cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacokinetics of Inhaled Rifampicin Porous Particles for Tuberculosis Treatment: Insight into Rifampicin Absorption from the Lungs of Guinea Pigs

Tuberculosis (TB) is a life-threatening infection that requires a lengthy treatment process that is often associated with adverse effects. Pulmonary delivery of anti-TB drugs has the potential to increase efficacy of treatment by increasing drug concentrations at the lungs, the primary site of infection. The aim of the present study is to evaluate the disposition of rifampicin (RIF) after its pulmonary administration as porous particles (PPs) to guinea pigs and contrast it to that after oral administration. RIF microparticles were prepared by spray drying a solution of RIF and L-leucine (9:1), and the resulting particles were characterized for their physicochemical properties. Animals received RIF either as intravenous solution (iv), as oral suspension of micronized RIF (ORS) and RIF-PPs (ORPP), or by insufflation of the PPs (IRPP). Plasma samples were collected at preselected time points, and bronchoalveolar lavage (BAL) was performed at the end of the study. RIF concentrations in biological samples were analyzed by HPLC. Plasma concentration versus time data was analyzed by compartmental and noncompartmental methods. RIF PPs were thin walled porous particles with mass median aerodynamic diameter (MMAD) of 4.8±0.1 μm, GSD=1.29±0.03, and fine particle fraction below 5.8 μm of 52.9±2.0%. RIF content in the resulting particles was 91.8±0.1%. Plasma concentration vs time profiles revealed that the terminal slope of the iv group was different from that of the oral or pulmonary groups, indicating the possibility of flip-flop kinetics. RIF from IRPP appeared to be absorbed faster than that of ORPP or ORS as evidenced by higher RIF plasma concentrations up until 2 h. Notably, similar AUC (when corrected by dose), similar CL, λ, and half-life were obtained after oral administration of RIF at 40 mg/kg and pulmonary administration of RIF at 20 mg/kg. However, RIF in the IRPP group had a shorter Tmax and higher bioavailability than orally dosed groups. In addition, RIF concentrations in the BAL of animals in the IRPP group were 3-4-fold larger than those in the orally dosed groups. The disposition in ORS and ORPP were best described by a model with two sequential compartments, whereas the disposition of IRPP was best described by a two parallel compartment model. The advantages of delivering RIF by the pulmonary route are demonstrated in the present study. These include achieving higher RIF concentrations in the lungs and similar systemic levels after pulmonary delivery of one-half of the oral nominal dose. This is expected to result in a more effective treatment of pulmonary TB, as shown previously in published efficacy studies.
Altbekanntes, neue Leitlinien und zukünftige Herausforderungen

Harnwegsinfekte sind bei Kindern in den ersten Lebensjahren besonders haufig, lassen sich jedoch manchmal nur schwer zeitgerecht diagnostizieren. Ein leitlinienkonformes Vorgehen erleichtert die Diagnose, sodass rasch eine Therapie eingeleitet werden kann und sich Langzeitschaden vermeiden lassen.
General Strain Theory and White-Collar Crime

This paper applies general strain theory (GST) to the explanation of white-collar crime, including (a) occupational crimes committed by higher class individuals, (b) economic offenses such as fraud and embezzlement, which are committed by lower as well as higher class individuals, and (c) corporate crimes. Several strains or stressors are said to be especially relevant to the explanation of such crimes, including the blockage of economic goals, the experience of a range of other economic problems, the inability of achieve status goals, and a variety of work-related stressors. Whether these strains result in white-collar crime, however, is said to be influenced by such things as coping skills and resources, social support, opportunities for white-collar crime, social control, the perceived costs and benefits of white-collar crime, and association with criminal others.
Collapse Capacity of Corroded Pipes Under Combined Pressure, Longitudinal Force And Bending

The buckling/collapse strength of corroded pipes has been investigated for cost-effective and safe design of pipelines and risers. An analytical solution for calculating the collapse and bending moment capacity of corroded pipes is proposed. The solution is an extension of existing analytical equations for noncorroded pipes: (1) Elastic-plastic collapse of pipes under external pressure (Timoshenko’s equation); (2) collapse of pipes under internal pressure, bending and axial force (Mohareb’s analytical equations). The analytical equations agree well with results obtained by the finite element method, and may be used in strength assessment and risk-based corrosion allowance design. *ISOPE Member. Received January 1, 2000; revised manuscript received by the editors January 15, 2001. The original version (prior to the final revised manuscript) was presented at the Ninth International Offshore and Polar Engineering Conference (ISOPE-99), Brest, France, May 30-June 4, 1999.
Ecological investigations to select mitigation options to reduce vehicle-caused mortality of a threatened butterfly

Whereas roads that bisect habitat are known to decrease population size through animal-vehicle collisions or interruption of key life history events, it is not always obvious how to reduce such impacts, especially for flying organisms. We needed a quick, cost-efficient and effective way to determine how best to decrease vehicle-caused mortality while maintaining habitat connectivity for the federally listed Oregon silverspot butterfly, Speyeria zerene hippolyta. Therefore, we gathered targeted ecological information that informed selection of a mitigation option prior to implementation. We sampled butterfly behavior and environmental conditions along a highway and conducted a small-scale experiment along a decommissioned road corridor used by these butterflies. Using our findings, we recommended vegetation management and helped managers eliminate options they were considering that would be ineffective such as increasing shade or wind in the road, and installing fencing or hedgerows aimed at directing flight above traffic. This quick and inexpensive approach of using ecological observations and small-scale experiments to evaluate the likely success of each available mitigation option can be used to determine effective, species-specific solutions for reducing traffic impacts on pollinators and other small, flying organisms of conservation concern.
Carcinogens, Enzyme Induction, and Gene Action

Publisher Summary This chapter reviews the effects of polycyclic hydrocarbons and drugs on certain enzyme activities, along with a discussion on carcinogenesis and gene action. The term “enzyme induction” is used to describe the process that increases the rate of synthesis of a specific enzyme relative to its rate of synthesis in the uninduced organism. A large number of drugs of pharmacological value have been found to stimulate either their own metabolism or the metabolism of other compounds by liver microsomes. The kinds of enzyme activities that are stimulated by various drug pretreatment include C- and N-hydroxylation; N-, S-, and O-demethylation; and glucuronide formation. In addition to induction in hepatic tissue, there have been several reports of drug-induced increases in enzyme activity in the tissues other than the liver. The effects of oncogenic viruses on enzyme induction and the effects of polycyclic hydrocarbons and phenobarbital on microsomal drug-metabolizing enzymes are also discussed in the chapter, along with the pharmacological and physiological significance of polycyclic hydrocarbons and the drug-induced enzyme activity effect of polycyclic hydrocarbons on carcinogenesis. Although the diversity of carcinogenic agents implies that there is no single common, initial site of action for all carcinogens, the ability of these agents to act concertedly or antagonistically suggests their action to be the result of their impingement on common cellular systems altered during carcinogenesis. The phenotypic changes observed in carcinogenesis must be related either to the modifications in the chemical structure of the gene itself, or to the changes in the system that transcribes information from the gene into particular messages, which are then translated into specific enzyme proteins. Thus, carcinogenesis involves either mutational or genetic regulatory changes.
Competency Judgments: Case Studies From The Psychiatrist’s Perspective

Psychiatrists at times are consulted by colleagues in other specialties to assist in determining a patient’s capacity to give (or withhold) consent for medical treatment. Dr. Boisaubin rightly points out that in most instances, a properly trained physician alone can determine whether a patient is making informed choices about medical care. Using a combination of common sense, basic interviewing skills, and fundamental psychiatric concepts, practitioners usually know when patients have grasped the medical facts presented to them, and when they are making a choice based on that knowledge.
Recognition Decisions From Visual Working Memory Are Mediated by Continuous Latent Strengths

Making recognition decisions often requires us to reference the contents of working memory, the information available for ongoing cognitive processing. As such, understanding how recognition decisions are made when based on the contents of working memory is of critical importance. In this work we examine whether recognition decisions based on the contents of visual working memory follow a continuous decision process of graded information about the correct choice or a discrete decision process reflecting only knowing and guessing. We find a clear pattern in favor of a continuous latent strength model of visual working memory-based decision making, supporting the notion that visual recognition decision processes are impacted by the degree of matching between the contents of working memory and the choices given. Relation to relevant findings and the implications for human information processing more generally are discussed.
Ammonia, volatile fatty acids, phenolics, and odor offensiveness in manure from growing pigs fed diets reduced in protein concentration.

The objective of this study was to investigate whether reducing dietary CP concentration decreases fecal VFA, manure ammonia (NH 3 ) emission and odor, and urinary phenolic metabolites. Six barrows were allotted to one of six dietary treatments in a Latin square design. Treatments consisted of four corn-soybean meal based diets containing 15, 12, 9, and 6% CP, a casein-based diet containing 15% CP, and a protein-free diet (0% protein). Crystalline AA were included in the 12, 9, and 6% CP diets. The casein-based and protein-free diets were used to determine basal endogenous contribution of VFA, phenolics, NH 3 , and manure odor. Pigs were housed individually in metabolism cages to allow total collection of feces and urine. Feces and urine were collected and pooled within pig and period. Feces and urine were analyzed for VFA and phenolic metabolite concentrations, respectively. Feces and urine were then mixed, stored, and fermented at room temperature for 30 d. For NH 3 determination, headspace air was sampled from manure slurries at 24, 48, and 72 h after fermentation. Slurry samples were placed into vials, capped, and randomized before odor panel evaluation. Odor offensiveness was classified on severity: 1 = non-offensive; 2 = mildly offensive; 3 = moderately offensive; 4 = strongly offensive; and 5 = extremely offensive. Reducing dietary CP increased (P < 0.05) fecal VFA concentrations but did not affect phenolic concentrations in urine. Manure NH 3 emission was reduced (P < 0.05) as dietary CP concentration decreased from 15 to 0%. The 15% diet had the least offensive manure slurry with odor qualitative ranking of 2.58 (i.e., mild-moderately offensive). Compared with the 15% CP diet, manure from the 9 and 6% CP diets was found to be more offensive (P < 0.05), with qualitative rankings of 2.92 and 3.10, respectively. Odor qualitative rank for the 12% CP, protein-free diet, and casein-based diet did not differ from that of the 15% CP diet. These results indicate that reduction in dietary CP concentrations decreases manure NH 3 emission, but it does not diminish manure odor offensiveness and fecal VFA concentrations.
Judging guilt and accuracy: highly confident eyewitnesses are discounted when they provide featural justifications

ABSTRACTJurors are heavily swayed by confident eyewitnesses. Are they also influenced by how eyewitnesses justify their level of confidence? Here we document a counter-intuitive effect: when eyewitnesses identified a suspect from a lineup with absolute certainty (‘I am completely confident’) and justified their confidence by referring to a visible feature of the accused (‘I remember his nose’), participants judged the suspect as less likely to be guilty than when eyewitnesses identified a suspect with absolute certainty but offered an unobservable justification (‘I would never forget him’) or no justification at all. Moreover, people perceive an eyewitness’s identification as nearly 25% less accurate when the eyewitness has provided a featural justification than an unobservable justification or simply no justification. Even when an eyewitness’s level of confidence is clear because s/he has expressed it numerically (e.g. ‘I am 100% certain’) participants perceive eyewitnesses as not credible (i.e. inaccura...
Focus on growth hormone deficiency and bone in adults.

Growth hormone (GH) exerts several effects on the skeleton, mediated either directly or indirectly, leading to increased bone formation and resorption rates. Patients with growth hormone deficiency (GHD) of adult onset have decreased bone mineral density (BMD) and increased fracture risk. Some, but not all, studies have found that adults with childhood onset GHD also have lower BMD than healthy controls. Adults with GHD of childhood onset have smaller bone dimensions, leading to possible underestimation of areal BMD (measured by dual energy X-ray absorptiometry), thus potentially confounding the interpretation of densitometric data. Available data suggest that patients with childhood onset GHD are at increased fracture risk. Prospective studies and some clinical trials found that GH replacement for at least 18–24 months leads to increased BMD. Retrospective and prospective data suggest that GH replacement is associated with decreased fracture risk in adults. However, data from randomized clinical trials are lacking.
Identification of 4-(3-Pyridyl)-4-oxobutyl-2′-deoxycytidine Adducts Formed in the Reaction of DNA with 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone: A Chemically Activated Form of Tobacco-Specific Carcinogens

Metabolic activation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1) and N′-nitrosonornicotine (NNN, 2) results in the formation of 4-(3-pyridyl)-4-oxobutyl (POB)-DNA adducts, several of which have been previously identified both in vitro and in tissues of laboratory animals treated with NNK or NNN. However, 2′-deoxycytidine adducts formed in this process have been incompletely examined in previous studies. Therefore, in this study we prepared characterized standards for the identification of previously unknown 2′-deoxycytidine and 2′-deoxyuridine adducts that could be produced in these reactions. The formation of these products in reactions of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc, 3), a model 4-(3-pyridyl)-4-oxobutylating agent, with DNA was investigated. The major 2′-deoxycytidine adduct, identified as its stable cytosine analogue O2-[4-(3-pyridyl)-4-oxobut-1-yl]-cytosine (12), was O2-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deox...
The Dynamic Interplay Between Bottom-Up and Top-Down Processes Supporting Prospective Remembering

Like many dual process theories in the psychological sciences, existing models of prospective memory (i.e., remembering to execute future intentions) emphasize the role of singular top-down or bott...
Attacking Unexplored Networks - The Probe-and-Attack Problem

Attackers generally do not have complete information about the structure and function of a target network, and thus have to distribute resources between actions that directly achieve an objective to return some utility (‘Attack’), and actions that expose new knowledge about the network (‘Probe’) allowing new actions to be taken. We introduce the NP-hard two-action Probe-and-Attack Problem (PAP) and provide methods to compute upper and lower bounds on the optimal solution. We then compare the bounds to the performance of two greedy algorithms on specialized instances of the problem.
Heat Transfer Operability Limits for an Actively and Passively Cooled Hypersonic Vehicle

For a trimmed hypersonic waverider vehicle, computations were performed to investigate the operability limits that occur due to excessive heating of the external surface, including the nose region ...
Biopolitical Metaphor: Habitualized Embodiment between Discourse and Affect

This article theorizes the biopolitical production of embodiment through a consideration of biopolitical metaphor. It is argued that much recent theoretical work on biopower fails to provide an ade...
Diagnostic Features of Emphysematous Osteomyelitis.

Abstract Emphysematous osteomyelitis (EO) is a rare, aggressive, and potentially fatal variant of osteomyelitis related to gas-forming organisms. Imaging plays a vital role in diagnosis. The purpose of this study was to describe a novel and distinct imaging sign of EO, by analysis of the imaging characteristics of 3 newly identified cases of EO as well as all reported cases in the literature. Literature review and retrospective study in 2 tertiary care medical centers was conducted. During the course of clinical care over the last year, we have observed 2 cases of EO. An Institutional Review Board approved 1-year systematic retrospective review of our institutional radiology information system identified 1 additional case of EO. We conducted a MEDLINE literature search to identify all published EO case reports using key phrases. The imaging in all published cases was reviewed. To address the specificity of imaging characteristics, we identified cases demonstrating variants of intraosseous gas that were not caused by EO. We found 31 individual case reports of EO via MEDLINE search. Of the published cases, 25 of the 31 cases contained images of sufficient extent and quality for image analysis. Including our 3 cases, a total of 34 cases were identified. Of the 34 cases, 28 had images of sufficient quality and extent to determine the presence or absence of the “pumice stone” pattern. The “pumice stone” sign was identified in 27 of 28 cases (96%). The most commonly affected sites of infection include the pelvic bones (38%; 13 of 34), vertebral bodies (32%; 11 of 34), and femurs (24%; 8 of 34). Adjacent soft tissue inflammation and emphysema was evident in 23 of 29 cases (79%). Cortical destruction, a key diagnostic feature of traditional osteomyelitis, was absent in 79% of cases of EO. We describe the “pumice stone sign” as a radiological sign to identify EO. We found it present in 96% of all currently known cases of EO. EO commonly involves the pelvic bones (38%), vertebral bodies (32%), and femur (24%). Key features also include adjacent soft tissue emphysema (79%) and absence of cortical destruction (79%).
Maintaining an Inductive Database

Many “state-of-the-art” expert computer systems function through the application of a finite set of deductive production rules to a static database of knowledge. For some well-studied fields such a system is sufficient, as there are no significant changes being made in the fundamental theory behind the knowledge represented in the database. An example of such a system is MYCIN, a medical diagnosis system. MYCIN’S database is made up of the associations between symptoms and diseases.1 This system works because these associations are well-documented and supported by centuries of medical study.
Gradient Materials and Construction of Gradients

This chapter discusses the properties of the common gradient materials. Density gradients are usually prepared from solutions or sols of materials, which are considerably denser than water. The density of most gradient solutions is greater than 1.0 gm/cm 3 . Excluding nonaqueous gradients for the present, the properties of the ideal solute for gradients are—freely soluble in water, very dense, nonviscous, negligible osmotic pressure, physiologically and chemically inactive, transparent in visible and ultraviolet light, and cheap. Common sugar is easily the most widely used gradient material. Although sucrose gradients have been used more than any other for the separation of the membrane-bound organelles, they are almost certainly inferior to silica and Ficoll. Mannitol was greatly favored over sucrose by early physiologists as an osmoticum, presumably because it penetrated cell membranes less rapidly than sucrose. More recently, mannitol has been recommended over sucrose in the isolation of mitochondria. Ficoll has become the most generally useful among polymeric gradient materials.
Positive Electrodes in Lithium Systems

Several types of lithium batteries are used in a variety of commercial products, and are produced in very large numbers. According to various reports, the sales volume in 2008 was approximately 10 billion dollars per year, and it was growing rapidly. Most of these products are now used in relatively small electronic devices, but there is also an extremely large potential market if lithium systems can be developed sufficiently to meet the requirements for hybrid, or even plug-in hybrid vehicles.
Quantum state preparation by a shaped photon pulse in a one-dimensional continuum

We propose a method to deterministically prepare a desired quantum state in a one-dimensional (1D) continuum by a shaped photon pulse. This method is based on time reversal of the quantum emission process. We show that the desired quantum state such as a Dicke or timed Dicke state can be successfully prepared with very high fidelity even if the dissipation to the environment is non-negligible and the pulse shaping is not perfect. We also show that large quantum entanglement between emitters can be created by just a single-photon pulse. This method is experimentally feasible in a 1D waveguide QED or a circuit QED system.
Investigation of aerosol and gas emissions from a coal-fired power plant under various operating conditions

ABSTRACTThe concentrations of fine particles and selected gas pollutants in the flue gas entering the stack were measured under several common operation modes in an operating coal power plant producing electricity. Particle size distributions in a diameter range from 10 nm to 20 μm were measured by a scanning mobility particle sizer (SMPS), and the flue gas temperature and concentrations of CO2 and SO2 were monitored by a continuous emission monitoring system (CEMS). During the test campaign, five plant operating modes were studied: soot blowing, bypass of flue-gas desulfurization (FGD), reheat burner operating at 0% (turned off), 27%, and 42% (normal condition) of its full capacity. For wet and dry aerosols, the measured mode sizes were both around 40 nm, but remarkable differences were observed in the number concentrations (#/cm3, count per square centimeter). A prototype photoionizer enhanced electrostatic precipitator (ESP) showed improved removal efficiency of wet particles at voltages above +11.0 kV...
Analysis of oxidative stress-mediated degeneration in retina and RPE using sodium iodate (NaIO3) Model

In the eye, the retina and RPE (retinal pigmented epithelium) are exposed to high levels of oxidative radicals generated by light exposure and high metabolic rate. Degeneration of these cells due to cumulative oxidative damage plays an important role in diseases like AMD (Age-related Macular Degeneration) and subsequent blindness. The underlying mechanisms of AMD remain unclear, and therefore extensive studies are needed to help combat the disease. We use sodium iodate, an oxidizing agent that preferentially degenerate RPE, to induce oxidative stress in young and old mice. DJ-1, Parkinson’s Disease (PD)-associated gene protects neurons from oxidative damages. High levels of DJ-1 were observed in RPE and photoreceptors of adult mice retina. DJ-1 loss results in age-related mild structural and physiological changes in retinas of DJ-1 knockout mice. Control (C57BL/6) and DJ-1 knockout 3- and 15- month-old mice were injected with 10mg/kg sodium iodate to gain insight into oxidative stress mechanisms in RPE and retina.Histological sections revealed that oxidative stress in DJ-1 knockout resulted in increased RPE and photoreceptor cells degeneration compared to controls. Gene expression analysis for antioxidant genes was carried out. The transcript levels of these genes were significantly upregulated in RPE of DJ-1 knockout compared to control but downregulated in the retina in 3-month-old mice. In 15-month-old mice, transcript levels of these genes were significantly downregulated in RPE of DJ-1 knockout compared to control but remained unchanged in the retina. Injection of mice with 10mg/Kg NaIO3 differentially regulated the expression of these transcripts in the RPE and retinas. Overall, our data suggest that loss of DJ-1 renders RPE and retina more susceptible to oxidative damage.
On Professionalization Through Scholarship: A Conversation with Dr. Leigh Shaffer (1947-2017)

Craig M. McGill interviews the late Leigh Shaffer on the professionalization of academic advising and his contributions to the field. Shaffer responds to critiques of his work and how he sees the field needing to increase its scholarly base in order to move towards professionalization.
Observational vs Experimental Data When Making Automated Decisions Using Machine Learning

Decisions supported by machine learning algorithms often have the goal of improving (and thus affecting) an outcome by means of an intervention. Common examples include influencing someone's purchasing behavior with an advertisement or increasing customer retention with a special offer. Unfortunately, if these algorithms use observational data to estimate the effect of the interventions, the resulting estimates will likely suffer from confounding bias. Investing in experimental data offers a way to deal with confounding, but such data are often costly to acquire and may be prone to other sources of bias. This paper addresses the question of whether using readily-available (but confounded) data can lead to decisions that are at least as good as when investing in costly unconfounded data. We present a theoretical comparison between the use of confounded and unconfounded data when the goal is to build models to make automated intervention decisions. The key insight of the work is that optimizing to make the correct decision generally involves understanding whether a causal effect is above or below a given threshold, which is different from optimizing to reduce the magnitude of the bias in a causal-effect estimate. As a result, models trained with confounded data may lead to decisions that are just as good (or better) in certain scenarios, such as when larger causal effects are more likely to be overestimated or when the benefits of larger and cheaper data outweigh the detrimental effects of confounding. The theoretical results are tested by comparing the two approaches using the wide variety of benchmark data sets (77 scenarios and 7,700 data sets in total) from the 2016 ACIC causal modeling competition. Finally, we provide several straightforward tools that may be used in practice to determine whether a confounded model should be deployed to make automatic intervention decisions. It is our hope that a better understanding of this perspective---that confounding does not affect causal effect estimation and causal decision making in the same way---will help improve the chance of success of future methodological developments for automated decision making.
Symptomatic Radial Neck Nonunion Following Traumatic Impacted Radial Neck Fracture.

Purpose Minimally displaced or impacted radial neck fractures are commonly sustained after elbow trauma, although few require surgical treatment or result in lasting complications. Whereas they are rare, radial neck nonunion after this injury can have adverse implications for patient function and quality of life. The current study presents a case series of 8 radial neck nonunions after minimally displaced or impacted radial neck fractures. Methods Using our institution’s electronic medical record database, referred to as the Synthetic Derivative database, we performed a retrospective review of all radial neck fractures that presented to our institution over 15 years. Results Of 472 minimally displaced or impacted radial neck fractures, 8 progressed to symptomatic nonunion. Average age of these patients was 54 ± 9.3 years. One patient presented with bilateral radial neck nonunions. Conclusions Nonunion after an impacted radial neck fracture is a rare yet frustrating outcome for patients and providers alike. Our results estimate the rate of symptomatic radial neck nonunion after minimally displaced or impacted radial neck fractures to be 1.7%. Type of study/level of evidence Prognostic IV.
IPSA: Integer Programming via Sparse Approximation for Efficient Test-Chip Design

Logic test chips are a key component of the yield learning process, which aim to investigate the yield characteristics of actual products that will be fabricated at high volume. Mathematically, the design of a logic test chip with such an objective may involve solving a constrained under-determined equation for an integer vector solution, which is unfortunately, NP-hard. Existing solving methods are not applicable due to lack of accuracy or high computational complexity. We propose a method called IPSA (Integer Programming via Sparse Approximation) to solve this integer programming (IP) problem in an effective and efficient manner. By solving a transformed sparse-regression problem and a subsequent rounding process, a solution can be achieved with comparable error to the optimal solution of the original IP problem but using far less time and memory. Experiments with seven industrial examples demonstrate that with more than 100× speed-up, IPSA achieves a similar or even better solution compared to directly solving the original problem with a commercial IP solver.
CSAG2 is a cancer-specific activator of SIRT1.

SIRT1 is a NAD+ -dependent deacetylase that controls key metabolic and signaling pathways, including inactivating the p53 tumor suppressor. However, the mechanisms controlling SIRT1 enzymatic activity in the context of cancer are unclear. Here, we show that the previously undescribed CSAG2 protein is a direct activator of SIRT1. CSAG2 is normally restricted to expression in the male germline but is frequently re-activated in cancers. CSAG2 is necessary for cancer cell proliferation and promotes tumorigenesis in vivo. Biochemical studies revealed that CSAG2 directly binds to and stimulates SIRT1 activity toward multiple substrates. Importantly, CSAG2 enhances SIRT1-mediated deacetylation of p53, inhibits p53 transcriptional activity, and improves cell survival in response to genotoxic stress. Mechanistically, CSAG2 binds SIRT1 catalytic domain and promotes activity independent of altering substrate affinity. Together, our results identify a previously undescribed mechanism for SIRT1 activation in cancer cells and highlight unanticipated approaches to therapeutically modulate SIRT1.
Raptor Zonal Statistics: Fully Distributed Zonal Statistics of Big Raster + Vector Data [Pre-Print].

Recent advancements in remote sensing technology have resulted in petabytes of data in raster format. This data is often processed in combination with high resolution vector data that represents, for example, city boundaries. One of the common operations that combine big raster and vector data is the zonal statistics which computes some statistics for each polygon in the vector dataset. This paper models the zonal statistics problem as a join problem and proposes a novel distributed system that can scale to petabytes of raster and vector data. The proposed method does not require any preprocessing or indexing which makes it perfect for ad-hoc queries that scientists usually want to run. We devise a theoretical cost model that proves the efficiency of our algorithm over the baseline method. Furthermore, we run an extensive experimental evaluation on large scale satellite data with up-to a trillion pixels, and big vector data with up-to hundreds of millions of edges, and we show that our method can perfectly scale to big data with up-to two orders of magnitude performance gain over Rasdaman and Google Earth Engine.
Harnessing Recent Advances in Synthetic DNA and Electroporation Technologies for Rapid Vaccine Development Against COVID-19 and Other Emerging Infectious Diseases

DNA vaccines are considered as a third-generation vaccination approach in which antigenic materials are encoded as DNA plasmids for direct in vivo production to elicit adaptive immunity. As compared to other platforms, DNA vaccination is considered to have a strong safety profile, as DNA plasmids neither replicate nor elicit vector-directed immune responses in hosts. While earlier work found the immune responses induced by DNA vaccines to be sub-optimal in larger mammals and humans, recent developments in key synthetic DNA and electroporation delivery technologies have now allowed DNA vaccines to elicit significantly more potent and consistent responses in several clinical studies. This paper will review findings from the recent clinical and preclinical studies on DNA vaccines targeting emerging infectious diseases (EID) including COVID-19 caused by the SARS-CoV-2 virus, and the technological advancements pivotal to the improved responses - including the use of the newer intradermal electroporation (ID-EP) technology, DNA-encoded adjuvant cytokines, and DNA-launched nano-vaccine technology. With continuous advancement over the past three decades, the DNA approach is now well-poised to develop vaccines against COVID-19, as well as other EIDs.
Identification of molecular scaffolds from Caatinga Brazilian biome with potential against Aedes aegypti by molecular docking and molecular dynamics simulations

Abstract In this paper, we performed a virtual screening by docking and molecular dynamics approaches to identify molecular scaffolds as potential inhibitors of the Sterol Carrier Protein-2 (PDB ID: 1PZ4) from Aedes aegypti, using a homemade data bank of 248 secondary metabolites, found on Caatinga Brazilian biome. The insect is a known vector of important diseases around the world, as Zika, Chikungunya and Dengue fever. The compounds were selected after a search on SciFinderⓇ online platform, crossing the name of 40 Caatinga biome plants with words indicating the identification and/or isolation of molecules. Initial re-docking and docking procedures showed that the co-crystalized ligand (“palmitic acid”) presented a binding energy (-6.9 kcal/mol) higher than seventy-six of the total number of compounds evaluated (two hundred forty-eight). Five compounds were considered for sequential Molecular Dynamics (MD) calculations, by energetic and structural analysis. The MD plots and average binding energies obtained by MM/PBSA method confirm that the biflavonoid loniflavone, founded in the leaves of a Brazilian plant called “catingueira” (Cenostigma pyramidale (Tul.) E. Gagnon & G. P. Lewis, previously Caesalpinia priamidalis) was the most promissory in the interaction with 1PZ4. Two additional compounds from lignan and sesquiterpene molecular scaffolds were also identified as potential against A. aegypti. These results can be used as guidelines for testing compounds with larvicidal application.
Evolution of pathogen response genes associated with increased disease susceptibility during adaptation to an extreme drought in a Brassica rapa plant population.

Pathogens are key components in natural and agricultural plant systems. There is evidence of evolutionary changes in disease susceptibility as a consequence of climate change, but we know little about the underlying genetic basis of this evolution. To address this, we took advantage of a historical seed collection of a Brassica rapa population, which we previously demonstrated evolved an increase in disease susceptibility to a necrotrophic fungal pathogen following a drought. Previously, we combined a resurrection experiment with genome-wide sequencing of 124 pooled ancestral and descendant plants. Here, using these previously generated sequence data (Franks et al. in Mol Ecol 25(15):3622–3631, 2016), we show that well-characterized necrotrophic fungal pathogen response (NFPR) genes have evolved, as indicated by changes in allele frequency, between ancestors and descendants, with several of them identified as extreme FST outliers. The jasmonic acid (JA) signaling pathway in particular seems to underlie the evolution of disease susceptibility, in addition to its well characterized role in plastic disease response. We identify a list of 260 genes that are both NFPR genes and are differentially expressed in response to drought, based on publicly available data. We present evidence that five of these genes evolved between ancestors and descendants, suggesting that the drought acted as the evolutionary driver, and that the accompanying increase in disease susceptibility may have been a consequence of genetic pleiotropy. Our study provides evidence that for this population, standing variation in NFPR genes is affected by natural selection related to climate change. Our results reveal potentially important candidates that may underlie trait evolution in both crops and natural systems. Additionally, this trade-off between adaptation to biotic and abiotic stresses is an example of how climate change can have diverse and unexpected consequences.
Business alignment for the “Decade of Action”

The SDGs and Paris Climate Agreement, taken together, constitute the best hope for charting a new course for the world’s politics and economics, to produce “the future we want.” This paper briefly explores the central environmental, social, and economic challenges; the pathways to sustainability; and the central role of companies in achieving our global goals. We are facing four very deep and interconnected global environmental crises: human-induced climate change, unsustainable land use, mega-pollution, and increased frequency and intensity of pandemic zoonotic diseases. At the same time, we face massive social crises, including increasing inequality. There are six necessary SDG Transformations that each requires a major change in the organization of societal, political, and economic activities – which delineates also the critical role of business. The paper specifies four key questions that companies and their stakeholders can ask to effectively align with the "Decade of Action" needed to achieve the SDG ambitions.
N-Heterocyclic Carbene-Stabilized Gold Nanoparticles: Mono- Versus Multidentate Ligands

Over the past decade, N-heterocyclic carbenes (NHCs) have attracted remarkable attention as metal-coordinating ligands because of their ability to strongly interact with transition metal complexes ...
Telemedicine for HIV Care: Current Status and Future Prospects

Due to the COVID-19 pandemic, the use of telemedicine has been highlighted, especially in specialties, such as the management of HIV. Recent data were reviewed between January 1, 2019 and March 20, 2021 by searching English language manuscripts for studies documenting clinical outcomes in HIV care and the patient experience. A PubMed, Google Scholar, and bibliography review based on the search terms "HIV," "telemedicine," and "telehealth" was conducted. Studies included in this analysis were comprised of adult patients living with HIV, receiving care for HIV via telemedicine with reported clinical outcomes or perceptions of using telemedicine in the management of their HIV care. Of the 179 studies identified, 12 met inclusion for this analysis. Only two studies provided data on clinical outcomes of HIV (virologic outcomes), one pre-pandemic and one during COVID-19. The study evaluating viral suppression during COVID-19 demonstrated lower rates of virologic suppression and lower rates of missed appointments when shelter-in-place orders were issued compared to before the start of the pandemic. The remaining studies focused on patient-related outcomes as they related to the usability and adoption of telehealth models. Many practices documented the benefits and limitations of telemedicine based on the rapid switch from traditional in-person clinics. Benefits included retention in care for patients who lived a far distance from clinic, privacy for patients not wanting to be seen attending an HIV clinic, and more flexibility in scheduling appointments. Some limitations included patients' access to technology, ability and willingness to use technology, and privacy of patients who are homeless and reside in a shelter where homelessness is 3 times greater in people living with HIV compared to the general population. Healthcare should be tailored to the individual patient by assessing their needs and limitations, particularly with patients who may be at risk for discontinuation of care, particularly in the homeless population. In addition, there are mixed data on factors such as age, sex, and race being limiting factors in willingness to use technology. From the studies reviewed, willingness to engage with technology did not differ by age, sex, or race but did differ by access and willingness to use technology. Greater limitations were access to appropriate devices for telemedicine and digital literacy. Although there have been difficulties with the switch to telemedicine in clinics during the COVID-19 pandemic, many patients have reported being satisfied with care and would be interested in continuing once the shelter-in-place order is lifted. Future studies should focus on the provision of HIV care using telemedicine beyond the pandemic and focus on ways to improve the telemedicine experience for the patient.
A Cerebral Perfusion Pressure Greater than 80 mm Hg is More Beneficial

The issue of determining the most beneficial CPP was a topic of considerable discussion during the last ICP meeting. From that discussion, it was apparent that the data gathered over the last 9 years at the University of Louisville Trauma Center could best answer that question.
TH‐AB‐304‐05: Predicting Distant Failure in Lung SBRT Using Clinical Parameters

Purpose: To predict distant failure in lung Stereotactic Body Radiation Therapy (SBRT) using clinical parameters by machine learning algorithms with a new optimal parameter selection strategy. Methods: Support Vector Machine (SVM) based method is used to construct the model to predict distant failure using 143 lung cancer patients underwent SBRT at our institute. Meanwhile, Artificial Neural Network (ANN) and Logistic Regression (LR) based methods are applied for comparisons. The clinical parameters for each patient include demographic parameters (4), tumor characteristics (6), treatment faction schemes (2) and pretreatment medicines (6). The total number of clinical parameters is 18. The model construction method consists of two steps: (1) selecting optimal parameter set by a new Clonal Selection Algorithm (CSA); and (2) constructing SVM, ANN and LR based models for predicting distant failure in lung SBRT. Selecting optimal parameter set is considered as a combinatorial optimization problem. The proposed CSA method is one of the evolutionary algorithms that can obtain global optimal solutions, overcoming the limitation of the ranking based selection method that lead to local optimization. In addition, to overcome the effect of imbalanced data in training process, a Synthetic Minority Over-sampling Technique (SMOTE) is applied. Sensitivity, specificity and accuracy are used to evaluate the performance of the constructed models. Results: The accuracies for ANN, LR and SVM are 70.59%, 72.04%, 75.47%, respectively. The sensitivities for ANN, LR and SVM are 76%, 60.47% and 82%, while the specificities for the three models are 58.14%, 69.77% and 60.47%. Conclusion: A new CSA based parameter selection method is proposed. The SVM with the proposed CSA optimal parameter set selection strategy can achieve better performance than ANN and LR for predicting distant failure in lung SBRT patients based on clinical parameters.
Engineering systems for the generation of patterned co-cultures for controlling cell-cell interactions.

Abstract Background Inside the body, cells lie in direct contact or in close proximity to other cell types in a tightly controlled architecture that often regulates the resulting tissue function. Therefore, tissue engineering constructs that aim to reproduce the architecture and the geometry of tissues will benefit from methods of controlling cell–cell interactions with microscale resolution. Scope of the review We discuss the use of microfabrication technologies for generating patterned co-cultures. In addition, we categorize patterned co-culture systems by cell type and discuss the implications of regulating cell–cell interactions in the resulting biological function of the tissues. Major conclusions Patterned co-cultures are a useful tool for fabricating tissue engineered constructs and for studying cell–cell interactions in vitro , because they can be used to control the degree of homotypic and heterotypic cell–cell contact. In addition, this approach can be manipulated to elucidate important factors involved in cell–matrix interactions. General significance Patterned co-culture strategies hold significant potential to develop biomimetic structures for tissue engineering. It is expected that they would create opportunities to develop artificial tissues in the future. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.
The Teachers Union-Charter Impasse: Moving Forward from the New York Caps Fight

The public narrative generally frames teachers unions and the charter movement as mistrustful opponents locked in an unresolved impasse. There is little scholarly literature to correct this simplistic narrative of the relationship between charters and unions. This article examines the teachers union- charter relationship through a recent case of active and sometimes bitter charter politics: the fight to lift the charter cap in New York state in 2006 and 2007. This study examines the dynamics of the relationship through an analysis of media coverage of the New York caps fight and interviews with nearly 30 experts with varied views on charter schooling and from a wide range of professional backgrounds. The New York case suggests that ultimately, creating strong unions and effective charter schooling depends on these two sides finding common ground.