Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant immunotoxins for cancer therapy

Recombinant immunotoxins consist of Fv regions of tumour-selective antibodies fused to toxins found in bacteria, plants or fungi. These toxins must be modified to remove normal-tissue binding sites but to retain all other functions of cytotoxicity. The recombinant antibody fragments target the modified toxin to cancer cells which are killed, either by direct inhibition of protein synthesis, or by concomitant induction of apoptosis. Cells that are not recognised by the antibody fragment because they do not carry the tumour antigen, are spared. Many factors influence the in vivo antitumour activity of recombinant immunotoxins. Among them are considerations of which types of cancer may be the best targets for immunotoxin therapy as well as tumour specificity of the antigen that is targeted by the recombinant antibody. Other relevant issues are the affinity of immunotoxins and their ability to enter and penetrate into tissues and tumours, which in turn is dependent on the size of the protein. A great deal of protein-engineering is required to stabilise the recombinant antibody moiety of immunotoxins, since stability of the molecules is crucial for good clinical efficacy. Excellent activity and specificity can be observed for many recombinant immunotoxins in in vitro assays using cultured cancer cells as well as in animal tumour models. Ongoing clinical trials provide examples where the promising preclinical data correlate with successful results in experimental cancer therapy.
Localization of Palatal Area in Human Somatosensory Cortex

To determine the ’hard palate representing’ area in the primary somatosensory cortex, we recorded somatosensory-evoked magnetic fields from the cortex in ten healthy volunteers, using magnetoencephalography. Following electrical stimulation of 3 sites on the hard palate (the first and third transverse palatine ridges, and the greater palatine foramen), magnetic responses showed peak latencies of 15, 65, and 125 ms. Equivalent current dipoles for early magnetic responses were found along the posterior wall of the inferior part of the central sulcus. These dipoles were localized anterior-inferiorly, compared with locations for the hand area in the cortex. However, there were no significant differences in three-dimensional locations among the 3 selected regions for hard palate stimulation. These results demonstrated the precise location of palatal representation in the primary somatosensory cortex, the actual area being small.
MicroRNA-142-5p promotes cell growth and migration in renal cell carcinoma by targeting BTG3.

PURPOSE Some microRNA (miRNA) levels have been found to be dysregulated in cancer patients, suggesting the potential usefulness of miRNAs in cancer therapies. The purpose of this study was to investigate the expression of miR-142-5p in human renal cell carcinoma (RCC) and its potential role in tumor growth and metastasis. METHODS The expression level of miR-142-5p in human RCC tissue and cell lines was determined by quantitative reverse transcription polymerase chain reaction analysis. MTT, colony formation, Transwell, and cell cycle assays were performed to explore the potential functions of miR-142-5p in human RCC cells. The potential target gene of miR-142-5p was identified and confirmed via luciferase reporter assays. RESULTS miR-142-5p expression was elevated in RCC tissues and cell lines. Overexpression of miR-142-5p significantly promoted cell proliferation and colony formation and could prevent G1 phase arrest among RCC 786-O cells. Meanwhile, the migration potential of 786-O cells was greater than that of control cells. BTG3 was identified as a direct target of miR-142-5p, and re-expression of BTG3 reversed the miR-142-5p-induced cell proliferation. CONCLUSION miR-142-5p promoted the proliferation and migration of RCC cells by targeting BTG3. With this potential onco-miRNA role in the progression of RCC, miR-142-5p may be a therapeutic target for the treatment of RCC.
Cloning of a Streptococcus sanguis adhesin which mediates binding to saliva-coated hydroxyapatite

Chromosomal DNA from a salivary aggregating strain of Streptococcus sanguis 12 was partially digested with PstI and ligated into the plasmid vector pUC18 and transformed into Escherichia coli JM83. A total of 1,700 recombinant clones of E. coli were examined by a colony immunoassay with antisera raised against either S. sanguis 12 whole cells or S. sanguis 12 surface fibrils. Five clones which reacted with one or the other antiserum were shown to be unique by Western blotting (immunoblotting) and restriction endonuclease digestion. One recombinant plasmid pSA2 expressed two proteins with Mrs of 20,000 and 36,000. The 36,000-Mr protein has been designated SsaB. Both proteins were purified to homogeneity by Sephadex G-75 and ion-exchange chromatography. The proteins were present in mutanolysin digests of whole-cell lysates of S. sanguis 12 and in the non-saliva-aggregating variant 12na and the hydrophilic variant 12L. Polyclonal antiserum raised against the SsaB protein reacted strongly with the cell surfaces of S. sanguis 12 and 12na but not with that of 12L. SsaB inhibited the adhesion of S. sanguis 12na to saliva-coated hydroxyapatite, indicating that the adhesin mediates the binding to the pH-sensitive receptor.
Dynamic fault tolerance in FPGAs via partial reconfiguration

In this paper we present an on-line, multi-level fault tolerant (FT) technique for system functions and applications mapped to partially and dynamically reconfigurable FPGAs. Our method is based on the roving self testing areas (STARs) fault detection/location strategy presented in Abramovici et al. (1999). In STARs, the area under test uses partial reconfiguration properties to modify the configuration of the area under test without affecting the configuration of the system function and dynamic reconfiguration properties to allow uninterrupted execution of the system function while reconfiguration takes place. In this paper we take this one step further. Once a fault (or multiple faults) is detected we dynamically reconfigure the working area application around the fault with no additional system function interruption (other than the interruption when a STAR moves to a new location). We also apply the concept of partially usable blocks to increase fault tolerance. Our method has been successfully implemented and demonstrated on the ORCA 2CA series FPGAs from Lucent Technologies.
Two-Pore-Domain (Kcnk) Potassium Channels: Dynamic Roles in Neuronal Function

Leak K+ currents contribute to the resting membrane potential and are important for modulation of neuronal excitability. Within the past few years, an entire family of genes has been described whose members form leak K+ channels, insofar as they generate potassium-selective currents with little voltage- and time-dependence. They are often referred to as “two-pore-domain” channels because of their predicted topology, which includes two pore-forming regions in each subunit. These channels are modulated by a host of different endogenous and clinical compounds such as neurotransmitters and anesthetics, and by physicochemical factors such as temperature, pH, oxygen tension, and osmolarity. They also are subject to long-term regulation by changes in gene expression. In this review, the authors describe multiple roles that modulation of leak K+ channels play in CNS function and discuss evidence that members of the two-pore-domain family are molecular substrates for these processes.
Dynamics of oxygen uptake for submaximal exercise and recovery in patients with chronic heart failure.

STUDY DESIGN AND OBJECTIVES Attainment of a steady state for oxygen uptake (VO2) during constant work rate exercise has been reported to take longer for patients with chronic heart failure (CHF) compared with normal. The steady state is also delayed in normal subjects during high-intensity exercise compared with moderate exercise, however, and the delay correlates with the degree of associated lactic acidosis. To determine whether prolonged kinetics of VO2 are attributable solely to the reduction of exercise capacity in CHF, VO2 kinetics were compared for patients with CHF and normal subjects, both for exercise of matched absolute work rate and for matched relative work intensity. SUBJECTS Eighteen men with CHF and 10 normal men. METHODS AND RESULTS Subjects performed 6 min of constant work rate cycle ergometry with breath-by-breath measurement of VO2. Patients were studied using 25 W, and a work rate midway between the lactic acidosis threshold and maximal capacity (50 percent delta). Normal subjects were tested similarly, and also at a work rate matched to the patients' average 50 percent delta work rate. The VO2 kinetics were characterized by the mean response time (MRT) to attain the 6 min VO2 value. Rates of recovery of VO2 were analyzed for 2 min following exercise. For the same absolute work rate, VO2 MRTs were significantly longer for patients than controls (25 W, 67 +/- 26 vs 37 +/- 25 s; approximately 60 W, 87 +/- 20 vs 54 +/- 27 s), but there was no significant difference in VO2 MRT between the two groups at a matched intensity of 50 percent delta (87 +/- 20 vs 81 +/- 18 s). However, the decrease in VO2 during 2 min of recovery was slower for the patients on all comparisons, even for matched exercise intensity. CONCLUSION The VO2 dynamics for submaximal exercise are slowed in CHF. The slower dynamics are not entirely accounted for by the relatively higher intensity of a given work rate, since delayed recovery is evident even at a matched relative work intensity. Exercise intolerance in CHF is characterized not only by decreased maximal exercise capacity, but also by slower adaptations to and from submaximal levels of exercise.
A novel multi-port solid state transformer enabled isolated hybrid microgrid architecture

This paper proposes a multi-port solid state transformer (SST) to integrate a hybrid microgrid with 380 V dc, 48 V dc and 415 V ac sub-grids to the medium voltage distribution network. The system replaces multiple single phase transformers in the conventional SST with one multi-winding transformer thereby reducing the magnetics involved. Moreover, the individual dual active bridges (DAB) in the conventional SST is replaced by Multiple Active Bridge (MAB) configuration which reduces the number of H-bridges. The individual sub-grids are isolated, thus eliminating circulating current flow between them. The control architecture and power management for the system are discussed and verified through simulations using MATLAB Simulink.
A brief review of closed curve approximation technique using iterative point elimination

Closed Curve approximation is a technique to approximate a digital planar curve with piece straight line segments. The terminating point of a candidate line segment is known as pseudo point. By detecting good choice of the pseudo point on the digital planar one may be able to visibly recognize the shape of the curve. The techniques analyzed in this paper makes closed curve approximation by deleting the redundant pseudo high high curvature points and retains the real pseudo high curvature point. This paper makes an attempt to summarize the deficiency of the closed curve approximation techniques under geometric invariance and the response for the noisy curve.
Chemotherapy: Low-Grade Gliomas of the Hypothalamus and Thalamus

Chemotherapy is an increasing component of the management of diencephalic gliomas. It can result in tumor shrinkage and significant disease control in some patients. However, decisions concerning the institution of treatment should be based on the goals of treatment. Factors include: (1) age of the patient; (2) whether the child has neurofibromatosis type 1; (3) tumor size and location; (4) the potential sequelae of radiotherapy, and (5) the acute and long-term toxicity of the chemotherapeutic approach utilized. The erratic natural history of diencephalic tumors confounds evaluation of efficacy of the regimen chosen.
Apoptotic DNA fragmentation.

Degradation of nuclear DNA into nucleosomal units is one of the hallmarks of apoptotic cell death. It occurs in response to various apoptotic stimuli in a wide variety of cell types. Molecular characterization of this process identified a specific DNase (CAD, caspase-activated DNase) that cleaves chromosomal DNA in a caspase-dependent manner. CAD is synthesized with the help of ICAD (inhibitor of CAD), which works as a specific chaperone for CAD and is found complexed with ICAD in proliferating cells. When cells are induced to undergo apoptosis, caspases-in particular caspase 3-cleave ICAD to dissociate the CAD:ICAD complex, allowing CAD to cleave chromosomal DNA. Cells that lack ICAD or that express caspase-resistant mutant ICAD thus do not show DNA fragmentation during apoptosis, although they do exhibit some other features of apoptosis and die. In this review, the molecular mechanism of and the physiological roles played by apoptotic DNA fragmentation will be discussed.
Increased resistance to mycobacterial infection in the absence of interleukin‐10

Interleukin‐10 (IL‐10) down‐regulates T helper type 1 cell and macrophage functions. As IL‐10 is induced along with tumour necrosis factor (TNF) and IL‐12 in mycobacterial infection, we asked whether endogenous IL‐10 plays a role in the antimycobacterial response. We demonstrate here that IL‐10‐deficient mice eliminate Mycobacterium bovis Calmette–Guérin bacillus faster than wild‐type mice. Granulomas are significantly larger, containing more CD‐11b‐ and CD11c‐positive antigen‐presenting cells and T cells, and the expression of major histocompatibility complex class II and intracellular adhesion molecule‐1 is increased. Macrophages in granulomas of IL‐10‐deficient mice express high levels of TNF, acid phosphatase and inducible nitric oxide synthase (iNOS). Finally, an increased cutaneous delayed‐type hypersensitivity reaction to mycobacterial proteins is further evidence of an augmented cell‐mediated immune response. In conclusion, the cell‐mediated immunity is enhanced in the absence of IL‐10, resulting in a robust granuloma response, which accelerates the clearance of mycobacteria. Therefore, endogenous IL‐10 attenuates mycobacterial immunity.
WEIERSTRASS THEOREMS AND RINGS OF HOLOMORPHIC FUNCTIONS

We organize this set of notes around a few theorems of Weierstrass. Write OCn for the sheaf of holomorphic functions on C. In the first three sections, we deduce the following “algebraic” results as consequences of the Weierstrass theorems: (i) for each open set Ω ⊂ C, the ring OCn(Ω) is not Noetherian, (ii) the local ring OCn,0 is factorial, (iii) the local ring OCn,0 is Noetherian. The two later sections can be read independently of the first.
Hidden Sources of Grapefruit in Beverages: Potential Interactions with Immunosuppressant Medications

Purpose The interaction between grapefruit-containing beverages and immunosuppressants is not well defined in the literature. This study was conducted to investigate possible sources of grapefruit juice or grapefruit extract in common US-manufactured beverages. The goal was to identify those products that might serve as hidden sources of dietary grapefruit intake, increasing a transplant patient's risk for drug interactions. Methods A careful review of the ingredients of the 3 largest US beverage manufacturer's product lines was conducted through manufacturer correspondence, product labeling examination, and online nutrition database research. Focus was placed on citrus-flavored soft drinks, teas, and juice products and their impact on a patient's immunosuppressant regimens. Results Twenty-three beverages were identified that contained grapefruit. Five did not contain the word “grapefruit” in the product name. In addition to the confirmed grapefruit-containing products, 17 products were identified as possibly containing grapefruit juice or grapefruit extract. Conclusion A greater emphasis should be placed upon properly educating patients regarding hidden sources of grapefruit in popular US beverages and the potential for food-drug interactions.
Identification and Quantitative Analysis of Project Success Factors for Large Scale Projects

Software projects require a right mix of the software resources and the expertise to increase the chances of timely completion. The interface for the resource allocation to the software projects is provided by the project factors. The identification of the comprehensive project factors for the diversified nature of projects in itself is an open research area. This paper is based on a quantitative study that helps in identifying the prominent software project factors for large scale projects. The paper then, as a result provides a list of project success factors and provides the statistical evidence to support the result of the survey.
Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging

Aging is a major risk factor for metabolic disease and loss of skeletal muscle mass and strength, a condition known as sarcopenia. Both conditions present a major health burden to the elderly population. Here, we analyzed the effect of mildly increased PGC-1α expression in skeletal muscle during aging. We found that transgenic MCK-PGC-1α animals had preserved mitochondrial function, neuromuscular junctions, and muscle integrity during aging. Increased PGC-1α levels in skeletal muscle prevented muscle wasting by reducing apoptosis, autophagy, and proteasome degradation. The preservation of muscle integrity and function in MCK-PGC-1α animals resulted in significantly improved whole-body health; both the loss of bone mineral density and the increase of systemic chronic inflammation, observed during normal aging, were prevented. Importantly, MCK-PGC-1α animals also showed improved metabolic responses as evident by increased insulin sensitivity and insulin signaling in aged mice. Our results highlight the importance of intact muscle function and metabolism for whole-body homeostasis and indicate that modulation of PGC-1α levels in skeletal muscle presents an avenue for the prevention and treatment of a group of age-related disorders.
OsmiR396d-Regulated OsGRFs Function in Floral Organogenesis in Rice through Binding to Their Targets OsJMJ706 and OsCR41[W][OPEN]

MicroRNA-regulated growth-regulating factors activate expression of specific targets to regulate floral organ development, affecting characteristics such as husk openness and sterile lemma length. Inflorescence and spikelet development determine grain yields in cereals. Although multiple genes are known to be involved in the regulation of floral organogenesis, the underlying molecular network remains unclear in cereals. Here, we report that the rice (Oryza sativa) microRNA396d (OsmiR396d) and its Os Growth Regulating Factor (OsGRF) targets, together with Os Growth Regulating Factor-Interacting Factor1 (OsGIF1), are involved in the regulation of floral organ development through the rice JMJD2 family jmjC gene 706 (OsJMJ706) and crinkly4 receptor-like kinase (OsCR4). Transgenic knockdown lines of OsGRF6, a predicted target of OsmiR396d, and overexpression lines of OsmiR396d showed similar defects in floral organ development, including open husks, long sterile lemmas, and altered floral organ morphology. These defects were almost completely rescued by overexpression of OsGRF6. OsGRF6 and its ortholog OsGRF10 were the most highly expressed OsGRF family members in young inflorescences, and the grf6/grf10 double mutant displayed abnormal florets. OsGRF6/OsGRF10 localized to the nucleus, and electrophoretic mobility shift assays revealed that both OsGRF6 and OsGRF10 bind the GA response element in the promoters of OsJMJ706 and OsCR4, which were reported to participate in the regulation of floral organ development. In addition, OsGRF6 and OsGRF10 could transactivate OsJMJ706 and OsCR4, an activity that was enhanced in the presence of OsGIF1, which can bind both OsGRF6 and OsGRF10. Together, our results suggest that OsmiR396d regulates the expression of OsGRF genes, which function with OsGIF1 in floret development through targeting of JMJ706 and OsCR4. This work thus reveals a microRNA-mediated regulation module for controlling spikelet development in rice.
Surface expression of Fc epsilon RI on Langerhans' cells of clinically uninvolved skin is associated with disease activity in atopic dermatitis, allergic asthma, and rhinitis.

BACKGROUND Fc epsilon RI expressed on the surface of human epidermal Langerhans' cells facilitates uptake of IgE-associated allergens and plays a pivotal role in the pathogenesis of atopic dermatitis. Seminal results from studies investigating Langerhans' cell Fc epsilon RI in skin biopsy sections or epidermal cell suspensions demonstrate the highest receptor expression in lesional skin of patients with active atopic dermatitis. OBJECTIVE We sought to investigate and localize Fc epsilon RI expression on Langerhans' cells within a minimally disturbed tissue environment in clinically uninvolved skin and to compare receptor expression between healthy donors and patients with atopic dermatitis or other allergic diseases. METHODS Intact epidermal sheets from skin suction blisters, immunofluorescently stained with Langerhans' cell markers and anti-Fc epsilon RI alpha (mAbs 15E5 and 22E7) or anti-IgE, were examined by means of confocal microscopy. Samples incubated with anti-Fc epsilon RI alpha before or after cell fixation-permeabilization were compared to discriminate between cytoplasmic and membrane localization. RESULTS Cytoplasmic Fc epsilon RI alpha chain was found in Langerhans' cells from all donors, irrespective of atopic status. Surface Fc epsilon RI-bound IgE was detected in the skin of individuals with active atopic dermatitis and in the skin of those with active asthma or rhinitis. No surface Fc epsilon RI was expressed in the skin of patients with a clinical history of atopic dermatitis, asthma, or rhinitis whose disease was in remission or in the skin of nonatopic individuals. CONCLUSION In clinically uninvolved skin, Langerhans' cell-surface Fc epsilon RI expression is not only linked to atopic dermatitis but is also generally associated with allergic disease. This supports the concept of a systemic regulatory mechanism associated with active allergic disease, which is further aggravated by local inflammation in atopic skin lesions.
KIF5A de novo mutation associated with myoclonic seizures and neonatal onset progressive leukoencephalopathy

The KIF5A gene (OMIM 602821) encodes a neuron‐specific kinesin heavy chain involved in intracellular transport of mitochondria and other cargoes. KIF5A protein comprises the N terminal motor domain, the stalk domain and the C‐terminal cargo binding domain. The binding between KIF5A and its cargoes is mediated by kinesin adaptor proteins such as TRAK1 and TRAK2. Numerous missense KIF5A mutations in the motor and stalk domains cause spastic paraplegia type 10 (SPG10, OMIM 604187). Conversely, the role of loss‐of‐function mutations, especially those affecting the cargo binding domain, is unclear. We describe a novel de novo KIF5A p.Ser974fs/c.2921delC mutation found by whole exome sequencing in a patient with a congenital severe disease characterized by myoclonic seizures and progressive leukoencephalopathy. Since this phenotype differs considerably from the KIF5A/SPG10 disease spectrum we propose that the KIF5A p.Ser974fs and possibly other mutations which lead to truncation of the C‐terminal tail of the protein cause a novel disorder. We speculate that the unique effect of the C‐terminal truncating KIF5A mutations may result from the previously described complex role of this protein domain in binding of the TRAK2 and possibly other kinesin adaptor protein(s).