Miracle-dz/UniFAR-FTUs huggingface dataset:
Flow cytometric in situ proximity ligation analyses of protein interactions and post‐translational modification of the epidermal growth factor receptor family

Interactions between members of the epidermal growth factor receptor (EGFR) family mediates cellular responses to ligand stimulation. Measurement of these interactions could provide important information and may prove useful as prognostic markers in malignancy. Therefore, to develop methods to study these interactions in genetically unmodified cells, such as clinical samples, in a sensitive and selective way, with good statistical accuracy, is important. The in situ proximity ligation assay (in situ PLA) was used to quantify homo‐ and heteromeric interactions between EGFR and HER2 in cultured cells, using flow cytometry as the readout method. Cells were monitored for changes in dimerization patterns and phosphorylation status upon stimulation. The different cell lines displayed varying amounts of interactions between EGFR and HER2, but the amount of dimerization was not found to be affected significantly upon stimulation by EGF. Activation of EGFR could be visualized by in situ PLA, but not by immunofluorescence staining. In situ PLA was successfully used to study receptor dimerization and activation of the EGF‐receptor family with high selectivity and sensitivity. The combination of in situ PLA and flow cytometry provided a statistically powerful way of analyzing protein‐protein interactions and post‐translational modifications on a single‐cell basis. © 2009 International Society for Advancement of Cytometry
Inferring the Distribution and Demography of an Invasive Species from Sighting Data: The Red Fox Incursion into Tasmania

A recent study has inferred that the red fox (Vulpes vulpes) is now widespread in Tasmania as of 2010, based on the extraction of fox DNA from predator scats. Heuristically, this inference appears at first glance to be at odds with the lack of recent confirmed discoveries of either road-killed foxes—the last of which occurred in 2006, or hunter killed foxes—the most recent in 2001. This paper demonstrates a method to codify this heuristic analysis and produce inferences consistent with assumptions and data. It does this by formalising the analysis in a transparent and repeatable manner to make inference on the past, present and future distribution of an invasive species. It utilizes Approximate Bayesian Computation to make inferences. Importantly, the method is able to inform management of invasive species within realistic time frames, and can be applied widely. We illustrate the technique using the Tasmanian fox data. Based on the pattern of carcass discoveries of foxes in Tasmania, we infer that the population of foxes in Tasmania is most likely extinct, or restricted in distribution and demographically weak as of 2013. It is possible, though unlikely, that that population is widespread and/or demographically robust. This inference is largely at odds with the inference from the predator scat survey data. Our results suggest the chances of successfully eradicating the introduced red fox population in Tasmania may be significantly higher than previously thought.
Blue Nevi and Related Lesions: A Review Highlighting Atypical and Newly Described Variants, Distinguishing Features and Diagnostic Pitfalls

Blue nevi and related entities are a heterogenous group of congenital and acquired melanocytic tumors that includes established entities such as dendritic (“common”) blue nevus and cellular blue nevus, and their numerous clinical and pathologic variants, such as deep penetrating nevus. They share several clinical and morphologic features including their blue tinctorial properties, the presence of a dermal proliferation of spindle, fusiform or ovoid cells, associated melanin pigment (both within the melanocytic tumor cells and also within macrophages) and stromal sclerosis and, at least focal positivity for HMB-45 (Gp100). Some variants, such as deep penetrating nevus, often show considerable variation in nuclear size and shape, and, as a consequence, are at risk of being misdiagnosed as melanoma by those unfamiliar with their characteristic morphologic features. The so-called malignant blue nevus is a controversial term denoting melanomas arising in association with or exhibiting some morphologic similarities to blue nevus. There are also lesions that are probably related to blue nevi, such as the recently described pigmented epithelioid melanocytoma and the neurocristic hamartomas, whose nature, biologic behavior, and relationship to the better established entities remains to be clearly established. This review aims to present a brief overview of these lesions, highlighting their pathologic characteristics, distinguishing features and potential diagnostic pitfalls, with particular emphasis on recently described entities, molecular findings, controversial areas, and approaches to diagnosis.
Debt Structure Adjustments and Long-Run Stock Price Performance

We examine the long-run implications of debt structure adjustments using a sample of U.S. bond IPOs from 1971 to 1994. Bond IPOs result in simultaneous and pronounced changes in both debt maturity and debt ownership structures. We document that firms engaging in debt IPOs substantially underperform their size-and-book-to-market matched benchamarks by 33.39% and 55.99% over the tree- and five-year post-offer periods. Our results are strikingly similar to those reported for equity offers but contrast the evidence for seasoned debt offers. We find evidence that debt IPOs are timed to coincide with the market having the highest expectations concernig firms' prospects. A negative relation is documented between debt maturity and future growth opportunities. In part, the underperformance can be attributed to significantly reduced growth opportunities following the offering. Post-offer underperformance is more pronounced for (a) longer maturity issues, and (b)firms that do not experience an increase in bank monitoring.
Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Background and Purpose— Hematoma clearance occurs in the days after intracerebral hemorrhage (ICH) and has not been well studied. In the current study, we examined changes in the hematoma in a piglet ICH model. The effect of deferoxamine on hematoma was also examined. Methods— The ICH model was induced by an injection of autologous blood into the right frontal lobe of piglets. First, a natural time course of hematoma changes ⩽7 days was determined. Second, the effect of deferoxamine on hematoma changes was examined. Hemoglobin and membrane attack complex levels in the hematoma were examined by enzyme-linked immunosorbent assay. Immunohistochemistry and Western blotting were used to examine CD47 (a regulator of erythrophagocytosis), CD163 (a hemoglobin scavenger receptor), and heme oxygenase-1 (a heme degradation enzyme) in the clot. Results— After ICH, there was a reduction in red blood cell diameter within the clot with time. This was accompanied by membrane attack complex accumulation and decreased hemoglobin levels. Erythrophagocytosis occurred in the hematoma, and this was associated with reduced clot CD47 levels. Activated macrophages/microglia were CD163 and hemeoxygenase-1 positive, and these accumulated in the clot with time. Deferoxamine treatment attenuated the process of hematoma resolution by reducing member attack complex formation and inhibiting CD47 loss in the clot. Conclusions— These results indicate that membrane attack complex and erythrophagocytosis contribute to hematoma clearance after ICH, which can be altered by deferoxamine treatment.
Structure-Guided Recombination Creates an Artificial Family of Cytochromes P450

Creating artificial protein families affords new opportunities to explore the determinants of structure and biological function free from many of the constraints of natural selection. We have created an artificial family comprising ˜3,000 P450 heme proteins that correctly fold and incorporate a heme cofactor by recombining three cytochromes P450 at seven crossover locations chosen to minimize structural disruption. Members of this protein family differ from any known sequence at an average of 72 and by as many as 109 amino acids. Most (>73%) of the properly folded chimeric P450 heme proteins are catalytically active peroxygenases; some are more thermostable than the parent proteins. A multiple sequence alignment of 955 chimeras, including both folded and not, is a valuable resource for sequence-structure-function studies. Logistic regression analysis of the multiple sequence alignment identifies key structural contributions to cytochrome P450 heme incorporation and peroxygenase activity and suggests possible structural differences between parents CYP102A1 and CYP102A2.
Alloimmunization to platelets in heavily transfused patients with sickle cell disease.

Bone marrow transplantation (BMT) is now an option for some patients with sickle cell disease (SCD). Many SCD patients are multiply transfused with red blood cells (RBCs), and may be immunized to alloantigens other than erythrocyte antigens. Because platelet refractoriness is a significant complication during BMT, we wished to determine the prevalence of alloimmunization to platelets in transfused SCD patients. Sera collected from 47 transfused and 14 untransfused SCD patients were screened for HLA and platelet-specific antibodies. Transfusion and RBC antibody histories were reviewed. A subset of the patients were rescreened 1 year later. Eighty-five percent of patients with at least 50 RBC transfusions (22 of 26), 48% of patients with less than 50 transfusions (10 of 21), and none of 14 untransfused patients demonstrated platelet alloimmunization (P < .05). Platelet alloimmunization was more prevalent than RBC alloimmunization (20% to 30%). Half of the platelet reactivity was chloroquine-elutable. Eighteen of 22 patients (82%) on chronic RBC transfusion remained platelet-alloimmunized 11 to 22 months after initial testing. In summary, 85% of heavily transfused SCD patients are alloimmunized to HLA and/or platelet-specific antigens. These patients may be refractory to platelet transfusion, a condition that would increase their risk during BMT. Leukodepletion in the transfusion support of SCD patients should be considered to prevent platelet alloimmunization.
A Study of Low Elastic Modulus Expandable Pedicle Screws in Osteoporotic Sheep

Study Design Low elastic modulus expandable pedicle screw (L-EPS) was inserted into osteoporotic sheep. Biomechanical tests, micro-CT analysis and histologic observation were performed. Objective To find out whether the L-EPS can further improve fixation strength compared to the expandable pedicle screws (EPS) in osteoporotic sheep spine. The screw-bone interface is also detected by micro-computed tomography (CT) and histologic techniques. Summary of Background Data There are some studies on EPS in vivo; however, no earlier study has focused on the elastic modulus of EPS, especially in osteoporosis. Methods Twelve months after ovariectomy, bilateral pedicles of lumbar vertebrae (L1 to L5) of 4 female sheep were fixed with EPSs. The L-EPS and EPS were randomly placed into each pedicle and then were expanded. Six months later, the sheep were sacrificed and biomechanical tests, micro-CT analysis, and histologic observation were conducted on the isolated specimen vertebrae. Results Twelve months after ovariectomy, animal model of osteoporosis was established successfully. The axial pull-out strength in L-EPS group was significantly enhanced compared with that in the EPS group (P < 0.05). Micro-CT reconstruction and analysis showed that there was more bone around the L-EPS group compared with those in EPS group (P < 0.05), meanwhile the more homogeneous bone formation distribution around the screws was found in the L-EPS group. Histologic observation showed that newly formed bone extended along the expandable fissures and grew into the center of EPS; meanwhile, the more direct contact and the less fibrous tissue on the screw-bone interface were observed in the L-EPS group. Conclusions The L-EPS can further improve the biomechanical fixation strength of EPS in the osteoporotic sheep. The screw elastic matching with surrounding bone is helpful to distribute stress uniformly, relieve the stress shielding effect, and strengthen the screw-bone interface. Although the experience with the L-EPS is very limited and preliminary, results to date indicate that it is of value in treating patients with osteoporosis and warrants further study.
CONDITION MONITORING FOR INDEXABLE CARBIDE END MILL USING ACCELERATION DATA

In order to automate machining operations, it is necessary to develop robust tool condition monitoring techniques. In this paper, a tool monitoring strategy for indexable tungsten carbide end milling tools is presented based on the Fourier transform and statistical analysis of the vibrations of the tool during the machining operations. Using a low-cost, tri-axial piezoelectric accelerometer, the presented algorithm demonstrates the ability to accurately monitor the condition of the tools as the wear increases during linear milling operations. One benefit of using accelerometer signals to monitor the cutting process is that the sensor does not limit the machine's capabilities, as a workpiece mounted dynamometer does. To demonstrate capabilities of the technique, four tool wear life tests were conducted under various conditions. The indirect method discussed herein successfully tracks the tool's wear and is shown to be sensitive enough to provide sufficient time to replace the insert prior to damage of the machine tool, cutter, and/or workpiece.
ParMAC: distributed optimisation of nested functions, with application to learning binary autoencoders

Many powerful machine learning models are based on the composition of multiple processing layers, such as deep nets, which gives rise to nonconvex objective functions. A general, recent approach to optimise such “nested” functions is the method of auxiliary coordinates (MAC) (Carreira-Perpiñán and Wang, 2014). MAC introduces an auxiliary coordinate for each data point in order to decouple the nested model into independent submodels. This decomposes the optimisation into steps that alternate between training single layers and updating the coordinates. It has the advantage that it reuses existing singlelayer algorithms, introduces parallelism, and does not need to use chain-rule gradients, so it works with nondifferentiable layers. With large-scale problems, or when distributing the computation is necessary for faster training, the dataset may not fit in a single machine. It is then essential to limit the amount of communication between machines so it does not obliterate the benefit of parallelism. We describe a general way to achieve this, ParMAC. ParMAC works on a cluster of processing machines with a circular topology and alternates two steps until convergence: one step trains the submodels in parallel using stochastic updates, and the other trains the coordinates in parallel. Only submodel parameters, no data or coordinates, are ever communicated between machines. ParMAC exhibits high parallelism, low communication overhead, and facilitates data shuffling, load balancing, fault tolerance and streaming data processing. We study the convergence of ParMAC and propose a theoretical model of its runtime and parallel speedup. To illustrate our general results in a specific algorithm, we develop ParMAC to learn binary autoencoders with application to fast, approximate image retrieval. We implement this using Message Passing Interface (MPI) in a distributed system and demonstrate nearly perfect speedups in a 128-processor cluster with a training set of 100 million high-dimensional points. The speedups achieved agree well with the prediction of our theoretical speedup model.
Activities of Dalbavancin against a Worldwide Collection of 81,673 Gram-Positive Bacterial Isolates

ABSTRACT Dalbavancin, a long-acting lipoglycopeptide, was evaluated against 81,673 isolates of staphylococci, enterococci, and streptococci collected from 33 countries during worldwide resistance surveillance (2002 to 2007). Regardless of susceptibility to oxacillin, comparable potencies for dalbavancin against Staphylococcus aureus and coagulase-negative staphylococci from all countries were noted (MIC90, 0.06 to 0.12 μg/ml). Vancomycin-susceptible Enterococcus spp. had dalbavancin MIC90s comparable to those for staphylococci, whereas vancomycin-resistant strains were more resistant (MIC50, >4 μg/ml). β-Hemolytic and viridians group streptococci were very susceptible to dalbavancin (MIC90, ≤0.03 μg/ml). Overall, dalbavancin was ≥16-fold more active than vancomycin against the monitored gram-positive species.
Cell cycle synchronization and analysis of apoptosis‐related gene in skin fibroblasts from domestic cat (Felis silvestris catus) and kodkod (Leopardus guigna)

The kodkod population is in constant decrease and the somatic cell nuclear transfer (SCNT) might help to preserve the genetic pool of this species. The cell cycle synchronization of donor cells plays a crucial role in SCNT. The objective of this research was to evaluate two different methods for quiescence induction, serum starvation (SS) and contact inhibition (CI), both for 1, 3 and 5 days, on skin fibroblast from domestic cat and kodkod. Flow cytometry analysis revealed that in domestic cat, SS and CI, both at 3 and 5 days, increased the percentage of fibroblasts in G0/G1 compared to growing cells (GC) (p < .05). In kodkod, only SS for 3 and 5 days and CI for 1 and 3 days increased the percentage of fibroblasts in G0/G1 compared to GC (p < .05). Viability analysis by differential staining revealed that SS for 5 days decreased the proportion of live fibroblasts in domestic cat and kodkod (p < .05). Regarding gene expression analysis, in domestic cat fibroblasts, no differences were found in the BAX/BCL2 ratio in SS and CI (both at 1, 3 and 5 days) compared to GC. In kodkod fibroblasts, BAX/BCL2 ratio was increased in CI at 3 and 5 days compared to SS at 3 and 5 days (p < .05). In conclusion, in kodkod fibroblasts SS for 5 days and CI after 3 days might have a negative impact on cellular viability. According to these results, we suggest SS for 3 days for cell cycle synchronization in kodkod fibroblasts.
A Framework for Flexible User Profile Mashups

Exploiting the rich traces of users' Web interaction promises to enable cross-application user modeling techniques, which is in particu- lar interesting for applications that have a small user population or that are used infrequently. In this paper we present a framework for the eec- tive interchange of user proles. In addition to derivation rules for user prole reasoning, the framework employs exible mash-ups of RSS-based user data streams for combining heterogeneous user data in a Web 2.0 environment.
Postoperative Pain Relief through Relaxation in Elderly Patients with Fractured Hips

This study examined the effect of the Jacobson relaxation technique involving the tongue and jaw, coordinated rhythmic breathing, and a lack of attention to thoughts, words, and speech on the postoperative comfort level in elderly patients with fractured hips. An experimental design was used to test three hypotheses that subjects who used the technique would express a lower level of pain and distress immediately after turning from their back to the unoperated hip within the first 24 hours following surgery. It was also hypothesized that subjects who used the technique would have a lower mean intake of analgesics during the initial 24-hour postoperative period. The sample consisted of 20 older adults, aged 56 to 89, admitted to two hospitals in northern Ohio for the surgical repair of a fractured hip. Ten subjects each were randomly assigned to a control and an experimental group. Experimental group subjects were taught the Jacobson relaxation technique according to a three-step instructional protocol that considered the learning needs of older adults. Control group subjects were not taught the technique. Data were collected using Johnson's Sensation of Pain and Distress scales. The intake of analgesics was collected from the medical record. Results of the study supported the use of the Jacobson relaxation technique in this population as a means of increasing the postoperative level of comfort. Subjects who used the technique when they were turned during the first 24 hours following surgery stated a statistically significant lower level of pain (p <.05) and distress (p <.001). Subjects also had a statistically significant lower intake of analgesics (p <.05).
Electrolytic corrosion as an adjunct to DC tracking and erosion on insulators

Tests with a modified IEC 587 'Inclined plane' procedure show that with DC a form of tracking and severe erosion can occur on toughened glass and on porcelain insulators at stresses used in service (Mason et al., 1987). In these tests polarity effects, which are consistent with service experience, apparently arise from electrolytic corrosion at the positive electrodes. This paper discusses, effects with stainless steel, or platinum electrodes and solutions of NH/sub 4/Cl, FeCl/sub 3/ or ZnCl/sub 2/.
Population study of depressive symptoms and risk factors in pregnant and parenting Mexican adolescents.

OBJECTIVE To study the prevalence of, severity of, and risk factors for depressive symptoms in a probabilistic sample of Mexican adolescent mothers. METHODS A sample of adolescents aged 13-19 years, drawn from a national survey, was interviewed in relation to severity of depressive symptoms [Center for Epidemiological Studies Depression Scale (CES-D) 16-23 and CES-D > 24] and pregnancy or parenting status. RESULTS Depressive symptoms (CES-D 16-23) ranged from 2.3% in the first postpartum semester to 32.5% in the second trimester of pregnancy; high depressive symptoms (CES-D > 24) ranged from 3.0% in the second postpartum semester to 24.7% in mothers of an infant more than 1 year old. Significant differences between groups were in mothers in the second gestation trimester, who had significantly more symptoms than those who had never been pregnant and those in the first postpartum semester. In those with high symptomatology, no significant differences were observed between groups. A multinomial logistic regression model used to estimate the likelihood of depression found increased risk of depressive symptoms (CES-D 16-23) in those without a partner in the first, second, or third trimester of pregnancy; in the second postpartum semester; and with a child over the age of 1 year. Increased risk of high symptomatology (CES-D > 24) was found in those not in school or with a child over the age of 1 year. CONCLUSIONS Depressive symptoms entail an enormous burden of disease for the mother and mental health risks to the infant; mothers should therefore be targeted in prevention and intervention actions.
Results of 115 Rubis II reverse thumb carpometacarpal joint prostheses with a mean follow-up of 10 years

The aim of this study was to assess the clinical and radiological results of the Rubis II thumb carpometacarpal joint reverse prosthesis, at a mean follow-up of 10 years. Between 1997 and 2008, 253 prostheses were implanted in 199 patients; 115 were reviewed. The survival after a mean of 10 years was 89%. At the last follow-up, 70% of prostheses were painless; the others reported moderate or intermittent pain. The satisfaction rate was 98%. The mean opposition was 9 on the Kapandji scale; the mean QuickDASH score was 30. Wrist, key and tip pinch strengths were comparable with the non-operated side. Of the 115 implants, one was radiologically loose (1%) and 15 had suffered dislocations (13%), 12 of which were caused by an injury. Eleven thumbs had revision surgery. This study confirms that the good clinical results of the Rubis II prosthesis are maintained in the medium and long term, and represents a useful alternative to trapeziectomy for selected patients. Level of evidence: IV