Miracle-dz/UniFAR-FTUs huggingface dataset:
The use of computer-assisted image analysis in measuring the histological structure of the human median nerve.

BACKGROUND AND AIM The aim of this study was to assess the histological structure of the median nerve and its motor branch (number and arrangement of nerve bundles) and the cross-sectional area (CSA) of the median nerve (on the level of the carpal tunnel). MATERIAL AND METHODS This study has been conducted using median nerves dissected from cadavers stored in a 10% solution of formaldehyde at the Department of Anatomy of the Jagiellonian University Medical College and cadavers from the Department of Forensic Medicine of the Jagiellonian University Medical College. After dissection the median nerves were stained with haematoxylin and eosin and histological slides were prepared. These were later photographed (16 x magnification) and analysed using ImageJ software. The research protocol was approved by the Jagiellonian University Ethics Committee (registry KBET/209/B/2002). RESULTS The studied group comprised 8 women and 22 men (age between 23-92 years), yielding a total of 60 median nerves (30 right vs. 30 left). In 4 (6.67%) cases an accessory motor branch was found. The mean CSA of the median nerve was 0.19 cm(2). The median nerves from the right hand had a statistically larger CSA (p = 0.017). The number of nerve bundles in the median nerve varied between 13 to 38 and in the motor branch of the median nerve between 4 to 14. CONCLUSIONS The nerve bundles of the median nerve, at the level of the carpal tunnel, display no particular type of arrangement. ImageJ software proved useful in the assessment of the histological structure of the human median nerve and its motor branch.
Identification of the Fenretinide Metabolite 4-Oxo-Fenretinide Present in Human Plasma and Formed in Human Ovarian Carcinoma Cells through Induction of Cytochrome P450 26A1

Purpose: The synthetic retinoid fenretinide (4-HPR) exhibits preventive and therapeutic activity against ovarian tumors. An unidentified polar metabolite was previously found in 4-HPR-treated subjects and in A2780 human ovarian carcinoma cells continuously treated with 4-HPR (A2780/HPR). The metabolite and the enzyme involved in its formation in tumor cells are herein identified. Experimental Design: The metabolite was identified by mass spectrometry in A2780/HPR cell extracts and in plasma from 11 women participating in a phase III trial and treated with 200 mg/d 4-HPR for 5 years. The expression of proteins involved in retinoid metabolism and transport, cytochrome P450 26A1 (CYP26A1), cellular retinol-binding protein I (CRBP-I), and cellular retinoic acid-binding protein I and II (CRABP-I, CRABP-II) were evaluated in tumor cells by reverse transcription-PCR and Western blot analyses. Overexpression of CYP26A1 and retinoic acid receptors (RARs) in A2780 cells were obtained by cDNAs transfection. Results: The polar metabolite was 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) i.e., an oxidized form of 4-HPR with modification in position 4 of the cyclohexene ring. 4-oxo-4-HPR plasma levels were slightly lower (0.52 ± 0.17 μmol/L) than those of the parent drug (0.84 ± 0.53 μmol/L) and of the already identified metabolite N-(4-methoxyphenyl)retinamide (1.13 ± 0.85 μmol/L). In A2780/HPR cells continuously treated with 4-HPR and producing 4-oxo-4-HPR, CYP26A1 and CRBP-I were markedly up-regulated compared with A2780 untreated cells. In A2780 cells, not producing 4-oxo-4-HPR, overexpression of CYP26A1 caused formation of 4-oxo-4-HPR, which was associated with no change in 4-HPR sensitivity. Moreover, the addition of 4-oxo-4-HPR to A2780 cells inhibited cell proliferation. Elevated levels of CYP26A1 protein and metabolism of 4-HPR to 4-oxo-4-HPR were found in A2780 cells transfected with RARβ and to a lesser extent in those transfected with RARγ. Conclusions: A new metabolite of 4-HPR, 4-oxo-4-HPR, present in human plasma and in tumor cells, has been identified. The formation of this biologically active metabolite in tumor cells was due to CYP26A1 induction and was influenced by RAR expression. Moreover evidence was provided that 4-HPR up-modulates the expression of CRBP-I transcript, which is lost during ovarian carcinogenesis.
Exercise intensity criteria for routine rehabilitation therapy for stroke patients

[Purpose] The aim of this study was to observe the relationships among heart rate, rate of perceived exertion, and oxygen consumption in stroke patients and the effectiveness of improving aerobic capacity during routine rehabilitation therapy. [Subjects and Methods] Thirty-six stroke patients participated in the study. A K4b2 pulmonary function device was used to record heart rate (beats per minute), oxygen consumption (Equation Section (Next)ml·min−1·kg−1), and rate of perceived exertion. Results were recorded after completing the following activities continuously: (1) silent sitting, (2) sit-to-stand transfers, (3) hip extension while standing against a wall, (4) weight loading on the affected leg, (5) upward and downward leg movements on a stall bar, (6) walking up and down a flight of stairs, and (7) a 60-meter walk. Correlation analyses were performed to demonstrate the relationship of oxygen consumption with HR and RPE. [Results] Moderate correlation was found between HR and oxygen consumption, and low correlation was found between rate of perceived exertion and oxygen consumption. The routine rehabilitation therapy could reduce the accumulation of lactate. [Conclusion] HR is a better index than rate of perceived exertion in evaluating exercise intensity in stroke patients. The routine rehabilitation therapy can improve the aerobic capacity of stroke patients.
ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension

The renin–angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE–Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling.
Higher fasting plasma glucose is associated with striatal and hippocampal shape differences: the 2sweet project

Objective Previous studies have demonstrated associations between higher normal fasting plasma glucose levels (NFG) (<6.1 mmol/L), type 2 diabetes (T2D) and hippocampal atrophy and other cerebral abnormalities. Little is known about the association between plasma glucose and the striatum despite sensorimotor deficits being implicated in T2D. This study aimed to investigate the relationship between plasma glucose levels and striatal and hippocampal morphology using vertex-based shape analysis. Design A population-based, cross-sectional study. Setting Canberra and Queanbeyan, Australia. Participants 287 cognitively healthy individuals (mean age 63 years, 132 female, 273 Caucasian) with (n=261) or without T2D (n=26), selected from 2551 participants taking part in the Personality & Total Health (PATH) Through Life study by availability of glucose data, MRI scan, and absence of gross brain abnormalities and cognitive impairment. Outcome measures Fasting plasma glucose was measured at first assessment, and MRI images were collected 8 years later. Shape differences indicating outward and inward deformation at the hippocampus and the striatum were examined with FMRIB Software Library-Integrated Registration and Segmentation Toolbox (FSL-FIRST) after controlling for sociodemographic and health variables. Results Higher plasma glucose was associated with shape differences indicating inward deformation, particularly at the caudate and putamen, among participants with NFG after controlling for age, sex, body mass index (BMI), hypertension, smoking and depressive symptoms. Those with T2D showed shape differences indicating inward deformation at the right hippocampus and bilateral striatum, but outward deformation at the left hippocampus, compared with participants with NFG. Conclusions These findings further emphasize the importance of early monitoring and management of plasma glucose levels, even within the normal range, as a risk factor for cerebral atrophy.
Stable Transfection of Human Malignant Melanoma Cells with Basic Fibroblast Growth Factor Antisense cDNA a

Among the growth factors constitutively produced by melanoma cells, basic fibroblast growth factor (bFGF) has emerged as an important growth regulator. For in vitro growth, normal melanocytes depend on supplementation of culture medium with bFGF, whereas primary and metastatic melanoma cells grow independently of exogenous bFGF. In short-term assays, both neutralizing antibodies to bFGF as well as antisense oligonucleotides targeted against bFGF mRNA have been shown to inhibit melanoma cell growth in vitro.I. * Besides its role in autocrine growth stimulation, bFGF may have other important functions during melanoma development and progression such as regulation of extracellular matrix formation and stimulation of tumor neoangiogenesis. To study potential paracrine functions of bFGF, we attempted to suppress or increase bFGF synthesis in melanoma cells by stable transfection of bFGF antisense or sense cDNA. Expression vectors were constructed using a 480-bp bFGF cDNA fragment covering the entire coding region for human bFGF.3 This fragment was placed in either sense or antisense orientation downstream of the cytomegalovirus immediate early gene enhancer and promoter. For selection of stable transfectants these vectors also contained the neomycin resistance gene under expression control of the SV40 promoter. Sense and antisense vectors were transfected into the bFGF expressing metastatic melanoma cell line WM852 using liposome-mediated transfection. After transfection, cells were selected for geneticin resistance and grown in the presence of exogenous bFGF (40 ng/ml) to compete for a negative effect on cell proliferation after expression of antisense bFGF mRNA. Individual clones, resistant to 800 kg of G418 per milliliter of medium, were isolated and further analyzed. To confirm the integration of vector DNA, cellular DNA of individual clones was digested with Hind111 and BamHI and hybridized with a neo probe. All isolated clones showed integration of vector DNA, and the estimated copy number ranged between 5 and 50 copies per genome. Total RNA was analyzed for transcription of the integrated DNA. Hybridization with a bFGF cDNA fragment showed strong overexpression of bFGF mRNA in bFGF-transfected cells. The morphology of sense-transfected cells did not differ from that of untransfected parental cells, whereas antisensetransfected cells showed an increase in cell size with a wide cytoplasm. In monolayer culture, antisense-transfected cells in contrast to untransfected cells did show signs of contact inhibition and did not overgrow. To further study the effects of bFGF
Effects of habitat and season on the grouping of forest buffalo resting places

Effects of habitat and season on the grouping of forest buffalo resting places M. Melletti*, V. Penteriani, M. Mirabile and L. Boitani Department of Animal and Human Biology, University of Rome ‘‘La Sapienza’’, Vle. dell’Universita 32, 00185 Rome, Italy, Department of Conservation Biology, Estacion Biologica de Donana, C.S. I.C. , Avda. de Maria Luisa s ⁄ n. Pabellon del Peru, 41013 Seville, Spain and Italian Agency for the Environmental Protection and Technical Services, Via Brancati 48, 00144 Rome, Italy
Surge and destroy: the role of auxin in plant embryogenesis

For nearly a century, the plant hormone auxin has been recognized for its effects on post-embryonic plant growth. Now recent insights into the molecular mechanism of auxin transport and signaling are uncovering fundamental roles for auxin in the earliest stages of plant development, such as in the development of the apical-basal (shoot-root) axis in the embryo, as well as in the formation of the root and shoot apical meristems and the cotyledons. Localized surges in auxin within the embryo occur through a sophisticated transcellular transport pathway causing the proteolytic destruction of key transcriptional repressors. As we discuss here, the resulting downstream gene activation, together with other, less well-understood regulatory pathways, establish much of the basic body plan of the angiosperm embryo.
Electrospun Composite Mats of Poly[(D,L‐lactide)‐co‐glycolide] and Collagen with High Porosity as Potential Scaffolds for Skin Tissue Engineering

Electrospun composite mats of poly[(D,L-lactide)-co-glycolide] and collagen with high porosities of 85-90% and extended pore sizes of 90-130 μm were prepared to mimic the ECM morphologically and chemically. The existence of collagen molecules on the fiber surface was confirmed, enabling the cells to find enhanced binding sites for their integrin receptors. The mechanical data for the blended fibrous mats indicated that they were sufficiently durable for dermal tissue engineering. Fibroblasts derived from GFP transgenic C57BL/6 mice were used to directly observe cell proliferation, and the inoculation of collagen enhanced cell attachment, proliferation and extracellular matrix secretion, which were found to be dependent on the amount of collagen in the composite scaffold.
HDAC8 functions in spindle assembly during mouse oocyte meiosis

HDAC8 is a class I histone deacetylase that functions in a variety of biological processes through its non-histone substrates. However, its roles during oocyte meiosis remain elusive. Here, we document that HDAC8 localizes at spindle poles and positively participates in the regulation of microtubule organization and spindle assembly in mouse oocytes. Depletion of HDAC8 by siRNA-based gene silencing results in various spindle defects and chromosome misalignment during oocyte meiotic maturation, accompanied by impaired kinetochore-microtubule attachments. Consequently, a higher incidence of aneuploidy is generated in HDAC8-depleted MII eggs. In addition, inhibition of HDAC8 activity with its selective inhibitor PCI-34051 phenocopies the spindle/chromosome defects resulting from HDAC8 depletion by siRNA injection. Finally, we find that HDAC8 is required for the correct localization of ϕ-tubulin to spindle poles. Collectively, these data reveal that HDAC8 plays a significant role in regulating spindle assembly and thus ensuring the euploidy in mouse eggs.
ARCS: Adaptive Runtime Configuration Selection for Power-Constrained OpenMP Applications

Power is the most critical resource for the exascale high performance computing. In the future, system administrators might have to pay attention to the power consumption of the machine under different work loads. Hence, each application may have to run with an allocated power budget. Thus, achieving the best performance on future machines requires optimal performance subject to a power constraint. This additional performance requirement should not be the responsibility of HPC~(High Performance Computing) application developers. Optimizing the performance for a given power budget should be the responsibility of high-performance system software stack. Modern machines allow power capping of CPU and memory to implement power budgeting strategy. Finding the best runtime environment for a node at a given power level is important to get the best performance. This paper presents ARCS (Adaptive Runtime Configuration Selection) frameworkthat automatically selects the best runtime configuration for each OpenMPparallel region at a given power level. The framework uses OMPT (OpenMP Tools) API, APEX(Autonomic Performance Environment for eXascale), and Active Harmony frameworksto explore configuration search space and selects the best number of threads, scheduling policy, and chunk size for a given power level at run-time. We test ARCS using the NAS Parallel Benchmark, and proxy application LULESH with Intel Sandybridge, and IBM Power multi-core architectures. We show that for a given power level, efficient OpenMP runtime parameter selection can improve the execution time and energy consumption of an application up to 40% and 42% respectively.
The Role of Selective Estrogen Receptor Modulators (SERMs) in Postmenopausal Health

Abstract: Concerns about long‐term therapy with HRT have recently highlighted interest in a class of compounds active in the estrogen receptor, but with selectivity in their actions, known as the selective estrogen receptor modulators (SERMs). Tamoxifen is recognized as the first widely marketed SERM, but its selectivity focuses interest on its approved indications: the treatment and prevention of breast cancer. Raloxifene has been approved in most countries of the world for the treatment and prevention of oseoporosis, and it displays a pattern of actions highly matched to the needs and concerns of many postmenopausal women. Further study of current and future SERMs promises to open new vistas in patient‐specific management of the field of postmenopausal health.
Statistical models for the analysis of heterogeneous biological data sets

STATISTICAL MODELS FOR THE ANALYSIS OF HETEROGENEOUS BIOLOGICAL DATA SETS Eugen Buehler Lyle Ungar The focus of this thesis is on developing methods of integrating heterogeneous biological feature sets into structured statistical models, so as to improve model predictions and further understanding of the complex systems that they emulate. Combining data from different sources is an important task in genomics because of the increasing variety of large-scale data being generated, all of which reflect different components of the same complicated network of biological interactions that make up an organism. We contend that traditional machine learning techniques are too general to accurately model heterogeneous biological data and provide insufficient feedback to researchers concerning the systems being modeled. In contrast, we will show that interpretable statistical models specifically designed for and inspired by the underlying structure of biological problems yield more accurate predictions and provide valuable insight into biological systems. Toward proving this thesis, we introduce maximum entropy biological sequence models. Maximum entropy sequence models have been used previously to integrate arbitrary features in other (non-biological) domains, such as natural language modeling. Here, we apply the same model structure to amino acid and nucleotide sequences. We first propose a broad variety of biologically inspired features, define them mathematically, and test their ability to improve models of amino acid sequences. Of these features, particular attention is paid to long distance features such as triggers, which incorporate information unavailable to more conventional Markovian models and reflect the non-local nature of protein sequence constraints. The ability of these features to improve gene-finding models is demonstrated. We next extend maximum entropy models to nucleotide coding sequences and apply them to the detection of lateral gene transfer. This allows us to evaluate a diverse set of features in a statistically rigorous manner, improving understanding of the problem and eliminating the tendency to inaccurately label short genes. We also develop methods for integrating positional and gene expression data with our maximum entropy sequence model, allowing more accurate predictions of lateral gene transfer and resulting in significant biological insight.
Differential Effect of Ketamine and Lidocaine on Spontaneous and Mechanical Evoked Pain in Patients with Nerve Injury Pain

Background: The mechanisms underlying neuropathic pain are incompletely understood. Targeting specific molecular mechanisms in the pain signaling system may assist in understanding key features in neuropathic pains such as allodynia. This study examined the effect of systemically administered ketamine, an N-methyl-d-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain. Methods: Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion. Results: Ketamine significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains. Conclusions: N-methyl-d-aspartate receptor-linked systems and sodium channels are involved in generation and maintenance of pain in patients with peripheral nerve injury. It is likely that ongoing pain as well as mechanical hyperalgesia in individual patients is dependent on several separate molecular mechanisms.
Self-organized Vortex State in Two-Dimensional Dictyostelium Dynamics

We present results of experiments on the dynamics of Dictyostelium discoideum in a novel setup which constrains cell motion to a plane. After aggregation, the amoebae collect into round “pancake” structures in which the cells rotate around the center of the pancake. To provide a mechanism for the self-organization of the Dictyostelium cells, we have developed a new model of the dynamics of selfpropelled deformable objects. In this model, we show that cohesive energy between the cells, together with a coupling between the self-generated propulsive force and the cell’s configuration, produces a self-organized vortex state. The mechanism for self-organization reported here can possibly explain similar vortex states in other biological systems.
The role of macrophage IL-10/innate IFN interplay during virus-induced asthma

Activation through different signaling pathways results in two functionally different types of macrophages, the pro‐inflammatory (M1) and the anti‐inflammatory (M2). The polarization of macrophages toward the pro‐inflammatory M1 phenotype is considered to be critical for efficient antiviral immune responses in the lung.