Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Protein C Inhibitor in Human Reproduction

Protein C inhibitor (PCI) is a heparin-dependent serine protease inhibitor found in human plasma, urine, and other body ﬂuids. In blood plasma, PCI is present at (cid:1) 0.08 m M and inactivates activated protein C and other coagulation and ﬁbrinolytic enzymes. In seminal plasma, PCI is present at 2.2 to 3.7 m M. The main sources of seminal PCI are the seminal vesicles, where it remains fully active. Following ejaculation, PCI completely looses its activity in approximately 2 hours, when it partially complexes with prostate-speciﬁc antigen, two plasminogen activators (urokinase-type and tissue-type plasminogen activators), and tissue kallikrein. PCI is also present in an active form in follicular ﬂuid at (cid:1) 0.1 m M. Puriﬁed functionally active human blood plasma-derived as well as inactive semen-derived PCI inhibited both binding and penetration of zona-free hamster oocytes by human sperm. The binding inhibition by PCI was dose dependent. A concentration of 0.04 m M PCI ( (cid:1) 100-fold lower than that present in seminal plasma) inhibited 50% of the binding and penetration ability. Given that capacitated sperm used for in vitro fertilization usually contains more than 0.05 m M of PCI, fertilization rates might be signiﬁcantly reduced. All of these data suggest that PCI is involved in human reproduction at several steps, including the fertilization process.
Sepsis and the Lung Host Response

Sepsis is the leading cause of death in critically ill patients and is the most common risk factor for the development of acute lung injury in medical patients. Initially investigators hypothesized that an excessive proinﬂammatory response contributed to the pathogenesis of sepsis. However, this hypothesis overlooked the beneﬁcial effects of proinﬂammatory mediators and the detrimental effects of an excessive anti-inﬂammatory response. This has led to a new hypothesis where sepsis is characterized by imbalances of the pro-and anti-inﬂammatory responses, with tissue injury the result of an excessive proinﬂammatory response and impaired pulmonary host defense the result of an excessive anti-inﬂammatory response. This article reviews clinical studies and animal models which show that sepsis results in an impaired lung host response to bacteria. Information in this article should provide the reader with an increased understanding of the pathogenesis of sepsis and the realization that new therapeutic strategies for sepsis need to take into account the need to balance pro-and anti-inﬂammatory responses to maintain pulmonary host defenses and prevent the development of acute lung injury.
Thyroid Disorders and Hypocoagulability

This review focuses attention on some practical aspects of the relationship between thyroid disorders and hypocoagulability, as related to an impairment of hemostasis and ﬁbrinolysis. An understanding of this topic in daily clinical practice is important given that the interaction between hemostatic abnormalities and thyroid disorders is still poorly recognized by the medical community. Even if the bleeding tendency is in general mild and may be reversed by restoration of an euthyroid state, severe hemorrhagic events may complicate the course of both hyper-and hypothyroidism, as precipitated by such conditions as thrombocytopenia, acquired von Willebrand syndrome, and acquired hemophilia. The pathogenesis of the hemostatic abnormalities resides in either the direct effect of thyroid hormones or some conditions in an autoimmune mechanism. Physicians and endocrinologists should pay close attention to both clinical hemorrhagic events in their patients as well as to any laboratory abnormalities identiﬁed by blood coagulation testing.
Current Issues in Endovascular Surgical Neuroradiology

Endovascular surgical neuroradiology is a newly recognized specialty within the American Medical Association. Remarkable advances in the specialty with regard to stroke prevention and therapy as well as the treatment of ruptured and unruptured cerebral aneurysms have provided patients and their treating physicians with novel treatment options that complement existing therapy. The issues surrounding the efﬁcacy of endovascular treatment of intracranial atherosclerosis and cerebral aneurysms will be reviewed using a case-based learning format.
Hepatic Vascular Malformations in Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that can involve the liver diffusely in the form of vascular malformations ranging from small telangiectases to discrete arteriovenous malformations. Anatomically, three different patterns of abnormal vascular communications can occur in liver: portal vein to hepatic vein (portovenous), hepatic artery to hepatic vein (arteriovenous) and hepatic artery to portal vein (arterioportal), with the most common being arteriovenous. Only 5 to 8% of patients with these vascular malformations are symptomatic. When symptomatic, patients present with high-output cardiac failure, biliary ischemia (which, when severe, can progress to biliary and hepatic necrosis and lead to acute liver failure), or portal hypertension. Other less common presentations include portosystemic encephalopathy and abdominal angina. Diagnosis is conﬁrmed by Doppler ultrasonography or multidetector computed tomography. The hallmark ﬁndings are intrahepatic hypervascularization and an enlarged common hepatic artery. Focal nodular hyperplasia and nodular regenerative hyperplasia are common ﬁndings. Symptomatic patients are treated with intensive medical treatment aimed at the predominant clinical presentation. Patients who fail aggressive medical therapy and those with acute biliary/hepatic necrosis should be considered for liver transplantation.
Dynamic responses of unsaturated half‐space soil to a moving harmonic rectangular load

The problem of the dynamic responses of a semi‐infinite unsaturated poroelastic medium subjected to a moving rectangular load is investigated analytical/numerically. The dynamic governing equations are obtained with consideration of the compressibility of solid grain and pore fluid, inertial coupling, and viscous drag as well as capillary pressure in the unsaturated soil, and they can be easily degraded to the complete Biot's theory. Using the Fourier transform, the general solution for the equations is derived in the transformed domain, and then a corresponding boundary value problem is formulated. By introducing fast Fourier transform algorithm, the unsaturated soil vertical displacements, effective stresses, and pore pressures induced by moving load are computed, and some of the calculated results are compared with those for the degenerated solution of saturated soils and confirmed. The influences of the saturation, the load speed, and excitation frequency on the response of the unsaturated half‐space soil are investigated. The numerical results reveal that the effects of these parameters on the dynamic response of the unsaturated soil are significant.
Heterogeneity in Endothelial Responsiveness to Cytokines, Molecular Causes, and Pharmacological Consequences

Microvascular endothelial cells play an essential role in inﬂammatory diseases. Functional heterogeneity between microvascular segments in normal organ homeostasis has been appreciated for a long time, and more recent studies have revealed heterogeneity in endothelial reactivity to inﬂammatory stimuli as well. This review summarizes the state-of-the-art knowledge regarding endothelial cell responses to the proinﬂammatory cytokines tumor necrosis factor a , interleukin-1 b , and the bacterial product lipopolysaccharide. It focuses on similarities and differences in reactivity between endothelial cell subsets in vitro and endothelial cells in their pathophysiological environment in vivo, and culminates into a mainly theoretical model of possible intracellular control mechanisms that can assist to ultimately explain the molecular causes of endothelial heterogeneity. The last part of this review contains some pharmacological considerations, and, with the aim to further unravel the molecular basis of in vivo endothelial heterogeneity, descriptions of new techniques that will be essential to achieve this.
Platelet-Induced Differentiation of Endothelial Progenitor Cells

Endothelial progenitor cells (EPCs) have the potential to home at sites of vascular lesions and to contribute to revascularization. This homing is a highly concerted mechanism, which involves chemotaxis, adhesion, migration, and ﬁnally integration of the cells into the target tissue. Only recently has the platelet been identiﬁed as a central mediator of EPC homing. Adherent platelets were able to mediate chemotaxis and adhesion of EPCs, a process that involved P-selectin glycoprotein ligand 1 and very late antigen-4 (VLA-4). Recent studies suggest that platelet-derived stromal cell–derived factor-1 is also involved centrally in the recruitment of EPCs. Furthermore, platelets induce progenitor cell migration by platelet-derived growth factor AB. Recent in vivo data conﬁrm the recruitment of EPCs to sites of vascular lesions after vessel denudation by activated platelets and ﬁbrin. Moreover, when coincubated with platelets, EPCs differentiate to mature endothelial cells and have the potential to migrate and colonize a platelet thrombus. The described interaction of EPCs with platelets represents a novel mechanism of vascular remodeling and healing of endothelial lesions.
Inhibition of Platelet Function: Does It Offer a Chance of Better Cancer Progression Control?

Thrombocytosis is frequently (10 to 57%) observed in cancer patients. Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity, growth factors, platelet-derived microparticles, and factors released from bone marrow endothelial cells as well as growth factors secreted by megakaryocytes (acting via an autocrine loop) are claimed to inﬂuence this process. The course of cancer is strongly associated with hypercoagulable state, which results from direct inﬂuences of tumor cells themselves and various indirect mechanisms. Activated platelets provide procoagulant surface amplifying the coagulation process. It is well documented that proteins of the hemostatic system inﬂuence different steps of metastasis, angiogenesis, and proteolytic events. Much less is known about the role of platelets in tumor growth and their possible contribution to prevention of tumor cells from the host immune system. Multidirectional activities of platelets during tumor development and metastatic dissemination create a possibility of introducing antiplatelet agents in anti-cancer therapy. The spectrum of plausible therapies includes antibodies against glycoprotein IIb-IIIa, direct thrombin inhibitors, protease activated receptor-1 targeted therapy, as well as cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors. However, there is no sufﬁcient information on a speciﬁc type of cancer where progression does depend on platelet function. Despite numerous experimental studies conducted, to date none of the new speciﬁc antiplatelet agents were tested in clinical trials in a cancer patient population.
A Review of Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) is a protein that prevents enzymes such as elastin from degrading normal host tissue. Individuals who are deﬁcient in AAT (those with levels < 11 m mol/L) are at risk for developing such clinical manifestations as emphysema, cirrhosis, panniculitis, and anticytoplasmic neutrophilic antibody (C-ANCA)-positive vasculitis (Wegener’s granulomatosis). Estimates suggest that 75 to 85% of those with severe deﬁciency of AAT will develop emphysema. Smoking appears to be the most important risk factor for the development of emphysema among AAT deﬁcient persons. Severe deﬁciency of AAT also seems to be associated with a shorter lifespan. Among smokers, mild to moderate reductions in AAT levels may be associated with a more rapid decline in lung function. Diagnosis of AAT deﬁciency is made by measuring serum levels of AAT and, if reduced, an effort should then be made to identify the genetic abnormality responsible for the reduction. A recent evidence-based review has offered testing recommendations for AAT deﬁciency and includes the recommendation that all patients with COPD be tested for AAT deﬁciency. Augmentation with an intravenous form of puriﬁed pooled human plasma has been shown to increase the serum levels of AAT among deﬁcient patients and its use appears to impact the rate of forced expiratory volume in 1 second (FEV 1 ) decline and overall survival; to date, no conﬁrmatory, large, prospective, randomized trials are available.
Optimizing Therapy for Infections Caused by Enterobacteriaceae Producing Extended-Spectrum β-Lactamases

The spread of multidrug-resistant Enterobacteriaceae is complicating the treat-ment of nosocomial infections. In many parts of the world, resistance to third-generation cephalosporins exceeds 10% of total nosocomial isolates and 30% of isolates detected in the intensive care unit. This resistance is frequently due to the acquisition of plasmids containing genes encoding for extended-spectrum b -lactamases (ESBLs). Furthermore, these mobile elements often carry genes encoding resistance to other drugs such as aminoglycosides. A high risk of poor clinical outcome has been observed in patients infected with ESBL producers receiving third-generation cephalosporins, even if the organism appears susceptible to the antibiotic. For this reason, clinical microbiology laboratories are advised to incorporate speciﬁc ESBL detection methodology into routine clinical practice. This should prevent erroneous use of cephalosporins for these infections. Most ESBL producers remain susceptible to carbapenems, and these agents are considered the drugs of choice against ESBL-producing organisms. Unfortunately, there is now an increasing occurrence of carbapenem resistance in the Enterobacteriaceae. In this context, clinical response to new antibiotics (e.g., tigecycline) and old antibiotics (e.g., colistin) with good in vitro activity against ESBL producers needs to be evaluated.
Process Standardization for the Manufacture of Shrikhand Spread

Purpose : Shrikhand Spread, a unique sweetened fermented Indian milk product is made by separation of whey from dahi , the Indian counterpart of Western yoghurt, followed by addition of sugar. Production of dahi employing traditional method involved undefined mixed starter cultures, uncontrolled fermentation and longer production time resulting in wide variation in its chemical and microbiological qualities. In order to cater to a product with desirable properties like lower post-acidification, higher flavour profile, firm body and lower syneresis coupled with shorter production time, conjugated application of yoghurt cultures and dahi cultures were tried. Since the shelf-life of dahi is limited, conversion into shrikhand spread may be used as a tool to extend the shelf-life and therefore the market reach towards commercialization into the global market as a potential functional food. Design/Methodology/Approach : Different batches of dahi were made from homogenized (Stage I - 2500 psi, Stage II - 500 psi) and pasteurized (74-78 °C/16-19 Sec) milk, pre-adjusted to 3.15-3.20% fat and 11.40% snf with diverse starter combinations selected upon the extent of post acidification, volatile acid production, syneresis and rheological characteristics. Homogenized, pasteurized and regulated milk was further subjected to a heat-treatment (90°C/10 min) and seeded with selected starter combinations to obtain firm curd intended for shrikhand spread manufacture. Shelf-life of shrikhand spread was evaluated in terms of chemical and microbiological criteria upto 7 days of storage at 8±1°C. Findings : Starter combination of eXactDahi 2+YoFlex Express 1.0 at an incubation temperature-time combination of 45°C/5h was found most suitable for producing dahi with smooth body, higher volatile acidity and low syneresis. Utilization of dahi obtained employing the above starter combination for the manufacture shrikhand spread was suggested and the product was found to retain its goodness when stored for 7 days at 8±1°C. Originality/Value : Conjugated use of yoghurt cultures with dahi cultures was suggested to overcome the drawbacks of traditional process of dahi manufacture suitable for conversion into shrikhand spread. This dahi was found capable of enhancing its dietetic value in addition.
Numerical quadrature on the intersection of planar disks

We provide an algorithm that computes algebraic quadrature formulas with cardinality not exceeding the dimension of the exactness polynomial space, on the intersection of any number of planar diskswitharbitraryradius. Applicationsariseforexampleincomputationalopticsandinwirelessnetworks analysis. By the inclusion-exclusion principle, we can also compute algebraic formulas for the union of a small number of disks. The algorithm is implemented in Matlab, via subperiodic trigonometric Gaussian quadrature and compression of discrete measures.
Genomics of Liver Fibrosis and Cirrhosis

Hepatic ﬁbrosis is the response to chronic injury from viral, toxic, metabolic, cholestatic, or autoimmune liver injury. However, only a minority of affected individuals develop advanced ﬁbrosis or cirrhosis, suggesting that modiﬁers determine the individual risk. Aside from well-established progression factors including gender, duration of exposure to the disease, and ethnicity, unknown host genetic factors are likely to inﬂuence disease progression and prognosis. Potential genetic susceptibility loci are single nucleotide polymorphisms in ﬁbrosis-associated genes, point mutations, microsatellites, and haplotype blocks composed of genes pivotal for ﬁbrosis development. However, the study of complex polygenetic diseases poses numerous pitfalls in contrast to the elucidation of monogenetic (i.e., Mendelian) diseases. Many publications on the role of certain genetic variants in modulating the progression of hepatic ﬁbrosis have been limited by inadequate study design and low statistical power. At present, powerful research strategies are being developed that allow the application of knowledge derived from the successful sequencing of the human genome that will help to translate our newly acquired insight into practical improvements for research activities and medical practice.
The Applicability of Hormonal Effects on Atherosclerosis in Animals to Heart Disease in Postmenopausal Women

The discrepancy between estrogen’s beneﬁcial cardiovascular effects found in animal studies and observational studies in women compared with the recently published randomized clinical trials have stimulated a great deal of controversy. Possibilities for the discrepancy include the age of the women, number of years postmenopausal, and amount of atherosclerotic complication (necrosis and inﬂammation) present when hormone therapy is initiated. Many of the previous beneﬁts of estrogens noted in both animal studies and observational studies were found in primary prevention studies that experimentally refer to a decrease in the progression of atherosclerosis extent rather than prevention of clinical events, which often occur in women with undiagnosed atherosclerotic plaques. In support of this notion, animal studies in which artery damage was present prior to hormone treatment, due to either consumption of an atherogenic diet or balloon injury of the endothelium, found no beneﬁt with estrogen treatment. These animal studies are consistent with the lack of protection found in secondary prevention studies in women. Other areas of concern deal with the route of hormone delivery or dose of hormones used. Higher doses of oral estrogens may result in increased risk of inﬂammation and thrombosis. Future studies should be directed at studying hormone therapy in relevant ages of women (perimenopausal women) using the lowest effective doses of hormones and comparing oral and parenteral forms of delivery.
Optimizing Use of Colistin and Polymyxin B in the Critically Ill

Polymyxin B and colistin are being used increasingly for the treatment of infections caused by gram-negative bacteria that are resistant to all other currently available antibiotics. Although the polymyxins have been available in the clinic for around 50 years, they have never been subjected to the drug development procedures required of modern pharmaceuticals. As a result, the available knowledge on the pharmacokinetics (PK), pharmacodynamics (PD), and toxicodynamics (TD) of the polymyxins is limited. Although signiﬁcant advances have been made in the last 5 years or so, there are still large gaps in our understanding of the PK, PD, and TD, and of the PK/PD and PK/TD relationships. This information is required to generate recommendations on dosage regimens for various categories of critically ill patients. This paper reviews the growing understanding of the pharmacology of the polymyxins and factors that may impact on the optimization of the dose of these antibiotics in critically ill patients.
Liquid–Ice Mass Partition in Tropical Maritime Convective Clouds

AbstractThe liquid–ice mass partitioning in tropical maritime convective clouds is studied using data collected by the National Center for Atmospheric Research C-130 research aircraft during the Ice in Clouds Experiment–Tropical project. The clouds investigated by the C-130 in this study generally contained weak to moderate updrafts. The liquid water content (LWC) is calculated using a combination of hot-wire and imaging probes. The total condensed water content (CWC) is measured by a counterflow virtual impactor. The ice water content (IWC) is calculated as CWC minus LWC. Taking into account potential significant measurement uncertainties, the liquid fraction [i.e., LWC/(LWC + IWC)] between 0° and −15°C appears to decrease by a factor of about 3 in updrafts near ( 500 m) cloud top. The decrease in liquid fraction as a function of temperature is also correlated with cloud life cycle. In dissipating clouds, ice dominates in all temperature ranges.
Genetics, Genomics, and Proteomics: Implications for the Diagnosis and the Treatment of Chronic Hepatitis C

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. The severity of disease varies widely from mild illness to cirrhosis and hepatocellular carcinoma. The progression of liver ﬁbrosis in HCV patients determines the prognosis and, thus, the need for and urgency of therapy. In addition to viral and environmental behavioral factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes of patients chronically infected with HCV. The sequencing of the human genome together with the development of high-throughput technologies has provided opportunities to distinguish discrete subsets of HCV disease and predict the disease outcome or the response to therapy. This article reviews genetic, genomic, and proteomic aspects associated with the natural history of HCV infection (i.e., viral clearance, ﬁbrosis progression) and the response to therapy.