Bargaining, Revenue Sharing and Control Rights Allocation

In a two-period, double moral hazard model with incomplete contracting, this paper explores the relationship between revenue sharing and control rights. Specifically, we endogenize the allocation of both the income rights and the control rights and show why the two are often bundled together in the context of a two-party joint venture. Moreover, we study how the use of different bargaining solutions for the ex post contract renegotiation game may affect the optimal allocation of income and control rights. Our results can be used to explain the commonly observed ownership structures of equity joint ventures.

Two-tiered Online Optimization of Region-wide Datacenter Resource Allocation via Deep Reinforcement Learning

This paper addresses the important need for advanced techniques in continuously allocating workloads on shared infrastructures in data centers, a problem arising due to the growing popularity and scale of cloud computing. It particularly emphasizes the scarcity of research ensuring guaranteed capacity in capacity reservations during large-scale failures. To tackle these issues, the paper presents scalable solutions for resource management. It builds on the prior establishment of capacity reservation in cluster management systems and the two-level resource allocation problem addressed by the Resource Allowance System (RAS). Recognizing the limitations of Mixed Integer Linear Programming (MILP) for server assignment in a dynamic environment, this paper proposes the use of Deep Reinforcement Learning (DRL), which has been successful in achieving long-term optimal results for time-varying systems. A novel two-level design that utilizes a DRL-based algorithm is introduced to solve optimal server-to-reservation assignment, taking into account of fault tolerance, server movement minimization, and network affinity requirements due to the impracticality of directly applying DRL algorithms to large-scale instances with millions of decision variables. The paper explores the interconnection of these levels and the benefits of such an approach for achieving long-term optimal results in the context of large-scale cloud systems. We further show in the experiment section that our two-level DRL approach outperforms the MIP solver and heuristic approaches and exhibits significantly reduced computation time compared to the MIP solver. Specifically, our two-level DRL approach performs 15% better than the MIP solver on minimizing the overall cost. Also, it uses only 26 seconds to execute 30 rounds of decision making, while the MIP solver needs nearly an hour

Mineral and organic fertilization alters the microbiome of a soil nematode Dorylaimus stagnalis and its resistome

Although the effects of fertilization on the abundance and diversity of soil nematodes have been widely studied, the impact of fertilization on soil nematode microbiomes remains largely unknown. Here, we investigated how different fertilizers: no fertilizer, mineral fertilizer, clean slurry (pig manure with a reduced antibiotic burden) and dirty slurry (pig manure with antibiotics) affect the microbiome of a dominant soil nematode and its associated antibiotic resistance genes (ARGs). The results of 16S rRNA gene high throughput sequencing showed that the microbiome of the soil nematode Dorylaimus stagnalis is diverse (Shannon index: 9.95) and dominated by Proteobacteria (40.3%). Application of mineral fertilizers significantly reduced the diversity of the nematode microbiome (by 28.2%; P < 0.05) but increased the abundance of Proteobacteria (by 70.1%; P = 0.001). Microbial community analysis, using a null hypothesis model, indicated that microbiomes associated with the nematode are not neutrally assembled. Organic fertilizers also altered the diversity of the nematode microbiome, but had no impact on its composition as illustrated by principal coordinates analysis (PCoA). Interestingly, although no change of total ARGs was observed in the nematode microbiome and no significant relationship existed between nematode microbiome and resistome, the abundance of 48 out of a total of 75 ARGs was enriched in the organic fertilizer treatments. Thus, the data suggests that ARGs in the nematode microbiome still had a risk of horizontal gene transfer under fertilization and nematodes might be a potential refuge for ARGs

Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals

Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat—the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a ‘self-poisoning’ scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk