Miracle-dz/UniFAR-FTUs huggingface dataset:
Simian Retrovirus 4 Induces Lethal Acute Thrombocytopenia in Japanese Macaques

ABSTRACT In 2001-2002, six of seven Japanese macaques (Macaca fuscata) died after developing hemorrhagic syndrome at the Kyoto University Primate Research Institute (KUPRI). While the cause of death was unknown at the time, we detected simian retrovirus 4 (SRV-4) in samples obtained from a similar outbreak in 2008-2011, during which 42 of 43 Japanese macaques died after exhibiting hemorrhagic syndrome. In this study, we isolated SRV-4 strain PRI-172 from a Japanese macaque showing severe thrombocytopenia. When inoculated into four Japanese macaques, the isolate induced severe thrombocytopenia in all within 37 days. We then constructed an infectious molecular clone of strain PRI-172, termed pSR415, and inoculated the clone-derived virus into two Japanese macaques. These animals also developed severe thrombocytopenia in just 31 days after inoculation, and the virus was reisolated from blood, bone marrow, and stool. At necropsy, we observed bleeding from the gingivae and subcutaneous bleeding in all animals. SRV-4 infected a variety of tissues, especially in digestive organs, including colon and stomach, as determined by real-time reverse transcription-PCR (RT-PCR) and immunohistochemical staining. Furthermore, we identified the SRV-4 receptor as ASCT2, a neutral amino acid transporter. ASCT2 mRNA was expressed in a variety of tissues, and the distribution of SRV-4 proviruses in infected Japanese macaques correlated well with the expression levels of ASCT2 mRNA. From these results, we conclude that the causative agent of hemorrhagic syndrome in KUPRI Japanese macaques was SRV-4, and its receptor is ASCT2. IMPORTANCE During two separate outbreaks at the KUPRI, in 2001-2002 and 2008-2011, 96% of Japanese macaques (JM) that developed an unknown hemorrhagic syndrome died. Here, we isolated SRV-4 from a JM developing thrombocytopenia. The SRV-4 isolate and a molecularly cloned SRV-4 induced severe thrombocytopenia in virus-inoculated JMs within 37 days. At necropsy, we observed bleeding from gingivae and subcutaneous bleeding in all affected JMs and reisolated SRV-4 from blood, bone marrow, and stool. The distribution of SRV-4 proviruses in tissues correlated with the mRNA expression levels of ASCT2, which we identified as the SRV-4 receptor. From these results, we conclude that SRV-4 was the causative agent of hemorrhagic syndrome in JMs in KUPRI.
Biosynthesis of Tetrapyrrole Pigment Precursors : Pyridoxal Requirement of the Aminotransferase Step in the Formation of delta-Aminolevulinate from Glutamate in Extracts of Chlorella vulgaris.

The aminotransferase that catalyzes the formation of delta-aminolevulinic acid from glutamate-1-semialdehyde or from glutamate in a reconstituted enzyme system was isolated and partially purified from Chlorella vulgaris. The apparent molecular weight of the aminotransferase was determined by Sephadex G-100 and Ultrogel AcA 54 gel filtration to be 60,000 +/- 5,000. Catalytic activity of the aminotransferase required pyrixodal phosphate (PALP). The cofactor could not be removed by gel filtration after exposure of the enzyme to PALP. Aminotransferase was inhibited by gabaculine (3-amino-2,3-dihydrobenzoic acid). The concentration of gabaculine required for half maximal inhibition was about 0.05 micromolar. Aminotransferase activity could be regained upon the removal of gabaculine by gel filtration and supplementing the assay medium with PALP. Neither the inhibitory action of gabaculine nor its reversibility was affected by preincubation of the enzyme with the keto acids levulinate and delta-aminolevulinic acid.
Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses

Eosinophil‐derived neurotoxin (EDN) is an eosinophil granule‐derived secretory protein with ribonuclease and anti‐viral activity. We have previously shown that EDN can induce the migration of dendritic cells (DCs). Here we report that EDN can activate myeloid DCs by triggering the TLR2/Myd88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independent of TLR1 or TLR6. EDN also enhances antigen‐specific Th2‐biased immune responses as evidenced by predominant production of antigen‐specific IL‐5 and IL‐13 as well as higher levels of IgG1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen‐specific immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen‐specific Th2 immune responses. (Funded in whole or in part with federal funds from the NCI, NIH, under contract N01‐CO‐12400).
THE GLYCOCALYX AND TRAUMA: A REVIEW

ABSTRACT In the United States trauma is the leading cause of mortality among those under the age of 45, claiming approximately 192,000 lives each year. Significant personal disability, lost productivity, and long-term healthcare needs are common and contribute 580 billion dollars in economic impact each year. Improving resuscitation strategies and the early acute care of trauma patients has the potential to reduce the pathological sequelae of combined exuberant inflammation and immune suppression that can co-exist, or occur temporally, and adversely affect outcomes. The endothelial and epithelial glycocalyx has emerged as an important participant in both inflammation and immunomodulation. Constituents of the glycocalyx have been used as biomarkers of injury severity and have the potential to be target(s) for therapeutic interventions aimed at immune modulation. In this review, we provide a contemporary understanding of the physiologic structure and function of the glycocalyx and its role in traumatic injury with a particular emphasis on lung injury.
Contrasting reservoirs for Schistosoma japonicum between marshland and hilly regions in Anhui, China – a two-year longitudinal parasitological survey

SUMMARY Schistosoma japonicum remains highly endemic in many counties in China and has recently re-emerged, to a large extent, in previously controlled areas. To test the hypothesis that small rodents and less agriculturally important domestic animals such as dogs and cats may play an important role in the transmission and potential re-emergence of this disease, an annual investigation of S. japonicum among humans, domestic animals and rodents, combined with detailed surveys of the snail intermediate host, was performed across 3 marshland villages and 3 hilly villages in Anhui province of China over 2 consecutive years. The highest infection prevalence and intensity observed across all mammals was in rodents in the hilly region; while in the marshland, bovines were suspected as the main reservoirs. However, relatively high infection prevalence levels were also found in dogs and cats in both regions. Such results may have implications for the current human- and bovine-oriented control policy for this medically and veterinarily important disease, particularly within the hilly regions of mainland China.
Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1.

UNLABELLED Small cell lung cancer (SCLC) is an aggressive malignancy distinct from non-small cell lung cancer (NSCLC) in its metastatic potential and treatment response. Using an integrative proteomic and transcriptomic analysis, we investigated molecular differences contributing to the distinct clinical behavior of SCLCs and NSCLCs. SCLCs showed lower levels of several receptor tyrosine kinases and decreased activation of phosphoinositide 3-kinase (PI3K) and Ras/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) pathways but significantly increased levels of E2F1-regulated factors including enhancer of zeste homolog 2 (EZH2), thymidylate synthase, apoptosis mediators, and DNA repair proteins. In addition, PARP1, a DNA repair protein and E2F1 co-activator, was highly expressed at the mRNA and protein levels in SCLCs. SCLC growth was inhibited by PARP1 and EZH2 knockdown. Furthermore, SCLC was significantly more sensitive to PARP inhibitors than were NSCLCs, and PARP inhibition downregulated key components of the DNA repair machinery and enhanced the efficacy of chemotherapy. SIGNIFICANCE SCLC is a highly lethal cancer with a 5-year survival rate of less than 10%. To date, no molecularly targeted agents have prolonged survival in patients with SCLCs. As a step toward identifying new targets, we systematically profiled SCLCs with a focus on therapeutically relevant signaling pathways. Our data reveal fundamental differences in the patterns of pathway activation in SCLCs and NSCLCs and identify several potential therapeutic targets for SCLCs, including PARP1 and EZH2. On the basis of these results, clinical studies evaluating PARP and EZH2 inhibition, together with chemotherapy or other agents, warrant further investigation.
Delay Bounds in Communication Networks With Heavy-Tailed and Self-Similar Traffic

Traffic with self-similar and heavy-tailed characteristics has been widely reported in communication networks, yet, the state-of-the-art of analytically predicting the delay performance of such networks is lacking. This work addresses heavy-tailed traffic that has a finite first moment, but no second moment, and presents end-to-end delay bounds for such traffic. The derived performance bounds are non-asymptotic in that they do not assume a steady state, large buffer, or many sources regime. The analysis follows a network calculus approach where traffic is characterized by envelope functions and service is described by service curves. The system model is a multi-hop path of fixed-capacity links with heavy-tailed self-similar cross traffic at each node. A key contribution of the paper is a probabilistic sample-path bound for heavy-tailed arrival and service processes, which is based on a scale-free sampling method. The paper explores how delay bounds scale as a function of the length of the path, and compares them with lower bounds. A comparison with simulations illustrates pitfalls when simulating self-similar heavy-tailed traffic, providing further evidence for the need of analytical bounds.
Bacterial Infections in Children with HIV/AIDS

HIV/AIDS affects over 850 000 children in Africa. Bacterial infections are frequent in this group of children. Pneumonia, meningitis and septicaemia are especially common, recurrent and most often caused by Streptococcus pneumoniae. Salmonella spp are the most frequently isolated causative agent of septicaemia in malarial areas. Soft tissue, eye and oral infections have a higher incidence in HIV-infected than uninfected children. In all instances the causative agents are not dissimilar from those that cause disease in HIV-uninfected children, but the mortality is greater. Increased bacterial resistance to first line antibiotics has been reported and the use of cotrimoxazole prophylaxis may further influence the resistance pattern of common bacteria.
Usefulness of transthoracic and transoesophageal echocardiography in recognition and management of cardiovascular injuries after blunt chest trauma.

OBJECTIVE: To assess the diagnostic potential of transthoracic and transoesophageal echocardiography for the detection of traumatic cardiovascular injuries in patients suffering from severe blunt chest trauma. DESIGN: Prospective study over a three year period. SETTING: A regional cardiothoracic centre. PATIENTS: 134 consecutive patients (94 M/40 F; mean age 38 (SD 14) years) suffering from severe blunt chest trauma (injury severity score 33.5 (18.2)). Most patients (89%) were victims of motor vehicle accidents. EVALUATION: All patients underwent transthoracic and transoesophageal echocardiography within 8 h of admission. Aortography was performed in the first 20 patients and in a further five equivocal cases. RESULTS: Transthoracic echocardiography provided suboptimal images in 83 patients, detecting three aortic ruptures, 28 pericardial effusions (one cardiac tamponade), 35 left pleural effusions, and 15 myocardial contusions. Transoesophageal echocardiography was feasible in 131 patients and detected 14 aortic ruptures (13 at the isthmus), 40 pericardial effusions, 51 left pleural effusions, 34 periaortic haematomas, 45 myocardial contusions, right atrial laceration in one patient with cardiac tamponade, one tricuspid valve rupture, and one severe mitral regurgitation caused by annular disruption. For the detection of aortic rupture transoesophageal echocardiography showed 93% sensitivity, 98% specificity, and 98% accuracy. Time to surgery was significantly shorter (30 (12) v 71 (21) min; P < 0.05) for patients operated on only on the basis of transoesophageal echocardiographic findings. CONCLUSIONS: Transthoracic echocardiography has low diagnostic yield in severe blunt chest trauma, while transoesophageal echocardiography provides accurate diagnosis in a short time at the bedside, is inexpensive, minimally invasive, and does not interfere with other diagnostic or therapeutic procedures.
Targeting Human Telomeric G-Quadruplex DNA and Inhibition of Telomerase Activity With [(dmb)2Ru(obip)Ru(dmb)2]4+

Inhibition of telomerase by inducing/stabilizing G-quadruplex formation is a promising strategy to design new anticancer drugs. We synthesized and characterized a new dinuclear complex [(dmb)2Ru(obip)Ru(dmb)2]4+ (dmb = 4,4’-dimethyl-2,2’-bipyridine, obip = (2-(2-pyridyl)imidazo[4,5-f][1,10]phenanthroline) with high affinity for both antiparallel and mixed parallel / antiparallel G-quadruplex DNA. This complex can promote the formation and stabilize G-quadruplex DNA. Dialysis and TRAP experiments indicated that [(dmb)2Ru(obip)Ru(dmb)2]4+ acted as an excellent telomerase inhibitor due to its obvious selectivity for G-quadruplex DNA rather than double stranded DNA. In vitro co-culture experiments implied that [(dmb)2Ru(obip)Ru(dmb)2]4+ inhibited telomerase activity and hindered cancer cell proliferation without side effects to normal fibroblast cells. TUNEL assay indicated that inhibition of telomerase activity induced DNA cleavage further apoptosis in cancer cells. Therefore, RuII complex represents an exciting opportunity for anticancer drug design by specifically targeting cancer cell G-quadruplexes DNA.
Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

Purpose Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism. Methods To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea. Results The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm2 to 2.29 ± 0.61 mm2, respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced the expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea on day 6 after suturing. Conclusion CNPs significantly inhibited suture-induced CNV by suppressing macrophage infiltration and the expression of vascular endothelial growth factor and matrix metalloproteinase 9 in the rat cornea.
An experimental study of microstructure-induced ultrasonic signal fluctuations in jet-engine titanium alloys

Ultrasonic echoes from identical defects in a metal component will vary due to the influence of the local microstructure in which each defect is embedded. Two effects are responsible: (1) the scattering of sound at nearby crystallite boundaries results in “grain noise” which is superimposed on the defect echo; and (2) the intervening microstructure modulates or distorts the sonic field that is incident on the defect, thus modifying its echo. Both effects can be significant in engine titanium alloys, and both influence inspection reliability. In this work, a series of experiments is performed to investigate signal fluctuations primarily arising from the second effect. Arrays of nominally identical #1 flat-bottomed holes (FBHs) in Ti-17 and Ti 6-4 specimens are scanned using a 10-MHz, broadband, focused transducer. The peak echo amplitude of each FBH in the array is measured, and the ratio of the standard deviation of the peak amplitudes to their mean serves as a dimensionless measure of the fluctuation lev.
Principles of ceramics processing

Partial table of contents: Ceramics Processing and Ceramic Products. Surface Chemistry. CERAMIC RAW MATERIALS. Special Inorganic Chemicals. MATERIALS CHARACTERIZATION. Particle Size and Shape. Density, Pore Structure, and Specific Surface Area. PROCESSING ADDITIVES. Liquids and Wetting Agents. Flocculants, Binders, and Bonds. PARTICLE PACKING, CONSISTENCY, AND BATCH CALCULATIONS. Batch Consistency and Formulation. PARTICLE MECHANICS AND RHEOLOGY. Mechanics of Unsaturated Bodies. BENEFICIATION. Comminution. Granulation. FORMING. Pressing. Injection Molding. POSTFORMING PROCESSES. Drying. Firing. Appendices. Index.
The LAMBADA dataset: Word prediction requiring a broad discourse context

We introduce LAMBADA, a dataset to evaluate the capabilities of computational models for text understanding by means of a word prediction task. LAMBADA is a collection of narrative passages sharing the characteristic that human subjects are able to guess their last word if they are exposed to the whole passage, but not if they only see the last sentence preceding the target word. To succeed on LAMBADA, computational models cannot simply rely on local context, but must be able to keep track of information in the broader discourse. We show that LAMBADA exemplifies a wide range of linguistic phenomena, and that none of several state-of-the-art language models reaches accuracy above 1% on this novel benchmark. We thus propose LAMBADA as a challenging test set, meant to encourage the development of new models capable of genuine understanding of broad context in natural language text.
Stability Boundary for Haptic Rendering: Influence of Damping and Delay

The influence of viscous damping and delay on the stability of haptic systems is studied in this paper. The stability boundaries have been found by means of different approaches. Although the shape of these stability boundaries is quite complex, a new linear condition which summarizes the relation between virtual stiffness, viscous damping and delay is proposed. This condition is independent of the mass of the haptic device. The theoretical results are supported by simulations and experimental data using the DLR light-weight robot.
Expanding the Indications for Laparoscopic Gastric Resection for Gastrointestinal Stromal Tumors

Objective: Laparoscopic resection of large gastric gastrointestinal stromal tumors (GIST) has been controversial. This generally has been limited to small lesions. We hypothesize that laparoscopic mobilization and resection using, in some cases, extracorporeal anastomosis of the gastrointestinal (GI) tract is an oncologically safe alternative to open surgery even when tumors are large. Methods: Four patients underwent a laparoscopic approach for gastric GIST tumors >2 cm at Methodist Dallas Medical Center over a 6-month period. Patient demographics, operative findings, postoperative course, and pathologic characteristics were examined. Results: The mean age in this patient group was 58 years (range, 36 to 77). Gastrointestinal bleeding and dyspepsia were the most common symptoms. Seventy-five percent of the patients were females. Mean tumor size was 10 cm (range, 2.5 to 20) with distribution in the stomach as follows: 75% greater curvature and 25% antrum. Tumors were removed by wedge, sleeve, and partial gastrectomies. Two of these tumors showed a high grade and the other 2 a moderate grade of differentiation. The number of mitoses was <5/50 HPF in all the tumors. No intraoperative spillage occurred in any patients, even with the largest tumor (20 cm). Importantly, all tumors were excised with a negative gross and microscopic margin. Average length of stay was 4 days. No patients required reoperation, and there were no complications postoperatively. Conclusion: Minimally invasive assisted approaches may be an option to treat large GIST tumors. Obeying principles of minimal touch, no spillage, and obtaining a negative margin, a safe operation with a laparoscopic approach is feasible, even in giant tumors. The large size of diagnosed GIST tumors should not preclude a minimally invasive approach.
Novel Approach of Designing Spreading Code using Genetic Algorithm

Modern communication systems extensively use Code Division Multiple Access (CDMA) technology that associates one unique code to each user. Therefore the generation of these spreading codes has drawn considerable attention amongst the researchers with a fundamental requirement of having as much distinct members as possible along with a constraint of minimizing the inter-code correlation. Since the operation of trade-off between the number of unique codes and peak cross-correlation value is nothing but a task of optimization; one such intelligent technique called Genetic Algorithm (GA) has been employed in this paper for the design of spreading codes. This has proved the uniqueness of our code generation algorithm over existing ones as it provides flexibility in selecting the number of orthogonal code pairs even when the codelength is constant. Interdependence between the characteristics of the designed code and the parameters of genetic optimization has been revealed by means of a number of design examples. Inherent properties of the GA-optimized spreading code have been analyzed from a number of perspectives. Finally, the worth of the proposed code in current wireless system has been substantiated by comparing its performance with other stateof-the-art spreading codes. Key-words: Code Division Multiple Access (CDMA), Genetic Algorithm (GA), Kasami sequence, Orthogonal Gold code, Semi-Orthogonal Modified Large Set Kasami (SOMLK) sequence, Small Set Orthogonal Kasami (SSOK) code, Walsh code