Miracle-dz/UniFAR-FTUs huggingface dataset:
Subcellular Compartment and Molecular Subdomain of β-Amyloid Precursor Protein Relevant to the Aβ42-promoting Effects of Alzheimer Mutant Presenilin 2*

Increased production of amyloid β peptides ending at position 42 (Aβ42) is one of the pathogenic phenotypes caused by mutant forms of presenilins (PS) linked to familial Alzheimer's disease. To identify the subcellular compartment(s) in which familial Alzheimer's disease mutant PS2 (mt PS2) affects the γ-cleavage of βAPP to increase Aβ42, we co-expressed the C-terminal 99-amino acid fragment of βAPP (C100) tagged with sorting signals to the endoplasmic reticulum (C100/ER) or to thetrans-Golgi network (C100/TGN) together with mt PS2 in N2a cells. C100/TGN co-transfected with mt PS2 increased levels or ratios of intracellular as well as secreted Aβ42 at similar levels to those with C100 without signals (C100/WT), whereas C100/ER yielded a negligible level of Aβ, which was not affected by co-transfection of mt PS2. To identify the molecular subdomain of βAPP required for the effects of mt PS2, we next co-expressed C100 variously truncated at the C-terminal cytoplasmic domain together with mt PS2. All types of C-terminally truncated C100 variants including that lacking the entire cytoplasmic domain yielded the secreted form of Aβ at levels comparable with those from C100/WT, and co-transfection of mt PS2 increased the secretion of Aβ42. These results suggest that (i) late intracellular compartments including TGN are the major sites in which Aβ42 is produced and up-regulated by mt PS2 and that (ii) the anterior half of C100 lacking the entire cytoplasmic domain is sufficient for the overproduction of Aβ42 caused by mt PS2.
Vascular Endothelial Growth Factor and Blood-Brain Barrier Disruption in Tuberculous Meningitis

Background: Tuberculous meningitis (TBM) is characterized by disruption of the blood-brain barrier (BBB), cerebral edema and increased intracranial pressure (ICP). Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. Aims: To investigate whether in children with TBM disruption of the BBB relates to VEGF production and to assess the effect of corticosteroids on Mycobacterium tuberculosis-induced VEGF production by mononuclear leukocytes. Methods: Blood and CSF samples were collected from 26 children with stage 2–3 TBM and 20 controls. All patients received antituberculous and adjuvant corticosteroid therapy. Children were evaluated by ICP recording, computerized tomography scanning and outcome assessment at 6 months follow-up. BBB disruption was quantified by cerebrospinal fluid (CSF)-serum albumin ratios. VEGF concentrations were measured by enzyme-linked immunosorbent assay. In vitro human monocytic THP-1 cells were stimulated with M. tuberculosis sonicate or culture supernatant, and VEGF production was measured in the presence or absence of corticosteroids. Results: CSF VEGF concentrations were significantly higher in TBM patients than in the controls and correlated with mononuclear cell counts (r = 0.64; P = 0.001) and CSF-serum albumin ratio (r = 0.49; P = 0.015). CSF VEGF did not significantly correlate with elevated ICP. In vitro induction of VEGF production by M. tuberculosis sonicate or culture supernatant could be completely abrogated by corticosteroid treatment. Conclusions: Inflammatory cells secrete VEGF during TBM. CSF VEGF correlates with BBB disruption. Inhibition of VEGF may explain part of the clinical effect of adjuvant corticosteroid therapy in TBM.
Precise image-guided irradiation of small animals: a flexible non-profit platform

Preclinical in vivo studies using small animals are essential to develop new therapeutic options in radiation oncology. Of particular interest are orthotopic tumour models, which better reflect the clinical situation in terms of growth patterns and microenvironmental parameters of the tumour as well as the interplay of tumours with the surrounding normal tissues. Such orthotopic models increase the technical demands and the complexity of preclinical studies as local irradiation with therapeutically relevant doses requires image-guided target localisation and accurate beam application. Moreover, advanced imaging techniques are needed for monitoring treatment outcome. We present a novel small animal image-guided radiation therapy (SAIGRT) system, which allows for precise and accurate, conformal irradiation and x-ray imaging of small animals. High accuracy is achieved by its robust construction, the precise movement of its components and a fast high-resolution flat-panel detector. Field forming and x-ray imaging is accomplished close to the animal resulting in a small penumbra and a high image quality. Feasibility for irradiating orthotopic models has been proven using lung tumour and glioblastoma models in mice. The SAIGRT system provides a flexible, non-profit academic research platform which can be adapted to specific experimental needs and therefore enables systematic preclinical trials in multicentre research networks.
[Treatment of pancreatic pseudocysts].

According to the Atlanta classification an acute pseudocyst is a collection of pancreatic juice enclosed by a wall of fibrous or granulation tissue, which arises as a consequence of acute pancreatitis or pancreatic trauma, whereas a chronic pseudocyst is a collection of pancreatic juice enclosed by a wall of fibrous or granulation tissue, which arises as a consequence of chronic pancreatitis and lack an antecedent episode of acute pancreatitis. It is generally agreed that acute and chronic pseudocysts have a different natural history, though many reports do not differentiate between pseudocysts that complicate acute pancreatitis and those that complicate chronic disease. Observation – “conservative treatment” – of a patient with a pseudocyst is preponderantly based on the knowledge that spontaneous resolution can occur. It must, however, be admitted that there is substantial risk of complications or even death; first of all due to bleeding. There are no randomized studies for the management protocols for pancreatic pseudocysts. Therefore, today we have to rely on best clinical practice, but still certain advice may be given. First of all it is important to differentiate acute from chronic pseudocysts for management, but at the same time not miss cystic neoplasias. Conservative treatment should always be considered the first option (pseudocysts should not be treated just because they are there). However, if intervention is needed, a procedure that is well known should always be considered first. The results of percutaneous or endoscopic drainage are probably more dependent on the experience of the interventionist than the choice of procedure and if surgery is needed, an intern anastomosis can hold sutures not until several weeks (if possible 6 weeks).
Two-qubit correlations revisited: average mutual information, relevant (and useful) observables and an application to remote state preparation

Understanding how correlations can be used for quantum communication protocols is a central goal of quantum information science. While many authors have linked the global measures of correlations such as entanglement or discord to the performance of specific protocols, in general the latter may require only correlations between specific observables. In this work, we first introduce a general measure of correlations for two-qubit states, based on the classical mutual information between local observables. Our measure depends on the state’s purity and the symmetry in the correlation distribution, according to which we provide a classification of maximally mixed marginal states (MMMS). We discuss the complementarity relation between correlations and coherence. By focusing on a simple yet paradigmatic example, i.e. the remote state preparation protocol, we introduce a method to systematically define the proper protocol-tailored measures of the correlations. The method is based on the identification of those correlations that are relevant (useful) for the protocol. On the one hand, the approach allows the role of the symmetry of the correlation distribution to be discussed in determining the efficiency of the protocol, both for MMMS and general two-qubit quantum states, and on the other hand, it allows an optimized protocol for non-MMMS to be devised, which is more efficient with respect to the standard one. Overall, our findings clarify how the key resources in simple communication protocols are the purity of the state used and the symmetry of the correlation distribution.
HIV and marital outcomes: dissolution and remarriage in Kisesa, Tanzania.

Marriage is usually related to HIV as a crucial component of the milieu determining sexual behaviour, with debate focusing on the scenarios in which marriage can either protect against, or increase, risk of infection (e.g. Boerma et al, 2002; Clark, 2004). Yet, while it is self-evident that marital status represents a fundamental component of family and household structure, very little of the literature considering the sociodemographic impacts of HIV/AIDS discusses the effects of the pandemic on unions. Any such effects will be shaped by the contexts of the marriage systems in which they are situated. Marriage in Africa is largely characterized by patriarchy. Females typically marry at a young age, often well below twenty years, to husbands who are considerably older; wives are, for the most part, socio-economically subordinate to (and dependent on) their husbands. Consequently, divorce frequently isolates women from economic and family resources (Gregson et al, 2002). That HIV is likely to be associated with socioeconomic vulnerabilities as a result of widowhood is one obvious relationship with marriage outcomes. If it is also the case that HIV infection is associated with increased probability of divorce/separation, it becomes a matter of concern that women will be affected especially adversely.
Comparison of Gastric Relaxation and Sensory Functions between Functional Dyspepsia and Healthy Subjects Using Novel Drinking-Ultrasonography Test

Background: Functional dyspepsia (FD) is a heterogeneous disease characterized by various upper abdominal symptoms. The major mechanism of FD includes impaired fundic accommodation, delayed gastric emptying and visceral hypersensitivity. We developed a novel drinking-ultrasonography test to combine a drink test with ultrasonography to assess gastric motility and sensory function of FD patients. Method: Subjects were 20 healthy volunteers and 26 successive FD patients according to the Rome III criteria. The subjects ingested 200 ml of water at 2-min intervals 4 times (total 800 ml) through a straw. The maximum cross section of the proximal stomach was visualized before water intake, after each water intake, and 5 and 10 min after the completion of drinking using extracorporeal ultrasonography. Abdominal symptoms were evaluated using the visual analog scale (VAS) a total of 5 times. Results: The mean cross-sectional area of the fornix after 800 ml of water intake was significantly lower in the FD group compared with the control group. In the FD group, marked abdominal symptoms developed immediately after initiation of water intake, and VAS score differed significantly (p <0.01) between the control and FD groups at each time point. Conclusion: We developed the novel drinking-ultrasonography test which revealed abnormalities in gastric accommodation and sensation in patients with FD compared with healthy controls. This approach can be readily performed and allows the simultaneous evaluation of gastric accommodation, emptying and sensation.
Anxiety, depression, and posttraumatic stress in Iranian survivors of chemical warfare.

CONTEXT In the 1980-1988 Iran-Iraq War, extensive use of chemical weapons resulted in high rates of morbidity and mortality. While much is known about the physical consequences of chemical warfare, there is a paucity of information about the long-term effects of chemical attacks on mental health. OBJECTIVE To assess the long-term psychological impact of chemical warfare on a civilian population. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional randomized survey conducted in July 2004 of 153 civilians in 3 towns exposed to warfare in northwestern Iran: Oshnaviyeh (low-intensity conventional warfare), Rabat (high-intensity conventional warfare), and Sardasht (both high-intensity conventional warfare and chemical weapons). MAIN OUTCOME MEASURES Full or partial posttraumatic stress disorder (PTSD) diagnosis, anxiety symptoms, and depressive symptoms were assessed using Farsi versions of the Clinician-Administered PTSD Scale, Hamilton Scale for Anxiety, and Beck Depression Inventory, respectively. RESULTS Overall participation rate was 93%. Respondents had a mean age of 45 years and were all of Kurdish ethnicity. Among individuals exposed to both high-intensity warfare and chemical weapons, prevalence rates for lifetime PTSD, current PTSD, major anxiety symptoms, and severe depressive symptoms were 59%, 33%, 65%, and 41%, respectively. Among the low-intensity warfare group, the corresponding rates were 8%, 2%, 18%, and 6%, respectively, while intermediate rates were found among those exposed to high-intensity warfare but not to chemical weapons (31%, 8%, 26%, and 12%, respectively). Compared with individuals exposed to low-intensity warfare, those exposed to both high-intensity warfare and chemical weapons were at higher risk for lifetime PTSD (odds ratio [OR], 18.6; 95% confidence interval [CI], 5.8-59.4), current PTSD (OR, 27.4; 95% CI, 3.4-218.2), increased anxiety symptoms (OR, 14.6; 95% CI, 6.0-35.6), and increased depressive symptoms (OR, 7.2; 95% CI, 3.3-15.9). Exposure to high-intensity warfare but not to chemical weapons was also significantly associated with lifetime PTSD (OR, 5.4; 95% CI, 1.7-17.6), compared with those in the low-intensity warfare group. Further, compared with individuals exposed to high-intensity warfare alone, those exposed to both high-intensity warfare and chemical weapons were at higher risk for lifetime PTSD (OR, 3.4; 95% CI, 1.5-7.4), current PTSD (OR, 6.2; 95% CI, 2.0-20.1), increased anxiety symptoms (OR, 5.6; 95% CI, 2.5-12.6), and increased depressive symptoms (OR, 3.7; 95% CI, 1.8-7.2). CONCLUSION Exposure to chemical warfare is an extreme traumatic event that has long-lasting adverse consequences on mental health.
Functional Characterization of Core Promoter Elements: the Downstream Core Element Is Recognized by TAF1

ABSTRACT Downstream elements are a newly appreciated class of core promoter elements of RNA polymerase II-transcribed genes. The downstream core element (DCE) was discovered in the human β-globin promoter, and its sequence composition is distinct from that of the downstream promoter element (DPE). We show here that the DCE is a bona fide core promoter element present in a large number of promoters and with high incidence in promoters containing a TATA motif. Database analysis indicates that the DCE is found in diverse promoters, supporting its functional relevance in a variety of promoter contexts. The DCE consists of three subelements, and DCE function is recapitulated in a TFIID-dependent manner. Subelement 3 can function independently of the other two and shows a TFIID requirement as well. UV photo-cross-linking results demonstrate that TAF1/TAFII250 interacts with the DCE subelement DNA in a sequence-dependent manner. These data show that downstream elements consist of at least two types, those of the DPE class and those of the DCE class; they function via different DNA sequences and interact with different transcription activation factors. Finally, these data argue that TFIID is, in fact, a core promoter recognition complex.
Inhibition of Protein Tyrosine Phosphatase 1B Improves IGF-I Receptor Signaling and Protects Against Inflammation-Induced Gliosis in the Retina.

PURPOSE Insulin-like growth factor-I receptor (IGF-IR) signaling mediates retinal growth and survival and its failure may contribute to aggravate diabetic retinopathy (DR). Protein tyrosine phosphatase 1B (PTP1B) negatively modulates IGF-IR signaling, but its involvement in inflammation during DR remains unknown. We investigated whether PTP1B participates in the cross-talk between proinflammatory signaling pathways and IGF-IR-mediated signaling in the retina. METHODS 661W photoreceptors or mouse retinal explants were treated with TNFα, IL6, and IL1β. Insulin-like growth factor-I receptor signaling cascade was evaluated in the absence or presence of PTP1B. db/db mice were used to test a PTP1B inhibitor in retinal gliosis. RESULTS 661W retinal cells and retinal explants responded to IGF-I by inducing IGF-IR tyrosine (13-fold) and Akt phosphorylations (7- and 3-fold for serine 473 and threonine 308, respectively). Cytokines triggered early activation of stress kinases (c-jun [NH2] terminal kinase [JNK] and p38 MAPK), resulting in insulin receptor substrate 1 (IRS1) serine 307 phosphorylation that precedes its degradation. Pretreatment of 661W cells or retinal explants with cytokines upregulated PTP1B protein levels (1.45- and 4.5-fold, respectively), induced IRS1 degradation and decreased IGF-I-mediated IGF-IR/Akt phosphorylation. Silencing or deficiency in PTP1B ameliorated the negative effects of cytokines on IGF-IR signaling. Cytokines increased glial fibrillary acidic protein (GFAP) expression in retinal explants by 4.5-fold, this response being reduced by 2-fold with a PTP1B inhibitor. Protein tyrosine phosphatase 1B protein levels increased by 3-fold in retinas from db/db mice and its inhibition reduced gliosis. CONCLUSIONS Targeting PTP1B might be useful for modulating IGF-I effects in retinal cells during DR.
Towards Better Topic Models For Contemporary Textual Documents Of Social Media

The vast scale information available online is a rich source of collective human knowledge. The major transition from conventional information sources such as books and archives to online sources such as web pages, etc. has introduced the need to categorize, organize and mine the digital corpus since the advent of the internet age. Immense effort has been put into this direction since the last decade or so resulting in a lot of improvement in mining conventional documents. One of the major improvement in better understanding of textual documents has been because of Topic Models such as LDA (Latent Dirichlet Allocation) which are used to learn and highlight abstract predominant topics in the documents. However, more recently, due to advances in technology, new age social media platforms have equipped their users to communicate, network and share knowledge but changed the way information is being generated, propagated and consumed. It has not only affected the means of information sharing but also the characteristics of the documents in terms of their language, style, size and vocabulary. The document size and style pose several challenges to conventional data mining tools to be used to their full potential because they rely on document level word co-occurrences to learn important topics in the corpus. They need larger documents compared to a “typical” social media post. In this thesis, we focus on improving the performance of topic models for contemporary documents and text corpus generated in the form of social media posts. We discuss and propose an improvement to previous efforts in the direction and also introduce a new algorithm, sentence2cluster, which also helps in document categorization and organization. Our first proposition to improve the topic models is an extension of previous efforts, which mainly focuses on prepossessing of the documents in terms of document pooling or aggregation. A popular aggregation scheme is user-based document pooling, where the underlying assumption is that a person has an interest in a limited number of topics, therefore, it is useful to club all his documents into one big document. We extend this approach and propose to aggregate documents not only for a single user but also for users who share similar interests. We use many indicators such as the use of hashtags, communication amongst users, influences, etc. to identify a community of users who can pool their documents to learn a potentially better topic model. This community-based pooling instead of a single user based pooling not only increases the context and document size but also helps highlight niche
Nitrogen Reserve Mobilization during Regrowth of Medicago sativa L. (Relationships between Availability and Regrowth Yield)

An experiment was designed to study the role of N and C reserves on regrowth of the shoots following defoliation of forage species. Starch and N accumulation in root and crown tissue of nonnodulated Medicago sativa L. were modified during regrowth by applying different levels of N and different cutting heights. Plants were obtained with similar crown and root dry weights, but having either low starch and high tissue N or high starch and low tissue N. The plants were then submitted to a second defoliation and supplied with optimal N nutrition, and N flow from reserve was quantified using pulse-chase 15N labeling. Maximum yields following the second regrowth were obtained from those plants having a high tissue N, despite their low level of nonstructural carbohydrate. When N in the roots and crown exceeded 5 mg N plant-1 at the beginning of regrowth, about 68% was translocated to regrowing shoots. Highly significant correlations were also found between the amounts of N available in roots and crown at the beginning of regrowth and (a) the amount of N that was mobilized to new tissues, (b) the amount of N taken up during the regrowth period, and (c) the final shoot yield after 24 d of regrowth. No similar correlations were found for plants that varied in their initial starch content of roots and crown. It is suggested that N reserves were used mainly during the first 10 d after defoliation, and that the resulting aerial growth during this period should be sufficient to restore N2 fixation and/or N uptake to levels equal to those prior to defoliation. These data emphasize (a) the importance of root N reserves in initiating and sustaining new shoot growth, and (b) the need for a re-evaluation of the contribution of C reserves to shoot regrowth.