessment in Diagnosis and Research

The clinical evaluation of eye movements can contribute substantially to the diagnosis of parkinsonian disorders, provided the physician performs a proper examination and interprets the findings by referring to a simple scheme of the neurobiology of eye movements (1). Further diagnostic information can often be obtained by recording eye movements, which are more accessible to measurement and analysis than limb movements or gait. A good part of the neurobiological substrate of eye movements has been defined, which makes it possible to attribute disordered properties of eye movements to dysfunction of specific neuronal populations or structures in the brain. In this chapter, first, we review pertinent aspects of the ocular motor examination; second, we highlight some important test paradigms and technical aspects of measuring eye movements; and third, we summarize disorders of ocular motility reported with parkinsonian disorders and diseases affecting the basal ganglia.
Minimal Residual Disease Negativity Does Not Overcome Poor Prognosis in High-Risk Multiple Myeloma: A Single-Center Retrospective Study

Abstract Background Minimal residual disease (MRD) is a standard measurement for response assessment in multiple myeloma (MM). Despite new treatments, high-risk MM patients continue to have poor prognosis. We evaluated the effect of MRD negativity in high-risk versus standard-risk patients. Patients and Methods We retrospectively evaluated all consecutive MM patients who underwent routine MRD testing by 1-tube 8-color advanced flow cytometry with 2,000,000 events and sensitivity level 10−5 at our center from 2015 to 2018 after initial therapy. Kaplan-Meier and log-rank test were used to assess survival estimates and differences between study groups. Results One hundred thirty-six patients with MRD testing after initial therapy or autologous stem-cell transplantation were identified. At a median follow-up of 14 months (range, 1-36 months), progression-free survival and overall survival were significantly worse in high-risk versus standard-risk patients. During the study period, 50% of high-risk group had experienced disease progression (relapse and/or death) versus 20% in the standard-risk group (P = .0006). No patients with standard-risk died, but 4 (14%) in the high-risk group did (P = .0007). Regardless of MRD status, high-risk patients had statistically significant worse progression-free survival than standard-risk patients. At median follow-up, those with disease 10% standard-risk/MRD negative; 20% standard-risk/MRD positive; 40% high-risk/MRD negative; and 45% high-risk/MRD positive had either experienced relapse or died (P = .0041). MRD status did not significantly affect overall survival in either group (P = .0914); however, longer follow-up is needed to assess survival. Conclusion Genetic abnormalities remain a powerful prognostic indicator for MM, regardless of MRD status. For newly diagnosed MM patients treated with novel triple-drug initial therapy and frontline autologous stem-cell transplantation, MRD-negative status did not mitigate the poor-prognosis outcomes of high-risk MM patients.
Baptizing the Romans

This article focuses on Ordo Romanus XI, a liturgical script that describes the process for performing baptism. Including its preparatory meetings. First, the essay discusses the context in which the source was created, and second draws on its evidence to understand elements of the society of its origin. It is argued that the source was composed in the city of Rome in the second half of the seventh century, and it was intended to introduce innovations into the celebration and conception of baptism there. While previous research has characterized the source as one milestone in the history of baptism, a close reading of it provides valuable hints as to the behavior, attitudes, and identity of seventh-century Romans, both on individual and collective levels. Baptism inducted people into Christian society, cleansed them from sin, and made salvation possible. It mediated both human and supernatural relationships. Further, it strengthened Christian belief, gender roles, and the conception that Romans were the new Israelites. On cover:Monks singing the Office and decorated initial A[sperges me.]. Gradual Olivetan Master (Use of the Olivetan Benedictines), illuminated manuscript on parchment ca. 1430-1439. Italy, Monastero di Santa Maria di Baggio near Milan, Ca 1400-1775.Beinecke Ms1184: The olivetan Gradual. Gradual. General Collection, Beinecke Rare Book and Manuscript Library, Yale University.
Chapter 8 – Metals

Metals and metalloids are naturally occurring elements comprising about two-thirds of the periodic table of elements. They are primarily found in soil but also may be dissolved in water, especially at low pH. Several metals are essential for living organisms, such as copper, iron, and zinc. Others, such as arsenic, lead, and mercury, are highly toxic to most organisms. Exposure to metals usually comes through ingestion of food, water, or soil, but actual assimilation is complex and depends on the presence of other metals and whether the metal of concern is in its elemental form, an ionic form, or attached to some organic molecule such as methyl. Organometals are particularly toxic because they are more readily taken into cells, where they can cause many issues, including cancer and genotoxicity.
Part and Parcel? Examining Al Shabaab and Boko Haram’s Violence Targeting Civilians and Violence Targeting Women

In an effort to produce a more holistic and nuanced understanding of the violence women face in conflict, this article describes al Shabaab and Boko Haram’s respective patterns of political violenc...
The Impact of Socioeconomic Status on the Clinical Outcomes of COVID-19; a Retrospective Cohort Study.

There have been limited data assessing the influence of disadvantaged socioeconomic status (SES) on the incidence and clinical outcomes of COVID-19 patients within the diverse communities of the United States. Here, we aim to investigate the association between poverty level, as an indicator of SES, and COVID-19 related clinical outcomes including hospitalization and all-cause mortality. This retrospective cohort study included 3528 patients with laboratory confirmed COVID-19 seen at a large New York City health system between March 1, 2020 and April 1, 2020. Data for neighborhood level poverty was acquired from the American Community Survey 2014–2018 and defined as the percent of residents in each ZIP code whose household income was below the federal poverty threshold (FPT): 0% to 20% below FPT (high poverty). COVID-19 positive patients who resided in high poverty areas were significantly younger, had a higher prevalence of comorbidities and were more likely to be of female gender or a racial minority when compared to individuals living in low poverty areas. Residence in a high poverty area was not associated with an increased risk of COVID-19 related hospitalization and was found to be associated with a decreased risk of in-hospital mortality. This study suggests the existence of an unequal socioeconomic gradient in the demographic and clinical presentation of COVID-19 patients including differences in age, gender and race between poverty groups. Further studies are needed to fully assess the intersectionality of SES with the COVID-19 pandemic.
The Role of Death Anxiety and Self-Esteem in Suicide Attitudes:

The persistent stigmatization of suicide calls for a careful examination of the thought processes involved in perceptions of suicide. Hence, the present study is the first to apply terror management theory (TMT) and use experimental methods to examine whether reminders of death lead to increased stigma towards suicide and whether self-esteem moderates these stigmatized reactions. Consistent with the predicted effect of the death anxiety and self-esteem hypothesis, findings revealed that, for respondents with low self-esteem, thinking about their own death led to more stigma, less willingness to intervene, and allocated less money to a suicide prevention organization as compared to those who did not think about death. Findings from this study could have important implications for how we understand the psychological underpinnings of stigma and the role of death anxiety in hostile attitudes and decreased altruism - especially for mental health professionals working with individuals affected by suicide.
Phase I Study of Stereotactic Body Radiotherapy plus Nivolumab and Urelumab or Cabiralizumab in Advanced Solid Tumors

Purpose: CD137 agonism and CSF1R blockade augment stereotactic body radiotherapy (SBRT) and anti-programmed death-1 in preclinical models. We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor). Patients and Methods: This phase I clinical trial enrolled patients with advanced solid tumors that had progressed on standard therapies. SBRT was delivered to 1–4 metastases with nivolumab+urelumab or nivolumab+cabiralizumab given concurrently and following SBRT. Dose-limiting toxicity (DLT) was the primary endpoint with anatomic location-specific SBRT doses deemed safe if ≤33% DLT frequency was observed. Secondary endpoints included RECISTv1.1 response, progression-free survival (PFS), overall survival (OS), and molecular correlative studies. Results: Sixty patients were enrolled, and median follow-up for living patients is 13.8 months. Of these, 23 (38%) received SBRT+nivolumab+urelumab and 37 (62%) received SBRT+nivolumab+cabiralizumab. Seven patients (12%) experienced a DLT (n = 3 grade 3, n = 4 grade 4) in the following anatomic cohorts: abdominal/pelvic (3/17, 18%), liver (1/13, 8%), central lung (2/14, 14%), and peripheral lung (1/12, 8%). Of 41 patients radiographically evaluable for best overall response including 55 radiated and 23 unirradiated RECIST target lesions, 2 had complete responses (5%), 7 had partial responses (17%), 12 had stable disease (29%), and 20 had progression (49%). Median estimated PFS and OS are 3.0 months [95% confidence interval (CI), 2.9–4.8] and 17.0 months (95% CI, 6.8–undetermined), respectively. No patients with elevated pre-SBRT serum IL8 experienced a response. Conclusions: SBRT to ≤4 sites with nivolumab+urelumab or nivolumab+cabiralizumab for treating advanced solid tumors is feasible with acceptable toxicity and modest antitumor activity. See related commentary by Rodriguez-Ruiz et al., p. 5443
DeepREAL: A Deep Learning Powered Multi-scale Modeling Framework Towards Predicting Out-of-distribution Receptor Activity of Ligand Binding

Drug discovery has witnessed intensive exploration of the problem of drug-target physical interactions over two decades, however, a strong drug binding affinity to a single target often fails to translate into desired clinical outcomes. A critical knowledge gap needs to be filled for correlating drug-target interactions with phenotypic responses: predicting the receptor activities or function selectivity upon the ligand binding (i.e., agonist vs. antagonist) on a genome-scale and for novel chemicals. Two major obstacles compound the difficulty on this direction: known data of receptor activity is far too scarce to train a robust model in light of genome-scale applications, and real-world applications need to deploy a model on data from various shifted distributions. To address these challenges, we have developed an end-to-end deep learning framework, DeepREAL, for multi-scale modeling of genome-wide receptor activities of ligand binding. DeepREAL utilizes self-supervised learning on tens of millions of protein sequences and pre-trained binary interaction classification to solve the data distribution shift and data scarcity problems. Extensive benchmark studies that simulate real-world scenarios demonstrate that DeepREAL achieves state-of-the-art performance in out-of-distribution settings.
Regulation of ion channels in cystic fibrosis (869.8)

Cystic Fibrosis (CF) is an autosomal recessive disease, characterized by mutations in the CFTR gene, incorrect protein folding, and impaired chloride secretion. In addition to the maintenance of ch...
Mobilising upland Filipino youth to serve as infomediaries

Purpose – The purpose of this paper is to operationalise infomediaries in an agricultural context, specifically upland rice farming. Infomediaries are people who facilitate access to information and communication technologies (ICTs). This offers a socially grounded solution to the nagging issue of the digital divide. Design/methodology/approach – This research is predominantly qualitative. The methods used were time transects, mobility mapping, photovoice, individual and key informant interviews. In total, 38 farmers' children from the upland communities in the provinces of Albay and Aurora participated in this research. Theoretically, this paper aims to contribute to literature on ICT 2.0. Findings – The participants showed strong desire to help their parents on the rice farm, directly or indirectly. They had varying levels of proficiency in using ICTs. Average weekly expenditure on purchasing prepaid mobile phone credits was US$1.50. Evidence of mobile addiction (sending more than 200 text messages dail...
The Convergent Conceptions of Being in Mainstream Analytic and Postmodern Continental Philosophy

This article argues that there is ultimately a very close convergence between prominent conceptions of being in mainstream Anglo-American philosophy and mainstream postmodern Continental philosophy. One characteristic idea in Anglo-American or analytic philosophy is that we establish what is meaningful and so what we can say about what is, by making evident the limits of sense or what simply cannot be meant. A characteristic idea in Continental philosophy of being is that being emerges through contrast and interplay with what it is not, with what has no being at all and so is beyond sense. The two traditions consequently conceive being in significantly related ways. As a result, what the Continental tradition gets at with “the meaning of being as such and in general,” and how it gets at it, has much in common with what the Anglo-American tradition gets at, and how it gets at it, by establishing “what can be meaningfully said.”
Effects of Repetition and Inactivity on Laparoscopic Skills Training

Abstract Study Objective To describe the impact of task repetition and time between practice sessions on time to complete a surgical task using a high-fidelity laparoscopic simulator. Design An Institutional Review Board–approved retrospective cohort study of 33 obstetrics/gynecology residents with unlimited access to a high-fidelity laparoscopic simulator over a period of 12 months. Canadian Task Force design classification II-2. Setting Academic medical center and obstetrics/gynecology residency training program. Participants Obstetrics/gynecology residents. Interventions Participation in a high-fidelity laparoscopic training exercise. Measurements Residents completed a standardized peg transfer exercise with data collected on the time to completion of the exercise, number of the attempt, and interval since the last day of practice. Data were analyzed using Spearman correlation coefficients and mixed-effects linear regression. Main Results A total of 33 residents participated during the 12-month period, completing 484 peg transfer exercises (mean, 16.2 per resident). Each repetition was correlated with a mean decrease in time to completion of 2.28 seconds (p Conclusion The number of previous completed exercises was significantly correlated with decreased time to completion of this standardized exercise. Lapses in practice did not correlate with slower times to completion, suggesting that repetitive exposure to a simple surgical task has a greater impact on efficiency than lapse in practice.
Concepts in Thyroid, Parathyroid, and Adrenal Surgery

Surgery of the thyroid, parathyroid, and adrenal glands is an anatomically and physiologically complex field. Operative intervention on the thyroid gland involves either a thyroid lobectomy, total thyroidectomy, or completion thyroidectomy after previous thyroid surgery. The operative extent is dependent on the symptoms and specific pathology being treated, as well as the underlying risk for malignancy. In cases of possible malignancy, patients are treated with thyroid lobectomy with completion thyroidectomy for proven malignancy.
Sucralose: The Sugar of the New Millennium - FDA's Role: A Hindrance or a Help?

On April 3, 1998, McNeil Specialty Products was granted approval by the Food and Drug Administration (FDA) to market sucralose under the trademarked name "SPLENDA." Americans have been deprived the opportunity of this "miraculous" sugar substitute due to the laborious and politicized FDA approval process for new food additives. As a result, the FDA deprived consumers, or consumers in consultation with health care providers, from making choices about the use of this important food additive. The Amendments that passed in 1958 required FDA approval for the use of a food additive. As stated previously, the FDA is empowered with the responsibility of insuring that the use of any food additive is safe. In order for the FDA to approve a food additive, the sponsor must present data that the food additive is safe for that use. For example, a petition for the proposed food additive must be filed, similar to the FDA petition process. In 1991, the FDA proclaimed stevia as an unsafe food additive and completely banned the use of stevia. As such, an increasingly popular avenue to avoiding the FDA route is to classify a product not as a food additive, but simply as a food or a dietary supplement.
Die sozialen Grundlagen des Verhaltens

Die Sozialpsychologie hat als Fach eine besondere Stellung innerhalb der Psychologie. Hier werden die Informationen aus anderen Bereichen psychologischer Forschung oft anders akzentuiert. Diese Ergebnisse verweisen darauf, das Wahrnehmung, Lernen, Denken usw. sehr deutlich von sozialen Faktoren beeinflust werden.
Legal History as Foreign Relations History

This paper is for a leading work on the methodologies of foreign relations history. Traditionally, diplomatic historians have been skeptical about law as a causal force in international relations, and have often ignored it. Challenging that assumption, this essay shows that law is already present in aspects of foreign relations history scholarship. Using human rights as an example, I explore the way periodization of legal histories is tied to assumptions and arguments about causality. I illustrate the way law has worked as a tool in international affairs, and the way law makes an indelible mark, or acts as a legitimizing force, affecting what historical actors imagine to be possible. Drawing from Robert Gordon’s influential work on the methodology of legal history, the essay shows the way law can help to constitute the social and political context within which international affairs are conducted. I argue that the presence of law and lawyers in the history of U.S. foreign relations is too central to be ignored.For a scholar without legal training, taking up law-related topics can pose special challenges. This essay ends with a Legal History Survival Guide that includes advice about how to get started and how to avoid mistakes.
Evidence for suppression of radiation damage in Li-doped MgO

The net production of stable intrinsic defects in MgO, such as anion vacancies and divacancies, produced be electron and neutron irradiations is shown to be suppressed by doping with Li impurities.
Evaluation of Magnetic Grain Feeder for Lactating Dairy Cows

Abstract A grain feeder activated by magnet to provide supplemental grain to high producing cows without physical separation of cows was tested with Holstein cows in early lactation. In trial 1 (30 wk), 20 cows were assigned alternately at calving to either a control group of 10 cows which received grain in the parlor at 1kg per 3kg milk or a magnet group of 10 cows which was offered 4.5kg of grain in the parlor plus access to the magnetic feeder 1h per cow per day until milk production dropped below 18kg daily. Corn silage was fed free choice and hay fed at approximately 3.0kg per head daily to both groups. Cows with magnets consumed more grain (9.1kg from the feeder) and more total dry matter daily and produced 3.5kg more milk per day with a lower fat test than control cows. When previous lactations were considered, milk yield was 1.5kg greater by the magnet group. In trial 2 (25 wk), 20 Holstein cows were assigned randomly to a total mixed ration of corn silage and grain (60:40 ratio) plus 2.2kg hay per cow or to a magnet group fed corn silage free choice, 2.2kg hay per cow daily, and the entire grain ration from the magnet activated feeder. Cows with magnets consumed more grain and less total dry matter daily and produced a similar amount of milk with a lower fat test than control cows. Number of meals per cow daily was large with short eating time per meal. The relationship between milk yield and eating time was low during both trials.
Local cubic and bicubic C 1 surface interpolation with linearly varying boundary normal

Abstract An algorithm for the interpolation of a ‘mesh of points’ in 3-space by a C1 surface is developed. At each point, the surface normal can be specified. The surface is constructed locally and consists of cubic and bicubic patches to match the underlying mesh facets. The surface construction is special in that it generates a piecewise parametric surface such that the normal along patch boundaries varies linearly.
Photon Information Efficient Communication Through Atmospheric Turbulence—Part II: Bounds on Ergodic Classical and Private Capacities

Vacuum-propagation optical communication with high photon efficiency (many bits/photon) and high spectral efficiency (many bits/s ·Hz) requires operation in the near-field power transfer regime with a large number of spatial modes. For terrestrial propagation paths, however, the effects of atmospheric turbulence must be factored into the photon and spectral efficiency assessments. In Part I of this study [N. Chandrasekaran and J. H. Shapiro, “Photon Information Efficient Communication Through Atmospheric Turbulence-Part I: Channel Model and Propagation Statistics,” J. Lightw. Technol., vol. 32, no. 6, pp. 1075-1087, Mar. 2014], modal-transmissivity statistics were derived for the turbulent channel that depend solely on the mutual coherence function of the atmospheric Green's function, and these bounds were evaluated for ~ 200 spatial-mode systems whose transmitters used either focused-beam (FB), Hermite-Gaussian (HG), or Laguerre-Gaussian (LG) modes and whose receivers either did or did not employ adaptive optics. This Part II paper derives upper and lower bounds for the ergodic Holevo capacities of classical and private information transmission over the multiple spatial-mode turbulent channel that can be evaluated from Part I's transmissivity statistics. Also included are bounds on the ergodic capacity for on-off keying encoding and direct detection. It is shown that: 1) adaptive optics are not necessary to realize high photon information efficiency and high spectral efficiency simultaneously; 2) an FB-mode system with perfect adaptive optics outperforms its HG-mode and LG-mode counterparts; and 3) the converse is true when adaptive optics are not employed.
ON THE COSTWISE OPTIMALITY OF HIERARCHICAL MULTIRESPONSE RANDOMIZED BLOCK DESIGNS UNDER THE TRACE CRITERION

Abstract : Consider the class of general incomplete multiresponse (GIM) designs in which the set of units is divided into blocks of equal size, such that in any block the same subset of responses is measured on each unit. It is shown that with respect to the trace criterion and a reasonable cost restriction, the subclass of hierarchical multiresponse (HM) designs is complete in the sense that given any GIM design, there exists a HM design such that the cost involved under the two designs is the same, but the trace of the covariance matrix of the estimates of the parameters under the HM design is less than or equal to the similar quantity under the GIM design. The results also establish the important fact that there is a large class of situations where the standard multiresponse model (under which all responses are measured on each unit) should not be used. The nonlinear programming problem associated with obtaining the optimum HM design is stated and solved. (Author)
Exchange of Carbon Dioxide by a Deciduous Forest: Response to Interannual Climate Variability

The annual net uptake of CO2 by a deciduous forest in New England varied from 1.4 to 2.8 metric tons of carbon per hectare between 1991 and 1995. Carbon sequestration was higher than average in 1991 because of increased photosynthesis and in 1995 because of decreased respiration. Interannual shifts in photosynthesis were associated with the timing of leaf expansion and senescence. Shifts in annual respiration were associated with anomalies in soil temperature, deep snow in winter, and drought in summer. If this ecosystem is typical of northern biomes, interannual climate variations on seasonal time scales may modify annual CO2 exchange in the Northern Hemisphere by 1 gigaton of carbon or more each year.
THE POTENTIAL IMPACT OF RAPID DIAGNOSIS OF BACTEREMIA ON HOSPITALIZATION OF INFANTS SUSPECTED OF HAVING SERIOUS BACTERIAL INFECTION (SBI). 1036

THE POTENTIAL IMPACT OF RAPID DIAGNOSIS OF BACTEREMIA ON HOSPITALIZATION OF INFANTS SUSPECTED OF HAVING SERIOUS BACTERIAL INFECTION (SBI). 1036
Incoherent neutron scattering and the dynamics of confined polycarbonate films.

Incoherent elastic neutron scattering measurements are performed on thin (75 to 1015 \AA{}) polycarbonate films supported on Si wafers. We find that the mean-square atomic displacement $〈{u}^{2}〉$ is diminished by thin film confinement. For film thicknesses comparable to the unperturbed dimensions of the macromolecule, we observe two characteristic crossover temperatures in $〈{u}^{2}〉$ as a function of temperature $T$, one above and the other below the bulk ${T}_{g}$. Furthermore, the harmonic force constant $\ensuremath{\kappa}$, defined by the low temperature dependence of $〈{u}^{2}〉$ (i.e., $\ensuremath{\kappa}\ensuremath{\approx}{k}_{B}T/〈{u}^{2}〉$), increases as the film thickness decreases. These observations suggest that the atoms are more strongly localized in the thin supported films.
A Citation Analysis of Doctoral Dissertations in Atmospheric Science at the University at Albany

A citation analysis of doctoral dissertations was conducted for the department of Atmospheric and Environmental Sciences at the University at Albany. A total of twenty-nine dissertations submitted between the years 2000 and 2010 yielded 3,298 citations. These graduate students relied on journal articles (85.1 percent) more than books (7.6 percent). A list of twenty-six core titles was created. These results will be useful for the University Libraries and other institutions with collections in atmospheric sciences.
Electron precipitation events driven by lightning in hurricanes

[1] In mid-September of 2003, Hurricane Isabel passed through the Great Circle Path (GCP) of a subionospherically propagating LF signal between the NAU transmitter in Puerto Rico and a receiver located outside Boston. Cloud-to-ground lightning flashes detected by the Long-Range Lightning Detection Network (LRLDN) and located in the outer rainbands of the hurricane were associated with perturbations in the received LF signal consistent with lightning-induced electron precipitation (LEP) events. The number of perturbations, detected on the LF signal, exhibiting the known characteristics (rapid onset followed by slow recovery) of LEP events tended to increase with the occurrence of hurricane-associated lightning near the GCP. The majority (>65%) of causative lightning flashes (those flashes recorded in the LRLDN data that were time-correlated with spherics associated with LEP events in the VLF/LF data) occurred within 500 km of the GCP; and those flashes associated with Isabel typically occurred in the outer rainbands of the hurricane. While lightning generally occurs more frequently in the outer rainbands of hurricanes than in other tropical oceanic storms, there is no indication that the hurricane-associated lightning is more likely to induce electron precipitation events than lightning associated with other storm systems. Hurricane Floyd (in September of 1999) and Hurricane Fabian (in August/September of 2003) also passed near the GCP of subionospherically propagating VLF/LF signals, and the received signals exhibited similar perturbation patterns.