Miracle-dz/UniFAR-FTUs huggingface dataset:
Mixed Messages: Transcription Patterns in Failing and Recovering Human Myocardium

In previous studies, mechanical support of medically refractory hearts with a left ventricular assist device (LVAD) has induced regression of many morphological and functional abnormalities characteristic of failing human hearts. To identify transcriptional adaptations in failing and LVAD-supported hearts, we performed a comprehensive transcription analysis using the Affymetrix microarray platform and 199 human myocardial samples from nonfailing, failing, and LVAD-supported human hearts. We also used a novel analytical strategy that defines patterns of interest based on multiple intergroup comparisons. Although over 3088 transcripts exhibited significantly altered abundance in heart failure, most of these did not exhibit a consistent response to LVAD support based on our analysis. Of those 238 with a consistent response to LVAD support, more than 75% exhibited persistence or exacerbation of HF-associated transcriptional abnormalities whereas only 11%, 5%, and 2% exhibited partial recovery, normalization, and overcorrection responses, respectively. Even among genes implicated by previous reports of LVAD-associated myocardial improvements, partial or complete normalization of transcription did not predominate. The magnitude of differences in transcript abundance between nonfailing and failing hearts, and between failing an LVAD-supported hearts, tended to be low with changes greater than or equal to 2-fold infrequently observed. Our results indicate that morphological or functional myocardial improvements may occur without widespread normalization of pathological transcriptional patterns. These observations also suggest that many failure-associated transcriptional changes have only a limited role in regulating cardiac structure and function and may represent epiphenomena and/or nonspecific myocardial plasticity responses. Differences in mRNA localization, translation efficiency, and posttranslational protein modifications or interactions may be more pivotal in regulating myocardial structure and function.
Detection of synthetic speech for the problem of imposture

In this paper, we present new results from our research into the vulnerability of a speaker verification (SV) system to synthetic speech. We use a HMM-based speech synthesizer, which creates synthetic speech for a targeted speaker through adaptation of a background model and both GMM-UBM and support vector machine (SVM) SV systems. Using 283 speakers from the Wall-Street Journal (WSJ) corpus, our SV systems have a 0.35% EER. When the systems are tested with synthetic speech generated from speaker models derived from the WSJ journal corpus, over 91% of the matched claims are accepted. We propose the use of relative phase shift (RPS) in order to detect synthetic speech and develop a GMM-based synthetic speech classifier (SSC). Using the SSC, we are able to correctly classify human speech in 95% of tests and synthetic speech in 88% of tests thus significantly reducing the vulnerability.
BslA, a pXO1‐encoded adhesin of Bacillus anthracis

The Gram‐positive pathogen Bacillus anthracis causes anthrax, a fulminant and lethal infection of mammals. Two large virulence plasmids, pXO1 and pXO2, harbour genes required for anthrax pathogenesis and encode secreted toxins or provide for the poly γ‐d‐glutamic acid capsule. In addition to capsule, B. anthracis harbours additional cell wall envelope structures, including the surface layer (S‐layer), which is composed of crystalline protein arrays. We sought to identify the B. anthracis envelope factor that mediates adherence of vegetative forms to human cells and isolated BslA (B. anthracisS‐layer protein A). Its structural gene, bslA, is located on the pXO1 pathogenicity island (pXO1‐90) and bslA expression is both necessary and sufficient for adherence of vegetative forms to host cells. BslA assembly into S‐layers and surface exposure is presumably mediated by three N‐terminal SLH domains. Twenty‐three B. anthracis genes, whose products harbour similar SLH domains, may provide additional surface molecules that allow bacilli to engage cells or tissues of specific hosts during anthrax pathogenesis.
Deep Class Aware Denoising

The increasing demand for high image quality in mobile devices brings forth the need for better computational enhancement techniques, and image denoising in particular. At the same time, the images captured by these devices can be categorized into a small set of semantic classes. However simple, this observation has not been exploited in image denoising until now. In this paper, we demonstrate how the reconstruction quality improves when a denoiser is aware of the type of content in the image. To this end, we first propose a new fully convolutional deep neural network architecture which is simple yet powerful as it achieves state-of-the-art performance even without being class-aware. We further show that a significant boost in performance of up to $0.4$ dB PSNR can be achieved by making our network class-aware, namely, by fine-tuning it for images belonging to a specific semantic class. Relying on the hugely successful existing image classifiers, this research advocates for using a class-aware approach in all image enhancement tasks.
High-dose rate brachytherapy of bronchial cancer: treatment optimization using three schemes of therapy.

PURPOSE Our aim is to demonstrate that a fractionated high-dose rate endobronchial brachytherapy (HDRBT) treatment is tolerable for patients with advanced (IIIA-IIIB) non-small cell lung cancer and gives an improvement of symptoms. Patients and Methods. From January 1992 to July 1997, we treated 320 patients with external beam radiotherapy (EBRT) and concomitant HDRBT with Ir192. Eighty-four patients received 10 Gy in one fraction from January 1992 to March 1993 (Group A); 47 patients received two fractions of 7 Gy each from April 1993 to December 1993 (Group B), and 189 patients received three fractions of 5 Gy each from January 1994 to July 1997 (Group C). RESULTS Mean survival from diagnosis is 11.1 months and mean survival from last HDRBT is 9.7 months. The symptomatic response rate is 90% for dyspnea, 82% for cough, 94% for hemoptysis and 90% for obstructive pneumonia. Performance status was improved in 70% of patients. Follow-up is in the range of 5-36 months with 280/320 evaluable patients (87.5%) (40 patients were lost to follow-up). For the patients treated with three fractions of HDRBT plus EBRT, a smaller number of side effects occurred while relief from symptoms linked to bronchial obstruction and survival was similar for the three groups. CONCLUSIONS A three-fraction brachytherapy results in fewer side effects, such as bronchial fibrosis with or without stenosis, while survival and symptomatic relief are similar in the three groups treated.
Rural Retiree Volunteer Motivations for Nonfamily-Based Intergenerational Communication

Rural Retiree Volunteer Motivations for Nonfamily-Based Intergenerational Communication by Jennifer JM Salisbury MBA, Walden University, 2007 MEM, Old Dominion University, 2004 BS, U. S. Naval Academy, 1998 Proposal Submitted in Partial Fulfillment of the Requirements for the Degree of
A New Species of Laricobius (Coleoptera: Derodontidae) from Japan with Phylogeny and a Key for Native and Introduced Congeners in North America

ABSTRACT Laricobius osakensis Montgomery and Shiyake sp. nov., collected from Adelges tsugae Annand on hemlock [Tsuga sieboldii Carr. and Tsuga diversifolia (Maxim.) Mast. ] in Japan, is described and illustrated. The new species was collected from several localities on Honshu, Shikokou, and Kyushu Islands. The genus has not been reported previously from Japan. Morphological features, a molecular phylogeny, and diagnostic DNA sites are provided to distinguish this new species from previously described species of the genus. Because of plans to release L. osakensis for the biological control of A. tsugae in eastern North America, a key and discussion are provided to differentiate it from the native North American species, Laricobius nigrinus Fender, Laricobius laticollis Fall, and Laricobius rubidus LeConte, and from two previously imported species—Laricobius erichsonii Rosenhauer, which is endemic in Europe, and Laricobius kangdingensis Zilahi-Balogh & Jelinek, which is endemic in China.
The effects of specific medical conditions on the functional limitations of elders in the Framingham Study.

OBJECTIVES The purpose of this study was to identify associations between specific medical conditions in the elderly and limitations in functional tasks; to compare risks of disability across medical conditions, controlling for age, sex, and comorbidity; and to determine the proportion of disability attributable to each condition. METHODS The subjects were 709 noninstitutionalized men and 1060 women of the Framingham Study cohort (mean age 73.7 +/- 6.3 years). Ten medical conditions were identified for study: knee osteoarthritis, hip fracture, diabetes, stroke, heart disease, intermittent claudication, congestive heart failure, chronic obstructive pulmonary disease, depressive symptomatology, and cognitive impairment. Adjusted odds ratios were calculated for dependence on human assistance in seven functional activities. RESULTS Stroke was significantly associated with functional limitations in all seven tasks; depressive symptomatology and hip fracture were associated with limitations in five tasks; and knee osteoarthritis, heart disease, congestive heart failure, and chronic obstructive pulmonary disease, were associated with limitations in four tasks each. CONCLUSIONS In general, stroke, depressive symptomatology, hip fracture, knee osteoarthritis, and heart disease account for more physical disability in noninstitutionalized elderly men and women than other diseases.
Identification of sequence-dependent DNA features correlating to activity of DNA sites interacting with proteins

MOTIVATION The commonly accepted statistical mechanical theory is now multiply confirmed by using the weight matrix methods successfully recognizing DNA sites binding regulatory proteins in prokaryotes. Nevertheless, the recent evaluation of weight matrix methods application for transcription factor binding site recognition in eukaryotes has unexpectedly revealed that the matrix scores correlate better to each other than to the activity of DNA sites interacting with proteins. This observation points out that molecular mechanisms of DNA/protein recognition are more complicated in eukaryotes than in prokaryotes. As the extra events in eukaryotes, the following processes may be considered: (i) competition between the proteins and nucleosome core particle for DNA sites binding these proteins and (ii) interaction between two synergetic/antagonist proteins recognizing a composed element compiled from two DNA sites binding these proteins. That is why identification of the sequence-dependent DNA features correlating with affinity magnitudes of DNA sites interacting with a protein can pinpoint the molecular event limiting this protein/DNA recognition machinery. RESULTS An approach for predicting site activity based on its primary nucleotide sequence has been developed. The approach is realized in the computer system ACTIVITY, containing the databases on site activity and on conformational and physicochemical DNA/RNA parameters. By using the system ACTIVITY, an analysis of some sites was provided and the methods for predicting site activity were constructed. The methods developed are in good agreement with the experimental data. AVAILABILITY The database ACTIVITY is available at http://wwwmgs.bionet. nsc.ru/systems/Activity/ and the mirror site, http://www.cbil. upenn.edu/mgs/systems/acti vity/.
Fibrocystin/Polyductin, Found in the Same Protein Complex with Polycystin-2, Regulates Calcium Responses in Kidney Epithelia

ABSTRACT Recent evidence suggests that fibrocystin/polyductin (FPC), polycystin-1 (PC1), and polycystin-2 (PC2) are all localized at the plasma membrane and the primary cilium, where PC1 and PC2 contribute to fluid flow sensation and may function in the same mechanotransduction pathways. To further define the exact subcellular localization of FPC, the protein product encoded by the PKHD1 gene responsible for autosomal recessive polycystic kidney disease (PKD) in humans, and whether FPC has direct and/or indirect cross talk with PC2, which, in turn, is pivotal for the pathogenesis of autosomal dominant PKD, we performed double immunostaining and coimmunoprecipitation as well as a microfluorimetry study of kidney tubular epithelial cells. FPC and PC2 are found to completely or partially colocalize at the plasma membrane and the primary cilium and can be reciprocally coimmunoprecipitated. Although incomplete removal of FPC by small interfering RNA and antibody 803 to intracellular epitopes of FPC did not abolish flow-induced intracellular calcium responses, antibody 804 to extracellular epitopes of FPC blocked cellular calcium responses to flow stimulation. These findings suggest that FPC and polycystins share, at least in part, a common mechanotransduction pathway.
Sequence-Specific Transcriptional Repression by KS1, a Multiple-Zinc-Finger–Krüppel-Associated Box Protein

ABSTRACT The vertebrate genome contains a large number of Krüppel-associated box–zinc finger genes that encode 10 or more C2-H2 zinc finger motifs. Members of this gene family have been proposed to function as transcription factors by binding DNA through their zinc finger region and repressing gene expression via the KRAB domain. To date, however, no Krüppel-associated box–zinc finger protein (KRAB-ZFP) and few proteins with 10 or more zinc finger motifs have been shown to bind DNA in a sequence-specific manner. Our laboratory has recently identified KS1, a member of the KRAB-ZFP family that contains 10 different C2-H2 zinc finger motifs, 9 clustered at the C terminus with an additional zinc finger separated by a short linker region. In this study, we used a random oligonucleotide binding assay to identify a 27-bp KS1 binding element (KBE). Reporter assays demonstrate that KS1 represses the expression of promoters containing this DNA sequence. Deletion and site-directed mutagenesis reveal that KS1 requires nine C-terminal zinc fingers and the KRAB domain for transcriptional repression through the KBE site, whereas the isolated zinc finger and linker region are dispensable for this function. Additional biochemical assays demonstrate that the KS1 KRAB domain interacts with the KAP-1 corepressor, and mutations that abolish this interaction alleviate KS1-mediated transcriptional repression. Thus, this study provides the first direct evidence that a KRAB-ZFP binds DNA to regulate gene expression and provides insight into the mechanisms used by multiple-zinc-finger proteins to recognize DNA sequences.
The Life and Fate of Mesenchymal Stem Cells

Mesenchymal stem cells (MSC) are present throughout the body and are thought to play a role in tissue regeneration and control of inflammation. MSC can be easily expanded in vitro and their potential as a therapeutic option for degenerative and inflammatory disease is therefore intensively investigated. Whilst it was initially thought that MSC would replace dysfunctional cells and migrate to sites of injury to interact with inflammatory cells, experimental evidence indicates that the majority of administered MSC get trapped in capillary networks and have a short life span. In this review, we discuss current knowledge on the migratory properties of endogenous and exogenous MSC and confer on how culture-induced modifications of MSC may affect these properties. Finally, we will discuss how, despite their limited survival, administered MSC can bring about their therapeutic effects.
Calculating the probability of rare events: why settle for an approximation?

OBJECTIVE Health services researchers often need to compute the probability of observing a certain number of events when only a few such events are expected. Our objective is to show that the standard approaches (Poisson, binomial, and normal approximations) are inappropriate in such instances, and to suggest an alternative. DATA SOURCES Patients undergoing cholecystectomy (34,234) in 465 California hospitals in 1983 are used to demonstrate the biases arising from various methods of calculating the probability of observing a given number of deaths in each hospital. Similar data from other procedures and diagnoses with lower and higher mortality rates are also used for illustration. STUDY DESIGN The computational methods to derive probabilities using the Poisson, normal, simulation, and exact probabilities are discussed. Using a previously developed risk factor model, the probability of observing the actual number of deaths (or more) is calculated given the expectation of death for each patient in each hospital. Results for the four methods are compared, showing the types of random and systematic errors in the Poisson, normal, and simulation approaches. DATA COLLECTION Routinely collected hospital discharge abstract data were provided by the California Office of Statewide Planning and Development. PRINCIPAL FINDINGS The Poisson and normal approximations are often biased substantially in calculating upper-tail p-values, especially when the expected number of adverse outcomes is less than five. Simulations allow unbiased calculations, and the degree of random error can be made arbitrarily small given enough trials. Exact calculations using a simple recursive algorithm can be done very efficiently on either a mainframe or personal computer. For example, the whole set of cholecystectomy patients can be assessed in less than 90 seconds on a Macintosh. CONCLUSIONS Calculating the probability of observing a small number of events using standard approaches may result in substantial errors. The availability of a simple and inexpensive method of calculating these probabilities exactly can avoid these errors.
Deletion of Tumor Necrosis Factor-α Receptor 1 (TNFR1) Protects against Diet-induced Obesity by Means of Increased Thermogenesis*

In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-α (TNF-α) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most of TNF-α inflammatory signals are delivered by TNF receptor 1 (R1); however, the role played by this receptor in the context of obesity-associated inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1 KO) mice are protected from diet-induced obesity due to increased thermogenesis. Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less body mass despite increased caloric intake. Visceral adiposity and mean adipocyte diameter are reduced and blood concentrations of insulin and leptin are lower. Protection from hypothalamic leptin resistance is evidenced by increased leptin-induced suppression of food intake and preserved activation of leptin signal transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO mice present a significantly increased expression of the thermogenesis-related neurotransmitter, TRH. Further evidence of increased thermogenesis includes increased O2 consumption in respirometry measurements, increased expressions of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and increased O2 consumption by isolated skeletal muscle fiber mitochondria. This demonstrates that TNF-α signaling through TNFR1 is an important mechanism involved in obesity-associated defective thermogenesis.
Shared Parental Responsibility

Abstract The purpose of this article is twofold. First, our aim is to provide a selective overview and analysis of divorce research in the past five year period (2000-2005), during which important new data on children, families, and divorce have appeared. Much of this data challenges current socio-legal policy and “practice wisdom,” and includes: (1) the emergent perspective of adult children of divorce reflecting upon their experiences and preferences growing up as children of divorce; (2) studies comparing child and family outcomes in joint and sole custody families; and (3) new data on the distribution of child care tasks and responsibilities in families. These data support an approach to postdivorce parenting based on reducing the harms attendant to divorce for children and parents, parental equality, and family autonomy as most in keeping with children's needs and the principle of “the best interests of the child, from the perspective of the child,” which, it is argued, provides a more child-focused standard for child custody determination than current approaches. Second, building on this research foundation, we propose a new model of post-divorce parenting: a “shared parental responsibility” framework, in which parental responsibilities precede custodial rights, and children's “best interests” are addressed by means of identifying both their needs and parental and societal responsibilities corresponding to these needs.
Suppressors of selection

Inspired by recent works on evolutionary graph theory, an area of growing interest in mathematical and computational biology, we present examples of undirected structures acting as suppressors of selection for any fitness value r > 1. This means that the average fixation probability of an advantageous mutant or invader individual placed at some node is strictly less than that of this individual placed in a well-mixed population. This leads the way to study more robust structures less prone to invasion, contrary to what happens with the amplifiers of selection where the fixation probability is increased on average for advantageous invader individuals. A few families of amplifiers are known, although some effort was required to prove it. Here, we use computer aided techniques to find an exact analytical expression of the fixation probability for some graphs of small order (equal to 6, 8 and 10) proving that selection is effectively reduced for r > 1. Some numerical experiments using Monte Carlo methods are also performed for larger graphs and some variants.
Ursodeoxycholate Reduces Ethinylestradiol Glucuronidation in the Rat: Role in Prevention of Estrogen-Induced Cholestasis

Ethinylestradiol (EE) administration (5 mg/kg, s.c., daily for 5 days) to rats leads to cholestasis, and its derivative EE 17β-glucuronide is a likely mediator of this effect. Coadministration of ursodeoxycholate (UDC) was shown to prevent ethinylestradiol-induced cholestasis. The aim of this study was to evaluate the inhibitory effect of UDC on EE glucuronidation in vivo and in vitro as a potential mechanism to explain UDC protection. UDC treatment (25 mg/kg, i.p., daily for 5 days) decreased the biliary excretion of EE 17β-glucuronide in bile after administration of a trace dose of [3H]EE and reduced microsomal EE 17β-glucuronidation activity by 20% and expression of UGT2B1, one of the enzymes involved in EE conjugation, by 30%. Glucuronidation kinetic studies were performed in vitro using normal microsomes and isolated hepatocytes in the presence of tauroursodeoxycholate (TUDC), the major endogenous derivative of UDC in the rat. Kinetic enzymatic studies in microsomes showed a noncompetitive inhibition of EE 17β-glucuronidation by TUDC, which was unique for this bile salt since other endogenous bile salts such as taurocholate, taurochenodeoxycholate, or taurodeoxycholate did not affect the enzyme activity. Studies in isolated hepatocytes confirmed the inhibitory effect of TUDC on EE glucuronidation and indicated that TUDC can reach the enzyme active site in intact cells. In conclusion, both in vivo and in vitro experiments indicate that UDC decreased the metabolic pathways involved in EE glucuronidation, hence decreasing the formation of the cholestatic derivative EE 17β-glucuronide.