Miracle-dz/UniFAR-FTUs huggingface dataset:
Monitoring the intracellular store Ca2+ concentration in agonist‐stimulated, intact human platelets by using Fluo‐5N

Summary. Background: Most Ca2+ signaling research in platelets has relied solely on monitoring the cytosolic Ca2+ concentration ([Ca2+]cyt). Changes in [Ca2+]cyt constitute the net effect of Ca2+ fluxes into the cytosol across the plasma membrane (PM) and from intracellular stores, and Ca2+ sequestration into the stores and Ca2+ removal across the PM. This makes interpretation of the effects of pharmacologic or genetic interventions on Ca2+ signaling difficult and subject to error. Objectives: To validate the use of the low‐affinity Ca2+ indicator Fluo‐5N to monitor the concentration of Ca2+ in the intracellular stores ([Ca2+]st) of human platelets as a first step in developing assays for a systems‐level analysis of platelet Ca2+ signaling. Methods: Fluo‐5N‐loaded and Fura‐2‐loaded human platelets were used to observe the effects of agonist stimulation and other manipulations on [Ca2+]cyt and [Ca2+]st. Results: Fluo‐5N fluorescence changed appropriately in response to compounds that induce passive depletion of intracellular Ca2+ stores and to physiologic agonists. Ca2+ reuptake inhibitors and blockers of Ca2+ release channels had the expected effects on Fura‐2 and Fluo‐5N fluorescence. Agonist‐evoked Ca2+ release was reversed by Ca2+ addition to the medium, and required intact Ca2+ reuptake mechanisms. Store refilling was observed in the presence of sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase (SERCA) inhibitors and ionomycin, suggesting the presence of a non‐SERCA Ca2+ reuptake mechanism. Evidence for a role for Ca2+‐induced Ca2+ release in agonist‐evoked responses was obtained. Conclusions: Our data provide a validation of the use of Fluo‐5N as a method for monitoring changes in [Ca2+]st in human platelets.
rpoS regulation of acid, heat, and salt tolerance in Escherichia coli O157:H7

An rpoS mutant (rpoS::pRR10) of Escherichia coli O157:H7 ATCC 43895 was generated. Stationary-phase acid, heat, and salt tolerance was significantly reduced, and starvation-induced acid tolerance did not develop in the mutant. RpoS was also important for survival of E. coli O157:H7 in dry, fermented sausage.
Risk factors for intracerebral hemorrhage differ according to hemorrhage location

ABSTRACT Objectives: Risk factors have been described for spontaneous intracerebral hemorrhage (ICH); their relative contribution to lobar vs nonlobar hemorrhage location is less clear. Our purpose here was to investigate risk factors by hemorrhage location. Methods: This case-control study prospectively enrolled subjects with first-ever spontaneous ICH and matched each with up to 3 controls by age, race, and gender. Conditional stepwise logistic regression modeling was used to determine significant independent risk factors for lobar and nonlobar ICH. Results: From December 1997 through December 2006, 597 cases and 1,548 controls qualified for the analysis. Hypertension, warfarin use, first-degree relative with ICH, personal history of ischemic stroke, less than a high school education, and APOE ε2 or ε4 genotype were more common in ICH cases. Hypercholesterolemia and moderate alcohol consumption (≤2 drinks per day) were less common in ICH cases. The associations of hypertension and hypercholesterolemia were specific for nonlobar ICH. Conversely, the association of APOE ε2 or ε4 genotype was specific for lobar ICH. Conclusions: APOE ε2 or ε4 genotype was associated specifically with lobar ICH. Hypertension was associated specifically with nonlobar ICH. A protective association was seen between hypercholesterolemia and nonlobar ICH; no such association was identified for lobar ICH.
Intravenous infection of mice with Naegleria fowleri.

Naegleria fowleri produced fatal meningoencephalitis in mice following intravenous (i.v.) inoculation. Amebae were present in the peripheral circulation for 120 minutes after i.v. inoculation with a dose of 10(7) trophozoites per mouse. Amebae were cultured from and observed in brain (days 1-21), lung (days 1-12), and liver and kidney (days 1-5). Infected mice exhibited weight loss, leukocytosis, reduced lymphocyte/neutrophil ratio, neurologic symptoms, and mortality. Histologically, the disease was characterized by an acute, hemorrhagic, necrotizing meningoencephalitis. Although amebae were detected in tissues other than brain, pathologic involvement of these tissues was minimal.
The influence of payer mix on electronic prescribing by physicians

Background: Limited studies have examined electronic prescribing (e-prescribing) adoption in physician office practices. Specifically, none have explored the influence of payer mix on e-prescribing adoption among physicians. Purpose: This study examines the impact of practice composition of Medicare, Medicaid, and private insurance on e-prescribing adoption among physicians. Methodology/Approach: Logistic regression was used to analyze data collected from a large-scale information technology-related survey of Florida physicians. Findings: After controlling for practice and physician characteristics, physicians with the highest (odds ratio = 1.67, 95% confidence interval = 1.01-2.78) and above-average (odds ratio [OR] = 1.83, 95% confidence interval = 1.04-3.22) volume of Medicare patients were significantly more likely to e-prescribe as compared with those in the low-volume category. No differences in adoption were found across all Medicaid and private insurance practice composition categories. Practice Implications: Our findings support the notion that direct incentives, such as those in the Medicare Modernization Act of 2003, may influence physician adoption of e-prescribing.
Low incidence of acute graft-versus-host disease, using unrelated HLA-A-, HLA-B-, and HLA-DR-compatible donors and conditioning, including anti-T-cell antibodies.

BACKGROUND Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD). METHODS HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n=43), acute lymphoblastic leukemia (n=29), acute myeloid leukemia (n=27), myelodysplastic syndrome (n=4), lymphoma (n=3), myeloma (n=1), myelofibrosis (n=1), severe aplastic anemia (n=12), and metabolic disorders (n=12). The median age was 25 years (range 1-55 years). HLA class I was typed serologically, and class II was typed by polymerase chain reaction using sequence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate combined with cyclosporine. RESULTS Engraftment was seen in 127 of 132 patients (96%). Bacteremia occurred in 47%, cytomegalovirus (CMV) infection in 49%, and CMV disease in 8%. The cumulative incidences of acute GVHD > or = grade II and of chronic GVHD were 23% and 50%, respectively. The 5-year transplant-related mortality rate was 39%. The overall 5-year patient survival rate was 49%; in patients with metabolic disorders and severe aplastic anemia, it was 61% and 48%, respectively. The disease-free survival rate was 47% in patients with hematological malignancies in first remission or first chronic phase and 38% in patients with more advanced disease (P=0.04). Acute GVHD was associated with early engraftment of white blood count (P=0.02). Poor outcome in multivariate analysis was associated with acute myeloid leukemia (P=0.01) and CMV disease (P=0.04). CONCLUSION Using HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow and immunosuppression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable.
Atypical Erythema Toxicum Neonatorum of Delayed Onset in a Term Infant

We describe a 10‐day‐old term infant who presented to the emergency room with an acute pustular eruption. Laboratory tests and clinical outcome confirmed the diagnosis of erythema toxicum neonatorum. A full septic workup was performed and all cultures were negative. Wright‐stained smear of pustular contents showed a predominance of neutrophils with 10% eosinophils. The white blood cell count was 19,000/mm3 with 10% eosinophils. The eruption resolved spontaneously at 15 days of age leaving no sequelae. This is the first fully documented case of erythema toxicum in a term infant occurring as late as 10 days of age. When erythema toxicum presents in an atypical fashion, diagnostic tests are important to exclude other causes of pustular dermatoses of the neonate.
Melatonin and hormonal changes in disturbed sleep during late pregnancy

Abstract: Although sleep disturbance is commonly reported in pregnancy, there have been surprisingly few studies on the etiology of this condition. Since most hormones show circadian rhythmicity and maintain specific phase relationships with that of the sleep‐wake cycle, it was of interest to establish whether sleep disturbances covaried with endocrine changes. This overnight study of pregnant women compared melatonin, cortisol, and prolactin secretion rhythms in six good sleepers and six poor sleepers. The groups were compared by ratios of the areas under the various hormonal curves. Significant differences in the cortisol/melatonin ratio were found between the poor sleeper group (lower values) and the good sleeper group (higher values). Nonsignificant trends, which might be expected to become significant with larger sample sizes, were found for decreased amplitude in the cortisol rhythm and increased amplitude in the melatonin rhythm in poor sleepers. The decreased amplitude of the cortisol rhythm in poor sleepers appeared to be due to a suppression of the early morning (0500–0800) rise. Prolactin levels were high and showed no rhythmicity in both groups. These differences may reflect changes in the circadian pacemaker system of poor sleepers, with increases in melatonin release being a response to counteract poor sleep.
Thyroid hormones and TSH, prolactin and LH responses to repeated TRH and LRH injections in depressed patients

Twelve patients with unipolar depressive disorders received 600 μg of synthetic TRH or LRH, in a random order, for 3 days each. Placebo injections were given as two 3‐day courses prior to and between the active treatments. Serum TSH, prolactin (Prl) and LH were measured by radioimmunoassays prior to the experiment as well as immediately before and 20 min after each injection. Serum T4 and T3 were determined by radioimmunoassays before the treatments and 24 h after the first two TRH injections.
Intracranial carotid artery atherosclerosis and the risk of stroke in whites: the Rotterdam Study.

IMPORTANCE Intracranial atherosclerosis represents a relatively unexplored, but potentially important, cause of stroke in a white population. OBJECTIVE To investigate the relationship between intracranial carotid artery calcification (ICAC) as a marker of intracranial atherosclerosis and the risk of stroke in whites. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort study in the general community with 6 years of follow-up was conducted (the Rotterdam Study). Between 2003 and 2006, a random sample of 2323 stroke-free persons (mean age, 69.5 years) underwent computed tomography scanning to quantify ICAC volume. All participants were continuously monitored for the occurrence of stroke until January 1, 2012. EXPOSURE Atherosclerotic calcification in the intracranial internal carotid arteries. MAIN OUTCOME AND MEASURE Incident stroke. RESULTS During 14,055 person-years of follow-up, 91 participants had a stroke, of which 74 were ischemic. Larger ICAC volume was related to a higher risk of stroke, independent of cardiovascular risk factors, ultrasound carotid plaque score, and calcification in other vessels (fully adjusted hazard ratio per an increase of 1 SD in ICAC volume, 1.43 [95% CI, 1.04-1.96]). Intracranial carotid artery calcification contributed to 75% of all strokes; for aortic arch and extracranial carotid artery calcification this incidence was only 45% and 25%, respectively. CONCLUSIONS AND RELEVANCE Our findings establish intracranial atherosclerosis as a major risk factor for stroke in the general white population and suggest that its contribution to the proportion of all strokes may be greater than that of large-artery atherosclerosis in more proximally located vessel beds.
Modernizing the Tree of Life

A few enterprising researchers are using the tactics of big science to come up with ways to simplify and speed up the assessment of biodiversity. Others have pushed their colleagues into new ways of thinking about creating phylogenies, as they build ever-larger trees on their way to the one grand tree of life--a goal once considered unreachable.
Comparison of Corneal Thickness with Online Optical Coherence Pachymetry and Ultrasound Pachymeter

Purpose: To evaluate the accuracy of the intraoperative online optical coherence pachymetry (OCP) during LASIK surgery and assess its value during laser ablation. Setting: International Eye Hospital, Cairo, Egypt Methods: A prospective comparative study of 78 patients (156 eyes) with mild to moderate myopic/myopic astigmatic refractive error who underwent LASIK with Schwind Amaris Excimer Laser system equipped with optical coherence pachymetry (OCP). Preoperative, preand postablation stromal beds were measured with ultrasound pachymetry and optical coherence pachymetry. Only the Moria M2 microkeratome was used, and the flap thickness and actual ablation depth were calculated. Results: The preoperative measurements taken with the non-contact OCP were significantly lower than that with the contact ultrasound pachymeter, while there was a good correlation between them in the preablation stromal bed and postablation stromal bed thicknesses. The calculated ablation depth by both techniques also matched the assumed maximum ablation depth calculated preoperatively with Schwind-CAM software.Conclusion: Intraoperative online optical coherence pachymetry may be considered a useful tool to assess the flap thickness and the residual stromal bed during LASIK surgery. [Rany E. Mitwally, M. Tarek El-Naggar, FRCS, Mohamed A. Marzouk. Comparison of Corneal Thickness with Online Optical Coherence Pachymetry and Ultrasound Pachymeter. Life Science Journal. 2011;8(2):791-795] (ISSN:1097-8135). http://www.lifesciencesite. com.
Beam-based HOM Study in Third Harmonic SC Cavities for Beam Alignment at FLASH

An electron beam entering an accelerator cavity excites higher order modes (HOM). These are radiated to HOM couplers and subsequently damped. They can also be used to facilitate beam position monitoring. The modes excited by off-axis beams are the focus of this study. Results are presented on the first analysis of HOM dependency on the beam position for the third harmonic cavities at FLASH. The analysis is based on the beampipe and cavity dipole modes. Various analysis methods are used and compared to satisfy the needs emerging from the characteristics of those modes. The electric center of each mode is observed by looking for the minima of the HOM signals of different beam positions. A single electron bunch per RF pulse is used.
Immunolocalization and Cell Expression of Lung Resistance-related Protein (LRP) in Normal and Tumoral Human Respiratory Cells

Lung resistance-related protein (LRP) is an integral part of the multidrug resistance (MDR) phenotype involved in cell resistance toward xenobiotics or chemotherapy. The aim of this study was to compare the intracellular localization and cell expression of LRP in normal bronchial cells and their tumoral counterparts from non-small cell lung cancer (NSCLC). LRP expression was also investigated concurrently with DNA ploidy and chromosome 16 (lrp gene locus) aberrations. Confocal microscopy showed that LRP localization was exclusively intracytoplasmic regardless of the cell type and was never observed in the nuclear pore complex. Flow cytometry demonstrated a similar level of LRP expression in normal bronchial cells and in cancer cells from NSCLC samples. FISH analysis, performed to evaluate the number of chromosome 16 and lrp loci, demonstrated a significant gain of chromosome 16 in DNA aneuploid tumors. Furthermore, we did not find any link between LRP expression and DNA ploidy status or chromosome 16 number. These results suggest that LRP expression observed in NSCLC, maintained through the carcinogenesis process of respiratory cells, is not altered by the increased number of copies of chromosome 16 and probably controlled by mechanisms different from those of MRP1 expression, whereas both proteins are associated with the MDR phenotype. (J Histochem Cytochem 55: 773–782, 2007)
Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2.

The principal alpha subunit of voltage-gated sodium channels is associated with auxiliary beta subunits that modify channel function and mediate protein-protein interactions. We have identified a new beta subunit termed beta4. Like the beta1-beta3 subunits, beta4 contains a cleaved signal sequence, an extracellular Ig-like fold, a transmembrane segment, and a short intracellular C-terminal tail. Using TaqMan reverse transcription-PCR analysis, in situ hybridization, and immunocytochemistry, we show that beta4 is widely distributed in neurons in the brain, spinal cord, and some sensory neurons.beta4 is most similar to the beta2 subunit (35% identity), and, like the beta2 subunit, the Ig-like fold of beta4 contains an unpaired cysteine that may interact with the alpha subunit. Under nonreducing conditions, beta4 has a molecular mass exceeding 250 kDa because of its covalent linkage to Nav1.2a, whereas on reduction, it migrates with a molecular mass of 38 kDa, similar to the mature glycosylated forms of the other beta subunits. Coexpression of beta4 with brain Nav1.2a and skeletal muscle Nav1.4 alpha subunits in tsA-201 cells resulted in a negative shift in the voltage dependence of channel activation, which overrode the opposite effects of beta1 and beta3 subunits when they were present. This novel, disulfide-linked beta subunit is likely to affect both protein-protein interactions and physiological function of multiple sodium channel alpha subunits.
Aquaporin-4 serostatus does not predict response to immunotherapy in neuromyelitis optica spectrum disorders

Background: Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. Objective: We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. Methods: We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. Results: In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p < 0.0001) and 0.12 (seronegative; p = 0.0001). In those started on mycophenolate mofetil, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.79 and 1.45, respectively. On-treatment annualized relapse rates declined to 0.29 (seropositive; p < 0.0001) and 0.30 (seronegative; p < 0.005). Conclusion: In this international collaboration involving a large number of neuromyelitis optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments.
Towards physics-based segmentation of photographic color images

In many digital image processing applications, image segmentation is required to provide initial partitioning of local image regions based on certain statistical or contextual homogeneity measures. One goal of image segmentation would be to segment the image into regions that correspond to physically and semantically coherent objects in the scene. We propose an improved color segmentation algorithm by taking advantage of a simple "k-mode" algorithm and an adaptive Bayesian k-means algorithm. The "k-mode" algorithm uses a physics-based distance metric to generate regular partitioning of the color space. The adaptive k-means algorithm utilizes two additional mechanisms, i.e., spatial homogeneity constraints and spatial adaptivity, to achieve more robust and coherent segmentation. The proposed algorithm integrates a physically more meaningful color space and the corresponding color difference metric into the the adaptive Bayesian K-means framework in an effort towards physics-based segmentation of photographic color images.
Plasmacytoid Dendritic Cell Dynamics and Alpha Interferon Production during Simian Immunodeficiency Virus Infection with a Nonpathogenic Outcome

ABSTRACT We addressed the role of plasmacytoid dendritic cells (PDC) in protection against AIDS in nonpathogenic simian immunodeficiency virus (SIVagm) infection in African green monkeys (AGMs). PDC were monitored in blood and lymph nodes (LNs) starting from day 1 postinfection. We observed significant declines in blood during acute infection. However, PDC then returned to normal levels, and chronically infected AGMs showed no decrease of PDC in blood. There was a significant increase of PDC in LNs during acute infection. Blood PDC displayed only weak alpha interferon (IFN-α) responses to TLR9 agonist stimulation before infection. However, during acute infection, both blood and LN PDC showed a transiently increased propensity for IFN-α production. Bioactive IFN-α was detected in plasma concomitant with the peak of viremia, though levels were only low to moderate in some animals. Plasma interleukin 6 (IL-6) and IL-12 were not increased. In conclusion, PDC were recruited to the LNs and displayed increased IFN-α production during acute infection. However, increases in IFN-α were transient. Together with the lack of inflammatory cytokine responses, these events might play an important role in the low level of T-cell activation which is associated with protection against AIDS in nonpathogenic SIVagm infection.
An I/O-efficient Distance Oracle for Evolving Real-World Graphs

Computing shortest path distance is a fundamental primitive in many graph applications. On graphs that do not fit in the main memory of the computing device, computing such distances requires hours to months even with the best I/O-efficient shortest path implementations. For applications requiring many such shortest path distances, one would ideally like to preprocess the input graph into a space-efficient data structure I/O-efficiently, such that the distance queries can be answered with a small additive distortion using only O(1) I/Os. Furthermore, in a batch setting, one would like to answer O(n) such distance queries in O (n/B) I/Os. In this paper, we focus on engineering an I/O-efficient distance oracle for large graphs that model real-world interactions. Our engineered oracle (i) preprocesses graphs with multi-billion edges in less than an hour using a single core of a typical PC, (ii) answers online shortest path queries in milliseconds using a SSD, (iii) answers batched shortest path queries using HDDs with an average time per query of a few microseconds, (iv) results in a highly accurate shortest path estimate and (v) uses space linear in the number of nodes. Our implementation creates small oracle labels (i.e., they can still be kept in internal memory for rather large graphs) but also efficiently handles the case when both the graph and these labels have to reside on external storage. Dynamic settings where new edges are continuously inserted into the graph are efficiently supported, too.