Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-13 Receptor-Targeted Cytotoxin Cancer Therapy Leads to Complete Eradication of Tumors with the Aid of Phagocytic Cells in Nude Mice Model of Human Cancer1

Tumor-directed therapeutic approaches require unique or overexpressed specific Ag or receptor as a target to achieve selective tumor killing. However, heterogeneous expression of these targets on tumor cells limits the efficacy of this form of therapy. In this study, we forced abundant expression of IL-13Rα2 chain by plasmid-mediated gene transfer in head and neck, as well as prostate tumors to provide a potential target. This was followed by successfully treating xenograft tumor-bearing nude mice with IL-13R-directed cytotoxin (IL13-PE38QQR). Although we did not observe an indirect cytotoxic bystander effect conveyed to nontransduced tumor cells in vitro, our approach in vivo led to a complete regression of established tumors transfected with IL-13Rα2 chain in most animals. We found that the tumor eradication was achieved in part by infiltration of macrophages and NK cells, assessed by immunohistochemistry. Moreover, head and neck tumors xenografted in macrophage-depleted nude mice were less sensitive to the antitumor effect of IL-13 cytotoxin. Because we did not observe vector-related toxicity in any vital organs, our novel combination strategy of gene transfer of IL-13Rα2 chain and receptor-directed cytotoxin therapy may be a useful approach for the treatment of localized cancer.
Assessment of a Bovine Viral Diarrhea Virus Antigen Capture ELISA and a Microtiter Virus Isolation ELISA Using Pooled Ear Notch and Serum Samples

To reduce the cost of whole herd screening for bovine viral diarrhea virus persistently infected animals, the sensitivity and specificity of an antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) and a microtiter virus isolation ELISA using saline from ear notch samples or pooled serum was determined. Pooled saline from ear notch samples, assayed by AC-ELISA, gave a sensitivity and specificity of 98% and 94%, respectively, for pools containing 2 samples and 72% and 100%, respectively, for pools of 5. The sensitivity of pooled ear notch or serum samples for bovine viral diarrhea virus detection by microtiter virus isolation (sensitivity < 5%) or serum samples for detection by AC-ELISA (sensitivity < 15%) is too low to be used for whole herd screening. Pooling saline from ear notch samples from 2 animals tested by AC-ELISA, however, could provide a less expensive, reliable method for whole herd screening for bovine viral diarrhea virus.
Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons

ABSTRACT The ability of sensory neurons to detect potentially harmful stimuli relies on specialized molecular signal detectors such as transient receptor potential (TRP) A1 ion channels. TRPA1 is critically implicated in vertebrate nociception and different pain states. Furthermore, TRPA1 channels are subject to extensive modulation and regulation - processes which consequently affect nociceptive signaling. Here we show that the neuropeptide Nocistatin sensitizes TRPA1-dependent calcium influx upon application of the TRPA1 agonist mustard oil (MO) in cultured sensory neurons of dorsal root ganglia (DRG). Interestingly, TRPV1-mediated cellular calcium responses are unaffected by Nocistatin. Furthermore, Nocistatin-induced TRPA1-sensitization is likely independent of the Nocistatin binding partner 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) as assessed by siRNA-mediated knockdown in DRG cultures. In conclusion, we uncovered the sensitization of TRPA1 by Nocistatin, which may represent a novel mechanism how Nocistatin can modulate pain.
Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease

Objective: To examine long-term safety and efficacy of bosentan—an oral dual endothelin receptor antagonist—in patients with pulmonary hypertension associated with congenital heart disease or Eisenmenger’s syndrome. Design: Retrospective study. Setting: Tertiary cardiology referral centre. Patients: All adult patients with pulmonary arterial hypertension associated with congenital heart disease treated with bosentan at the Royal Brompton Adult Congenital Heart Centre were included. Main outcome measures: Oxygen saturation, functional (WHO) class, 6-minute walk test distance and liver enzymes were analysed. Results: Eighteen patients (14 female) with pulmonary arterial hypertension associated with congenital heart disease (15 patients with Eisenmenger’s syndrome) with a mean (SD) age of 41 (9) years (range 23–69) were included. Median follow-up was 29 months (range 1–39). One patient died during follow-up. Patients tolerated bosentan well and no significant rise in liver transaminases was seen. Arterial oxygen saturation remained stable throughout follow-up. Mean (SD) functional class (p = 0.001) and the 6-minute walk test distance improved compared with baseline (284 (144) vs 363 (124) m, 380 (91) m and 408 (114) m at baseline, 0–6 months, 6–12 months and 1–2 years of treatment, respectively; p<0.05 for each). Conclusions: Bosentan appears to be safe and well tolerated in adults with pulmonary arterial hypertension associated with congenital heart disease or Eisenmenger’s syndrome during mid- to long-term follow-up. In addition, functional class and the 6-minute walk test distance improved and this effect was maintained for up to 2 years of bosentan treatment.
The interplay of HuR and miR-3134 in regulation of AU rich transcriptome

MicroRNAs and AU Rich element (ARE)-mediated degradation of transcripts are thought to be two independent means of gene regulation at the post-transcriptional level. However, since their site of action is the same (3‘UTR of mRNA), there exists a high probability that specific miRNAs may bind to AREs and, thus, interact with ARE-binding proteins (ARE-BPs) to regulate transcript levels. In this study, we have characterized AREs as potential targets of hsa-miR-3134. An analysis of the global gene expression profile of breast cancer cell line MCF7 overexpressing miR-3134 revealed the presence of at least one AUUUA element in the 3′-UTRs of 63% of miR-3134 regulated protein coding genes. Quantitative RT-PCR or 3′UTR luciferase assays show that miR-3134 mediates an up to 4–8-fold increase in the levels of ARE bearing transcripts-SOX9, VEGFA, and EGFR, while mutated miR-3134 shows a decreased effect. The miR-3134-mediated increase in transcript levels was unaffected by treatment with transcription inhibitor (actinomycin D), indicating that miR-3134 enhances transcript stability. To investigate a possible interplay between miR-3134 and a prototype ARE-BP, HuR, we compared their overexpression transcriptome profiles. Interestingly, up to 80% of miR-3134-regulated genes were also regulated by HuR. Overexpression studies of HuR alone or in combination with miR-3134 shows that wt miR-3134 but not a mutated miR-3134 promotes stabilization of HuR-regulated transcripts SOX9, VEGFA, and EGFR as confirmed by qRT-PCR or RNA-immunoprecipitation experiments. Overall, this report suggests that collaboration between ARE-binding microRNAs and ARE-binding proteins could be a general mechanism of 3′-UTR mediated regulation of gene expression in human cells.
Single‐Dose Pharmacokinetics of Repaglinide in Subjects with Chronic Liver Disease

Repaglinide is a novel insulin secretagogue developed in response to the need for a fast‐acting, oral prandial glucose regulator for the treatment of type 2 (non‐insulin‐dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. This open, parallel‐group study compared the pharmacokinetics and tolerability of a single 4 mg dose of repaglinide in healthy subjects (n = 12) and patients with chronic liver disease (CLD) (n = 12). Values for AUC and Cmax were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients. Values for tmax did not differ between the groups, but t1/2 was significantly prolonged in CLD patients compared with previously determined values in healthy subjects. AUC was inversely correlated with caffeine clearance in CLD patients but not in healthy subjects. Blood glucose profiles were similar in both groups. Adverse events (principally hypoglycemia) were similar in the two groups; none was serious. Repaglinide clearance is significantly reduced in patients with hepatic impairment; the agent should be used with caution in this group.
Anti‐myeloperoxidase antibodies in sera from patients with propylthiouracil‐induced vasculitis might recognize restricted epitopes on myeloperoxidase molecule

Myeloperoxidase (MPO) is one of the major target antigens of antineutrophil cytoplasmic antibodies (ANCA) in primary systemic vasculitis. It is known that propylthiouracil (PTU) could induce MPO–ANCA‐positive vasculitis. The production of anti‐MPO antibodies in patients with PTU‐induced vasculitis may be different from that in patients with primary microscopic polyangiitis (MPA). One possible reason for this may be differences in epitope recognition. The aim of this study is to compare the epitopes of antibodies to MPO in sera from patients with PTU‐induced vasculitis (n = 10) and MPA (n = 10). The sera were collected and used to inhibit monoclonal antibodies against human MPO (3D8 and 6B9) and affinity purified, horseradish peroxidase conjugated human anti‐MPO antibodies (Pab1‐HRP, Pab2‐HRP) in a competitive inhibition enzyme‐linked immunosorbent assay (ELISA) system using soluble human MPO as solid phase ligand. The Pab1‐HRP and Pab2‐HRP were affinity purified from plasma exchanges of a patient with PTU‐induced vasculitis and a patient with MPA, respectively. The inhibition rates were evaluated and compared between the PTU and primary MPA groups. In the PTU group all 10 sera could inhibit 3D8: the average inhibition rate was 44·7% ± 5·0%; 9/10 sera could inhibit 6B9: the average inhibition rate was 35·6% ± 6·0%. However, in the MPA group all 10 sera could inhibit 3D8 and 6B9; the average inhibition rates were 68·4% ± 16·1% (P < 0·01) and 62·2% ± 17·2% (P < 0·01), respectively. Sera in both the PTU and MPA groups could inhibit Pab1‐HRP and the inhibition rates were 81·4% ± 9·4%versus 86·6% ± 17·2% (P > 0·05). However, the average inhibition rate for Pab2‐HRP in the MPA group was significantly higher than that in the PTU group (76·3% ± 7·8%versus 58·9% ± 15·5%, P < 0·01). We conclude that anti‐MPO antibodies from patients with PTU‐induced vasculitis and from patients with primary MPA could recognize more than one epitope on the native MPO molecule. Although the epitopes overlapped between the two groups, the epitopes of anti‐MPO antibodies from patients with PTU‐induced vasculitis might be more restricted.
Multi-objective, Decentralized Dynamic Virtual Machine Consolidation using ACO Metaheuristic in Computing Clouds

Underutilization of computing resources and high power consumption are two primary challenges in the domain of Cloud resource management. This paper deals with these challenges through offline, migration impact-aware, multi-objective dynamic Virtual Machine (VM) consolidation in the context of large-scale virtualized data center environments. The problem is formulated as an NP-hard discrete combinatorial optimization problem with simultaneous objectives of minimizing resource wastage, power consumption, and the associated VM migration overhead. Since dynamic VM consolidation through VM live migrations have negative impacts on hosted applications performance and data center components, a VM live migration overhead estimation technique is proposed, which takes into account pragmatic migration parameters and overhead factors. In order to tackle scalability issues, a hierarchical, decentralized dynamic VM consolidation framework is presented that helps to localize migration-related network traffic and reduce network cost. Moreover, a multi-objective, dynamic VM consolidation algorithm is proposed by utilizing the Ant Colony Optimization (ACO) metaheuristic, with integration of the proposed VM migration overhead estimation technique. Comprehensive performance evaluation makes it evident that the proposed dynamic VM consolidation approach outpaces the state-of-the-art offline, migration-aware dynamic VM consolidation algorithm across all performance metrics by reducing the overall power consumption by up to 47%, resource wastage by up to 64%, and migration overhead by up to 83%.
Sample prefractionation with Sephadex isoelectric focusing prior to narrow pH range two‐dimensional gels

Due to their heterogeneity and huge differences in abundance, the detection and identification of all proteins expressed in eukaryotic cells and tissues is a major challenge in proteome analysis. Currently the most promising approaches are sample prefractionation procedures prior to narrow pH range two‐dimensional gel electrophoresis (IPG‐Dalt) to reduce the complexity of the sample and to enrich for low abundance proteins. We recently developed a simple, cheap and rapid sample prefractionation procedure based on flat‐bed isoelectric focusing (IEF) in granulated gels. Complex sample mixtures are prefractionated in Sephadex gels containing urea, zwitterionic detergents, dithiothreitol and carrier ampholytes. After IEF, up to ten gel fractions alongside the pH gradient are removed with a spatula and directly applied onto the surface of the corresponding narrow pH range immobilized pH gradient (IPG) strips as first dimension of two‐dimensional (2‐D) gel electrophoresis. The major advantages of this technology are the highly efficient electrophoretic transfer of the prefractionated proteins from the Sephadex IEF fraction into the IPG strip without any sample dilution, and the full compatibility with subsequent IPG‐IEF, since the prefactionated samples are not eluted, concentrated or desalted, nor does the amount of the carrier ampholytes in the Sephadex fraction interfere with subsequent IPG‐IEF. Prefractionation allows loading of higher protein amounts within the separation range applied to 2‐D gels and facilitates the detection of less abundant proteins. Also, this system is highly flexibile, since it allows small scale and large scale runs, and separation of different samples at the same time. In the current study, this technology has been successfully applied for prefractionation of mouse liver proteins prior to narrow pH range IPG‐Dalt.
An Asymmetry Between Memory Encoding and Retrieval

Transfer-appropriate-processing accounts of memory emphasize the similarity of encoding and retrieval processes, and imply that experimental manipulations should have similar effects on encoding and retrieval. Exceptions to this expectation are thus of great interest, but extant exceptions (produced by studies using divided attention, alcohol, and benzodiazepines) are debatable, single dissociations between encoding and retrieval. The present experiments demonstrate a reversed dissociation, in which the same variable produced opposite effects when implemented at encoding and retrieval. At encoding, participants either solved anagrams of study words or read intact study words. At retrieval, participants likewise solved anagrams or read intact words prior to making recognition memory judgments. Compared with reading intact words, solving anagrams at encoding enhanced later recognition accuracy, whereas solving anagrams at test impaired accuracy. These results were obtained with old/new decisions (Experiment 1) and with confidence ratings (Experiment 2).
Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of the archaeon Thermococcus litoralis

The members of the ABC transporter family transport a wide variety of molecules into or out of cells and cellular compartments. Apart from a translocation pore, each member possesses two similar nucleoside triphosphate‐binding subunits or domains in order to couple the energy‐providing reaction with transport. In the maltose transporter of several Gram‐negative bacteria and the archaeon Thermo coccus litoralis, the nucleoside triphosphate‐binding subunit contains a C‐terminal regulatory domain. A dimer of the subunit is attached cytoplasmically to the translocation pore. Here we report the crystal structure of this dimer showing two bound pyrophosphate molecules at 1.9 Å resolution. The dimer forms by association of the ATPase domains, with the two regulatory domains attached at opposite poles. Significant deviation from 2‐fold symmetry is seen at the interface of the dimer and in the regions corresponding to those residues known to be in contact with the translocation pore. The structure and its relationship to function are discussed in the light of known mutations from the homologous Escherichia coli and Salmonella typhimurium proteins.
Isolation and partial characterization of a monoclonal antibody to the Rous sarcoma virus transforming protein pp60src

Transformation of cells by Rous sarcoma virus is mediated by the product of the viral src gene, pp60src. A hybridoma cell line producing an immunoglobulin G3 antibody to pp60src was isolated after lymph node cells from immune mice were fused with mouse myeloma cells (P3-NS1-1). Mice were immunized with p60src purified from Escherichia coli cells expressing the src gene product. The monoclonal antibody immunoprecipitated pp60src from Rous sarcoma virus-transformed cells and recognized an antigenic determinant located in the amino-terminal third of the pp60src protein.
Topological Insulator-Assisted Dual-Wavelength Fiber Laser Delivering Versatile Pulse Patterns

We report on the generation of dual-wavelength mode-locked pulses in an erbium-doped fiber laser incorporating a topological insulator (TI): Bi2Se3/Polyvinyl Alcohol (PVA) film which could operate as both an excellent saturable absorber (SA) for mode-locking and a high-nonlinear medium for mitigating the mode competition of erbium-doped fiber and stabilizing the dual-wavelength oscillation. The TI: Bi2Se3/PVA film is prepared through a liquid-phase exfoliation/spin-coating method. Its saturating intensity and modulation depth are measured to be about 31.5 MW/cm2 and 3.4%, respectively. Taking advantage of the high nonlinearity and saturable absorption of the TI: Bi2Se3, three dual-wavelength pulse patterns, namely bright pulse, bright-dark soliton pair, and hybrid step-like and dark pulse, could be achieved under different lengths of single mode fiber by properly adjusting the pump power and the polarization state. For the bright pulse operation, we obtain its fundamental repetition rate of 9.75 MHz. For the bright-dark soliton pair operation, we find that it contains two distinct parts in the whole optical spectrum: one is at shorter wavelength corresponds to bright soliton and the other one is at longer wavelength corresponds to dual-wavelength dark soliton. In addition, we also achieved the harmonic mode-locking (HML) of the bright-dark soliton pair. The highest obtained repetition rate is about 433.8 MHz, which corresponds to the 280th harmonic of the fundamental repetition rate. For the hybrid step-like and dark pulse operation, we achieve its fundamental repetition rate of 8.805 MHz. Our findings suggest that TI: Bi2Se3 can operate as both an excellent SA for short pulse generation and a promising highly nonlinear photonic material for the related nonlinear optics applications.
Aggressive look-ahead earliest deadline first algorithm

Dynamic voltage and frequency scaling technology is a promising way to save system energy. We proposed an energy-efficient scaling algorithm which utilizes both static and dynamic slack to adjust the frequency and voltage of a processor for running periodic tasks. Instead of excessively using up slack for the task under consideration, our proposed algorithm takes a global approach by intelligently assigning proper slices of slack to tasks and scaling the processor correspondingly. Experiments with an example system demonstrate that the energy consumption of our proposed algorithm is not larger than 3% of the theoretical limit.
Healthcare resource availability and cardiovascular health in the USA

Objectives Cardiovascular disease (CVD) remains the leading cause of death in the USA. Reducing the population-level burden of CVD disease will require a better understanding and support of cardiovascular health (CVH) in individuals and entire communities. The objectives for this study were to examine associations between community-level healthcare resources (HCrRes) and CVH in individuals and entire communities. Setting This study consisted of a retrospective, cross-sectional study design, using multivariable epidemiological analyses. Participants All participants in the 2011 Behavioral Risk Factor Surveillance System (BRFSS) survey were examined for eligibility. CVH, defined using the American Heart Association CVH Index (CVHI), was determined using self-reported responses to 2011 BRFSS questions. Data for determining HCrRes were obtained from the Area Health Resource File. Regression analysis was performed to examine associations between healthcare resources and CVHI in communities (linear regression) and individuals (Poisson regression). Results Mean CVHI was 3.3±0.005 and was poorer in the Southeast and Appalachian regions of the USA. Supply of primary care physicians and physician assistants were positively associated with individual and community-level CVHI, while CVD specialist supply was negatively associated with CVHI. Individuals benefiting most from increased supply of primary care providers were: middle aged; female; had non-Hispanic other race/ethnicity; those with household income <$25 000/year; and those in non-urban communities with insurance coverage. Conclusions Our results support the importance of primary care provider supply for both individual and community CVHI, though not all sociodemographic groups benefited equally from additional primary care providers. Further research should investigate policies and factors that can effectively increase primary care provider supply and influence where they practice.
Pathology of hepatocellular carcinoma in Japan: 232 consecutive cases autopsied in ten years

The pathologic findings of 232 consecutive cases of hepatocellular carcinoma (HCC) autopsied during the past ten years at Kurume, Japan, were analyzed from the point of view of global epidemiology, in relation to clinical feature, and in regard to incidence, age, sex, etiologic factors, size of liver, changes in noncancer parenchyma, gross type of tumor, extrahepatic metastases, intravascular and intraductal growths, cancer cell histology, hepatitis B surface antigen (HBsAg) in hepatocytes and cancer cells, liver cell dysplasia, and frequency and clinicopathologic characteristics of minute HCC. Furthermore, postmortem hepatic arteriography and portography were done in 152 livers for comparison with gross anatomy and celiac angiograms. It was found that: (1) epidemiologicall), HCC in Japan is distinct from that in the West that it is frequently encapsulated, livers are generally small because of frequent and advanced cirrhosis and small cancer, minute HCC, is not uncommon at autopsy, cirrhosis most commonly associated is the one with thin stroma and medium size nodules, and micronodular cirrhosis is very rare despite frequent alcohol abuse; (2) HCC is increasing in incidence; (3) HBsAg is frequently found in parenchyma; (4) liver cell dysplasia is indirectly related to HBsAg with no evidence for premalignancy; (5) the lung is the most frequent site of metastasis but peritoneal dissemination is unusual; (6) intraportal tumor growth is very common and the hepatic vein is less frequently affected; (7) growth in the major bile duct is frequently associated with intraportal growth and clinically presents as obstructive jaundice; and (8) tumor is supplied solely by arteries and celiac arteriograms are closely correlated with gross pathologic findings.