gebhart/patrepeval huggingface dataset:
Ghrelin mediates stress-induced food-reward behavior in mice (2011)

The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.
Treatment of Sickle Cell Anemia with Hydroxyurea and Erythropoietin (1990)

This study confirms that hydroxyurea therapy increases hemoglobin F production and provides objective evidence that hydroxyurea reduces the rate of hemolysis and intracellular polymerization of hemoglobin S. In contrast, recombinant human erythropoietin, whether alone or in combination with hydroxyurea, offers no measurable benefit.
Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development (2014)

The quest for a prophylactic AIDS vaccine is ongoing, but it is now clear that the successful vaccine must elicit protective antibody responses. Accordingly, intense efforts are underway to identify immunogens that elicit these responses. Regardless of the mechanism of antibody-mediated protection, be it neutralization, Fc-mediated effector function, or both, antibody persistence and appropriate T-cell help are significant problems confronting the development of a successful AIDS vaccine. Here, we discuss the evidence illustrating the poor persistence of antibody responses to Env, the envelope glycoprotein of HIV-1, and the related problem of CD4(+) T-cell responses that compromise vaccine efficacy by creating excess cellular targets of HIV-1 infection. Finally, we propose solutions to both problems that are applicable to all Env-based AIDS vaccines regardless of the mechanism of antibody-mediated protection.
Tunable Vancomycin Releasing Surfaces for Biomedical Applications (2010)

Local drug delivery methods allow for the opportunity to supply potent multispectrum antibiotics such as vancomycin hydrochloride to sites of infection, while avoiding systemic toxicity. In this work, layer-by-layer assembly of polymer multilayer films is applied to create vancomycin delivery coatings. By taking advantage of the versatile layer-by-layer spray and dip coating techniques, thin films were generated based on electrostatic and other secondary interactions discovered to exist between the film components. The importance of film interdiffusion during growth in promoting interactions between film components is found to be critical in the direct incorporation of the weakly charged vancomycin drug in these multilayer films. The resulting coatings are engineered with unprecedented drug densities ranging from 17-220 μg mm(-3) (approximately 20 wt%) for films that are micron to submicron scale in thickness, delivering vancomycin over timescales of 4 h to 2.5 days. The released drug is highly effective in inhibiting Staphylococcus aureus growth in vitro. Taking advantage of the difference in release characteristics between dip and spray assembled films, a composite film architecture was engineered to have both a bolus vancomycin release followed by a period of linear sustained drug release. The control over drug densities and release profiles displayed in this work is necessary to address the requirements of varying medical conditions, including those where immediate infection elimination is needed or long term infection prevention is required.
Polarized Expression of Tamm-Horsfall Protein by Renal Tubular Epithelial Cells Activates Human Granulocytes (2002)

In renal bacterial infections granulocytes are of major importance in the primary immune defense against invading pathogens. However, the mechanisms of granulocytic activation in renal interstitial invasion have not been clarified. Renal tubular epithelial cell mechanisms inducing granulocytic activation and bacterial killing may include tubular cell expression of Tamm-Horsfall protein (THP), a urinary protein that is known to enhance cytokine expression in monocytes. We studied the role of THP in granulocytic activation. A strong binding of THP to human granulocytes was demonstrated by fluorescence-activated cell sorter analysis. Urinary THP and supernatants of THP-expressing cultured tubular epithelial cells (MDCK) enhanced interleukin-8 (IL-8) expression by human granulocytes. Renal tubular cells growing polarized on polycarbonate membranes were used to study apical versus basal THP expression. By electron microscopy THP immunoreactivity was exclusively found on the apical surfaces of tubular cells and was absent on the basolateral cell membrane. In the apical cell culture compartment we found significantly more stimulatory activity for granulocytic IL-8 expression. CD62L, a selectin less expressed in activated granulocytes, was decreased in granulocytes incubated with urinary THP and in supernatants of THP-producing renal tubular cells but not in supernatants from THP-negative cells. Again, the effect on CD62L expression was found only in apical culture media and was absent in the basal compartment. In summary our data give evidence that renal tubular cell THP expression may be relevant in kidney diseases since THP is a potent activator of human granulocytes. The regulation of apical versus basal THP expression and release in vivo may be crucial in the induction of the inflammatory response, e.g., in bacterial renal diseases.
Computation Reuse in DNNs by Exploiting Input Similarity (2018)

In recent years, Deep Neural Networks (DNNs) have achieved tremendous success for diverse problems such as classification and decision making. Efficient support for DNNs on CPUs, GPUs and accelerators has become a prolific area of research, resulting in a plethora of techniques for energy-efficient DNN inference. However, previous proposals focus on a single execution of a DNN. Popular applications, such as speech recognition or video classification, require multiple back-to-back executions of a DNN to process a sequence of inputs (e.g., audio frames, images). In this paper, we show that consecutive inputs exhibit a high degree of similarity, causing the inputs/outputs of the different layers to be extremely similar for successive frames of speech or images of a video. Based on this observation, we propose a technique to reuse some results of the previous execution, instead of computing the entire DNN. Computations related to inputs with negligible changes can be avoided with minor impact on accuracy, saving a large percentage of computations and memory accesses. We propose an implementation of our reuse-based inference scheme on top of a state-of-the-art DNN accelerator. Results show that, on average, more than 60% of the inputs of any neural network layer tested exhibit negligible changes with respect to the previous execution. Avoiding the memory accesses and computations for these inputs results in 63% energy savings on average.
Synthesis and stereoselective reduction of (±)-, (+)- and (–)-6-substituted-6-azabicyclo[3.2.1]octan-3-one (1991)

Starting with 6-oxabicyclo[3.2.1]oct-3-en-7-one 6, a three step, general synthetic route to both racemic and optically active 6-substituted 6-azabicyclo[3.2.1]octan-3-ones has been developed. Opening of the lactone ring of 6 with amines gave amides which were reduced with lithium aluminium hydride to amino alcohols. Allylic oxidation of amino alcohols 8a, 8b, 12 and 13 with manganese dioxide provided the bicyclic ketones 1b, 1c, 14 and 15, respectively, without isolation of the intermediate monocyclic ketones. Methods for stereoselective reduction of the bicyclic ketones to the corresponding 6-substituted 6-azabicyclo[3.2.1]octan-3α-ols and -3β-ols have been developed. Displacement of the R-α-methylbenzyl chiral auxiliary from the diastereomeric alcohols 16, 17, and 20, 21 by catalytic debenzylation followed by reductive amination provided the optically active 6-methyl-6-azabicyclo [3.2.1]octan-3-ols 1d–1e, respectively. The absolute stereochemistry of all reported optically active compounds has been established by comparison of diastereoisomers 10 and 11 with the R-(+)-methylbenzylamine amides derived from optically enriched lactone 6.
Corneal Collagen Crosslinking: A Systematic Review (2014)

Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal fibrosis and visual deterioration. Other ectatic corneal disorders include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD). Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with ultraviolet A radiation induces stromal crosslinks. This alters corneal biomechanics, causing an increase in corneal stiffness. In recent years, CXL has been an established treatment for the arrest of KCN, PLE and PMD progression. CXL has also been shown to be effective in the treatment of corneal infections, chemical burns, bullous keratopathy and other forms of corneal edema. This is a current review of CXL - its biomechanical principles, the evolution of CXL protocols in the past, present and future, indications for treatment, treatment efficacy and safety.
Defining the Role of Sirolimus in the Management of Graft-versus-Host Disease: From Prophylaxis to Treatment (2012)

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Measures developed that have significantly reduced GVHD were also frequently associated with an increased risk of relapse. GVHD and graft-versus-tumor (GVT) effects are tightly linked, and balance between both reactions is difficult to achieve. To have an impact on the outcome and quality of life after HSCT, improvements in current strategies to prevent and treat GVHD while preserving the GVT effect are clearly needed. Sirolimus (rapamycin) is a lipophilic macrocytic lactone with immunosuppressive, antitumor, and antiviral properties. Because of its multiple modes of activities, it is being increasingly used in the management of GVHD. This review aims to summarize its mechanisms of action and potential advantages over other immunosuppressors and to analyze the most relevant studies investigating its role in both prevention and treatment of GVHD.
Members of the Ikaros Gene Family Are Present in Early Representative Vertebrates (2000)

Abstract Members of the Ikaros multigene family of zinc finger proteins are expressed in a tissue-specific manner and most are critical determinants in the development of both the B and T lymphocytes as well as NK and dendritic APC lineages. A PCR amplification strategy that is based on regions of shared sequence identity in Ikaros multigene family members found in mammals and several other vertebrates has led to the recovery of cDNAs that represent the orthologues of Ikaros, Aiolos, Helios, and Eos in Raja eglanteria (clearnose skate), a cartilaginous fish that is representative of an early divergence event in the phylogenetic diversification of the vertebrates. The tissue-specific patterns of expression for at least two of the four Ikaros family members in skate resemble the patterns observed in mammals, i.e., in hematopoietic tissues. Prominent expression of Ikaros in skate also is found in the lymphoid Leydig organ and epigonal tissues, which are unique to cartilaginous fish. An Ikaros-related gene has been identified in Petromyzon marinus (sea lamprey), a jawless vertebrate species, in which neither Ig nor TCRs have been identified. In addition to establishing a high degree of evolutionary conservation of the Ikaros multigene family from cartilaginous fish through mammals, these studies define a possible link between factors that regulate the differentiation of immune-type cells in the jawed vertebrates and related factors of unknown function in jawless vertebrates.
Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An Integrative Approach (2017)

Proinflammatory cytokines/chemokines play an essential role in the pathogenesis of DR. Therefore, circulating biomarkers and retinal imaging aimed at assessing inflammation have emerged as useful tools for monitoring the onset and progression of DR. In addition, "liquid biopsy" of AH seems a good option in patients with advanced stages of DR requiring intravitreous injections. This strategy may permit us to implement a more personalized treatment with better visual function outcome. Further evaluation and validation of circulating and local biomarkers, as well as multimodal imaging is needed to gain new insights into this issue.
Pitfalls of in situ polymerase chain reaction (PCR) using direct incorporation of labelled nucleotides. (1993)

False positivity is reported of in situ PCR reactions in a direct incorporation assay with digoxigenin-labelled dUTP. It is recommended that in situ hybridization with specific labelled probe replaces the direct incorporation method for the detection of in situ PCR amplicon.
Engineering Escherichia coli to overproduce aromatic amino acids and derived compounds (2014)

The production of aromatic amino acids using fermentation processes with recombinant microorganisms can be an advantageous approach to reach their global demands. In addition, a large array of compounds with alimentary and pharmaceutical applications can potentially be synthesized from intermediates of this metabolic pathway. However, contrary to other amino acids and primary metabolites, the artificial channelling of building blocks from central metabolism towards the aromatic amino acid pathway is complicated to achieve in an efficient manner. The length and complex regulation of this pathway have progressively called for the employment of more integral approaches, promoting the merge of complementary tools and techniques in order to surpass metabolic and regulatory bottlenecks. As a result, relevant insights on the subject have been obtained during the last years, especially with genetically modified strains of Escherichia coli. By combining metabolic engineering strategies with developments in synthetic biology, systems biology and bioprocess engineering, notable advances were achieved regarding the generation, characterization and optimization of E. coli strains for the overproduction of aromatic amino acids, some of their precursors and related compounds. In this paper we review and compare recent successful reports dealing with the modification of metabolic traits to attain these objectives.
Non-starch plant polysaccharides in broiler nutrition – towards a physiologically valid approach to their determination (1996)

The physicochemical properties of non-starch polysaccharides (NSPs) are responsible for their antinutritive activities in the broiler chicken. In particular, soluble viscous NSPs depress the digestibilities of protein, starch and fat. On the other hand, insoluble and non-viscous NSPs may have a beneficial effect. Fat digestion is used here to illustrate how the physicochemical properties of NSP may interfere with digestion and absorption. It is suggested that the gut microflora can mediate the antinutritive effects of soluble and viscous NSP. It is concluded that the determinations of crude fibre and/or acid detergent fibre and neutral detergent fibre in feedstuffs are not appropriate for predicting and understanding the physiological action of NSPs in broilers. The determination of the in vitro solubility of NSP and the viscosity of the feed ingredient could become of major importance for ‘antinutritional’ evaluation. More research needs to be conducted to study the interactions of NSPs with the microbial activity in the intestinal tract of the broiler chicken.
The melatonin receptor subtype MT2 is present in the human cardiovascular system (2003)

We showed that the melatonin receptor subtype, MT1, is expressed in healthy and diseased human coronary arteries. As studies in experimental animals suggest that the MT2 melatonin receptor subtype is also present in the vasculature, we investigated whether the MT2 is expressed in human aorta and coronary arteries. Additionally, MT2 expression in human ventricular specimens was analysed, as melatonin was shown to affect myocyte function. Expression of the MT2-receptor was studied in sections of isolated coronary arteries, aorta and left ventricular specimens from healthy heart donors (control) and patients with dilated or ischemic cardiomyopathy. MT2 expression was found by reverse transcriptase (RT)-nested-polymerase chain reaction (PCR) in all of the specimens (aorta, left ventricle and coronary arteries) derived from controls. Also, visible evidence for receptor expression was found in 12 of 15 samples from cardiomyopathy patients and 10 of 15 of coronary heart disease patients. Additionally, the expression of MT2-receptor between aorta, left ventricle and coronary arteries varied among the individuals, some of them showing highest expression in the aorta while in others principal expression sites were coronary arteries or left ventricles. In conclusion, the MT2-receptor subtype is present in human arteries and left ventricles and it is suggested that in coronary heart disease MT2-receptor expression is altered. Furthermore, there is evidence for heterogeneous MT2 expression patterns in individual patients.
Analysis of O‐glycosylation site occupancy in bovine κ‐casein glycoforms separated by two‐dimensional gel electrophoresis (2005)

The ability of two-dimensional gel electrophoresis (2-DE) to separate glycoproteins was exploited to separate distinct glycoforms of kappa-casein that differed only in the number of O-glycans that were attached. To determine where the glycans were attached, the individual glycoforms were digested in-gel with pepsin and the released glycopeptides were identified from characteristic sugar ions in the tandem mass spectrometry (MS) spectra. The O-glycosylation sites were identified by tandem MS after replacement of the glycans with ammonia / aminoethanethiol. The results showed that glycans were not randomly distributed among the five potential glycosylation sites in kappa-casein. Rather, glycosylation of the monoglycoform could only be detected at a single site, T152. Similarly the diglycoform appeared to be modified exclusively at T152 and T163, while the triglycoform was modified at T152, T163 and T154. While low levels of glycosylation at other sites cannot be excluded the hierarchy of site occupation between glycoforms was clearly evident and argues for an ordered addition of glycans to the protein. Since all five potential O-glycosylation sites can be glycosylated in vivo, it would appear that certain sites remain latent until other sites are occupied. The determination of glycosylation site occupancy in individual glycoforms separated by 2-DE revealed a distinct pattern of in vivo glycosylation that has not been recognized previously.
Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer (2005)

Alterations of the cell adhesion molecule E-cadherin have been demonstrated in sporadic and hereditary gastric carcinomas. A cell adhesion molecule with functional similarity to E-cadherin is desmoglein 2 (Dsg2), a major component of the desmosomes. In this study, we investigated whether alterations of Dsg2 are involved in gastric carcinogenesis and whether germline mutations contribute to a genetic predisposition in familial gastric cancer patients with no germline mutations in the E-cadherin gene. Seventy-five formalin-fixed, paraffin-embedded tissues from 37 familial and 38 sporadic gastric carcinomas were analysed for Dsg2 expression by immunohistochemistry. DNA from 31 familial gastric cancer patients was analysed for germline mutations and five sporadic tumours were analysed for somatic mutations by DHPLC. Of the 75 tumours, 25 (33%) demonstrated abnormal (reduced and/or non-membrane-associated) Dsg2 expression. There was a trend towards more frequent abnormal expression in diffuse type (42%) than in intestinal type tumours (18%) (p = 0.066). One germline missense variant leading to a non-conservative amino acid change (c. 2810 C > A, Thr 937 Asn) was found in a familial gastric cancer patient with a diffuse type tumour. No somatic mutations were identified. The observed abnormal expression of Dsg2 protein suggests that this molecule is involved in the carcinogenesis of a subset of gastric carcinomas, in particular of the diffuse type. Somatic mutations in the gene do not seem to be a very frequent inactivation event and the finding of no clear pathogenic germline mutation rules out Dsg2 as a major gastric cancer predisposition gene.
Hypoxia Response Elements in the Aldolase A, Enolase 1, and Lactate Dehydrogenase A Gene Promoters Contain Essential Binding Sites for Hypoxia-inducible Factor 1 (1996)

Hypoxia-inducible factor 1 (HIF-1) is a basic helix-loop-helix transcription factor which is expressed when mammalian cells are subjected to hypoxia and which activates transcription of genes encoding erythropoietin, vascular endothelial growth factor, and other proteins that are important for maintaining oxygen homeostasis. Previous studies have provided indirect evidence that HIF-1 also regulates transcription of genes encoding glycolytic enzymes. In this paper we characterize hypoxia response elements in the promoters of the ALDA, ENO1, and Ldha genes. We demonstrate that HIF-1 plays an essential role in activating transcription via these elements and show that although absolutely necessary, the presence of a HIF-1 binding site alone is not sufficient to mediate transcriptional responses to hypoxia. Analysis of hypoxia response elements in the ENO1 and Ldha gene promoters revealed that each contains two functionally-essential HIF-1 sites arranged as direct and inverted repeats, respectively. Our data establish that functional hypoxia-response elements consist of a pair of contiguous transcription factor binding sites at least one of which contains the core sequence 5'-RCGTG-3' and is recognized by HIF-1. These results provide further evidence that the coordinate transcriptional activation of genes encoding glycolytic enzymes which occurs in hypoxic cells is mediated by HIF-1.