Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammation and Coagulation in Inflammatory Bowel Disease: The Clot Thickens

Inflammation and coagulation play crucial roles in the pathogenesis of multiple chronic inflammatory disorders. Growing evidence highlights a tight mutual network in which inflammation, coagulation, and fibrinolysis play closely related roles. Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), are chronic inflammatory conditions, characterized by a hypercoagulable state and prothrombotic conditions, and accompanied by abnormalities in coagulation. From a pathophysiological point of view, cells and molecules classically implicated in the physiological process of coagulation have now been shown to behave abnormally in IBD and possibly to also play an active role in disease pathogenesis and/or disease progression. This paper reviews studies performed on the coagulation profile and risk factors for thrombosis in IBD. In particular, an overview is provided of the epidemiology, clinical features, and etiology of thromboembolic complications in IBD. Furthermore, we review hemostatic abnormalities in IBD, as well as the cell types involved in such processes. Finally, we highlight the coagulation system as a dynamic participant in the multifaceted process of chronic intestinal inflammation. Overall, an overview is provided that the coagulation system represents an important, though previously underestimated, component of IBD pathogenesis, and may be a possible target for therapeutic intervention.
Defective HIV-1 Particle Assembly in AP-3-Deficient Cells Derived from Patients with Hermansky-Pudlak Syndrome Type 2

ABSTRACT Adaptor protein complex 3 (AP-3) is a heterotetramer that is involved in signal-mediated protein sorting to endosomal-lysosomal organelles. AP-3 deficiency in humans, induced by mutations in the AP3B1 gene, which encodes the β3A subunit of the AP-3 complex, results in Hermansky-Pudlak syndrome 2 (HPS2), which is a rare genetic disorder with defective lysosome-related organelles. In a previous study, we identified the AP-3 complex as an important contributor to HIV-1 assembly and release. We hypothesized that cells from patients affected by HPS2 should demonstrate abnormalities of HIV-1 assembly. Here we report that HIV-1 particle assembly and release are indeed diminished in HPS2 fibroblast cultures. Transient or stable expression of the full-length wild-type β3A subunit in HPS2 fibroblasts restored the impaired virus assembly and release. In contrast, virus-like particle release mediated by MA-deficient Gag mutants lacking the AP-3 binding site was not altered in HPS2 cells, indicating that the MA domain serves as the major viral determinant required for the recruitment of the AP-3 complex. AP-3 deficiency decreased HIV-1 Gag localization at the plasma membrane and late endosomes and increased the accumulation of HIV-1 Gag at an intermediate step between early and late endosomes. Blockage of the clathrin-mediated endocytic pathway in HPS2 cells did not reverse the inhibited virus assembly and release imposed by the AP-3 deficiency. These results demonstrate that the intact and stable AP-3 complex is required for HIV-1 assembly and release, and the involvement of the AP-3 complex in late stages of the HIV-1 replication cycle is independent of clathrin-mediated endocytosis.
From honeybees to Internet servers: biomimicry for distributed management of Internet hosting centers

An Internet hosting center hosts services on its server ensemble. The center must allocate servers dynamically amongst services to maximize revenue earned from hosting fees. The finite server ensemble, unpredictable request arrival behavior and server reallocation cost make server allocation optimization difficult. Server allocation closely resembles honeybee forager allocation amongst flower patches to optimize nectar influx. The resemblance inspires a honeybee biomimetic algorithm. This paper describes details of the honeybee self-organizing model in terms of information flow and feedback, analyzes the homology between the two problems and derives the resulting biomimetic algorithm for hosting centers. The algorithm is assessed for effectiveness and adaptiveness by comparative testing against benchmark and conventional algorithms. Computational results indicate that the new algorithm is highly adaptive to widely varying external environments and quite competitive against benchmark assessment algorithms. Other swarm intelligence applications are briefly surveyed, and some general speculations are offered regarding their various degrees of success.
Simultaneous detection of intracellular target and off‐target binding of small molecule cancer drugs at nanomolar concentrations

Background and purpose: In vitro assays that determine activities of drug candidates with isolated targets have only limited predictive value for activities in cellular assays. Poor membrane permeability and off‐target binding are major reasons for such discrepancies. However, it still difficult to directly analyse off‐target binding at the same time as target binding, on a subcellular level. Here, we present a combination of fluorescence correlation spectroscopy (FCS) and fluorescence cross‐correlation spectroscopy (FCCS) as a solution to this problem.
Catecholaminergic Polymorphic Ventricular Tachycardia: A Rare Cause of Cardiac Arrest Following Blunt Chest Trauma.

UNLABELLED Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an electrophysiological disorder of a physically normal heart that occurs in children when the body is subjected to intense emotional or physical stress that causes adrenergic discharge. This troubling disease can be sporadic (spontaneous) or familial (genetic/inherited). Unfortunately, its associated ventricular tachycardia may cause sudden death, so early diagnosis of CPVT is very important. Treatment modalities include medical treatment, implantation of a cardioverter defibrillator, or surgical sympatectomy; but the implantable cardioverter defibrillator (ICD) should be the first choice in patients with a history of cardiac arrest. We herein present the case of a patient diagnosed with CPVT after a successful cardiopulmonary resuscitation triggered by blunt chest trauma. We implanted an implantable cardioverter defibrillator and started oral B-blocker treatment. During the course of follow-up, flecainide was added to his treatment depending on the patient's status regarding recurrent ICD shock. The patient has now continued follow-up without recurrent ICD shock since flecainide treatment was initiated. In conclusion, in patients with syncope and sudden cardiac arrest secondary to physical stress or blunt chest trauma, CPVT should be considered and an implantable cardioverter defibrillator must be implanted. Additionally, flecainide theraphy should be considered to decrease recurrent ICD shock. KEY WORDS Blunt chest trauma; Cardiac arrest; CPVT.
The effect of tailoring a model HIV prevention program for local adolescent target audiences.

In five U.S. sites (Nashville, Tennessee; Newark, New Jersey; northern Virginia; Phoenix, Arizona; and Sacramento, California), HIV risk-reduction workshops were mounted as a part of the Prevention Marketing Initiative (PMI). In four of the five sites, the workshop curriculum was a version of Be Proud! Be Responsible! (Jemmott, Jemmott, & McCaffree, 1996) that had been tailored to fit the needs of local target audiences. This article describes the evaluation of the PMI workshops. Protective effects on several behavioral determinants and behavioral outcome measures were observed 1 month after the workshops. Based on the overall pattern of results, it was concluded that the PMI workshops reduced the likelihood of unprotected sex among participants. The intervention developed by Jemmott and colleagues appears to have retained its effectiveness after it was tailored to meet perceived local needs.
Complications and Short-Term Patient Outcomes of Periacetabular Osteotomy for Symptomatic Mild Hip Dysplasia

Introduction The purpose of our study is to identify complications and early functional outcome scores in patients treated with periacetabular osteotomy (PAO) for mild acetabular dysplasia. Methods The study population consisted of patients from a single centre prospective hip registry undergoing PAO with mild acetabular dysplasia (LCEA ≥18° and ≤25°; n = 27 patients; Mild Dysplasia group). A comparison group of patients undergoing PAO with more severe acetabular dysplasia (lateral centre-edge angle [LCEA] ≤17°; n = 50 patients; Severe Dysplasia group) were included as a comparison cohort. Demographics, radiographic findings, complications, and functional outcome scores were recorded at 6 months, 1 year, and 2 years postoperatively (mean 15 months [range 6-30]). Results Demographic characteristics were similar in patients with mild dysplasia undergoing PAO compared with more severe dysplasia. Achievement of radiological correction and complication rates were not different between the 2 groups. Functional outcome scores showed similar improvements in modified Harris Hip Score (mHHS), hip outcome score (HOS) activities of daily living (ADL), HOS Sport, and the international Hip Outcome Tool-33 (iHOT-33) at all time points between the 2 groups with over 90% of patients in the mild dysplasia group achieving a minimum important change (MIC) in functional outcome scores at final follow-up. Discussion Patients with symptomatic mild acetabular dysplasia undergoing PAO have similar complication rates and functional outcomes as a cohort of patients with more severe dysplasia.
Some properties of a system for sodium‐dependent outward movement of magnesium from metabolizing human red blood cells.

1. In agreement with the report by Féray & Garay (1986) it is shown that Mg2+ leaves human red cells mainly by a saturable pathway at a maximal rate of some 200 mumol 1(‐1) cells h(‐1) only if the medium contains Na+. Mg2+0.5 (i.e. the free Mg2+ concentration for half‐maximal rate) at the internal membrane surface is 1.3 mM and the dissociation constant for Na+, KNa, at the external surface is 16‐17 mM. Mg2+ shows co‐operative behaviour. The Na+o‐stimulated Mg2+ outflow is sensitive to millimolar amiloride concentrations. Implication of the Na+ or Ca+ pump can be ruled out. 2. Na+i is inhibitory by simple competition with Na+o. The affinity for Na+ inside is the same as outside. There is no detectable competition between Na+i and Mg2+i. 3. At approximately 1 mM‐[Mg2+]i the outward Mg2+ movement stimulated by Na+o still proceeds when [Mg2+]o is increased up to 20 mM. Thus the Mg2+ movement is uphill and the apparent Mg2+0.5 at the external surface is larger than 20 mM. 4. Reversing the Na+ gradient (making [Na+]i greater than [Na+]o) does not elicit an inward Mg2+ movement, even if [Mg2+]o is simultaneously made larger than [Mg2+]i. 5. The Na+o‐dependent Mg2+ outflow ceases nearly completely (falling to 5% of the control) in metabolically depleted cells. 6. The behaviour observed is compatible with the assumptions that (1) the system possesses distinct binding sites for Na+ and for Mg2+, (2) the ionophoric moiety is passively mobile when loaded with Na+, (3) the movement of the Na+ form is rate limiting, and (4) the Mg2+ form preferentially moves in the outward direction owing to an input of metabolic energy (ATP hydrolysis) and is immobile in starved cells. 7. Mg2+ may be required at a further site(s) not involved in the actual Mg2+ translocation but in the energy input. The simple kinetics suggesting translocation of one Na+ ion in exchange for one Mg2+ ion were found in selected cells of average maximum transport rate (Vmax) and may not hold for all cell specimens. 8. The conclusion is that the system is a Mg2+ extrusion pump driven by metabolic energy directly and not by the inward Na+ gradient, although net inward Na+ movement is necessary to bring the ionophoric part of the system back to the in‐position. It appears that in intact cells the system operates far below saturation by Mg2+i and, by compensating for an inward leak of less than 5 mumol,1(‐1) cells h(‐1), sets the internal free Mg2+ concentration at about 0.5 of the equilibrium value.
Purification, Cloning, Expression, and Mechanism of Action of a Novel Platelet Aggregation Inhibitor from the Salivary Gland of the Blood-sucking Bug, Rhodnius prolixus *

Rhodnius prolixus aggregation inhibitor 1 (RPAI-1), a 19-kDa protein isolated from the salivary gland of R. prolixus, was purified by strong cation exchange and reverse-phase high performance liquid chromatographies. Based on 49 amino-terminal amino acid sequences of RPAI-1, primers were produced to generate probes to screen an R. prolixus salivary gland cDNA library. A phage containing the full-length clone of RPAI-1 codes for a mature protein of 155 amino acids. RPAI-1 shows sequence homology to triabin and pallidipin, lipocalins from Triatoma pallidipennis. The cDNA sequence was cloned in Pet17BEscherichia coli expression vector, producing an active peptide. RPAI-1 inhibits human platelet-rich plasma aggregation triggered by low concentrations of ADP, collagen, arachidonic acid, thromboxane A2 mimetics (U46619), and very low doses of thrombin and convulxin. Here we show that ADP is the target of RPAI-1 since (i) RPAI-1 inhibits ADP-dependent large aggregation formation and secretion triggered by U46619, without affecting Ca2+ increase and shape change; (ii) ADP restored the inhibition of U46619-induced platelet aggregation by RPAI-1, (iii) PGE1-induced increase of cAMP (which is antagonized by U46619 in an ADP-dependent manner) was restored by RPAI-1, (iv) RPAI-1 inhibits low concentrations of ADP-mediated responses of indomethacin-treated platelets, and (v) RPAI-1 binds to ADP, as assessed by large zone chromatography. RPAI-1 affects neither integrin α2β1- nor glycoprotein VI-mediated platelet responses. We conclude that RPAI-1 is the first lipocalin described that inhibits platelet aggregation by a novel mechanism, binding to ADP.
Cluster analysis and disease mapping—why, when, and how? A step by step guide

Growing public awareness of environmental hazards has led to an increased demand for public health authorities to investigate geographical clustering of diseases. Although such cluster analysis is nearly always ineffective in identifying causes of disease, it often has to be used to address public concern about environmental hazards. Interpreting the resulting data is not straightforward, however, and this paper presents a guide for the non-specialist. The pitfalls include the fact that cluster analyses are usually done post hoc, and not as a result of a prior hypothesis. This is particularly true for investigations prompted by reported clusters, which have the inherent danger of overestimating the disease rate through "boundary shrinkage" of the population from which the cases are assumed to have arisen. In disease surveillance the problem of making multiple comparisons can be overcome by testing for clustering and autocorrelation. When rates of disease are illustrated in disease maps undue focus on areas where random fluctuation is greatest can be minimised by smoothing techniques. Despite the fact that cluster analyses rarely prove fruitful in identifying causation, they may-like single case reports-have the potential to generate new knowledge.
A New Fuzzy Guaranteed Cost Control Design for a Class of Nonlinear  Discrete-Time System with Uncertainties

This paper studies fuzzy hyperbolic guaranteed cost control for certain nonlinear systems with parameter uncertainties. As same as Takagi-Sugeno (T-S) fuzzy model, fuzzy hyperbolic model (FHM) can be used to establish the model for certain unknown complex system. Furthermore, the main advantage of using FHM over T-S fuzzy model is that no premise structure identification is need and no completeness design of premise variables space is need. Also a FHM is a kind of valid global description and nonlinear model in nature. First, the fuzzy hyperbolic model (FHM) is proposed to represent the state-space model for certain nonlinear systems. Next, a nonlinear quadratic cost function is considered as a performance measurement of the closed-loop fuzzy system. Some sufficient conditions are provided for the construction of a fuzzy hyperbolic guaranteed cost controller via state feedback. These conditions are given in terms of the feasibility of linear matrix inequalities (LMIs). A simulation example is provided to illustrate the design procedure of the proposed method.
Performance of free-space optical MIMO systems using SC-QAM over atmospheric turbulence channels

We theoretically analyze the performance of free-space optical (FSO) multiple-input multiple-output (MIMO) systems using rectangular sub-carrier quadrature modulation (SC-QAM) signaling. The systems's average symbol-error rate (ASER) is derived taking into account the atmospheric turbulence effects on the FSO MIMO channel, which is modeled by lognormal and the gamma-gamma processes for the cases of weak-to-strong turbulence conditions. We quantitatively discuss the influence of turbulence strength, link distance and different MIMO configurations on the ASER. We also derive and discuss the FSO MIMO average (ergodic) channel capacity (ACC), which is expressed in terms of average spectral efficiency (ASE), under the impact of various channel conditions.
Collective Vortex Behaviors: Diversity, Proximate, and Ultimate Causes of Circular Animal Group Movements

Ant mill, caterpillar circle, bat doughnut, amphibian vortex, duck swirl, and fish torus are different names for rotating circular animal formations, where individuals turn around a common center. These “collective vortex behaviors” occur at different group sizes from pairs to several million individuals and have been reported in a large number of organisms, from bacteria to vertebrates, including humans. However, to date, no comprehensive review and synthesis of the literature on vortex behaviors has been conducted. Here, we review the state of the art of the proximate and ultimate causes of vortex behaviors. The ubiquity of this behavioral phenomenon could suggest common causes or fundamental underlying principles across contexts. However, we find that a variety of proximate mechanisms give rise to vortex behaviors. We highlight the potential benefits of collective vortex behaviors to individuals involved in them. For example, in some species, vortices increase feeding efficiency and could give protection against predators. It has also been argued that vortices could improve collective decision-making and information transfer. We highlight gaps in our understanding of these ubiquitous behavioral phenomena and discuss future directions for research in vortex studies.
Leptin: in search of role(s) in human physiology and pathophysiology

Obesity, a health problem reaching epidemic proportions in western countries, is an important risk factor for the most frequent diseases in the western world, i.e. diabetes, hypertension, cardiovascular diseases and certain types of cancer. Thus, significant research efforts have been focusing on its aetiology, prevention and treatment. The recent discovery of leptin (from the Greek wordleptos: i.e. thin), the product of theob gene (Zhanget al., 1994), has greatly advanced our understanding of body adiposity and energy balance regulation. This hormone, produced mainly by adipose tissue, conveys to the brain information about the size of energy stores and activates hypothalamic centres that regulate energy intake and expenditure (Flier, 1997). Moreover, leptin affects several neuroendocrine mechanisms and regulates multiple hypothalamic– pituitary axes (Flier, 1997). The realization that adipose tissue is not simplyastorage depot, butalsoan important endocrine gland, has created new opportunities for the investigation and, possibly, treatment of diseases such as obesity and eating disorders. In this review, we discuss the biology of leptin secretion and regulation, as well as our current knowledge of the role leptin plays in various physiological and pathophysiological states. Although most available research studies have been based on animal models, a substantial amount of information has been accumulated over the last 3 years on the role of leptin in humans. Thus, this article mainly focuses on our current knowledge about the role of leptin in human physiology and pathophysiology. Finally, some of the important unanswered questions about leptin physiology are discussed and future directions for leptin research are suggested.
Bone Marrow Cells: The Source of Gastric Cancer?

On page 1568 of this issue of Science, researchers working with mice show that the damage a Helicobacter pylori relative causes to the epithelial cells of the stomach lining leads to an influx of bone marrow stem cells that apparently try to repair the lining and that these visiting cells--and not the cells of the epithelium--ultimately give rise to stomach cancer.
FMS-Like Tyrosine Kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) in Iranian Adult Acute Myeloid Leukemia Patients with Normal Karyotypes: Mutation Status and Clinical and Laboratory Characteristics

Objective: In this study, we evaluated the frequency of FMS-like tyrosine kinase 3 (FLT3-ITD and FLT3-TKD) and nucleophosmin (NPM1) mutations in Iranian patients with cytogenetically normal acute myeloid leukemia (CN-AML). The clinical and laboratory characteristics were compared between wild-type and mutant cases. Materials and Methods: Seventy newly diagnosed de novo AML patients were recruited at the time of diagnosis prior to chemotherapy; among them, 54 had CN-AML. For detecting mutations, the FLT3 and NPM1 genes were amplified by the polymerase chain reaction method, followed by direct sequencing. Results: Our results showed that the frequencies of FLT3-ITD, FLT3-TKD, and NPM1 mutations in CN-AML patients were 25.9%, 5.9%, and 20.8%, respectively. The most frequent NPM1 mutation type was the type A mutation. The FLT3-ITD mutation was seen more frequently in non-M3 patients compared with M3 patients. No mutation was observed in either the FLT3-TKD or the NPM1 gene in patients in the M3 French-American-British group. There was no significant association between the presence of FLT3-ITD and NPM1 mutations in CN-AML patients (p>0.05). The frequency of FLT3-ITD, FLT3-TKD, and NPM1 mutation was higher in CN-AML patients in comparison with AML patients with cytogenetic aberrations, although the differences were not statistically significant (p>0.05). There were no significant differences in mean white blood cell and platelet counts, serum hemoglobin levels, and bone marrow blast percentages between patients with wild-type and mutant FLT3-ITD and NPM1 genes (p>0.05). No difference was observed in the frequency of FLT3-ITD or NPM1 mutation regarding age or sex (p>0.05). Conclusion: Given the high stability of NPM1 during the disease course, it can be used in combination with FLT3 as well as other known genetic markers to monitor patients, especially for minimal residual disease detection.
The potential of hexatungstotellurate(VI) to induce a significant entropic gain during protein crystallization

Hexatungstotellurate(VI) (TEW), an Anderson–Evans-type polyoxometalate (POM), was found to be a promising cocrystallization agent that mediates new strong crystal contacts and contributes significantly to the solvent entropy which presumably leads to a lower free energy of protein crystallization. The results presented herein strongly encourage the use of TEW as a powerful additive in protein crystallization, particularly within or near the liquid–liquid phase separation (LLPS) region.