bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative view of strategies to engineer cell-selective ligand binding
Authors: Tan Zhixin Cyrillus , Orcutt-Jahns Brian T , Meyer Aaron S
Published: December 2021

A critical property of many therapies is their selective binding to target populations. Exceptional specificity can arise from high-affinity binding to surface targets expressed exclusively on target cell types. In many cases, however, therapeutic targets are only expressed at subtly different levels relative to off-target cells. More complex binding strategies have been developed to overcome this limitation, including multi-specific and multivalent molecules, creating a combinatorial explosion of design possibilities. Guiding strategies for developing cell-specific binding are critical to employ these tools. Here, we employ a uniquely general multivalent binding model to dissect multi-ligand and multi-receptor interactions. This model allows us to analyze and explore a series of mechanisms to engineer cell selectivity, including mixtures of molecules, affinity adjustments, valency changes, multi-specific molecules and ligand competition. Each of these strategies can optimize selectivity in distinct cases, leading to enhanced selectivity when employed together. The proposed model, therefore, provides a comprehensive toolkit for the model-driven design of selectively binding therapies.
Assessing the prevalence of refractive errors and accuracy of vision screening by schoolteachers in Liberia
Authors: Tobi Patrick , Ibrahim Nazaradden , Bedell Alex , Khan Imran , Jolley Emma , Schmidt Elena
Published: December 2021

Background

Evidence indicates that school-based vision screening by trained teachers is an effective way of identifying and addressing potential vision problems in schoolchildren. However, inconsistencies have been reported in both the testing methods and accuracy of the screeners. This study assessed the prevalence of refractive errors and accuracy of screening by teachers in Grand Kru County, Liberia.

Methods

We conducted a retrospective analysis of data from four schools where, in February 2019, children were screened for refractive errors by trained teachers and then re-examined by ophthalmic technicians. One row of five optotypes of the Snellen 6/9 (0.2 logMar) scale (tumbling E chart) was used at a distance of 3 m. The prevalence of visual impairment and associations with sex, age and school were explored. Sensitivity, specificity and predictive values were calculated.

Results

Data were available for 823 of 1095 eligible children with a mean age of 13.7 y (range 5–18) and male:female ratio of 1:0.8. Poor vision was identified in 24 (2.9%) children with no differences by either sex or age but small differences by school. Screening by teachers had a sensitivity of 0.25 (95% confidence interval [CI] 0.077 to 0.423) and a specificity of 0.996 (95% CI 0.992 to 1.000). Positive and negative predictive values were 0.667 (95% CI 0.359 to 0.975) and 0.978 (95% CI 0.968 to 0.988), respectively. The results were influenced by a high number of misclassifications in one of the four schools.

Conclusions

Teachers can be trained to conduct vision screening tests on schoolchildren to an acceptable level of accuracy, but strong monitoring and quality assurance systems should be built into screening programmes from the onset. In settings like Liberia, where many children do not attend school regularly, screening programmes should extend to community platforms to reach children out of school.
Using mystery shoppers to determine practices pertaining to antibiotic dispensing without a prescription among community pharmacies in South Africa—a pilot survey
Authors: Mokwele R. Nelly , Schellack Natalie , Bronkhorst Elmien , Brink Adrian J. , Schweickerdt Louise , Godman Brian
Published: December 2021

Background

Inappropriate use of antimicrobials is a key factor increasing antimicrobial resistance, a major global public health problem including in South Africa. Key drivers include antibiotics being dispensed without a prescription.

Objectives

To determine the accessibility of antibiotics without a prescription in community pharmacies in urban areas in South Africa and determine whether counselling was provided when antibiotics were dispensed.

Patients and methods

Prospective, observational study, employing simulated patients (SPs), presenting with upper respiratory tract infections (URTIs) and urinary tract infections (UTIs), undertaken to establish whether antibiotics can be obtained without a valid prescription in South Africa. This pilot study was conducted in privately owned (n = 20) and corporate (franchised, n = 14) community pharmacies in three regions in Gauteng Province.

Results

Antibiotics were sold in privately owned pharmacies without a prescription in 80% (16/20) of cases while no antibiotics were dispensed in corporate (franchised) pharmacies. Of the 16 pharmacies selling antibiotics without a prescription, pharmacist assistants were involved in 37.5% (n = 6) and counselling was not provided to 19% of SPs. Ciprofloxacin (42.9%) and metronidazole (28.6%) were the most common antibiotics dispensed. No antibiotics were dispensed for URTIs, only UTIs.

Conclusions

Dispensing antibiotics without prescriptions can be common among privately owned pharmacies in urban areas in South Africa. Corporate pharmacies, which probably have a greater income, appear to follow current legislation banning such activities. To limit selling with no prescription, community pharmacists and assistants especially in urban areas should be educated on appropriate patient care and legal requirements, with dispensing electronically monitored.
Analysis of Fragrance Allergens in Personal Care Products, Toys, and Water Samples: A Review
Authors: Chen Jing , Yi Zonghui , Sun Rui , Ning Wei , Zhou Chen , Tian Ziyi , Sun Chengjun , Li Yongxin
Published: December 2021

Fragrance allergens (FAs) refer to these volatile or semi-volatile fragrance compounds that can cause irritation and negative reactions. A large number of emerging FAs are widely used in household goods, and cause contact allergy or allergic contact dermatitis in eczema population and the general population. It shows an increasing prevalence and is regarded as a concern to public health. Recently, more and more studies have focused on the analytical methods of FAs in a variety of samples with different matrixes. Therefore, a systematic and comprehensive overview of recent progress of analysis of FAs in various samples is needed. In this review, the physical and chemical properties, applications, hazards, and the recent advances of sample preparation and determination methods of common FAs in personal care products, toys, and water samples are systematically and comprehensively summarized. Meanwhile, this review also discusses the advantages and limitations of different sample pretreatment and detection methods, thus offering a deep-going discussion of the development and future trends in this area
Determination of Heavy Metals in a Variety of Cannabis and Cannabis-Derived Products, First Action 2021.03
Authors: Nelson Jenny , Jones Craig , Heckle Sam , Anderson Leanne
Published: December 2021

Background

The legalization of medicinal or recreational marijuana across many states in the United States and other countries has driven demand for cannabis, hemp, and related products.

Objective

In the absence of federal regulations to ensure the product quality and safety of these products, each state issues its own guidance and sets its own regulations. Like food and pharmaceuticals, cannabis testing should include the analysis of heavy metals, which may be toxic if ingested or inhaled.

Methods

Based on established methods for the preparation and multi-elemental analysis of plant materials, a range of cannabis and cannabis-related products were prepared for analysis using microwave-assisted acid digestion followed by testing with inductively coupled plasma-mass spectrometry (ICP-MS). The sample preparation procedure was validated by measuring arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in four plant-based certified reference materials (CRMs).

Results

The mean ICP-MS results for As, Cd, Hg, and Pb were in good agreement (85–110%) with the certified concentrations. The accuracy and precision of the ICP-MS method for the determination of As, Cd, Hg, and Pb, as well as other elements, were tested by spiking the various cannabis samples at different concentration levels and determining the spike recoveries. The spike recoveries for As, Cd, Hg, and Pb in all spiked samples met the AOAC Standard Method Performance Requirements (SMPR®) for Determination of Heavy Metals in a Variety of Cannabis and Cannabis-Derived Products (SMPR 2020.001) of 60–115% for low-level spike and 80–115% for mid- and high-level spikes.

Conclusion

Microwave-assisted acid digestion and ICP-MS are suitable for trace metal preparation and analysis of cannabis, as well as related products, as shown by the results of this method. The repeatability and recovery results for As, Cd, Hg, and Pb met the method requirement criteria in the AOAC SMPR 2020.001. This method can be used for all stages of production to ensure safety with respect to toxic metals.

Highlights

A wide range of cannabis and hemp samples, from raw materials to finished products, are within scope for analysis using the microwave-assisted acid digestion/ICP-MS method.
Pre-hatching and post-hatching environmental factors related to epigenetic mechanisms in poultry
Authors: Dunislawska Aleksandra , Pietrzak Elzbieta , Wishna Kadawarage Ramesha , Beldowska Aleksandra , Siwek Maria
Published: December 2021

Epigenetic modifications are phenotypic changes unrelated to the modification of the DNA sequence. These modifications are essential for regulating cellular differentiation and organism development. In this case, epigenetics controls how the animal’s genetic potential is used. The main epigenetic mechanisms are microRNA activity, DNA methylation, and histone modification. The literature has repeatedly shown that environmental modulation has a significant influence on the regulation of epigenetic mechanisms in poultry. The aim of this review is to give an overview of the current state of the knowledge in poultry epigenetics in terms of issues relevant to overall poultry production and the improvement of the health status in chickens and other poultry species. One of the main differences between birds and mammals is the stage of embryonic development. The bird’s embryo develops outside its mother, so an optimal environment of egg incubation before hatching is crucial for development. It is also the moment when many factors influence the activation of epigenetic mechanisms, i.e., incubation temperature, humidity, light, as well as in ovo treatments. Epigenome of the adult birds might be modulated by nutrition, supplementation, and treatment, as well as modification of the intestinal microbiota. In addition, the activation of epigenetic mechanisms is influenced by pathogens (i.e., pathogenic bacteria, toxins, viruses, and fungi) as well as the maintenance conditions. Farm animal epigenetics is still a big challenge for scientists. This is a research area with many open questions. Modern methods of epigenetic analysis can serve both in the analysis of biological mechanisms and in the research and applied to production system, poultry health, and welfare.
Spending and Happiness: The Role of Perceived Financial Constraints
Authors: Dias Rodrigo S , Sharma Eesha , Fitzsimons Gavan J
Published: December 2021

Perceived financial constraints are ubiquitous, and prior research suggests that consumers who feel financially constrained are especially likely to engage in compensatory consumption to signal positive attributes or offset the aversiveness associated with their state. However, it is unclear whether spending confers greater happiness when consumers feel financially constrained. Seven high-powered studies (N = 7,228) demonstrate that perceived financial constraints decrease the happiness consumers derive from their purchases. This effect is robust across several purchase types and occurs in part because consumers who perceive greater financial constraints are more likely to consider opportunity costs when evaluating their purchases (studies 2A and 2B). Consistent with this mechanism, the effect attenuates when all consumers are prompted to consider opportunity costs (study 3) and when consumers consider planned purchases (study 4). The negative effect of perceived financial constraints on purchase happiness results in an important behavioral outcome: less favorable consumer reviews (studies 5A and 5B). The authors conclude by meta-analyzing their file drawer (25,765 participants; 42 studies) to explore how the effect differs across several purchase types and discussing theoretical and practical implications for consumers and marketers.
Transcriptome Analysis of Detoxification-Related Genes in Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Chen Haoliang , Xie Minghui , Lin Lulu , Zhong Yongzhi , Zhang Feng , Su Weihua
Published: December 2021

Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) is an important pest on maize, and it can cause large yield losses. As S. frugiperda has invaded many developing countries in Africa and Asia in recent years, it could impact food security. Pesticides remain the main method to control S. frugiperda in the field, and this pest has developed resistance to some pesticides. In this study, we used second-generation sequencing technology to detect the gene expression change of S. frugiperda after treatment by LC20 of three pesticides, lufenuron, spinetoram, and tetrachloroamide, which have different modes of actions. The sequence data were first assembled into a 60,236 unigenes database, and then the differential expression unigenes (DEUs) after pesticide treatment were identified. The DEU numbers, Gene Ontology catalog, and Kyoto Encyclopedia of Genes and Genomes pathway catalog were analyzed. Finally, 11 types of unigenes related to detoxification and DEUs after pesticide treatment were listed, and Cytochrome P450, Glutathione S-transferase, and ATP-binding cassette transporter were analyzed. This study provides a foundation for molecular research on S. frugiperda pesticide detoxification.
Endoscopic duodenal stent placement versus gastrojejunostomy for unresectable pancreatic cancer patients with duodenal stenosis before introduction of initial chemotherapy (GASPACHO study): a multicenter retrospective study
Authors: Azemoto Nobuaki , Ueno Makoto , Yanagimoto Hiroaki , Mizuno Nobumasa , Kawamoto Yasuyuki , Maruki Yuta , Watanabe Kazuo , Suzuki Rei , Kaneko Junichi , Hisada Yuya , Sato Hiroki , Kobayashi Satoshi , Miyata Hideki , Furukawa Masayuki , Mizukami Takuro , Miwa Haruo , Ohno Yoshinori , Tsuji Kunihiro , Tsujimoto Akiko , Nagano Hiroaki , Okuyama Hiroyuki , Asagi Akinori , Okano Naohiro , Ishii Hiroshi , Morizane Chigusa , Ikeda Masafumi , Furuse Junji
Published: December 2021

Background

Endoscopic duodenal stent placement is an alternative technique to gastrojejunostomy for gastric outlet obstruction due to pancreatic cancer. We compared the efficacy of endoscopic duodenal stent placement with that of gastrojejunostomy for treating patients with pancreatic cancer who are candidates for intensive combination chemotherapies as the first line of treatment.

Methods

This retrospective observational study included 100 patients from 18 institutions in Japan. Inclusion criteria were as follows: (1) cytologically or histologically confirmed adenocarcinoma of the pancreas, (2) good performance status, (3) gastric outlet obstruction scoring system score of 0–1 and (4) no history of treatment for pancreatic cancer.

Results

There was no significant difference in the background characteristics of patients in the endoscopic duodenal stent placement (n = 57) and gastrojejunostomy (n = 43) groups. The median overall survival in the endoscopic duodenal stent placement and gastrojejunostomy groups was 5.9 and 6.0 months, respectively. Clinical success was achieved in 93 cases; the median time to food intake resumption was significantly shorter in the endoscopic duodenal stent placement group (median: 3 days, n = 54) than in the gastrojejunostomy group (median: 5 days, n = 43). Chemotherapy was introduced in 63% of the patients in both groups after endoscopic duodenal stent placement or gastrojejunostomy. Chemotherapy was started earlier in the endoscopic duodenal stent placement group (median: 14 days) than in the gastrojejunostomy (median: 32 days) group.

Conclusions

Endoscopic duodenal stent placement showed similar or better clinical outcomes than gastrojejunostomy. Thus, it might be a promising option in patients with good performance status.
Mechanisms modulating the activities of intestinal stem cells upon radiation or chemical agent exposure
Authors: Liao Zebin , Hu Changkun , Gao Yue
Published: December 2021

Intestinal stem cells (ISCs) are essential for the regeneration of intestinal cells upon radiation or chemical agent damage. As for radiation-induced damage, the expression of AIM2, YAP, TLR3, PUMA or BVES can aggravate ISCs depletion, while the stimulation of TLR5, HGF/MET signaling, Ass1 gene, Slit/Robo signaling facilitate the radio-resistance of ISCs. Upon chemical agent treatment, the activation of TRAIL or p53/PUMA pathway exacerbate injury on ISCs, while the increased levels of IL-22, β-arrestin1 can ease the damage. The transformation between reserve ISCs (rISCs) maintaining quiescent states and active ISCs (aISCs) that are highly proliferative has obtained much attention in recent years, in which ISCs expressing high levels of Hopx, Bmi1, mTert, Krt19 or Lrig1 are resistant to radiation injury, and SOX9, MSI2, clusterin, URI are essential for rISCs maintenance. The differentiated cells like Paneth cells and enteroendocrine cells can also obtain stemness driven by radiation injury mediated by Wnt or Notch signaling. Besides, Mex3a-expressed ISCs can survive and then proliferate into intestinal epithelial cells upon chemical agent damage. In addition, the modulation of symbiotic microbes harboring gastrointestinal (GI) tract is also a promising strategy to protect ISCs against radiation damage. Overall, the strategies targeting mechanisms modulating ISCs activities are conducive to alleviating GI injury of patients receiving chemoradiotherapy or victims of nuclear or chemical accident.
Orbital metastasis of invasive lobular carcinoma of the breast
Authors: Tsutsui Shinichi , Kawata Koto , Ubagai Tsutomu , Okimoto Satoshi , Fujihara Megumu , Maeda Takashi , Sonoda Takashi
Published: December 2021

We herein report a case of orbital metastasis from the breast cancer in a 58-year-old woman presenting with visual disturbance and bilateral periorbital swelling. She had undergone radical mastectomy for right breast cancer 9 years previously and been receiving hormone therapy for bone metastasis of breast cancer for the past 4 years. Computed tomography and magnetic resonance imaging revealed an ill-defined mass in the bilateral orbits, whereas an excisional biopsy confirmed metastasis of invasive lobular carcinoma (ILC) of the breast. The appearance of eye symptoms in patients who have a history of breast cancer, especially ILC should be investigated, with a consideration of orbital metastasis.
Multimessenger time-domain signatures of supermassive black hole binaries
Authors: Charisi Maria , Taylor Stephen R , Runnoe Jessie , Bogdanovic Tamara , Trump Jonathan R
Published: December 2021

Supermassive black hole binaries (SMBHBs) are a natural outcome of galaxy mergers and should form frequently in galactic nuclei. Sub-parsec binaries can be identified from their bright electromagnetic emission, e.g. Active Galactic Nuclei (AGNs) with Doppler shifted broad emission lines or AGN with periodic variability, as well as from the emission of strong gravitational radiation. The most massive binaries (with total mass >108M⊙) emit in the nanohertz band and are targeted by Pulsar Timing Arrays (PTAs). Here we examine the synergy between electromagnetic and gravitational wave signatures of SMBHBs. We connect both signals to the orbital dynamics of the binary and examine the common link between them, laying the foundation for joint multimessenger observations. We find that periodic variability arising from relativistic Doppler boost is the most promising electromagnetic signature to connect with GWs. We delineate the parameter space (binary total mass/chirp mass versus binary period/GW frequency) for which joint observations are feasible. Currently multimessenger detections are possible only for the most massive and nearby galaxies, limited by the sensitivity of PTAs. However, we demonstrate that as PTAs collect more data in the upcoming years, the overlapping parameter space is expected to expand significantly.
Measuring the Milky Way mass distribution in the presence of the LMC
Authors: Correa Magnus Lilia , Vasiliev Eugene
Published: December 2021

The ongoing interaction between the Milky Way (MW) and its largest satellite – the Large Magellanic Cloud (LMC) – creates a significant perturbation in the distribution and kinematics of distant halo stars, globular clusters and satellite galaxies, and leads to biases in MW mass estimates from these tracer populations. We present a method for compensating these perturbations for any choice of MW potential by computing the past trajectory of LMC and MW and then integrating the orbits of tracer objects back in time until the influence of the LMC is negligible, at which point the equilibrium approximation can be used with any standard dynamical modelling approach. We add this orbit-rewinding step to the mass estimation approach based on simultaneous fitting of the potential and the distribution function of tracers, and apply it to two data sets with the latest Gaia EDR3 measurements of 6D phase-space coordinates: globular clusters and satellite galaxies. We find that models with LMC mass in the range $(1\!-\!2) \times 10^{11}\, \mathrm{M}_\odot$ better fit the observed distribution of tracers, and measure MW mass within 100 kpc to be $(0.75\pm 0.1)\times 10^{12}\, \mathrm{M}_\odot$, while neglecting the LMC perturbation increases it by ∼15 per cent.
No strong dependence of Lyman continuum leakage on physical properties of star-forming galaxies at ≲ z ≲ 3.5
Authors: Saxena A , Pentericci L , Ellis R S , Guaita L , Calabrò A , Schaerer D , Vanzella E , Amorín R , Bolzonella M , Castellano M , Fontanot F , Hathi N P , Hibon P , Llerena M , Mannucci F , Saldana-Lopez A , Talia M , Zamorani G
Published: December 2021

We present Lyman continuum (LyC) radiation escape fraction (fesc) measurements for 183 spectroscopically confirmed star-forming galaxies in the redshift range 3.11 < z < 3.53 in the Chandra Deep Field South. We use ground-based imaging to measure fesc, and use ground- and space-based photometry to derive galaxy physical properties using spectral energy distribution (SED) fitting. We additionally derive [O iii]  +  H β equivalent widths (that fall in the observed K band) by including nebular emission in SED fitting. After removing foreground contaminants, we report the discovery of 11 new candidate LyC leakers at ≳ 2σ level, with fesc in the range 0.14−0.85. From non-detections, we place 1σ upper limits of fesc <0.12, where the Lyman-break selected galaxies have fesc <0.11 and ‘blindly’ discovered galaxies with no prior photometric selection have fesc <0.13. We find a slightly higher 1σ limit of fesc <0.20 from extreme emission line galaxies with rest-frame [O iii]  +  H β equivalent widths >300 Å. For candidate LyC leakers, we find a weak negative correlation between fesc and galaxy stellar masses, no correlation between fesc and specific star-formation rates (sSFRs) and a positive correlation between fesc and EW0([O iii]  +  H β). The weak/no correlations between stellar mass and sSFRs may be explained by misaligned viewing angles and/or non-coincident time-scales of starburst activity and periods of high fesc. Alternatively, escaping radiation may predominantly occur in highly localized star-forming regions, or fesc measurements may be impacted by stochasticity of the intervening neutral medium, obscuring any global trends with galaxy properties. These hypotheses have important consequences for models of reionization.
The post-common-envelope binary central star of the planetary nebula Ou 5: a doubly eclipsing post-red-giant-branch system
Authors: Jones David , Munday James , Corradi Romano L M , Rodríguez-Gil Pablo , Boffin Henri M J , Zak Jiri , Sowicka Paulina , Parsons Steven G , Dhillon Vik S , Littlefair S P , Marsh T R , Reindl Nicole , García-Rojas Jorge
Published: December 2021

We present a detailed study of the stellar and orbital parameters of the post-common envelope binary central star of the planetary nebula Ou 5. Low-resolution spectra obtained during the primary eclipse – to our knowledge the first isolated spectra of the companion to a post-common-envelope planetary nebula central star – were compared to catalogue spectra, indicating that the companion star is a late K- or early M-type dwarf. Simultaneous modelling of multiband photometry and time-resolved radial velocity measurements was then used to independently determine the parameters of both stars as well as the orbital period and inclination. The modelling indicates that the companion star is low mass (∼0.25 M⊙) and has a radius significantly larger than would be expected for its mass. Furthermore, the effective temperature and surface gravity of nebular progenitor, as derived by the modelling, do not lie on single-star post-AGB evolutionary tracks, instead being more consistent with a post-RGB evolution. However, an accurate determination of the component masses is challenging. This is principally due to the uncertainty on the locus of the spectral lines generated by the irradiation of the companion’s atmosphere by the hot primary (used to derive companion star’s radial velocities), as well as the lack of radial velocities of the primary.
Photocaged amplified FRET nanoflares: spatiotemporal controllable of mRNA-powered nanomachines for precise and sensitive microRNA imaging in live cells
Authors: Li Jing , Liu Shiyuan , Wang Jiaoli , Liu Ruiting , Yang Xiaohai , Wang Kemin , Huang Jin
Published: December 2021

There is considerable interest in creating a precise and sensitive strategy for in situ visualizing and profiling intracellular miRNA. Present here is a novel photocaged amplified FRET nanoflare (PAFN), which spatiotemporal controls of mRNA-powered nanomachine for precise and sensitive miRNA imaging in live cells. The PAFN could be activated remotely by light, be triggered by specific low-abundance miRNA and fueled by high-abundance mRNA. It offers high spatiotemporal control over the initial activity of nanomachine at desirable time and site, and a ‘one-to-more’ ratiometric signal amplification model. The PAFN, an unprecedented design, is quiescent during the delivery process. However, upon reaching the interest tumor site, it can be selectively activated by light, and then be triggered by specific miRNA, avoiding undesirable early activation and reducing nonspecific signals, allowing precise and sensitive detection of specific miRNA in live cells. This strategy may open new avenues for creating spatiotemporally controllable and endogenous molecule-powered nanomachine, facilitating application at biological and medical imaging.
Comprehensive analysis of prime editing outcomes in human embryonic stem cells
Authors: Habib Omer , Habib Gizem , Hwang Gue-Ho , Bae Sangsu
Published: December 2021

Prime editing is a versatile and precise genome editing technique that can directly copy desired genetic modifications into target DNA sites without the need for donor DNA. This technique holds great promise for the analysis of gene function, disease modeling, and the correction of pathogenic mutations in clinically relevant cells such as human pluripotent stem cells (hPSCs). Here, we comprehensively tested prime editing in hPSCs by generating a doxycycline-inducible prime editing platform. Prime editing successfully induced all types of nucleotide substitutions and small insertions and deletions, similar to observations in other human cell types. Moreover, we compared prime editing and base editing for correcting a disease-related mutation in induced pluripotent stem cells derived form a patient with α 1-antitrypsin (A1AT) deficiency. Finally, whole-genome sequencing showed that, unlike the cytidine deaminase domain of cytosine base editors, the reverse transcriptase domain of a prime editor does not lead to guide RNA-independent off-target mutations in the genome. Our results demonstrate that prime editing in hPSCs has great potential for complementing previously developed CRISPR genome editing tools.
Neutrophil depletion enhanced the Clostridium novyi-NT therapy in mouse and rabbit tumor models
Authors: Staedtke Verena , Gray-Bethke Tyler , Liu Guanshu , Liapi Eleni , Riggins Gregory J , Bai Ren-Yuan
Published: December 2021

Background

Hypoxia is a prominent feature of solid tumors and can function as fertile environment for oncolytic anaerobic bacteria such as Clostridium novyi-NT (C. novyi-NT) where it can induce tumor destruction in mice and patients. However, two major obstacles have limited its use, namely the host inflammatory response and the incomplete clearance of normoxic tumor areas.

Methods

In this study, we first used a subcutaneous tumor model of a glioblastoma (GBM) cell line in immunocompetent mice to investigate the local distribution of tumor hypoxia, kinetics of C. novyi-NT germination and spread, and the local host immune response. We subsequently applied the acquired knowledge to develop a C. novyi-NT therapy in an orthotopic rabbit brain tumor model.

Results

We found that local accumulation of granular leukocytes, mainly neutrophils, could impede the spread of bacteria through the tumor and prevent complete oncolysis. Depletion of neutrophils via anti-Ly6G antibody or bone marrow suppression using hydroxyurea significantly improved tumor clearance. We then applied this approach to rabbits implanted with an aggressive intracranial brain tumor and achieved long-term survival in majority of the animals without apparent toxicity.

Conclusion

These results indicated that depleting neutrophils can greatly enhance the safety and efficacy of C. novyi-NT cancer therapy for brain tumors.
Bringing the Outside In
Authors: Aronczyk Melissa , Espinoza Maria I.
Published: December 2021

Chapter 2, Bringing the Outside In, examines the industrial infrastructures within which the burgeoning profession of public relations coalesced: rail, steel, and coal, and the simultaneous development of information infrastructures to situate these industries as paragons of democracy in the American imagination. It was in struggles over labor rights, workers’ rights, employee welfare, and industrial reform that the practice of public relations forged its methods, as scions of power and privilege attempted to manage the “external environment” of public and political opinion to reduce friction for the machinations of heavy industry. While the “external environment” does not directly map onto the natural environment, we see in these struggles the porousness of the boundaries between the inside and the outside of industrial production, allowing industrial leaders to control the outside world in addition to the one within their walls.
“Shared Value”
Authors: Aronczyk Melissa , Espinoza Maria I.
Published: December 2021

Chapter 7, “Shared Value”: Promoting Climate Change for Data Worlds, begins with a provocation. In the growing movement to deploy big data for big solutions to mitigate global warming, are the data serving the climate cause? Or is the climate a convenient form of promotional capital for the benefit of big data adherents? This chapter reviews the shape of the Data for Climate Action (D4CA) campaign, showing how the campaign’s greatest impact is in the realm of publicity. Under the banner of shared value and social good, business, NGO and political leaders promote data solutions to climate problems, privileging technical and private sector expertise and digital “evidence” of global climate transformations. Despite its datafied package, the chapter reveals the continuity of mechanisms of public relations to generate facts that further reinforce the informational and technical character of environmentalism.
Introduction
Authors: Ferracioli Luara
Published: December 2021

This introductory chapter lays out the key questions of the book. It explains the background assumptions at play and the key philosophical commitments supporting the different arguments in the book. This chapter also explains the key arguments of the following chapters and how they come together to support a partial theory of immigrations that avoids both open borders and complete control of immigration on the part of states. It also explains how the theoretical framework defended in the first part of the book affects the applied questions pursued in the second part of the book, such as the ethics of asylum, family migration schemes, the brain drain, and immigration enforcement.
Family Migration Schemes and Liberal Neutrality
Authors: Ferracioli Luara
Published: December 2021

This chapter argues that the privileging of romantic and familial ties by those who believe in the liberal state’s prima facie right to exclude prospective immigrants cannot be justified. The reasons that count in favor of these relationships count equally in favor of a great array of relationships, from friends to creative collaborators, and whatever else falls in between. The result of the discussion is that liberal states must either focus on the interests of children only or the interests of all citizens who would like to be reunited with a person they enjoy a valuable and irreplaceable relationship.
Epilogue
Authors: Zuber Mike A.
Published: December 2021

The epilogue summarises the book’s narrative and outlines avenues for future research. Spiritual alchemy is chiefly important as a hybrid that defies a straightforward distinction between science and religion. In a way, its story is one of religious dissenters productively appropriating natural philosophy to articulate their faith. After laboratory alchemy was effectively eclipsed and the link to Jacob Boehme weakened, spiritual alchemy lost its internal cohesion and gave way to many divergent interpretations of alchemy that distanced it from the manipulation of material substances through chemical processes. Future studies will be able to shed more light on various alternative interpretations of alchemy that can now be perceived more clearly in contrast to the long tradition of spiritual alchemy described in this book.
Meltdown
Authors: Taillant Jorge Daniel
Published: December 2021

Climate change is happening all around us, and one of the telltale signs is melting glaciers. We hear about it almost daily, pieces of ice the size of continents breaking off of Antarctica or the polar arctic ice breaking up and disappearing more and more quickly opening up navigational routes once unavailable due to thick winter ice cover. Will melting ice and glaciers so far away change our lives? Meltdown takes us deep into the cryosphere, the Earth’s frozen environment and picks apart why glacier melt caused by climate change will alter (and already is altering) the way we live around the world. From rising seas that will destroy property and flood millions of acres of coastal lands, displacing hundreds of millions of people, to rising global temperatures due to reflectivity changes of the Earth because of decreased white glacier surface area, to colossal water supply changes from glacier runoff reduction, to deadly glacier tsunamis caused by the structural weakening of ice on high mountaintops that will take out entire communities living in glacier runoff basins, to escaping methane gas from thawing frozen permafrost grounds, and changing ocean temperatures that affect jet streams and ocean water currents around the planet, glacier melt is altering our global ecosystems in ways that will drastically change our everyday lives. Meltdown takes us into the little-known periglacial environment, a world of invisible subterranean glaciers in our coldest mountain ranges that will survive the initial impacts of climate change but that are also ultimately at risk due to a warming climate. By examining the dynamics of melting glaciers, Meltdown helps us grasp the impacts of a massive geological era shift occurring right before our eyes.
And Then There Was Ice
Authors: Taillant Jorge Daniel
Published: December 2021

This chapter introduces the basic definitions of a glacier and of the glaciosystem (a term coined by the author which refers to the glacier ecosystem). It describes glaciers, and through interactive links, shows the reader glaciers that can be viewed on a smart phone or computer. The chapter also describes the origin and formation of glaciers and their various functions. It introduces the life cycle of a glacier and also explains past and likely future ice ages (or glacial periods) as well as dynamics that may deepen global warming and impede the natural glacial age cycles, including the orbit of the Earth around the sun and its tilt and its relative influence on ice ages.
Ocean Currents, Jet Streams, and Polar Bears
Authors: Taillant Jorge Daniel
Published: December 2021

This chapter is divided into four sections, describing various impacts of glacier melt on different Earth ecosystems, including the effects of melting ice and water temperature on changes to ocean currents, on the global air Jet Stream, and on land surfaces, such as the popping up effect (the surface rebound effect) of the Earth once glaciers recede. It discusses the role of glacier meltwater for energy generation, as well as the impacts of the acceleration of glacier melt on flora and fauna, such as polar bears, salmon, and river bed and riparian biota.
Conclusion
Authors: Schonig Jordan
Published: December 2021

This conclusion examines a methodological similarity between the book’s attention to small details of movement and the discourse of “cinephilic moments,” which describes a mode of spectatorship that fixates on brief fragments of movement on screen. While cinephilic moments are often understood as resistant to formal analysis due to their apparent contingency, this conclusion shows how each chapter of The Shape of Motion has demonstrated a method of locating formal significance in cinephilic moments through the close analysis of motion. Rather than simply dwelling on the apparent uniqueness of those individual moments, each chapter collects and groups those singular moments according to the forms of movement they take, thereby yielding new theories of cinematic experience in addition to new insights about individual films.
Introduction
Authors: Waller James
Published: December 2021

Today, more than 50 years since the Troubles began and more than 20 years after they “ended,” has Northern Ireland rebuilt differently enough so as to ensure nonrecurrence of violent conflict? Has the conflict, while perhaps managed and contained, been transformed—structurally and relationally—into a win-win situation for both sides embroiled in the conflict? Does Northern Ireland have the resiliency to withstand the internal and external stressors that may threaten a destabilization of its fragile peace? To answer those questions requires an honest analysis of the current vulnerabilities in Northern Ireland related to memory, governance, and social fragmentation, as well as an assessment of the actors, organizations, and strategies that can reduce or reverse those vulnerabilities. Engaging these coupled realities of risk and resilience, situated in a contextual understanding of contemporary accelerators and triggers of potential conflict, is where reasons for hope, however fragile, will be found.
“The Walls Entered into Our Souls”
Authors: Waller James
Published: December 2021

Negative trends among risk factors in the categories of memory (Chapter 3) and governance (Chapter 4) shackle a society in the bonds of fragility. This can lead to, as well as be the result of, an increased susceptibility to social disharmony and isolation. This state of disconnect between the larger society and the groupings of some members of that society is known as fragmentation. While fragmentation can manifest itself along economic, institutional, or geographic lines, this chapter focuses on risk factors related specifically to social fragmentation. In everyday life in contemporary Northern Ireland, social fragmentation undeniably rules over the full spectrum of the lived experience. This chapter examines five specific risk factors related to social fragmentation: (1) identity-based social divisions, (2) demographic pressures, (3) unequal access to basic goods and services, (4) gender inequalities, and (5) political instability.
Organizing Warfare and Diplomacy in Western India, 1778–83
Authors: Sehgal Manu
Published: December 2021

This chapter examines the origins of a distinctive system of organizing military conquest in the final quarter of the eighteenth century. It seeks to de-centre the study of politics and military contestation by looking at the war against the Marathas (1778–82) from the vantage point of the region most directly affected by it—the western peninsular territory of the Bombay presidency. The advantage in shifting the focus away from the politically dominant Bengal presidency allows identification of a critical component in the political economy of conquest—the transfer of political authority from a civilian council to the commander of a military force. This shift in political power was essential to the success of the EIC regime of conquest even as it became a perennial source of conflict within the governing structures of the Company state. The debate and dissension that accompanied the deployment of military force both enabled the success of the machine of war and characterized the creation of a distinctive early colonial ideology of rule that subverted civilian control of the military.
Provincializing Bollywood
Authors: Kumar Akshaya
Published: December 2021

This book situates Bhojpuri cinema within the long history of vernacular media production, which was kick-started by audio cassettes and spurred on further with VCDs and DVDs. The emergence of multiplex-malls and the evacuation of single-screen theatres all over north India, at a time of massive real estate development, particularly in peninsular Indian cities, which required working class migrants’ ‘manual labour’ also prepared the ground for new linguistic consolidations and cultural forms. Investigating the historical, theoretical and empirical bases of Bhojpuri media production, the book tries to make sense of cinema within the ‘comparative media crucible’, in which film history sits alongside floods, droughts, musical traditions, gendered segregation, real estate boom, libidinal youth cultures, urban resettlements and highway modernities. The book grapples with Bhojpuri media from within Hindi film history, from the vantage point of provincial north India, in the light of the socio-technical upheavals of the last three decades. Foregrounding the libidinal energies, language politics and curatorial informalities, the book argues that Bhojpuri cinema could be conceptualized via the logic of overflow. Animated by libidinal affordances which have breached all formal embankments, it thrives on a curious blend of scandalizing and moralizing overtones.
The Libidinal Dwellings of Bhojpuri Media
Authors: Kumar Akshaya
Published: December 2021

This chapter provides an account of Bhojpuri popular culture, highlighting its standout features and tendencies. Historicizing the libidinal solidarity of assertive masculinities, the chapter recounts the history of Bhojpuri cinema from the origins to the contemporary period, in which it has emerged as a public scandal. Engaging at length with three particularly iconic Bhojpuri films – Sasura Bada Paisawala (2004), Nirahua Rickshawala (2007) and Jaan Tere Naam (2013) – the chapter navigates a formal grammar shifting from rural melodramas towards action cinema, celebrating the eruption of masculine energy and the increasingly scandalous portrayal of the female body. The chapter also highlights recurrent exchanges between Hindi and Bhojpuri film industries, and their interdependence on infrastructure, personnel and locales, with particular stress on gender politics and male stardom. In summary, the chapter argues that the libidinal economy of Bhojpuri cinema is anchored within a twin-logic which toggles between moralizing and scandalizing imperatives.
The Struggle for Sports Commons
Authors: Janaka Biyanwila S.
Published: December 2021

S.Janaka Biyanwila’s essay captures the trajectory of sports cultures in the Global South from their emergence in the aftermath of decolonization struggles with their democratization, but subsequent transformation post-1990s wave of globalization into sports consumers cultures. How can these new markets in sports cultures dominated by male oligarchies celebrating ‘sports spectacles’ be transformed to sports commons that encourage participatory democratic sports cultures? Focusing on the sports markets in cricket, badminton, football and even kabaddi and using a labour perspective, the presence of the invisible underside of sports workers is highlighted to reclaim sports as a public good, for local communities, and an accessible common cultural property.
India’s Olympic Encounter
Authors: Majumdar Boria
Published: December 2021

Boria Majumdar’s essay steps back into colonial times through newly discovered material, and describes the making of India’s Olympic moment connecting it to nationalism and representation, that was truly political providing a sportive lens to understand the complex evolution of modern Indian society. Local benefactors encouraged sporting institutions making cricket and athletics accessible to Indians. Prior to the 1920s popularly known for India’s entry into Olympic competition through the support of philanthropists, in the previous decade there was feverish correspondence between colonial officials and the Olympic association discussing prospects of ‘Indian’ participation in the 1912 Stockholm Games.
A Sociological Understanding of Sport in India
Authors: Pike Elizabeth C.J.
Published: December 2021

Elizabeth Pike’s essay explains how theoretical concepts and understandings have been utilised with effect to perceive and understand sports in society, illustrating it with emerging issues in India. The importance of developing a genuinely post-colonial sociology of sports is underlined through adopting theoretical frameworks located within the discipline of sociology to explore and explain specific case studies of sports across regions, structures of operation, social distinctions, and the like. The focus is on dwelling on interdisciplinarity grounded in a range of perspectives that shed light on the social dimensions of sport in India.
Labours of Care in Sport
Authors: Gopal Meena
Published: December 2021

Meena Gopal’s essay employs a feminist perspective of care and an autoethnographic method to explore the dimensions of a nurturing, mentoring practice in athletics. It is done through an unravelling of school, club and social intersections, illuminating possibilities of a sports commons even while nurturing competitive excellence. The labours of mentoring and care in the arena of athletics hopes to generate sport as a space that is participatory, inclusive and emancipatory. In the 1980s, the skewed nature of public schools meant that sport received less state support, while private institutions were able to nurture some sports talent due to sustained mentorship.