Miracle-dz/UniFAR-FTUs huggingface dataset:
Practicing environmental data justice: From DataRescue to Data Together

Correspondence Dawn Walker Email: dawn.walker@utoronto.ca The Environmental Data and Governance Initiative (EDGI) formed in response to the 2016 US elections and the resulting political shifts which created widespread public concern about the future integrity of US environmental agencies and policy. As a distributed, consensus‐based organisation, EDGI has worked to document, contextualise, and analyse changes to environmental data and governance practices in the US. One project EDGI has undertaken is the grassroots archiving of government environmental data sets through our involvement with the DataRescue movement. However, over the past year, our focus has shifted from saving environmental data to a broader project of rethinking the infrastructures required for community stewardship of data: Data Together. Through this project, EDGI seeks to make data more accessible and environmental decision‐making more accountable through new social and technical infrastructures. The shift from DataRescue to Data Together exemplifies EDGI's ongoing attempts to put an “environmental data justice” prioritising community self‐determination into practice. By drawing on environmental justice, critical GIS, critical data studies, and emerging data justice scholarship, EDGI hopes to inform our ongoing engagement in projects that seek to enact alternative futures for data stewardship.
Dramatic Changes in 67 miRNAs During Initiation of First Wave of Spermatogenesis in Mus musculus Testis: Global Regulatory Insights Generated by miRNA-mRNA Network Analysis1

ABSTRACT We mapped global changes in miRNA and mRNA profiles spanning the first wave of spermatogenesis using prepubertal (Postnatal Day 8 [P8]), pubertal (P16), and adolescent (P24) Mus musculus testes and identified the differential expression of 67 miRNAs and 8226 mRNAs. These two data sets were integrated into miRNA-dependent regulatory networks based on miRWalk predictions. In a network representing the P8 to P16 transition, downregulation of four miRNAs and upregulation of 19 miRNAs were linked with 81 upregulated target mRNAs and 228 downregulated target mRNAs, respectively. Furthermore, during the P16 to P24 transition, two miRNAs were downregulated, and eight miRNAs were upregulated, which linked with 64 upregulated mRNAs and 389 downregulated mRNAs, respectively. Only three of the miRNAs present in the network (miR-34b-5p, miR-34c, and miR-449a) showed a progressive increase from P8 through P16 to P24, while the remaining miRNAs in the network showed statistically significant changes in their levels either during the P8 to P16 transition or during the P16 to P24 transition. Analysis of the chromosomal location of these differentially expressed miRNAs showed that 14 out of 25 miRNAs upregulated from P8 to P16, and 18 out of 40 miRNAs upregulated from P8 to P24 were X-linked. This is suggestive of their escape from meiotic sex chromosome inactivation and postmeiotic sex chromatin. This integrated network of miRNA-level and mRNA-level changes in mouse testis during the first wave of spermatogenesis is expected to build a base for evaluating the role of miRNA-mediated gene expression regulation in maturing mammalian testis.
The Propeptides of the Vitamin K-dependent Proteins Possess Different Affinities for the Vitamin K-dependent Carboxylase*

The vitamin K-dependent γ-glutamyl carboxylase catalyzes the modification of specific glutamates in a number of proteins required for blood coagulation and associated with bone and calcium homeostasis. All known vitamin K-dependent proteins possess a conserved eighteen-amino acid propeptide sequence that is the primary binding site for the carboxylase. We compared the relative affinities of synthetic propeptides of nine human vitamin K-dependent proteins by determining the inhibition constants (K i ) toward a factor IX propeptide/γ-carboxyglutamic acid domain substrate. TheK i values for six of the propeptides (factor X, matrix Gla protein, factor VII, factor IX, PRGP1, and protein S) were between 2–35 nm, with the factor X propeptide having the tightest affinity. In contrast, the inhibition constants for the propeptides of prothrombin and protein C are ∼100-fold weaker than the factor X propeptide. The propeptide of bone Gla protein demonstrates severely impaired carboxylase binding with an inhibition constant of at least 200,000-fold weaker than the factor X propeptide. This study demonstrates that the affinities of the propeptides of the vitamin K-dependent proteins vary over a considerable range; this may have important physiological consequences in the levels of vitamin K-dependent proteins and the biochemical mechanism by which these substrates are modified by the carboxylase.
Attachment of diaminopimelic acid to bdelloplast peptidoglycan during intraperiplasmic growth of Bdellovibrio bacteriovorus 109J

An early event in the predatory lifestyle of Bdellovibrio bacteriovorus 109J is the attachment of diaminopimelic acid (DAP) to the peptidoglycan of its prey. Attachment occurs over the first 60 min of the growth cycle and is mediated by an extracellular activity(s) produced by the bdellovibrio. Some 40,000 DAP residues are incorporated into the Escherichia coli bdelloplast wall, amounting to ca. 2 to 3% of the total initial DAP content of its prey cells. Incorporation of DAP occurs when E. coli, Pseudomonas putida, or Spirillum serpens are the prey organisms. The structurally similar compounds lysine, ornithine, citrulline, and 2,4-diaminobutyric acid are not attached. The attachment process is not affected by heat-killing the prey nor by the addition of inhibitors of either energy generation (cyanide, azide, or arsenate), protein or RNA synthesis (chloramphenicol and rifamycin), or de novo synthesis of cell wall (penicillin or vancomycin). Approximately one-third of the incorporated DAP is exchangeable with exogenously added unlabeled DAP, whereas the remaining incorporated DPA is solubilized only during the lysis of the bdelloplast wall. Examination of DAP incorporation at low prey cell densities suggests that bdellovibrios closely couple the incorporation to an independent, enzymatic solubilization of DAP by a peptidase. The data indicate that DAP incorporation is a novel process, representing the second example of the ability of the bdellovibrio to biosynthetically modify the wall of its prey.
γ-Secretase-mediated Release of the Low Density Lipoprotein Receptor-related Protein 1B Intracellular Domain Suppresses Anchorage-independent Growth of Neuroglioma Cells*

The low density lipoprotein receptor related protein 1B (LRP1B) is a large endocytic receptor that was first identified as a candidate tumor suppressor gene. In the current investigation we demonstrate that LRP1B undergoes regulated intramembrane proteolysis in a γ-secretase-dependent process. The released intracellular domain (ICD) then translocates to the nucleus via a nuclear localization signal that is present within this domain. ICD release first requires shedding of the LRP1B ectodomain, which appears to be catalyzed by a member of the metalloproteinase family. Employing site-directed mutagenesis studies, we identified lysine residues 4432 and 4435 and arginine 4442 as key amino acids important for ectodomain shedding of LRP1B. We also demonstrate that an LRP1B minireceptor as well as the ICD domain alone suppresses anchorage-independent growth of LRP1B-deficient neuroglioma cells (H4 cells). Interestingly, abrogating ectodomain shedding resulted in a loss of the ability of LRP1B minireceptors to suppress anchorage-independent growth. Together, these studies reveal that LRP1B has tumor suppression function that is mediated by proteolytic processing of the receptor resulting in ICD release.
Consequences of Periodic α-to-β3 Residue Replacement for Immunological Recognition of Peptide Epitopes

Oligomers that contain both α- and β-amino acid residues, or “α/β-peptides”, have emerged as promising mimics of signal-bearing polypeptides that can inhibit or augment natural protein–protein interactions. α/β-Peptides that contain a sufficient proportion of β residues evenly distributed along the sequence can be highly resistant to enzymatic degradation, which is favorable with regard to in vivo applications. Little is known, however, about recognition of α/β-peptides by the immune system. Prior studies have focused almost entirely on examples that contain a single β residue; such α/β-peptides frequently retain the immunological profile of the analogous α-peptide. We have conducted α-peptide vs α/β-peptide comparisons involving higher β residue content, focusing on molecules with αααβ and ααβαααβ backbone repeat patterns. Among analogues of an 18-mer derived from the Bim BH3 domain and an 8-mer derived from secreted phospholipase-2 (sPLA2), we find that recognition by antibodies raised against the prototype α-peptide is suppressed by periodic α → β replacements. Complementary studies reveal that antibodies raised against Bim BH3- or sPLA2-derived α/β-peptides fail to recognize prototype α-peptides displaying identical side chain repertoires. Because polypeptides containing d-α-amino acid residues are of growing interest for biomedical applications, we included the enantiomer of the sPLA2-derived α-peptide in these studies; this d-peptide is fully competent as a hapten, but the resulting antibodies do not cross react with the enantiomeric peptide. Among analogues of the 9-mer CD8+ T-cell viral epitope GP33, we observe that periodic α → β replacements suppress participation in the MHC I + peptide + T-cell receptor ternary complexes that activate cytotoxic T-lymphocytes, due in part to disruption of MHC binding.
Transatlantic burden sharing: suggesting a new research agenda

ABSTRACT Current studies on NATO burden sharing are only able to show some weak statistical trends between selective variables; they are unable to explain and show why this trend exists and why it occurred at particular times (or not). This is due to the dominant deductive and hypothesis testing research designs that prevent researchers to produce richer causal explanations or intersubjective understandings of how states, for example, construct and assign meaning to burdens or what forms of social representation, values, norms and ideals influence the making of (national) burden sharing decisions. Thus, we charge, the literature needs to adopt an eclecticist approach to studying NATO burden sharing – that is to combine rationalist with sociological approaches and methodologies highlighting the importance of intersubjective meanings and the role of social forces, norms, beliefs, and values. The article lays out what such a research programme might look like and how one could operationalise it.
Clinical correlative study on early detection of oral cancer and precancerous lesions by modified oral brush biopsy and cytology followed by histopathology.

BACKGROUND Oral cancer accounts for 5% of all malignant tumors and 60% of these lesions are well advanced at the time of diagnosis. The early diagnosis could prevent a large number of deaths due to this disease. AIMS This study aims to evaluate and compare the clinical usefulness of exfoliative cytology, modified brush biopsy (without computer assisted analysis), and biopsy in early detection of oral premalignant and malignant lesions. MATERIALS AND METHODS Modified oral brush biopsy (using baby toothbrush) and exfoliative cytology was performed on 225 clinically diagnosed oral precancerous lesions (suspected) selected from among 1099 lesions in 877 patients. Scalpel or punch biopsy was performed based on clinic-cytological evidence (test result and/or clinical judgment) on only 117 lesions. All the specimens were analyzed manually in a double-blinded fashion. STATISTICAL ANALYSIS USED RESULTS were analyzed using Statistical package for Social Sciences version 12 (SPSS Inc., Chicago, IL, USA) and subjected to Fischer exact test. RESULTS Of 117 lesions that underwent all the three tests, modified oral brush biopsy showed a reasonably higher specificity (68.42%) and sensitivity (81.69%) when compared with specificity (86.48%) and sensitivity (48.57%) of cytology. CONCLUSION The results demonstrate that modified oral brush biopsy has higher efficacy than routine cytology and can be used as a potentially practical oral cancer screening tool in resource challenged settings. However, clinical judgment is of prime importance. Immediate biopsy is mandatory in highly suspicious lesions proposed under the diagnostic criteria of "clinically diagnosed carcinoma in situ".
Validation of higher-throughput high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry assays to conduct cytochrome P450s CYP2D6 and CYP3A4 enzyme inhibition studies in human liver microsomes.

In the early stage of drug discovery, thousands of new chemical entities (NCEs) may be screened before a single drug candidate can be identified for development. In order to accelerate the drug discovery process, we have developed higher-throughput enzyme assays to evaluate the inhibition of cytochrome P450 isoforms 2D6 (CYP2D6) and 3A4 (CYP3A4) in human liver microsomes. The assays are based on high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) techniques. The analysis time for each sample was reduced from approximately 20 minutes for the conventional HPLC assay to 30 seconds for the LC/MS/MS assay. For both LC/MS/MS assays, the linearity (r(2) > 0.99), precision (%CV < 15%) and accuracy (% bias <15%) for both inter- and intraday validations were satisfactory. Since the implementation of the LC/MS/MS assays, our sample throughput has increased by over 40-fold.
Towards an auto-tuning system design for optimal sparse compression format selection with user expertise

Several applications in numerical scientific computing process sparse matrices with either a regular or irregular structure. The very large size of these matrices requires to use compressing formats and target parallel/distributed architectures in order to reduce both space complexity and processing time. The optimal compression format (OCF) of such matrices may in fact vary according to both the application context of the numerical method and the target hardware architecture. In this paper, we propose a design of a system that automatically selects the OCF according to the two above cited parameters. The expert system obtained from our model targets dynamic integration of the user expertise thus allowing better performances. The optimal format selection is based on the makespan criterion. As a first validation test of our system, we studied the representative case of Horner scheme in the context of data parallel programming model and multicore cluster. Our experiments focus on the four compression formats CSR, CSC, COO and ELLPACK and their complexities in a data parallel programming model context.
Distinct tyrosine autophosphorylation sites negatively and positively modulate neu-mediated transformation

A number of cytoplasmic signaling molecules are thought to mediate mitogenic signaling from the activated Neu receptor tyrosine kinase through binding specific phosphotyrosine residues located within the intracellular portion of Neu/c-ErbB-2. An activated neu oncogene containing tyrosine-to-phenylalanine substitutions at each of the known autophosphorylation sites was generated and assessed for its specific transforming potential in Rat1 and NIH 3T3 fibroblasts. Mutation of these sites resulted in a dramatic impairment of the transforming potential of neu. To assess the role of these tyrosine phosphorylation sites in cellular transformation, the transforming potential of a series of mutants in which individual tyrosine residues were restored to this transformation-debilitated neu mutant was evaluated. Reversion of any one of four mutated sites to tyrosine residues restored wild-type transforming activity. While each of these transforming mutants displayed Ras-dependent signaling, the transforming activity of two of these mutants was correlated with their ability to bind either the GRB2 or SHC adapter molecules that couple receptor tyrosine kinases to the Ras signaling pathway. By contrast, restoration of a tyrosine residue located at position 1028 completely suppressed the basal transforming activity of this mutated neu molecule or other transforming neu molecules which possessed single tyrosine residues. These data argue that the transforming potential of activated neu is mediated both by positive and negative regulatory tyrosine phosphorylation sites.
Ductal carcinoma in situ – update on risk assessment and management

Ductal carcinoma in situ (DCIS) accounts for ~20–25% of breast cancers. While DCIS is not life‐threatening, it may progress to invasive carcinoma over time, and treatment intended to prevent invasive progression may itself cause significant morbidity. Accurate risk assessment is therefore necessary to avoid over‐ or undertreatment of an individual patient. In this review we will outline the evidence for current management of DCIS, discuss approaches to DCIS risk assessment and challenges facing identification of novel DCIS biomarkers.
Endocrine responses to critical illness: novel insights and therapeutic implications.

CONTEXT Critical illness, an extreme form of severe physical stress, is characterized by important endocrine and metabolic changes. Due to critical care medicine, survival from previously lethal conditions has become possible, but many patients now enter a chronic phase of critical illness. The role of the endocrine and metabolic responses to acute and prolonged critical illness in mediating or hampering recovery remains highly debated. EVIDENCE ACQUISITION The recent literature on changes within the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-adrenal axis and on hyperglycemia in relation to recovery from critical illness was critically appraised and interpreted against previous insights. Possible therapeutic implications of the novel insights were analyzed. Specific remaining questions were formulated. EVIDENCE SYNTHESIS In recent years, important novel insights in the pathophysiology and the consequences of some of these endocrine responses to acute and chronic critical illness were generated. Acute endocrine adaptations are directed toward providing energy and substrates for the vital fight-or-flight response in a context of exogenous substrate deprivation. Distinct endocrine and metabolic alterations characterize the chronic phase of critical illness, which seems to be no longer solely beneficial and could hamper recovery and rehabilitation. CONCLUSIONS Important novel insights reshape the current view on endocrine and metabolic responses to critical illness and further clarify underlying pathways. Although many issues remain unresolved, some therapeutic implications were already identified. More work is required to find better treatments, and the optimal timing for such treatments, to further prevent protracted critical illness, to enhance recovery thereof, and to optimize rehabilitation.
Physical and psychosocial functioning and adjustment to breast cancer. Long‐term follow‐up of a screening population

The effects of age, recency of breast cancer (BC) diagnosis, and severity of the disease on adjustment outcomes were investigated in a sample of 349 women from the 10,059 women screened for BC by the University of Michigan Breast Cancer Detection Demonstration Project between 1974 and 1981. In the 1985 follow‐up, data were collected from the 173 surviving BC patients who had invasive BC, and from a matched control group of 176 women who were asymptomatic of BC. Fifty‐five percent of the BC patients were 5 years past diagnosis and treatment at the time of data collection. The BC patients group as a whole did not differ from the asymptomatic control group on indicators of mental health, social and psychological well‐being, or physical functioning. However, the BC group reported a greater number of diagnosed medical conditions that limited their activities, and taking more medications, than the asymptomatic group. Within the BC group, severity and recency of the cancer had strong independent adverse effects on several of the indicators of mental health and physical functioning. Advanced age had the same main effects in both groups: greater number of medications and diagnosed medical conditions that cause limitatieas in activities, but, in contrast, better mental health and well‐being. Age had interactive effects with the recency and with severity of BC: more recent and severe cases of BC appeared to produce particularly serious difficulties in psychological adjustment for younger patients, and particularly serious medical problems and physical difficulties in adjustment for older patients.
Remembering more than meets the eye: A study of memory confusions about incomplete visual information

The purpose of this series of four experiments was to examine the possible role of spontaneous imagery in memory confusions about the way in which visual information had been experienced. After viewing pictures of familiar objects, complete or incomplete in visual form, participants were asked to remember the way in which the objects had been presented. Although, as predicted, memory for the objects themselves was quite good, participants falsely remembered seeing complete versions of pictures that were actually presented as incomplete. These false reports were observed across a variety of encoding and testing conditions. The results suggest that the false reports (referred to here as completion errors) are due to internal representations based on filling-in processes in response to the encoding of incomplete visual information. As such, the results also speak to alternative explanations for the completion errors and, more broadly, to theoretical perspectives that draw on filling-in processes when accounting for object identification and object memory.
Financial Shocks, Supply-Chain Relationships, and the Great Trade Collapse

The collapse in trade relative to GDP during 2008-09 was unusually large historically and puzzling relative to the predictions of canonical two-country models.In a calibrated dynamic general equilibrium two-country model where firms must build supply chain relationship in order to sell their product, we show that a tightening of credit can cause a sizable fall in the trade-GDP ratio (44 percent of the observed value) while productivity shocks cannot. The key mechanism underlying the sharper fall in trade relative to GDP involves an endogenous reallocation of scarce resources from international to domestic supply-chains, that are acquired and maintained at lower cost.