Miracle-dz/UniFAR-FTUs huggingface dataset:
VEGF-dependent conjunctivalization of the corneal surface.

PURPOSE To investigate the mechanisms governing corneal neovascularization and the appearance of goblet cells in a murine model of limbal insufficiency. METHODS The spatial and time-dependent relationship between corneal neovascularization and goblet cell density was analyzed in corneal flatmounts. Immunohistochemical detection of the vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR1) was performed in paraffin-embedded sections. A transgenic mouse that expresses the reporter gene lacZ targeted to the Flt-1 locus through homologous recombination was used to analyze corneal expression of Flt-1. The presence of soluble and membranous goblet cell Flt-1 mRNA and protein content was assessed with Northern and Western blot analyses, respectively. Finally, systemic adenoviral expression of a soluble Flt-1/Fc construct was used to study the effect of inhibition of VEGF bioactivity on the appearance of goblet cells and neovascularization. RESULTS Corneal neovascularization preceded the appearance of goblet cells, although both processes overlapped temporally. Flt-1 was abundant in the conjunctiva-like epithelium covering the cornea, as well as in the goblet cells, invading leukocytes, and vasculature. A similar expression pattern was observed in the transgenic mice expressing the lacZ gene downstream from the Flt-1 promoter. Isolated human and rat goblet cells in culture expressed Flt-1 mRNA and protein, as did freshly isolated human conjunctiva. The systemic inhibition of VEGF bioactivity potently suppressed both corneal neovascularization (8.3% +/- 8.1% vs. 41.1% +/- 15.3% corneal area; P < 0.001) and corneal goblet cell density (1.6% +/- 2.5% vs. 12.2% +/- 2.4% corneal area; P < 0.001). CONCLUSIONS Two important features of corneal conjunctivalization, the appearance of goblet cells and neovascularization, are regulated by VEGF. Both processes are probably mediated, in part, through the Flt-1 receptor. Taken together, these data indicate that an anti-VEGF therapeutic approach may limit the visual loss associated with conjunctivalization of the corneal surface.
Device characterization and impact of CNT diameter variation on the read write stability of CNTFET 6t SRAM cell

Carbon nano tube FETs are most promising candidates of nano electronic system design. Their recent evolution has been leveraging advantages such as high channel mobility and increased gate capacitance in short channel regime. The conventional MOSFETS suffer with exponential increase in leakage currents under down scaling whereas the CNTFETS overcome this limitation and deliver optimal voltage current characteristics. Considering the vast amount of data storage requirements in modern day systems, memories act as the vital blocks and they need to be thoroughly investigated with respect area, power and performance constraints before implementation. SRAM cell is one of the important building blocks in design of memories and a significant amount of attention is being paid into its functionality. The submicron scaling of conventional CMOS devices affect their performance due to short channel effects and circuits become unreliable. To overcome its challenges, in this work, MOSFET like ballistic CNTFETs have found to be the best alternatives for conventional CMOS devices under the 32 nm technology regime. The work focuses on the design and evaluation of the performance metrics of CNTFET based 6T SRAM cells at 32nm technology with observation on variation in chirality of the CNT. The design infers that the designed SRAM cell offer a good SNM at a power supply of 1 V, and also a stable read write operation can be achieved due to the high process variation tolerance of CNT.
A Novel Apoptotic Pathway Induced by Nerve Growth Factor-mediated TrkA Activation in Medulloblastoma*

Nerve growth factor (NGF) induces apoptosis in a human medulloblastoma cell line (MED283) engineered to express TrkA (MED283-TrkA) (Muragaki, Y., Chou, T. T., Kaplan, D. R., Trojanowski, J. Q., and Lee, V. M. (1997) J. Neurosci. 17, 530–542). To dissect the molecular signaling pathway that mediates this novel effect, specific receptor mutations in Trk have been employed. We showed that phosphorylation of tyrosine 490 is required for activation of phosphoinositide 3-OH kinase, whereas phosphorylation of tyrosine 785 is required for activation of phospholipase C-γ. TrkA-mediated apoptosis was abolished when either the ATP-binding site or both tyrosines 490 and 785 were mutated. Because tyrosines 490 and 785 mediate redundant signaling through the Ras-extracellular signal-regulated kinase (Ras-ERK) pathway, we examined the role of Ras-ERK signaling in NGF-induced apoptosis. We found that MED283-TrkA cells expressing a dominant negative Ras inhibitor (N17Ras) failed to undergo ERK activation and apoptosis following NGF treatment, whereas the ERK kinase (mitogen-activated protein kinase kinase) inhibitors PD98059 and U0126 eliminated ERK activation but had no effect on apoptosis. We infer from these data that NGF-induced apoptosis is mediated by a novel Ras and/or Raf signaling pathway.
In Vitro Bypass Replication of the Cisplatin-d(GpG) Lesion by Calf Thymus DNA Polymerase β and Human Immunodeficiency Virus Type I Reverse Transcriptase Is Highly Mutagenic*

Eukaryotic DNA polymerase β and the reverse transcriptases are the most inaccurate of the known DNA polymerases. We report here mutagenic replication in vitro past intrastrand N(7)G-N(7)G chelates of the cis-diamminedichloroplatinum(II), the major DNA adduct of the antitumor agent cisplatin by calf thymus DNA polymerase β and human immunodeficiency virus type I reverse transcriptase (42% and 26% mutations, respectively). The most frequent modifications generated by both enzymes were one-base frameshift deletions. Only one mutational hot spot opposite the platinated guanines was observed with human immunodeficiency virus type I reverse transcriptase, while two hot spots were generated by DNA polymerase β, one at the base situated 5′ to the lesion and the other situated 4–6 nucleotides 5′ to the adduct. An unusual mutagenic event, tandem replication of a 12-base pair sequence, was observed with DNA polymerase β. The mutational spectra of the two DNA polymerases suggest that template slippage occurred with higher frequency in the presence of the more distributive DNA polymerase β.
Odontoblast Function Seen as the Response of Dentinal Tissue to Dental Caries

Microbes are responsible for the initiation and maintaining of carious processes. They have an efficient machinery for dissolving crystalline hydroxyapatite. When initiating carious processes, microbial acid formation determines the rate of the process in enamel. When the process reaches dentin, the micro-environment changes. Dentinal fluid in dentin tubules is the liquid where dissolving products of apatites are destroyed. Inorganic composition of dentinal fluid, however, is not altered much during the carious process, indicating that a functional secretory domain is working to pump the dissolved calcium and phosphate ions out of the fluid. Activation of odontoblast alkaline phosphatase and dentin latent collagenases is the known cellular event during the carious process in dentin. Because the caries lesion is by definition undermining, this suggests that, in this degradation process, the extracellular compartment, crystalline hydroxyapatite is dissolved by microbial acids, and a mixture of proteinases degrades the organic matrix. The degradation products of collagen and other matrix components in dentinal fluid must be transported either through the caries lesion in the enamel to saliva or through the odontoblast to the pulp (active transport). This facilitates further processing of the degradation products intracellularly during the passage through the cell.
Experience of Oral Care among Elderly in Nursing Homes

Life expectancy among the elderly has been improving for decades and edentulousness is constantly decreasing among the senior citizens. The steady decrease of tooth loss among the elderly is a challenge to the dental profession due to the increased demand of oral care. This study aims to explore the perspectives regarding oral health and oral care among the elderly living in nursing homes.Ten subjects from two nursing homes in Umea were interviewed based on a defined interview guide. The interview guide contained open-ended questions regarding oral health and oral care. The subjects were interviewed, all the interviews were recorded and transcribed verbatim. Categories, subcategories and codes were created using qualitative content analysis.Two categories and six subcategories were established based on qualitative content analysis. The two categories revealed opposing attitudes, the first promoted oral care and the second disfavored oral health. The oral care promoted factors included general satisfaction with the elderly’s’ present oral status, positive experiences associated with oral care and strong desire to maintain their own oral hygiene. The most notable negative factors for good oral health was the lack of thorough oral examinations and individually adapted assistance with daily oral hygiene. The informants took oral hygiene as a part of their integrity and expressed wishes to be independent.In general, the informants held positive attitudes toward their current oral status and understood that proper oral care is a prerequisite to good oral health. However, it should be noted that assistance with oral hygiene is not practiced in either of the two nursing homes on a regular basis. This may be attributed to staff shortages and the residents desire to maintain their independence.
Histopathology of human renal allograft rejection under FK 506: a comparison with cyclosporine.

FK 506, a powerful new immunosuppressant, was first used in humans in an attempt to salvage liver and kidney allografts that were failing because of rejection.1 Thereafter, allograft recipients who were experiencing disabling side effects of standard cyclosporine (CyA) and steroid baseline therapy were switched to FK 506 as well.1 The relative safety of the drug then permitted trials of FK 506 as the initial immunosuppressant as maintenance therapy for primary liver allograft recipients.2 Bolstered by the success with liver allografts. FK 506 was tested as primary therapy in recipients of new kidney allografts.3 In our initial report, we detailed the pathologic findings in the earliest recipients of FK 506, most of whom had received liver allografts.4 Comparison of the incidence and histologic features of acute cellular rejection in this group to historic controls maintained on CyA revealed some distinct differences. First, the incidence of acute cellular rejection was less in those treated with FK 506 than in the historic CyA treated controls.4 Second, although the histologic appearance of liver allograft rejection in patients treated with FK 506 was similar to that seen under CyA and steroids,4 central venulitis as part of rejection was more prominent in the former. This report focuses on the histopathology of renal allograft rejection in comparison to contemporaneous CyA/steroid treated controls. Since the initial renal allograft recipients treated with FK 506 were “high risk,” they were not randomly assigned to treatment groups.3 Also, the renal biopsies in this series of patients were performed because of dissatisfaction with the clinical course or uncertainty about the diagnosis. It should be noted that pathology specimens were obtained more often in the CyA treated patients. Therefore, a distinct comparison of the incidence or severity of rejection was not considered valid. We had, however, more simple goals in mind for this initial study. They were (1) to determine if histologic features observed in renal allograft biopsies during episodes of clinically suspected rejection differ in patients with FK 506 compared with those treated with CyA as the baseline immunosuppressant: (2) to determine if histologic features associated with clinical rejection correlate with renal dysfunction as measured by serum creatinine levels: and (3) to determine if classic prognostic features of rejection are valid under this new immunosuppressive agent.
The emerging phenotype of the testicular carcinoma in situ germ cell

This review summarises the existing knowledge on the phenotype of the carcinoma in situ (CIS) cell. CIS is a common pre‐invasive precursor of testicular germ cell tumours of adolescents and young adults. These tumours display a variety of histological forms. Classical seminoma proliferates along the germ cell lineage, whereas embryonal carcinoma retains embryonic features and readily differentiates into teratomas that resemble various somatic cell lineages. A thorough review of the gene expression in CIS cells in comparison to normal testicular germ cells and overt tumours supports the view that CIS is a common precursor for both tumour types. Impaired cell differentiation resulting in a partial retention of the embryonic features, associated with an increasing genomic instability may be responsible for a remarkable phenotypic heterogeneity of CIS cells. Depending on the degree of differentiation and pluripotency, CIS cells found in adult patients seem to be predestined for further malignant progression into one or the other of the two main types of overt tumours. A new concept of phenotypic continuity of differentiation of germ cells along germinal lineage with a gradual loss of embryonic features based on the analysis of gene expression in all types of germ cells during their ontogeny is presented in this review. The data point out that despite the phenotypic continuum of gene expression, there are two periods of rapid changes of gene expression: first at the transition from primordial germ cells to pre‐spermatogonia, and later during the pubertal switch from the mitotic to meiotic cell division. The persistent expression of embryonic traits in CIS cells, and the high expression of the cell cycle regulators that are typical of mitotic germ cells support our long‐standing hypothesis that CIS cells originate from primordial germ cells or gonocytes and not from germ cells in the adult testis.
Leading Clinical Handover Improvement: A Change Strategy to Implement Best Practices in the Acute Care Setting

Objective: Many contemporary acute care facilities lack safe and effective clinical handover practices resulting in patient transitions that are vulnerable to discontinuities in care, medical errors, and adverse patient safety events. This article is intended to supplement existing handover improvement literature by providing practical guidance for leaders and managers who are seeking to improve the safety and the effectiveness of clinical handovers in the acute care setting. Methods: A 4-stage change model has been applied to guide the application of strategies for handover improvement. Change management and quality improvement principles, as well as concepts drawn from safety science and high-reliability organizations, were applied to inform strategies. Results: A model for handover improvement respecting handover complexity is presented. Strategies targeted to stages of change include the following:Enhancing awareness of handover problems and opportunities with the support of strategic directions, accountability, end user involvement, and problem complexity recognition.Identifying solutions by applying and adapting best practices in local contexts.Implementing locally adapted best practices supported by communication, documentation, and training.Institutionalizing practice changes through integration, monitoring, and active dissemination. Finally, continued evaluation at every stage is essential. Conclusions: Although gaps in handover process and function knowledge remain, efforts to improve handover safety and effectiveness are still possible. Continued evaluation is critical in building this understanding and to ensure that practice changes lead to improvements in patient safety, organizational effectiveness, and patient and provider satisfaction. Through handover knowledge building, fundamental changes in handover policies and practices may be possible.
Aggregation of Multiple Reinforcement Learning Algorithms

Reinforcement learning (RL) has been successfully used in many fields. With the increasing complexity of environments and tasks, it is difficult for a single learning algorithm to cope with complicated problems with high performance. This paper proposes a new multiple learning architecture, "Aggregated Multiple Reinforcement Learning System (AMRLS)", which aggregates different RL algorithms in each learning step to make more appropriate sequential decisions than those made by individual learning algorithms. This architecture was tested on a Cart-Pole system. The presented simulation results confirm our prediction and reveal that aggregation not only provides robustness and fault tolerance ability, but also produces more smooth learning curves and needs fewer learning steps than individual learning algorithms.
Postprandial mononuclear NF-kappaB activation is independent of the AGE-content of a single meal.

OBJECTIVE Dietary uptake of Advanced Glycation Endproducts (AGE) is supposed to potentially contribute to inflammatory reactions linked to vascular dysfunction and late diabetic complications. One mechanism by which dietary AGE might exert these effects is by activation of the proinflammatory transcription factor NF-kappa-B. The aim of this study was to analyze the postprandial effects of a casein meal with low or high AGE content on postprandial NF-kappaB activation in peripheral blood mononuclear cells (pBMC) of healthy volunteers. RESEARCH DESIGN AND METHODS Casein was heated for 40 h at 50 degrees C in the presence of sorbitol or glucose, resulting in either minimal (Sorbitol [S]-casein) or large (glucose [G]-casein) amounts of AGE-modified casein. Nine healthy volunteers ate 250 g of both types of casein, whereas both meals were separated at least by 2 weeks. Plasma and pBMC were taken before and 2 h after each meal. Thereafter, the defined AGE carboxymethyllysine (CML) was determined by ELISA and Western blot. NF-kappaB activation in pBMC was assayed using Electrophoretic Mobility Shift Assays (EMSA) and Western blot analysis. RESULTS S-casein contained only minor amounts of CML and no pentosidine, while G-casein contained large amounts of both. 2 h after ingestion, the S-casein or the G-casein-meal, both, resulted in a non-significant increase in plasma CML and in the intracellular CML-content of pBMC. This was paralleled by a highly significant increase in postprandial mononuclear NF-kappaB-binding activity. Remarkably, neither the extent of NF-kappaB induction (178% for S-casein, 188% for G-casein), nor composition of the NF-kappaB heterodimer (mainly consisting of NF-kappaB p50/p65) were significantly different after intake of S-casein or G-casein. Consistently, Western blots confirmed an increased NF-kappaBp65 nuclear translocation and a decrease of NF-kappaBp65 in the cytoplasm, while no difference in postprandial NF-kappaB nuclear translocation was observed following intake of S-casein or G-casein. CONCLUSION Postprandial mononuclear NF-kappaB activation after a single meal is independent of the AGE-content of the ingested protein.
Biogenic Amines in Dairy Products

Biogenic amines (BA) are organic, basic, nitrogenous compounds with biological activity, mainly formed by the decarboxylation of amino acids. BA are present in a wide range of foods, including dairy products, and can accumulate in high concentrations. In some cheeses more than 1000 mg of BA have been detected per kilogram of cheese. The consumption of food containing large amounts of these amines can have toxicological consequences. Although there is no specific legislation regarding the BA content in dairy products, it is generally assumed that they should not be allowed to accumulate. Greater knowledge of the factors involved in the synthesis and accumulation of BA should lead to a reduction in their incidence in foods. This article focuses on the factors that affect BA production, in particular environmental conditions, the microorganisms that produce them, the genetic organization and regulation of the biosynthetic pathways involved, and the available methods for detecting the presence of BA or BA-producing microorganisms in dairy products.
Routes to indirect fitness in cooperatively breeding vertebrates: kin discrimination and limited dispersal

Hamilton demonstrated that the evolution of cooperative behaviour is favoured by high relatedness, which can arise through kin discrimination or limited dispersal (population viscosity). These two processes are likely to operate with limited overlap: kin discrimination is beneficial when variation in relatedness is higher, whereas limited dispersal results in less variable and higher average relatedness, reducing selection for kin discrimination. However, most empirical work on eukaryotes has focused on kin discrimination. To address this bias, we analysed how kin discrimination and limited dispersal interact to shape helping behaviour across cooperatively breeding vertebrates. We show that kin discrimination is greater in species where the: (i) average relatedness in groups is lower and more variable; (ii) effect of helpers on breeders reproductive success is greater; and (iii) probability of helping was measured, rather than the amount of help provided. There was also an interaction between these effects with the correlation between the benefits of helping and kin discrimination being stronger in species with higher variance in relatedness. Overall, our results suggest that kin discrimination provides a route to indirect benefits when relatedness is too variable within groups to favour indiscriminate cooperation.
Human Behavioral Ecology, Phenotypic (Developmental) Plasticity, and Agricultural Origins

The fields of human behavioral ecology (HBE) and evolutionary developmental biology (evo‐devo) both stand to make significant contributions to our understanding of agricultural origins. These two approaches share a concern with phenotypic plasticity and its evolutionary significance. HBE considers the adaptive plasticity of the human phenotype in response to resource distribution in time and space and has helped to advance understanding of the economic costs and benefits of food production. However, evo‐devo and the associated subject of phenotypic (developmental) plasticity have so far been largely neglected as sources of insight into the domestication of plants, despite growing evidence for their evolutionary importance in nature and their roles in the origins of novel traits. We argue that it is important to consider environmentally induced phenotypic variation resulting directly from both natural‐ and human‐induced ecological change as a source of the distinctive morphologies of domesticated plants.