Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Global and Local Topology in the Regulation of Gene Expression in Streptococcus pneumoniae

The most basic level of transcription regulation in Streptococcus pneumoniae is the organization of its chromosome in topological domains. In response to drugs that caused DNA-relaxation, a global transcriptional response was observed. Several chromosomal domains were identified based on the transcriptional response of their genes: up-regulated (U), down-regulated (D), non-regulated (N), and flanking (F). We show that these distinct domains have different expression and conservation characteristics. Microarray fluorescence units under non-relaxation conditions were used as a measure of gene transcriptional level. Fluorescence units were significantly lower in F genes than in the other domains with a similar AT content. The transcriptional level of the domains categorized them was D>U>F. In addition, a comparison of 12 S. pneumoniae genome sequences showed a conservation of gene composition within U and D domains, and an extensive gene interchange in F domains. We tested the organization of chromosomal domains by measuring the relaxation-mediated transcription of eight insertions of a heterologous Ptccat cassette, two in each type of domain, showing that transcription depended on their chromosomal location. Moreover, transcription from the four promoters directing the five genes involved in supercoiling homeostasis, located either in U (gyrB), D (topA), or N (gyrA and parEC) domains was analyzed both in their chromosomal locations and in a replicating plasmid. Although expression from the chromosomal PgyrB and PtopA showed the expected domain regulation, their expression was down-regulated in the plasmid, which behaved as a D domain. However, both PparE and PgyrA carried their own regulatory signals, their topology-dependent expression being equivalent in the plasmid or in the chromosome. In PgyrA a DNA bend acted as a DNA supercoiling sensor. These results revealed that DNA topology functions as a general transcriptional regulator, superimposed upon other more specific regulatory mechanisms.
Prevalence of symptoms, with a focus on fatigue, and changes of symptoms over three months in outpatients receiving cancer chemotherapy.

QUESTIONS UNDER STUDY Prevalence of symptoms, with a focus on fatigue, and changes of symptoms were explored over three months in outpatients with lymphoma, lung, breast or colorectal cancer, receiving chemotherapy in the oncology outpatient clinic of a Swiss tertiary care hospital. METHODS Prospective, descriptive design; symptom prevalence was measured at start of chemotherapy (T1), and one week prior to the third and fourth cycle (T2, T3). Included were patients starting chemotherapy, with expected survival of >3 months, irrespective of stage of disease. The Memorial Symptom Assessment Scale was used to assess 32 symptoms; fatigue was measured with the FACIT-Fatigue Scale (negative scale). Data were analysed using descriptive statistics and random-intercept regression models. RESULTS 77 patients participated at T1, 58 and 50 at T2 and T3. Patients experienced on average 9.8, 14.4, and 13.7 symptoms, showing a significant increase over time. Lack of energy and feeling drowsy were most frequent. Symptom scores for lack of energy, changes in skin, pain, and feeling drowsy remained >2 over time (scale 0-4, higher scores = more symptoms). Fatigue mean scores were 36.3, 30.2, and 31.3, showing a significant increase of fatigue over time. Individual symptom trajectories varied widely within and among patients. CONCLUSIONS High symptom prevalence at start of chemotherapy as well as over time and great variability in symptom experience call for an individual, systematic symptom assessment and management that does not focus solely on side-effects of therapy but includes disease-related symptoms to achieve satisfactory control of symptoms in outpatients receiving chemotherapy.
Integrating testing into the curriculum — arsenic in small doses

Testing accounts for 50% of the cost of software, yet it receives little treatment in most curricula. This paper presents some approaches to giving all students multiple, incremental exposures to software testing throughout the curriculum. A unifying framework is presented which identifies a minimal set of test experiences, skills and concepts students should accumulate. The integrated approach combines common test experiences in core courses, an elective course in software testing, and volunteer participation in a test laboratory.
Network-on-SSD: A Scalable and High-Performance Communication Design Paradigm for SSDs

In recent years, flash memory solid state disks (SSDs) have shown a great potential to change storage infrastructure because of its advantages of high speed and high throughput random access. This promising storage, however, greatly suffers from performance loss because of frequent ``erase-before-write'' and ``garbage collection'' operations. Thus, novel circuit-level, architectural, and algorithmic techniques are currently explored to address these limitations. In parallel with others, current study investigates replacing shared buses in multi-channel architecture of SSDs with an interconnection network to achieve scalable, high throughput, and reliable SSD storage systems. Roughly speaking, such a communication scheme provides superior parallelism that allows us to compensate the main part of the performance loss related to the aforementioned limitations through increasing data storage and retrieval processing throughput.
FUZZY SOFT TOPOLOGY

In the present paper we introduce the topological structure of fuzzy soft sets and fuzzy soft continuity of fuzzy soft mappings. We show that a fuzzy soft topological space gives a parametrized family of fuzzy topological spaces. Furthermore, with the help of an example it is shown that the constant mapping is not continuous in general. Then the notions of fuzzy soft closure and interior are introduced and their basic properties are investigated. Finally, the initial fuzzy soft topology and some properties of projection mappings are studied.
Ontogenetic changes in fl ippers morphometrics in bottlenose dolphins ( Tursiops truncatus )

The aim of the present study was to investigate and compare the morphometric characteristics of the fl ippers in male and female bottlenose dolphins (Tursiops truncatus) of various ages. We investigated the right fl ippers of 64 bottlenose dolphinc specimens 36 males and 28 females, in an age span of from 6 months to 28 years. Two numeric indices were suggested in order to establish the numerical relationship between the external measures of the fl ipper and the total body length of each animal. The index of the fl ipper measurements (IxF) directly showed the differences in fl ipper sizes in the investigated dolphins, whereas the index of the fl ipper measurements and the total body length (IxBL) displayed the differences in the fl ipper size in relation to the body length of the studied dolphins. By comparing these indices in dolphins of different ages, noticeable variations in fl ipper dimensions during total body growth were observed. In bottlenose dolphins, both fl ipper indices were highly correlated with the animal’s body length. The mean value of the index of the fl ipper measurements and the total body length (IxBL) was somewhat higher in female bottlenose dolphins. Both the fl ipper indices were highly correlated with the animal’s age, and our results suggest that the fl ipper grows until the tenth year of age, after which it does not change substantially until the 25th year of age. After that age the fl ipper size starts to decrease.
Left Ventricular Midwall Mechanics in Systemic Arterial Hypertension Myocardial Function is Depressed in Pressure‐Overload Hypertrophy

BackgroundLeft ventricular (LV) midwall geometry has been described conventionally as the sum of the chamber radius and half of the wall thickness; this convention is based on the assumption of uniform transmural thickening during systole. However, theoretical considerations and experimental data indicate that the inner half (inner shell) of the LV wall thickens more than the outer half (outer shell). Thus, an end-diastolic circumferential midwall fiber exhibits a relative migration toward the epicardium during systole. As a result, the conventional method provides an overestimate of the extent of the midwall fiber shortening. Methods and ResultsWe developed an ellipsoidal model with a concentric two-shell geometry (nonuniform thickening) to assess midwall fiber length transients throughout the cardiac cycle. This modified midwall method was used in the analysis of LV cineangiograms from 15 patients with systemic arterial hypertension and 14 normal subjects. Study groups were classified according to LV mass index (LVMI): 14 normal subjects (group I), eight hypertensive patients with a normal LVMI (group II), and seven hypertensive patients with an increased LVMI (group III). There were no significant differences in LV end-diastolic pressure or volume among the three groups; the ejection fraction was slightly greater in group 11 (70 + 5%) than in groups I (65±8%) and III (664±4%), but this trend did not achieve statistical significance. Values for endocardial and conventional midwall fractional shortening (FS) were also similar in the three groups. By contrast, FS by the concentric two-shell geometry (modified midwall method) in group III (16±2%) was significantly less than that seen in groups I and II (21±4% and 21 + 5%, respectively; both p < 0.05). This difference achieves greater importance when it is recognized that mean systolic circumferential stress was lower in group III (151±22 g/cm2) than in groups I and 11 (244±37 g/cm2 and 213+38 g/cm2, respectively; both p<0.01). The midwall stressshortening coordinates in six of the seven group III patients were outside the 95% confidence limits for the normal (group I) subjects. Thus, despite a normal ejection fraction, systolic function is subnormal in hypertensive patients with LV hypertrophy. ConclusionsChamber dynamics provide an overestimate of myocardial function, especially when LV wall thickness is increased. This is due to a relatively greater contribution of inner shell thickening in pressure-overload hypertrophy.
Chromosome segregation in plant meiosis

Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.
Tentative guidelines for using clinical and economic evaluations revisited.

W e thank Gafni and Birch (see pages 913 to 917) and Naylor and associates (see pages 921 to 924) for their thoughtful and useful comments on our paper in which we outlined tentative guidelines for using clinical and economic evaluations. ' The comments cover three general areas: (a) the appropriateness of quality-adjusted lifeyears (QALYs) as a measure of outcome in economic evaluations, (b) the appropriateness of the dollar value of the boundaries of cost-effectiveness that categorize technologies as B, C or D and the accuracy with which those judgements can be made and (c) the potential adverse consequences of using the guidelines (Will they lead to an increase in health care expenditure? Will policymakers respond to changes in cost-effectiveness ratios that occur over time? Are there undesirable ethical implications associated with the use of the guidelines? ).
Far-Field Acoustic Source Localization and Bearing Estimation Using $\Sigma\Delta$  Learners

Localization of acoustic sources using miniature microphone arrays poses a significant challenge due to fundamental limitations imposed by the physics of sound propagation. With sub-wavelength distances between the microphones, resolving acute localization cues become difficult due to precision artifacts. In this paper we propose a framework which overcomes this limitation by integrating signal-measurement (analog-to-digital conversion) with statistical learning (bearing estimation). At the core of the proposed approach is a min-max stochastic optimization of a regularized cost function that embeds manifold learning within ¿¿ modulation. As a result, the algorithm directly produces a quantized sequence of the bearing estimates whose precision can be improved asymptotically similar to a conventional ¿¿ modulators. In this paper we present a hardware implementation of a miniature acoustic source localizer which comprises of: (a) a common-mode canceling microphone array and (b) a ¿¿ integrated circuit which produces bearing parameters. The parameters are then combined in an estimation procedure that can achieve a linear range from 0°-90°. Measured results from a prototype fabricated in a 0.5 ¿m CMOS process demonstrate that the proposed localizer can reliably estimate the bearing of an acoustic source with a resolution less than 2° while consuming less than 75 ¿W of power.
Robust nonnegative matrix factorization with ordered structure constraints

Nonnegative matrix factorization (NMF) as a popular technique to find parts-based representations of nonnegative data has been widely used in real-world applications. Often the data which these applications process, such as motion sequences and video clips, are with ordered structure, i.e., consecutive neighbouring data samples are very likely share similar features unless a sudden change occurs. Therefore, traditional NMF assumes the data samples and features to be independently distributed, making it not proper for the analysis of such data. In this paper, we propose an ordered robust NMF (ORNMF) by capturing the embedded ordered structure to improve the accuracy of data representation. With a novel neighbour penalty term, ORNMF enforces the similarity of neighbouring data. ORNMF also adopts the L2,1-norm based loss function to improve its robustness against noises and outliers. A new iterative updating optimization algorithm is derived to solve ORNMF's objective function. The proofs of the convergence and correctness of the scheme are also presented. Experiments on both synthetic and real-world datasets have demonstrated the effectiveness of ORNMF.
Systemic inflammatory response syndrome in patients hospitalized for gastrointestinal bleeding.

OBJECTIVE To describe the incidence and causes of systemic inflammatory response syndrome (SIRS), to determine the risk factors for its development, and to assess its impact on the outcome of patients hospitalized for gastrointestinal bleeding. DESIGN Prospective, observational study. SETTING A 528-bed, university-affiliated, teaching hospital. PATIENTS The study included 411 adults hospitalized for gastrointestinal bleeding from January 1, 1995, through June 30, 1996. MEASUREMENTS We obtained the demographic data, selected clinical findings, laboratory values, length of hospital stay, presence and cause of SIRS, presence of organ failure, and in-hospital mortality for each patient. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated. Univariate and multivariate logistic regression analyses were used to determine differences between groups. RESULTS Patients' ages (mean +/- SD) were 55.9 +/- 17.3 yr; 227 (55%) were male; 247 (60%) were African-American. SIRS developed in 112 patients (27%). Sepsis was the cause of SIRS in 63% of patients (70/112). Severe sepsis developed in 20 patients and septic shock in 5 patients. The most common cause of sepsis was pneumonia (19). There were no significant differences in age, gender, race, and the presence of liver disease between patients with and without SIRS. Upper gastrointestinal bleeding (76/211 vs. 36/ 200; p = .0196), intensive care unit admission (73/152 vs. 391259; p < .0001), and higher APACHE II scores (median, 17 vs. 11; p< .0001) were associated with the development of SIRS. The length of hospital stay was longer (median, 9.5 vs. 3 days; p < .0001), and the number of organ failures (median, 1 vs. 0; p < .0001) and in-hospital mortality rates (23 vs. 4%; p < .0001) were higher in patients with SIRS than in those without SIRS. CONCLUSIONS SIRS occurs in 27% of patients admitted for gastrointestinal bleeding and is associated with a poor prognosis. Intensive care unit admission, upper gastrointestinal bleeding, and high APACHE II scores are risk factors for the development of SIRS in patients hospitalized for gastrointestinal bleeding.
Lung cancer in HIV positive patients: the GICAT experience.

PURPOSE AIDS incidence and mortality have decreased since the introduction of highly active antiretroviral therapy (HAART) into clinical practice. HIV-related malignancies, namely Kaposi's sarcoma and Non-Hodgkin's lymphoma, have decreased, whereas non-AIDS defining tumors have been increasing. Our aim was to study the impact of HAART on natural history of lung cancer in HIV-positive patients, comparing patients with HIV-lung cancer treated in the pre-HAART era versus the HAART era. PATIENTS AND METHODS We collected 68 patients with HIV-lung cancer diagnosed from 1986 to 2003. Pre-HAART era included 34 patients who did not receive HAART, whereas the HAART era included 34 patients diagnosed after January 1997 who received HAART. RESULTS At diagnosis Performance Status (PS) was significantly different, patients with PS ≥ 2 were 44% in the pre-HAART era, versus 29% in the post-HAART era, p = 0.02. The 79.4% of patients in the post-HAART era received chemotherapy alone or with radiotherapy versus 47% in the pre-HAART era, p = 0.04. Cancer was the leading cause of death for both groups, with 29 (85.3%) and 21 (61.8%) patients in the pre- and post-HAART settings, respectively. The median overall survival (OS) was 3.8 months for the pre-HAART population vs. 7 months for the post-HAART patients, p = 0.01. CONCLUSIONS HIV-lung cancer patients have a longer overall survival in the post-HAART era versus the pre-HAART era, due to a not detrimental effect of chemotherapy and positive effect of HAART. Lung cancer is the leading cause of death, showing that treatment of the cancer is the most important target now to improve their outcome.
Delimitation of problem areas in Poland

Abstract The study presents the delimitation of problem areas carried out at the Institute of Geography and Spatial Organization of PAS on behalf of the Ministry of Development of Poland (2015-2016), first and foremost to meet the practical needs of the development policy being pursued at state, regional and local government levels. The study was elaborated for the 2479 Polish communes (gminas) by reference to 21 indicators mainly concerned with the state of the natural environment and socio-economic conditions, as well as features of spatial and local development. The three categories of area ultimately identified were the natural, the social and the economic aspects, the combination of which yielded several main types of problem area. A last stage then entailed a division into regions, i.e. the designation and naming of particular geographical areas.
Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude

Pregnancy at high altitude is associated with a reduction in birth weight of ~100 g/1000 m of ascent. The underlying mechanisms are unclear but may involve alteration in energy‐demanding activities, such as protein synthesis. To test this hypothesis, both in vivo and in vitro approaches were used. Placental tissues from pregnant women residing at 3100 m were studied, and placental cells were incubated under hypoxia. In the 3100‐m placentas, we observed dilation of endoplasmic reticulum (ER) cisternae, increased phosphorylation of eukaryotic initiation factor 2 subunit α (P‐eIF2α), reduced AKT phosphorylation, and reduced P‐4E‐BP1 but increased 4E‐BP1 protein compared to sea level controls. These findings suggest the presence of ER stress and protein synthesis inhibition. Hypoxia (1% O2) reduced proliferation of trophoblast‐like JEG‐3 cells, BeWo cells, and placental fibroblasts by ~40, ~60, and ~18%, respectively. Sublethal dosage of salubrinal, an eIF2α phosphatase inhibitor, increased P‐eIF2α and reduced BeWo cell and placental fibroblast proliferation by ~50%. Administration of the PI‐3K inhibitor LY294002 also reduced JEG‐3 proliferation. Our results demonstrate that exposure to chronic hypobaric hypoxia causes mild placental ER stress, which, in turn, modulates protein synthesis and slows proliferation. These effects may account for the reduced placental villous volume, and contribute to the low birth weight that typifies high‐altitude populations. —Yung, H. W. , Cox, M. , Tissot van Patot, M. , Burton, G. J. Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non‐native women at high altitude. FASEB J. 26, 1970‐1981 (2012). www.fasebj. org
Reversible Deactivation of Motor Cortex Reveals Functional Connectivity with Posterior Parietal Cortex in the Prosimian Galago (Otolemur garnettii)

We examined the functional macrocircuitry of frontoparietal networks in the neocortex of prosimian primates (Otolemur garnettii) using a microfluidic thermal regulator to reversibly deactivate selected regions of motor cortex (M1). During deactivation of either forelimb or mouth/face movement domains within M1, we used long-train intracortical microstimulation techniques to evoke movements from the rostral division of posterior parietal cortex (PPCr). We found that deactivation of M1 movement domains in most instances abolished movements evoked in PPCr. The most common effect of deactivating M1 was to abolish evoked movements in a homotopic domain in PPCr. For example, deactivating M1 forelimb lift domains resulted in loss of evoked movement in forelimb domains in PPCr. However, at some sites, we also observed heterotopic effects; deactivating a specific domain in M1 (e.g., forelimb lift) resulted in loss of evoked movement in a different movement domain in PPCr (e.g., hand-to-mouth or eye-blink). At most sites examined in PPCr, rewarming M1 resulted in a reestablishment of the baseline movement at the same amplitude as that observed before cooling. However, at some sites, reactivation did not result in a return to baseline movement or to the full amplitude of the baseline movement. We discuss our findings in the context of frontoparietal circuits and how they may subserve a repertoire of ecologically relevant behaviors. SIGNIFICANCE STATEMENT The posterior parietal cortex (PPC) of primates integrates sensory information used to guide movements. Different modules within PPC and motor cortex (M1) appear to control various motor behaviors (e.g., reaching, defense, and feeding). How these modules work together may vary across species and may explain differences in dexterity and even the capacity for tool use. We investigated the functional connectivity of these modules in galagos, a prosimian primate with relatively simple frontoparietal circuitry. By deactivating a reaching module in M1, we interfered with the function of similar PPC modules and occasionally unrelated PPC modules as well (e.g., eye blink). This circuitry in galagos, therefore, is more complex than in nonprimates, indicating that it has been altered with the expansion of primate PPC.