Miracle-dz/UniFAR-FTUs huggingface dataset:
Reversible impairment of long‐term potentiation in transgenic Cu/Zn‐SOD mice

Copper/zinc superoxide dismutase (CuZn‐SOD) is a key enzyme in the metabolism of oxygen free radicals. The gene encoding CuZn‐SOD resides on human chromosome 21 and is overexpressed in Down syndrome (DS) patients. Overexpression of CuZn‐SOD in transgenic (Tg) mice and cultured cells creates chronic oxidative stress leading to enhanced susceptibility to degeneration and apoptotic cell death. We have now found that three lines of Tg‐CuZn‐SOD mice, one of which also overexpresses S100β, a glial calcium binding protein, are deficient in spatial memory. Furthermore, hippocampal slices taken from these mice have an apparently normal synaptic physiology, but are impaired in the ability to express long‐term potentiation (LTP). This effect on hippocampal LTP was abrogated by treatment of slices with the H2O2 scavenger catalase or the antioxidant N‐t‐butyl‐phenylnitrone (BPN). It is proposed that elevated CuZnSOD causes an increase in tetanic stimulation‐evoked formation of H2O2 which leads to diminished LTP and cognitive deficits in these mice.
Instrumental activities of daily living: a stepping‐stone towards Alzheimer's disease diagnosis in subjects with mild cognitive impairment?

This paper challenges the requirements of normal activities of daily living/instrumental activities of daily living (ADL/IADL) functioning in mild cognitive impairment and stresses the need for further research and assessment refinement. Although people who develop dementia seem to experience subtle changes in complex IADLs long before the disease onset, studies that compare cognitively mildly impaired subjects with demented and nondemented subjects present no clear consensus regarding differentiation according to IADL ability. The traditional ADL/IADL assessment instruments and techniques seem to present a major problem when the purpose is to predict or differentiate between diagnoses. It is therefore argued that the diagnosis of MCI should include rather than exclude observed or experienced changes in complex everyday life activities.
Optimizing Screening for Acute Human Immunodeficiency Virus Infection with Pooled Nucleic Acid Amplification Tests

ABSTRACT Recent studies have shown the public health importance of identifying individuals with acute human immunodeficiency virus infection (AHI); however, the cost of nucleic acid amplification testing (NAAT) makes individual testing of at-risk individuals prohibitively expensive in many settings. Pooled NAAT (or group testing) can improve efficiency and test performance of testing for AHI, but optimizing the pooling algorithm can be difficult. We developed simple, flexible biostatistical models of specimen pooling with NAAT for the identification of AHI cases; these models incorporate group testing theory, operating characteristics of biological assays, and a model of viral dynamics during AHI. Pooling algorithm sensitivity, efficiency (test kits used per individual specimen evaluated), and positive predictive value (PPV) were modeled and compared for three simple pooling algorithms: two-stage minipools (D2), three-stage hierarchical pools (D3), and square arrays with master pools (A2m). We confirmed the results by stochastic simulation and produced reference tables and a Web calculator to facilitate pooling by investigators without specific biostatistical expertise. All three pooling strategies demonstrated improved efficiency and PPV for AHI case detection compared to individual NAAT. D3 and A2m algorithms generally provided better efficiency and PPV than D2; additionally, A2m generally exhibited better PPV than D3. Used selectively and carefully, the simple models developed here can guide the selection of a pooling algorithm for the detection of AHI cases in a wide variety of settings.
Mode-dependent fuzzy control for positive fuzzy Markov jump systems with guaranteed L1-gain performance

Positive fuzzy Markov jump systems (FMJSs) can describe dynamic systems with positive, nonlinear and stochastic features. The peculiar positivity makes a difference in the stability analysis and controller synthesis in contrast to general fuzzy systems and Markov jump systems. For the positive FMJSs, the definitions of exponential mean stability and l1-gain performance are firstly introduced, and some stability and performance conditions are established in the form of linear programming, respectively. In special cases, these conditions can reduce to be the corresponding results of positive fuzzy systems and positive Markov jump linear systems. Then a mode-dependent fuzzy controller is designed such that the closed-loop fuzzy system is positive, exponentially mean stable and has prescribed l1-gain performance. Finally, the control design validity is confirmed by a numerical example.
Central Importance of Immunoglobulin A in Host Defense against Giardia spp

ABSTRACT The protozoan pathogen Giardia is an important cause of parasitic diarrheal disease worldwide. It colonizes the lumen of the small intestine, suggesting that effective host defenses must act luminally. Immunoglobulin A (IgA) antibodies are presumed to be important for controlling Giardia infection, but direct evidence for this function is lacking. B-cell-independent effector mechanisms also exist and may be equally important for antigiardial host defense. To determine the importance of the immunoglobulin isotypes that are transported into the intestinal lumen, IgA and IgM, for antigiardial host defense, we infected gene-targeted mice lacking IgA-expressing B-cells, IgM-secreting B-cells, or all B-cells as controls with Giardia muris or Giardia lamblia GS/M-83-H7. We found that IgA-deficient mice could not eradicate either G. muris or G. lamblia infection, demonstrating that IgA is required for their clearance. Furthermore, although neither B-cell-deficient nor IgA-deficient mice could clear G. muris infections, IgA-deficient mice controlled infection significantly better than B-cell-deficient mice, suggesting the existence of B-cell-dependent but IgA-independent antigiardial defenses. In contrast, mice deficient for secreted IgM antibodies cleared G. muris infection normally, indicating that they have no unique functions in antigiardial host defense. These data, together with the finding that B-cell-deficient mice have some, albeit limited, residual capacity to control G. muris infection, show that IgA-dependent host defenses are central for eradicating Giardia spp. Moreover, B-cell-dependent but IgA-independent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.
On the augmentation of Luenberger Observer-based state feedback design for better robustness and disturbance rejection

This paper addresses the fundamental problem of improving the Luenberger Observer (LO)-based feedback control so that it can deal with effectively a wide range of uncertainties, both internal and external. It is shown that the effect of such uncertainties can be estimated and cancelled in real time, all based on the yet untapped source of information: the estimation error in the existing LO. The result is quite significant in that, by augmenting the LO without changing its original structure or parameters, the LO-based design can be improved in terms of robustness and disturbance rejection. In other words, there is hidden information of uncertainties in the LO tracking error and it can be extracted, often with a mere integrator, to great benefits, as shown in both mathematical analysis and simulation studies.
Lactate production in adipose tissue; a regulated function with extra‐adipose implications

Estimates of the quantitative contribution of adipose tissue to whole‐body glucose metabolism, previously reported as 1–3%, have been revised to be on the order of 10–30%, These revised estimates come, in part, from a recognition that adipose tissue uses glucose to produce lactate and pyruvate, in addition to CO2 and triglycerides. Lactate production by adipose tissue is modulated in vitro by changes in glucose, insulin, and epinephrine concentrations. In vivo, lactate production is regulated acutely by the animal's nutritional state (fed or fasted) and chronically by the degree of obesity. A strong positive correlation exists between rat fat cell size and relative conversion of glucose to lactate (r = 0.89, P < 0.001). Diabetes is also associated with markedly increased lactate production in adipocytes. Fat cells from obese or diabetic rats (or humans) can metabolize to lactate as much as 50‐70% of the glucose taken up. From these recent studies, a picture is emerging in which the adipose organ may provide lactate for hepatic gluconeogenesis during fasting, and also lactate for hepatic glycogen synthesis after food ingestion. Modulation of adipocyte lactate production and contribution of adipose tissue lactate to the body's fuel economy in physiological and pathological states are the focus of this review. —DiGirolamo, M. ; Newby, F. D. ; Lovejoy, J. Lactate production in adipose tissue: a regulated function with extra‐adipose implications. FASEB J. 6: 2405‐2412; 1992.
Connectivity of cone photoreceptor telodendria in the zebrafish retina

The connectivity amongst photoreceptors is critical to their function, as it underpins lateral inhibition and effective translation of stimuli into neural signals. Despite much work characterizing second‐order interneurons in the outer retina, the synapses directly connecting photoreceptors have often been overlooked. Telodendria are fine processes that connect photoreceptor pedicles. They have been observed in diverse vertebrate groups, yet their roles in vision remain speculative. Here, we visualize telodendria via fluorescent protein expression in photoreceptor subtypes. We characterized short wavelength cone telodendria in adult and larval zebrafish retina. Additionally, in the larval retina, we investigated rod telodendria and UV cone telodendria in mutant and transgenic retinas with altered complements of cone types. In the adult retina, telodendria are twice as abundant and branch almost twice as often on blue cones compared to UV cones. Pedicles of neighboring UV and blue cones typically converge into contiguous pairs, despite the regular spacing of their cell bodies. In contrast to adults, larval UV cone telodendria are more numerous (1.3 times) than blue cone telodendria. UV cone telodendria are not detectably affected by ablation of blue cones, and are reduced twofold in mutant larval retina with few UV cones. We thus saw no evidence that telodendria increase in number in the absence of their typical cellular neighbors. We also found that larval rod telodendria are less abundant than short wavelength cone telodendria. In summary, we describe the development and morphology of zebrafish photoreceptor synaptic connectivity toward appreciating the function of telodendria in visual signal processing.
Naturally occurring basal core promoter A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma: a meta-analysis

Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis.
Cloning and Sequence of the Gene Encoding a Novel Cefotaxime-Hydrolyzing β-Lactamase (CTX-M-9) fromEscherichia coli in Spain

ABSTRACT A new CTX-M-type β-lactamase (CTX-M-9) has been cloned from a clinical cefotaxime-resistant Escherichia coli strain. Despite the close identity that exists between the CTX-M-9 and Toho-2 β-lactamases (88%), the 35 amino acids located between residues Ala-185 and Ala-219 are totally different in both enzymes. Outside of this region there are only six amino acids substitutions between both proteins.
Interleukin 17A and F and asthma in Saudi Arabia: gene polymorphisms and protein levels.

BACKGROUND Asthma is a multifactorial disorder, and both genetic and environmental factors contribute to its development. We investigated the possible association between asthma and 5 single-nucleotide polymorphisms (SNPs) in the interleukin 17 (IL17) gene--rs17880588 (G/A) and rs17878530 (C/T) in IL17A and rs763780 (T/C), rs11465553 (T/C), and rs2397084 (G/A) in IL17F--and compared levels of the proteins IL17A and IL17F in asthma patients with those of controls. PATIENTS AND METHODS The study group included 100 asthma patients and 102 ethnically matched controls. Genotyping was performed on purified DNA using reverse transcriptase-polymerase chain reaction with specific primers and probes. Levels of IL17A and IL17F were measured in plasma using enzyme-linked immunosorbent assay. RESULTS Genotyping showed that AG heterozygotes of rs17880588 in IL17A were significantly more common in the control group than among the asthma patients (P < .05); no significant associations were observed for any of the other SNPs examined. Levels of IL17A and IL17F were both higher in asthma patients (IL17A, 2.242 [0.099] vs 2.752 [0.287] pg/mL; IL17F, 236.01 [38.28] vs 700 [201.078] pg/mL). The difference was statistically significant for IL17F (P = .025, t test). Levels of IL17A and IL17F were positively and significantly correlated in the asthma patients CONCLUSION Of all the SNPs analyzed, only rs17880588 showed a significant association with asthma in the Saudi population we studied. Levels of IL17A and IL17F were significantly upregulated in the asthma patients. The morphology of IL17F appeared to affect expression levels.
Quality of life following allogeneic stem cell transplantation, comparing parents' and children's perspective

Abstract: There is insufficient knowledge about the quality of life (QoL) among children after allogeneic stem cell transplantation (SCT). We recently reported an overall, good self‐assessed QoL and health in 52 children who were three yr or more beyond SCT. The focus of this paper is the QoL as assessed by their parents, of whom 42 participated in the study. Using Swedish child health questionnaire (SCHQ)‐PF50, parents rated their children's QoL lower on both the psychosocial (p<0.001) and physical summary scales (p<0.001) than the normative group of parents of children without chronic disease. Although essentially following each other, parent scores tended to be lower than children's own SCHQ‐CF87 scores, particularly in the domains ‘role socially due to physical limitations’ (p<0.01) and ‘self‐esteem’ (p<0.05). In the ‘bodily pain’ domain, patients' and parents' low scores agreed. The child's condition had a greater impact on parents' emotional situation than in the norm population (p<0.001). The severity of the child's physician‐rated late effects (p<0.05) or of self‐assessed subjective symptoms (p<0.01–0.05) was associated with a lower parental rating of the child's QoL. High Lansky or Karnofsky scores corresponded, respectively, to higher psychosocial (p<0.05) and physical (p<0.05) summary scores. It is concluded that as children, parents, and clinicians do not necessarily adopt similar views of a child's illness and of its impact on the child's life, clarity with regard to who is responsible for assessing the child's QoL is crucial when interpreting pediatric QoL studies.
FairFuzz: A Targeted Mutation Strategy for Increasing Greybox Fuzz Testing Coverage

In recent years, fuzz testing has proven itself to be one of the most effective techniques for finding correctness bugs and security vulnerabilities in practice. One particular fuzz testing tool, American Fuzzy Lop (AFL), has become popular thanks to its ease-of-use and bug-finding power. However, AFL remains limited in the bugs it can find since it simply does not cover large regions of code. If it does not cover parts of the code, it will not find bugs there. We propose a two-pronged approach to increase the coverage achieved by AFL. First, the approach automatically identifies branches exercised by few AFL-produced inputs (rare branches), which often guard code that is empirically hard to cover by naïvely mutating inputs. The second part of the approach is a novel mutation mask creation algorithm, which allows mutations to be biased towards producing inputs hitting a given rare branch. This mask is dynamically computed during fuzz testing and can be adapted to other testing targets. We implement this approach on top of AFL in a tool named FairFuzz. We conduct evaluation on real-world programs against state-of-the-art versions of AFL. We find that on these programs FairFuzz achieves high branch coverage at a faster rate that state-of-the-art versions of AFL. In addition, on programs with nested conditional structure, it achieves sustained increases in branch coverage after 24 hours (average 10.6% increase). In qualitative analysis, we find that FairFuzz has an increased capacity to automatically discover keywords.
On the theory of dielectric spectroscopy of protein solutions

We present a theory of the dielectric response of solutions containing large solutes, of the nanometer size, in a molecular solvent. It combines the molecular dipole moment of the solute with the polarization of a large subensemble of solvent molecules at the solute–solvent interface. The goal of the theory is two-fold: (i) to formulate the problem of the dielectric response avoiding the reliance on the cavity-field susceptibility of dielectric theories and (ii) to separate the non-additive polarization of the interface, jointly produced by the external field of the laboratory experiment and the solute, from specific solute–solvent interactions contributing to the dielectric signal. The theory is applied to experimentally reported frequency-dependent dielectric spectra of lysozyme in solution. The analysis of the data in the broad range of frequencies up to 700 GHz shows that the cavity-field susceptibility, critical for the theory formulation, is consistent with the prediction of Maxwell’s electrostatics in the frequency range of 10–200 GHz, but deviates from it outside this range. In particular, it becomes much smaller than the Maxwell result, and shifts to negative values, at small frequencies. The latter observation implies a dia-electric response, or negative dielectrophoresis, of hydrated lysozyme. It also implies that the effective protein dipole recorded by dielectric spectroscopy is much smaller than the value calculated from the protein’s charge distribution. We suggest an empirical equation that describes both the increment of the static dielectric constant and the decrement of the Debye water peak with increasing protein concentration. It gives fair agreement with broad-band dispersion and loss spectra of protein solutions, but misses the δ-dispersion region.
Papillary Tubal Hyperplasia: The Putative Precursor of Ovarian Atypical Proliferative (Borderline) Serous Tumors, Noninvasive Implants, and Endosalpingiosis

In contrast to the controversy regarding the terminology and behavior of ovarian noninvasive low-grade serous tumors [atypical proliferative serous tumor (APST) and serous borderline tumor], little attention has been directed to their origin. Similarly, until recently, proliferative lesions in the fallopian tube had not been extensively studied. The recent proposal that ovarian high-grade serous carcinomas are derived from intraepithelial carcinoma in the fallopian tube prompted us to evaluate the possible role of fallopian tube in the genesis of low-grade serous tumors. We have identified a lesion, designated “papillary tubal hyperplasia (PTH),” characterized by small rounded clusters of tubal epithelial cells and small papillae, with or without associated psammoma bodies, that are present within the tubal lumen and which are frequently associated with APSTs. Twenty-two cases in this study were selected from a population-based study in Denmark of approximately 1000 patients with low-grade ovarian serous tumors in whom implants were identified on the fallopian tube. Seven additional cases were seen recently in consultation at The Johns Hopkins Hospital (JHH). These 7 cases were not associated with an ovarian tumor. PTH was found in 20 (91%) of the 22 cases in the Danish study. On the basis of this association of PTH with APSTs with implants and the close morphologic resemblance of PTH, not only to primary ovarian APSTs but also to noninvasive epithelial implants and endosalpingiosis, we speculate that the small papillae and clusters of cells from the fallopian tube implant on ovarian and peritoneal surfaces to produce these lesions. The 7 JHH cases of PTH that were not associated with an ovarian tumor support the view that PTH is the likely precursor lesion. We propose a model for the development of ovarian and extraovarian low-grade serous proliferations (APST, noninvasive epithelial implants, and endosalpingiosis) that postulates that all of these lesions are derived from PTH, which appears to be induced by chronic inflammation. If this hypothesis is confirmed, it can be concluded that low-grade and high-grade ovarian tumors develop from tubal epithelium and involve the ovary secondarily.
Expression cloning of an equine T-lymphocyte glycoprotein CD2 cDNA. Structure-based analysis of conserved sequence elements.

An equine CD2 cDNA has been isolated by monoclonal antibody screening of a T-lymphocyte cDNA library. The cDNA contained an open reading frame of 1041 bp encoding a translated product of 347 amino acids. Northern blotting analysis revealed a single mRNA species expressed in spleen, thymus and activated peripheral lymphocytes. The predicted amino acid sequence has 50-65% identity with the human, rat and mouse CD2 sequences with greatest similarity shared with the human homologue. Evolutionarily conserved structural and functional domains in CD2 were identified by comparing the sequences of the equine, human, mouse and rat CD2 homologues in the context of the recently derived crystal structure of rat soluble CD2 [Jones, E. Y. , Davis, S. J., Williams, A. F. , Harlos, K. & Stuart, D. I. (1992) Nature 360, 232-239]. The key conserved features of the extracellular region included core residues necessary to preserve the structural integrity of the molecule, residues in the linker region likely to maintain the unique domain organization of CD2, an array of highly charged residues in the putative ligand-binding face of the molecule and glycosylation-signal distributions that render the putative ligand-binding GFCC'C" face of domain 1 relatively unhindered by glycosylation.