cssi/SciSciGPT-SciSciNet huggingface dataset:
Identifying Barriers Among Childhood Cancer Survivors Transitioning to Adult Health Care

The aim of this study was to identify and describe barriers of young adult childhood cancer survivors transitioning to adult health care within 5 years of leaving a pediatric oncology practice. Several barriers have been identified in the literature, but other obstacles as to why this vulnerable population may be avoiding health care are unknown. This is a descriptive pilot study of a convenience sample of childhood cancer survivors, currently 20 to 25 years of age, who were diagnosed at less than 21 years of age. The Transition to Adult Care Survey assessing survivor barriers is an online survey consisting of 15 questions, with a drop-down menu for answers and 2 open-ended questions. The survey was accessible by smartphone or computer. Standard descriptive statistics were used to describe variables of interest. Our population consisted of 48 childhood cancer survivors. Their mean age was 23.21 years. Only 74% reported following through with annual preventive screening, and 57% reported that they consider themselves at risk for further medical problems as a result of their cancer treatment. Lack of knowledge of the importance of health screening may be a potential barrier to consistent follow-up care.
위암 환자에 있어서 p53 유전자 돌연변이, 종양 p53 단백질 과발현 및 혈청 p53 항체

【Purpose: The clinical implication of p53 mutation in gastric cancer is still unclear, as shown by the discordant results that continue to be reported in the literature. Materials and Methods: To assess p53 gene mutation, tumor p53 overexpression, and serum anti-p53 antibody, we employed a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, an immunohistochemistry using monoclonal antibody DO-7, and an enzymelinked immunosorbent assay (ELISA), respectively. Results: Of 169 surgical specimens of gastric cancer, mutation at exon $5\∼8$ of the p53 was identified in 33 ( $19.5\%$ ) and was significantly correlated with lymph node metastasis. Overexpression of p53 was found in 62 specimens ( $36.7\%$ ) and had a significant correlation with tumor differentiation. Serum anti-p53 antibody was positive in 18 patients ( $10.7\%$ ). Twenty-three of the mutated tumors ( $69.7\%$ ) and 39 of the non-mutated tumors ( $28.7\%$ ) displayed immunoreactivity. Twelve of the immunopositive tumors ( $19.4\%$ ) and 6 of the immunonegative tumors produced anti-p53 antibody. These differences were statistically significant (P】
LOCALIZATION AND RELEASE OF FMRFAMIDE-LIKE IMMUNO- REACTIVITY IN AN INSECT CEREBRAL NEUROENDOCRINE SYSTEM

Neuropeptides secreted by insect cerebral neurosecretory cells (NSCs) are primary endocrine regulators of physiology, development, and behavior. Recently, many workers have shown that insect NSCs and neurohemal organs are immunoreactive to antisera directed against vertebrate and invertebrate neuropeptides. Thus, the insect homologues of these neuropeptides may serve a neurohormonal function. A possible neuroendocrine role in insects for the tetrapeptide Phe-Met-Arg-Phe-NH2(FMRFamide) (Price and Greenberg, 1977) or analogues thereof was suggested by immunocytochemical staining of neurohemal corpora cardiaca (Boer et al., 1980). Because cerebral NSCs of the moth, Manduca sexta, have been identified (Carrow et al., 1984), we used this model system to further clarify the role of FLI in insects. We briefly describe here the distribution of FMRFamide-like immunoreactivity (FLI) in this cerebral neuroendocrine system and provide evidence for storage and calcium dependent release of FLI from the neurohemal organs (Carroll et al., 1986).
Coalescence in the Housing Finance Reform Debate

In the wake of the stalled Johnson-Crapo bill, the overarching goal of housing finance reform continues to be the efficient provision of long-term fixed-rate mortgages to credit-worthy borrowers in all markets throughout the business cycle. This Issue Brief analyzes three newly-proposed plans for reforming the U.S. housing finance system: (1) a proposal from Jim Parrott et al. to merge Fannie Mae and Freddie Mac into a new government corporation; (2) Andrew Davidson’s proposal for mutual ownership of the GSEs by mortgage originators; and (3) an opposing plan from Mark Calabria, arguing against securitization altogether and for a return to the regime of originate-and-hold. Despite differences regarding implementation and governance philosophy, a new consensus may be emerging for reform, demonstrated most clearly in the first two proposals, which recognize the efficiency of centralizing and concentrating control of the housing finance system’s infrastructure and credit risk. Notwithstanding the important points of consensus, the new proposals still leave certain issues unresolved, including the potential for cyclicality. Still, broad support for centralized functions (i.e., promoting standardization, liquidity, consumer protection, and access to credit), as well as the organic growth of credit risk transfer transactions in recent years, may be important to reigniting the push for resolution of GSE conservatorship.
Beyond the Gaussian Approximation in Exafs

The extended x-ray absorption fine structure (EXAFS) technique was first introduced as an atomic structure determining technique [1] in 1971. Since then its applications have grown dramatically, expanding into many diverse fields [2–9]. With the decade or so of experience in using EXAFS, its limitations and strengths have been defined. Yet there still appears to be a misconception that EXAFS cannot be used to determine the atomic arrangement in highly disordered materials such as amorphous and anharmonic solids. This misconception arose because, although the original formulation of the EXAFS formula was for a general distribution of atoms [10], the formula most commonly employed [11] assumed a Gaussian distribution of the atoms about their average value, introducing a Debye-Waller-type factor. The Gaussian distribution is not generally valid when the disorder is large or anharmonic. In addition, it was thought [10] that multiple scattering effects in the x-ray absorption near-edge structure (XANES) regions would limit the low k information available from EXAFS to above k ≃ 3 A-1. Loss of this low k information would mean that EXAFS cannot determine rms disoorder greater than about 0.1 A.
Subscapularis tendon loading during activities of daily living.

Background The purpose of this study was to determine the relative amount of load that is transmitted through the superior portion of the subscapularis during activities of daily living as compared with the load that is transmitted through the middle and inferior portions in a normal shoulder and in a shoulder with a supraspinatus tear. Methods By use of the Newcastle shoulder model, the subscapularis was modeled with 3 lines of action encircling the humeral head. The load was measured in the entire subscapularis, and the percentage of this load in each of the 3 tendinous bands was calculated. Subsequently, a supraspinatus tear was simulated, and the forces generated by the subscapularis and glenohumeral joint contact forces were measured. Results The maximum force produced by the entire subscapularis muscle for the various activities ranged from 3 to 43 N. Load sharing between the 3 subscapularis bands showed that the superior band bore the largest percentage of the total load of the muscle (95% ± 2%). The load in the subscapularis, particularly in the superior band, increased significantly when a supraspinatus tear was simulated (P Conclusion The superior band of the subscapularis tendon bears the highest percentage of load compared with the middle or inferior band. The load in the subscapularis increased significantly in the presence of a simulated supraspinatus tear. Because a disproportionate amount of force is transmitted through the superior subscapularis, more clinical research is warranted to determine whether tears in this region should be routinely repaired.
Comparison of Listeria monocytogenes recoveries from spiked mung bean sprouts by the enrichment methods of three regulatory agencies.

Abstract Three selective enrichment methods, the United States Food and Drug Administration's (FDA method), the United States Department of Agriculture Food Safety Inspection Service's (USDA method), and the EN ISO 11290-1 standard method, were assessed for their suitability for recovery of Listeria monocytogenes from spiked mung bean sprouts. Three parameters were evaluated; the enrichment L . monocytogenes population from singly-spiked sprouts, the enrichment L . monocytogenes population from doubly-spiked ( L . monocytogenes and Listeria innocua ) sprouts, and the population differential resulting from the enrichment of doubly-spiked sprouts. Considerable L . monocytogenes inter-strain variation was observed. The mean enrichment L . monocytogenes populations for singly-spiked sprouts were 6.1 ± 1.2, 4.9 ± 1.2, and 6.9 ± 2.3 log CFU/mL for the FDA, USDA, and EN ISO 11290-1 methods, respectively. The mean L . monocytogenes populations for doubly-spiked sprouts were 4.7 ± 1.1, 5.5 ± 1.3, and 4.6 ± 1.4 log CFU/mL for the FDA, USDA, and ISO 11290–1 enrichment methods, respectively. The corresponding mean population differentials were 2.8 ± 1.1, 3.3 ± 1.3, and 3.6 ± 1.4 Δlog CFU/mL for the same three enrichment methods, respectively. The presence of L . innocua and resident microorganisms on the sprouts negatively impacted final levels of L . monocytogenes with all three enrichment methods.
Academic correlates of unwanted sexual contact, intercourse, stalking and intimate partner violence: An understudied but important consequence for college students

Sexual assault, partner abuse, and stalking are major problems on college campuses. Past research has demonstrated a host of physiological and psychological outcomes associated with victimization; however, there has been little research conducted on the potential academic outcomes associated with victimization. The purpose of this study was to measure the relation between academic outcomes and experiences of sexual violence, intimate partner violence, and stalking victimization among college students. A sample of 6,482 undergraduate students currently enrolled at one of eight universities in New England was surveyed using items from the subscales of the College Persistence Questionnaire (Academic Efficacy, Collegiate Stress, Institutional Commitment, and Scholastic Conscientiousness). All four types of victimization were associated with significant differences on academic outcomes after controlling for sex and year in school, with victimized students reporting lower academic efficacy, higher college-related stress, lower institutional commitment, and lower scholastic conscientiousness. Polyvictimization was also significantly correlated with outcomes, with the greater number of types of victimization experienced by students being associated with more negative academic outcomes. Implications for future research and campus response were discussed.
First demonstration of simultaneous localization and propulsion of a magnetic capsule in a lumen using a single rotating magnet

This paper presents a method for closed-loop propulsion of a screw-type magnetic capsule with embedded Hall-effect sensors using a single rotating actuator magnet. The method estimates the six-degree-of-freedom (6-DOF) pose of the capsule while it is synchronously rotating with the applied field. It is intended for application in active capsule endoscopy of the intestines. An extended Kalman filter, which uses a simplified 2-DOF process model restricting the capsule to forward or backward movement and rotation about its principle axis, is used to provide a full 6-DOF estimate of the capsule's pose as the capsule travels through a lumen. The capsule's movement in the applied field is constantly monitored to determine if the capsule is synchronously rotating with the applied field. Based on this information, the rotation speed of the external source is adjusted to prevent a loss in the desired magnetic coupling. We experimentally demonstrate, for the first time, simultaneous localization and closed-loop propulsion of a capsule through a lumen using a single rotating magnet. Prior work assumed the capsule had no net motion during the localization phase, requiring decoupled localization and propulsion. This closed-loop performance results in a three times speed up in completion time, compared to the previous decoupled approach.
The Science and Politics of Water Quality

Water quality is a complex resource to analyze in the context of environmental justice, and so specific frameworks and proxies have been developed which in turn have become the basis for governmental regulations and compliance standards. A Critical Physical Geography approach applied to examples from small rural community water systems in Puerto Rico demonstrates how enacting environmental justice through water quality regulation can be counterproductive and even unjust, and reveals the risk in exporting regulations conceived for the United States to systems in its ecologically distinct territories. The case study leads to the conclusion that assessments of water quality and resulting disparities in access should be grounded in a critical understanding of biophysical and social processes.
Germline SDHA mutations in children and adults with cancer

Mutations in succinate dehydrogenase complex genes predispose to familial paraganglioma-pheochromocytoma syndrome (FPG) and gastrointestinal stromal tumors (GIST). Here we describe cancer patients undergoing agnostic germline testing at Memorial Sloan Kettering Cancer Center and found to harbor germline SDHA mutations. Using targeted sequencing covering the cancer census genes, we identified 10 patients with SDHA germline mutations. Cancer diagnoses for these patients carrying SDHA germline mutations included neuroblastoma (n = 1), breast (n = 1), colon (n = 1), renal (n = 1), melanoma and uterine (n = 1), prostate (n = 1), endometrial (n = 1), bladder (n = 1), and gastrointestinal stromal tumor (GIST) (n = 2). Immunohistochemical staining and assessment of patient tumors for second hits and loss of heterozygosity in SDHA confirmed GIST as an SDHA-associated tumor and suggests SDHA germline mutations may be a driver in neuroblastoma tumorigenesis.
Obstetric Outcomes Associated with Fetal Cyanotic Congenital Heart Disease.

Objective To characterize obstetric outcomes associated with cyanotic congenital heart disease (CCHD) in a contemporary population. Study Design We conducted a population-based retrospective cohort study of all livebirths in Ohio (2006–2015). Obstetric characteristics of pregnancies complicated by fetal CCHD were compared with those without CCHD, excluding those with other anomalies and aneuploidy. The primary objective was to determine the risk of cesarean delivery among CCHD affected pregnancies. Multivariate logistic regression estimated the influence of CCHD on these obstetric outcomes. Results Among 1,463,506 live births in Ohio, there were 863 (0.06%) CCHD affected births. The overall cesarean rate was 45.9 versus 31.0% (p Conclusion Obstetric outcomes associated with CCHD include higher risk for cesarean delivery, PTB, SGA, and FIOL.
Association of Positive Affect with Cognitive Health and Decline for Elder Mexican Americans

The goal of this study was to investigate the linkages of positive affect (PA) with cognitive health and its decline among elder Mexican Americans. We conducted secondary analysis of longitudinal data from the Sacramento Area Latino Study on Aging (SALSA). We used the structural equation modeling framework to achieve three specific aims: (1) identify a valid measure of PA, (2) describe within-person trajectories of PA and cognitive health, and (3) test the inter-relations of these two processes over time. Results showed that, on average, PA and cognitive ability (including verbal memory) decreased over time. Yet, there was significant variability in these patterns of change. Bivariate latent growth curve models showed significant correlations of baseline levels and rates of change of PA and cognitive ability even after controlling for age, education, sex, bilingualism, and depression. Results support the hypothesis that increases and decreases in PA tend to be related to increases and decreases in cognitive health at old age among Mexican Americans.
Zeptomole per milliliter detection and quantification of edema factor in plasma by LC-MS/MS yields insights into toxemia and the progression of inhalation anthrax

Inhalation of Bacillus anthracis spores can cause a rapidly progressing fatal infection. B. anthracis secretes three protein toxins: lethal factor (LF), edema factor (EF), and protective antigen (PA). EF and LF may circulate as free or PA-bound forms. Both free EF (EF) and PA-bound-EF (ETx) have adenylyl cyclase activity converting ATP to cAMP. We developed an adenylyl cyclase activity-based method for detecting and quantifying total EF (EF+ETx) in plasma. The three-step method includes magnetic immunocapture with monoclonal antibodies, reaction with ATP generating cAMP, and quantification of cAMP by isotope-dilution HPLC-MS/MS. Total EF was quantified from 5PL regression of cAMP vs ETx concentration. The detection limit was 20 fg/mL (225 zeptomoles/mL for the 89 kDa protein). Relative standard deviations for controls with 0.3, 6.0, and 90 pg/mL were 11.7–16.6% with 91.2–99.5% accuracy. The method demonstrated 100% specificity in 238 human serum/plasma samples collected from unexposed healthy individuals, and 100% sensitivity in samples from 3 human and 5 rhesus macaques with inhalation anthrax. Analysis of EF in the rhesus macaques showed that it was detected earlier post-exposure than B. anthracis by culture and PCR. Similar to LF, the kinetics of EF over the course of infection were triphasic, with an initial rise (phase-1), decline (phase-2), and final rapid rise (phase-3). EF levels were ~ 2–4 orders of magnitude lower than LF during phase-1 and phase-2 and only ~ 6-fold lower at death/euthanasia. Analysis of EF improves early diagnosis and adds to our understanding of anthrax toxemia throughout infection. The LF/EF ratio may also indicate the stage of infection and need for advanced treatments.
Dissecting aneurysm of coronary artery associated with drug abuse and pulmonary lesions.

The rare isolated dissecting aneurysm of a coronary artery (DACA), known to be causally related to trauma and Marfan's syndrome, has also been linked with pregnancy and the postpartum state [1]. Hormonal effects on the ground substance or connective tissue of the coronary vessels have been invoked to explain this phenomenon [2]. The well-known relationship of dissecting aneurysms of the aorta with cystic medial necrosis prompted a search for the association of this degenerative change with dissecting aneurysms of the coronary artery. Various authors have confirmed this association [3,4].
Persistence of a novel regeneration-associated transitional cell state in pulmonary fibrosis

Abstract Stem cell senescence is often seen as an age associated pathological state in which cells acquire an abnormal and irreversible state. Here, we show that alveolar stem cell differentiation during lung regeneration involves a unique previously uncharacterized transitional state that exhibits cardinal features normally associated with cell senescence. Specifically, using organoid cultures, multiple in vivo injury models coupled with single cell transcriptomics and lineage tracing analysis, we find that alveolar stem cell differentiation involves a novel, pre-alveolar type-1 transitional state (PATS) en route to their terminal maturation. PATS can be distinguished based on their unique transcriptional signatures, including enrichment for TP53, TGFβ, and DNA damage repair signaling, and cellular senescence in both in vivo and ex vivo regenerating tissues. Significantly, PATS undergo extensive cell stretching, which makes them vulnerable to DNA damage, a feature commonly associated with most degenerative lung diseases. Importantly, we find enrichment of PATS-like state in human fibrotic lung tissues, suggesting that persistence of such transitional states underlies the pathogenesis of pulmonary fibrosis. Our study thus redefines senescence as a state that can occur as part of a normal tissue maintenance program, and can be derailed in human disease, notably fibrosis.
Low Human Papillomavirus Literacy Among Asian-American Women in California: an Analysis of the California Health Interview Survey

Asian-Americans are one of the fastest growing minority groups in the USA, and the literature notes high rates of human papillomavirus (HPV). In this study, we aimed to address whether key social determinants of health, especially health literacy, in combination with English language proficiency, and immigration status, were key factors in HPV knowledge and awareness among Asian-Americans. The data was collected from the California Health Interview Survey (CHIS). The study population consisted of Asian adult females from 18 to 65 years of age, with a sample size of 2050 representing a population of 1,552,710. Survey-weighted descriptive, bivariate, and multivariable Poisson regression were conducted with alpha less than .05 to denote significance. Nearly 45% of the population reported that they never heard of HPV, while 14% reported thinking HPV can cause AIDS, and 13% reported that HPV can go away on its own. HPV knowledge, however, was varied by Asian-American ethnicity as well as being foreign-born. Survey-weighted multivariable robust Poisson regression results show that, when compared with Japanese subgroup, Chinese, South Asians, and Koreans were less likely to have heard of HPV. Having heard of HPV was 31% lower among Asian-Americans who were foreign-born, as compared with those who were US-born. Foreign-born Asian-Americans were 196% more likely to think HPV causes AIDS. Ever having heard of HPV was also associated with low English language proficiency (70% lower), low health literacy (45% lower), and a combination of both (55%). While, those with low English language proficiency understood HPV is a sexually transmitted infection, a substantially high number associated it with AIDS. Interventions towards increasing health literacy among Asian Americans are imperative in order increase HPV vaccination rates to reduce cervical cancer rates/deaths.
Assessing the Effectiveness of Point-of-Use Residential Drinking Water Filters for Perfluoroalkyl Substances (PFASs)

Per- and polyfluoroalkyl substances (PFASs) have come under increased scrutiny due to concerns about their potential toxicity and prevalence in the environment, particularly drinking water. PFASs a...
Determinate perfect foresight forecasting in overlapping generations models

In this paper, we show the existence of the perfect foresight forecast functions which generate unique and stable equilibrium price dynamics for comparative static analysis and calibration in multi-period overlapping generations models with cohort heterogeneity, multiple goods, and fiat money. We also show how to recover such forecast functions up to the first order using the eigenvalues and eigenvectors of the Jacobian matrix of the equilibrium conditions. In a special one good case, our construction of the forecast functions requires information about only the eigenvalues. In addition, we demonstrate that the stable subspace where the price sequences generated by the linearized forecast functions exist is also an invariant cyclic subspace.
Chapter 13 – Cholinomimetics

Any drug that can reproduce the effects and mimic the actions of the neurotransmitter acetylcholine (ACh), the primary transmitter of nerve impulses within the parasympathetic nervous system, that dilates blood vessels, contracts smooth muscles (eye pupils), slows the heart rate, and increases bodily secretions (salvia, sweat, tears, mucus in the respiratory tract, intestinal cramps) is considered a cholinomimetic. Cholinomimetics are classified as direct-acting drugs, that is, drugs that activate the receptor site by mimicking the effects of Ach, and as indirectly acting drugs that prevent the enzyme cholinesterase (AChE) from hydrolyzing ACh at the receptor site. In turn, indirectly acting drugs can be reversible or irreversible. ACh acts on two vastly functionally and structurally distinct different classes of receptors: nicotinic receptors (nAChRs) (with two subtypes, one at the neuromuscular junction of skeletal muscle, the other within ganglia and the central nervous system [CNS]), and muscarinic receptors (mAChRs) (widely distributed within both peripheral and central nervous systems). These receptors originally were distinguished from each other by the selectivity of the alkaloid agonists—muscarine and nicotine, respectively. Neuronal nAChRs are pentameric ligand-gated ion channels. Molecular cloning has identified nine α subunits (α2 to α10) and three β-subunits (β2 to β4). Homomeric nAChRs are composed only of α subunits, whereas heteromeric nAChRs have different combinations of α and β subunits. The most abundant neuronal subunits are α4, α7, and β2. More than 90% of all neuronal nAChRs are made up of the heteromeric α4β2 receptor subtype. Five molecularly distinct mammalian subtypes of mAChRs, M1 to M5, have been cloned. Each of the five mAChR subtypes is a seven-transmembrane protein that can be further divided into two major functional classes based on G-protein coupling. The major therapeutic uses of the cholinomimetics are to treat diseases of the eye (glaucoma), the diseases of the gastrointestinal and urinary tracts (postoperative atony, neurogenic bladder), and the neuromuscular junction (myasthenia gravis, curare-induced neuromuscular paralysis). Their last implementation is attempts to treat patients with Alzheimer and Parkinson diseases and schizophrenia. Donepezil is the single cholinesterase inhibitor found on the list of Top 200 Drugs by sales for the 2010s.
SUGAR: Speeding Up GPGPU Application Resilience Estimation with Input Sizing

As Graphics Processing Units (GPUs) are becoming a de facto solution for accelerating a wide range of applications, their reliable operation is becoming increasingly important. One of the major challenges in the domain of GPU reliability is to accurately measure GPGPU application error resilience. This challenge stems from the fact that a typical GPGPU application spawns a huge number of threads and then utilizes a large amount of potentially unreliable compute and memory resources available on the GPUs. As the number of possible fault locations can be in the billions, evaluating every fault and examining its effect on the application error resilience is impractical. Application resilience is evaluated via extensive fault injection campaigns based on sampling of an extensive fault site space. Typically, the larger the input of the GPGPU application, the longer the experimental campaign. In this work, we devise a methodology, SUGAR (Speeding Up G PGPU Application Resilience Estimation with input sizing), that dramatically speeds up the evaluation of GPGPU application error resilience by judicious input sizing. We show how analyzing a small fraction of the input is sufficient to estimate the application resilience with high accuracy and dramatically reduce the duration of experimentation. Key to our estimation methodology is the discovery of repeating patterns as a function of the input size. Using the well-established fact that error resilience in GPGPU applications is mostly determined by the dynamic instruction (DI) count at the thread level, we discover the patterns that allow to accurately predict application error resilience for arbitrarily large inputs. For the cases that we examine in this paper, this new resilience estimation provides significant speedups (up to 1336 times) and 97.0 on the average, while keeping estimation errors to less than 1%, for details see the full version of this SIGMETRICS paper.
Early inhibition of subchondral bone remodeling slows load-induced posttraumatic osteoarthritis development in mice.

Posttraumatic osteoarthritis (PTOA) is associated with abnormal and increased subchondral bone remodeling. Inhibiting altered remodeling immediately following joint damage can slow PTOA progression. Clinically, however, inhibiting remodeling when significant joint damage is already present has minimal effects in slowing further disease progression. We sought to determine the treatment window following PTOA initiation in which inhibiting remodeling can attenuate progression of joint damage. We hypothesized that the most effective treatment would be to inhibit remodeling immediately after PTOA initiation. We used an animal model in which a single bout of mechanical loading was applied to the left tibia of 26-week-old male C57Bl/6 mice at a peak load of 9 N to initiate load-induced PTOA development. Following loading, we inhibited bone remodeling using daily alendronate (ALN) treatment administered either immediately or with 1 or 2 weeks' delay up to 3 or 6 weeks post-loading. A vehicle (VEH) treatment group controlled for daily injections. Cartilage and subchondral bone morphology and osteophyte development were analyzed and compared among treatment groups. Inhibiting remodeling using ALN immediately after load-induced PTOA initiation reduced cartilage degeneration, slowed osteophyte formation, and preserved subchondral bone volume compared to VEH treatment. Delaying the inhibition of bone remodeling at 1 or 2 weeks similarly attenuated cartilage degeneration at 6 weeks, but did not slow the development of osteoarthritis (OA)-related changes in the subchondral bone, including osteophyte formation and subchondral bone erosions. Immediate inhibition of subchondral bone remodeling was most effective in slowing PTOA progression across the entire joint, indicating that abnormal bone remodeling within the first week following PTOA initiation played a critical role in subsequent cartilage damage, subchondral bone changes, and overall joint degeneration. These results highlight the potential of anti-resorptive drugs as preemptive therapies for limiting PTOA development after joint injury, rather than as disease-modifying therapies after joint damage is established. © 2021 American Society for Bone and Mineral Research (ASBMR).
Saving Mabira Rainforest: Using Public Interest Litigation in Uganda to Save Mabira and Other Rainforests

In August 2011, President Yoweri Kaguta Museveni announced that he planned to give away part of Mabira rainforest to a sugar corporation to grow a sugarcane plantation and enhance sugar production in the country. The President had made a similar proposal in 2007 and only abandoned it after public and environmental groups received it with immense resistance. The Ugandan government has also given away other forest land to private investors, including parts of Bugala Island in Lake Victoria to a vegetable company to grow palm trees. This Note argues that the Ugandans opposed to the give-away of forest land to private companies can bring public interest litigation under Article 50 of the Uganda Constitution. The Note further proposes that to save private forests, Uganda should seek guidance from U.S. case law on applying the public trust doctrine to trust resources on private property.
Segmentation-based analysis of single-cell immunoblots.

From genomics to transcriptomics to proteomics, microfluidic tools underpin recent advances in single-cell biology. Detection of specific proteoforms - with single-cell resolution - presents challenges in detection specificity and sensitivity. Miniaturization of protein immunoblots to single-cell resolution mitigates these challenges. For example, in microfluidic western blotting, protein targets are separated by electrophoresis and subsequently detected using fluorescently labeled antibody probes. To quantify the expression level of each protein target, the fluorescent protein bands are fit to Gaussians; yet, the method is difficult to use with noisy, low-abundance or low-SNR protein bands, and with significant band skew or dispersion. In this study, we investigate segmentation-based approaches to robustly quantify protein bands from single-cell protein immunoblots. As compared to a Gaussian fitting pipeline, the segmentation pipeline detects >1.5x more protein bands for downstream quantification as well as more of the low-abundance protein bands (i.e., with SNR ∼3). Utilizing deep learning-based segmentation approaches increases the recovery of low SNR protein bands by an additional 50%. However, we find that segmentation-based approaches are less robust at quantifying poorly resolved protein bands (separation resolution, Rs < 0.6). With burgeoning needs for more single-cell protein analysis tools, we see microfluidic separations as benefitting substantially from segmentation-based analysis approaches. This article is protected by copyright. All rights reserved.
Internship alternatives: Solutions for the COVID-19 pandemic and beyond

Internships are an integral component of most undergraduate and graduate public administration programs. These learning opportunities allow students to get practical experience in a workplace setti...
Assessing the relationships between neurological and psychiatric diseases with astrocyte subtypes and psychotropic medications

Astrocytes have many important functions in the brain, but their roles in CNS disorders and their responses to psychotropic medications are still being elucidated. In this study, we used gene enrichment analysis to assess the relationships between different astrocyte subtypes, neurological and psychiatric diseases, and psychotropic medications. We also carried out qPCR analyses and "look-up" studies to further assess the chronic effects of these drugs on astrocyte marker gene expression. Our bioinformatic analysis identified differential gene enrichment of different astrocyte subtypes in CNS disorders. The "common" astrocyte subtype was the most frequently enriched across disorders, but the highest level of enrichment was found in depression, supporting a role for astrocytes in this disorder. We also identified common enrichment of metabolic and signal transduction-related biological processes in astrocyte subtypes and CNS disorders. However, enrichment of different psychotropic medications, including antipsychotics, antidepressants, and mood stabilizers, was limited in astrocyte subtypes. These results were confirmed by "look-up" studies and qPCR analysis, which also reported little effect of common psychotropic medications on astrocyte marker gene expression, suggesting that astrocytes are not a primary target of these medications. Overall, this study provides a unique view of astrocyte subtypes and the effect of medications on astrocytes in disease, which will contribute to our understanding of their role in CNS disorders and offers insights into targeting astrocytes therapeutically.
Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors.

The intracellular bacterial pathogen Legionella pneumophila (L.p.) secretes ∼330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five L.p. effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In this study, we discovered a subset of L.p. toxins that selectively activate the UPR sensor ATF6, resulting in its cleavage, nuclear translocation, and target gene transcription. In a deviation from the conventional model, this L.p.–dependent activation of ATF6 does not require its transport to the Golgi or its cleavage by the S1P/S2P proteases. We believe that our findings highlight the unique regulatory control that L.p. exerts upon the three UPR sensors and expand the repertoire of bacterial proteins that selectively perturb host homeostatic pathways.
Leaching and reclamation of a biochar and compost amended saline–sodic soil with moderate SAR reclaimed water

Abstract Remediating saline–sodic soils with organic amendments is increasingly seen as a cheaper and sustainable alternative to inorganic materials. The reclamation potential of biochar, biosolids and greenwaste composts applied to a saline–sodic soil was evaluated in a laboratory leaching experiment using moderate SAR reclaimed water. Treatments included biochar, biosolids co-compost, greenwaste compost (all applied at a 75 t ha−1 rate), gypsum (50% soil gypsum requirement), biochar + gypsum, biosolids + gypsum, greenwaste + gypsum and a non-amended control. All treatments were subjected to a one month incubation after which, soils were filled in columns and leached using reclaimed water until 7 PV of water had passed. Cumulative leachate losses of Na+, Ca2+, and Mg2+ were evaluated in addition to soil properties after leaching. Results show that leaching with moderate SAR water was effective in reducing the soil salinity and sodicity of all soils, irrespective of amendment application. However, incorporating biochar and composts significantly enhanced this effect. Salt leaching was higher in soils treated with organic amendments. Cumulative leachate losses of cations were significantly higher from biochar and compost treated soils compared to gypsum and unamended controls. Improvements in soil aggregate stability and saturated hydraulic conductivity were prominent in compost treated soils. After leaching, soil analyses indicated that organic amendments lowered significantly more soil ECe, ESP and SAR than that of the control soils and saturated the exchange complex with Ca2+. Soil pH was significantly reduced and CEC was significantly increased in only compost treated soils. Although individual organic amendment applications proved to be significant enough to remediate a saline–sodic soil, combined applications of gypsum and organic amendments were more effective in improving soil properties directly related to sodium removal including sodium leaching, hydraulic conductivity, ESP, and SAR, and therefore could have a supplementary benefit of accelerating the reclamation process.
Intraoperative Urologic Ultrasound

Interventional ultrasonography (US) in urology includes many different diagnostic and therapeutic minimally invasive procedures. It also represents a noninvasive tool that, if placed in the hands of a trained surgeon, can aid various types of urologic interventions, allowing for on-the-fly, real-time visualization of important structures and operative activity that is both safe and inexpensive. Newer machines and probes allow for ultrasound application intraoperatively in virtually all areas of the urogenital tract and are increasingly used by urologists as an adjunct to standard operating techniques.
Job selection in two-stage shops with ordered machines

We consider job selection problems in shops with ordered machines.We solve the open shop problem in polynomial time.We show that the job shop problem is ordinary NP-hard.We consider the flow shop problem with the total job completion time objective. We consider job selection problems in two-stage flow shops, open shops and job shops. The objective is to select the best job subset with a given cardinality to minimize either the total job completion time or the maximum job completion time (makespan). An O ( n 2 ) algorithm is available for the two-stage flow shop with ordered machines and the minimum makespan objective; we utilize this algorithm to solve the same problem for the total job completion time objective. We then propose an O ( n 1 ) algorithm for the two-machine open shop job selection problem with ordered machines and the minimum makespan objective. We also consider a two-machine job shop in which the first operation of each job is no longer than the second one. We show that the job selection problem in this job shop with the minimum makespan objective is ordinary NP-hard and that the problem becomes solvable in O ( n log n ) time with the additional assumption of ordered jobs.
A Conceptual Framework for Multiple Stakeholder Educational Decision Making

The purpose of this paper is to construct a conceptual framework of educational decision making that accounts for critical factors in decision processes. Elements of the framework include multiple stakeholders’ objectives and influence, varying degrees of collaboration, the concept of coupling between decision makers and stakeholders, and feedback as decisions evolve. The theoretical and conceptual contributions of this paper help to fill in an important gap in the decision making and leadership literature by explaining the dynamics of multiple actors involved in a series of decisions over time. This conceptual framework is developed by presenting areas of inquiry that are not addressed in the current literature and responding to them in a step-wise fashion. A brief school district case is used for illustration. The paper concludes with research and practice applications of the conceptual framework.
Language design for distributed stream processing

Applications that combine live data streams with embedded, parallel, and distributed processing are becoming more commonplace. WaveScript is a domain-specific language that brings high-level, type-safe, garbage-collected programming to these domains. This is made possible by three primary implementation techniques, each of which leverages characteristics of the streaming domain. First, WaveScript employs an evaluation strategy that uses a combination of interpretation and reification to partially evaluate programs into stream dataflow graphs. Second, we use profile-driven compilation to enable many optimizations that are normally only available in the synchronous (rather than asynchronous) dataflow domain. Finally, an empirical, profile-driven approach also allows us to compute practical partitions of dataflow graphs, spreading them across embedded nodes and more powerful servers. We have used our language to build and deploy applications, including a sensor-network for the acoustic localization of wild animals such as the Yellow-Bellied marmot. We evaluate WaveScript's performance on this application, showing that it yields good performance on both embedded and desktop-class machines. Our language allowed us to implement the application rapidly, while outperforming a previous C implementation by over 35%, using fewer than half the lines of code. We evaluate the contribution of our optimizations to this success. We also evaluate WaveScript's ability to extract parallelism from this and other applications. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)
The mechanism of 2-keto-3-deoxy-6-phosphogluconate aldolase. 3. Nature of the inactivation by fluorodinitrobenzene.

Abstract 2-Keto-3-deoxy-6-phosphogluconate aldolase of Pseudomonas putida reacts with about 4 moles of 1-fluoro-2,4-dinitrobenzene per mole of aldolase; this is accompanied by 85 to 90% loss in activity. Both the arylation reaction and the inactivation are prevented by 2-keto-3-deoxy-6-phosphogluconate, 2-keto-3-deoxy-6-phosphogalactonate, and inorganic phosphate. The substrate binding site was then blocked by adding 2-keto-3-deoxy-6-phosphogalactonate and reducing the azomethine linkage to a lysine residue with sodium borohydride. Subsequent dialysis of the treated enzyme to remove noncovalently bound 2-keto-3-deoxy-6-phosphogalactonate, followed by reaction with fluorodinitrobenzene, results in only one of the four originally observed dinitrophenylations. This indicates that 3 molecules of fluorodinitrobenzene react in or close to the active site. Only the lysine e-amino group is dinitrophenylated, and these lysines were shown to be distinct from those forming an azomethine with pyruvate, 2-keto-3-deoxy-6-phosphogalactonate, and, presumably, 2-keto-3-deoxy-6-phosphogluconate. The Km of dinitrophenylated aldolase for 2-keto-3-deoxy-6-phosphogluconate is about 2-fold higher than that of native aldolase, whereas there is a 10-fold decrease in Vmax. Thus, the loss in activity by dinitrophenylation seen at saturating 2-keto-3-deoxy-6-phosphogluconate concentration is attributed to a decrease in catalysis rather than to a decrease in binding of 2-keto-3-deoxy-6-phosphogluconate. The rate of tritium exchange from T2O into pyruvate decreased about 10-fold following dinitrophenylation. Since tritium exchange in native 2-keto-3-deoxy-6-phosphogluconate aldolase is only 2 to 3 times the rate of cleavage, the 10-fold loss of activity may be attributed to either direct or indirect impairment of the C—H bond cleavage part of the reaction mechanism. Discrepancies between the rate and extent of dinitrophenylation and the loss in activity were observed. These are attributed to a conformational change elicited by addition of the first molecule of fluorodinitrobenzene. An altered conformation is also supported by the unexpected change in pI to a more basic region, increased thermal stability, and decreased number of sulfhydryl groups available for titration with dithiodinitrobenzoate. The data do not support the hypothesis that dinitrophenylation impairs the substrate phosphate group binding site but, rather, that it effects changes in conformation which indirectly diminish catalysis.
Coherent Flaw Reflectivity Estimation in Nonstationary Noise

This paper presents a model for RF broadband ultrasonic A-scans obtained from materials composed of microstructures, in which isolated flaws or impurities may exist. The model incorporates both the RF phase and magnitude differences between the microstructure and coherent flaw echo spectra. An adaptive implementation of the maximum-likelihood estimator (MLE) is presented for estimating A-scan amplitudes associated with coherent scatterers embedded in grain echoes. The adaptive implementation is motivated by the nonstationary behavior of the back-scattered energy received over the duration of the A-scan [1]. This nonstationarity results from the frequency dependent absorption, scattering, and diffraction that occurs as the pulse propagates through the material
The Challenge of Understanding Health Care Costs and Charges.

Physicians can contribute to the reduction of medical costs and improvement of patient compliance by becoming familiar with Choosing Wisely’s list of wasteful or marginally beneficial medical practices and by monitoring patients for financial harm.
Faster cover trees

The cover tree data structure speeds up exact nearest neighbor queries over arbitrary metric spaces (Beygelzimer et al., 2006). This paper makes cover trees even faster. In particular, we provide 1. A simpler definition of the cover tree that reduces the number of nodes from O(n) to exactly n, 2. An additional invariant that makes queries faster in practice, 3. Algorithms for constructing and querying the tree in parallel on multiprocessor systems, and 4. A more cache efficient memory layout. On standard benchmark datasets, we reduce the number of distance computations by 10-50%. On a large-scale bioinformatics dataset, we reduce the number of distance computations by 71%. On a large-scale image dataset, our parallel algorithm with 16 cores reduces tree construction time from 3.5 hours to 12 minutes.