cssi/SciSciGPT-SciSciNet huggingface dataset:
Confronting Cosmopolitanism: Judicial Transnationalism and the Contemporary Supreme Court

Since the end of the Cold War, the Supreme Court and its decisions have gained visibility abroad through the United States’ involvement in constitution drafting and judicial reform. As a result, the prominence of our national judicial system has grown and members of foreign and international courts have become more familiar with and likely to consider its decisions. However, when considering the increasingly global network of legal norms and actors, the United States’ role is generally considered to be limited to that of an exporter, not an importer. This paper explores resistance to transnationalism among legal scholars and actors over the past two decades, distinguishing between the conceptualization of cosmopolitanism as a philosophical threat and the mundane realities of global changes in the American judicial process. Suggesting that these changes may have an impact, at least indirectly, on the Court in ways not adequately explored in the existing literature, it considers their possible effects on its decisions and the way that the justices consider their role within increasingly globalized legal networks.
Alterations in Smad Signaling in Carcinogenesis

The importance of TGF-β signaling in the suppression of tumorigenesis is supported by the presence of frequent mutations in genes encoding both TGF-β receptors and intermediates in this signaling pathway in cancer. In epithelial cancers sporadic mutations have been found in the genes encoding both the receptor-activated Smad2 (MADH2) and the common intermediate, Smad4 (MADH4). Germline mutations in MADH4 and in BMPR1 (BMP type 1 receptor gene) are the most common mutations in the familial cancer syndrome, Familial Juvenile Polyposis, FJP. More recent studies have revealed epigenetic mechanisms that also play important roles in subverting the function of this pathway. In this chapter, we discuss some of these mechanisms, and provide insight into novel ways in which Smad signaling contributes to the maintenance of tissue homeostasis and ultimately to the suppression of cancer
Extrapolation of a Predictive Model for Growth of a Low Inoculum Size of Salmonella Typhimurium DT104 on Chicken Skin to Higher Inoculum Sizes

Validation of model predictions for independent variables not included during model development can save time and money by identifying conditions for which new models are not needed. A single strain of Salmonella Typhimurium DT104 was used to develop a general regression neural network (GRNN) model for growth of a low inoculum size (0.9 log) on chicken skin with native microflora as a function of time (0 to 8 h) and temperature (20 to 45°C). The ability of the GRNN model to predict growth of higher inoculum sizes (2, 3, or 4.1 log) was evaluated. When the proportion of residuals in an acceptable prediction zone (pAPZ) from −1 log (fail-safe) to 0.5 log (fail-dangerous) was ≥0.7, the GRNN model was classified as providing acceptable predictions of the test data. The pAPZ for dependent data was 0.93 and for independent data for interpolation was 0.88. The pAPZs for extrapolation to higher inoculum sizes of 2, 3, or 4.1 log were 0.92, 0.73, and 0.77, respectively. However, residual plots indicated local pred...
Plantar pressures in the forefoot after lateral column lengthening: a cadaver study comparing the Evans osteotomy and calcaneocuboid fusion.

Background: Excessive varus alignment of the forefoot after lateral column lengthening has been reported to lead to overloading of the lateral foot. The purpose of this study was to investigate whe...
nD--PDPA: n Dimensional Probability Density Profile Analysis

Structure characterization of a protein is expensive and time-consuming regardless of the novelty of the target protein. Probability density profile analysis (PDPA) has been previously introduced to directly address the economies of structure determination of routine proteins and subsequently, identification of novel structures from minimal sets of residual dipolar coupling (RDC) data. The 2D-PDPA, denoting incorporation of data from two alignment media, has been successful in identifying the structural homologue of an unknown protein within a library of ~ 1000 decoy structures. To further expand the selectivity and sensitivity of 2D-PDPA, incorporation of additional data was necessary. However, expansion of the original 2D-PDPA approach was limited by its computational requirements where inclusion of additional data would render it computationally intractable. The n D-PDPA method is the most recent developments of the PDPA method that eliminates 2D-PDPA's computational limitations and allows inclusion of RDC data from multiple vector types in multiple alignment media.
Communicative Unclarity: Some Comments on the Rhetoric of Confusion †.

(1967). Communicative Unclarity: Some Comments on the Rhetoric of Confusion. Psychiatry: Vol. 30, No. 4, pp. 332-349.
Should obtaining a preoperative audiogram before tympanostomy tube placement be used as a quality metric? A survey of pediatric otolaryngologists

Abstract Introduction Obtaining a preoperative audiogram prior to tympanostomy tube placement is recommended by the American Academy of Otolaryngology-Head and Neck Surgery clinical practice guideline (CPG): Tympanostomy tubes in Children , and this process measure is also used as a quality metric by payers. However, whether audiograms should be mandated in cases of tube placement for both chronic otitis media with effusion (COME) and recurrent acute otitis media (RAOM) is controversial. The objective of this study is to determine reports of practice patterns of pediatric otolaryngologists regarding obtaining audiograms before and after tympanostomy tube placement and opinions regarding utility of CPGs and use of this process measure as a quality metric. Methods A 16-question cross-sectional survey of American Society of Pediatric Otolaryngology (ASPO) members was conducted. Per ASPO policy, no repeated requests or other enhanced response techniques were permitted. Independent t -tests for proportions were used to compare responses. Results 127 pediatric otolaryngologists completed the survey (response rate 26.9%). Nearly 70% of respondents reported being in practice for >10 years. 74% of respondents reported obtaining preoperative audiograms “always” or “most of the time” for COME, vs. 56.7% for RAOM (p Conclusion There is no consensus among pediatric otolaryngologists regarding the necessity of a preoperative audiogram in tympanostomy tube placement, especially for RAOM. Further evidence demonstrating the benefit of preoperative audiogram obtainment should be developed prior to inclusion as a guideline recommendation and as a quality metric.
Measuring the Impact of Sharing Abuse Data with Web Hosting Providers

Sharing incident data among Internet operators is widely seen as an important strategy in combating cybercrime. However, little work has been done to quantify the positive benefits of such sharing. To that end, we report on an observational study of URLs blacklisted for distributing malware that the non-profit anti-malware organization StopBadware shared with requesting web hosting providers. Our dataset comprises over 28,000 URLs shared with 41 organizations between 2010 and 2015. We show that sharing has an immediate effect of cleaning the reported URLs and reducing the likelihood that they will be recompromised; despite this, we find that long-lived malware takes much longer to clean, even after being reported. Furthermore, we find limited evidence that one-time sharing of malware data improves the malware cleanup response of all providers over the long term. Instead, some providers improve while others worsen.
Comment on "In-Plane Lattice Reconstruction of Cu(100)"

A Comment on the Letter by S. M{umlt u}ller {ital et} {ital al}., Phys. Rev. Lett. {bold 75}, 2959 (1995). The authors of the Letter offer a Reply. {copyright} {ital 1996 The American Physical Society.}
Towards a Better Understanding of On and Off Target Effects of the Lymphocyte-Specific Kinase LCK for the Development of Novel and Safer Pharmaceuticals

Abstract In this work we have developed a multi-tiered computational platform to study protein-drug interactions. At the beginning of the workflow more efficient and less accurate methods are used to enable large libraries of proteins in many conformations and massive chemical libraries to be screened. At each subsequent step in the workflow a subset of input data is investigated with increased accuracy and more computationally expensive methods. We demonstrate the developed workflow with the investigation of the lymphocyte-specific kinase LCK, which is implicated as a drug target in many cancers and also known to have toxic effects when unintentionally targeted. Several LCK states and conformations are investigated using molecular docking and generalized Born and surface area continuum solvation (MM/GBSA). Different variations in the drug screening process provide unique results that may elucidate the biological mechanisms underlying the drug interactions.
Subcarrier Assignment and Power Allocation for Device-to-Device Video Transmission in Rayleigh Fading Channels

Subcarrier assignment and power allocation for device-to-device (D2D) video transmission using a filter bank multicarrier waveform in a Rayleigh fading environment are investigated. We analyze the co-channel interference between D2D pairs, and propose a cross-layer algorithm with a subcarrier assignment outer loop and a power allocation inner loop, which aims to optimize the overall video quality. Unlike the non-convexity in physical layer power allocation for maximizing the total throughput, the cross-layer power allocation problem is convex under certain conditions, so a high quality solution for power allocation can be efficiently found. Simulation results demonstrate a higher overall video quality by the proposed cross-layer algorithm compared with baseline algorithms.
Homeostasis and the Forgotten Vitalist Roots of Adaptation

Through most of the twentieth century, biology’s image as a valid science has been gauged by how closely it adheres to the norms of “objective” sciences like physics, chemistry and mathematics. Strains of biological thought that depart from this norm are deemed non-scientific. This presumes that life is fundamentally a physical, chemical and thermodynamic phenomenon. While this approach has been very fruitful, it is questionable that it can lead to a coherent theory of biology. This is particularly the case for certain obvious (self-evident?) properties of living systems, including purposefulness, design, and intentionality. The tendency has been to treat these phenomena as illusions, as in numerous invocations of “apparent” design, “apparent” purposefulness and “apparent” intentionality. I argue in this essay that these phenomena are far from illusory, but are in fact quite real. I further argue that a coherent theory of biology must account for purpose, design and intentionality, and I offer one possible way to do so through the fundamental phenomenon of homeostasis.
The Black–White Cardiovascular Health Disparity Is Narrowing, But Not for the Reason You Think

Disparities in cardiovascular health remain pervasive in the United States, with higher mortality in blacks than whites. Brown and colleagues' report showed a narrowing of the black–white gap in ca...
Resident attitudes - A Structural Modeling Approach

Abstract The objective of this research is to model host community support for tourism development based on the factors found to influence reactions towards it. Using the literature, a tourism support model with hypotheses involving several paths was proposed. Data were collected from five counties surrounding a Virginia (USA) recreation area, and the model and hypothesized paths were tested. The LISREL-8 structural equation analysis package was utilized with maximum likelihood method of estimation in combination with the two-stage process. The findings revealed that the host community support is affected by the level of concern, ecocentric values, utilization of resource base, perceived costs and benefits of the tourism development.
Impact of SR-ARQ with Finite Buffer on TDD/TDMA Wireless LAN

In this paper, the influence of some implementation parameters of Selective Repeat Automatic Repeat Request (SR-ARQ) on system performance is investigated. In the framework of the specific SR-ARQ algorithm specified by the ETSI BRAN HIPERLAN/2 (H/2) Wireless LAN standard, the need for optimizing the ARQ signalling bandwidth is illustrated and several signalling strategies are presented. Even with optimum management of the signalling bandwidth, the finite transmit and receive buffers can seriously limit the throughput. This effect is modeled by using a simple probabilistic approach, relying on the TDD/TDMA access scheme, and is evaluated by simulation. The interaction of SR-ARQ with scheduling and Link Adaptation is also discussed and finally, an ARQ aware scheduling strategy is proposed.
The Use of Imidacloprid Patches to Control Japanese Beetles on Roses

The past few years have been difficult for rose growers in the Midwest region due to an increase in Japanese beetle (Popillia japonica) populations. Japanese beetles can cause damage to many different areas on the rose plant. Their first target is normally the rose bud, feeding on pollen. Damage appears as a small, round hole going through the side of the flower bud. Buds that are able to fully open are normally the next target. The damage to the flowers is a small hole in the flower petals. As beetle populations increase, and after the first bloom of the rose is finished, they begin to attack the foliage. Typical damage to the foliage ranges from small holes in the leaf to complete destruction, resulting in unattractive plants in the landscape. In recent years, because of the Japanese beetle problem, homeowners are eliminating roses from the landscape. An efficient way of getting rid of these pests is needed.
Adolescents at risk for mistreating their children. Part I: Prenatal identification.

OBJECTIVE: To determine if the Family Stress Checklist helps prenatal care providers identify adolescents who are at risk for mistreating their children. METHODS: We studied 262 participants in a comprehensive, adolescent-oriented maternity program. During the prenatal period, the Family Stress Checklist was used to quantify abuse potential, with scores >25 defining high risk. Information about the social context of the pregnancy and the pattern of health care utilization was obtained with a self-administered questionnaire, and by reviewing the medical records. Major disruption of primary care giving by the adolescent mother was classified hierarchically as abuse, neglect, and abandonment. RESULTS: Family Stress Checklist scores ranged from 0 to 65 (mean + SD = 20.1 + 1.4); 113 (43%) of the 262 teenagers were classified as high risk. High and low risk adolescent mothers made an equivalent number of health maintenance and Emergency Department visits, but the high risk group initiated significantly more acute care visits (6.0 + 4.1 compared to 3.9 + 3.3; p Language: en
The effect of dietary phytoestrogen content on the development of systemic lupus erythematosus in the MRL/lpr mouse.

Systemic lupus erythematosus is a prototypical autoimmune disease, characterized by the loss of immune cell tolerance to self-antigens, and the subsequent production of autoantibodies leading to multi-organ damage. SLE is an incurable, highly variable autoimmune disease that most often affects women of child-bearing age. We investigated the effects of three standard commercial diets with varying phytoestrogen content on the development of lupus in female MRL/lpr mice. The diets include Harlan 2018 which contains soybean meal, Teklad 7013 which contains both soy and alfalfa, and Research Diets Inc. D11112226 (RD) purified ingredients diet, containing no measurable phytoestrogens. Mice fed the 2018 diet developed severe glomerulonephritis with high levels of complement C3 protein deposition and moderate IgG immune-complex deposition, while mice fed the RD diet developed minimal evidence of renal damage and protein deposition. The mice fed the RD diet, however, had increased levels of multiple pro-inflammatory cytokines, while immune cell populations remained unchanged. Immunofluorescence revealed distinct infiltrating cellular phenotypes in the kidney, dependent on dietary source. Splenocyte miRNA-148a was markedly elevated in mice fed the 2018 and 7013 diets, while circulating miRNA values were not statistically different. Our results suggest that dietary isoflavones can worsen the development of glomerulonephritis due to enhanced immune complex protein deposition and altered cellular infiltration phenotypes. Our results also support that each organ system must be evaluated independently, and that what is measured in circulation does not necessarily reflect what is occurring in disease target organs.
Right Mini-Thoracotomy Subaortic Membrane Resection.

ObjectiveSubaortic membrane is an anatomical intracardiac anomaly that may cause discrete subaortic stenosis and aortic insufficiency. Patients requiring subaortic membrane resection may benefit fr...
Making Space for Every Body: Ending Sizeism in Psychotherapy and Training

The importance of addressing weight bias as a social justice issue in psychotherapy and psychology education and training is introduced. The history of the development of fat studies is briefly rev...
Impact of MDM2, TP53 and P14ARF Polymorphisms on Endometrial Cancer Risk and Onset.

BACKGROUND/AIM The aim of this study was to determine the joint effect of single nucleotide polymorphisms (SNPs) of MDM2, TP53, and CDKN2A (P14ARF) genes on the onset and course of endometrial cancer (EC) in postmenopausal women. MATERIALS AND METHODS The study group consisted of 144 EC women and 50 non-cancer controls. MDM2 rs22279744, TP53 rs1042522, and P14ARF rs3088440, rs3731217, and rs3731245 SNPs were analysed. RESULTS The double-SNP combinations T-C, T-T, or T-G in MDM2 SNP 309 and P14ARF polymorphisms decreased EC risk. The triple-SNP combinations T-C-T, T-C-G, or T-T-G in MDM2 SNP and two P14ARF polymorphisms decreased EC risk. The multiple-SNP combination T-C-T-G in MDM2 and three P14ARF polymorphisms decreased EC risk. The G-Arg-C-T-G carriers were at increased EC risk, while the T-Arg-C-T-G carriers were at decreased EC risk. CONCLUSION MDM2 SNP309 plays a role in EC onset in postmenopausal women.
Big Data helps SDN to manage traffic

Traffic management plays a crucial role in achieving high-performance networking with optimal resource utilization. However, efficient and effective traffic management could be very challenging in large-scale dynamic networking environments. Software-defined networking (SDN) together with Big Data analytics offers a promising approach to addressing this challenging problem. We first provide an overview of the general process of network traffic management, in both conventional Internet Protocol (IP)-based networks and the emerging SDN networks. Then, we present an architectural framework of Big Data-based traffic management in SDN. We discuss some possible Big Data analytics applications for data analysis and decision-making in SDN for traffic management. We also identify some open issues and challenges that must be addressed for applying Big Data analytics techniques in SDN traffic management, which offer possible topics for future research and technology development.
Chapter 12 – Cake Filtration: Mechanism, Parameters and Modeling*

Models for the interpretation and prediction of incompressible and compressible filter-cake thickness, as well as filtrate volume and rate data for linear and radial filtration cases, under static and dynamic filtration conditions, are presented. Effects of compressibility and small particle invasion and deposition inside the cake and formation, as well as the Darcy versus non-Darcy flow regimes, are considered. Methods and diagnostic charts for determining the model parameters from experimental filtration data are reviewed. Applications for radial and linear filtration cases are presented, and the results are compared for constant rate and constant pressure drive filtration. Model assisted analyses of experimental data demonstrate the diagnostic and predictive capabilities of the models. The parametric studies indicate that the particle screening efficiency of the formation is an important factor on the filter-cake properties and filtration rate, the differences between the linear and radial cake filtration performances are more pronounced, and the cake thickness and filtrate volume are smaller, for constant pressure filtration than constant rate filtration. The present thickness-averaged ordinary differential models are shown to reproduce the predictions of the previous partial differential model rapidly with significantly less computational effort. Because of the simplicity of the equations and reduction of computational effort, the thickness-averaged linear and radial filter-cake formation models offer significant advantages over the partial differential models for the analysis, design, and optimization of the cake filtration processes involving the wellbore and hydraulically created fracture surfaces. Simplified models considering incompressible particles and carrier fluids, and analytical solutions for incompressible cakes without fines invasion are also presented. These models provide insight into the mechanism of cake filtration and offer practical means of interpreting experimental data, estimating the model parameters, and simulating the linear and radial filtration processes.
The Association of Women Surgeons research grant: An analysis of the first 25 years.

Abstract Background The impact of the Association of Women Surgeons (AWS) Research Grant on academic productivity is unknown. Methods Grant applications were obtained from AWS archives. Applicant bibliometrics and National Institutes of Health (NIH) grants were identified via public databases. Results Twenty-four recipients between 1996 and 2020 and 68 nonrecipients between 2012 and 2017 were identified. $596,700 was awarded over the 25 years. Twenty-five percent of recipients subsequently acquired NIH funding amounting to $6,611,927.00, an 885–1008% return on investment. Compared to nonrecipients, grant recipients produced a greater mean number of publications (50.6 versus 36.4; p = 0.05), had a higher h-index (15.92 versus 10.7; p = 0.01), and were cited in higher impact factor journals (6.32 versus 3.9; p = 0.02). Conclusions Overall, previous AWS Research Grant recipients were more likely to become more impactful surgeon-scientists, as indicated by a higher post-award rate of NIH funding, total number of publications, and h-index than nonrecipients.
Lack of Clinical Benefit of Implantoplasty to Improve Implant Survival Rate.

The objective of this study was to compare postsurgical outcomes of resective treatment for peri-implantitis with and without implant surface modification (implantoplasty [IP]). This was accomplished by a retrospective analysis with data from patients with ≥1 implant who were surgically treated for peri-implantitis by resective therapy. Patients were divided into 2 groups regarding treatment approach: IP (test) and no IP (control). Retrospective data were obtained after implant placement (T0) and the day of peri-implantitis surgical treatment (T1). Patients were then recalled (≥1 y after T1) for clinical and radiographic examination (T2). The findings were conclusive. A total of 41 patients (68 implants; mean ± SD follow-up, 41.6 ± 24.4 mo) were included in this study. The survival rate at the implant level was 90% in the test group and 81.6% in the control group (P > 0.05). Multilevel regression analysis showed that the probability of implant failure was influenced by marginal bone loss (MBL) at T1 and not surgical modality. For example, peri-implantitis defects ≥50% and 25% to 50% MBL were 18.6 and 8.86 times more likely to lose the implant, respectively, when compared with 0.05). Multilevel regression analysis indicated that clinical improvement of these parameters was influenced by the number of supportive peri-implant therapy visits (P < 0.01). The results demonstrate little difference between the procedures. Regardless of the implant surface modification (IP) being performed or not, the survival rate of implants treated for peri-implantitis was primarily influenced by the amount of bone loss at the time of treatment. Other clinical parameters (MBL, probing pocket depth, bleeding on probing, suppuration) were influenced by the frequency of supportive peri-implant therapy visits and not by the IP procedure (ClinicalTrials.gov NCT04259840).
Apuntes para un análisis de clase de la política urbana del estado mexicano

1) El conocimiento directo de la realidad urbana mexicana que pude obtener durante mi estancia de varias semanas, en agosto y septiembre de 1976, como Profesor visitante del Departamento de Sociologia de la Universidad Autonoma Metropolitana (Unidad Azcapotzalco). Durante ese periodo pude aproximarme a la comnprension de algunos de los procesos sefialados en el texto mediante una serie de contactos directos en diversas esferas. En primer lugar, y sobre todo, a traves del contacto directo con los colonos y vecinos que me invitaron a discutir con ellos de su vida y experiencia de lucha en numerosas colonias y vecindades de las ciudades de Mexico y de Monterrey. Sin su aporte, sin su enfoque, mi conocimiento del problema hubiera sido abstracto y, por tanto, necesariamente err6neo. En segundo lugar, discusiones e informaciones obtenidas de expertos e investigadores de distintas instituciones, en particular de la Universidad Metropolitana (Xochimilco y Azcapotzalco), del Colegio de Mexico, de la Universidad de Puebla, de la UNAM, del Infonavit, de la Secretanra de la Presidencia y, mnuy particularmente, del Centro Operacional de Vivienda y Poblamiento (Copevi).
Persistent and Widespread Pain Among Blacks Six Weeks after MVC: Emergency Department-based Cohort Study.

Introduction Blacks in the United States experience greater persistent pain than non-Hispanic Whites across a range of medical conditions, but to our knowledge no longitudinal studies have examined the risk factors or incidence of persistent pain among Blacks experiencing common traumatic stress exposures such as after a motor vehicle collision (MVC). We evaluated the incidence and predictors of moderate to severe axial musculoskeletal pain (MSAP) and widespread pain six weeks after a MVC in a large cohort of Black adults presenting to the emergency department (ED) for care. Methods This prospective, multi-center, cohort study enrolled Black adults who presented to one of 13 EDs across the US within 24 hours of a MVC and were discharged home after their evaluation. Data were collected at the ED visit via patient interview and self-report surveys at six weeks after the ED visit via internet-based, self-report survey, or telephone interview. We assessed MSAP pain at ED visit and persistence at six weeks. Multivariable models examined factors associated with MSAP persistence at six weeks post-MVC. Results Among 787 participants, less than 1% reported no pain in the ED after their MVC, while 79.8 (95% confidence interval [CI], 77.1 - 82.2) reported MSAP and 28.3 (95% CI, 25.5 - 31.3) had widespread pain. At six weeks, 67% (95% CI, 64, 70%) had MSAP and 31% (95% CI, 28, 34%) had widespread pain. ED characteristics predicting MSAP at six weeks post-MVC (area under the curve = 0.74; 95% CI, 0.72, 0.74) were older age, peritraumatic dissociation, moderate to severe pain in the ED, feeling uncertain about recovery, and symptoms of depression. Conclusion These data indicate that Blacks presenting to the ED for evaluation after MVCs are at high risk for persistent and widespread musculoskeletal pain. Preventive interventions are needed to improve outcomes for this high-risk group.
Point/Counterpoint: Supraclavicular Decompression Is the Best Approach for Neurogenic Thoracic Outlet Syndrome

In this point/counterpoint chapter, we present the view that supraclavicular decompression is the best approach for the surgical treatment of neurogenic thoracic outlet syndrome (TOS). This is based on consideration of the limitations and deficiencies of transaxillary first rib resection, as well as the advantages of supraclavicular decompression. Potential complications are discussed along with the results of treatment. We conclude that in the hands of surgeons with experience and expertise, supraclavicular decompression offers the most thorough, versatile and safe approach to the treatment of neurogenic TOS, and it has the flexibility to be applicable to all other forms of TOS and intraoperative contingencies.
Brood Parasitism of Greater Sage-Grouse by California Quail in Idaho

We describe a case of brood parasitism of a Greater Sage-Grouse (Centrocercus urophasianus; hereafter, sage-grouse) nest by California Quail (Callipepla californica; hereafter, quail) in southwestern Idaho during 2019. We observed one quail egg in the parasitized nest; the egg partially hatched, but the chick was dead upon the final nest check. Of the 6 sage-grouse eggs in the nest, only 2 hatched, although the eggs contained chicks that appeared nearly completely developed. Identification of the quail chick was confirmed using mitochondrial DNA. Additional monitoring and documentation of this behavioral interaction is warranted to better understand its prevalence and any reproductive consequences for sage-grouse.
Targeting Adaptation to Cancer Treatment by Drug Combinations

Adaptation of tumors to therapeutic interventions contributes to dismal long-term patient outcomes. Adaptation to therapy involves co-action of functionally related proteins that together activate cell survival programs and compensate for the therapeutic impact. Oncogenic dependencies to such adaptive events, however, can generate new therapeutic vulnerabilities that can be targeted with drug combinations. The precision medicine approaches in which targeted drugs are matched to pre-existing genomic aberrations fail to address the adaptive responses and resulting vulnerabilities. Here, we provide the mathematical formulation, implementation and validation of the TargetScore method. The TargetScore identifies collective adaptive responses to targeted interventions as concurrent changes of phospho-proteins that are connected within a signaling network. Based on the adaptive responses, the method predicts drug-induced vulnerabilities. Using TargetScore, we inferred the adaptive responses with short-term (i.e., days) stress and long-term (i.e., months) acquired resistance to inhibitors of anti-apoptotic mediators, MCL1 and BCL2. With experiments guided by the predictions, we identified synergistic interactions between inhibitors of PARP, SHP2, and MCL1 in breast cancer cells. TargetScore is readily applicable to existing precision oncology efforts by matching targeted drug combinations to emerging molecular signatures under therapeutic stress.
Complex functionality of protein phosphatase 1 isoforms in the heart

Protein phosphatase 1(PP1) is a key regulator of cardiac function through dephosphorylating serine/threonine residues within target proteins to oppose the function of protein kinases. Studies from failing hearts of animal models and human patients have demonstrated significant increase of PP1 activity in myocardium, while elevated PP1 activity in transgenic mice leads to cardiac dysfunction, suggesting that PP1 might be a therapeutic target to ameliorate cardiac dysfunction in failing hearts. In fact, cardiac overexpression of inhibitor 1, the endogenous inhibitor of PP1, increases cardiac contractility and suppresses heart failure progression. However, this notion of PP1 inhibition for heart failure treatment has been challenged by recent studies on the isoform-specific roles of PP1 in the heart. PP1 is a holoenzyme composed of catalytic subunits (PP1α, PP1β, or PP1γ) and regulatory proteins that target them to distinct subcellular locations for functional specificity. This review will summarize how PP1 regulates phosphorylation of some of the key cardiac proteins involved in Ca2+ handling and cardiac contraction, and the potential role of PP1 isoforms in controlling cardiac physiology and pathophysiology.
Revising Conventional Wisdom About Histoplasmosis in the United States

Studies performed during the 1940s-1960s continue to serve as the foundation of the epidemiology of histoplasmosis given that many knowledge gaps persist regarding its geographic distribution, prevalence, and burden in the United States. We explore 3 long-standing, frequently cited, and somewhat incomplete epidemiologic beliefs about histoplasmosis: (1) histoplasmosis is the most common endemic mycosis in the United States, (2) histoplasmosis is endemic to the Ohio and Mississippi River Valleys, and (3) histoplasmosis is associated with bird or bat droppings. We also summarize recent insights about the clinical spectrum of histoplasmosis and changes in underlying conditions associated with the severe forms. Continuing to identify prevention opportunities will require better epidemiologic data, better diagnostic testing, and greater awareness about this neglected disease among health care providers, public health professionals, and the general public.
Quarantine Authority in Texas: A COVID-19 Case Study

During the COVID-19 pandemic, governments around the world grappled with how to protect their citizens from disease. Governments had to carefully balance the tension between individual rights and public health measures, while also considering which level of government was best situated to act. This paper, focusing on the response to COVID-19 in Texas, discusses the constitutionality of quarantines by balancing individual rights and public health. This paper also discusses how quarantine authority is shared among local, state, and federal levels of government in Texas. Finally, this paper analyzes some of the early actions taken in response to the COVID-19 pandemic. [ABSTRACT FROM AUTHOR] Copyright of Journal of Biosecurity, Biosafety & Biodefense Law is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Neural Recruitment During Conventional, Burst, and 10-kHz Spinal Cord Stimulation for Pain.

Abstract Spinal cord stimulation (SCS) is a popular neurostimulation therapy for severe chronic pain. To improve stimulation efficacy, multiple modes are now used in the clinic, including conventional, burst, and 10-kHz SCS. Clinical observations have produced speculation that these modes target different neural elements and/or work via distinct mechanisms of action. However, in humans, these hypotheses cannot be conclusively answered via experimental methods. Therefore, we utilized computational modeling to assess the response of primary afferents, interneurons, and projection neurons to conventional, burst, and 10-kHz SCS. Contrary to previous reports, axon collateralization produced complex changes in activation thresholds of primary afferents. Furthermore, local cell thresholds were always higher than afferent thresholds, arguing against direct recruitment of these local cells. Finally, although we observed relative threshold differences between conventional, burst, and 10-kHz SCS, the recruitment order was the same. These results motivate future work to contextualize clinical observations across SCS paradigms.
Understanding the prevalence of SARS-CoV-2 (COVD-19) exposure in companion, captive, wild, and farmed animals.

Several animal species, including ferrets, hamsters, monkeys, and raccoon dogs, have been shown to be susceptible to experimental infection by the human severe acute respiratory syndrome coronaviruses, such as SARS-CoV and SARS-CoV-2, which were responsible for the 2003 SARS outbreak and the 2019 coronavirus disease (COVID-19) pandemic, respectively. Emerging studies have shown that SARS-CoV-2 natural infection of pet dogs and cats is also possible, but its prevalence is not fully understood. Experimentally, it has been demonstrated that SARS-CoV-2 replicates more efficiently in cats than in dogs and that cats can transmit the virus through aerosols. With approximately 470 million pet dogs and 370 million pet cats cohabitating with their human owners worldwide, the finding of natural SARS-CoV-2 infection in these household pets has important implications for potential zoonotic transmission events during the COVID-19 pandemic as well as future SARS-related outbreaks. Here, we describe some of the ongoing worldwide surveillance efforts to assess the prevalence of SARS-CoV-2 exposure in companion, captive, wild, and farmed animals, as well as provide some perspectives on these efforts including the intra- and inter-species coronavirus transmissions, evolution, and their implications on the human-animal interface along with public health. Some ongoing efforts to develop and implement a new COVID-19 vaccine for animals are also discussed. Surveillance initiatives to track SARS-CoV-2 exposures in animals are necessary to accurately determine their impact on veterinary and human health, as well as define potential reservoir sources of the virus and its evolutionary and transmission dynamics.
NASA Center for Climate Simulation (NCCS) Presentation

The NASA Center for Climate Simulation (NCCS) offers integrated supercomputing, visualization, and data interaction technologies to enhance NASA's weather and climate prediction capabilities. It serves hundreds of users at NASA Goddard Space Flight Center, as well as other NASA centers, laboratories, and universities across the US. Over the past year, NCCS has continued expanding its data-centric computing environment to meet the increasingly data-intensive challenges of climate science. We doubled our Discover supercomputer's peak performance to more than 800 teraflops by adding 7,680 Intel Xeon Sandy Bridge processor-cores and most recently 240 Intel Xeon Phi Many Integrated Core (MIG) co-processors. A supercomputing-class analysis system named Dali gives users rapid access to their data on Discover and high-performance software including the Ultra-scale Visualization Climate Data Analysis Tools (UV-CDAT), with interfaces from user desktops and a 17- by 6-foot visualization wall. NCCS also is exploring highly efficient climate data services and management with a new MapReduce/Hadoop cluster while augmenting its data distribution to the science community. Using NCCS resources, NASA completed its modeling contributions to the Intergovernmental Panel on Climate Change (IPCG) Fifth Assessment Report this summer as part of the ongoing Coupled Modellntercomparison Project Phase 5 (CMIP5). Ensembles of simulations run on Discover reached back to the year 1000 to test model accuracy and projected climate change through the year 2300 based on four different scenarios of greenhouse gases, aerosols, and land use. The data resulting from several thousand IPCC/CMIP5 simulations, as well as a variety of other simulation, reanalysis, and observationdatasets, are available to scientists and decision makers through an enhanced NCCS Earth System Grid Federation Gateway. Worldwide downloads have totaled over 110 terabytes of data.
Expression of Macrophage Inflammatory Protein 1-α is Elevated in Alzheimer's Vessels and is Regulated by Oxidative Stress

Inflammatory mediators are highly expressed in the Alzheimer's disease (AD) brain. We have shown that in AD the cerebral microcirculation is a rich source of cytokines and chemokines including interleukins (IL) 1beta, IL-6, IL-8, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1. However, the factors that regulate expression of these inflammatory proteins have not been defined. The objective of this study is to compare expression of macrophage inflammatory protein 1-alpha (MIP-1alpha) in brain microvessels isolated from AD patients to vessels from age-matched controls and further to determine whether expression of MIP-1alpha in brain endothelial cells is altered by oxidative stress. The data show that brain AD-derived microvessels express high levels of MIP-1alpha mRNA and release high levels of MIP-1alpha protein compared to brain microvessels isolated from controls. Treatment of brain endothelial cell cultures with menadione, a superoxide releasing compound, hydrogen peroxide, lipopolysacharride, or oxidatively modified low density lipoproteins (LDL) (Ox-LDL, HNE-LDL) results in a dose- dependent increase in MIP-1alpha mRNA levels and MIP-1alpha release into the media. These results suggest that oxidative and lipid insults to the brain microvasculature are likely to contribute to the inflammatory milieu of the AD brain.
SPARROW Modeling of Nitrogen Sources and Transport in Rivers and Streams of California and Adjacent States, U.S.

The SPARROW (SPAtially Referenced Regressions On Watershed attributes) model was used to evaluate the spatial distribution of total nitrogen (TN) sources, loads, watershed yields, and factors affecting transport and decay in the stream network of California and portions of adjacent states for the year 2002. The two major TN sources to local catchments on a mass basis were fertilizers and manure (51.7%) and wastewater discharge (15.9%). Other sources contributed < 12%. Fertilizer use is widespread in the Central Valley region of California, and also important in several other regions because of the diversity of California agriculture. Precipitation, sand content of surficial soils, wetlands, and tile drains were important for TN movement to stream reaches. Median streamflow in the study area is about 0.04 m3/s. Aquatic losses of nitrogen were found to be most important in intermittent and small to medium sized streams (0.2-14 m3/s), while larger streams showed less loss, and therefore are important for TN transport. Nitrogen loss in reservoirs was found to be insignificant, possibly because most of the larger ones are located upstream of nitrogen sources. The model was used to show loadings, sources, and tributary inputs to several major rivers. The information provided by the SPARROW model is useful for determining both the major sources contributing nitrogen to streams and the specific tributaries that transport the load.
Synthesis and Molecular Structure of Tris(pentamethylphenyl)aluminum, (C6Me5)3Al, and the Magnesium Cluster [Mg6(μ3-OH)2(μ3-Br)2(μ2-Br)8(OEt2)8]

The synthesis and molecular structures of tris(pentamethylphenyl)aluminum, (C6Me5)3Al, (I), and the magnesium cluster [Mg6(μ3-OH)2(μ3-Br)2(μ2-Br)8(OEt2)8] (II), are reported. Both compounds were isolated from the same system. The aluminum atom in (I) resides in an almost idealized trigonal planar environment. The dihedral angles of the pentamethylphenyl rings relative to the AlC3plane in (I) are 67.2, 62.4, and 61.2°. The neutral magnesium cluster, (II), is interesting in that contains six magnesium atoms each of which resides in octahedral environments.
Debugging mapped parallel programs

As more sophisticated tools for parallel programming become available, programmers will inevitably want to use them together. However, some parallel programming tools can interact with each other in ways that make them less useful. In particular, it a mapping tool is used to adapt a parallel program to run on relatively few processors, the information presented by a debugger may become difficult to interpret. The authors examine the problems that can arise when programmers use debuggers to interpret the patterns of message traffic in mapped parallel programs. They also suggest how to avoid these problems and made debugging tools more useful. >
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Although uncommon, intra-abdominal neoplasms may spread when tumor cells seed the surrounding peritoneal surfaces. Although intraperitoneal dissemination of neoplastic cells represents a universally fatal problem that is difficult to treat, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a treatment paradigm that can prolong survival in patients with peritoneal surface disease (PSD) arising from a variety of primary tumors. The goal is the complete cytoreduction of all macroscopic disease prior to perfusion with HIPEC. Therefore, appropriate candidates are identified based not only on their ability to tolerate aggressive CRS but also the likelihood of obtaining a complete or near-complete cytoreduction. Resection is accomplished with the removal of all involved organs and peritonectomy procedures to remove tumor implants. Although morbidity and mortality are significant, our group and others have shown that CRS-HIPEC can achieve meaningful prolongation of survival with acceptable quality of life. Careful selection of patients can help ensure that only those who can expect to have the greatest benefits are subjected to the inherent risks of this treatment paradigm.
Energy transfer processes in reactions of He(2 3S) and Ne(3P0,2) with CS2

Abstract A comparative spectroscopic study in the visible and ultraviolet ranges was conducted on the flowing afterglows resulting from the reactions of He(2 3S) and Ne(3P0,2) metastables with CS2. Penning ionization was found to be the predominant energy transfer process. However, electron—ion recombination within the afterglows constitutes a major secondary process and gives rise to the most intense emitting system, CS(A 1 Π → X 1Σ+). Both afterglows were found to produce the CS+2( B 2Σ+u- X 2Πg), CS+2( A 2Πu- X 2Πg) and CS(a 3Π-X 1Σ+) emission systems as well as some atomic sulfur emission lines. Some intensity differences were observed and are interpreted in terms of energetics and the formation mechanisms of the emitting species. A moderately strong CS+(A 2Πi-X 2Σ+) emission system was also observed in the ehlium afterglow. In addition, a weak, sharp group of bands in the 390–420 nm range in the helium afterglow has been determined to be due to the presence of a small amount of He+ ions. This group of bands consists of two overlapping emission systems and are identified as CS(B 1Σ+ → A 1Π) and CS+(B 2Σ+ → A 2Πi).
5-thio-l-rhamnose

Abstract Two routes for the synthesis of methyl 5- S -acetyl-6-deoxy-2,3- O -isopropylidene-5-thio- l -mannofuranoside (8) have been examined. Reaction of l -rhamnose with methanol in the presence of the cation-exchange resin gives methyl 6-deoxy-α- l -mannofuranoside (2) , which on conventional acetonation yields methyl 6-deoxy-2,3- O - isopropylidene-α- l -mannofuranosides (3) . Compounds 3 is also obtained by acetonation of l -rhamnose followed by treatment with a mixture of methanol, acetonation, Amberlite IR-120(H + ) resin. Chlorination of 3 with triphenylphosphine-carbon tetrachloride gives methyl 5-chloro-5,6-dideoxy-2,3- O -isopropylidene-β- d -gulofuranoside (7) , which reacts with potassium thioacetate to give 8 . Alternatively, 3 is iodized with ruthenium tetraoxide to methyl 6-deoxy-2,3- O -isopropylidene-α- l - lyxo -hexofuranosid-5-ulose (9) , which reduced by sodium borohydride mainly to methyl 6-deoxy-2,3- O -isopropylidene-β- d -gulofuranoside (10) . The O -tosyl derivative of 10 reacts with potassium thioacetate to produced 8 . Hydrolysis of 8 with 90% aqueous triflouroacetic acid, followed by acetolysis with a solution of acetic acid, acetic anhydride, and sulfuric acids gives an anomeric mixture of 1,2,3,4,-tetra- O -acetyl-6-deoxy-5-thio- l -mannopyranoses (12) , together with a small proportion of 1,2,3,-tri- O -acetyl-5- S -acetyl-6-deoxy-5-thio-β- l -mannofuranose (13) . Deacetylation of 12 or 13 gives 5-thio- l -rhamnose (6) , from which crystalline 1,2,3,4-tetra- O -( p -nitrobenzoyl)-5-thio-β- l -rhamnopyranose (14) is obtained.
The social context of homeless women's alcohol and drug use

Background Substance use poses a significant threat to the health of women, and homeless women are more likely to use alcohol and drugs than other women. Addressing risk factors in this population requires a focus on the social context of substance use among homeless women.