Miracle-dz/UniFAR-FTUs huggingface dataset:
Pro-apoptotic Effect of Pifithrin-α on Preimplantation Porcine In vitro Fertilized Embryo Development

The aim of this study was to investigate the impact of a reported p53 inhibitor, pifithrin-α (PFT-α), on preimplantation porcine in vitro fertilized (IVF) embryo development in culture. Treatment of PFT-α was administered at both early (0 to 48 hpi), and later stages (48 to 168 hpi) of preimplantation development, and its impact upon the expression of five genes related to apoptosis (p53, bak, bcl-xL, p66Shc and caspase3), was assessed in resulting d 7 blastocysts, using real-time quantitative PCR. Total cell numbers, along with the number of apoptotic nuclei, as detected by the in situ cell death detection assay, were also calculated on d 7 in treated and non-treated control embryos. The results indicate that PFT-α, when administered at both early and later stages of porcine IVF embryo development, increases the incidence of apoptosis in resulting blastocysts. When administered at early cleavage stages, PFT-α treatment was shown to reduce the developmental competence of porcine IVF embryos, as well as reducing the quality of resulting blastocysts in terms of overall cell numbers. In contrast, at later stages, PFT-α administration resulted in marginally increased blastocyst development rates amongst treated embryos, but did not affect cell numbers. However, PFT-α treatment induced apoptosis and apoptotic related gene expression, in all treated embryos, irrespective of the timing of treatment. Our results indicate that PFT-α may severely compromise the developmental potential of porcine IVF embryos, and is a potent apoptotic agent when placed into porcine embryo culture media. Thus, caution should be exercised when using PFT-α as a specific inhibitor of p53 mediated apoptosis, in the context of porcine IVF embryo culture systems.
Mitochondrial Structure and Function Are Disrupted by Standard Isolation Methods

Mitochondria regulate critical components of cellular function via ATP production, reactive oxygen species production, Ca2+ handling and apoptotic signaling. Two classical methods exist to study mitochondrial function of skeletal muscles: isolated mitochondria and permeabilized myofibers. Whereas mitochondrial isolation removes a portion of the mitochondria from their cellular environment, myofiber permeabilization preserves mitochondrial morphology and functional interactions with other intracellular components. Despite this, isolated mitochondria remain the most commonly used method to infer in vivo mitochondrial function. In this study, we directly compared measures of several key aspects of mitochondrial function in both isolated mitochondria and permeabilized myofibers of rat gastrocnemius muscle. Here we show that mitochondrial isolation i) induced fragmented organelle morphology; ii) dramatically sensitized the permeability transition pore sensitivity to a Ca2+ challenge; iii) differentially altered mitochondrial respiration depending upon the respiratory conditions; and iv) dramatically increased H2O2 production. These alterations are qualitatively similar to the changes in mitochondrial structure and function observed in vivo after cellular stress-induced mitochondrial fragmentation, but are generally of much greater magnitude. Furthermore, mitochondrial isolation markedly altered electron transport chain protein stoichiometry. Collectively, our results demonstrate that isolated mitochondria possess functional characteristics that differ fundamentally from those of intact mitochondria in permeabilized myofibers. Our work and that of others underscores the importance of studying mitochondrial function in tissue preparations where mitochondrial structure is preserved and all mitochondria are represented.
Carbon nanotubes impregnated with subventricular zone neural progenitor cells promotes recovery from stroke

The present in vivo study was conducted to evaluate whether hydrophilic (HL) or hydrophobic (HP) carbon nanotubes (CNTs) impregnated with subventricular zone neural progenitor cells (SVZ NPCs) could repair damaged neural tissue following stroke. For this purpose, stroke damaged rats were transplanted with HL CNT-SVZ NPCs, HP CNT-SVZ NPCs, or SVZ NPCs alone for 1, 3, 5, and 8 weeks. Results showed that the HP CNT-SVZ NPC transplants improved rat behavior and reduced infarct cyst volume and infarct cyst area compared with the experimental control and the HL CNT-SVZ NPC and SVZ NPCs alone groups. The transplantation groups showed an increase in the expression of nestin (cell stemness marker) and proliferation which was evident with the increased number of doublecortin and bromodeoxyuridine double-stained immunopositive cells around the lesion site. But, these effects were more prominent in the HP CNT-SVZ NPC group compared with the other transplantation groups. The HP CNT-SVZ NPC and HL CNT-SVZ NPC transplants increased the number of microtubule-associated protein 2 (marker for neurons) and decreased the number of glial fibrillary acidic protein (marker for astroglial cells) positive cells within the injury epicenter. The majority of the transplanted HP CNT-SVZ NPCs collectively broadened around the ischemic injured region and the SVZ NPCs differentiated into mature neurons, attained the synapse morphology (TUJ1, synaptophysin), and decreased microglial activation (CD11b/c [OX-42]). For these reasons, this study provided the first evidence that CNTs can improve stem cell differentiation to heal stroke damage and, thus, deserve further attention.
Juvenile Hyaline Fibromatosis: Clinical Heterogeneity in Three Patients

Background: Systemic hyalinoses are genetic generalized fibromatoses characterized by an accumulation of hyalin in the dermis. Two distinctive syndromes are recognized in the literature: infantile systemic hyalinosis (ISH) and juvenile hyaline fibromatosis (JHF). ISH and JHF are sometimes difficult to separate since they show significant overlap. Observations: We report on 3 children from two unrelated families suffering from JHF. The first child is severely handicapped by joint contracture, massive hyperplasia of the gingivae, diffuse skin papules and subcutaneous nodules occupying the scalp, face, perianal area, palms, soles and chest. At the same age, the second child only shows pearly skin papules on the face, groin and perianal area and gingival hyperplasia without joint stiffness or any other subjective complaint. The third patient, a brother of the second child, developed mild skin abnormalities by the end of the first year. The occurrence in siblings and consanguinity in the second family suggests autosomal recessive inheritance. Histological skin examination in the 3 cases showed hyaline deposition in the dermis and abnormal ultrastructure of fibroblasts. Biochemical findings showed mucopolysaccharide abnormalities in both families. Conclusion: Our patients do not only illustrate the different expressions of JHF but also show some overlap with ISH, suggesting a common cause for both disorders. Genetic studies will finally answer this question.
Non-Covalent Interactions in π-Functionalized Potassium Fluoroalkoxides

Secondary interactions stabilize coordinatively demanding complexes of s-block metals. The structures of potassium fluoroalkoxides that, in addition to intraand intermolecular K+···F contacts, also exhibit K···Cπ interactions with tethered π ligands, are reported. A potassium–arene, a rare potassium–alkyne, and a potassium–olefin complex have been prepared by deprotonation of functionalized α,α-bis(trifluoromethyl)alcohols with KN(SiMe2R)2. They all feature a cuboid K4O4 core with μ3-bridging O atoms, and multiple stabilizing K+···F contacts in the range 2.71–3.33 Å. The potassium–arene complex shows η2, η3, and η6 K···Cπ(arene) interactions in the range 3.35–3.47 Å. The potassium–alkyne and potassium–olefin compounds are stabilized by η2 interactions with the unsaturated carbon–carbon bond, in the range 3.17–3.49 Å and 3.15–3.19 Å, respectively. Comparison with the parent complex devoid of a flanking π ligand illustrates the role of K···Cπ interactions.
Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial.

BACKGROUND AND PURPOSE Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth. METHODS IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed. RESULTS Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume. CONCLUSIONS Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.
Sex, Subdivision, and Domestic Dispersal of Trypanosoma cruzi Lineage I in Southern Ecuador

Background Molecular epidemiology at the community level has an important guiding role in zoonotic disease control programmes where genetic markers are suitably variable to unravel the dynamics of local transmission. We evaluated the molecular diversity of Trypanosoma cruzi, the etiological agent of Chagas disease, in southern Ecuador (Loja Province). This kinetoplastid parasite has traditionally been a paradigm for clonal population structure in pathogenic organisms. However, the presence of naturally occurring hybrids, mitochondrial introgression, and evidence of genetic exchange in the laboratory question this dogma. Methodology/Principal Findings Eighty-one parasite isolates from domiciliary, peridomiciliary, and sylvatic triatomines and mammals were genotyped across 10 variable microsatellite loci. Two discrete parasite populations were defined: one predominantly composed of isolates from domestic and peridomestic foci, and another predominantly composed of isolates from sylvatic foci. Spatial genetic variation was absent from the former, suggesting rapid parasite dispersal across our study area. Furthermore, linkage equilibrium between loci, Hardy-Weinberg allele frequencies at individual loci, and a lack of repeated genotypes are indicative of frequent genetic exchange among individuals in the domestic/peridomestic population. Conclusions/Significance These data represent novel population-level evidence of an extant capacity for sex among natural cycles of T. cruzi transmission. As such they have dramatic implications for our understanding of the fundamental genetics of this parasite. Our data also elucidate local disease transmission, whereby passive anthropogenic domestic mammal and triatomine dispersal across our study area is likely to account for the rapid domestic/peridomestic spread of the parasite. Finally we discuss how this, and the observed subdivision between sympatric sylvatic and domestic/peridomestic foci, can inform efforts at Chagas disease control in Ecuador.
Botulinum Toxin for the Treatment of Genital Pain Syndromes

Our purpose was to test the effect of botulinum toxin injections on hypertonic pelvic floor muscles of patients suffering from genital pain syndromes. We report two cases of women complaining of a genital pain syndrome resistant to pharmacological therapies and rehabilitation exercises associated with a documented involuntary tonic contraction of the levator ani muscle as a defense reaction triggered by vulvar pain. We performed botulinum toxin injections into the levator ani with the intent to relieve pelvic muscular spasms. Within a few days after the injections both the patients reported a complete resolution of the painful symptomatology, lasting for several months. Our experience suggests that botulinum injections are indicated in patients with genital pain syndrome with documented pelvic muscle hyperactivity, whose symptoms arise not only from genital inflammation and lesions, but also, and sometimes chiefly, from levator ani myalgia.
Knowledge-based fuzzy MLP for classification and rule generation

A new scheme of knowledge-based classification and rule generation using a fuzzy multilayer perceptron (MLP) is proposed. Knowledge collected from a data set is initially encoded among the connection weights in terms of class a priori probabilities. This encoding also includes incorporation of hidden nodes corresponding to both the pattern classes and their complementary regions. The network architecture, in terms of both links and nodes, is then refined during training. Node growing and link pruning are also resorted to. Rules are generated from the trained network using the input, output, and connection weights in order to justify any decision(s) reached. Negative rules corresponding to a pattern not belonging to a class can also be obtained. These are useful for inferencing in ambiguous cases. Results on real life and synthetic data demonstrate that the speed of learning and classification performance of the proposed scheme are better than that obtained with the fuzzy and conventional versions of the MLP (involving no initial knowledge encoding). Both convex and concave decision regions are considered in the process.
A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer.

PURPOSE Farnesyltransferase (FTase) inhibitors, which were designed to inhibit oncogenic Ras, act synergistically with tamoxifen in preclinical breast cancer models. We studied the safety and toxicity of tipifarnib in combination with tamoxifen in metastatic breast cancer. The pharmacokinetics and pharmacodynamics of tipifarnib were also assessed. PATIENTS AND METHODS Patients with metastatic, hormone receptor-positive breast cancer were enrolled. Two cohorts of patients were treated with tipifarnib at either 200 or 300 mg p.o. twice daily for 21 of 28 days. Tamoxifen (20 mg once daily) was started after 1 week of tipifarnib monotherapy to perform pharmacokinetics and FTase inhibition levels in peripheral blood mononuclear cells with tipifarnib alone and with tipifarnib and tamoxifen. RESULTS A total of 12 heavily pretreated patients with prior progression on hormonal therapy were enrolled. Minimal toxicity was observed at the 200-mg dose level of tipifarnib. At the 300-mg dose, all six patients required dose reduction of tipifarnib due to toxicities that included grade 2 nausea, rash, and fatigue and grade 3 diarrhea and neutropenia. Tipifarnib pharmacokinetic and pharmacodynamic variables were similar in the presence and absence of tamoxifen. Average FTase inhibition was 42% at 200 mg and 54% at 300 mg in peripheral blood mononuclear cells. Of the 12 patients treated, there were two partial responses and one stable disease for >6 months. CONCLUSIONS Tipifarnib (200 mg twice daily for 21 of 28 days) and tamoxifen (20 mg once daily) can be given safely with minimal toxicity. Tamoxifen does not have a significant effect on tipifarnib pharmacokinetics.
Activated protein C (Xigris®) treatment in sepsis: a drug in trouble

Drotrecogin alfa (activated) or recombinant human activated protein C (rhAPC) has been registered for use as adjuvant treatment in severe sepsis since 2001 under the trade name Xigris® essentially based on the results from one large clinical trial (the PROWESS trial). In a recently published second randomized clinical trial (the ADDRESS trial), enrolling patients with severe sepsis but with less risk of death, no effect of the treatment was shown, not even a trend to a positive effect in the subgroup of patients with a high risk of death that would match the present prescription label for Xigris®. In addition, a large randomized, placebo‐controlled trial with rhAPC in paediatric sepsis has recently been terminated prematurely because of lack of efficacy. Altogether, the robustness of the data supporting the use of rhAPC in treating patients with severe sepsis may indeed be questioned. A confirmatory clinical trial is required before rhAPC can be used with confidence. The side‐effects and the cost of rhAPC are well documented but its efficacy is not.
Improving telephone follow-up for patients discharged from the emergency department: results of a randomized controlled trial.

OBJECTIVES Reliable telephone follow-up offers physicians a timely method to notify patients of unexpected laboratory and imaging results, clarify discharge instructions, evaluate health status changes, and potentially boost patient satisfaction. This study sought to determine if verifying telephone numbers, obtaining best contact times, and informing patients that they will be contacted would increase the proportion of emergency department (ED) patients contacted at 48 to 72 hours postdischarge. Secondary outcomes included estimating successful postdischarge follow-up across demographic categories. METHODS This was a prospective, randomized controlled trial of adult patients in an inner-city, public hospital ED. Patients were excluded for critical illness, no telephone number, non-English- or non-Spanish-speaking, or anyone admitted as an inpatient. All subjects completed a demographic questionnaire. In the intervention arm, research assistants (RAs) verified the telephone number, obtained best contact times, and informed subjects that they would be called. In the control arm, telephone numbers were obtained from registration materials and were not verified, and subjects were not informed that postdischarge telephone calls were planned. RAs made four telephone attempts to contact each subject 48 to 72 hours after discharge. RESULTS The intervention did not significantly improve postdischarge contact. Most subjects, 72.8% in the intervention group and 68.2% in the control group, were successfully contacted (difference = 4.6%, 95% confidence interval [CI] = -2.2% to 11.4%). On multivariate analysis, Hispanic ethnicity and owning a mobile phone were associated with increased odds of successful postdischarge follow-up. CONCLUSIONS Verifying contact information, obtaining best contact times, and notifying patients of impending follow-up calls did not substantially improve postdischarge telephone contact rates.
Effects of the Artificial Skin's Thickness on the Subsurface Pressure Profiles of Flat, Curved, and Braille Surfaces

The primary interface of contact between a robotic or prosthetic hand and the external world is through the artificial skin. To make sense of that contact, tactile sensors are needed. These sensors are normally embedded in soft synthetic materials for protecting the subsurface sensor from damage or for better hand-to-object contact. It is important to understand how the mechanical signals transmit from the artificial skin to the embedded tactile sensors. In this paper, we made use of a finite element model of an artificial fingertip with viscoelastic and hyperelastic behaviors to investigate the subsurface pressure profiles when flat, curved, and Braille surfaces were indented on the surface of the model. Furthermore, we investigated the effects of 1, 3, and 5 mm thickness of the skin on the subsurface pressure profiles. The simulation results were experimentally validated using a 25.4 μm thin pressure detecting film that was able to follow the contours of a non-planar surface, which is analogous to an artificial bone. Results show that the thickness of the artificial skin has an effect on the peak pressure, on the span of the pressure distribution, and on the overall shape of the pressure profile that was encoded on a curved subsurface structure. Furthermore, the flat, curved, and Braille surfaces can be discriminated from one another with the 1 and 3 mm artificial skin layers, but not with the 5 mm thick skin.
Test architecture design and optimization for three-dimensional SoCs

Core-based system-on-chips (SoCs) fabricated on three-dimensional (3D) technology are emerging for better integration capabilities. Effective test architecture design and optimization techniques are essential to minimize the manufacturing cost for such giga-scale integrated circuits. In this paper, we propose novel test solutions for 3D SoCs manufactured with die-to-wafer and die-to-die bonding techniques. Both testing time and routing cost associated with the test access mechanisms in 3D SoCs are considered in our simulated annealing-based technique. Experimental results on ITC'02 SoC benchmark circuits are compared to those obtained with two baseline solutions, which show the effectiveness of the proposed technique.
Mirage: a microeconomic resource allocation system for sensornet testbeds

In this paper, we argue that a microeconomic resource allocation scheme, specifically the combinatorial auction, is well suited to testbed resource management. To demonstrate this, we present the Mirage resource allocation system. In Mirage, testbed resources are allocated using a repeated combinatorial auction within a closed virtual currency environment. Users compete for testbed resources by submitting bids which specify resource combinations of interest in space/time (e.g., "any 32 MICA2 motes for 8 hours anytime in the next three days") along with a maximum value amount the user is willing to pay. A combinatorial auction is then periodically run to determine the winning bids based on supply and demand while maximizing aggregate utility delivered to users. We have implemented a fully functional and secure prototype of Mirage and have been operating it in daily use for approximately four months on Intel Research Berkeley's 148-mote sensornet testbed.
Targeting Co-Stimulatory Pathways in Gene Therapy

Gene therapy with recombinant viral vectors such as adenovirus and adenovirus-associated virus holds great promise in treating a wide range of diseases because of the high efficiency with which the viruses transfer their genomes into host cells in vivo. However, the activation of the host immune responses remains a major hurdle to successful gene therapy. Studies in the past two decades have elucidated the important role co-stimulation plays in the activation of both T and B cells. This review summarizes our current understanding of T cell co-stimulatory pathways, and strategies targeting these co-stimulatory pathways in gene therapy applications as well as potential future directions.