Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays

Forkhead box protein A1 (FOXA1) is essential for the growth and differentiation of breast epithelium, and has a favorable outcome in breast cancer (BC). Elevated FOXA1 expression in BC also facilitates hormone responsiveness in estrogen receptor (ESR)-positive BC. However, the interaction between these two pathways is not fully understood. FOXA1 and GATA binding protein 3 (GATA3) along with ESR1 expression are responsible for maintaining a luminal phenotype, thus suggesting the existence of a strong association between them. The present study utilized the Oncomine™ microarray database to identify FOXA1:ESR1 and FOXA1:ESR1:GATA3 co-expression co-regulated genes. Oncomine™ analysis revealed 115 and 79 overlapping genes clusters in FOXA1:ESR1 and FOXA1:ESR1:GATA3 microarrays, respectively. Five ESR1 direct target genes [trefoil factor 1 (TFF1/PS2), B-cell lymphoma 2 (BCL2), seven in absentia homolog 2 (SIAH2), cellular myeloblastosis viral oncogene homolog (CMYB) and progesterone receptor (PGR)] were detected in the co-expression clusters. To further investigate the role of FOXA1 in ESR1-positive cells, MCF7 cells were transfected with a FOXA1 expression plasmid, and it was observed that the direct target genes of ESR1 (PS2, BCL2, SIAH2 and PGR) were significantly regulated upon transfection. Analysis of one of these target genes, PS2, revealed the presence of two FOXA1 binding sites in the vicinity of the estrogen response element (ERE), which was confirmed by binding assays. Under estrogen stimulation, FOXA1 protein was recruited to the FOXA1 site and could also bind to the ERE site (although in minimal amounts) in the PS2 promoter. Co-transfection of FOXA1/ESR1 expression plasmids demonstrated a significantly regulation of the target genes identified in the FOXA1/ESR1 multi-arrays compared with only FOXA1 transfection, which was suggestive of a synergistic effect of ESR1 and FOXA1 on the target genes. In summary, the present study identified novel FOXA1, ESR1 and GATA3 co-expressed genes that may be involved in breast tumorigenesis.
Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200.

PURPOSE Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer. PATIENTS AND METHODS Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity. RESULTS The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting. CONCLUSION The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal.
Classic type of Kaposi's sarcoma and human herpesvirus 8 infection in Xinjiang, China

We report 17 cases of the classic type of Kaposi's sarcoma in Xinjiang, which is located in the north‐western area of China surrounded by Mongolia in the east, Russia in the north and Kazakhstan in the west. Fifteen of the patients were of the Uygur people. All patients were male and did not have acquired immunodeficiency syndrome. Most of the lesions were found in the lower and/or upper extremities, with 16 patients showing multiple lesions. Immunohistochemical examination of the lesions revealed that human herpesvirus 8 (HHV‐8)‐encoded latency‐associated nuclear antigen was expressed in the nuclei of spindle‐shaped tumor cells. HHV‐8 DNA was detected by polymerase chain reaction in all seven cases examined. Phylogenetic tree analysis revealed that DNA sequences of the HHV‐8‐encoded K1 gene in the seven Kaposi's sarcoma cases were classified as subtype C that was common in the Mediterranean, the Middle East and East Asian countries. In addition, using immunofluorescence we investigated the seroprevalence of HHV‐8 in 73 Uygur patients with diseases other than Kaposi's sarcoma. Surprisingly, the serological study revealed that 34 of the patients (46.6%) were positive for antibodies against HHV‐8, suggesting that HHV‐8 infection is widespread in Xinjiang area. The occurrence of the classic type of Kaposi's sarcoma with a high seropositivity rate implies that Xinjiang is the most endemic area for HHV‐8 infection in the world known to date. Considering that Xinjiang is located at the middle point of the Silk Road that used to extend from Rome to China, these data imply that the virus may have been in circulation in this area due to the migration of the people via the Silk Road.
A Two-Step Precoding Scheme for Multi-User Joint Transmission in Coordinated Multi-Point System

Joint transmission (JT) allows multiple base stations (BSs) to serve multiple users (UEs) in the same time and frequency resources, which will causes inter-user interference (IUI). Moreover, different signals from different BSs can't be executed coherent combination directly in non-coherent JT. In this paper, a two-step precoding scheme (TSPS) is proposed to solve these problems. Firstly, an alternating minimization algorithm over the precoders at BSs and the interference subspace matrixes at UEs based on interference alignment (IA) is applied, which can force interference at each UE into the subspace and make each UE observe the interference-free desired signals. Secondly, we use the phase adjustment (PHA) based on QR decomposition to implement the coherent combination of desired signals from different BSs. This paper proves the convergence of alternating minimization algorithm in TSPS. Furthermore, numerical results show TSPS can improve the system performance by the IUI suppression and the signal coherent combination.
Plasmid partition and incompatibility – the focus shifts

The mitotic apparatus that a plasmid uses to ensure its stable inheritance responds to the appearance of an additional copy of the plasmid's centromere by segregating it from the pre‐existing copies: if the new copy arises by replication of the plasmid the result is partition, if it arrives on a different plasmid the result is incompatibility. Incompatibility thus serves as a probe of the partition mechanism. Coupling of distinct plasmids via their shared centromeres to form mixed pairs has been the favoured explanation for centromere‐based incompatibility, because it supports a long‐standing assumption that pairing of plasmid replicas is a prerequisite for their partition into daughter cells. Recent results from molecular genetic and fluorescence microscopy studies challenge this mixed pairing model. Partition incompatibility is seen to result from various processes, including titration, randomized positioning and a form of mixed pairing that is based on co‐activation of the same partition event rather than direct contact between partition complexes. The perspectives thus opened onto the partition mechanism confirm the continuing utility of incompatibility as an approach to understanding bacterial mitosis. The results considered are compatible with the view that direct pairing of plasmids is not essential to plasmid partition.
Bacterial community in copper sulfide ores inoculated and leached with solution from a commercial-scale copper leaching plant

Most copper bioleaching plants operate with a high concentration of sulfate salts caused by the continuous addition of sulfuric acid and the recycling of the leaching solution. Since the bacteria involved in bioleaching have been generally isolated at low sulfate concentrations, the bacterial population in ores leached with the high-sulfate solution (1.25 M) employed in a copper production plant was investigated. The complexity of the original population was assessed by the length pattern of the spacer regions between the 16S and 23S rRNA genes, observed after PCR amplification of the DNA extracted from the leached ore. Six main spacers were distinguished by electrophoretic migration, but they could be further resolved into eight spacers by nucleotide sequence homology. The degree of homology was inferred from the electrophoretic migration of the heteroduplexes formed after hybridization. One of the spacers was indistinguishable from that found in Thiobacillus thiooxidans, four could be related to Thiobacillus ferrooxidans, and three could be related to Leptospirillum ferrooxidans. Only five of the spacers in the original sample could be recovered after culturing in media containing different inorganic energy source. Altogether, the results indicate that the bacteria in the leached ore formed a community composed of at least three species: a fairly homogeneous population of T. thiooxidans strains and two heterogeneous populations of T. ferrooxidans and L. ferrooxidans strains.
Principal component regression models for life prediction of plastic ball grid arrays on copper-core and no-core assemblies

In this paper, principal component regression models (PCR) have been investigated for reliability prediction and part selection of area package architectures under thermo- mechanical loads in conjunction with stepwise regression methods. Package architectures studied include, BGA packages mounted on CU-CORE and NO-CORE printed circuit assemblies in harsh environments. The models have been developed based on thermo-mechanical reliability data acquired on copper-core and no-core assemblies in four different thermal cycling conditions. Solder alloys examined include SnPb and SAC Alloys. The models presented in this paper provide decision guidance for smart selection and substitution to address component obsolescence by perturbing product designs for minimal risk insertion of new packaging technologies. It is conceivable for commercial off the shelf parts to become unavailable during the production-life of a product. Typical Commercial-of-the-Shelf parts are manufactured for a period of two to four years, and IC manufacturing processes are available for five to six years. It is envisioned that the reliability assessment models will enable turn-key evaluation of geometric architecture, material properties, and operating conditions effects on thermo-mechanical reliability. The presented approach enables the evaluation of qualitative parameter interaction effects, which are often ignored in closed-form modeling, have been incorporated in this work. Previously, the feasibility of using multiple linear regression models for reliability prediction has been demonstrated for flex-substrate BGA packages [1, 2], flip-chip packages [3, 4] and ceramic BGA packages [5] Convergence of statistical models with experimental data and finite element models has been demonstrated using a single factor design of experiment study. In addition, the power-law dependencies of individual variables have been correlated with established failure mechanics models. PCR approach uses the potentially important variables from stepwise regression. The statistics models are based on accelerated test data acquired as part of this paper, in harsh environments, while finite-element models are based on damage mechanics and material constitutive behavior. Sensitivity relations for geometry, materials, and architectures based on statistical models, and FEA models have been developed.
Inhibition of Corneal Neovascularization by Genetic Ablation of CCR2

Purpose. To determine if genetic ablation of the chemokine receptor CCR2 (involved in leukocyte and endothelial chemotaxis) inhibits the development of corneal neovascularization. Methods. Wild-type C57BL/6J mice, as well as species-specific counterparts with targeted homozygous disruption of the CCR2, underwent chemical and mechanical denudation of corneal and limbal epithelium. Corneas were harvested 2 weeks after injury. Neovascularization was quantified by CD31 immunostaining. Results. The mean percentages of neovascularized corneal area in control mice and CCR2-deficient mice 2 weeks after denudation were 58.3% and 38.8% (P = 0.047), respectively. Conclusions. Development of corneal neovascularization is inhibited in CCR2-deficient mice.
SYNOVIAL MEMBRANE HISTOPATHOLOGY IN THE DIFFERENTIAL DIAGNOSIS OF RHEUMATOID ARTHRITIS, GOUT, PSEUDOGOUT, SYSTEMIC LUPUS ERYTHEMATOSUS, INFECTIOUS ARTHRITIS AND DEGENERATIVE JOINT DISEASE

The synovial membrane histologic sections from patients with six common rheumatic diseases were reviewed without knowledge of the clinical diagnosis. After histopathologic evaluation, the synovial membrane characteristics were grouped according to the patient's clinical diagnosis, and included 29 patients with rheumatoid arthritis, 13 with systemic lupus erythematosus, 17 with degenerative joint disease, 10 with acute bacterial arthritis, 8 with gout, and 13 with pseudogout. The only specific characteristics identified were bacteria (infectious arthritis), crystals (gout, pseudogout), and lymphoid follicles (rheumatoid arthritis). Nevertheless, other characteristic features of differential diagnostic utility were recognized, including the intensity and nature of synovial lining cell hyperplasia and of leukocyte infiltration. Light microscopic histopathologic changes in the common rheumatic diseases are not specific, but are of diagnostic utility. Complete and exhaustive review of each pathologic synovial membrane characteristic provides more justification for the routine use of synovial membrane biopsy as an adjunct to arthrocentesis in the evaluation of common rheumatic diseases.
Decreased levels of stem cell factor in subjects with incident coronary events

It has been proposed that vascular progenitor cells play an important role in vascular repair, but their possible clinical importance in cardiovascular disease has not been fully characterized. Vascular endothelial growth factor A, placental growth factor and stem cell factor (SCF) are three growth factors that are important in recruiting vascular progenitor cells. In this study, we investigated the association between the plasma levels of these growth factors and incident coronary events (CEs).
Chronotropic and inotropic effects of terikalant on isolated, blood‐perfused atrial and ventricular preparations of dogs

Summary— We investigated the effects of terikalant, which blocks inward rectifier K+ current, on the sinus rate, atrial and ventricular contractile force in the isolated, blood‐perfused right atrial and left ventricular preparations of dogs, and the effects of terikalant on the negative cardiac responses to acetylcholine, adenosine or pinacidil (an ATP‐sensitive K+ channel opener) and on the positive cardiac responses to norepinephrine. Terikalant (1–100 nmol) decreased sinus rate and briefly and slightly increased atrial contractile force in isolated atria. However, terikalant did not increase ventricular contractile force in isolated ventricles. Neither propranolol nor atropine inhibited the positive inotropic and negative chronotropic responses to terikalant, respectively. Terikalant (10 or 30 nmol) did not significantly affect the negative cardiac responses to acetylcholine, adenosine nor pinacidil and the positive responses to norepinephrine. These results suggest that terikalant decreases sinus rate with a small changes in myocardial contractile force and does not affect the cardiac responses to muscarinic and adenosine receptor agonists, ATP‐sensitive K+ channel openers nor β‐adrenoceptor agonists in the dog heart.
Cell-free sorting of peroxisomal membrane proteins from the endoplasmic reticulum

Several yeast and mammalian peroxisomal membrane proteins (PMPs) are delivered to peroxisomes via the endoplasmic reticulum (ER). Fluorescence microscopy showed a focused assembly of PMPs in a specialized domain of the ER, referred to as the preperoxisomal ER. It is proposed that preperoxisomal vesicles containing PMPs bud from this domain to either fuse with preexisting peroxisomes or to mature into functional peroxisomes by uptake of peroxisomal membrane and matrix proteins. However, such vesicular entities are not identified nor are the biochemical requirements for the budding process known. We developed an in vitro cell-free ER-budding assay using Pichia pastoris and followed two endogenous PMPs, Pex11p and Pex3p during their ER exit. Both the PMPs were copackaged in the ER-budded vesicles that float on a Nycodenz gradient. PMP budding from the ER was dependent on ATP, temperature, cytosol, and Pex19p and generated preperoxisomal vesicles with an incomplete complement of PMPs. Surprisingly, Pex11p budding was independent of Pex3p; however, the budded vesicles were devoid of most of the PMPs otherwise present in the wild-type vesicles and might represent peroxisomal remnants. Our findings provide a biochemical platform to uncover the mechanism of PMP budding from the ER.
Causes of macrocytosis in HIV-infected patients not treated with zidovudine. Swiss HIV Cohort Study.

OBJECTIVE Zidovudine is a well known cause of macrocytosis. However, many HIV-infected patients develop macrocytosis even though they do not receive zidovudine. The aim of this case-control study was to evaluate other causes of high mean corpuscular volumes (MCV) in HIV infected patients. METHODS Thirty patients with a MCV > or = 100 fl (cases) were compared to 60 randomly selected controls with MCV A< or = 99 fl, none of them receiving zidovudine. RESULTS Sex ratio, age, mean CD4, prevalence of alcohol abuse and liver disease were similar in both groups. Vitamin B12 or folic acid levels were not decreased in patients with macrocytosis. In contrast, there was an association between macrocytosis and use of stavudine alone or in combination with another antiviral drug (28/30 cases, 15/60 controls, odds ratio 40.6 (95% confidence interval 5.1-325.2), P< 0.001). The haemoglobin concentration among cases (mean 13.5 g/dl) was similar to that of controls (mean 13.0 g/dl). CONCLUSIONS Stavudine use increase the risk of macrocytosis more than 40-fold in HIV-infected patients who do not receive zidovudine. None of the stavudine-treated patients, however, developed anaemia or had to interrupt treatment because of this side effect.
GENETICS OF INTRACRANIAL ANEURYSMS

DESPITE ADVANCES IN the treatment of intracranial aneurysms (IA) in recent years, the overall outcome of patients with aneurysmal subarachnoid hemorrhage has shown only modest improvement. Given this poor prognosis, diagnosis of IA before rupture is of paramount importance. Currently, there are no reliable methods other than screening imaging studies of high-risk individuals to diagnose asymptomatic patients. Multiple levels of evidence suggest that environmental factors acting in concert with genetic susceptibilities lead to the formation, growth, and rupture of aneurysms in these patients. Epidemiological studies have already identified aneurysm-specific risk factors such as size and location, as well as patient-specific risk factors, such as age, sex, and presence of medical comorbidities, such as hypertension. In addition, exposure to certain environmental factors such as smoking have been shown to be important in the formation of IA. Furthermore, substantial evidence proves that certain loci contribute genetically to IA pathogenesis. Genome-wide linkage studies using relative pairs or rare families that are affected with the Mendelian forms of IA have already shown genetic heterogeneity of IA, suggesting that multiple genes, alone or in combination, are important in the disease pathophysiology. The linkage results, along with association studies, will ultimately lead to the identification of IA susceptibility genes. Identification of the genes important in IA pathogenesis will not only provide novel insights into the primary determinants of IA, but will also result in new opportunities for early diagnosis in the preclinical setting. Ultimately, novel therapeutic strategies based on biology will be developed, which will target these newly elucidated genetic susceptibilities.
Inhibitory effects of intestinal mucus on bacterial adherence to cultured intestinal epithelial cells after surface burns.

OBJECTIVE To investigate the relationship between intestinal mucus IgA content and mucus barrier function after surface burns. METHODS Detection of IgA content in mucus was performed by enzyme linked immunosorbent assay (ELISA) at different time points after burns. Bacterial adherence to cultured epithelial cells (IEC-6) in vitro using E. coli was assessed for each group. RESULTS The intestinal mucus barrier function declined, parallel to a decrease in IgA content after surface burn in mice. In the normal control group, mucus IgA content was 2.32 D lambda, and 2.51, 1.76, 1.49, 1.06 D lambda at 0.5 h, 1 h, 6 h and 24 h after burn, respectively. Bacterial adherence rate was 0.53 in control group, and 0.46, 0.69, 0.58, 0.81 at 0.5 h, 1 h, 6 h, 24 h after burn, respectively. CONCLUSION The decrease of intestinal mucus IgA contents is one of the reasons why intestinal mucus barrier function declines after burns.
Longitudinal study of blood pressure and white matter hyperintensities

Objective: To investigate the relationship between baseline hypertension and severity of white matter hyperintensities (WMH) at 4-year follow-up in a sample of subjects aged 59 to 71 years old at entry. Methods: Subjects were participants in the Epidemiology of Vascular Ageing study, a longitudinal study on vascular aging and cognitive decline. At 4-year follow-up, 845 subjects had a cerebral MRI. MRI examinations were read by a single rater to determine the severity of WMH, ranging from absent to severe. Hypertension at each wave of the study was defined as systolic blood pressure ≥160 mm Hg, diastolic blood pressure ≥95 mm Hg, or use of antihypertensive medication. Results: Hypertension at baseline was significantly associated with an increased risk of having severe WMH at 4-year follow-up. When taking into account both blood pressure levels and antihypertensive drug intake, analysis showed that the risk of having severe WMH was significantly reduced in subjects with normal blood pressure taking antihypertensive medication compared with those with high blood pressure taking antihypertensive agents. Cross-sectional relationships between hypertension and WMH at 4-year follow-up showed that the frequency of severe WMH was significantly higher in people who were hypertensive at both baseline and 4-year follow-up than those who were hypertensive only at 4-year follow-up. Conclusions: Hypertension is a major risk factor for severe WMH. Subjects taking antihypertensive drugs and who have controlled blood pressure had a reduced risk of severe WMH. Longitudinal studies are needed to investigate whether reduction of the development of WMH, by treatment and prevention of hypertension, might reduce the subsequent risk of cognitive deterioration or stroke.