Miracle-dz/UniFAR-FTUs huggingface dataset:
Approximate Pareto Set for Fair and Efficient Allocation: Few Agent Types or Few Resource Types

In fair division of indivisible goods, finding an allocation that satisfies fairness and efficiency simultaneously is highly desired but computationally hard. We solve this problem approximately in polynomial time by modeling it as a bi-criteria optimization problem that can be solved efficiently by determining an approximate Pareto set of bounded size. We focus on two criteria: max-min fairness and utilitarian efficiency, and study this problem for the setting when there are only a few item types or a few agent types. We show in both cases that one can construct an approximate Pareto set in time polynomial in the input size, either by designing a dynamic programming scheme, or a linear-programming algorithm. Our techniques strengthen known methods and can be potentially applied to other notions of fairness and efficiency as well.
Improving Tandem Mass Spectra Analysis with Hierarchical Learning

Tandem mass spectrometry is the most widely used technology to identify proteins in a complex biological sample, which produces a large number of spectra representative of protein subsequences named peptide. In this paper, we propose a hierarchical multi-stage framework, referred as DeepTag, to identify the peptide sequence for each given spectrum. Compared with the traditional one-stage generation, our sequencing model starts the inference with a selected high-confidence guiding tag and provides the complete sequence based on this guiding tag. Besides, we introduce a cross-modality refining module to asist the decoder focus on effective peaks and fine-tune with a reinforcement learning technique. Experiments on different public datasets demonstrate that our method achieves a new state-of-the-art performance in peptide identification task, leading to a marked improvement in terms of both precision and recall.
Exploring Patients' Values and Preferences for Initial Atrial Fibrillation Education

Background People with a new diagnosis of atrial fibrillation (AF) require knowledge to build skills and confidence to engage in decision making for AF treatment and prevention of AF-related complications. Data to guide development of content and approaches that enable acquisition of knowledge to support effective self-management are lacking. Objective The aim of this study was to explore patients' values concerning the content of initial AF education, describe how providers delivered education, and identify patients' preferences for approaches to education. Methods We used a qualitative inductive approach. Twenty-five participants given a diagnosis of AF within 18 months of enrollment were recruited from midwest US healthcare system clinics. Data were collected using a semistructured interview guide and were analyzed using qualitative content analysis. Results Themes emerging were as follows: (1) important to know, (2) recollections of the how and what of education, and (3) preferences for educational resources. Participants highly valued providers' explanations that AF was not immediately life-threatening and did not require limitations to usual activities. This reassurance from providers decreased fear and then enabled participants to learn about AF management. Verbal explanations were the primary approach to delivering education, but participants consistently expressed preferences for receiving written information and videos to supplement verbal explanations. Conclusions Addressing emotional and quality of life concerns at the time of AF diagnosis reduced fear and was critical for enabling participants to attend to discussions about treatment and self-management. The value participants placed on written and video resources as an adjunct to verbal explanation suggests that providers should consider educational approaches beyond verbal explanations.
Decision Platform for Pattern Discovery and Causal Effect Estimation in Contraceptive Discontinuation

Contraceptive use improves the health of women and children in several ways, yet data shows high rates of discontinuation which is not well understood. We introduce an AI-based decision platform capable of analyzing event data to identify patterns of contraceptive uptake that are unique to a subpopulation of interest. These discriminatory patterns provide valuable, interpretable insights to policy-makers. The sequences then serve as a hypothesis for downstream causal analysis to estimate the effect of specific variables on discontinuation outcomes. Our platform presents a way to visualize, stratify, compare, and perform a causal analysis on covariates that determine contraceptive uptake behavior, and yet is general enough to be extended to a variety of applications.
Intestinal epithelial chemokine (C-C motif) ligand 7 overexpression protects against high fat diet-induced obesity and hepatic steatosis in mice

Abstract Background We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice. Methods Intestinal epithelial CCL7 overexpression (CCL7tgIEC) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing. Results We found that the CCL7tgIEC mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7tgIEC mice compared to WT. Furthermore, HFD-fed CCL7tgIEC mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis. Conclusions Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.
Multilevel studies on the two phenological forms of Large Blue (Maculinea arion) (Lepidoptera: Lycaenidae)

The main goal of our research was to study comprehensively the differences between the two phenological forms of the socially parasitic and globally threatened Large Blue (Maculinea arion) in the Carpathian Basin using four character sets (mitochondrial sequences, allozymes, male genitalia and wing morphometrics). Comparative analyses of distance matrices, phylogenetic trees and ordination patterns have been applied. The genetic and morphometric patterns revealed by our studies were discordant. While we experienced a significant differentiation between the ‘spring’ and ‘summer type’ of M. arion in both wing and genital traits, the two phenological forms did not show any genetic differentiation on two mitochondrial loci and in allozymes. At the same time, all individuals were infected by Wolbachia. Although certain wing traits may not represent reliable tracers of phylogeny because of the particular adaptive significance, the wing characteristics involved in our research are probably determined genetically. Additionally, the significant differentiation of male genitalia also indicates incipient prezygotic isolation arising from phenological differentiation between the ‘spring and summer arion’. It is possible that all extant differences between the two forms are attributable to (1) different host-ant use, (2) incipient speciation, (3) cytoplasmatic incompatibility (CI) by Wolbachia or the combination of these factors. In addition, discordant results indicate that the combined use of different approaches and data sets is strictly necessary to clarify systematic and evolutionary relationships.
Elevated blood pressure in childhood and hypertension risk in adulthood: a systematic review and meta-analysis.

OBJECTIVE Several longitudinal studies have investigated the association between elevated blood pressure (BP) in childhood and hypertension in adulthood but the strength of the association has not been always consistent. This study aimed at quantitatively assessing the strength of the association between elevated BP in childhood and hypertension in adulthood based on both a meta-analysis and a systematic review. METHODS We identified eligible studies using PubMed and Embase databases up to 1 November, 2019 and by manually searching the reference lists of all identified studies. All longitudinal studies on the association between elevated BP in childhood and hypertension in adulthood were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model in this meta-analysis. RESULTS Eleven articles (N = 39 714) were included in our meta-analysis and five additional articles were used for systematic review (two providing ORs without 95% CIs, one not using standard cut-offs for elevated BP in childhood, and two not using standard criteria for adult hypertension). Elevated BP in childhood (3--18 years in the included studies) was significantly associated with hypertension in adulthood (18--57 years in the included studies), with a summary OR of 2.02 (95% CI 1.62--2.53). We also found that an increase of 1 standard deviation in systolic BP and diastolic BP, respectively, in childhood (3--19 years in the included studies) was associated with hypertension in adulthood (21--49 years in the included studies), with summary ORs of 1.71 (1.50-1.95) and 1.57 (1.37-1.81). Our systematic review of the five additional articles not eligible for meta-analysis also suggested a significant association between elevated BP in childhood and hypertension in adulthood. CONCLUSION This meta-analysis and systematic review demonstrated a significant association between elevated BP in childhood and hypertension in adulthood. The findings support measures to promote healthy BP during childhood to reduce the risk of hypertension later in life.
Exploring the regulatory role of behaviour and genome architecture in the socially polymorphic ant, Leptothorax acervorum

Eusocial species show incredible variation in all aspects of social living, which has facilitated their ecological success. Investigating the mechanisms which regulate variation in social traits is an important goal for evolutionary biology, since understanding fundamental mechanisms underpinning variation can inform social evolutionary theory. In this thesis, I investigate aggressive behaviour and genome architecture as essential mechanisms in regulating variation in the polymorphic social phenotype of the multiple queened ant species L. acervorum. I investigated the role of enforcement behaviour in maintaining reproductive skew in functionally monogynous colonies. I show that in the absence of worker aggression (enforcement), functionally monogynous queens continue to engage in highly aggressive interactions and, crucially, high colony skew was not affected. Furthermore, I show that low skew is not affected by aggressive worker enforcement in polygynous colonies. Therefore, enforcement behaviour is likely to be important in regulating skew in functionally monogynous colonies but not in polygynous colonies, where potentially the loss of sensitivity to enforcement may be an evolved response to fitness benefits associated with the polygynous social phenotype. Furthermore, I investigated the role of genome architecture in regulating variation between the two social phenotypes. I scanned the genomes of four populations (two polygynous and two functionally monogynous) for extreme population differentiation (FST) at SNP loci, which were associated with a difference in the social phenotype. I found a large (6.2Mb) contiguous region associated with different social phenotypes (the social region), which mapped to LG2 on the S. invicta linkage map. The social region displayed some similarities with the social chromosomes in S. invicta and F. selysi. Furthermore, the region contained potential gene candidates, such as odorant binding proteins, which have been associated with divergent social phenotypes in S. invicta. The work presented in this thesis highlights the importance of different mechanisms, both behavioural and genomic, in regulating variation in fundamental social traits. Furthermore, it demonstrates the importance of understanding how mechanisms can bridge the gap between genotype and phenotype.
Weed seed production, crop planting pattern, and mechanical weeding in wheat

Abstract Experiments were carried out to investigate weed seed production in widely spaced spring wheat crops that received aggressive mechanical weed control (hoeing and harrowing) compared with that in narrowly spaced crops receiving less aggressive mechanical control (harrowing only). Three species (wild buckwheat [Polygonum convolvulus], ladysthumb [Polygonum persicaria], and common chickweed [Stellaria media]) were studied in three row-spacing treatments (10, 20, and 30 cm) and two sowing densities (140 and 180 kg ha−1). Average seed production per surviving plant was up to three times higher in the 30-cm treatments compared with the 10-cm treatments. Taking into account the 40–50% weed mortality resulting from control in the 30-cm treatments, seed production per seedling was still higher in the 30-cm treatments than in the 10-cm treatments. Differences in wheat yield were not found among treatments. From the perspective of long-term weed population management, using a narrow row spacing would be more effective in spring wheat on the basis of experiments with the weed species considered here. Nomenclature: Ladysthumb, Polygonum persicaria L. , POLPE; wild buckwheat, Polygonum convolvulus L. , POLCO; common chickweed, Stellaria media (L.) Vill. , STEME; wheat, Triticum aestivum L.
A Novel HER2-targeted Antibody–drug Conjugate Offers the Possibility of Clinical Dosing at Trastuzumab-equivalent Exposure Levels

Trastuzumab and the related ADC, ado-trastuzumab emtansine (T-DM1), both target HER2-overexpressing cells. Together, these drugs have treatment indications in both early-stage and metastatic settings for HER2+ breast cancer. T-DM1 retains the antibody functionalities of trastuzumab and adds the potency of a cytotoxic maytansine payload. Interestingly, in the clinic, T-DM1 cannot always replace the use of trastuzumab plus chemotherapy administered together as single agents. We hypothesize that this failure may be due, in part, to the limited systemic exposure achieved by T-DM1 relative to trastuzumab because of toxicity-related dosing constraints on the ADC. We have developed a trastuzumab-based ADC site specifically conjugated to maytansine through a noncleavable linker. This construct, termed CAT-01-106, has a drug-to-antibody ratio (DAR) of 1.8, approximately half the average DAR of T-DM1, which comprises a mixture of antibodies variously conjugated with DARs ranging from 0 to 8. The high DAR species present in T-DM1 contribute to its toxicity and limit its clinical dose. CAT-01-106 showed superior in vivo efficacy compared with T-DM1 at equal payload dosing and was equally or better tolerated compared with T-DM1 at equal payload dosing up to 120 mg/kg in Sprague–Dawley rats and 60 mg/kg in cynomolgus monkeys. CAT-01-106 also showed improved pharmacokinetics in rats relative to T-DM1, with 40% higher ADC exposure levels. Together, the data suggest that CAT-01-106 may be sufficiently tolerable to enable clinical dosing at trastuzumab-equivalent exposure levels, combining the functions of both the antibody and the payload in one drug and potentially improving patient outcomes.
Cotranslational folding of alkaline phosphatase in the periplasm of Escherichia coli

Cotranslational protein folding studies using Force Profile Analysis, a method where the SecM translational arrest peptide is used to detect folding-induced forces acting on the nascent polypeptide, have so far been limited mainly to small domains of cytosolic proteins that fold in close proximity to the translating ribosome. In this study, we investigate the cotranslational folding of the periplasmic, disulfide bond-containing E. coli protein alkaline phosphatase (PhoA) in a wild-type strain background and a strain background devoid of the periplasmic thiol:disulfide interchange protein DsbA. We find that folding-induced forces can be transmitted via the nascent chain from the periplasm to the polypeptide transferase center in the ribosome, a distance of ~160 Å, and that PhoA appears to fold cotranslationally via at least two disulfide-stabilized folding intermediates. Thus, Force Profile Analysis can be used to study cotranslational folding of proteins in an extra-cytosolic compartment, like the periplasm.
Development of a Single-Sampling Noninvasive Hair Snare

Abstract Noninvasive hair and fecal DNA sampling provides a means of collecting information on elusive species, while causing little or no disturbance. However, current methods of hair collection do not preclude multiple sampling, thus risking sample contamination. We developed a hair snare that prevents multiple sampling, is cost-effective, easy to construct, and safe for target and nontarget species. Our initial field tests on endangered San Joaquin kit foxes (Vulpes macrotis mutica) and swift foxes (Vulpes velox) suggest that this hair snare may be effective in collecting uncontaminated samples for DNA analysis.
The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor

The human pregnane X receptor (hPXR) is activated by a large set of endogenous and exogenous compounds and plays a critical role in the control of detoxifying enzymes and transporters regulating liver and gastrointestinal drug metabolism and clearance. hPXR is also involved in both the development of multidrug resistance and enhanced cancer cells aggressiveness. Moreover, its unintentional activation by pharmaceutical drugs can mediate drug–drug interactions and cause severe adverse events. In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet. Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813, whereas it does not activate mouse or zebrafish PXR nor hCAR. We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells. Our study reveals that by using a panel of different cellular techniques it is possible to improve the assessment of hPXR agonist activity for new developed drugs.
Distinct Proteomic Profile of Spermatozoa from Men with Seminomatous and Non-Seminomatous Testicular Germ Cell Tumors

Testicular germ cell tumors (TGCTs) are predominant in young males (15–44 years). Seminomatous and non-seminomatous TGCTs account for about 98% of all TGCTs cases. In this study, we aimed to compare the sperm proteome of patients with seminomatous and non-seminomatous TGCTs to identify possible protein biomarkers that could help distinguish between them in a non-invasive manner. We analyzed semen samples from patients with seminomatous or non-seminomatous TGCTs (n = 15/group) that were cryopreserved before the start of cancer treatment. Quantitative proteomic analysis was conducted on pooled samples (n = 3/group) and a total of 258 differentially expressed proteins (DEPs) were identified. The overexpression of acrosin precursor (ACR) and chaperonin containing TCP1 subunit 6B (CCT6B) as well as the underexpression of S100 calcium-binding protein A9 (S100A9) in the spermatozoa of patients with non-seminomatous TGCTs were validated by western blotting conducted on individual samples (n = 6 for seminomatous group and n = 6 for non-seminomatous group). Our overall results suggest an association between the higher and faster invasiveness of non-seminomatous TGCTs and the altered protein expressions, providing important information for future studies.
What can Multi-Biomarker Approach Tells Us about the Impact of Pollution on Freshwater Biota Health?

The health of freshwater ecosystems and their biota exposed to continuous detrimental effects of environmental contaminants can be better assessed by integrating analytical chemical analysis with carefully selected biological endpoints measured in tissues of species of concern. These biological endpoints include molecular, biochemical and physiological markers (i.e. biomarkers) that when integrated, can clarify issues of contaminant bioavailability, bioaccumulation and ecological effects while enabling a better understanding of the effects of non-chemical stressors. Here, a battery of biomarkers, devised to measure cellular damage, antioxidant enzyme activity and physiological impairment, were combined with chemical analysis of water column, sediment and tissue, to determine exposure to and the effects of pollution at sites within Sitnica River (Kosovo). Carp fish, Cyprinus carpio, collected in situ through electrofishing were used as test species to determine the possible alterations in biochemical and physiological biomarkers. Our results confirmed a significant increase of hepatic alanine transaminase (ALT), aspartate transaminase (AST), glutathione-S-transferase (GST), catalase (CAT) and superoxide-dismutase (SOD) in blood. Both, blood glucose (GLU) and cortisol concentration were also significantly increased. Alteration in liver histological structure, increased in the frequency of micronuclei (MN) and nuclear abnormalities (ENA) in erythrocytes, were the most discriminating biomarkers among sites. This holistic approach to environmental assessment is encouraged as it helps to identify the integrated impact of chemical contamination on organisms and to provide a realistic measure of environmental quality.