Miracle-dz/UniFAR-FTUs huggingface dataset:
Polysulfides as Intermediates in the Oxidation of Sulfide to Sulfate by Beggiatoa spp

ABSTRACT Zero-valent sulfur is a key intermediate in the microbial oxidation of sulfide to sulfate. Many sulfide-oxidizing bacteria produce and store large amounts of sulfur intra- or extracellularly. It is still not understood how the stored sulfur is metabolized, as the most stable form of S0 under standard biological conditions, orthorhombic α-sulfur, is most likely inaccessible to bacterial enzymes. Here we analyzed the speciation of sulfur in single cells of living sulfide-oxidizing bacteria via Raman spectroscopy. Our results showed that under various ecological and physiological conditions, all three investigated Beggiatoa strains stored sulfur as a combination of cyclooctasulfur (S8) and inorganic polysulfides (S n 2−). Linear sulfur chains were detected during both the oxidation and reduction of stored sulfur, suggesting that S n 2− species represent a universal pool of bioavailable sulfur. Formation of polysulfides due to the cleavage of sulfur rings could occur biologically by thiol-containing enzymes or chemically by the strong nucleophile HS− as Beggiatoa migrates vertically between oxic and sulfidic zones in the environment. Most Beggiatoa spp. thus far studied can oxidize sulfur further to sulfate. Our results suggest that the ratio of produced sulfur and sulfate varies depending on the sulfide flux. Almost all of the sulfide was oxidized directly to sulfate under low-sulfide-flux conditions, whereas only 50% was oxidized to sulfate under high-sulfide-flux conditions leading to S0 deposition. With Raman spectroscopy we could show that sulfate accumulated in Beggiatoa filaments, reaching intracellular concentrations of 0.72 to 1.73 M.
Importins fulfil a dual function as nuclear import receptors and cytoplasmic chaperones for exposed basic domains

Many nuclear transport pathways are mediated by importin β‐related transport receptors. Here, we identify human importin (Imp) 4b as well as mouse Imp4a, Imp9a and Imp9b as novel family members. Imp4a mediates import of the ribosomal protein (rp) S3a, while Imp9a and Imp9b import rpS7, rpL18a and apparently numerous other substrates. Ribosomal proteins, histones and many other nuclear import substrates are very basic proteins that aggregate easily with cytoplasmic polyanions such as RNA. Imp9 effectively prevents such precipitation of, for example, rpS7 and rpL18a by covering their basic domains. The same applies to Imp4, Imp5, Imp7 and Impβ and their respective basic import substrates. The Impβ–Imp7 heterodimer appears specialized for the most basic proteins, such as rpL4, rpL6 and histone H1, and is necessary and sufficient to keep them soluble in a cytoplasmic environment prior to rRNA or DNA binding, respectively. Thus, just as heat shock proteins function as chaperones for exposed hydrophobic patches, importins act as chaperones for exposed basic domains, and we suggest that this represents a major and general cellular function of importins.
Seeing objects in motion

This paper reports estimates of the conjoint spatiotemporal tuning functions of the neural mechanisms of the human vision system which detect image motion. The functions were derived from measurements of the minimum contrast necessary to detect the direction of drift of a sinusoidal grating, in the presence of phase-reversed masking gratings of various spatial and temporal frequencies. A mask of similar spatial and temporal frequencies to the test grating reduces sensitivity considerably, whereas one differing greatly in spatial or temporal frequency has little or no effect. The results show that for test gratings drifting at 8 Hz, the tuning function is bandpass in both space and time, peaked at the temporal and spatial frequency (SF) of the test (SFs were 0.1, 1 or 5 c deg–1; c represents cycles throughout). For a grating of 5 c deg–1 drifting at 0.3 Hz, the function is bandpass in space but lowpass in time. Fourier transform of the frequency results yields a function in space-time which we term the ‘spatiotemporal receptive field’. For movement detectors (bandpass in space and time) the fields comprise alternating ridges of opposing polarity, elongated in space-time along the preferred velocity axis of the detector. We suggest that this organization explains how detectors analyse form and motion concurrently and accounts, at least in part, for a variety of perceptual phenomena, including summation, reduction of motion smear, metacontrast, stroboscopic motion and spatiotemporal interpolation.
Optimizing cyanobacterial product synthesis: Meeting the challenges

ABSTRACT The synthesis of renewable bioproducts using photosynthetic microorganisms holds great promise. Sustainable industrial applications, however, are still scarce and the true limits of phototrophic production remain unknown. One of the limitations of further progress is our insufficient understanding of the quantitative changes in photoautotrophic metabolism that occur during growth in dynamic environments. We argue that a proper evaluation of the intra- and extracellular factors that limit phototrophic production requires the use of highly-controlled cultivation in photobioreactors, coupled to real-time analysis of production parameters and their evaluation by predictive computational models. In this addendum, we discuss the importance and challenges of systems biology approaches for the optimization of renewable biofuels production. As a case study, we present the utilization of a state-of-the-art experimental setup together with a stoichiometric computational model of cyanobacterial metabolism for quantitative evaluation of ethylene production by a recombinant cyanobacterium Synechocystis sp. PCC 6803.
Genetic epidemiology of cancer: From families to heritable genes

A reliable determination of familial risks for cancer is important for clinical counseling, prevention and understanding cancer etiology. Family‐based gene identification efforts may be targeted if the risks are well characterized and the mode of inheritance is identified. Medically verified data on familial risks have not been available for all types of cancer but they have become available through the use of the nationwide Swedish Family‐Cancer Database, which includes all Swedes born in 1932 and later with their parents, totaling over 10 million individuals. Over 150 publications have emanated from this source. The familial risks of cancer have been characterized for all main cancers and the contribution of environmental and heritable effects to the familial aggregation has been assessed. Furthermore, the mode of inheritance has been deduced by comparing risks from parental and sibling probands. Examples are shown on familial clustering of cancers, for which heritable susceptibility genes are yet unknown, such as squamous cell carcinoma of the skin, intestinal carcinoids, thyroid papillary tumors, brain astrocytomas and pituitary adenomas. Some common cancers, such as lung and kidney cancers, appear to show an early‐onset recessive component because familial risks among siblings are much higher than those in families where parents are probands. Many of the cancer sites showing high familial risks lack guidelines for clinical counseling or action level. In conclusion, we recommend that any future gene identification efforts, either using linkage or association designs, devise their strategies based on data from family studies. Clinical genetic counseling would benefit from reviewing established familial risks on all main types of cancer. © 2004 Wiley‐Liss, Inc.
Augmentation of 17-1A–Induced Antibody-Dependent Cellular Cytotoxicity by the Triple Cytokine Combination of Interferon-&agr;, Interleukin-2, and Interleukin-12

Previously, interferon-&agr; (IFN-&agr;), interleukin-2 (IL-2), and interleukin-12 (IL-12) were shown to increase the antibody-dependent cellular cytotoxicity (ADCC) induced by the murine monoclonal antibody 17-1A, which recognizes the tumor-associated antigen EpCAM. In this study, the authors wanted to determine whether the combination of these three cytokines would yield greater cytotoxicity than the single cytokines. For cytotoxicity assessment, a new flow cytometric assay was used that allows the analysis of long-term ADCC exerted by macrophages. Peripheral blood mononuclear cells from healthy donors were used as effector cells against the colorectal carcinoma cell line HT29 at a low effector-to-target ratio of 4.5:1. With this test, the effectiveness of the combinations IL-2 and IFN-&agr;, IL-2 and IL-12, and IL-12 and IFN-&agr; were compared with each other. The combinations IL-2 plus IL-12 and IFN-&agr; plus IL-12 were more potent at the concentrations tested. Furthermore, the triple cytokine combination of IFN-&agr;, IL-2, and IL-12 revealed significantly greater ADCC than dual cytokine combinations. Next, CD14+, CD4+, and CD4− cells were isolated by paramagnetic beads and magnetic activated cell sorter (MACS) columns. The CD14+ and CD4− cell populations contained the ADCC effectors. The addition of CD4+ cells to CD14+ or CD4− cells resulted in augmented ADCC, indicating that cooperation between immune cells occurs. These results suggest that multiple cytokine combinations with monoclonal antibodies may be more effective for cancer immunotherapy.
Multifractal ECG Mapping of Ventricular Epicardium During Regional Ischemia in the Pig

Myocardial ischemia creates abnormal electrophysiological substrates that can result in life-threatening ventricular arrhythmias. Early clinical identification of ischemia in patients is important to managing their condition. We analyzed electrograms from an ischemia-reperfusion animal model in order to investigate the relationship between myocardial ischemia and variability of electrocardiogram (ECG) multifractality. Ventricular epicardial electropotential maps from the anesthetized pig during LAD ischemia-reperfusion were analyzed using multifractal methods. A new parameter called the singularity spectrum area reference dispersion (SARD) is presented to represent the temporal evolution of multifractality. By contrasting the ventricular epicardial SARD and range of singularity strength (Deltaalpha) maps against activation-recovery interval (ARI) maps, we found that the dispersions of SARD and Deltaalpha increased following the onset of ischemia and decreased with tissue recovery. In addition, steep spatial gradients of SARD and Deltaalpha corresponded to locations of ischemia, although the distribution of multifractality did not reflect the degree of myocardial ischemia. However, the multifractality of the ventricular epicardial electrograms was useful for classifying the recoverability of ischemic tissue. Myocardial ischemia significantly influenced the multifractality of ventricular electrical activity. Recoverability of ischemic myocardium can be classified using the multifractality of ventricular epicardial electrograms. The location and size of regions of severe ischemic myocardium with poor recoverability is detectable using these methods
Outcomes of children treated for tuberculosis with second-line medications in Georgia, 2009-2011.

BACKGROUND Drug-resistant tuberculosis (DR-TB) is a major public threat in countries of the former Soviet Union, including Georgia. There are few studies of pediatric DR-TB cases, especially at a national level. OBJECTIVE To report the characteristics and treatment outcomes of pediatric multidrug-resistant TB (MDR-TB) cases in Georgia. METHODS We extracted data on all pediatric (age <16 years) MDR-TB cases notified in Georgia from 2009 to 2011. We assessed the baseline and treatment characteristics and treatment outcomes of this cohort. RESULTS Between 2009 and 2011, there were 45 notified pediatric DR-TB cases in Georgia. Just over half had previously received anti-tuberculosis treatment and the median age was 7.7 years. Time from diagnosis to treatment was short (median 16 days), and the median length of treatment was 20.2 months. Of those not still on treatment, 77.1% (95%CI 61.0-87.9) had a successful outcome. CONCLUSIONS One of the first reports of pediatric DR-TB treatment outcomes at a national level, this study demonstrates that successful outcomes can be achieved.
Realization of a 15-channel, hermetically-encased wireless subretinal prosthesis for the blind

A miniaturized, hermetically-encased, wirelessly-operated retinal prosthesis has been developed for implantation and pre-clinical studies in Yucatan mini-pig animal models. The prosthesis conforms to the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially-designed ab externo surgical technique that affixes the bulk of the prosthesis to the surface of the sclera. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete power supply components. Feedthroughs from the case connect to secondary power- and data-receiving coils. In addition, long-term in vitro pulse testing was performed on the electrodes to ensure their stability for the long lifetime of the hermetic case. The final assembly was tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a custom graphical user interface. Operation of the retinal implant has been verified in vivo in one pig for more than three months by measuring stimulus artifacts on the eye surface using a contact lens electrode.
Improvement in fusion and stereopsis following surgery for intermittent exotropia.

PURPOSE To evaluate fusion stereopsis in patients with intermittent exotropia before and after strabismus surgery. METHODS Fifty-three patients (mean age: 11.8 years, range: 5 to 25 years) with intermittent exotropia were enrolled. Fusion was measured with the Worth 4-dot test. Near stereopsis was examined with Titmus and stereoscopic test charts (created in China by Shao-Ming Yan). Distance stereopsis was tested with random-dot stereograms produced by Tianjin Eye Hospital. All patients completed the tests preoperatively and 2 and 6 weeks postoperatively. RESULTS There were no statistically significant differences in stereoscopic test charts among groups preoperatively (P > .05) and postoperatively (P > .05) or on Titmus tests preoperatively (P > .05) and postoperatively (P > .05). Among 53 patients, the percentage of distance stereoscopic improvement was 49% after 2 weeks and 77% after 6 weeks compared to 13% preoperatively. Six weeks postoperatively, random-dot stereograms were significantly different in those younger than 7 years and older than 13 years (P < .05), as well as those 7 to 13 years and older than 13 years (P < .05). Fifty (94%) demonstrated peripheral fusion and only 21 (40%) demonstrated central fusion preoperatively. Six weeks postoperatively, all patients exhibited peripheral fusion and 52 (98%) demonstrated central fusion. Central fusion in patients with intermittent exotropia significantly increased after 6 weeks (chi-square = 42.29, P < .01). CONCLUSIONS Patients with intermittent exotropia have good near stereoacuity preoperatively and postoperatively. Even if surgery is postponed until adolescence, distance stereopsis can still be recovered. Surgical intervention can restore central fusion and stereoacuity in patients with intermittent exotropia.
Novel miniaturized branch-line coupler using bond-wire slow-wave structure

In this paper, one compact branch-line coupler is presented. The new structure consists of four lambda/4 transmission line which is shorten by slow-wave effect. Each slow-wave transmission line consists of inductive section using a bondwire as series inductor, and capacitive section using a metal island as capacitor. Because of slow-wave effect, the proposed coupler has 31% physical size of the conventional coupler at 1 GHz. The analyzed result has been achieved phase difference between S21 and S31, which is within 90deg plusmn 1deg. Furthermore, the insertion loss of the proposed branch-line coupler is comparable to that of conventional branch-line coupler. The new coupler can be easily implemented by using the standard printed-circuit-board etching processes and the wire bonding process that has very low tolerance. The proposed structure is very useful for wireless communication system.
Diabetes, oxidative stress, and antioxidants: A review

Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:24–38, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10058
[Alterations in the decision making processes linked to the ventromedial prefrontal cortex in drug-abusing patients].

INTRODUCTION The somatic marker hypothesis proposes that somatic signals guide the decision making processes in an adaptive sense for the organism. The processing of these somatic signals is linked to the ventromedial prefrontal cortex activity. The influence of somatic markers on decision making processes has been studied by means of the 'gambling task' (GT). Several studies using the GT in substance abusers have showed the existence of decision making impairments in these patients. AIMS To examine the performance in the GT of a Spanish sample of substance abusers; and to study the influence of clinically relevant variables: type of substance, years of abuse and abstinence period on GT performance. PATIENTS AND METHODS 106 substance abusers patients during the dishabituation phase participated in the study. We administered a computerized version of the GT in a single individual session. We used descriptive analyses to study the patients' performance in the GT. Next we carried out multiple regression analyses to study the influence of the clinical variables on the GT performance. RESULTS A 76.4% of the sample patients showed impairments in the decision making processes measured by the GT. None of the clinical variables significantly predicted performance in the task. CONCLUSIONS These results suggest the existence of decision making impairments in substance abusers that may be related to pre morbid alterations, or to a neurotoxic effect of drugs of abuse on the activity of the ventromedial prefrontal cortex.
Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiac Disorders

Objective: To evaluate the literature about the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of cardiac disorders, specifically myocardial infarction (MI) and heart failure (HF). Data Sources: Searches were conducted in MEDLINE (1946-May 2016) and Excerpta Medica (1980-May 2016) using EMBASE with the search terms glucagon-like peptide 1, exenatide, albiglutide, liraglutide, dulaglutide, myocardial infarction, heart failure, and cardiovascular. The references of relevant articles were reviewed to identify additional citations. Study Selection and Data Extraction: Clinical trials were limited to the English language and human trials. In all, 18 trials explored the use of GLP-1 RAs in the treatment of cardiac disorders in patients with and without diabetes mellitus. Data Synthesis: Of the 18 trials reviewed, 11 trials studied the impact of GLP-1 RAs in MI. All showed a significant beneficial effect on various cardiac parameters. Favorable outcome improvements included myocardial blood flow, left ventricular (LV) function, and MI size. Seven trials reviewed the use of GLP-1 RAs in the treatment of HF. Three trials showed significant improvements in LV ejection fraction, cardiac index, and peak oxygen consumption. Conclusions: Limited data suggest that GLP-1 RAs may be effective for the treatment of cardiac disorders in patients with and without diabetes mellitus. These studies suggest that GLP-1 RAs may have potential pleiotropic beneficial effects in patients with cardiovascular disease beyond their role in managing diabetes. These medications may be cardioprotective after a MI but are less promising in HF.
Exploration of system availability during software-based self-testing in many-core systems under test latency constraints

As technology scales, the increased vulnerability of modern systems due to unreliable components becomes a major problem in the era of multi-/many-core architectures. Recently, several on-line testing techniques have been proposed, aiming towards error detection of wear-out/aging-related defects that can appear during the lifetime of a system. In this work, we investigate the relation between system test latency and testtime overhead in multi-/many-core systems with shared LastLevel Cache (LLC) for periodic Software-Based Self-Testing (SBST), under different test scheduling policies. The investigated scheduling policies primarily vary the number of cores concurrently under test in the overall system testing session. Our extensive, workload-driven dynamic exploration reveals that there is an inverse relation between the two test measures; as the number of cores concurrently under test increases, system test latency decreases, but at the cost of significantly increased test time, which sacrifices system availability for running normal workloads. Under given system test latency constraints, which should be utilized in order to be able to control system recovery time in the event of an error detection, our exploration framework identifies the scheduling policy under which overall test time overhead is minimized and, hence, system availability is maximized. Without any loss of generality, a 16-core system is explored in a full-system, execution-driven simulation framework running multi-threaded PARSEC workloads [1].
Animal coloration: production, perception, function and application

Research on animal coloration is a vibrant area of biology currently involving evolutionary biologists, behavioural ecologists, psychologists, optical physicists, visual ecologists, geneticists and anthropologists. The proliferation of recent work requires that we take stock of the field, aiming to identify major themes, questions and future directions. This was the goal of the year-long Wissenschaftskolleg zu Berlin ‘focus group’ (2015–2016), in which many of the authors in this issue participated either as fellows or visitors. The result is this 19-chapter theme issue, in which we pinpoint the breakthroughs and challenges in animal coloration research, focusing on production, perception, function and evolution. We also explore animal coloration research as it applies to humans. This theme issue is by no means exhaustive but our goal has been to summarize …