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"Grant, Kevin Patrick"
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Exploration in the age of empire, 1750-1953
This volume examines European exploration and imperial expansion in Africa and Asia, using three themes to recount the experiences and achievements of individual explorers--the motives of the explorers, how changing ideas influenced the conduct and understanding of exploration, and how competition and politics of the European empires were shaped by exploration.
Book
\A civilised savagery\: British humanitarian politics and European imperialism in Africa, 1884-1926
Slavery took many forms in the age of emancipation. In the early twentieth century, a variety of organizations in Great Britain condemned European colonial regimes in Africa for imposing \"modern slaveries\" upon indigenous and migrant laborers. The high era of imperialism witnessed the largest resurgence of British popular debate over slavery since the Victorian campaigns against chattel labor on the plantations of the Caribbean and North America. This dissertation examines the relationship between British humanitarian politics and the labor systems of European imperialism in Africa from the Berlin Conference of 1884-85 to the League of Nations' Convention on Slavery of 1926. The participants in anti-slavery debates in Britain included the traditional abolitionist lobbies of Exeter Hall, missionary societies, merchants, non-conformist ministers and their congregations, the labor movement, the Liberal and Conservative parties, and colonial officials. This dissertation discusses the three major abolitionist controversies in which these groups engaged prior to the First World War, demonstrating how and why different conditions of colonial labor were contested as slavery within the multi-faceted forum of British humanitarian politics. The first and most significant of these controversies focused upon the forced labor and atrocities perpetrated against Africans by the Congo Free State, ruled by King Leopold II of Belgium. The second controversy involved the British government's importation of indentured Chinese laborers to the gold mines of the Transvaal Colony in South Africa, and the last scandal surrounded the abduction and sale of Africans for work on the cocoa plantations of Portuguese West Africa. On the basis of these cases, this dissertation examines how humanitarianism reflected religious, commercial, racial and class politics, while defining the moral authority of Great Britain as an imperial power. Most importantly, it highlights a growing conflict between the traditional tenets of evangelical philanthropy, premissed upon the \"civilising mission\" of Christian conversion, and the emerging, secular politics of \"human rights.\" The advocates of both of these ideologies encountered skepticism or hostility from British government officials, who regarded them as threats to the stability of Britain's foreign relations and colonial regimes. The tensions between these three groups, and the pre-war controversies over the \"modern slaveries\" of Africa, subsequently shaped of the League of Nations' Convention on Slavery of 1926, a document ultimately drafted by British officials in terms which substantiated European colonial authority and labor policies. In addressing the many forms of slavery and British humanitarianism, this dissertation thus concludes by illuminating the ideological and institutional sources of international government in the principles and practices of imperialism.
Dissertation
The Just-In-Time operating philosophy: Implications for workers and work teams
The Just-In-Time (JIT) operating philosophy has been adopted by many American companies during the last decade. As American companies have adopted JIT it has become very clear that the involvement and commitment of the work force is vital to the success of the JIT philosophy. This research effort was conducted in an electronics assembly plant which relies on work teams as the primary vehicle for employee involvement. The objective of this research was to examine the implications which the JIT operating philosophy holds for workers and work teams. First, this research examined worker perceptions of the JIT operating environment. Several aspects of the work environment were studied to include: equity of workload, control of work pace, comfort with work pace, sources of motivation and equity of rewards. The only significant change in worker perceptions concerned the adequacy and equity of rewards. This study determined that worker satisfaction with a reward system based on team performance rather than individual performance eroded somewhat over the course of this study. Second, this research investigated the development of work team characteristics as the teams transitioned to the JIT operating environment. Several team characteristics were studied to include: capacity to collaborate, inclination to collaborate, communication effectiveness, priority consonance, and participation in decision making. Only team capacity to collaborate as measured by team flexibility improved during the course of this study. The improvement is attributed to an informal cross-training program which was implemented by the company. Third, this study examined the link between team characteristics and team performance. The results indicate that team collaboration was positively related to schedule performance and labor efficiency. Further, priority consonance and participation in decision making were also positively related to schedule performance. Finally, team flexibility was positively related to product quality.
Dissertation
Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors
Understanding tumor origins and the similarities and differences between organ-specific cancers is important for determining treatment options. Young
et al.
generated more than 72,000 single-cell transcriptomes from healthy and cancerous human kidneys. From these data, they determined that Wilms tumor, a pediatric kidney cancer, originates from aberrant fetal cells, whereas adult kidney cancers are likely derived from a specific subtype of proximal convoluted tubular cell.
Science
, this issue p.
594
Single-cell mRNAs of normal and cancerous kidney cells reveal the cellular identity of childhood and adult tumors.
Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.
Journal Article
A clinical approach to diagnosis of autoimmune encephalitis
Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy.
Journal Article
Photochemically produced SO2 in the atmosphere of WASP-39b
Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability
1
. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program
2
,
3
found a spectral absorption feature at 4.05 μm arising from sulfur dioxide (SO
2
) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28
M
J
) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref.
4
). The most plausible way of generating SO
2
in such an atmosphere is through photochemical processes
5
,
6
. Here we show that the SO
2
distribution computed by a suite of photochemical models robustly explains the 4.05-μm spectral feature identified by JWST transmission observations
7
with NIRSpec PRISM (2.7
σ
)
8
and G395H (4.5
σ
)
9
. SO
2
is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H
2
S) is destroyed. The sensitivity of the SO
2
feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO
2
also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.
Observations from the JWST show the presence of a spectral absorption feature at 4.05 μm arising from SO
2
in the atmosphere of the gas giant exoplanet WASP-39b, which is produced by photochemical processes and verified by numerical models.
Journal Article
A kinase-cGAS cascade to synthesize a therapeutic STING activator
The introduction of molecular complexity in an atom- and step-efficient manner remains an outstanding goal in modern synthetic chemistry. Artificial biosynthetic pathways are uniquely able to address this challenge by using enzymes to carry out multiple synthetic steps simultaneously or in a one-pot sequence
1
–
3
. Conducting biosynthesis ex vivo further broadens its applicability by avoiding cross-talk with cellular metabolism and enabling the redesign of key biosynthetic pathways through the use of non-natural cofactors and synthetic reagents
4
,
5
. Here we describe the discovery and construction of an enzymatic cascade to MK-1454, a highly potent stimulator of interferon genes (STING) activator under study as an immuno-oncology therapeutic
6
,
7
(ClinicalTrials.gov study
NCT04220866
). From two non-natural nucleotide monothiophosphates, MK-1454 is assembled diastereoselectively in a one-pot cascade, in which two thiotriphosphate nucleotides are simultaneously generated biocatalytically, followed by coupling and cyclization catalysed by an engineered animal cyclic guanosine-adenosine synthase (cGAS). For the thiotriphosphate synthesis, three kinase enzymes were engineered to develop a non-natural cofactor recycling system in which one thiotriphosphate serves as a cofactor in its own synthesis. This study demonstrates the substantial capacity that currently exists to use biosynthetic approaches to discover and manufacture complex, non-natural molecules.
Leveraging enzymatic selectivity, a single reaction stream provides a single diastereomer of the cyclic dinucleotide MK-1454, a promising immune-oncology drug candidate, without the use of protecting groups or chiral auxiliaries.
Journal Article
Household air pollution and risk of pulmonary tuberculosis in HIV-Infected adults
Background
In low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection.
Methods
We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 – March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (
n
=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB.
Results
We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/week were more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm].
Conclusion
Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women.
Journal Article
