Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Engineering of Hematopoiesis for Targeted IFN-α Delivery Inhibits Breast Cancer Progression

Inhibition of primary and metastatic breast cancer by targeted delivery of interferon-α by tumor-infiltrating monocytes. Toasting Tumor Immunotherapy Tumor immunotherapy is a promising new strategy for cancer treatment but is somewhat limited by the immunosuppressive nature of the tumor microenvironment. Type I interferons (IFNs) have been shown to promote tumor immunity, but systemic toxicity has limited their use. Genetic engineering of hematopoietic stem cells (HSCs) is one way to modulate the immune response in the tumor microenvironment. Now, Escobar et al. attempt to overcome this immunosuppression by introducing IFN-α into tumor-infiltrating macrophages. The authors developed a way to insert an IFN-α transgene into HSCs, but restrict IFN-α expression to differentiated monocytes. They then tested their cells in human hematochimeric mice. HSC engraftment and repopulation is inhibited if IFN-α is expressed in the less differentiated cells. However, here, the HSCs engraft and repopulate NSG mice. What’s more, these cells inhibit tumor progression and experimental metastasis in an autologous model of breast cancer, effectively reprogramming the tumor microenvironment. The immunosuppressive tumor microenvironment represents a major hurdle to cancer therapy. We developed a gene transfer strategy into hematopoietic stem cells (HSCs) to target transgene expression to tumor-infiltrating monocytes/macrophages. Using a combination of transcriptional and microRNA-mediated control, we achieved selective expression of an interferon-α (IFN-α) transgene in differentiated monocytes of human hematochimeric mice. We show that IFN-α transgene expression does not impair engraftment and long-term multilineage repopulation of NSG (NOD/LtSz-scidIL2Rγnull) mice by transplanted human HSCs. By providing a source of human cytokines in the mice, we improved the functional reconstitution of human myeloid, natural killer, and T cell lineages, and achieved enhanced immune-mediated clearance of transplanted human breast tumors when hematopoiesis was engineered for tumor-targeted IFN-α expression. By applying our strategy to mouse breast cancer models, we achieved inhibition of tumor progression and experimental metastases in an autologous setting, likely through enhanced generation of effector T cells and their recruitment to the neoplastic tissues. By forcing IFN-α expression in tumor-infiltrating macrophages, we blunted their innate protumoral activity and reprogrammed the tumor microenvironment toward more effective dendritic cell activation and immune effector cell cytotoxicity. Overall, our studies validate the feasibility, safety, and therapeutic potential of a new cancer gene therapy strategy, and open the way to test this approach as adjuvant therapy in advanced breast cancer patients.
Licorice: A possible anti-inflammatory and anti-ulcer drug

The purpose of this investigation was to study the anti-inflammatory activities of both glycerrhitinic acid (GA) and the aqueous licorice extract (ALE) in comparison with diclofenac sodium (DS) (10 mg/kg), using the carrageenan-induced paw edema model in male albino rats. In addition, the anti-ulcer activities of ALE, famotidine (FT), and a combination of ALE and FT using indomethacin-induced ulceration technique in rat stomach were investigated. Conventional DS tablets containing GA, as well as DS chewable tablets containing either GA or ALE with different tastes were prepared. Also, rapidly disintegrating FT tablets were prepared using direct compression and camphor sublimation methods. ALE or GA produced significant anti-inflammatory activity similar to DS, and when taken concomitantly, there is no possible antagonism. The anti-ulcer activity of licorice was found to be similar to that of FT in indomethacin-induced ulceration technique in rat stomach. Combination therapy of both FT and licorice showed higher anti-ulcer activity than either of them alone. Generally, tablets containing the crosslinked sodium carboxymethyl cellulose (AcDisol) showed more rapidly disintegrating effect than those including Sodium starch glycolate (Primojel). The oral disintegration was very rapid for all the tested formulations. Also, the amount of FT absorbed from the oral cavity was nearly 9 from 10 mg theoretically present in each formula. It could be concluded that both GA and ALE have anti-inflammatory activity comparable with DS. It may be recommended to add ALE to either FT or diclofinac for more effective anti-inflammatory or anti-ulcer formulations, respectively.
Microtubule-organizing centers and cell migration: effect of inhibition of migration and microtubule disruption in endothelial cells

We have previously shown that microtubule-organizing centers (MTOC's) become preferentially oriented towards the leading edge of migrating endothelial cells (EC's) at the margin of an experimentally induced wound made in a confluent EC monolayer. To learn more about the mechanism responsible for the reorientation of MTOC's and to determine whether a similar reorientation takes place when cell migration is inhibited, we incubated the wounded cultures with colcemid (C) and cytochalasin B (CB), which disrupt microtubules (MT's) and microfilaments (MF's), respectively. The results obtained showed that the MTOC reorientation can occur independent of cell migration since MTOC's reoriented preferentially toward the wound edge in the CB- treated cultures, even though forward migration of the EC was inhibited. In addition, the MTOC reorientation is inhibited by C, indicating that it requires an intact system of MT's and/or other intracellular structures whose distribution is dependent on that of MT's.
Social Anxiety, Attributional Style, and Contemporary Dating Practices

Social anxiety is a debilitating condition that affects a significant percentage of the U. S. population. It has been found to have a negative and persistent effect upon academic achievement, employment, mental health, physical health, and social relationships, whether platonic or romantic. Social relationships are of prime importance to young adults who are moving away from home for the first time and establishing their independence and autonomy. Concerns about dating and establishing romantic relationships are particularly salient to these young persons. Past research has established dating frequencies for college students (Klaus, Rersen, & Bellack, 1977), but no current figures are presently available. A poll of male and female students at a private northwest university found that students were dating on average at lower frequencies than was formerly true (M = .46 dates per month) and that their dating propositions were accepted on average approximately 81 % of the time. This study also found that students preferred to initiate romantic relationships with others by proposing casual activities like hanging out, talking, or getting coffee. In additiori, two main definitions of hooking up were endorsed by students: to engage in some sort of physical or sexual contact, or to date or be in an exclusive relationship. This study also investigated whether students who suffered from social anxiety were more or less likely to make romantic invitations or to garner acceptances to their invitations. Independent t-tests established thatthey were about as likely as students low in social anxiety to ask others out on dates and were accepted about as often. Past research established an association between social anxiety and global, stable, and internal attributions, as well as negative expectations about social events (Alfano, Joiner, & Perry, 1994; Ishiyama, 1984; Turner, Beidel, & Larkin, 1986). The present study confirmed these findings and also investigated the association between such attributions and students' ability to make and obtain acceptance to their dating invitations. No significant correlations were found between negative or positive attributions and students' ability to issue romantic invitations. Positive trends were observed, however, linking dating invitations and Composite Positive, Stable Positive, and Global Positive attributions. A negative trend linking dating invitations and Global Negative attributions was also found. In addition, significant associations were found between Composite Positive, Global Positive, and Internal Negative attributions and percentage of acceptance of dating invitations. The data also demonstrated nonsignificant trends linking Composite Negative, Stable Positive, and Internal Positive attributions and acceptance of dating invitations. Degree Type Dissertation
On the recursive largest first algorithm for graph colouring

Abstract We present a reduction from the problem of colouring the vertices of the graph to the maximum independent set problem (MISP) showing that for an n-vertex graph G the sum of the chromatic number of G and the independence number of a graph derived from the complement of G is equal to n. We investigate the applicability of the MISP greedy algorithm to the graph colouring problem. We prove that the well-known Leighton RLF algorithm and an algorithm obtained by modifying the MISP greedy heuristic behave in exactly the same way.
Acute Multiple Sclerosis Lesion: Conversion of Restricted Diffusion Due to Vasogenic Edema

It is widely accepted that acute demyelinating plaques in patients with multiple sclerosis (MS) demonstrate increased apparent diffusion coefficient (ADC) and increased diffusion weighted imaging (DWI) signals on MRI. These imaging characteristics in acute MS lesions have been postulated to be due to peripheral vasogenic edema that typically increases the ADC. This assumption is commonly used to differentiate stroke from MS lesions since acute and subacute stroke lesions demonstrate increased DWI signal with reduced ADC due to acute cytotoxic edema.
Neuroeconomics: a sceptical view

Neuroeconomics has been hailed by its advocates as affording “ground-breaking” insights into human behaviour and significant theoretical advances through conceptual trading with neuroscience. The prospect of the discovery of the proximate causes of behaviour by measuring thoughts, feelings, and hence utility is, according to neuroeconomists, within reach. Thus, neuroeconomics will permit the completion of the work of the Classical School in providing a unified theory of human behaviour, and avoiding the problems of “as if” reasoning in standard economics – so its advocates declare.
Adaptation of the retina to stimulus correlations

Visual scenes in the natural world are highly correlated. To efficiently encode such an environment with a limited dynamic range, the retina ought to reduce correlations to maximize information. On the other hand, some redundancy is needed to combat the effects of noise. Here we ask how the degree of redundancy in retinal output depends on the stimulus ensemble. We find that retinal output preserves correlations in a spatially correlated stimulus but adaptively reduces changes in spatio-temporal input correlations. The latter effect can be explained by stimulus-dependent changes in receptive fields. We also find evidence that horizontal cells in the outer retina enhance changes in output correlations. GABAergic amacrine cells in the inner retina also enhance differences in correlation, albeit to a lesser degree, while gylcinergic amacrine cells have little effect on output correlation. These results suggest that the early visual system is capable of adapting to stimulus correlations to balance the challenges of redundancy and noise. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Neuroscience First Advisor Vijay Balasubramanian
Towards Creative Learning Spaces: Re-thinking the Architecture of Post-Compulsory Education

Introduction 1. Why Re-think Learning Spaces? Part 1: Reviewing our Frames 2. Learning Spaces from an Architectural Perspective 3. Learning Spaces from an Educationalist Perspective 4. Learning Spaces from an Estates Planning Perspective Part 2: Mapping the Terrain 5. Getting Beneath the Surface: Re-thinking Relationships Between Learning and Space 6. On the Ground: Searching for the Student Experience 7. Shaping Learning: (Re)designing the Institution Part 3: Shifting the Boundaries 8. Learning as a Transitional Space 9. Hybrid Spaces and the Impact of New Technologies 10. Creative Learning Spaces: Towards the Porous University?
Stereo electroencephalography–guided radiofrequency thermocoagulation (SEEG‐guided RF‐TC) in drug‐resistant focal epilepsy: Results from a 10‐year experience

Stereo electroencephalography (SEEG)–guided radiofrequency thermocoagulation (SEEG‐guided RF‐TC) has been proposed since 2004 as a possible treatment of some focal drug‐resistant epilepsy. The aim of this study is to provide extensive data about efficacy and safety of SEEG‐guided RF‐TC.
Social Anxiety, Motivation, Self-Disclosure, and Computer-Mediated Friendship

This study aims to investigate the mechanisms of individuals’ social interaction with new and existing friends in the blogosphere. It examines not only the direct association between social anxiety and online friendships but also the mediating effects of motivation and self-disclosure on the relation through path analysis. A total of 385 bloggers recruited online responded to the survey questionnaire. The results showed that compared with low socially anxious individuals, those with high social anxiety tended to make fewer new friends, communicated with fewer existing friends via blogs, and had lower relationship quality with those existing friends, but had higher relationship quality with new friends made through blogs. With regard to mediation, the higher the bloggers’ social anxiety, the more motivated they were to make new friends via blogs and the more intimate information they disclosed on their blogs, both of which were, in turn, associated with more new friends and higher quality of new friendships. Interpretations of the findings and implications for understanding the social use of the Internet, especially the competing social compensation hypothesis and rich-get-richer hypothesis, are discussed.
Novel Loci, Including Those Related to Crohn Disease, Psoriasis, and Inflammation, Identified in a Genome-Wide Association Study of Fibrinogen in 17 686 Women: The Women's Genome Health Study

Background—Fibrinogen is a multifunctional circulating glycoprotein involved in wound healing, thrombosis, platelet aggregation, and inflammation, and elevated levels predict vascular disease. Despite evidence of crucial biological function and moderate heritability, comprehensive analysis of the influence of genetic variation on fibrinogen is not available. Methods and Results—To address this issue, we undertook a genome-wide association study evaluating the potential relationships between 337 343 single-nucleotide polymorphisms (SNPs) and plasma fibrinogen levels among 17 686 apparently healthy women participating in the Women's Genome Health Study. As C-reactive protein is also an inflammatory marker known to predict cardiovascular diseases, we compared the determinants of fibrinogen levels with those of C-reactive protein. Four novel loci were identified, in addition to the fibrinogen gene cluster, which were associated with fibrinogen levels at genome-wide levels of significance (range of probability values from 8.82×10−09 to 8.04×10−39). Two of the loci are related to common chronic inflammatory diseases: the first, at locus 5q31.1 (SLC22A5, SLC22A4, IRF1), lies immediately adjacent to a locus linked to Crohn disease (P value for lead SNP, 1.24×10−12) and the second, at locus 17q25.1 (CD300LF, SLC9A3R1, NAT9), has been associated with psoriasis (P value for lead SNP, 7.72×10−11). A third locus at 1q21.3 (IL6R) lies within the interleukin 6 receptor gene, a critical component of the inflammatory cascade (P value for lead SNP, 1.80×10−11). A novel locus at 2q34 (CPSI) participates in the urea cycle (P=8.82×10−09). The majority of implicated SNPs showed little evidence of dual association with C-reactive protein levels. Conclusions—A genome-wide survey of the human genome identifies novel loci related to common chronic inflammatory diseases as genetic determinants of fibrinogen levels, in addition to loci that relate to the inflammatory cascade, the urea cycle, and the fibrinogen gene cluster.
Identification of Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (sTWEAK) as a Possible Biomarker of Subclinical Atherosclerosis

Objectives—Assessment of vascular risk in asymptomatic patients and the response to medical therapy is a major challenge for prevention of cardiovascular events. Our aim was to identify proteins differentially released by healthy versus atherosclerotic arterial walls, which could be found in plasma and serve as markers of atherosclerosis. Methods and Results—We have analyzed supernatants obtained from cultured human carotid plaques and healthy arteries by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry ProteinChip System. Surface-enhanced laser-desorption/ionization analysis unveiled an 18.4-kDa peak released in lower amount by carotid plaques than normal endarteries. This protein was identified as soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK). To confirm that sTWEAK was the protein of interest, Western blot and enzyme-linked immunosorbent assay were performed. Both techniques confirmed that sTWEAK levels were decreased in carotid plaque supernatants. Subsequent measurement of sTWEAK in plasma showed a reduced concentration in subjects with carotid stenosis (N=30) compared with healthy subjects matched by sex and age (N=28) (P<0.001). Furthermore, in a test population of 106 asymptomatic subjects, we showed that sTWEAK concentrations negatively correlated with the carotid intima-media thickness (r=−0.4; P<0.001), an index of subclinical atherosclerosis. Conclusions—These results suggest that sTWEAK could be a potential biomarker of atherosclerosis.
Robust observers and Pecora-Carroll synchronization with limited information

We study synchronization of nonlinear systems with robustness to disturbances that arise when measurements sent from the master system to the slave system are affected by quantization and time sampling. Viewing the synchronization problem as an observer design problem, we invoke a recently developed theory of nonlinear observers robust to output measurement disturbances and formulate a sufficient condition for robust synchronization. The approach is illustrated by a detailed analysis of the Pecora-Carroll synchronization scheme for the Lorenz system, for which an explicit bound on the synchronization error depending on the quantizer range and sampling period is derived.
Wartime Traumatic Aneurysms: Acute Presentation, Diagnosis, and Multimodal Treatment of 64 Craniocervical Arterial Injuries

OBJECTIVEOperation Iraqi Freedom has resulted in a significant number of closed and penetrating head injuries, and a consequence of both has been the accompanying neurovascular injuries. Here we review the largest reported population of patients with traumatic neurovascular disease and offer our experience with both endovascular and surgical management. METHODSA retrospective analysis of all military casualties returning to the Walter Reed Army Medical Center and the National Naval Medical Center, Bethesda, Maryland, from April 2003 until April 2008 was performed. All patients undergoing diagnostic cerebral angiography during their inpatient stay were included in the study. RESULTSA total of 513 war trauma-related consults were performed from April 2003 to April 2008, resulting in the evaluation of 408 patients with closed and penetrating head injuries. In this population, 279 angiographic studies were performed in 187 patients (25 closed craniocervical injuries, 162 penetrating craniocervical injuries), resulting in the detection of 64 vascular injuries in 48 patients (26.2% of those studied, 34% prevalence). Vascular injuries were characterized by traumatic intracranial aneurysms (TICAs) (n = 31), traumatic extracalvarial aneurysms (TECAs) (n = 19), arterial dissections (n = 11), and arteriovenous fistulae (n = 3). The average TICA size on admission was 4.1 mm, with an observed increase in aneurysm size in 11 cases. In the TICA/TECA group, 24 aneurysms in 23 patients were treated endovascularly with either coiling or stent-assisted coiling, resulting in preservation of the parent artery in 12 of 24 vessels (50%). The injuries in 3 patients in this group progressed despite endovascular treatment and required definitive clip exclusion. Thirteen additional aneurysms in 8 patients were treated surgically, resulting in parent artery preservation in 4 cases (30.8%). Eleven of the 13 remaining TICAs/TECAs resolved spontaneously without treatment. A total of 6 aneurysm ruptures (average size, 8.25 mm) occurred, resulting in 3 deaths. Four of 6 ruptures occurred in TICAs in which the interval size increase was noted angiographically. CONCLUSIONThe management of traumatic vascular injury has evolved with technological advancement and the willingness of the neurosurgeon to intervene. Although open surgical intervention remains a viable solution, endovascular options are available and safe and can effectively temporize a patient while acute sequelae of serious head injury resolve.
International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands

In 2005, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) published a catalog of all of the human gene sequences known or predicted to encode G protein-coupled receptors (GPCRs), excluding sensory receptors. This review updates the list of orphan GPCRs and describes the criteria used by NC-IUPHAR to recommend the pairing of an orphan receptor with its cognate ligand(s). The following recommendations are made for new receptor names based on 11 pairings for class A GPCRs: hydroxycarboxylic acid receptors [HCA1 (GPR81) with lactate, HCA2 (GPR109A) with 3-hydroxybutyric acid, HCA3 (GPR109B) with 3-hydroxyoctanoic acid]; lysophosphatidic acid receptors [LPA4 (GPR23), LPA5 (GPR92), LPA6 (P2Y5)]; free fatty acid receptors [FFA4 (GPR120) with omega-3 fatty acids]; chemerin receptor (CMKLR1; ChemR23) with chemerin; CXCR7 (CMKOR1) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC); succinate receptor (SUCNR1) with succinate; and oxoglutarate receptor [OXGR1 with 2-oxoglutarate]. Pairings are highlighted for an additional 30 receptors in class A where further input is needed from the scientific community to validate these findings. Fifty-seven human class A receptors (excluding pseudogenes) are still considered orphans; information has been provided where there is a significant phenotype in genetically modified animals. In class B, six pairings have been reported by a single publication, with 28 (excluding pseudogenes) still classified as orphans. Seven orphan receptors remain in class C, with one pairing described by a single paper. The objective is to stimulate research into confirming pairings of orphan receptors where there is currently limited information and to identify cognate ligands for the remaining GPCRs. Further information can be found on the IUPHAR Database website (http://www.iuphar-db.org).