Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical Role of Monocyte Chemoattractant Protein-1/CC Chemokine Ligand 2 in the Pathogenesis of Ischemic Cardiomyopathy

Background— Cardiac interstitial fibrosis plays an important role in the pathogenesis of ischemic cardiomyopathy, contributing to systolic and diastolic dysfunction. We have recently developed a mouse model of fibrotic noninfarctive cardiomyopathy due to brief repetitive myocardial ischemia and reperfusion. In this model, fibrotic changes are preceded by marked and selective induction of the CC chemokine monocyte chemoattractant protein-1 (MCP-1). We hypothesized that MCP-1 may mediate fibrotic remodeling through recruitment of mononuclear cells and direct effects on fibroblasts. Methods and Results— Wild-type (WT) and MCP-1-null mice underwent daily 15-minute coronary occlusions followed by reperfusion. Additional WT animals received intraperitoneal injections of a neutralizing anti-MCP-1 antibody after the end of each ischemic episode. Hearts were examined echocardiographically and processed for histological and RNA studies. WT mice undergoing repetitive brief myocardial ischemia and reperfusion protocols exhibited macrophage infiltration after 3 to 5 days and marked interstitial fibrosis in the ischemic area after 7 days, accompanied by ventricular dysfunction. MCP-1-null mice had markedly diminished interstitial fibrosis, lower macrophage infiltration, and attenuated ventricular dysfunction compared with WT animals. MCP-1 neutralization also inhibited interstitial fibrosis, decreasing left ventricular dysfunction and regional hypocontractility. Cardiac myofibroblasts isolated from WT but not from MCP-1-null animals undergoing repetitive myocardial ischemia and reperfusion demonstrated enhanced proliferative capacity. However, MCP-1 stimulation did not induce cardiac myofibroblast proliferation and did not alter expression of fibrosis-associated genes. Conclusions— Defective MCP-1 signaling inhibits the development of ischemic fibrotic cardiomyopathy in mice. The profibrotic actions of MCP-1 are associated with decreased macrophage recruitment and may not involve direct effects on cardiac fibroblasts.
Hubungan Antara Jumlah Leukosit dengan Motilitas Sperma Pada Hasil Analisa Sperma Pasien Infertilitas di RSUP dr. Kariadi Semarang

Latar belakang: Keberadaan sejumlah besar leukosit di saluran reproduksi pria dan pada ejakulat manusia disebut leukositospermia, terdapat hubungan dengan penurunan motilitas sperma. Secara fungsional, hampir seluruh leukosit berasal dari epididimis dan memiliki peran dalam pertahanan imunitas dan memfagosit sperma abnormal. Tujuan: Tujuan penelitian ini untuk mengetahui hubungan peningkatan jumlah leukosit pada semen dengan penurunan motilitas sperma pada hasil analisa sperma pasien infertilitas di RSUP dr. Kariadi Semarang. Metoda: Penelitian ini merupakan jenis penelitian adalah penelitian observasional retrospektif. Sampel penelitian adalah data sekunder hasil pemeriksaan analisa sperma pasien infertilitas yang diperoleh dari catatan medik RSUP dr. Kariadi Semarang selama periode 1 Januari 2005 sampai 31 Desember 2008. Kriteria inklusi meliputi pria dengan diagnosa infertilitas, tidak Azoospermia atau Aspermia, memeriksakan sperma dengan metode sperma analisa manual, dan ditemukan leukosit dalam sperma analisa. Hubungan antara jumlah leukosit dan motilitas sperma dianalisis menggunakan Spearman test dengan tingkat kepercayaan 95% Hasil: Penelitian menunjukkan terdapat korelasi negatif yang bermakna antara jumlah leukosit dan motilitas sperma (r= –0,305; p=0,012) dengan motilitas cepat lurus (r= –0,291; p=0,017), dan dengan motilitas lambat lurus / tidak lurus (r= –0,253; p=0,039). Kesimpulan: Hasil penelitian menunjukkan bahwa terdapat hubungan antara peningkatan jumlah leukosit dengan penurunan motilitas sperma.
Twitch and nontwitch motoneuron subgroups in the oculomotor nucleus of monkeys receive different afferent projections

Motoneurons in the primate oculomotor nucleus can be divided into two categories, those supplying twitch muscle fibers and those supplying nontwitch muscle fibers. Recent studies have shown that twitch motoneurons lie within the classical oculomotor nucleus (nIII), and nontwitch motoneurons lie around the borders. Nontwitch motoneurons of medial and inferior rectus are in the C group dorsomedial to nIII, whereas those of inferior oblique and superior rectus lie near the midline are in the S group. In this anatomical study, afferents to the twitch and nontwitch subgroups of nIII have been anterogradely labeled by injections of tritiated leucine into three areas and compared. 1) Abducens nucleus injections gave rise to silver grain deposits over all medial rectus subgroups, both twitch and nontwitch. 2) Laterally placed vestibular complex injections that included the central superior vestibular nucleus labeled projections only in twitch motoneuron subgroups. However, injections into the parvocellular medial vestibular nucleus (mvp), or Y group, resulted in labeled terminals over both twitch and nontwitch motoneurons. 3) Pretectal injections that included the nucleus of the optic tract (NOT), and the olivary pretectal nucleus (OLN), labeled terminals only over nontwitch motoneurons, in the contralateral C group and in the S group. Our study demonstrates that twitch and nontwitch motoneuron subgroups do not receive identical afferent inputs. They can be controlled either in parallel, or independently, suggesting that they have basically different functions. We propose that twitch motoneurons primarily drive eye movements and nontwitch motoneurons the tonic muscle activity, as in gaze holding and vergence, possibly involving a proprioceptive feedback system. J. Comp. Neurol. 479:117–129, 2004. © 2004 Wiley‐Liss, Inc.
The Economic Psychology of Tax Behaviour

Tax evasion is a complex phenomenon which is influenced not just by economic motives but by psychological factors as well. Economic-psychological research focuses on individual and social representations of taxation as well as decision-making. In this 2007 book, Erich Kirchler assembles research on tax compliance, with a focus on tax evasion, and integrates the findings into a model based on the interaction climate between tax authorities and taxpayers. The interaction climate is defined by citizens' trust in authorities and the power of authorities to control taxpayers effectively; depending on trust and power, either voluntary compliance, enforced compliance or no compliance are likely outcomes. Featuring chapters on the social representations of taxation, decision-making and self-employed income tax behaviour, this book will appeal to researchers in economic psychology, behavioural economics and public administration.
ω3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New Potential Role in Adjuvant Therapies

Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy. Dietary ω3 polyunsaturated fatty acids (PUFA) have been gaining great interest in recent years as possible anti-inflammatory and anticancer agents, especially in areas such as the large bowel, where the pro-inflammatory context promotes virtually all steps of colon carcinogenesis. Growing epidemiological, experimental, and clinical evidence suggests that ω3 PUFA may play a role in several stages of CRC management exhibiting antineoplastic activity against human CRC cells, improving the efficacy of radiation and chemotherapy, ameliorating cancer-associated secondary complications, and preventing CRC recurrence. These effects are most likely related to the immunomodulatory activities of ω3 PUFA that are able to influence several aspects of the inflammatory process ranging from inflammasome activation, leukocyte recruitment, production of immune mediators to differentiation, and activation of immune cells. In this review, we will focus on the potential use of ω3 PUFA as adjuvant agents together with chemo/radiotherapy, highlighting the immunomodulatory effects most likely responsible for their beneficial effects in different stages of CRC management.
Automatic spectral target recognition in hyperspectral imagery

Automatic target recognition (ATR) in hyperspectral imagery is a challenging problem due to recent advances of remote sensing instruments which have significantly improved sensor's spectral resolution. As a result, small and subtle targets can be uncovered and extracted from image scenes, which may not be identified by prior knowledge. In particular, when target size is smaller than pixel resolution, target recognition must be carried out at subpixel level. Under such circumstance, traditional spatial-based image processing techniques are generally not applicable and may not perform well if they are applied. The work presented here investigates this issue and develops spectral-based algorithms for automatic spectral target recognition (ASTR) in hyperspectral imagery with no required a priori knowledge, specifically, in reconnaissance and surveillance applications. The proposed ASTR consists of two stage processes, automatic target generation process (ATGP) followed by target classification process (TCP). The ATGP generates a set of targets from image data in an unsupervised manner which will subsequently be classified by the TCP. Depending upon how an initial target is selected in ATGP, two versions of the ASTR can be implemented, referred to as desired target detection and classification algorithm (DTDCA) and automatic target detection and classification algorithm (ATDCA). The former can be used to search for a specific target in unknown scenes while the latter can be used to detect anomalies in blind environments. In order to evaluate their performance, a comparative and quantitative study using real hyperspectral images is conducted for analysis.
RB 1 and p 53 at the crossroad of EMT and triple negative breast cancer

*Correspondence to: Eldad Zacksenhaus; Email: eldad.zacksenhaus@utoronto.ca Triple negative breast cancer (TNBC) is a heterogeneous disease that includes Basal-like and Claudin-low tumors. The Claudin-low tumors are enriched for features associated with epithelial-to-mesenchymal transition (EMT) and possibly for tumor initiating cells. Primary TNBCs respond relatively well to conventional chemotherapy; however, metastatic disease is virtually incurable. Thus, there is a great interest in identifying specific therapeutic targets for TNBC. The tumor suppressor RB1 is frequently lost in Basal-like breast cancer. To test for a causative role of RB1 gene loss in BC and for its effect on specific subtypes, we deleted mouse Rb in mammary stem/bipotent progenitor cells. This led to diverse mammary tumors including TNBC, with a subset of the latter containing p53 mutations and exhibiting features of Basal-like BC or EMT. Combined mutation of Rb and p53 in mammary stem/bipotent progenitors induced EMT type tumors. Here, we review our findings and those of others, which connect Rb and p53 to EMT in TNBC. Furthermore, we discuss how by understanding this circuit and its vulnerabilities, we may identify novel therapy for TNBC.
Myostatin is a procachectic growth factor during postnatal myogenesis

Purpose of reviewTo describe the most relevant recent observations concerning the molecular mechanisms behind myostatin-induced muscle wasting. Recent findingsThe main theme of this review is to summarize the biology and function of myostatin. Myostatin is a secreted growth factor that negatively regulates muscle growth. While inactivation of myostatin leads to muscle growth in vivo, excess levels of myostatin induces cachectic-like muscle wasting. Molecular analyses reveal that excess levels of myostatin induce Atrogin-1 expression by reducing Akt phosphorylation and thereby increasing FoxO1 activity. Recent findings have further speculated that myostatin may also play a role in cardiac cachexia. SummaryAs myostatin is a potent inducer of muscle wasting, antagonists to myostatin have been speculated to have great therapeutic value in alleviating muscle wasting. Indeed, myostatin peptide antagonists and antibodies have shown great promise in containing muscle loss in animal models of muscle wasting. Given the beneficial effects of myostatin antagonists in animal models, clinical trials are underway with myostatin antibodies, peptibodies and soluble receptor. Therefore, this review article on the role of myostatin in muscle wasting is highly relevant to current themes in muscle biology.
What Should the Courts Do About Memories of Sexual Abuse? Toward a Balanced Approach

One of the most heated and troubling debates to enter the courts in recent years involves the reliability of delayed memories of sexual abuse. A topic once limited to discussion among psychologists and research scientists now occupies headlines and, on occasion, court dockets. Can people forget and then remember events from earlier in their lives - and, in particular, traumatic events such as sexual abuse? Are memories always accurate, or can they sometimes be mistaken? To the uninitiated, there might seem to be a relatively simple and obvious answer to these questions - that memories of all kinds of events, whether from yesterday or from many years ago, can be accurate or inaccurate (or, often, some combination of both). Indeed, existing research seems to support this common sense response. The courts have for many years grappled with the general issue of how to assess the reliability of memory in testimony; it is an issue that crops up literally every time someone testifies about any event that occurred prior to the moment of testifying. The legal response in general has been a measured one, avoiding the pitfalls of extremism on either side (all memories are accurate, or all memories are unreliable). As in so many other areas, judges and juries have taken the more difficult, fact-specific path of sorting out the likelihood of accuracy in each individual case, weighing all that is known about the particular situation before them in determining what to believe. And yet, in the area of remembered childhood sexual abuse, both the courts and the media seem to be in danger of swinging between extremes - first accepting perhaps too credulously claims of remembered sexual abuse, but more recently showing signs of barring any such claim without reasoned consideration.
Target‐determined expression of α3 isoform of the Na+,K+‐ATPase in the somatic nervous system of rat

Factors that determine the differential expression of isoforms of Na+,K+‐ATPase in the nervous system of vertebrates are not understood. To address this question we studied the expression of α3 Na+,K+‐ATPase in the L5 dorsal root ganglia (DRG) of developing rat, the normal adult rat, and the adult rat after peripheral axotomy. During development, the first α3 Na+,K+‐ATPase‐positive DRG neurons appear by embryonic day 21. At birth, the L5 DRG have a full complement (14 ± 2%) of these neurons. By 15 days after sciatic nerve transection in adult rat, the number of α3 Na+,K+‐ATPase‐positive DRG neurons and small myelinated L5 ventral root axons decreases to about 35% of control counts. These results combined with data from the literature suggest that the expression of α3 Na+,K+‐ATPase by rat somatic neurons is determined by target‐muscle spindle‐derived factors. J. Comp. Neurol. 483:114–123, 2005. © 2005 Wiley‐Liss, Inc.
On the scalability of meta-models in simulation-based optimization of production systems

Optimization of production systems often involves numerous simulations of computationally expensive discrete-event models. When derivative-free optimization is sought, one usually resorts to evolutionary and other population-based meta-heuristics. These algorithms typically demand a large number of objective function evaluations, which in turn, drastically increases the computational cost of simulations. To counteract this, meta-models are used to replace expensive simulations with inexpensive approximations. Despite their widespread use, a thorough evaluation of meta-modeling methods has not been carried out yet to the authors' knowledge. In this paper, we analyze 10 different meta-models with respect to their accuracy and training time as a function of the number of training samples and the problem dimension. For our experiments, we choose a standard discrete-event model of an unpaced flow line with scalable number of machines and buffers. The best performing meta-model is then used with an evolutionary algorithm to perform multi-objective optimization of the production model.
Terbinafine Hydrochloride Trans-ungual Delivery via Nanovesicular Systems: In Vitro Characterization and Ex Vivo Evaluation

Treating a nail infection like onychomycosis is challenging as the human nail plate acts as a formidable barrier against all drug permeation. Available oral and topical treatments have several setbacks. Terbinafine hydrochloride (TBH), belonging to the allylamine class, is mainly used for treatment of onychomycosis. This study aims to formulate TBH in a nanobased spanlastic vesicular carrier that enables and enhances the drug delivery through the nail. The nanovesicles were formulated by ethanol injection method, using either Span® 60 or Span® 65, together with Tween 80 or sodium deoxycholate as an edge activator. A full factorial design was implemented to study the effect of different formulation and process variables on the prepared TBH-loaded spanlastic nanovesicles. TBH entrapment efficiency percentages, particle size diameter, percentage drug released after 2 h and 8 h were selected as dependent variables. Optimization was performed using Design-Expert® software to obtain an optimized formulation with high entrapment efficiency (62.35 ± 8.91%), average particle size of 438.45 ± 70.5 nm, and 29.57 ± 0.93 and 59.53 ± 1.73% TBH released after 2 and 8 h, respectively. The optimized formula was evaluated using differential scanning calorimetry and X-ray diffraction and was also morphologically examined using transmission electron microscopy. An ex vivo study was conducted to determine the permeation and retainment of the optimized formulation in a human cadaver nail plate, and confocal laser scanning microscope was used to show the extent of formulation permeation. In conclusion, the results confirmed that spanlastics exhibit promising results for the trans-ungual delivery of TBH.
Aldehyde Dehydrogenase-2 Is a Host Factor Required for Effective Bone Marrow Mesenchymal Stem Cell Therapy

Objective—Mesenchymal stem cell (MSC) therapy is a promising treatment for ischemic injury. However, the environmental regulatory mechanism is essentially unclear and thus greatly limits its application in clinical setting. Accumulating evidence suggests a vital role of aldehyde dehydrogenase-2 (ALDH2) in microenvironment homeostasis after ischemia. About 540 million people or 8% of population worldwide carry a loss-of-function allele of ALDH2. It is unknown whether ALDH2 functions as a host factor regulating the therapeutic potential of donor MSCs. Therefore, this study was designed to determine whether and how host ALDH2 regulates MSC retention and therapeutic efficacy after transplantation into ischemic tissues. Approach and Results—Mice limb ischemia was performed by femoral artery ligation. A total of 106 MSCs were injected into the ischemic thigh muscles. One, 2, and 4 weeks after transplantation, MSC retention, blood perfusion recovery, limb necrosis, and fibrosis were analyzed. Compared with wild-type tissue, ALDH2 deficiency tissue significantly limited MSC retention and its perfusion recovery and limb salvage effects after ischemia. Importantly, local overexpression of ALDH2 optimized tissue microenvironment and significantly magnified all these MSC-induced improvement. Further study indicated that host ALDH2 regulated transplanted MSC survival and therapy as a microenvironment homeostasis mediator via local capillary density, energy supply, and oxidative stress regulating after ischemia. Conclusions—Our study establishes ALDH2 as a key mediator of host stem cell niche for optimal MSC therapy and suggests that ALDH2 deficiency present in the general population is a limiting host factor to be considered for MSC therapy.
Mechanism of tumorigenesis of renal carcinomas associated with the constitutional chromosome 3;8 translocation.

PURPOSE Members of a family carrying a constitutional balanced translocation [t(3;8) (p14;q24)] have a high risk of developing multiple, bilateral clear-cell renal carcinomas. Two genetic mechanisms of carcinogenesis for this malignancy have been proposed: (1) disruption of a gene at the translocation breakpoint and (2) mutation of the von Hippel-Lindau tumor-suppressor gene at 3p25. This study further evaluates the role of the von Hippel-Lindau gene in the etiology and pathogenesis of t(3;8)-associated renal carcinomas. METHODS Two new t(3;8)-associated renal carcinomas were tested for mutations in the von Hippel-Lindau gene by single-stranded conformational polymorphism analysis followed by direct DNA sequencing, for loss of alleles on chromosomes 3p and 8, and for methylation abnormalities in the first cloned exon of the von Hippel-Lindau gene. RESULTS A missense mutation in the von Hippel-Lindau gene was found in one of the two t(3;8)-associated renal carcinomas. This mutation would produce a stop codon and a truncated protein. Both tumors showed a loss of alleles on the derivative 8 chromosome. When these results were combined with the results of our previous studies, two of the four t(3;8)-associated renal carcinomas, which were examined for molecular genetic changes, showed different von Hippel-Lindau somatic mutations. All renal tumors from the 3;8 translocation family showed loss of the translocated portion of chromosome 3. CONCLUSIONS These results support a mechanism of tumorigenesis in the chromosome (3;8) translocation family that involves the loss of both copies of the von Hippel-Lindau gene.
Discrimination and the distrust of democratic institutions in Latin America

This article analyzes the impact of ethnic and racial discrimination on political culture in six Latin American countries. Does experiencing discrimination alter a person's attitudes toward politics? If so, how? The analysis assesses the impact of discrimination on citizens' confidence in government – especially their trust in key liberal-democratic institutions such as legislatures and high courts. It finds that victims of discrimination distrust government institutions more than do citizens who have not faced discrimination. This distrust has implications for the quality and stability of democracy in the region. What is more, the site – and thus the perpetrators – of discrimination matters. Unfair treatment by agents of the state had corrosive effects on confidence in political institutions of all sorts, though the impact was particularly strong on trust in congress and high courts. By contrast, the effects of discrimination in private settings, at the hands of other private citizens, were at best indirect. These results support a “procedural justice” approach to theorizing the impact of discrimination on political culture.