gebhart/patrepeval huggingface dataset:
Identification of Gene Networks for Residual Feed Intake in Angus Cattle Using Genomic Prediction and RNA-seq (2016)

Improvement in feed conversion efficiency can improve the sustainability of beef cattle production, but genomic selection for feed efficiency affects many underlying molecular networks and physiological traits. This study describes the differences between steer progeny of two influential Angus bulls with divergent genomic predictions for residual feed intake (RFI). Eight steer progeny of each sire were phenotyped for growth and feed intake from 8 mo. of age (average BW 254 kg, with a mean difference between sire groups of 4.8 kg) until slaughter at 14-16 mo. of age (average BW 534 kg, sire group difference of 28.8 kg). Terminal samples from pituitary gland, skeletal muscle, liver, adipose, and duodenum were collected from each steer for transcriptome sequencing. Gene expression networks were derived using partial correlation and information theory (PCIT), including differentially expressed (DE) genes, tissue specific (TS) genes, transcription factors (TF), and genes associated with RFI from a genome-wide association study (GWAS). Relative to progeny of the high RFI sire, progeny of the low RFI sire had -0.56 kg/d finishing period RFI (P = 0.05), -1.08 finishing period feed conversion ratio (P = 0.01), +3.3 kg^0.75 finishing period metabolic mid-weight (MMW; P = 0.04), +28.8 kg final body weight (P = 0.01), -12.9 feed bunk visits per day (P = 0.02) with +0.60 min/visit duration (P = 0.01), and +0.0045 carcass specific gravity (weight in air/weight in air-weight in water, a predictor of carcass fat content; P = 0.03). RNA-seq identified 633 DE genes between sire groups among 17,016 expressed genes. PCIT analysis identified >115,000 significant co-expression correlations between genes and 25 TF hubs, i.e. controllers of clusters of DE, TS, and GWAS SNP genes. Pathway analysis suggests low RFI bull progeny possess heightened gut inflammation and reduced fat deposition. This multi-omics analysis shows how differences in RFI genomic breeding values can impact other traits and gene co-expression networks.
Differential induction of pro- and anti-inflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment (1997)

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.
Protein Structural Information and Evolutionary Landscape by In Vitro Evolution (2019)

Abstract Protein structure is tightly inter-twined with function according to the laws of evolution. Understanding how structure determines function has been the aim of structural biology for decades. Here, we have wondered instead whether it is possible to exploit the function for which a protein was evolutionary selected to gain information on protein structure and on the landscape explored during the early stages of molecular and natural evolution. To answer to this question, we developed a new methodology, which we named CAMELS ( C oupling A nalysis by M olecular E volution L ibrary S equencing), that is able to obtain the in vitro evolution of a protein from an artificial selection based on function. We were able to observe with CAMELS many features of the TEM-1 beta lactamase local fold exclusively by generating and sequencing large libraries of mutational variants. We demonstrated that we can, whenever a functional phenotypic selection of a protein is available, sketch the structural and evolutionary landscape of a protein without utilizing purified proteins, collecting physical measurements or relying on the pool of natural protein variants.
Distinct Mechanisms of Endomembrane Reorganization Determine Dissimilar Transport Pathways in Plant RNA Viruses (2022)

Plant viruses exploit the endomembrane system of infected cells for their replication and cell-to-cell transport. The replication of viral RNA genomes occurs in the cytoplasm in association with reorganized endomembrane compartments induced by virus-encoded proteins and is coupled with the virus intercellular transport via plasmodesmata that connect neighboring cells in plant tissues. The transport of virus genomes to and through plasmodesmata requires virus-encoded movement proteins (MPs). Distantly related plant viruses encode different MP sets, or virus transport systems, which vary in the number of MPs and their properties, suggesting their functional differences. Here, we discuss two distinct virus transport pathways based on either the modification of the endoplasmic reticulum tubules or the formation of motile vesicles detached from the endoplasmic reticulum and targeted to endosomes. The viruses with the movement proteins encoded by the triple gene block exemplify the first, and the potyviral system is the example of the second type. These transport systems use unrelated mechanisms of endomembrane reorganization. We emphasize that the mode of virus interaction with cell endomembranes determines the mechanism of plant virus cell-to-cell transport.
A Broad-Spectrum Caspase Inhibitor Attenuates Allergic Airway Inflammation in Murine Asthma Model (2003)

Asthma is characterized by acute and chronic airway inflammation, and the severity of the airway hyperreactivity correlates with the degree of inflammation. Many of the features of lung inflammation observed in human asthma are reproduced in OVA-sensitized/challenged mice. T lymphocytes, particularly Th2 cells, are critically involved in the genesis of the allergic response to inhaled Ag. In addition to antiapoptotic effects, broad-spectrum caspase inhibitors inhibit T cell activation in vitro. We investigated the effect of the broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), on airway inflammation in OVA-sensitized/challenged mice. OVA-sensitized mice treated with z-VAD-fmk immediately before allergen challenge showed marked reduction in inflammatory cell infiltration in the airways and pulmonary blood vessels, mucus production, and Th2 cytokine production. We hypothesized that the caspase inhibitor prevented T cell activation, resulting in the reduction of cytokine production and eosinophil infiltration. Treatment with z-VAD-fmk in vivo prevented subsequent T cell activation ex vivo. We propose that caspase inhibitors may offer a novel therapeutic approach to T cell-dependent inflammatory airway diseases.
The Mitogen-activated Protein Kinase Phosphatases PAC1, MKP-1, and MKP-2 Have Unique Substrate Specificities and Reduced Activity in Vivo toward the ERK2 sevenmaker Mutation (2021)

Mitogen-activated protein (MAP) kinases can be grouped into three structural families, ERK, JNK, and p38, which are thought to carry out unique functions within cells. We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK, respectively. Here we characterize a new MAP kinase phosphatase, MKP-2, that is induced in human peripheral blood T cells with phorbol 12-myristate 13-acetate and is expressed in a variety of nonhematopoietic tissues as well. We show that the in vivo substrate specificities of individual phosphatases are unique. PAC1, MKP-2, and MKP-1 recognize ERK and p38, ERK and JNK, and ERK, p38, and JNK, respectively. Thus, individual MAP kinase phosphatases can differentially regulate the potential for cross-talk between the various MAP kinase pathways. A hyperactive allele of ERK2 (D319N), analogous to the Drosophila sevenmaker gain-of-function mutation, has significantly reduced sensitivity to all three MAP kinase phosphatases in vivo.
Magnetic Resonance Spectroscopy for Studies of Neurotransmission in Vivo (2025)

Magnetic resonance spectroscopy (MRS) of hydrogen and carbon allow the study of neurochemical alterations in neuropsychiatric disorders. This paper discusses the basic theory of MRS in order to provide an understanding of this complicated technical area. A variety of applications of hydrogen MRS in the study of neuropsychiatric disorders are reviewed; these applications can generate useful hypotheses about brain metabolism. Following that is a description of neurotransmitter cycling and how kinetic carbon MRS can be used to extend hydrogen MRS measurements to evaluate the rate of cycling and energy metabolism. The remainder of the article focuses primarily on steps that are necessary for MRS to become more widely used, making it clinically viable and allowing the study of large populations.
OP003 Temporal changes in immune pathways with consecutive biological therapies as measured by serum proteomics (2018)

The last decade, anti-α4β7 (vedolizumab/VDZ) and anti-p40 (ustekinumab/UST) antibodies became available on top of anti-TNF agents (infliximab/IFX, adalimumab/ADM) for patients with inflammatory bowel disease. Biological-naïve patients consistently had better outcomes compared with exposed patients. It is unclear whether this is due to more refractory disease or alterations in immune pathways triggered by biological exposure. Using serum proteomics, we evaluated differences in immune profiles at start and after switch of different types of biologicals. Consecutive serum samples were collected at start of biological treatment (Time point/T1) and at time of switch to another biological (T2, T3) from 176 anti-TNF-treated patients (137 IFX, 39 ADM), 41 VDZ-treated patients, 5 UST-treated patients, 40 patients treated with IFX, ADM, and VDZ, and 13 patients treated with anti-TNF, VDZ, and UST. All patients starting anti-TNF were biological-naïve. With the proximity extension assay technology, 79 inflammatory markers were measured (OLINK). RNA sequencing on matched baseline mucosal biopsies (n = 54) was performed with Illumina HiSeq 4000NGS. Significance was reported after multiple testing correction (false discovery rate). In patients failing IFX, 34 serum markers involved in cell migration and immune response were significantly higher at T2 compared with T1. In contrast, patients failing ADM had significantly lower levels of 23 markers involved in immune process stimulation and chemotaxis at T2. IL-17A was significantly higher at T2 after both IFX and ADM. At ADM T1 vs. IFX T1, 9 markers involved in cell migration were significantly different, regardless of disease activity. In patients failing VDZ, five markers involved in cytokine signalling were lower at T2. Similar trends were observed at mRNA level (Table 1). In patients failing UST, 14 markers involved in immune regulation (e.g. TNF, CCL25) were lower at T2. Patients switching from IFX–>ADM(T2)–>VDZ(T3) had significantly higher levels of 21 cell migration markers (e.g. CCL7) at T2 and most of these decreased at T3. Patients switching from anti-TNF–>VDZ(T2)–>UST(T3) had higher levels of apoptotic markers at T2, and altered levels of lymphocyte differentiation markers (e.g. IL-12B) at T3. Overview of dysregulated inflammatory markers as measured by serum proteomics and mucosal transcriptomics. Exposure to different types of biological treatments is associated with specific changes in immune profiles. Future studies should now prospectively characterise these profiles on a larger scale to see whether they can aid clinicians in personalised therapeutic decision-making.
Whither biochemistry and chemistry?: Supporting Excellence in the Science Base (2004)

At the start of the 21st Century both biochemistry and chemistry appeared well-placed to capitalize on the ‘century of biology’ and the exciting possibilities promised by ‘nanotechnology’. In addition, both appeared to be essential elements in understanding and monitoring environmental quality and its impact on human health, with major sectors within the UK economy critically dependent on the flow of highly trained personnel in these fields. The future, surely, looked rosy. However, in the last 6 months, three major UK university chemistry departments have been closed down, and over the last 5 years or so, the numbers of biochemistry departments returning separately under the National Research Assessment Exercise (RAE) has fallen dramatically. Here, we explore the background to these apparently incongruous developments and what they could portend for the future.
Poly ( l -Lactic Acid)/Layered Silicate Nanocomposite:  Fabrication, Characterization, and Properties (2003)

The possibility of making rigid polymer layered nanocomposites from biocompatible/biodegradable matrixes was explored. Three types of commercially available organophilic clay were employed to concurrently study the effects of organic modifier miscibility with the matrix and of the extent of clay modification on overall nanocomposite formation. The nanocomposites were fabricated via the exfoliation−adsorption technique with the matrix polymer poly (l-lactic acid), PLLA, a widely used, biodegradable, synthetic polyester. X-ray diffraction (XRD) data reveal that increasing the miscibility of the surfactant/polymer matrix increases the tendency of the system to exfoliate and randomly distribute the silicate layers. Transmission electron microscopy (TEM) data show that the ordering of silicate platelets is consistent with d spacings obtained from XRD. Because of the nanometer-range dispersion of silicate layers, all the nanocomposites retain their optical clarity. Mechanical properties of the fabricated nanocomposites were probed by dynamic mechanical analysis and show significant improvements in the storage modulus when compared to neat PLLA. The extent of crystallinity was observed to be inversely proportional to the extent of modified clay loading in the final composites.
Chronic Pancreatitis: Managing a Difficult Disease (2019)

Chronic pancreatitis is characterized by progressive, irreversible morphologic and functional changes that are most commonly attributed to environmental insults, particularly when there is a genetic or anatomic predisposition. Heavy alcohol use and cigarette smoking are the most common environmental risk factors, but both may be absent. Antecedent episodes of acute pancreatitis occur in about half of patients. Abdominal pain is the most common symptom and requires a tailored approach depending on the anatomic changes in the pancreas. Other clinical manifestations include diabetes mellitus, exocrine pancreatic insufficiency, metabolic bone disease, pancreatic cancer, and anatomic complications. Current disease management is centered on risk factor reduction and screening for and treating disease complications. There are no current therapies to delay or retard disease progression, but there are ongoing efforts to more fully understand the natural history of chronic pancreatitis and underlying mechanisms of disease. These studies are expected to provide insights that will transform our approach to disease management and provide increased hope to patients.
Using temporal causal models to isolate failures in Power System protection devices (2014)

Power transmission systems are instrumented with a network of fast-acting protection devices that detect anomalies and arrest the fault propagation, thereby isolating the faulty components to protect the remaining system. However, often a local protection action leads to cascading effects to other regions resulting in blackouts. Also, inherent faults in protection devices such as relays and breakers could lead to failed or misguided protection action. A fault model associated with such a system needs to capture the dynamic behavior of the system as well as protection scheme in both nominal and faulty modes of operation. With an effort to capture the temporal behavior and the fault propagation of the system and its autonomous protection mechanism, we propose a new modeling formalism - the Temporal Causal Diagram (TCD). In this paper, we will describe the TCD modeling formalism and apply it to create fault-models that capture the fault propagation and state evolution of the Power Systems and their autonomous protection units. Further, we showcase simulation models derived from the TCD models and use these to simulate single and multi-fault scenarios in power transmission systems.
Low protein diets reduce greenhouse gas production in finisher pigs while maintaining animal performance (2003)

Reducing dietary protein maintained performance and reduced nutrient excretion of finisher pigs with wheat-barley based, but not corn based diets. Reducing dietary protein reduced N excretion and CH4 production, but had little effect on CO2 production. The CO2 equivalents arising from the animals themselves (CO2 and CH4 production) tended to be lower with reduced protein contents. The further greenhouse gas production depends on the conversion of excreted carbon and N into CO2, CH4 and N2O. Reducing dietary protein contents reduces the N excretion by pigs, which gives the potential to reduce greenhouse gas emissions by pigs by over 20%.
Modeling the effects of atmospheric emissions on groundwater composition (1994)

A composite model of atmospheric, unsaturated and groundwater transport is developed to evaluate the processes determining the distribution of atmospherically derived contaminants in groundwater systems and to test the sensitivity of simulated contaminant concentrations to input parameters and model linkages. One application is to screen specific atmospheric emissions for their potential in determining groundwater age. Temporal changes in atmospheric emissions could provide a recognizable pattern in the groundwater system. The model also provides a way for quantifying the significance of uncertainties in the tracer source term and transport parameters on the contaminant distribution in the groundwater system, an essential step in using the distribution of contaminants from local, point source atmospheric emissions to examine conceptual models of groundwater flow and transport.
Distinct Expression of miR-378 in Nonsyndromic Cleft Lip and/or Cleft Palate: A Cogitation of Skewed Sex Ratio in Prevalence (2020)

Our findings suggest that different expression of miR-378 is consistent with the skewed sex ratio in the prevalence of NSCL/P.
In Vivo β-Adrenergic Blockade by Propranolol Prevents Isoproterenol-induced Polycystic Ovary in Adult Rats (2012)

Increasing evidence in animal models and in humans shows that sympathetic nerve activity controls ovarian androgen biosynthesis and follicular development. Thus, sympathetic nerve activity participates in the follicular development and the hyperandrogenism characteristics of polycystic ovary syndrome, which is the most prevalent ovarian pathology in women during their reproductive years. In this study, we mimic sympathetic nerve activity in the rat via "in vivo" stimulation with isoproterenol (ISO), a β-adrenergic receptor agonist, and test for the development of the polycystic ovary condition. We also determine whether this effect can be reversed by the administration of propranolol (PROP), a β-adrenergic receptor antagonist. Rats were treated for 10 days with 125 μg/kg ISO or with ISO plus 5 mg/kg PROP. The ovaries were examined 1 day or 30 days following drug treatment. While ISO was present, the ovaries had an increased capacity to secrete androgens; ISO + PROP reversed this effect on androgen secretory activity. 30 days after treatment, androstenedione secretion reverted to normal levels, but an increase in the intra-ovarian nerve growth factor (NGF) concentration and luteinizing hormone (LH) plasma levels was detected. ISO treatment resulted in follicular development characterized by an increased number of pre-cystic and cystic ovarian follicles; this was reversed in the ISO + PROP group. The lack of change in the plasma levels of progesterone, androstenedione, testosterone, or estradiol and the increased LH plasma levels strongly suggests a local intra-ovarian effect of ISO indicating that β-adrenergic stimulation is a definitive component in the rat polycystic ovary condition.
Healing Nurb surfaces (1996)

Computer Aided Geometric Design has come a long way from designing car bodies in the 1960's to present day use in design, simulation and testing. Use of B-Splines and now NURBs (Non-Uniform Rational B-Splines) is fast becoming the de facto industry standard in representing-geometric forms. One of the many uses of NURBs is for analysis of surfaces. This could be fluid flow or the description of a part itself. For analysis of numerical data such as in fluid dynamics, a snap shot of the flow may be taken and represented by a NURB surface. This is done by interpolating to the points on the fluid surface. Depending on the criticality of the region, the data spread may be highly irregular. This poses a problem that no matter what parametrization scheme is used, interpolant results in a poorly parametrized surface. A methodology is presented here to approximate a surface within a given tolerance. The approximation is a chord length parameterized NURB surface. The healing process tunes the relationship between the geometry of the surface and its underlying parametrization. This requires approximating the boundary curves first followed by finding adequate interior-points to pass an interpolating-surface. Although not a goal of this work, it is observed that the process can be used, in some cases, for the purposes of data reduction. Methods to compute end conditions for NURB surface interpolation problem are also presented.