Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies.

PURPOSE To document the toxicity and activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with pretreated hematologic malignancies. PATIENTS AND METHODS Two formulations of SAHA (intravenous [IV] and oral) have been assessed in two consecutive phase I trials. In both trials, dose escalation was performed in parallel and independently in patients with solid tumors and hematologic malignancies. Eligible patients were required to have adequate hepatic and renal function, an absolute neutrophil count > or = 500/microL and a platelet count more than 25,000/mL. All patients provided informed consent for study inclusion. RESULTS A total of 39 patients with hematologic malignancy were enrolled (14 on IV SAHA and 25 on oral SAHA), of whom 35 were treated. The spectrum of diseases included patients with diffuse large B-cell lymphoma (n = 12), Hodgkin's disease (HD; n = 12), multiple myeloma (n = 2), T-cell lymphoma (n = 3), mantle cell lymphoma (n = 2), small lymphocytic lymphoma (n = 2), and myeloid leukemia (n = 2). Major adverse events with the oral formulation included fatigue, diarrhea, anorexia, and dehydration, whereas myelosuppression and thrombocytopenia were more prominent with the IV formulation. Typically, the hematologic toxicities resolved shortly after SAHA was stopped. There was no neutropenic fever or neutropenic sepsis. Reduction in measurable tumor was observed in five patients. One patient with transformed small lymphocytic lymphoma met criteria for complete response, whereas another met the criteria for partial response (PR). One patient with refractory HD had a PR, whereas three patients had stable disease for up to 9 months. CONCLUSION These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.
Real time measurement of the structural change in P3HT:PCBM thin films and the relation with device performance in OPV cells

The Al electrode on P3HT:PCBM blended thin films modified the nano structure of P3HT crystals during thermal annealing. The presence of an Al layer induced less preferred distribution of P3HT crystals after thermal annealing. In the surface region, the lateral growth of amorphous like (0.7 nm thick in [010] direction) face-on P3HT crystals was also affected by the inter diffusion of Al atoms into the active layer during thermal annealing in the presence of the Al layer. The inter diffusion of Al atoms produced an intermediate layer between the electrode and the active layer. By the real time measurement using synchrotron x-rays, we could confirm interfacial changes during annealing process. To understand the relation of structures and the device performance, we fabricated devices using pre and post annealing processes. The J-V characteristics show that more randomly distributed P3HT crystals are more advantageous to form the interpenetrating networks in the active layer. The short circuit current seems to be affected by nano structure of P3HT crystals in the bulk region, while the series resistance is more affected by the interfacial properties between the electrode and the active layer.
Streamlining Whole Function Vectorization in C Using Higher Order Vector Semantics

Taking full advantage of SIMD instructions in C programs still requires tedious and non-portable programming using intrinsics, despite considerable efforts spent developing auto-vectorization capabilities in recent decades. Whole Function Vectorization (WFV) is a recent technique for extending the use of SIMD across entire functions. WFV has so far only been used in data-parallel languages such as OpenCL and ISPC. We propose a vector-oriented programming framework that facilitates WFV directly in C. We show that our framework achieves competitive performance to Open CL and ISPC while maintaining C's original syntax and semantics. This allows C programmers to gain better performance for their applications by improving SIMD utilization, without stepping out of C.
Rate of growth of soft tissue metastases of breast cancer

The gross rates of growth of 171 soft tissue metastatic lesions of breast cancer in 54 patients seen at Ellis Fischel State Cancer Hospital were studied. The frequency distributions of these rates are lognormal and are analyzed statistically as such. Both the linear diametric growth rate (LR) and the exponential growth rate, expressed as volumetric doubling times (DT), of 66 untreated lesions were presented as baselines for further study (LR: mean 0.21 mm/day, 95% range of 0.04–1.05; DT: mean 17.1 days, 95% range 3.4–86.1). Rates of growth of simultaneous metastatic lesions of both the same and different sites (e.g., axilla, chest wall, supraclavicular, and other regions) in the same patients were compared. The mean ratios of growth of the paired lesions were close to “one”; however, in 95% of the cases the rates can be differentiated by a factor of one‐fifth to seven. In lesions that responded to radiation therapy, hormones, or chemotherapy, the ratios of rate of shrinkage after therapy to the rate of growth before therapy also had means of approximately “one” (95% range of ratios: 0.2–4.2). There is considerable variability of the data presented due to limited numbers of selected lesions that could be measured, the errors of data gathering, and assumptions made during calculations.
Analysis of Second-Order Modes of Linear Continuous-Time Systems under Positive-Real Transformations

This paper discusses the behavior of the second-order modes of linear continuous-time systems under variable transformations with positive-real functions. We first discuss the case of lossless positive-real transformations, and show that the second-order modes are invariant under any lossless positive-real transformation. We next consider the case of general positive-real transformations, and reveal that the values of the second-order modes are decreased under any general positive-real transformation. We achieve the derivation of these results by describing the controllability/observability Gramians of transformed systems, with the help of the lossless positive-real lemma, the positive-real lemma, and state-space formulation of transformed systems.
Ubiquitous Awareness Spaces

In this paper, I describe the present course of research we are pursuing related to the design, development, deployment and evaluation of ubiquitous and reactive environments for supporting casual interactions among intimate collaborators. I begin by briefly describing the work done in this area by us and by others and give some motivation for the design decisions made. I then step back from the problem to re-evaluate the designs, and question the suitability of ubiquitous computing for supporting teleawareness and facilitation of informal interaction. I examine problems relating to privacy in the ubiquitous media space, and expose them as failures resulting from the drive for a seamless user interface. I conclude by generalizing these problems to other applications of ubiquitous computing, and revisit previously held tenets about how reactive environments should be designed and question their sanctity in light of the problems identified.
Swallowing Problems in Adults with Traumatic Brain Injury

In patients with traumatic brain injury, the anatomic and physiologic status of the swallowing mechanism may be impaired. Patients typically compensate for these impairments by learning and using compensatory strategies to ensure safe and efficient food intake. However, when cognitive-communicative and behavioral impairments are also present, the rehabilitation of dysphagia is more complex and challenging. To facilitate maximum recovery from dysphagia, an interdisciplinary team approach is essential. Teams may include several medical and allied healthcare professionals such as the physician, nurse, speech-language pathologist, clinical dietitian, and physical and occupational therapist. The psychologist may be consulted to provide expertise in behavioral management strategies. The patient and caregiver also are integral members of this treatment team. Each team member needs to be aware of the food consistencies that are appropriate and the specific feeding techniques that are required. It is critical that all team members be consistent in their approach to feeding for the patient to learn and generalize the use of compensatory strategies. This article has presented a review of the literature on swallowing problems in traumatic brain injury. It is apparent that there are relatively few data-based studies that describe the impairments and even fewer that discuss the efficacy of treatment for dysphagia in these patients. In view of the frequency of oral intake problems in individuals with traumatic brain injury, and the added challenge of the cognitive-communicative problems, further studies are needed to increase our understanding of swallowing problems, their treatment, and recovery in this patient population.
Sub-50NM InGaAs/InAlAs/InP HEMT for sub-millimeter wave power amplifier applications

An InGaAs/InAlAs/InP HEMT with sub-50nm EBL gate has been developed for sub-millimeter wave (SMMW) power amplifier (PA) applications. In this paper, we report the device performance including high drain current, high gain, high breakdown voltage and scalability to large gate periphery, which are essential for achieving high output power at these frequencies. Excellent yield, process uniformity and repeatability are also demonstrated, which is critical for power amplifiers employing large number of devices and gate fingers. 10mW output power is demonstrated from a fixtured 338 GHz PA module.
Peyer's patch adherence of enteropathogenic Escherichia coli strains in rabbits

RDEC-1 (serotype O15) is an attaching and effacing strain of rabbit enteropathogenic Escherichia coli (REPEC) that causes diarrhea in postweanling rabbits. It expresses AF/R1 pili that mediate Peyer's patch M-cell adherence. We investigated Peyer's patch adherence, the presence of virulence genes, ileal brush border aggregation, and pilus expression in 9 strains representing several serotypes of REPEC as well as in two commensal strains. Postweanling rabbits were inoculated with 10(6) organisms and sacrificed at 24 h, and tissues were prepared for examination by light microscopy. Strains B10 and RDEC-1 were also studied at 12 and 72 h postinoculation. All REPEC strains were eaeA positive, expressed pili, and adhered to ileal brush borders. Both commensal strains expressed pili, and one strain adhered to brush borders. All REPEC strains demonstrated some degree of Peyer's patch lymphoid follicle adherence, ranging from diffuse coverage to small patches covering two to three dome epithelial cells. Strains C102 and C110 had genes homologous with the structural subunit gene of the AF/R1 pilus (afrA) of RDEC-1, which correlated with greater degrees of lymphoid follicle adherence and lesser degrees of ileal villus adherence. The observation that all REPEC strains adhere to Peyer's patch epithelium suggests the possibility that human strains of enteropathogenic E. coli (EPEC) might do likewise. EPEC strains might thus serve as mucosal vaccine vectors in humans. Better understanding of the molecular mechanism of REPEC adherence should provide a model for the targeting of the Peyer's patch in humans.
Synthesis of a Sequential Model of Muscles of a Man during Drop Landing on a Hard Platform

The objective of this paper is to identify the parameters of a new plane biodynamic model of a man jumping down on a hard base. In the modelling of this kind of dynamic phenomena, with dominant directions of human body motion and reactions, many simple and complex models have already been applied. Some of them were lumped parameter and unidirectional [Książek, 1999], [Fritz, 2001] or plane [Pandy, 1990], [Farley, 1998]. There are also spatial models, applied in the sport and medical investigations of the kinematics and dynamics of the human body [Morecki, 1990], [A. Nagano and col., 2005]. The presented approach has been founded on the results of experiments described in [Nosiadek, 2006] where body motions of 40 men volunteers were registered during drop jumping and landing from several assumed heights. By means of video cameras in 3D space and a dynamic platform linear and angular displacements of participants’ bodies and three mutually perpendicular components of the dynamical reactions between the feet and platform were measured. The numerical results of the displacements were numerically remodelled by the authors of the present paper and used for synthesis of models of muscles of a man during drop landing. Similar investigations can be found in [Pain and Challis, 2006].
Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion.
Optical properties of tissue simulators based on laser-induced spectroscopy and scattering measurements

Measurements of the tissue optical parameters and the theoretical modeling of the light propagation in biological tissues is very important for real time laser treatment dosimetry and non- invasive diagnosis. An integrating sphere based technique was used to determine the tissue optical properties. Soft tissue - like phantoms were irradiated with visible lasers and the optical parameters were compared with results calculated from the Beer's law model of light propagation and the Kubelka - Munk simulation.
Fundamental Theory for Typed Attributed Graphs and Graph Transformation based on Adhesive HLR Categories

The concept of typed attributed graphs and graph transformation is most significant for modeling and meta modeling in software engineering and visual languages, but up to now there is no adequate theory for this important branch of graph transformation. In this article we give a new formalization of typed attributed graphs, which allows node and edge attribution. The first main result shows that the corresponding category is isomorphic to the category of algebras over a specific kind of attributed graph structure signature. This allows to prove the second main result showing that the category of typed attributed graphs is an instance of "adhesive HLR categories". This new concept combines adhesive categories introduced by Lack and Sobocinski with the well-known approach of high-level replacement (HLR) systems using a new simplified version of HLR conditions. As a consequence we obtain a rigorous approach to typed attributed graph transformation providing as fundamental results the Local Church-Rosser, Parallelism, Concurrency, Embedding and Extension Theorem and a Local Confluence Theorem known as Critical Pair Lemma in the literature.
A global pathway crosstalk network

MOTIVATION Given the complex nature of biological systems, pathways often need to function in a coordinated fashion in order to produce appropriate physiological responses to both internal and external stimuli. Therefore, understanding the interaction and crosstalk between pathways is important for understanding the function of both cells and more complex systems. RESULTS We have developed a computational approach to detect crosstalk among pathways based on protein interactions between the pathway components. We built a global mammalian pathway crosstalk network that includes 580 pathways (covering 4753 genes) with 1815 edges between pathways. This crosstalk network follows a power-law distribution: P(k) approximately k(-)(gamma), gamma = 1.45, where P(k) is the number of pathways with k neighbors, thus pathway interactions may exhibit the same scale-free phenomenon that has been documented for protein interaction networks. We further used this network to understand colorectal cancer progression to metastasis based on transcriptomic data. CONTACT yong.2. li@gsk.com SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Tracking Chromatid Segregation to Identify Human Cardiac Stem Cells That Regenerate Extensively the Infarcted Myocardium

Rationale: According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening. Objective: Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration. Methods and Results: Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs. Additionally, their growth properties were determined by a series of in vitro and in vivo studies. We report that a small class of hCSCs retain during replication the mother DNA and generate 2 daughter cells, which carry the old and new DNA, respectively. hCSCs with immortal DNA form a pool of nonsenescent cells with longer telomeres and higher proliferative capacity. The self-renewal and long-term repopulating ability of these cells was shown in serial-transplantation assays in the infarcted heart; these cells created a chimeric organ, composed of spared rat and regenerated human cardiomyocytes and coronary vessels, leading to a remarkable restoration of cardiac structure and function. The documentation that hCSCs divide by asymmetrical and symmetrical chromatid segregation supports the view that the human heart is a self-renewing organ regulated by a compartment of resident hCSCs. Conclusions: The impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the “mother” DNA underscores the clinical relevance of this stem cell class for the management of heart failure in humans.
Estrogen Prevents the Lipopolysaccharide-Induced Inflammatory Response in Microglia

After neuronal injury and in several neurodegenerative diseases, activated microglia secrete proinflammatory molecules that can contribute to the progressive neural damage. The recent demonstration of a protective role of estrogen in neurodegenerative disorders in humans and experimental animal models led us to investigate whether this hormone regulates the inflammatory response in the CNS. We here show that estrogen exerts an anti-inflammatory activity on primary cultures of rat microglia, as suggested by the blockage of the phenotypic conversion associated with activation and by the prevention of lipopolysaccharide-induced production of inflammatory mediators: inducible form of NO synthase (iNOS), prostaglandin-E2 (PGE2), and metalloproteinase-9 (MMP-9). These effects are dose-dependent, maximal at 1 nm 17β-estradiol, and can be blocked by the estrogen receptor (ER) antagonist ICI 182,780. The demonstration of ERα and ERβ expression in microglia and macrophages and the observation of estrogen blockade of MMP-9 mRNA accumulation and MMP-9 promoter induction further support the hypothesis of a genomic activity of estrogen via intracellular receptors. This is the first report showing an anti-inflammatory activity of estrogen in microglia. Our study proposes a novel explanation for the protective effects of estrogen in neurodegenerative and inflammatory diseases and provides new molecular and cellular targets for the screening of ER ligands acting in the CNS.
ANCHOR: a web server and database for analysis of protein–protein interaction binding pockets for drug discovery

ANCHOR is a web-based tool whose aim is to facilitate the analysis of protein–protein interfaces with regard to its suitability for small molecule drug design. To this end, ANCHOR exploits the so-called anchor residues, i.e. amino acid side-chains deeply buried at protein–protein interfaces, to indicate possible druggable pockets to be targeted by small molecules. For a given protein–protein complex submitted by the user, ANCHOR calculates the change in solvent accessible surface area (ΔSASA) upon binding for each side-chain, along with an estimate of its contribution to the binding free energy. A Jmol-based tool allows the user to interactively visualize selected anchor residues in their pockets as well as the stereochemical properties of the surrounding region such as hydrogen bonding. ANCHOR includes a Protein Data Bank (PDB) wide database of pre-computed anchor residues from more than 30 000 PDB entries with at least two protein chains. The user can query according to amino acids, buried area (SASA), energy or keywords related to indication areas, e.g. oncogene or diabetes. This database provides a resource to rapidly assess protein–protein interactions for the suitability of small molecules or fragments with bioisostere anchor analogues as possible compounds for pharmaceutical intervention. ANCHOR web server and database are freely available at http://structure.pitt. edu/anchor.