Miracle-dz/UniFAR-FTUs huggingface dataset:
Gemcitabine and CHK1 Inhibition Potentiate EGFR-Directed Radioimmunotherapy against Pancreatic Ductal Adenocarcinoma

Purpose: To develop effective combination therapy against pancreatic ductal adenocarcinoma (PDAC) with a combination of chemotherapy, CHK1 inhibition, and EGFR-targeted radioimmunotherapy. Experimental Design: Maximum tolerated doses were determined for the combination of gemcitabine, the CHK1 inhibitor PF-477736, and Lutetium-177 (177Lu)–labeled anti-EGFR antibody. This triple combination therapy was investigated using PDAC models from well-established cell lines, recently established patient-derived cell lines, and fresh patient-derived xenografts. Tumors were investigated for the accumulation of 177Lu-anti-EGFR antibody, survival of tumor-initiating cells, induction of DNA damage, cell death, and tumor tissue degeneration. Results: The combination of gemcitabine and CHK1 inhibitor PF-477736 with 177Lu-anti-EGFR antibody was tolerated in mice. This triplet was effective in established tumors and prevented the recurrence of PDAC in four cell line–derived and one patient-derived xenograft model. This exquisite response was associated with the loss of tumor-initiating cells as measured by flow cytometric analysis and secondary implantation of tumors from treated mice into treatment-naïve mice. Extensive DNA damage, apoptosis, and tumor degeneration were detected in the patient-derived xenograft. Mechanistically, we observed CDC25A stabilization as a result of CHK1 inhibition with consequent inhibition of gemcitabine-induced S-phase arrest as well as a decrease in canonical (ERK1/2 phosphorylation) and noncanonical EGFR signaling (RAD51 degradation) as a result of EGFR inhibition. Conclusions: Our study developed an effective combination therapy against PDAC that has potential in the treatment of PDAC. Clin Cancer Res; 20(12); 3187–97. ©2014 AACR.
Mouse Monoclonal Antibodies to Anthrax Edema Factor Protect against Infection

ABSTRACT Bacillus anthracis is the causative agent of anthrax, and the tripartite anthrax toxin is an essential element of its pathogenesis. Edema factor (EF), a potent adenylyl cyclase, is one of the toxin components. In this work, anti-EF monoclonal antibodies (MAb) were produced following immunization of mice, and four of the antibodies were fully characterized. MAb 3F2 has an affinity of 388 pM, was most effective for EF detection, and appears to be the first antibody reported to neutralize EF by binding to the catalytic CB domain. MAb 7F10 shows potent neutralization of edema toxin activity in vitro and in vivo; it targets the N-terminal protective antigen binding domain. The four MAb react with three different domains of edema factor, and all were able to detect purified edema factor in Western blot analysis. None of the four MAb cross-reacted with the lethal factor toxin component. Three of the four MAb protected mice in both a systemic edema toxin challenge model and a subcutaneous spore-induced foreleg edema model. A combination of three of the MAb also significantly delayed the time to death in a third subcutaneous spore challenge model. This appears to be the first direct evidence that monoclonal antibody-mediated neutralization of EF alone is sufficient to delay anthrax disease progression.
The electric response of the human eye

The present work arose from an investigation of the electrical changes in the human brain, particularly those produced by the exposure of the eyes to a flickering light. Some years ago Adrian & Matthews (1934) found that potential waves, in phase with the flicker, could be recorded from the occipital part of the head. As a rule, the frequency of the occipital waves agreed with that of the flicker, but sometimes it occurred at double the rate and, as this doubling complicated the analysis of the cerebral events, it seemed necessary to find out how it arose and, in particular, whether it arose in the brain or in the eye. The simplest method of attack was to try to record the potential waves generated in the-retina as well as those in the brain. The attempt has been successful to the extent of showing that a double response may certainly arise in the eye, but the more important finding is that the human electroretinogram can be recorded without much difficulty and can give fresh information about the retinal mechanism. What follows is mainly concerned with the potential changes occurring in the eye in response to single flashes of light. Responses to flickering light are described in a later section. The doubling of the cerebral flicker rhythm will be dealt with elsewhere, although, in fact, it was the starting-point of the investigation. Previous work on the human electroretinogram is summarized in a paper by Cooper, Creed & Granit (1933). It has been established that the response of the human eye has the same general form as that recorded from other vertebrate eyes, isolated or in situ, or from the exposed retina, but technical difficulties have prevented any further study of it. One of the chief difficulties has been that eye movements are hard to avoid and give rise to potential changes resembling those of the electroretinogram. In the present experiments they have not caused much trouble, partly no doubt because the subject learnt to control them, but mainly because of the shortness of the period of iliumination. As a rule the stimulus was a flash lasting not more than 1/20 sec. , and no serious attempt was made to record with exposures lasting more than a second. Thus the inconveniences of a wandering base-line have not been serious.
Distinguishing between attention-deficit hyperactivity and fetal alcohol spectrum disorders in children: clinical guidelines

: Fetal alcohol spectrum disorders (FASD) are the physical and neurodevelopmental outcomes of fetal alcohol exposure. The behavioral phenotype of children with FASD includes difficulties with executive function, memory, planning, processing speed, and attention. Although attention deficit hyperactivity disorder (ADHD) is diagnosed in up to 94% of individuals with heavy prenatal alcohol exposure, the exact relationship between FASD and ADHD is unclear. There is some evidence that ADHD in FASD may be a specific clinical subtype and thus may require a different treatment approach. Although traditional behavioral observation scales may not distinguish between the two groups, there is evidence that children with FASD have a different profile on the four-factor model of attention than children with ADHD who do not have FASD. There is a paucity of good scientific evidence on effective interventions for individuals with ADHD and FASD. There is weak evidence that children with FASD and ADHD may have a better response to dexamphetamine than methylphenidate. There is a strong need for larger, high quality studies to examine the relationship between ADHD and FASD and identify effective treatments because management of inattention and hyperactivity may improve learning and ameliorate the common secondary disabilities associated with FASD.
Measuring UHF RFID tag reading for document localization

This study measured the reading reliability of UHF passive tags for Document Tracking. The main goal was verifying whether UHF RFID technology that relaxes the constraints of distance reading with respect to HF, is suitable for automating document workflow. A set of experiments was conducted using three types of commercial tags to verify how the reader's power and the spatial arrangement of tags may impact on the reading accuracy. The tests involve both the simultaneous reading of a stack of 50 tagged single-page documents (inventory mode) and the retrieval of one of them. Results showed that while search for a single document is successful when carried out at a reasonable distance (allowing the user to move naturally without distance constraints), inventory is only successful in close proximity. UHF RFID, identification, search, measurement, documents
Prevalence, Characteristics, and In-Hospital Outcomes of Metabolic Syndrome among Patients with Acute Coronary Syndrome in the United Arab Emirates

Objective: To evaluate clinical profiles, management and in-hospital outcomes of acute coronary syndrome (ACS) patients with metabolic syndrome (MetS) in the United Arab Emirates (UAE). Methods: MetS was defined according to the criteria for its diagnosis by the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI). Participants were admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 as part of the Gulf Registry of Acute Coronary Events (Gulf RACE) project. We compared baseline characteristics, treatment patterns, and in-hospital outcomes stratified by MetS status. Results: Of 1259 patients with ACS in the UAE (mean age: 52 ± 11 years, 88.8% males), the majority (n = 851, 67.6%) had MetS. MetS patients were more frequently males (86.4 vs 13.6%; P < 0.001). They were more obese (waist circumference and BMI, P < 0.001) as compared with non-MetS patients. MetS was more frequently associated with hypertension (51.1 vs 37.7%; P < 0.001) and diabetes mellitus (45.6 vs 24.3%; P < 0.001). After multivariate adjustment, certain MetS criteria rather than MetS itself were associated with higher in-hospital mortality and heart failure. Paradoxically, hypertension was associated with lower in-hospital mortality. Conclusions: Prevalence of MetS among patients with ACS in our study population was high. Certain MetS criteria were associated with higher in-hospital mortality and heart failure.
A review of termination of pregnancy: prevalent health care professional attitudes and ways of influencing them.

AIM To review the literature on attitudes of health care professionals to termination of pregnancy and draw out underlying themes. BACKGROUND The controversy surrounding therapeutic abortion is unremitting with public opinion often polemic and unyielding. Nurses and midwives are at the centre of this turmoil, and as more termination of pregnancies are being performed using pharmacological agents, they are becoming ever more involved in direct care and treatment. Attitudes towards termination of pregnancy have been found to vary depending on the nationality of those asked, the professionals involved, experience in abortion care, as well as personal attributes of those asked such as their obstetric history and religious beliefs. The reasons for women undergoing abortion were also found to influence attitudes to a greater or lesser extent. CONCLUSION This paper explores research studies undertaken into attitudes of health care professionals towards termination of pregnancy, to appreciate the complexity of the debate. It is possible that the increased involvement of nurses in termination of pregnancy, that current methods demand, may lead to change in attitudes. Consideration is given to a number of remedies to create an optimum environment for women undergoing termination of pregnancy. RELEVANCE TO CLINICAL PRACTICE This paper establishes via a literature review that attitudes in those working in this area of care depend upon a variety of influences. Suggestions are made for measures to be put into place to foster appropriate attitudes in those working in termination of pregnancy services.
A GC1 Acinetobacter baumannii isolate carrying AbaR3 and the aminoglycoside resistance transposon TnaphA6 in a conjugative plasmid

Objectives To locate the acquired antibiotic resistance genes, including the amikacin resistance transposon TnaphA6, in the genome of an Australian isolate belonging to Acinetobacter baumannii global clone 1 (GC1). Methods A multiply antibiotic-resistant GC1 isolate harbouring TnaphA6 was sequenced using Illumina HiSeq, and reads were used to generate a de novo assembly and determine multilocus sequence types (STs). PCR was used to assemble the AbaR chromosomal resistance island and a large plasmid carrying TnaphA6. Plasmid DNA sequences were compared with ones available in GenBank. Conjugation experiments were conducted. Results The A. baumannii GC1 isolate G7 was shown to include the AbaR3 antibiotic resistance island. It also contains an 8.7 kb cryptic plasmid, pAb-G7-1, and a 70 100 bp plasmid, pAb-G7-2, carrying TnaphA6. pAb-G7-2 belongs to the Aci6 Acinetobacter plasmid family. It encodes transfer functions and was shown to conjugate. Plasmids related to pAb-G7-2 were detected in further amikacin-resistant GC1 isolates using PCR. From the genome sequence, isolate G7 was ST1 (Institut Pasteur scheme) and ST231 (Oxford scheme). Using Oxford scheme PCR-based methods, the isolate was ST109 and this difference was traced to a single base difference resulting from the inclusion of the original primers in the gpi segment analysed. Conclusions The multiply antibiotic-resistant GC1 isolate G7 carries most of its resistance genes in AbaR3 located in the chromosome. However, TnaphA6 is on a conjugative plasmid, pAb-G7-2. Primers developed to locate TnaphA6 in pAb-G7-2 will simplify the detection of plasmids related to pAb-G7-2 in A. baumannii isolates.
Oxygen consumption and sodium reabsorption in the kidney.

Lassen N. A. , O. Munck J. H. Thaysen. Oxygen consumption and sodium reabsorption in the kidney. Renal oxygen consumption can be divided into a small but constant basal oxygen uptake and a variable suprabasal or functional oxygen uptake. The basal oxygen consumption is defined as the oxygen uptake of the non-filtering and hence non-reabsorbing kidney. It was measured during marked hypotension and was found to amount to 1 μmole of O2 per gram kidney per minute. The suprabasal or functional oxygen consumption is defined as the total oxygen uptake minus the basal. It was measured on normally functioning kidneys and was found to correlate very closely with the quantity of sodium reabsorbed. For each mol of oxygen consumed in excess of basal requirements 28 sodium equivalents were reabsorbed. The hypothesis, that sodium reabsorption represents the main renal work is forwarded. It provides a simple explanation for the various classical observations on renal oxygen uptake and is in agreement with data on other electrolyte transporting tissues.
Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum

Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.
Frequency-dependent viscosity of xenon near the critical point.

We used a novel, overdamped oscillator aboard the Space Shuttle to measure the viscosity eta of xenon near its critical density rho(c) and temperature Tc. In microgravity, useful data were obtained within 0.1 mK of Tc, corresponding to a reduced temperature t=(T-Tc)/Tc=3 x 10(-7). Because they avoid the detrimental effects of gravity at temperatures two decades closer to T(c) than the best ground measurements, the data directly reveal the expected power-law behavior eta proportional, variant t(-nuz(eta)). Here nu is the correlation length exponent, and our result for the viscosity exponent is z(eta)=0.0690+/-0.0006. (All uncertainties are one standard uncertainty.) Our value for z(eta) depends only weakly on the form of the viscosity crossover function, and it agrees with the value 0.067+/-0.002 obtained from a recent two-loop perturbation expansion [H. Hao, R.A. Ferrell, and J.K. Bhattacharjee, (unpublished)]. The measurements spanned the frequency range 2 Hz< or = f < or =12 Hz and revealed viscoelasticity when t < or = 10(-5), further from Tc than predicted. The viscoelasticity's frequency dependence scales as Aftau, where tau is the fluctuation-decay time. The fitted value of the viscoelastic time-scale parameter A is 2.0+/-0.3 times the result of a one-loop perturbation calculation. Near Tc, the xenon's calculated time constant for thermal diffusion exceeded days. Nevertheless, the viscosity results were independent of the xenon's temperature history, indicating that the density was kept near rho(c) by judicious choices of the temperature versus time program. Deliberately bad choices led to large density inhomogeneities. At t>10(-5), the xenon approached equilibrium much faster than expected, suggesting that convection driven by microgravity and by electric fields slowly stirred the sample.
Acute Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or Paraquat on Core Temperature in C57BL/6J Mice

Abstract Background: MPTP and paraquat are two compounds that have been used to model Parkinson’s disease in mice. Previous studies in two non-traditional strains of mice have shown that a single dose of MPTP can induce changes in body temperature, while the effects of paraquat have not been examined. Examination of body temperature is important since small fluctuations in an animal’s core temperature can significantly affect drug metabolism, and if significant enough can even culminate in an animal’s death. Objective: To determine how external heating can alter the survival of C57BL/6J mice following MPTP administration. Methods: In this study, we examine the effects of MPTP (4×20 mg/kg, 2 hours apart) and paraquat (2×10 mg/kg/week for 3 weeks) on core temperature of C57BL/6J mice. Correlations of purine and catecholamine levels were also done in mice treated with MPTP. Results: We find that MPTP induces a significant hypothermia in C57BL/6J mice that reduces their core temperature below the limit of fatal hypothermia. Unlike MPTP, paraquat did not induce a significant hypothermia. Placement of animals on heating pads significantly abrogates the loss of core temperature. In both heated and non-heated conditions, mice treated with MPTP showed a significant depletion of ATP within 2 hours of administration in both striatum and SN that started to recover 2 hours after MPTP administration was complete. Striatal DA and DOPAC are significantly reduced starting 4–6 hours after MPTP. Conclusions: The fatal hypothermic effects of MPTP can be abrogated through use of external heating.
Orthogonal Fuzzy Neighborhood Discriminant Analysis for Multifunction Myoelectric Hand Control

Developing accurate and powerful electromyogram (EMG) driven prostheses controllers that can provide the amputees with effective control on their artificial limbs, has been the focus of a great deal of research in the past few years. One of the major challenges in such research is extracting an informative subset of features that can best discriminate between the different forearm movements. In this paper, a new dimensionality reduction method, referred to as orthogonal fuzzy neighborhood discriminant analysis (OFNDA), is proposed as a response to such a challenge. Unlike existing attempts in fuzzy linear discriminant analysis, the objective of the proposed OFNDA is to minimize the distance between samples that belong to the same class and maximize the distance between the centers of different classes, while taking into account the contribution of the samples to the different classes. The proposed OFNDA is validated on EMG datasets collected from seven subjects performing a range of 5 to 10 classes of forearm movements. Practical results indicate the significance of OFNDA in comparison to many other feature projection methods (including locality preserving and uncorrelated variants of discriminant analysis) with accuracies ranging from 97.66% to 87.84% for 5 to 10 classes of movements, respectively, using only two EMG electrodes.
The C-terminal Tail Preceding the CAAX Box of a Yeast G Protein γ Subunit Is Dispensable for Receptor-mediated G Protein Activation in Vivo*

The γ subunits of heterotrimeric G proteins are required for receptor-G protein coupling. The C-terminal domains of Gγ subunits can contact receptors and influence the efficiency of receptor-G protein coupling in vitro. However, it is unknown whether receptor interaction with the C terminus of Gγ is required for signaling in vivo. To address this question, we cloned Gγ homologs with diverged C-terminal sequences from five species of budding yeast. Each Gγ homolog functionally replaced the Gγ subunit of the yeast Saccharomyces cerevisiae (STE18 gene product). Mutagenesis of S. cerevisiae Ste18 likewise indicated that specific C-terminal sequence motifs are not required for signaling. Strikingly, an internal in-frame deletion removing sequences preceding the C-terminal CAAX box of Ste18 did not impair signaling by either of its cognate G protein-coupled pheromone receptors. Therefore, receptor interaction with the C-terminal domain of yeast Gγ is not required for receptor-mediated G protein activation in vivo. Because the mechanism of G protein activation by receptors is conserved from yeast to humans, mammalian receptors may not require interaction with the tail of Gγ for G protein activation in vivo. However, receptor-Gγ interaction may modulate the efficiency of receptor-G protein coupling or promote activation of Gβγ effectors that co-cluster with receptors.