Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of angiogenesis by adhesive and mechanical cues from the extracellular matrix

Angiogenesis, the sprouting of new capillaries from existing blood vessels, is essential for the survival of tissues and normally occurs during development and wound healing. Successful vascularization of engineered tissues is currently a major challenge, as it is critical for the survival and incorporation of implanted tissue replacements. While the role of soluble factors in regulating angiogenesis is well established, there is significant interest in uncovering the contributions of cellular interactions with the extracellular matrix (ECM). We chose to study the role of cell-ECM adhesion in regulating angiogenesis, with the hypothesis that quantitative changes in the degree of cell-ECM adhesion can regulate endothelial cell behaviors important for angiogenesis. We also hypothesized that we could employ our basic knowledge of angiogenesis to develop a synthetic material system to support vascularization for potential applications in tissue engineering. We first examined whether quantitative changes in cell-ECM adhesion regulate angiogenesis and observed increased angiogenic sprouting in three-dimensional fibrin gels with progressively decreasing densities of fibrin. Examining changes in global gene expression, we demonstrated a vascular endothelial growth factor (VEGF)-induced upregulation of genes associated with vascular invasion and remodeling when cell adhesion was limited, whereas cells on highly adhesive surfaces upregulated genes associated with proliferation. We showed that proline-rich tyrosine kinase 2 (Pyk2) regulates both gene expression and endothelial sprouting through its enhanced activation by VEGF in limited adhesion contexts. These results suggest that limited cell adhesion can enhance endothelial responsiveness to VEGF and demonstrate a novel role for Pyk2 in the adhesive regulation of angiogenesis. Finally, we have developed poly(ethylene glycol) (PEG)-based hydrogels that support three-dimensional angiogenic sprouting. By tuning the mechanical, adhesive, and degradable parameters of these wholly synthetic materials, we have begun to identify conditions optimal for vascularization, as well as provided a tool to isolate the effects of single ECM parameters. We have demonstrated control of angiogenic sprouting by the MMP sensitivity of the hydrogels, as well as an interplay between ECM stiffness and adhesive ligand density in regulating sprouting. Together, these studies highlight the importance of cellular interactions with the ECM in regulating angiogenesis and demonstrate a path by which we can apply basic understanding toward vascularization of engineered tissues for tissue regeneration and repair. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Bioengineering This dissertation is available at ScholarlyCommons: http://repository.upenn. edu/edissertations/408 First Advisor Christopher Chen
Object Categorization: The Interface Theory of Perception: Natural Selection Drives True Perception to Swift Extinction

Introduction The jewel beetle Julodimorpha bakewelli is category challenged (Gwynne and Rentz 1983; Gwynne 2003). For the male of the species, spotting instances of the category “desirable female” is a pursuit of enduring interest and, to this end, he scours his environment for telltale signs of a female's shiny, dimpled, yellow-brown elytra (wing cases). Unfortunately for him, many males of the species Homo sapiens , who sojourn in his habitats within the Dongara area of Western Australia, are attracted by instances of the category “full beer bottle” but not by instances of the category “empty beer bottle,” and are therefore prone to toss their emptied bottles (stubbies) unceremoniously from their cars. As it happens, stubbies are shiny, dimpled, and just the right shade of brown to trigger, in the poor beetle, a category error. Male beetles find stubbies irresistible. Forsaking all normal females, they swarm the stubbies, genitalia everted, and doggedly try to copulate despite repeated glassy rebuffs. Compounding misfortune, ants of the species Iridomyrmex discors capitalize on the beetles' category errors; the ants sequester themselves near stubbies, wait for befuddled beetles, and consume them, genitalia first, as they persist in their amorous advances. Categories have consequences. Conflating beetle and bottle led male J. bakewelli into mating mistakes that nudged their species to the brink of extinction.
A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development

Cleft palate is among the most common birth defects in humans. Previous studies have shown that Shh signaling plays critical roles in palate development and regulates expression of several members of the forkhead-box (Fox) family transcription factors, including Foxf1 and Foxf2, in the facial primordia. Although cleft palate has been reported in mice deficient in Foxf2, whether Foxf2 plays an intrinsic role in and how Foxf2 regulates palate development remain to be elucidated. Using Cre/loxP-mediated tissue-specific gene inactivation in mice, we show that Foxf2 is required in the neural crest-derived palatal mesenchyme for normal palatogenesis. We found that Foxf2 mutant embryos exhibit altered patterns of expression of Shh, Ptch1, and Shox2 in the developing palatal shelves. Through RNA-seq analysis, we identified over 150 genes whose expression was significantly up- or down-regulated in the palatal mesenchyme in Foxf2-/- mutant embryos in comparison with control littermates. Whole mount in situ hybridization analysis revealed that the Foxf2 mutant embryos exhibit strikingly corresponding patterns of ectopic Fgf18 expression in the palatal mesenchyme and concomitant loss of Shh expression in the palatal epithelium in specific subdomains of the palatal shelves that correlate with where Foxf2, but not Foxf1, is expressed during normal palatogenesis. Furthermore, tissue specific inactivation of both Foxf1 and Foxf2 in the early neural crest cells resulted in ectopic activation of Fgf18 expression throughout the palatal mesenchyme and dramatic loss of Shh expression throughout the palatal epithelium. Addition of exogenous Fgf18 protein to cultured palatal explants inhibited Shh expression in the palatal epithelium. Together, these data reveal a novel Shh-Foxf-Fgf18-Shh circuit in the palate development molecular network, in which Foxf1 and Foxf2 regulate palatal shelf growth downstream of Shh signaling, at least in part, by repressing Fgf18 expression in the palatal mesenchyme to ensure maintenance of Shh expression in the palatal epithelium.
A Morphological and Syntactic Wide-coverage Lexicon for Spanish: The Leffe

In this paper, we introduce the Lde Formas Flexionadas del Espa˜ (Leffe), a wide-coverage morphological and syntactic Spanish lexicon based on the Alexina lexical framework. We explain how the Leffe has been created by merging together several heterogeneous lexicons and how the Alexina lexical framework has been applied to Spanish. We also introduce a semi-automatic technique based on a tagger to detect the lexicon's deficiencies. A preliminary evaluation shows the potential of the Leffe and the relevance of both creation and extension processes.
Revisiting Hartley's Normalized Eight-Point Algorithm

Hartley's eight-point algorithm has maintained an important place in computer vision, notably as a means of providing an initial value of the fundamental matrix for use in iterative estimation methods. In this paper, a novel explanation is given for the improvement in performance of the eight-point algorithm that results from using normalized data. It is first established that the normalized algorithm acts to minimize a specific cost function. It is then shown that this cost function I! ; statistically better founded than the cost function associated with the nonnormalized algorithm. This augments the original argument that improved performance is due to the better conditioning of a pivotal matrix. Experimental results are given that support the adopted approach. This work continues a wider effort to place a variety of estimation techniques within a coherent framework.
Predicting Structure-Property Relationships in Polymers through the Development of Thermodynamically Consistent Coarse-Grained Molecular Models

Improved knowledge connecting the chemistry, structure, and properties of polymers is necessary to develop advanced materials in a materials-by-design approach. Molecular dynamics (MD) simulations can provide tremendous insight into how the fine details of chemistry, molecular architecture, and microstructure affect many physical properties; however, they face well-known restrictions in their applicable temporal and spatial scales. These limitations have motivated the development of computationally-efficient, coarse-grained methods to investigate how microstructural details affect thermophysical properties. In this dissertation, I summarize my research work in structure-based coarse-graining methods to establish the link between molecular-scale structure and macroscopic properties of two different polymers. Systematically coarse-grained models were developed to study the viscoelastic stress response of polyurea, a copolymer that segregates into rigid and viscous phases, at time scales characteristic of blast and impact loading. With the application of appropriate scaling parameters, the coarse-grained models can predict viscoelastic properties with a speed up of 5-6 orders of magnitude relative to the atomistic MD models. Coarse-grained models of polyethylene were also created to investigate the thermomechanical material response under shock loading. As structure-based coarse-grained methods are generally not transferable to states different from which they were calibrated at, their applicability for modeling non-equilibrium processes such as shock and impact is highly limited. To address this problem, a new model is developed that incorporates many-body interactions and is calibrated across a range of different thermodynamic states using a least square minimization scheme. The new model is validated by comparing shock Hugoniot properties with atomistic and experimental data for polyethylene. Lastly, a high fidelity coarse-grained model of polyethylene was constructed that reproduces the joint-probability distributions of structural vari-
The coagulase of Staphylococcus aureus 8325‐4. Sequence analysis and virulence of site‐specific coagulase‐deficient mutants

The sequence of the coagulase gene (coa) from Staphylococcus aureus strain 8325‐4 is reported. The deduced amino acid sequence of the coagulase protein is compared with previously reported sequences of coagulases from strains 213 and BB. The secreted mature forms of coagulase proteins are composed of three distinct segments: (i) the N‐terminal 150–270 residues, which are c. 50% identical, (ii) a central region with high (>90%) residue identities, and (iii) a C‐terminal region composed of repeated 27‐amino‐acid residue sequences. The variable N‐terminal sequences are probably responsible for antigenic differences among coagulases of different serotype. The region of coagulase which binds to prothrombin and activates it to form staphylothrombin is also located in the N‐terminal half of the protein.
Homophily-Based Link Prediction in The Facebook Online Social Network: A Rough Sets Approach

Abstract Online social networks are highly dynamic and sparse. One of the main problems in analyzing these networks is the problem of predicting the existence of links between users on these networks: the link prediction problem. Many studies have been conducted to predict links using a variety of techniques like the decision tree and the logistic regression approaches. In this work, we will illustrate the use of the rough set theory in predicting links over the Facebook social network based on homophilic features. Other supervised learning algorithms are also employed in our experiments and compared with the rough set classifier, such as naive Bayes, J48 decision tree, support vector machine, logistic regression, and multilayer perceptron neural network. Moreover, we studied the influence of the “common groups” and “common page likes” homophilic features on predicting friendship between users of Facebook, and also studied the effect of using the Jaccard coefficient in measuring the similarity between users’ homophilic attributes compared with using the overlap coefficient. We conducted our experiments on two different datasets obtained from the Facebook online social network, where users in each dataset live within the same geographical region. The results showed that the rough set classifier significantly outperformed the other classifiers in all experiments. The results also demonstrated that the common groups and the common page likes features have a significant influence on predicting the friendship between users of Facebook. Finally, the results revealed that using the overlap coefficient homophilic features provided better results than that of the Jaccard coefficient features.
Development of two-dimensional transition metal dichalcogenides for electronic and optoelectronic applications

xvii Chapter 1: Introduction . 1 1.1 Motivations . 1 1.2 Objectives . 3 1.3 Major contributions of this thesis . 3 1.4 Organisation of the thesis. 5 Chapter 2: Literature review . 6 2.
Cytotoxic effect of rosemary extract on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cell lines

Aim: The present study was conducted to survey the potential cytotoxic influence of freeze-dried aqueous extract of its fruits on gastrointestinal cell lines, namely AGS (human gastric carcinoma) and KYSE30 (human esophageal squamous cell carcinoma. Background: Rosemary (Rosmarinus officinalis) is a wild medicinal plant shown to have anticancer activity. Carnosic and rosmarinic acids are compounds, obtained from it through several extraction methods. Methods: The aqueous extract of the fruits of R.officinalis was freeze-dried, and KYSE30 and AGS cancer cell lines were treated with crude extract. Cytotoxic effect of the extracts on the cell lines was examined using 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assay. Apoptotic cells were detected with ethidium bromide/acridine orange (EB/AO). Cell-cycle distributions were evaluated by flow cytometry. Results: IC50 values were 4.1, 1.8 and 1.3 mg/mL for AGS cell lines after 24, 48 and 72 hours by MTT assay, respectively, and 4.4, 2.1 and 1.1 mg/mL by neutral red assay, respectively. IC50 values for KYSE30 cell lines were 600, 180 and 150 mg/mL after 24, 48 and 72 hours by MTT assay, and 860, 270 and 230 mg/mL by neutral red. EB/AO staining increased in apoptotic cells. After 24 h of treatment at different concentrations, significant increases and decreases in population were shown at G2/M and G1 phases, respectively. Conclusion: The aqueous extract of the fruits of R.officinalis was freeze-dried, and KYSE30 and AGS cancer cell lines were treated with crude extract. Cytotoxic effect of the extracts on the cell lines was examined using 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assay. Apoptotic cells were detected with ethidium bromide/acridine orange (EB/AO). Cell-cycle distributions were evaluated by flow cytometry.
The pharmacogenetics of alcohol use disorder.

BACKGROUND Annually, the use and abuse of alcohol contributes to millions of deaths and billions of dollars in societal costs. To determine the impact of genetic variation on the susceptibility to the disorder and its response to treatment, studies have been conducted to assess the contribution of a variety of candidate genetic variants. These variants, which we review here, were chosen based upon their observed or hypothesized functional relevance to alcohol use disorder (AUD) risk or to the mechanism by which medications used to treat the disorder exert their effects. METHODS This qualitative review examines studies in which candidate polymorphisms were tested as moderator variables to identify pharmacogenetic effects on either the subjective response to alcohol or the outcomes of pharmacotherapy. RESULTS Although findings from these studies provide evidence of a number of clinically relevant pharmacogenetic effects, the literature is limited and there are conflicting findings that require resolution. CONCLUSIONS Pharmacogenetic studies of AUD treatment that use greater methodological rigor and better statistical controls, such as corrections for multiple testing, may help to resolve inconsistent findings. These procedures could also lead to the discovery of more robust and clinically meaningful moderator effects. As the field evolves through methodological standardization and the use of larger study samples, pharmacogenetic research has the potential to inform clinical care by enhancing therapeutic effects and personalizing treatments. These efforts may also provide insights into the mechanisms by which medications reduce heavy drinking or promote abstinence in patients with an AUD.
Evaluating evaluators: a case study in understanding the benefits and pitfalls of multi-evaluator modeling

Emotion perception is a complex process, often measured using stimuli presentation experiments that query evaluators for their perceptual ratings of emotional cues. These evaluations contain large amounts of variability both related and unrelated to the evaluated utterances. One approach to handling this variability is to model emotion perception at the individual level. However, the perceptions of specific users may not adequately capture the emotional acoustic properties of an utterance. This problem can be mitigated by the common technique of averaging evaluations from multiple users. We demonstrate that this averaging procedure improves classification performance when compared to classification results from models created using individualspecific evaluations. We also demonstrate that the performance increases are related to the consistency with which evaluators label data. These results suggest that the acoustic properties of emotional speech are better captured using models formed from averaged evaluations rather than from individual-specific evaluations.
Survey of UK and New Zealand gastroenterologists’ practice regarding dietary advice and food exclusion in irritable bowel syndrome and inflammatory bowel disease

Background This study aimed to assess the dietary advice practice of UK and New Zealand (NZ) adult gastroenterologists in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Methods A questionnaire regarding dietary advice practice was emailed or mailed to all members of the British Society of Gastroenterology (n=983) and the NZ Society of Gastroenterology (n=54). Results 363 questionnaires were returned in the UK (response rate 37%) and 51 in NZ (94%). More respondents gave specific dietary advice to more than 25% of their patients on IBS than IBD (84% vs 27% UK, 90% vs 55% NZ; p=0.001 for both) and gave advice about dietary exclusions to more than 25% of patients on IBS than IBD (61% vs 13% UK, 77% vs 14% NZ; p<0.001 for both). They were most likely to provide dietary advice to patients with small bowel Crohn's disease, difficult to control IBD, diarrhoea predominant IBS and difficult to control IBS. The majority of respondents agreed strongly or a little that dietary exclusion was effective in the treatment of IBS, compared to the minority in IBD (71% vs 39% UK, 84% vs 43% p<0.05 for both). Conclusions UK and NZ gastroenterologists give dietary advice more commonly to IBS than IBD patients. The majority of gastroenterologists have some confidence in the use of dietary exclusion in IBS, the converse is true in IBD. However, the advice given is largely empiric and mostly comprises the exclusion of fibre, dairy and wheat.
Aldose reductase inhibition prevents endotoxin-induced uveitis in rats.

PURPOSE The purpose of the present study was to elucidate the role of the polyol pathway enzyme aldose reductase (AR) in the mediation of ocular inflammation in a rat model of endotoxin-induced uveitis (EIU). METHODS EIU was induced by a subcutaneous injection of 200 microg lipopolysaccharide (LPS) in male Lewis rats treated with the AR inhibitor, zopolrestat (25 mg/kg body weight, intraperitoneally) or its carrier. The rats were killed 24 hours after LPS injection, the eyes were enucleated immediately, and aqueous humor (AqH) was collected. The number of infiltrating cells, protein concentration, and levels of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and prostaglandin E(2) (PGE(2)) in the AqH were determined. Immunohistochemical analysis was performed in paraformaldehyde-fixed eye sections by staining with antibodies against iNOS, COX-2, TNF-alpha, NF-kappaB, and AR. The levels of reactive oxygen species (ROS) in rat eye sections were determined by dihydroethidium (hydroethidine) fluorescence staining. RESULTS In the EIU rat eye AqH, both the number of infiltrating cells and protein concentrations of the inflammatory markers, TNF-alpha, NO, and PGE(2) were significantly higher than in the control rats, and inhibition of AR by zopolrestat suppressed the LPS-induced increases. The LPS-induced increased expression of AR, TNF-alpha, iNOS, and COX-2 proteins in the ciliary body, corneal epithelium, and retinal wall was also significantly inhibited by zopolrestat. Furthermore, AR inhibition prevented the LPS-induced increased levels of ROS and activation of NF-kappaB in the ciliary body, corneal epithelium, and retinal wall of the rat eye. AR inhibition also prevented the LPS-induced activation of NF-kappaB and expression of COX-2 and iNOS in the human monocyte cell line U-937. CONCLUSIONS The results indicate that AR inhibition suppresses the inflammation in EIU by blocking the expression and release of inflammatory markers in ocular tissues, along with the attenuation of NF-kappaB activation. This finding suggests that AR inhibition could be a novel therapeutic target for the treatment of uveitis and associated ocular inflammation.
Sparse Approximate Solutions to Linear Systems

The following problem is considered: given a matrix $A$ in ${\bf R}^{m \times n}$, ($m$ rows and $n$ columns), a vector $b$ in ${\bf R}^m$, and ${\bf \epsilon} > 0$, compute a vector $x$ satisfying $\| Ax - b \|_2 \leq {\bf \epsilon}$ if such exists, such that $x$ has the fewest number of non-zero entries over all such vectors. It is shown that the problem is NP-hard, but that the well-known greedy heuristic is good in that it computes a solution with at most $\left\lceil 18 \mbox{ Opt} ({\bf \epsilon}/2) \|{\bf A}^+\|^2_2 \ln(\|b\|_2/{\bf \epsilon}) \right\rceil$ non-zero entries, where $\mbox{Opt}({\bf \epsilon}/2)$ is the optimum number of nonzero entries at error ${\bf \epsilon}/2$, ${\bf A}$ is the matrix obtained by normalizing each column of $A$ with respect to the $L_2$ norm, and ${\bf A}^+$ is its pseudo-inverse.