cssi/SciSciGPT-SciSciNet huggingface dataset:
One-Carbon Metabolism in Health and Disease

One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention.
Collective intelligence of temporal statistics for segmenting sustained infant feeding behaviors in Videos

Converging evidence suggests that the risk of obesity may be at least partially determined during infancy. Instead of measuring total caloric intake, obesity research shifts its paradigm to examining infant feeding behaviors so that the risk of overeating can be detected in early life. To the best of our knowledge, this paper for the first time proposes a novel video analysis protocol with which to discover meaningful, objective, and valid estimates of infant feeding patterns, e.g., the sucking counts over a sustained feeding timeframe as an initial attempt. The underlying premise is that, after tracking a collection of visual features, a back-and-forth periodic movement exhibiting bimodality properties can be segmented from other cluttered ones to indicate sucking behavior, irrespective of camera angles and subjects. We introduce and formulate this motion-of-interest segmentation as a Linear Programming (LP) problem where the optimal solution intelligently infers the sucking count from a collection of temporal statistics after feature tracking. Preliminary experiments on video sequences of different camera angles and subjects successfully validate our hypothesis and show promising results of the solution.
Photodegradation of Metal Oxide Interlayers in Polymer Solar Cells

The effect of 1 sun illumination for 24 h on encapsulated inverted organic photovoltaic devices is studied through a series of electrical and optical characterizations for donor/acceptor polymer solar cells based on poly(dithienogermole-alt-thienopyrrolodione)/[6,6]-phenyl C71 butyric acid methyl ester blends. Power conversion efficiency is significantly reduced after light exposure due to a 45% drop in the device fill factor and a 40% drop in both the open circuit voltage and short circuit current. The decrease in open circuit voltage is attributed to a reduction in the built-in field in the device due to photodegradation of the ZnO interlayer. The reduction in fill factor and short circuit current is shown to be due to the formation of an extraction barrier for hole collection as a result of photodegradation of the MoOx interlayer. Using a 400 nm long pass filter to block the UV light, device stability is significantly enhanced, resulting in a decrease in power conversion efficiency of less than 5% under the same operation conditions.
Early phase trials bridging the gap between prevention and treatment.

ED04-03 Due to the low incidence and long process of cancer development, prevention trials typically require large sample size, long study duration and are costly. Furthermore, since prevention trials target relatively healthy population, successful prevention regimens require not only to be efficacious but also need to be well tolerated with little or no toxicity. With the advancement in the understanding of biology, cancer prevention and treatment share similar many molecular mechanisms in terms of carcinogenesis, cell promotion, cancer recurrence, progression, and metastasis. The advent in the development of targeted agents further lay out the common pathways in searching for effective preventive and therapeutic agents. Abbruzzese and Lippman (Cancer Cell 2004) pointed out the convergence of prevention and therapy and identified key elements in early-phase clinical drug development, which can facilitate the development of both preventive and therapeutic agents. A few important areas in the early phase of drug development include: (1) Identify high risk individuals. Individual cancer risk can be calculated be existing models, for example, via Gail model or Claus model for breast cancer and Bach model for lung cancer. Subjects with premalignant lesions or intra-epithelial neoplasm are ideal candidates for prevention trials; (2) Identify subjects with targets. For targeted agent trials, selecting subjects most likely to respond based on the agent9s mechanism of action can dramatically increase the study efficiency; (3) Apply efficient and flexible designs such that correct answers can be reached with a smaller number of patients in a shorter period of time; and (4) Calculate the risk benefit ratio. It is evident that all treatments come with certain side effects. Balancing the efficacy and toxicity is critically important for developing successful prevention strategies. Data and simulation studies from recent breast cancer, colorectal cancer, lung cancer, and oral cancer trials will be used to illustrate these design issues.
Asymmetric 1,5-diarylpenta-1,4-dien-3-ones: Antiproliferative activity in prostate epithelial cell models and pharmacokinetic studies.

Abstract To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones ( 25 – 58 ) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58 , with IC 50 values in the range of 0.03–0.12 μM, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G 0 /G 1 phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone.
Unexpected significant increase in bulk conductivity of a dielectric arising from charge injection

Charge injection is a common phenomenon in heterostructures or devices containing metal-insulator interfaces under a voltage bias ranging from dielectric capacitors to electroluminescent and lasing devices. It is generally believed that charge injection only significantly increases the conductivity near the interfacial region or in capacitors with very thin dielectric layers. In this work, the impact of charge injection on bulk conductivity of a 0.5 mm thick Fe-doped SrTiO3 single crystal is investigated with a combination of experimental impedance measurements and computational modelling. It is found that the interfacial charge injection may increase the predicted bulk conductivity of a dielectric by more than one order of magnitude as a consequence of Schottky barrier height lowering.
Upregulation of P2Y1 in neonatal nociceptors regulates heat and mechanical sensitization during cutaneous inflammation.

The upregulation of various channels and receptors classically linked to sensory transduction from the periphery tightly correspond with changes in the responsiveness of specific subpopulations of primary afferents to mechanical and heat stimulation of the skin at different ages. Previous reports in adults have suggested that the purinergic adenosine diphosphate receptor, P2Y1 can specifically regulate sensory neuron responsiveness to heat stimuli in addition to neurochemical alterations in primary afferents during cutaneous inflammation. To determine if the upregulation of P2Y1 found in the dorsal root ganglia of neonatal mice with cutaneous inflammation initiated at postnatal day 7 (P7) was responsible for the specific alteration in heat sensitivity found in faster conducting (“A”-fiber) nociceptors, we assessed the response properties of cutaneous afferents using an ex vivo hairy hindpaw skin-saphenous nerve-dorsal root ganglion-spinal cord preparation in conjunction with nerve-targeted knockdown of P2...
Sixty Years of Failing to Prosecute Sexual Crimes: From Raphaël Lemkin at Nuremberg to Lubanga at the International Criminal Court

The trial of Thomas Lubanga Dyilo at the International Criminal Court (ICC) is widely acknowledged as a landmark case in international criminal law. While the defendant was convicted of war crimes, he was cleared of charges for acts consistent with sexual crimes by the trial chamber, disappointing observers and human rights advocates who widely considered him to have facilitated mass rape in the Democratic Republic of Congo. This chapter argues that the two primary reasons why the prosecution of rape and other sexual crimes failed in the case at the ICC were the same challenges to the prosecution of sexual crimes that Raphael Lemkin identified when he urged his colleagues at Nuremberg to prosecute Nazi defendants for sexual crimes. The chapter pays particular attention to Lemkin’s insistence that prosecutors should present sexual crimes as integral to larger criminal programs, so that leaders can be held accountable in international criminal courts for acts of sexual crimes without having to prove a direct causal link between high-ranking defendants and the acts of sexual crimes committed by low-level perpetrators.
The direct role of 5-lipoxygenase on tau pathology, synaptic integrity and cognition in a mouse model of tauopathy.

Neurodegenerative tauopathies are characterized by pathological accumulation of highly phosphorylated isoforms of tau protein, which leads to progressive neuronal loss. Neuroinflammation often accompanies tau-driven diseases; however, the direct role of neuroinflammation in tauopathies remains unknown. The 5-lipoxygenase (5LO) is a pro-inflammatory enzyme, which produces several bioactive metabolites and is widely expressed in the central nervous system. Previously, our group showed that 5LO influences the Alzheimer’s disease (AD) phenotype of APP transgenic mice as well as a mouse model with plaques and tangles. However, whether this protein directly modulates tau phosphorylation and subsequent neuropathology remains to be fully investigated. In the current study, we provide evidence for an age-dependent and region-specific upregulation of the 5LO pathway (protein, message and activity) in a transgenic mouse model of tauopathy, the P301S line. In addition, we demonstrate that genetic deletion of 5LO in this mouse model results in significant memory improvement, reduces tau phosphorylation at specific epitopes as well as neuroinflammation and rescues synaptic pathology. In vitro studies confirmed that 5LO directly modulates tau phosphorylation at the same epitopes as for the brain tissues. Taken together, our data reveal an active involvement of the 5LO pathway in the development of the tauopathy phenotype and provide strong support to the hypothesis that this enzymatic protein should be considered a novel and viable therapeutic target for the treatment of human tauopathy.
GeoSecure: Towards secure outsourcing of GPS data over cloud

Today geolocation data is used extensively in multiple applications and devices. GPS trajectory data can reveal political, religious affiliations, personal habits, shopping preferences etc. It threatens large number of users who use location-based services on their devices, because they are afraid of revealing their locations and concerned about being tracked. Multiple approaches have been proposed to solve problems related with trajectory data such as encrypting geolocation data, decoupling from users' unique identifiable data using privacy algorithms, and storing the data using compression algorithms. Generally, Location Based Service (LBS) providers must perform these operations sequentially on data which turns out to be inefficient. In this paper, we propose a novel approach to resolve the issues of high data storage cost, security, and privacy threats all at once. Operations on encoded GPS trajectory data are performed using modified delta compression and the Haversine distance in a lossless and privacy ensured way. It can be used to calculate velocity, acceleration, distance, etc. without actually revealing location of the user. the cloud storage cost of the GPS data is reduced using modified delta compression.
SPECT Functional Neuroimaging in Patients with AIDS

This is the third in a four-part article series on AIDS. Upon completion of this article, the technologist will have an understanding of the neurological complications of the AIDS virus and how nuclear medicine techniques can be used for early detection of CNS disorders.
Descolonización del conocimiento: una mise en place epistemográfica

espanolEn este articulo analizo y cartografio algunos de los varios problemas conceptuales y filosoficos pertinentes a los discursos relacionados con la «descolonizacion epistemica». Estas discusiones ocurren en un amplio espectro de disciplinas y muchas veces implican ambiguedades o desacuerdos abiertos sobre puntos fundamentales. Este articulo ofrece una explicacion de porque la (des)colonizacion epistemica es un problema en primer lugar y pone en evidencia algunas de las diferencias claves entre varios enfoques distintos a la descolonizacion del conocimiento. La presente aclaracion, afirmo, es crucial para vincular proyectos de descolonizacion teorica a programas politicos concretos y para superar un enfoque prima facie para la descolonizacion del conocimiento. EnglishIn this paper I analyze and chart a number of the different conceptual and philosophical issues pertinent to discourses concerning ‘epistemic decolonization.’ Such discussions occur across a wide range of disciplines and often involve equivocations and/or overt disagreements about fundamental issues. This piece offers one account of why epistemic (de)colonization is a problem in the first place and brings to light some of the key differences between a number of different approaches to the decolonization of knowledge. The present clarification, I argue, is crucial to linking projects of theoretical decolonization to concrete political programs and to overcoming a prima facie approach to decolonizing knowledge. portuguesNo presente artigo, analisa-se um listado de diferentes conceitos e questoes filosoficas pertinentes para discursos relativos a descolonizacao epistemica. Tais discussoes perpassam um amplo espectro de disciplinas e com frequencia envolvem equivocos e/ou desacordos abertos sobre assuntos fundamentais. O artigo oferece uma narrativa sobre por que a descolonizacao epistemica e um problema e lanca luzes sobre diferencas fundamentais entre algumas abordagens acerca da descolonizacao do conhecimento. Argumenta-se que essa elucidacao e crucial para conectar projetos de descolonizacao teorica a programas politicos concretos e para superar uma abordagem prima facie acerca da descolonizacao do conhecimento.
Balancing Costs And Benefits Of New Privacy Mandates

Technological innovations that allow businesses unprecedented access to personal financial and medical records have prompted widespread calls for safeguards and increased security. In his working paper "Balancing the Costs and Benefits of New Privacy Mandates," Robert E. Litan, codirector of the AEI-Brookings Joint Center for Regulatory Studies, asserts that some safeguards may be necessary. But he cautions against over-regulation that could ultimately inconvenience consumers or inflate prices. In particular, Litan urges Congress to pass a limited, but comprehensive, federal statute that would require companies - whether doing business on or off the Internet - to notify consumers how information collected about them will be used and to afford them an opportunity to "opt out" of having their data shared with other parties for marketing purposes. Litan favors an even stricter regime for medical information, which is especially sensitive, and should not in his view be shared with affiliates or outsiders without consumers' explicit consent. Litan opposes, however, more far-reaching restrictions on the sharing of personal information, arguing that the costs would outweigh the benefits. A relatively unfettered flow of information allows investigators to root out fraud, increases competition that saves consumers money, and can result in people receiving product information tailored to their interests and financial status. Litan concludes that a limited notice and opt-out requirement would be in the self-interest of business, which would enhance customer trust, and thus would produce benefits in excess of the small costs involved.
Appraisals of President Obama's economic performance: Racial resentment and attributional responsibility

In this research, we show that positive and negative framings of the economy motivated racial resentments and consonant judgments among Whites about President Obama's responsibility for the economy. Using experimental data collected in the 2012 Cooperative Congressional Election Study (CCES), we find that Whites attributed more responsibility to Obama under negative economic conditions (i.e., blame) than positive economic conditions (i.e., credit). Partisanship influenced both patterns, but racial resentment matters only among Democrats and Independents, not Republicans. We also compared President Obama to governors, and found that Whites attributed equal responsibility to the President and governors for negative economic conditions, but gave more responsibility to governors than Obama for positive conditions. Whites also gave governors more responsibility for state improvements than they gave Obama for national ones. Our findings highlight the likely inescapability of racial biases regardless of positive information or shared political identity.
Irony and Dialectics: One-dimensional Man and 1968

In this article, the author analyses the role of irony in one of the texts that had the most influence in the 1968 movements around the world: The One-dimensional Man, by Herbert Marcuse. Understanding irony as an evident sign of human two-dimensionality, and emphasizing its dialectical potential, the author questions the subversive viability and the specific characteristics of every type of irony. To conclude, he focuses in the operability of irony in Marcuse’s work to encourage resilience and increase the possibility of inspiring political engagement through it.
Ultrastructural Changes of the Right Ventricular Myocytes in Pulmonary Arterial Hypertension.

Background Pulmonary arterial hypertension (PAH) is a serious disease without cure. Elevated pulmonary vascular resistance puts strain on the right ventricle (RV) and patients die of RV failure. Su...
A systematic review of the association between fatigue and cognition in chronic noncommunicable diseases.

ObjectivesFatigue is one of the most common symptoms associated with chronic noncommunicable diseases, and it may also increase cognitive impairment. However, associations between fatigue and cogni...
Early Outcomes from the Innovation Initiative at the Aerospace Corporation

The aerospace industry is undergoing tremendous changes causing a shift in focus, methodology, and the speed of innovation. At the same time, the “NewSpace” sector of the aerospace industry consists of almost 1,000 companies focused on creating different business models for accessing space. As a result, the role of The Aerospace Corporation (Aerospace) as a trusted advisor to the U.S. government, is taking on a new focus. The speed and agility of the NewSpace sector is pushing Aerospace to elevate our culture of innovation. In this paper, we describe the programs we created to stimulate an innovative culture and some examples of employee innovation that have resulted from those programs.
Fibroepithelial Vaginal Polyps in a Newborn Female

Abstract Discussion, diagnosis, and management of fibroepithelial polyps in a newborn female.
Mec1ATR Autophosphorylation and Ddc2ATRIP Phosphorylation Regulates DNA Damage Checkpoint Signaling.

Summary In budding yeast, a single DNA double-strand break (DSB) triggers the activation of Mec1ATR-dependent DNA damage checkpoint. After about 12 h, cells turn off the checkpoint signaling and adapt despite the persistence of the DSB. We report that the adaptation involves the autophosphorylation of Mec1 at site S1964. A non-phosphorylatable mec1-S1964A mutant causes cells to arrest permanently in response to a single DSB without affecting the initial kinase activity of Mec1. Autophosphorylation of S1964 is dependent on Ddc1Rad9 and Dpb11TopBP1, and it correlates with the timing of adaptation. We also report that Mec1’s binding partner, Ddc2ATRIP, is an inherently stable protein that is degraded specifically upon DNA damage. Ddc2 is regulated extensively through phosphorylation, which, in turn, regulates the localization of the Mec1-Ddc2 complex to DNA lesions. Taken together, these results suggest that checkpoint response is regulated through the autophosphorylation of Mec1 kinase and through the changes in Ddc2 abundance and phosphorylation.
New injective proofs of the Erdős–Ko–Rado and Hilton–Milner theorems

Abstract A set system F is intersecting if for any F , F ′ ∈ F , F ∩ F ′ ≠ ∅ . A fundamental theorem of Erdős, Ko and Rado states that if F is an intersecting family of r -subsets of [ n ] = { 1 , … , n } , and n ≥ 2 r , then | F | ≤ n − 1 r − 1 . Furthermore, when n > 2 r , equality holds if and only if F is the family of all r -subsets of [ n ] containing a fixed element. This was proved as part of a stronger result by Hilton and Milner. In this note, we provide new injective proofs of the Erdős–Ko–Rado and the Hilton–Milner theorems.
Strand Displacement Strategies for Biosensor Applications

DNA has many unique properties beyond encoding genetic information, one of which is its physicochemical stability based on Watson–Crick base pairing. Differences in sequence complementarity between multiple DNA strands can lead to the strand displacement reaction (SDR). SDRs have been regularly applied in synthetic biology, drug delivery, and, importantly, biosensing. SDR-based biosensors have high controllability, high sensitivity, and low interference, and can be used for multiplexed detection. Such biosensors have been demonstrated to detect nearly every class of biomolecule. As the field continues to mature, such platforms can be used as an integral tool for the manipulation of biomolecular reactions, bringing biosensors one step closer to the ultimate goal of point-of-care systems.
Calderón Preconditioned Spectral-Element Spectral-Integral Method for Doubly Periodic Structures in Layered Media

An efficient and accurate spectral-element spectral-integral method is developed for rigorously modeling arbitrary inhomogeneous objects with doubly periodicity embedded in a layered medium background. It is an improvement over the traditional finite-element boundary-integral (BI) method. In the proposed approach, the domain decomposition between the interior spectral-element domain and the outer surface BI domain enables the BI domain to be solved by a far more efficient spectral integral method using a uniform mesh; without any loss of generality, it leaves the interior spectral-element domain with flexibility to model any inhomogeneous objects. For the BI domain, with a uniform mesh and rooftop basis functions, we can exploit the Toeplitz structure of the BI matrices with the fast Fourier transform algorithm and apply the Calderon preconditioner to achieve a high iteration convergence rate that will not slow down as the problem gets larger. With the periodic layered medium Green’s functions, the layers without objects can be treated as background and the discretization is avoided. We show that this method is very promising for large-scale problems, because the CPU time and memory required with respect to the number of unknowns grow slowly. We validate this method with a commercial finite element solver and show its ability by solving a large-scale optical lithography problem.
Heart failure exacerbation as only presenting sign of COVID-19

With the increasing number of confirmed cases and accumulating clinical data, our understanding of COVID-19 continues to evolve. Here we describe the case of a patient who was initially admitted for decompensated heart failure with reduced ejection fraction (HFrEF). Only later in his course did he develop fever that led to testing for severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Although we are aware of the common respiratory failure induced by SARS-COV-2, we have scant information that describes cardiac manifestations caused by this novel virus.
Factors Associated With Fatigue in Patients with Breast Cancer Undergoing External Beam Radiation Therapy

Abstract Purpose Cancer-related fatigue (CRF), a prevalent symptom among cancer patients, is a side effect of external beam radiation therapy (EBRT). Even when targeting organs unrelated to caloric intake or the central nervous system, radiation therapy can increase CRF, a poorly understood toxicity resulting from patient-specific, systemic therapy-related, and radiation-specific factors. We sought to determine factors associated with fatigue among patients receiving EBRT for breast cancer. Methods and Materials To determine the variables associated with fatigue among patients with nonmetastatic breast cancer, we retrospectively analyzed prospectively collected toxicity data for a cohort of 1286 adult females with breast cancer who began curative-intent EBRT between April 4, 2010, and October 10, 2017. We hypothesized certain variables are associated with provider-reported Common Terminology Criteria for Adverse Events version 4 fatigue, graded 0 to 3, at baseline and over the course of radiation treatment. Results All patients were women, with a median age of 57 (range, 24-90). Mean fatigue was low (0.35 [95% confidence interval, 0.32-0.38]) at the start of radiation, increasing weekly and peaking at week 6 (0.85 [0.81-0.90]). Baseline fatigue was associated with higher American Joint Committee on Cancer stage (P Conclusions This work informs clinicians which factors are associated with CRF at the start of radiation therapy (more advanced disease and prescription of anxiolytics, anticonvulsants, antidepressants, antihistamines, and antipsychotics) and increase CRF over the course of radiation (smaller fraction size). This extensive analysis of factors associated with fatigue provides further evidence that hypofractionated radiation therapy for breast cancer is associated with less acute toxicity than conventionally fractionated treatment.
Use of the 1,3-β-D-Glucan Assay for the Early Detection of Fungal Endocarditis in a 45-Year-Old Man.

BACKGROUND The management of fungal endocarditis is difficult due to high mortality and incidence of embolization. Fungal blood cultures are the criterion standard for diagnosis but show slow growth or remain negative in more than 50% of cases. We present a case in which the 1,3-s-D-glucan (BG) assay was used to initiate antifungal treatment prior to growth in blood culture. CASE REPORT A 45-year-old man with known intravenous drug use presented to the Emergency Department in acute hypoxemic respiratory failure with a prominent aortic regurgitation murmur. Imaging findings were suggestive of endocarditis. In the Intensive Care Unit, investigations confirmed aortic valve infective endocarditis with abscess. Evidence of widespread embolization, including a shin abscess positive for Candida albicans combined with a positive BG assay prompted treatment with antifungal medication prior to positive fungal cultures. The patient underwent valve replacement and during recovery was incidentally found to have subclinical cerebral infarctions caused by a septic thrombus positive for C. albicans in the right carotid artery despite weeks of antifungal treatment. Carotid endarterectomy successfully removed the thrombus, but the patient developed a right-sided stroke. Four months later, the patient has no evidence of aortic insufficiency on echocardiogram and has made a nearly full recovery from the stroke. CONCLUSIONS We report a case of left-sided fungal endocarditis in which the BG assay was used for timely medical and surgical management leading to a successful cardiac outcome. Stroke from septic emboli is a potential complication even after weeks of antifungal therapy and valvular replacement.
Neuroendocrine and behavioral measures of negative valence in male sign-tracker and goal-tracker rats

Abstract Cues, or stimuli in the environment, attain the ability to guide behavior via learned associations. As predictors, cues can elicit adaptive behavior and lead to valuable resources (e.g., food). For some individuals, however, cues are transformed into incentive stimuli and can elicit maladaptive behavior. The goal-tracker/sign-tracker animal model captures individual differences in cue-motivated behaviors, with reward-associated cues serving as predictors of reward for both goal-trackers and sign-trackers, but becoming incentive stimuli only for sign-trackers. While these distinct phenotypes are characterized based on Pavlovian conditioned approach behavior, they exhibit differences on a number of behaviors of relevance to psychopathology. To further characterize the neurobehavioral endophenotype associated with individual differences in cue-reward learning, we investigated neuroendocrine and behavioral profiles associated with negative valence in male goal-trackers, sign-trackers, and intermediate responders. We found that baseline corticosterone increases with Pavlovian learning, and that this increase is positively associated with the development of sign-tracking. We did not observe significant differences between goal-trackers and sign-trackers in behavior during an elevated plus maze or open field test, nor did we see differences in the corticosterone response to the open field test or physiological restraint. We did, however, find that sign-trackers have greater glucocorticoid receptor mRNA expression in the ventral hippocampus, with no phenotypic differences in the dorsal hippocampus. These findings suggest that goal-trackers and sign-trackers do not differ on indices of negative valence; rather, differences in neuroendocrine measures between these phenotypes can be attributed to distinct cue-reward learning styles. Significance Statement While the goal-tracker/ sign-tracker animal model derives from individual differences in Pavlovian conditioned approach behavior, other traits, including some of relevance to addiction and post-traumatic stress disorder, have been shown to co-exist with the propensity to sign-track. The extent to which this model encompasses differences in negative valence systems, however, remains largely unexplored. Here we show that behavioral and corticosterone response to paradigms associated with negative valence do not differ between goal-trackers and sign-trackers; but baseline corticosterone levels appear to be linked to the development of sign-tracking, as do differences in glucocorticoid receptor expression in the ventral hippocampus. These findings suggest that neuroendocrine measures typically associated with negative valence may, in fact, play an important role in positive valence systems.
Every Body Counts: Measuring Mortality From the COVID-19 Pandemic.

As of mid-August 2020, more than 170 000 U.S. residents have died of coronavirus disease 2019 (COVID-19); however, the true number of deaths resulting from COVID-19, both directly and indirectly, is likely to be much higher. The proper attribution of deaths to this pandemic has a range of societal, legal, mortuary, and public health consequences. This article discusses the current difficulties of disaster death attribution and describes the strengths and limitations of relying on death counts from death certificates, estimations of indirect deaths, and estimations of excess mortality. Improving the tabulation of direct and indirect deaths on death certificates will require concerted efforts and consensus across medical institutions and public health agencies. In addition, actionable estimates of excess mortality will require timely access to standardized and structured vital registry data, which should be shared directly at the state level to ensure rapid response for local governments. Correct attribution of direct and indirect deaths and estimation of excess mortality are complementary goals that are critical to our understanding of the pandemic and its effect on human life.
Racial Diversity and Measuring Merit: Evidence from Boston's Exam School Admissions

The impact of admissions process design on the racial diversity of schools and colleges has sparked heated debates. We study the pipeline into Boston's three public exam schools to understand racia...
Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes

Cancers harboring mutations in the Kirsten rat sarcoma homolog (KRAS) gene have been associated with poor prognosis and lack of targeted therapies. KRAS mutations occur in approximately one in four patients diagnosed with non-small cell lung cancer (NSCLC) with KRAS G12C mutations harbored at approximately 11-16%. Research into KRAS-driven tumors and analytical chemistry have borne a new class of selective small molecules against the KRAS G12C isoform. Phase II data for sotorasib (AMG510) has demonstrated a 37.1% overall response rate (ORR). Adagrasib (MRTX849) has demonstrated a 45% ORR in an early study. While single agent efficacy has been seen, initial data suggest combination approaches are an opportunity to improve outcomes. Here, we present perspectives on the initial progress in targeting KRAS G12C, examine co-mutations evident in KRAS G12C NSCLC, and comment on potential future combinatorial approaches including SHP2, SOS1, MEK, EGFR, mTOR, CDK, and checkpoint blockade which are currently being evaluated in clinical trials. As of May 28, 2021, sotorasib has achieved US FDA approval for patients with KRAS G12C mutant lung cancer after one line of a prior therapy.
Double Torsion Technique as a Universal Fracture Toughness Test Method

A method of measuring the fracture toughness of materials is described that is both simple and universal. A specimen is failed in double torsion so that a crack is driven down the center of a rectangular specimen. The energetics of failure are such that the load causing the crack remains constant as the crack deepens and this load is directly related to the fracture toughness. This enables a simple specimen to be used and obviates the difficulties associated with crack depth or compliance measurements or both. Results are shown for aluminum alloys to supplement earlier work on glass and polymers.
Abstract T MP67: Physical Activity Reduces Stroke Risk Among Women in the California Teachers Study Cohort

Background: Major modifiable stroke risk factors are well-established, yet strategies for effective prevention remain challenging. Developing stroke prevention strategies for women is critical due to: (i) the higher fatality and disability rate that women suffer compared to men, (ii) the unique risks to women such as from post-menopausal hormone therapy use, and (iiii) the aging female population. We evaluated three important modifiable stroke risk factors- obesity, hormone therapy, and physical activity, in the California Teachers Study cohort to identify potential stroke prevention strategies. Methods: The California Teachers Study comprises 133,479 women who enrolled in 1995 and have since been continuously followed. Using linked California state hospitalization data from 1996-2010, 3126 stroke events were defined as ischemic (N=2416; ICD-9 433, 434, 436) or hemorrhagic (N=710; ICD-9 430-432, excluding 432.1) and were validated by medical record review. Information about obesity, physical activity, hormone therapy, and medical history was collected at baseline and in follow-up questionnaires. Multivariable-adjusted hazards ratios and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2010. Results: Consistent with previous reports, current post-menopausal hormone therapy use was associated with a 1.3-fold increased risk for stroke (95% CI=1.03-4.85). Moderate to strenuous physical activity in the 3 years before enrollment (but not lifetime activity) decreased stroke risk by 20% (HR=0.79, 95% CI=0.71-0.98). This decreased risk among physically active women was similar among current hormone therapy users, and appears to counteract the increased risk observed with current hormone therapy use. We found no association between obesity and stroke that was independent of diabetes. Conclusions: Recent physical activity reduces stroke risk and appears to counteract the increased risk associated with post-menopausal hormone therapy use.
Social transmission of food preference in mice

The social transmission of food preference (STFP) is an ethologically relevant test of olfactory memory that can be used in mice. In this test, "observer" mice interact with a "demonstrator" mouse that has recently eaten a novel food. When observer mice are presented with a choice between the food eaten by the demonstrator and some other novel food, observer mice prefer the food eaten by the demonstrator. This phenomenon depends on the observer mice detecting olfactory cues on the breath of the demonstrator mouse during their interaction. The subsequent food preference serves as a measure of memory for those olfactory cues. This unit describes a method for performing STFP in mutant mice. The method explains how to address potential confounding factors and avoid possible pitfalls.
Common LISP: A Gentle Introduction to Symbolic Computation

A highly accessible introduction to LISP, this is for inexperienced programmers and programmers new to LISP. A LISP "toolkit" in each chapter explains how to use Common LISP programming and debugging tools such as DESCRIBE, INSPECT, TRACE and STEP.
A seafloor observatory to monitor a cold seep in the Gulf of Mexico

Cold seeps occur widely on the continental shelf and slope of the northern Gulf of Mexico. Typically, they are located where faults intersect the sea floor and act as conduits for hydrocarbon fluids migrating upward from deep reservoirs. The fluids are sources of energy for microbes which proliferate in the vicinity of the seeps. The microbes precipitate a wide range of minerals that accumulate to form mounds which surround the seeps. The microbes also secrete biosurfactants that enhance the formation of natural gas hydrates (Rogers and Lee, 2001; Rogers et al., 2002; Rogers et al., 2003). Therefore, in water depths greater than about 450m, the mounds often contain hydrates. The photograph in fig.1 shows such a mound. Its vicinity is littered with mussel shells and other chemosynthetic detritus. Parts of the mound's surface are covered by orange-colored microbial mats. The white material outcropping from the lower part of the mound is gas hydrate.
Self-organizing linear output map (SOLO): An artificial neural network suitable for hydrologic modeling and analysis

Artificial neural networks (ANNs) can be useful in the prediction of hydrologic variables, such as streamflow, particularly when the underlying processes have complex nonlinear interrelationships. However, conventional ANN structures suffer from network training issues that significantly limit their widespread application. This paper presents a multivariate ANN procedure entitled self-organizing linear output map (SOLO), whose structure has been designed for rapid, precise, and inexpensive estimation of network structure/parameters and system outputs. More important, SOLO provides features that facilitate insight into the underlying processes, thereby extending its usefulness beyond forecast applications as a tool for scientific investigations. These characteristics are demonstrated using a classic rainfall-runoff forecasting problem. Various aspects of model performance are evaluated in comparison with other commonly used modeling approaches, including multilayer feedforward ANNs, linear time series modeling, and conceptual rainfall-runoff modeling.
TH-AB-303-12: Commissioning of Magnetic Resonance Imaging-Based Tumor Tracking and Beam Control

Purpose: To develop a methodology for commissioning the real-time tumor tracking and beam control capabilities of a magnetic resonance imaging radiation therapy (MR-IGRT) system. Methods: The MRIdian (ViewRay, Inc., Oakwood Village, OH) MR-IGRT machine consists of a 0.35-T magnet and a three-head Co-60 delivery system capable of real-time sagittal plane acquisition at 4 frames per second (fps). After obtaining a volumetric MR image, a “target” is chosen by contouring an area of interest with different signal intensity than the surrounding medium. A “boundary” is created by expanding the target by some margin or using a previous contour. After a sagittal plane is chosen, during delivery the system deforms the target contour on each acquired plane, and compares it to the boundary - if the target contour is observed outside the boundary, the beam is turned off. Since the system uses no external or internal surrogates, careful tests of the individual system components had to be created and executed to characterize the accuracy and potential dosimetric errors associated with real-time gating on real anatomy. Results: Tests for spatial, temporal, and dosimetric accuracy were devised; these included latency, spatial integrity of the magnetic field, film, and ionization chamber measurements. A new set of phantoms was created, including a CIRS (Norfolk, VA) motion phantom that was modified to function in the magnetic field and have appropriate signal intensities. This phantom also included optical sensors that allowed for signal readout of its target position, and subsequent comparison to “beam off” signal on the heads. Boundary margins and other parameters were evaluated with film dosimetry by comparing the spatial distribution of the dose for static vs. gated deliveries. Ionization chambers were used to confirm an implemented shutter dose correction. Conclusion: The first commercially-available MR-IGRT system’s gating capabilities were characterized and successfully implemented in the clinic. Drs. Green, Kashani, and Mutic have held non-compensated consultant roles, received honoraria, and had travel expenses paid by ViewRay, Inc.
When Professors Don't Return Essays

Issue: Students devote hundreds of hours to writing notes during medical school clerkships but receive very limited feedback on that work. Medical student notes are like college essays—both are persuasive compositions. But attending physicians rarely scrutinize student notes like college professors analyze essays. This is a missed opportunity to teach clinical reasoning. Evidence: A survey at our institution showed that only 16% of students received written feedback and 31% received oral feedback on their notes from more than 3 attending physicians during the first 8 months of 3rd-year clerkships. Many studies have reported a paucity of feedback across multiple domains and a sense among students that clinical reasoning is not being adequately taught during clerkships. Meanwhile, college professors teach written composition and reasoning through interactive methods that help students to develop structured, well-reasoned arguments. A recent study showed that 85% of Oxford undergraduates favored these demand...
THE EFFECT OF EXPERIENCE ON ADULTS' ACQUISITION OF A SECOND LANGUAGE

Previous research has suggested that child but not adult immigrants to the United States and Canada make regular progress learning English as their length of residence (LOR) increases. If children and adults received the same kind of second language (L2) input, such evidence would support the existence of a critical period for L2 acquisition. The present study compared groups of Chinese adults living in the United States who differed in LOR in order to assess the role of input in adults' naturalistic acquisition of an L2. We assessed the Chinese participants' identification of word-final English consonants (experiment 1), their scores on a 144-item grammaticality judgment test (experiment 2), and their scores on a 45-item listening comprehension test (experiment 3). The Chinese participants were assigned to one of four groups (n = 15 each) based on LOR in the United States and their primary occupation (students vs. nonstudents). Significantly higher scores were obtained for the students with relatively long LORs than for the students with relatively short LORs in all three experiments. However, the difference between the nonstudents differing in LOR was nonsignificant in each instance. The results suggested that the lack of an effect of LOR in some previous studies may have been due to sampling error. It appears that adults' performance in an L2 will improve measurably over time, but only if they receive a substantial amount of native speaker input.
Laminin α2 is a component of brain capillary basement membrane: Reduced expression in dystrophic dy mice

Abstract In the present study we demonstrate low level expression of the laminin α2 chain in brain and localize the α 2 protein to the capillary basement membrane. While in peripheral basement membranes the laminin α1 and α2 chains have an almost mutually exclusive distribution, the present results suggest both α1 and α2 in the cerebral capillary basement membrane. Towards elucidating the function of α2 in brain, we have performed ultrastructural analysis of the capillary basement membrane in dystrophic dy mice, which show a 70–90% and >95% reduction of α2 messenger RNA compared to heterozygous and wild-type mice, respectively, and show a nearly total absence of the α2 protein by immunoftuorescence. In contrast to the muscle and Schwann cell basement membrane, where α2 deficiency causes structural basement membrane abnormalities, the present results show that the lack of the α2 subunit in the cerebral capillary basement membrane is not detrimental to its structure. This observation might be explained by the fact that the cerebral capillary basement membrane expresses both α chains and therefore exhibits structural redundancy.
Case Report Alpha 1 Antitrypsin Deficiency and Plasma Thromboplastin Antecedent Deficiency — A New Association?

We report a 74-year-old woman presenting with vaginal bleeding and hepatomegaly and was found to have plasma thromboplastin antecedent deficiency and alpha 1 antitrypsin deficiency. She also had liver and lung disease of the type associated with the antiprotease deficiency. The relative rarity of the two deficient states led to family and genetic studies. The possibility of a new genetic syndrome is entertained.
A simple method for tosylation with inversion.

Abstract In this paper we describe a simple one-step procedure for tosylation with inversion, using zinc tosylate, diethylazodicarboxylate and triphenylphosphine.