Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced Intensity Transplantation for Metastatic Renal Cell Cancer With 2-year Follow-up

Metastatic renal cell carcinoma (RCC) is a disease that is resistant to conventional systemic therapy. Nonmyeloablative allogeneic stem cell transplant has activity in patients with metastatic RCC. This approach has been used in related donor transplantation but there are limited data on outcomes in the setting of unrelated donor (URD) transplantation. This phase II trial assessed the efficacy, safety, and responses in 16 patients, 10 related and 6 URD transplants after a reduced intensity conditioning regimen and stem cell transplant as a treatment for metastatic RCC. Sixteen patients received a conditioning consisting of either fludarabine, cyclophosphamide (n=11) or fludarabine, total body irradiation (n=5) followed by transplantation from an HLA-matched sibling donor or a unrelated HLA-donor. Cyclosporine and mycophenolate mofetil were administered as posttransplant immunosuppression. Patients were monitored for engraftment by short tandem repeat for myeloid and lymphoid lineages and clinical response was assessed by serial imaging. All patients achieved donor chimerism, 7 patients developed acute, grades 2 to 3, graft-versus-host disease. Chronic graft-versus-host disease occurred in 6 patients and transplant-related mortality was 12%. Of the 10 related donors, 1 obtained a complete response, 3 had a partial response, and 3 had stable disease. In the 6 patients who underwent URD transplant, 1 obtained a complete response and 1 patient had stable disease. These results suggest that similar outcomes are possible where either related or URD were used as the stem cell source in reduced intensity stem cell transplant for metastatic RCC.
The Notch Intracellular Domain Is Ubiquitinated and Negatively Regulated by the Mammalian Sel-10 Homolog*

The Caenorhabditis elegans sel-10 protein is structurally similar to E3 ubiquitin ligases and is a negative regulator of Notch (lin-12) and presenilin signaling. In this report, we characterize the mammalian Sel-10 homolog (mSel-10) and analyze its effects on Notch signaling. We find that mSel-10 localizes to the cell nucleus, and that it physically interacts with the Notch 1 intracellular domain (IC) and reduces Notch 1 IC-mediated activation of the HES 1 promoter. Notch 1 IC is ubiquitinated by mSel-10, and ubiquitination requires the presence of the most carboxyl-terminal region of the Notch IC, including the PEST domain. In the presence of the proteasome inhibitor MG132, the amount of Notch 1 IC and its level of ubiquitination are increased. Interestingly, this accumulation of Notch 1 IC in the presence of MG132 is accompanied by decreased activation of the HES 1 promoter, suggesting that ubiquitinated Notch 1 IC is a less potent transactivator. Finally, we show that mSel-10 itself is ubiquitinated and degraded by the proteasome. In conclusion, these data reveal the importance of ubiquitination and proteasome-mediated degradation for the activity and turnover of Notch ICs, and demonstrate that mSel-10 plays a key role in this process.
MSCs-Derived Exosomes: Cell-Secreted Nanovesicles with Regenerative Potential

Exosomes are membrane-enclosed nanovesicles (30–150 nm) that shuttle active cargoes between different cells. These tiny extracellular vesicles have been recently isolated from mesenchymal stem cells (MSCs) conditioned medium, a population of multipotent cells identified in several adult tissues. MSCs paracrine activity has been already shown to be the key mediator of their elicited regenerative effects. On the other hand, the individual contribution of MSCs-derived exosomes for these effects is only now being unraveled. The administration of MSCs-derived exosomes has been demonstrated to restore tissue function in multiple diseases/injury models and to induce beneficial in vitro effects, mainly mediated by exosomal-enclosed miRNAs. Additionally, the source and the culture conditions of MSCs have been shown to influence the regenerative responses induced by exosomes. Therefore, these studies reveal that MSCs-derived exosomes hold a great potential for cell-free therapies that are safer and easier to manipulate than cell-based products. Nevertheless, this is an emerging research field and hence, further studies are required to understand the full dimension of this complex intercellular communication system and how it can be optimized to take full advantage of its therapeutic effects. In this mini-review, we summarize the most significant new advances in the regenerative properties of MSCs-derived exosomes and discuss the molecular mechanisms underlying these effects.
Time minimal trajectories for a spin 1∕2 particle in a magnetic field

In this paper we consider the minimum time population transfer problem for the z component of the spin of a (spin 1/2) particle, driven by a magnetic field, that is constant along the z axis and controlled along the x axis, with bounded amplitude. On the Bloch sphere (i.e., after a suitable Hopf projection), this problem can be attacked with techniques of optimal syntheses on two-dimensional (2-D) manifolds. Let (−E,E) be the two energy levels, and ∣Ω(t)∣≤M the bound on the field amplitude. For each couple of values E and M, we determine the time optimal synthesis starting from the level −E, and we provide the explicit expression of the time optimal trajectories, steering the state one to the state two, in terms of a parameter that can be computed solving numerically a suitable equation. For M∕E≪1, every time optimal trajectory is bang-bang and, in particular, the corresponding control is periodic with frequency of the order of the resonance frequency ωR=2E. On the other side, for M∕E>1, the time optimal .
Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

Studies show that sex plays a role in stress-related depression, with women experiencing a higher vulnerability to its effect. Two major targets of antidepressants are brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element–binding protein (CREB). The aim of this study was to investigate the levels of CREB, phosphorylation of CREB (pCREB), and BDNF in stress-related brain regions of male and female rats after stress and recovery. CREB and pCREB levels were examined in CA1, CA2, CA3, paraventricular nucleus of the thalamus (PVT), amygdala, anterior cingulate area, dorsal part (ACAd), and infralimbic area of prefrontal cortex (PFC), whereas dentate gyrus (DG) and prelimbic area (PL) of PFC were examined for BDNF levels. Our results demonstrate that levels of CREB and pCREB in male CA1, CA2 and CA3, PVT, amygdala, and ACAd were reduced by stress, whereas the same brain regions of female rats exhibited no change. BDNF levels were decreased by chronic stress in female PL but were increased by acute stress in female DG. BDNF levels in male DG and PL were found not to undergo change in response to stress. Abnormalities in morphology occurred after chronic stress in males but not in females. In all cases, the levels of CREB, pCREB, and BDNF in recovery animals were comparable to the levels of these proteins in control animals. These findings demonstrate a sexual dimorphism in the molecular response to stress and suggest that these differences may have important implications for potential therapeutic treatment of depression.
Combination testing strategies: a survey

Combination strategies are test case selection methods that identify test cases by combining values of the different test object input parameters based on some combinatorial strategy. This survey presents 16 different combination strategies, covering more than 40 papers that focus on one or several combination strategies. This collection represents most of the existing work performed on combination strategies. This survey describes the basic algorithms used by the combination strategies. Some properties of combination strategies, including coverage criteria and theoretical bounds on the size of test suites, are also included in this description. This survey paper also includes a subsumption hierarchy that attempts to relate the various coverage criteria associated with the identified combination strategies. Copyright © 2005 John Wiley & Sons, Ltd.
Peripheral plasma adenosine release in patients with chronic heart failure

Objective: Chronic heart failure (CHF) is accompanied by increased adenosine plasma levels (APLs). It is unknown whether adenosine release occurs at the peripheral level or whether the myocardium itself is the source of adenosine release. To answer this question, we evaluated APLs in the coronary sinus of CHF patients during a resynchronisation procedure and compared the values with those at the peripheral level. We also investigated a possible correlation between APLs and ischaemia-modified albumin (IMA) levels, a useful marker of tissue ischaemia. Methods: 19 men and seven women were prospectively included. Blood samples for APLs were collected simultaneously from a brachial vein (peripheral) and from the coronary sinus. Blood samples for brain natriutretic peptide (BNP) and IMA were collected from a brachial vein. Results: APLs from the brachial vein were higher than those from the coronary sinus (1.69 vs 0.75 μM p<0.01). IMA levels were correlated with APLs from the brachial vein (r = 0.59, p<0.01). BNP concentrations were correlated with APLs from the brachial vein (r = 0.73, p<0.001) but not with APLs from the coronary sinus (r = 0.38, p>0.05). BNP concentrations and IMA levels were correlated (r = 0.71, p<0.001). Conclusions: In CHF patients, adenosine release occurs at a peripheral level and not at the myocardium level.
Research article CYCLOPHOSPHAMIDE INDUCED CHANGES IN CERTAIN HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS OF ADULT MALE RATTUS NORVEGICUS.

Background: Cyclophosphamide (CP), (2-(bis-/2-chloro-ethyl-amino)-tetrahydro-2H-1, 2, 3 oxazaphosphorine-2-oxide), is an alkylating chemotherapeutic agent, which is commonly used against malignancies, such as leukemia, lymphoma, breast, lung, prostrate, and ovarian cancer. The aim of this study is to evaluate the side effect of CP on male albino rat in response to certain hematological and hepatic and renal biochemical parameters. Methods: In this investigation, total 20 albino rats were divided in to two groups of ten each. Group first served as control received i.p. injection of 0.9 physiological saline fed with standard food and water ad libitum. While, Group second received a single dose (0.4ml/100g b/w) through i.p. injection of cyclophosphamide once in a week for a period of 7 and 35 days and hematological parameters i.e. Hb%, total count-RBCs, total count-WBCs along with some biochemical estimations i.e. protein and creatinine levels in liver and kidney were quantified after 7 and 35 days of the treatments. Results: The hematological parameters i.e. Hb%, total count-RBCs, total count -WBCs and protein and creatinine levels in liver and kidney were significantly lowered after 7 and 35 days treatment of cyclophosphamide. The lowering of these values was more prominent in later part of the experiment. Conclusion: Alteration in hematological parameters after cyclophosphamide exposure may impair the functional activities of liver and kidney of male Rattus norvegicus by interfering enzymatic metabolic activities and protein synthesis.
Finding consensus in speech recognition: word error minimization and other applications of confusion networks

We describe a new framework for distilling information from word lattices to improve the accuracy of the speech recognition output and obtain a more perspicuous representation of a set of alternative hypotheses. In the standard MAP decoding approach the recognizer outputs the string of words corresponding to the path with the highest posterior probability given the acoustics and a language model. However, even given optimal models, the MAP decoder does not necessarily minimize the commonly used performance metric, word error rate (WER). We describe a method for explicitly minimizing WER by extracting word hypotheses with the highest posterior probabilities from word lattices. We change the standard problem formulation by replacing global search over a large set of sentence hypotheses with local search over a small set of word candidates. In addition to improving the accuracy of the recognizer, our method produces a new representation of a set of candidate hypotheses that specifies the sequence of word-level confusions in a compact lattice format. We study the properties of confusion networks and examine their use for other tasks, such as lattice compression, word spotting, confidence annotation, and reevaluation of recognition hypotheses using higher-level knowledge sources.
Coenzyme Q10 Status as a Determinant of Muscular Strength in Two Independent Cohorts

Aging is associated with sarcopenia, which is a loss of skeletal muscle mass and function. Coenzyme Q10 (CoQ10) is involved in several important functions that are related to bioenergetics and protection against oxidative damage; however, the role of CoQ10 as a determinant of muscular strength is not well documented. The aim of the present study was to evaluate the determinants of muscular strength by examining hand grip force in relation to CoQ10 status, gender, age and body mass index (BMI) in two independent cohorts (n = 334, n = 967). Furthermore, peak flow as a function of respiratory muscle force was assessed. Spearman’s correlation revealed a significant positive association between CoQ10/cholesterol level and hand grip in the basic study population (p<0.01) as well as in the validation population (p<0.001). In the latter, we also found a negative correlation with the CoQ10 redox state (p<0.01), which represents a lower percentage of the reduced form of CoQ10 (ubiquinol) in subjects who exhibit a lower muscular strength. Furthermore, the age of the subjects showed a negative correlation with hand grip (p<0.001), whereas BMI was positively correlated with hand grip (p<0.01), although only in the normal weight subgroup (BMI <25 kg/m2). Analysis of the covariance (ANCOVA) with hand grip as the dependent variable revealed CoQ10/cholesterol as a determinant of muscular strength and gender as the strongest effector of hand grip. In conclusion, our data suggest that both a low CoQ10/cholesterol level and a low percentage of the reduced form of CoQ10 could be an indicator of an increased risk of sarcopenia in humans due to their negative associations to upper body muscle strength, peak flow and muscle mass.
Effect of various concentrations of antibiotics on osteogenic cell viability and activity

Infection is a common complication of open fractures. Systemic antibiotics often cause adverse events before eradication of infected bone occurs. The local delivery of antibiotics and the use of implants that deliver both growth factors and antimicrobials are ways to circumvent systemic toxicity while decreasing infection and to reach extremely high levels required to treat bacterial biofilms. When choosing an antibiotic for a local delivery system, one should consider the effect that the antibiotic has on cell viability and osteogenic activity. To address this concern, osteoblasts were treated with 21 different antibiotics over 8 concentrations from 0 to 5,000 µg/ml. Osteoblast deoxyribonucleic acid content and alkaline phosphatase activity (ALP) were measured to determine cell number and osteogenic activity, respectively. Antibiotics that caused the greatest decrement include rifampin, minocycline, doxycycline, nafcillin, penicillin, ciprofloxacin, colistin methanesulfonate, and gentamicin; their cell number and ALP were significantly less than control at drug concentrations ≤200 µg/ml. Conversely, amikacin, tobramycin, and vancomycin were the least cytotoxic and did not appreciably affect cell number and ALP until very high concentrations were used. This comprehensive evaluation of numerous antibiotics' effects on osteoblast viability and activity will enable clinicians and researchers to choose the optimal antibiotic for treatment of infection and maintenance of healthy host bone. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1070–1074, 2011
Bone marrow versus thymic pathways of natural killer cell development

Summary: Understanding natural killer (NK) cell developmental pathways is crucial for harnessing the potential therapeutic benefits of this specialized lymphocyte subset. The bone marrow (BM) plays a major role in NK cell development, providing the appropriate environmental cues for NK cell commitment and subsequent NK cell differentiation. Nevertheless, the molecular signals provided in this context remain enigmatic. It is widely assumed that BM seeds the periphery with NK cells. However, the precise origins of NK cells found in lymphoid organs and tissues are not defined. Recently, we found that thymic NK cells bear molecular markers and functional attributes that distinguish them from most peripheral NK cells. We find that NK cells are actively exported from the thymus to the periphery, suggesting that thymus‐derived NK cells may have unique roles both intrathymically and in secondary lymphoid organs. Here we compare the properties of thymic NK cells with properties of other NK cell subsets that have been identified in the mouse. We propose that heterogeneity in NK cell function can be achieved through distinct thymic and bone marrow pathways of NK cell development.
Binary Aggregations in Hierarchical Galaxy Formation: The Evolution of the Galaxy Luminosity Function

We develop a semianalytic model of hierarchical galaxy formation with an improved treatment of the evolution of galaxies inside dark matter halos. We take into account not only dynamical friction processes building up the central dominant galaxy but also binary aggregations of satellite galaxies inside a common halo. These deplete small to intermediate mass objects, affecting the slope of the luminosity function at its faint end, with significant observable consequences. We model the effect of two-body aggregations using the kinetic Smoluchowski equation. This flattens the mass function by an amount that depends on the histories of the host halos as they grow by hierarchical clustering. The description of gas cooling, star formation and evolution, and supernova feedback follows the standard prescriptions widely used in semianalytic modeling. We find that binary aggregations are effective in depleting the number of small/intermediate mass galaxies over the redshift range 1 < z < 3, thus flattening the slope of the luminosity function at the faint end. At z ≈ 0 the flattening occurs for -20 < MB < -18, but an upturn is obtained at the very faint end for MB > -16. We compare our predicted luminosity functions with those obtained from deep multicolor surveys in the Hubble Deep Field-North, Hubble Deep Field-South, and New Technology Telescope Deep Field in the rest-frame B and UV bands for the redshift ranges 0 < z < 1 and 2.5 < z < 3.5, respectively. The comparison shows that the discrepancy of the predictions of other semianalytic models with the observations is considerably reduced at z > 1 and even more at z ≈ 3 by the effect of the binary aggregations. The predictions from our dynamical model are discussed and compared with the effects of complementary processes (additional starburst recipes, alternative sources of feedback, different mass distribution of the dark matter halos) that may conspire in affecting the shape of the luminosity function.
Contrasting Roles for TLR Ligands in HIV-1 Pathogenesis

The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs). Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs) 5 and 9, we examined their effect on human immunodeficiency virus (HIV)-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist) treatment enhanced replication of CC chemokine receptor 5 (CCR 5)-tropic and CXC chemokine receptor 4 (CXCR4)-tropic HIV-1, treatment with oligodeoxynucleotide (ODN) M362 (TLR9 agonist) suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD) 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA)-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.
Influence of thickness on field distortion due to space charge migration in LDPE sheet

Influence of thickness in LDPE sheet on electrical field distortion and transient external current under dc step voltage are studied. Temporal change in space charge distribution in LDPE sheets of 100, 200 and 300 mum in thickness are measured by PEA method with evaporated A1 electrode or semiconduction rubber electrode under a mean applied field of 1 MV/cm. No temporal changes in space charge distribution are observed for 100 mum-thick-sheet with A1-anode/A1-cathode system. The external current exponentially decreases within a few minutes and then it keeps a constant value. For 300 mum-thick-sheet, however, positive charges from anode are penetrated deeply, so that the maximum field strength becomes much higher than the mean field strength. When semiconduction rubber is used as anode, field distortion due to positive-packet penetration is observed clearly even for 200 mum. The relation between packet-moving and current-increasing will be discussed.
Ingestion of toxic substances by children.

Ingestion of a harmful substance is among the most common causes of injury to children less than six years of age. Fortunately, in most cases, the ingested agent has minimal or no clinically important toxic effect. Occasionally, however, such ingestion can be life-threatening or can even result in death. Although preventive measures have been remarkably successful in reducing the frequency and severity of poisoning in children, poisoning continues to occur and requires strategies for treatment and prevention that are safe and effective. In this review, I discuss the management of poisoning in children, with an emphasis on current guidelines for .