Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of ABCG 2 in Transport of the Mammalian Lignan Enterolactone and its Secretion into Milk in Abcg 2 Knockout Mice

Lignans are phytoestrogens that are metabolized by the gut microbiota to enterodiol and enterolactone, the main biologically active enterolignans. Substantial interindividual variation in plasma concentration and urinary excretion of enterolignans has been reported, this being determined, at least in part, by the intake of lignan precursors, the gut microbiota, and the host’s phase 2 conjugating enzyme activity. However, the role of ATP-binding cassette (ABC) transporters in the transport and disposition of enterolactone has not been reported so far. Active transport assays using parental and Madin-Darby canine kidney epithelial cells transduced with murine and human ABCG2 showed a significant increase in apically directed translocation of enterolactone in transduced cells, which was confirmed by using the selective ABCG2 inhibitor Ko143. In addition, enterolactone also inhibited transport of the antineoplastic agent mitoxantrone as a model substrate, with inhibition percentages of almost 40% at 200 mM for human ABCG2. Furthermore, the endogenous levels in plasma and milk of enterolactone in wild-type and Abcg2 knockout female mice were analyzed. The milk/ plasma ratio decreased significantly in the Abcg2 phenotype, as compared with the wild-type mouse group (0.46 0.1 as against 6.46 2.6). This paper is the first to report that enterolactone is a transported substrate and therefore most probably a competitive inhibitor of ABCG2, which suggests it has a role in the interindividual variations in the disposition of enterolactone and its secretion into milk. The inhibitory activity identified provides a solid basis for further investigation in possible food-drug interactions.
Behavioral Health Medical Interpreters: Cluster Analysis of Vicarious Traumatization and Posttraumatic Growth

Behavioral Health Medical Interpreters: Cluster Analysis of Vicarious Traumatization and Posttraumatic Growth by Pauline N. Stahlbrodt MA, California Institute of Integral Studies, 1999 BA, Wittenberg University, 1992 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy School of Professional Psychology – Counseling Psychology
Cognitive functions in multiple sclerosis: impact of gray matter integrity

Objectives: Our aim was to investigate the impact of gray matter (GM) integrity on cognitive performance in multiple sclerosis (MS), and its relationship with white matter (WM) integrity and presence of lesions. Methods: Sixty-seven patients with MS and 26 healthy controls underwent voxel-based analysis of diffusion tensor images (DTI) in GM and tract-based spatial statistics (TBSS) from WM to identify the regional correlations between cognitive functions and integrity. Lesion probability mapping (LPM) was generated for correlation analysis with cognition. Multiple linear regression analyses were used to identify the imaging measures associated with cognitive scores. Results: Compared with controls, patients showed abnormal DTI indices in several GM regions and in most WM tracts. Impairment in DTI indices in specific GM regions was associated with worse performance of distinct cognitive functions. Those regions showed anatomical correspondence with cognitively relevant tracts in TBSS and LPM. The combination of regional GM and WM DTI and lesion volume accounted for 36–51% of the variance of memory and attention scores. Regional GM DTI explained less than 5% of that variance. Conclusion: GM and WM integrity of specific networks influences cognitive performance in MS. However, GM damage assessed by DTI only adds a small increment to the explained variance by WM in predicting cognitive functioning.
Biology of colorectal cancer

Colorectal cancer is a serious health problem, a challenge for research, and a model for studying the molecular mechanisms involved in its development. According to its incidence, this pathology manifests itself in three forms: family, hereditary, and most commonly sporadic, apparently not associated with any hereditary or familial factor. For the types having inheritance patterns and a family predisposition, the tumours develop through defined stages ranging from adenomatous lesions to the manifestation of a malignant tumour. It has been established that environmental and hereditary factors contribute to the development of colorectal cancer, as indicated by the accumulation of mutations in oncogenes, genes which suppress and repair DNA, signaling the existence of various pathways through which the appearance of tumours may occur. In the case of the suppressive and mutating tracks, these are characterised by genetic disorders related to the phenotypical changes of the morphological progression sequence in the adenoma/carcinoma. Moreover, alternate pathways through mutation in BRAF and KRAS genes are associated with the progression of polyps to cancer. This review surveys the research done at the cellular and molecular level aimed at finding specific alternative therapeutic targets for fighting colorectal cancer.
Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial.

OBJECTIVE Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.
Membrane-associated STAT3 and PY-STAT3 in the Cytoplasm*

Signal transduction from the plasma membrane to the nucleus by STAT proteins is widely represented as exclusively a soluble cytosolic process. Using cell-fractionation methods, we observed that ∼5% of cytoplasmic STAT3 was constitutively associated with the purified early endosome (EE) fraction in human Hep3B liver cells. By 15-30 min after interleukin-6 (IL-6) treatment, up to two-thirds of cytoplasmic Tyr-phosphorylated STAT3 can be associated with the purified early endosome fraction (Rab-5-, EEA1-, transferrin receptor-, and clathrin-positive fraction). Electron microscopy, immunofluorescence, and detergent dissection approaches confirmed the association of STAT3 and PY-STAT3 with early endosomes. STAT3 was constitutively associated with clathrin heavy chain in membrane and in the 1- to 2-MDa cytosolic complexes. The membrane association was dynamic in that, within 15 min of treatment with the vicinal-thiol cross-linker phenylarsine oxide, there was a dramatic increase in bulk STAT3 association with sedimentable membranes. The functional contribution of PY-STAT3 association with the endocytic pathway was evaluated in transient transfection assays using IL-6-inducible STAT3-reporter-luciferase constructs and selective regulators of this pathway. STAT3-transcriptional activation was inhibited by expression constructs for dominant negative dynamin K44A, epsin 2a, amphiphysin A1, and clathrin light chain but enhanced by that for the active dynamin species MxA. Taken together, these studies emphasize the contribution of the endocytic pathway to productive IL-6/STAT3 signaling.
The Enron Corpus: A New Dataset for Email Classi(cid:12)cation Research

Automated classi(cid:12)cation of email messages into user-speci(cid:12)c folders and information extraction from chronologically ordered email streams have become interesting areas in text learning research. However, the lack of large benchmark collections has been an obstacle for studying the problems and evaluating the solutions. In this paper, we introduce the Enron corpus as a new test bed. We analyze its suitability with respect to email folder prediction, and provide the baseline results of a state-of-the-art classi(cid:12)er (Support Vector Machines) under various conditions, including the cases of using individual sections (From, To, Subject and body) alone as the input to the classi(cid:12)er, and using all the sections in combination with regression weights.
Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells

The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells (APCs), and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells (DCs) and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by DCs. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and APCs and provide foundational information for the rational design of targeted nanovaccines against HIV-1.
A Role of Rab29 in the Integrity of the Trans-Golgi Network and Retrograde Trafficking of Mannose-6-Phosphate Receptor

Rab29 (also referred as Rab7L1) is a novel Rab protein, and is recently demonstrated to regulate phagocytosis and traffic from the Golgi to the lysosome. However, its roles in membrane trafficking have not been investigated extensively. Our results in this study revealed that Rab29 is associated with the trans-Golgi network (TGN), and is essential for maintaining the integrity of the TGN, because inhibition of the activity of Rab29 or depletion of Rab29 resulted in fragmentation of the TGN marked by TGN46. Expression of the dominant negative form Rab29T21N or shRNA-Rab29 also altered the distribution of mannose-6-phosphate receptor (M6PR), and interrupted the retrograde trafficking of M6PR through monitoring the endocytosis of CD8-tagged calcium dependent M6PR (cdM6PR) or calcium independent M6PR (ciM6PR), but without significant effects on the anterograde trafficking of vesicular stomatitis virus G protein (VSV-G). Our results suggest that Rab29 is essential for the integrity of the TGN and participates in the retrograde trafficking of M6PRs.
[Chronic endothelial cell loss of the graft after penetrating keratoplasty: influence of endothelial cell migration from graft to host].

BACKGROUND Chronic endothelial cell loss of the graft is common after penetrating keratoplasty. Some kind of subclinical immunological reaction that is not visible at the slitlamp has been suspected as main cause for this phenomenon. Furthermore, migration of graft endothelial cells towards the host cornea has been discussed to add to this loss in special cases. In this study, 3 homogenous patient groups with similar risk of immunological reactions were examined. Main difference between these groups was the potential of graft endothelial cells to migrate towards the host cornea. PATIENTS AND METHODS Patients with keratoconus without cataract surgery (group I with little migration potential, n = 273), patients with Fuchs endothelial dystrophy without/with cataract surgery (groups IIa/IIb with moderate migration potential, n = 89/n = 165) and patients with bullous keratopathy after cataract surgery (group III with potentially large migration tendency, n = 188) were included in the study. All patients had a first keratoplasty. Patients with glaucoma or further intraocular procedures after keratoplasty were excluded from the study. Clear graft survival and ratio of grafts without immune reactions were estimated according to Kaplan and Meier. Endothelial analysis concerned only patients without immune reactions and with at least 3 postoperative endothelial cell density values of the graft center (76 patients in I, 18 patients in IIa, 41 patients in IIb and 23 patients in III). RESULTS Mean relative loss of endothelial cells per year was 14.0 +/- 19.0 % in group I, 17.0 +/- 19.1 % in group IIa, 20.8 +/- 18.2 % in group IIb and 29.4 +/- 17.6 % in group III (ANOVA, p < 0.01). Five years postoperatively in group I 99 %, in group IIa 98 %, in group IIb 93 % and in group III 69 % of the grafts were centrally clear (log rank test, p < 0.001). In the same period in group I 88 %, in group IIa 86 %, in group IIb 83 % and in group III 81 % of the grafts were free of immune reactions (log rank test, p < 0.05). Reasons for irreversible graft failure were immune reactions (0 in group I; 0 in group IIa; 1 in group IIb; 9 in group III, ), surface disorders (1 in group I; 0 in IIa; 1 in group IIb; 3 in group III) and endothelial failure (0 in group I; 1 in group IIa; 5 in group IIb; 6 in group III) (chi square test, p < 0.01). CONCLUSIONS In patients with bullous keratopathy endothelial cell loss via migration seems to add significantly to the general chronic loss which is suspected to be immunological. Peripheral migration of endothelial cells, therefore, most probably contributes to limited prognosis of patients with bullous keratopathy in terms of clear graft survival. In consequence, corneal grafts for bullous keratopathy should be as large as immunologically tolerable, and endothelial cell density should be as high as possible in order to counteract this special endothelial loss factor.
Home Environment and School Performance among Black Elementary School Children

It is generally acknowledged that children's behavioral development is affected by the environments in which they live. Evidence supporting such a relationship has accumulated across a variety of settings, in a variety of cultures, and across most of the childhood years. Some twenty years ago, we began designing a technique, the HOME Inventory, to assess the quality and quantity of support for behavioral development available to children in their home environments. Since then, the HOME Inventory has been used in a series of investigations involving black and white children. ' The proportion of blacks in these studies has ranged from 50 percent to 100 percent. Evidence from these studies suggests that the specific transactions between parents and child, routine experiences and events in the family, and the objects available in the home are related to a wide array of developmental outcomes (intelligence, language, health and growth, social competence, locus of control, behavior at home and school, and school achievement) in the first seven years of life for both black and white children. Moreover these patterns appear to be affected by an array of factors, including the child's own characteristics, structural features of the family, social support,
Cost of a Ride: The Effects of Densities on Fixed-Guideway Transit Ridership and Capital Costs

The cost of building rail transit facilities in the United States has skyrocketed in recent decades. Sections of Los Angeles’s Red Line subway cost more than $750 million per mile to build and even less pricey light-rail systems can cost more than $200 million per mile. Soaring capital investment costs are today’s biggest deterrent, both political and financial, to constructing new transit infrastructure. It stands to reason that high-cost transit projects need high ridership levels. Without sufficient numbers of riders and the fares they generate, new rail investments will inevitably incur huge deficits. Nor will environmental benefits accrue. Transit only reduces traffic congestion and tailpipe emissions when it draws former motorists – and particularly single-occupant drivers – to trains and buses. A system with few riders and a high price tag is a poor investment compared to a system with many riders and a low price tag. Through the investigation of more than 50 transit investment projects built in the U.S. since 1970, we find a strong correspondence between costs and ridership. As one would expect, capital costs and ridership are positively correlated. Moreover, both ridership and capital costs typically rise with job and population densities. By clustering trip ends near stops, concentrated development tends to average far more transit trips per square mile than less concentrated development. But density often increases construction costs as well – via increased costs for right-of-way acquisitions and building demolitions, more complicated route alignments, utility relocation expenses, and higher labor costs. This symbiotic relationship between density and both ridership and costs begs the question: are there densities that offer the most “bang for the buck” in terms of the number of riders for the investment costs? If so, what minimum densities should municipalities zone for around existing or planned stations in different settings or for different types of investments? These are among the most frequently asked questions in the urban planning field today – questions for which there are surprisingly few good answers or widely accepted benchmarks. This paper aims to help fill this knowledge gap.
The development and maintenance of chronic pain and disability : A process theory

Chronic pain and associated disability are prevalent problems with considerable and widespread impact. Currently, a wealth of aetiological theories exist for these, with each focussing mainly on one small aspect of this complex area. These theories are summarised and discussed. The theories are generally cross-sectional in nature and usually focus solely on the endpoint of chronic pain and disability, rather than the ongoing processes by which chronic pain and disability are developed and maintained. Process theories are lacking in the chronic pain area. This thesis presents a new theory exan:iining the process involved in the development and maintenance of chronic pain and disability. The theory was derived using grounded theory methods. The participants interviewed were all currently suffering from chronic pain associated with a variety of medical diagnoses. The areas examined with respect to this research were wide-ranging, thus leading to the creation of a broad process theory. This theory encompasses much of the existing chronic pain literature in addition to identifying additional areas for examination. It proposes a data-driven micro model theory which examines the development and maintenance of chronic pain and disability at a process level. The theory of development and maintenance of chronic pain and disability identifies background I vulnerability factors which serve to predispose the individuals to develop chronic pain. These factors are based around the core concept of attachment, and continue, in a similar form, to maintain acute and chronic pain and disability. Once individuals experience pain they enter the acute pain phase of the theory. This identifies treatment beliefs and behaviour as important factors to the development of chronic pain. This section of the theory contains a cyclical treatment process. It is influenced by the background I vulnerability factors, particularly attachment style. If acute pain persists for at least six months, the individuals enter the chronic pain section of this theory. This is again a cyclical management process, primarily driven by the individuals' implicit theories about pain management, which were found to be influenced by the core category of attachment style. The concepts identified in this data-driven theory of the development and maintenance of chronic pain and disability are discussed in relation to the current literature. This includes chronic pain and health-related literature, existing chronic pain theories, and where applicable, general literature in the concept areas. Limitations of the study, directions for future research, and clinical implications are then presented.
Secondary victimization and the collective identity of crime victims: a qualitative analysis of Swedish crime news discourse

Abstract This article presents an analysis of how secondary victims of murder—in this context, the parents or close family members of a primary murder victim—are represented in Swedish crime news discourse. The study is based on a discourse analysis of media coverage of secondary victims, and statements made by them, in relation to four highly publicized murder cases during the last two decades. The analysis shows that portrayals of secondary victimization reinforce the conflictual character of victim–offender relationships in the news, but also limit the conditions for talking about the significance of social support, mediation and reconciliation for crime victims. News representations of crime victims become less clearly marked by the characteristics of the ‘ideal’ victim as secondary victims, and persons who are explicitly critical toward the legal system, claim victimhood. Furthermore, the identity of the crime victims’ movement as a collective becomes destabilized when the category of the victim is widened to include individuals whose interests are framed as subjective, rather than related to the needs of other crime victims or the general public. In sum, increased media focus on secondary victims may thus undermine the legitimacy of victim claims in public discourse.