gebhart/patrepeval huggingface dataset:
Deflections of anisotropic sandwich beams with variable face sheets and core thicknesses (1994)

A sandwich construction consists of a low-density core material with high strength face sheets bounded to the top and bottom surfaces. The construction has been widely used in the aerospace and marine industries due to its outstanding characteristics such as noise absorption, weight minimization, heat insulation, and better bending stiffness. In sandwich structures used in high-performance aircraft, the face sheets are often made of fiber-reinforced composite materials and the core is made of honeycomb. The structures may also have variable thickness so as to satisfy aerodynamic requirements. In the stress analysis, the constant-thickness face sheets are usually considered as membrane and the core is assumed to be inextensible but deformable in the thickness direction. The static behavior of variable-thickness, isotropic and homogeneous sandwich beams was successfully studied by employing a constant-thickness theory but allowing stiffnesses to vary in accordance with local thickness variations. It has been recently found in a refined theory that the analyses based on the constant thickness theory locally can lead to significant errors in structural responses if the sandwich beam is thickness-tapered and the cores are deformable in transverse shear. The errors arise mainly from two factors: (1) the transverse shear components of the membrane forces in the face sheets alter the transverse shears carried by the core; and (2) the face-sheet membrane strains arise from transverse shear deformation of the core. In practice the variable thickness may not only exist in core but also in face sheets. The thickness-variations may even be a type of step function. In this case the transverse shear stress in the face sheets and bending stress in the core should be taken into account in the refined theory mentioned. In the present study, energy principles are employed in deriving governing equations for general bending of anisotropic sandwich beams with variable thickness in both face sheets and cores. Solutions to these equations are based on a finite difference scheme. As an example in application, a simply supported thickness-tapered sandwich beam subject to a concentrated load at its center is considered. Let W' be the maximum deflection of the beam in which face sheets are considered as membrane, while W'' is that based on using the modified refined theory. It is found that W' is always larger than W'', however, the magnitude of (W'- W'') appears to be insensitive to the change of the taper of the beam.
Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro. (1990)

Bisphosphonates are useful in treatment of disorders with increased osteoclastic activity, but the mechanism by which bisphosphonates act is unknown. We used cultures of chicken osteoclasts to address this issue, and found that 1-hydroxyethylidenediphosphonic acid (EHDP), dichloromethylidenediphosphonic acid (Cl2MDP), or 3-amino-1-hydroxypropylidene-1,1-diphosphonic acid (APD) all cause direct dose-dependent suppression of osteoclastic activity. Effects are mediated by bone-bound drugs, with 50% reduction of bone degradation occurring at 500 nM to 5 microM of the different agents. Osteoclastic bone-binding capacity decreased by 30-40% after 72 h of bisphosphonate treatment, despite maintenance of cell viability. Significant inhibition of bone resorption in each case is seen only after 24-72 h of treatment. Osteoclast activity depends on ATP-dependent proton transport. Using acridine orange as an indicator, we found that EHDP reduces proton accumulation by osteoclasts. However, inside-out plasma membrane vesicles from osteoclasts transport H+ normally in response to ATP in high concentrations of EHDP, Cl2MDP, or APD. This suggests that the bisphosphonates act as metabolic inhibitors. Bisphosphonates reduce osteoclastic protein synthesis, supporting this hypothesis. Furthermore, [3H]leucine incorporation by the fibroblast, which does not resorb bone, is also diminished by EHDP, Cl2MDP and APD except when co-cultured with bisphosphonate-binding bone particles. Thus, the resorption-antagonizing capacities of EHDP, Cl2MDP and APD reflect metabolic inhibition, with selectivity for the osteoclast resulting from high affinity binding to bone mineral.
Conservation of IL‐6 trans‐signaling mechanisms controlling L‐selectin adhesion by fever‐range thermal stress (2007)

Fever is associated with improved survival during infection in endothermic and ectothermic species although the protective mechanisms are largely undefined. Previous studies indicate that fever-range thermal stress increases the binding activity of the L-selectin homing receptor in human or mouse leukocytes, thereby promoting trafficking to lymphoid tissues across high endothelial venules (HEV). Here, we examined the evolutionary conservation of thermal regulation of L-selectin-like adhesion. Leukocytes from animals representing four taxa of vertebrates (mammals, avians, amphibians, teleosts) were shown to mediate L-selectin-like adhesion under shear to MECA-79-reactive ligands on mouse HEV in cross-species in vitro adherence assays. L-selectin-like binding activity was markedly increased by fever-range thermal stress in leukocytes of all species examined. Comparable increases in L-selectin-like adhesion were induced by thermal stress, IL-6, or the IL-6/soluble IL-6 receptor fusion protein, hyper-IL-6. Analysis of the molecular basis of thermal regulation of L-selectin-like adhesion identified a common IL-6 trans-signaling mechanism in endotherms and ectotherms that resulted in activation of JAK/STAT signaling and was inhibited by IL-6 neutralizing antibodies or recombinant soluble gp130. Conservation of IL-6-dependent mechanisms controlling L-selectin adhesion over hundreds of millions of years of vertebrate evolution strongly suggests that this is a beneficial focal point regulating immune surveillance during febrile inflammatory responses.
Erythema migrans (1993)

Preview Because disseminated Lyme disease can be devastating, early recognition and treatment are important. The presence of erythema migrans offers the best opportunity for early diagnosis. Therefore, public awareness and patient education about the rash of Lyme disease are critical. Dr Masters gives practical pointers from his own experience in evaluation of erythema migrans and reviews current treatment recommendations.
Interleukin-3 and Hematopoiesis (2015)

Considerable information has accumulated over the past several years relating to the biological activities of IL-3 which supports that concept that IL-3 has a unique capacity to support the proliferation and differentiation of a wide spectrum of hematopoietic cells. The pleiotropic activity of IL-3 has in turn elicited considerable enthusiasm for clinical trials of IL-3 in humans. Such clinical trials are ongoing and will certainly reveal a variety of conditions that will benefit from IL-3 treatment alone or in combination with other lymphokines. Of particular note are conditions which would benefit from the proliferation and expansion of early myeloid progenitors. These include bone marrow reconstitutions, aplastic anemias, hematopoietic recovery following chemotherapy. A variety of data demonstrate that hematopoiesis is not dependent upon IL-3. Thus, alternative factors must exist that can also support the proliferation and differentiation of hematopoietic stem cells. This observation and the uniquely T cell origin of IL-3 have led to the concept the production of IL-3 has evolved within the immune system as a mechanism by which immunological reactions can broadly affect hematopoiesis. The lack of an essential role in constitutive hematopoiesis would be consistent with the divergence in the structure of the gene that is seen among species. Such a role would also predict that it will be easy to obtain mice in which the gene has been deleted by homologous recombination. Indeed, such mice will be essential to fully define the role that IL-3 has in the development and content of immune responses. Although IL-3 supports the proliferation of a variety of myeloid lineages and cells at various stages of differentiation, relatively little has been uncovered regarding the influence that IL-3 might have no differentiation. The results strongly suggest that IL-3 does not singularly control differentiation. The other extreme would suggest that IL-3 may support proliferation which allows the expression of a genetic program that is determined completely independent of IL-3. The most appealing hypothesis is that IL-3 can influence the outcome of a differentiation program. In particular, it can be hypothesized that a pluripotential stem cell that is proliferating in IL-3 has a somewhat different pattern of differentiation than cells proliferating in the presence of the factors that control constitutive hematopoiesis. Of particular interest are mechanisms by which IL-3 mediates its biological effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Thiol–Ene Click Chemistry (2010)

Following Sharpless' visionary characterization of several idealized reactions as click reactions, the materials science and synthetic chemistry communities have pursued numerous routes toward the identification and implementation of these click reactions. Herein, we review the radical-mediated thiol-ene reaction as one such click reaction. This reaction has all the desirable features of a click reaction, being highly efficient, simple to execute with no side products and proceeding rapidly to high yield. Further, the thiol-ene reaction is most frequently photoinitiated, particularly for photopolymerizations resulting in highly uniform polymer networks, promoting unique capabilities related to spatial and temporal control of the click reaction. The reaction mechanism and its implementation in various synthetic methodologies, biofunctionalization, surface and polymer modification, and polymerization are all reviewed.
Karma: know-it-all replacement for a multilevel cache (2007)

Multilevel caching, common in many storage configurations, introduces new challenges to traditional cache management: data must be kept in the appropriate cache and replication avoided across the various cache levels. Some existing solutions focus on avoiding replication across the levels of the hierarchy, working well without information about temporal locality-information missing at all but the highest level of the hierarchy. Others use application hints to influence cache contents.

We present Karma, a global non-centralized, dynamic and informed management policy for multiple levels of cache. Karma leverages application hints to make informed allocation and replacement decisions in all cache levels, preserving exclusive caching and adjusting to changes in access patterns. We show the superiority of Karma through comparison to existing solutions including LRU, 2Q, ARC, MultiQ, LRU-SP, and Demote, demonstrating better cache performance than all other solutions and up to 85% better performance than LRU on representative workloads.
Acidogenic Potential of “Sugar-Free” Cough Drops (2009)

A patient presented with extensive marginal ditching around restorations recently placed during whole-mouth rehabilitation. The patient was not xerostomic and was otherwise normal except for the self-reported excessive use of "sugar-free" cough drops sweetened with sorbitol and Isomalt® (an equimolar mix of glucosyl-mannitol and glucosylsorbitol). This prompted an in vitro investigation to determine whether Streptococcus sobrinus 6715, a cariogenic streptococcus, could grow and produce acid in growth medium containing an aqueous extract of such "sugar-free" cough drops. The results indicate that S. sobrinus 6715 uses Isomalt® and sorbitol extensively, producing terminal culture pH as low as 4.2 when grown on medium with cough drop extract containing these sugars. This pH is sufficient to demineralize dental enamel. Patients should be cautioned against the chronic overuse of "sugar-free" cough drops and other "sugar-free" confections sweetened with a mixture of Isomalt® and sorbitol.
Access to heterogeneous directory services (2002)

A description is given of the directory access service (DAS), which automates the process of searching multiple directories. DAS is directory service user interface that integrates the various directories into a single, uniform directory service. In response to a user query, DAS forwards queries to multiple directories. The responses are collected and formatted by DAS into a standard format for presentation to the user. The design of DAS is flexible and extensible, allowing convenient integration of new directories into DAS as they become available.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Emerging strategies in regulatory T-cell immunotherapies. (2009)

The ability of tumors to evade immune system surveillance is an important characteristic that allows for their growth and survival. Accumulating evidence suggests that the mechanisms which allow for tumor cell evasion are similar to those that exits to prevent autoimmune diseases. Thus, targeting the immune system may be a major strategy to develop novel anti-tumor therapies. Among these strategies are therapies directed against regulatory T cells, as well as therapies designed to enhance the immune response triggered by CD8+ T cells. In the clinical roundtable, several experts discuss emerging strategies in regulatory T-cell immunotherapies. First, the major concepts behind immune suppression of solid tumors are described, including the current challenges and therapeutic targets under investigation. Then, the strategies under development are examined for their ability to overcome the regulatory T-cell effects in tumors. Finally, the roundtable concludes with a discussion of how these basic immunomodulatory concepts are being translated into clinical application. By understanding this roundtable, the clinician or oncologist will have a strong understanding of the current state-of-the-art strategies under investigation for anti-tumor immunotherapy.
Everolimus for the Prevention of Allograft Rejection and Vasculopathy in Cardiac-Transplant Recipients (2003)

Everolimus was more efficacious than azathioprine in reducing the severity and incidence of cardiac-allograft vasculopathy, suggesting that everolimus therapy may alleviate this serious problem.
Versatile tuning of supramolecular hydrogels through metal complexation of oxidation-resistant catechol-inspired ligands (2013)

The mussel byssal cuticle employs DOPA-Fe<sup>3+</sup> complexation to provide strong, yet reversible crosslinking. Synthetic constructs employing this design motif based on catechol units are plagued by oxidation-driven degradation of the catechol units and the requirement for highly alkaline pH conditions leading to decreased performance and loss of supramolecular properties. Herein, a platform based on a 4-arm poly(ethylene glycol) hydrogel system is used to explore the utility of DOPA analogues such as the parent catechol and derivatives, 4-nitrocatechol (nCat) and 3-hydroxy-4-pyridinonone (HOPO), as structural crosslinking agents upon complexation with metal ions. HOPO moieties are found to hold particular promise, as robust gelation with Fe<sup>3+</sup> occurs at physiological pH and is found to be largely resistant to oxidative degradation. Gelation is also shown to be triggered by other biorelevant metal ions such as Al<sup>3+</sup>, Ga<sup>3+</sup> and Cu<sup>2+</sup> which allows for tuning of the release and dissolution profiles with potential application as injectable delivery systems.
Use of cellular and cytokine adjuvants in the immunotherapy of cancer (1998)

Cellular and cytokine adjuvants, often immune effector cells and soluble factors, respectively, are supplemental and/or follow-up treatments of human origin for cancer patients who have unsatisfactory clinical responses to conventional chemotherapy, radiotherapy, and surgery. Since many human studies with these reagents are in their infancy, extensive data collection is only now being performed to determine which strategy provides the greatest therapeutic benefit. Research published in the literature since the genesis of this approach to cancer treatment is summarized in this report. Methodologies attempting to generate anticancer responses by provoking or enhancing the patient's own immune system are new compared with the other standard types of cancer treatment. Although a few encouraging human studies can be discussed, many of the most promising techniques are only now being transferred from the laboratory to the clinic. The administration of immune effector cells in combination with immunomodulators, such as interferons or interleukins, often enhances clinical outcome. The literature cited in this report indicate that immune-cell- and cytokine-based therapies hold promise in our attempts to improve the quality and duration of life in those with cancer. With each report reaching the literature, more effective clinical trials are being designed and implemented.
Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. (2000)

Members of the Toll-like receptor family are essential components of the innate immune system. Herein we report the molecular cloning and characterization of three novel human Toll-like receptors (hTLRs) designated hTLR7, hTLR8, and hTLR9. Human TLR7-9, like the previously described members hTLR1-6 contain an ectodomain with multiple leucine-rich repeats (LRRs) and a cytoplasmic domain homologous to that of the human interleukin-1 (IL-1) receptor. When compared with hTLR1-6, the hTLR7-9 has a higher molecular weight largely as a result of a longer ectodomain. Phylogenetic analysis shows that hTLR7-9 belong to a new sub-family of the hTLRs. Analysis of mRNA expression at the tissue levels shows differential expression patterns; hTLR7 is predominantly expressed in lung, placenta and spleen, hTLR8 is more abundant in lung, peripheral blood leukocytes, and hTLR9 is preferentially expressed in immune cell rich tissues, such as spleen, lymph node, bone marrow and peripheral blood leukocytes. The hTLR7 and hTLR8 genes are located on the sex chromosome X, hTLR9 gene is located on chromosome 3. Expression of constitutively active hTLR7-9 stimulates an NF-kappaB signaling pathway indirectly supporting the contention that these receptors are involved in cellular responses to stimuli, which activate innate immunity.
Arbitrary strain profile measurement within fibregratings using interferometric Fourier transformtechnique (1997)

An interferometric Fourier transform technique of measuring arbitrary strain profiles within intra-core fibre Bragg gratings is described and demonstrated. Using an ~86 mm long grating sensor, measurement of the strain field along a non-uniform cross-section cantilever beam was made. A theoretical strain accuracy of ~25 µɛ is possible with an achieved spatial accuracy of 2.58 mm.
Backward pitch prediction for low-delay speech coding (2003)

A backward-adaptive pitch prediction algorithm is described. It is used in conjunction with a backward-adaptive short-term predictor in a low-delay speech coding system operating at 16 kb/s. The backward-adaptive pitch prediction algorithm is a hybrid algorithm which combines backward block adaptive pitch prediction and backward recursive pitch prediction. The pitch predictor tap gains and the pitch period are periodically initialized by using a backward block adaptive algorithm. Between these initializations, however, both the tap gains and the pitch period are adapted using backward recursive algorithms. The tap gains are adapted using the well-known gradient algorithm, in a manner similar to the way the short-term predictor coefficients are adapted. The pitch period is adapted using a novel pitch tracking algorithm. By combining backward recursive adaptation with backward block adaptation, it was possible to increase the prediction gain of the pitch predictor and reduce the interval required between initialization of the pitch predictor parameters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Iron Accumulation in Deep Brain Nuclei in Migraine: A Population-Based Magnetic Resonance Imaging Study (2008)

A small magnetic resonance imaging (MRI) study showed increased iron depositions in the periaqueductal grey matter in migraineurs, suggestive of a disturbed central antinociceptive neuronal network. With 1.5-T MRI, we assessed iron concentrations in seven deep brain nuclei in a large population-based cohort. We compared T2 values between migraineurs (n = 138) and controls (n = 75), with multivariate regression analysis. Analyses were conducted in age strata (< 50, n = 112; > or = 50) because iron measures are increasingly influenced by non-iron-related factors in the older group. Overall, migraineurs and controls did not differ, nor did migraineurs with vs. without aura. In the younger migraineurs compared with controls, T2 values were lower in the putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Similarly, in these younger migraineurs, controlling for age, those with longer migraine history had lower T2 values in the putamen (P = 0.01), caudate (P = 0.04) and red nucleus (P = 0.001). Repeated migraine attacks are associated with increased iron concentration/accumulation in multiple deep nuclei that are involved in central pain processing and migraine pathophysiology. It remains unclear whether iron accumulation in the antinociceptive network has a causative role in the development of (chronic) migraine headache.
The role of hypoxia in intestinal inflammation (2016)

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestine. IBD is a multifactorial disorder, and IBD-associated genes are critical in innate immune response, inflammatory response, autophagy, and epithelial barrier integrity. Moreover, epithelial oxygen tension plays a critical role in intestinal inflammation and resolution in IBD. The intestines have a dynamic and rapid fluctuation in cellular oxygen tension, which is dysregulated in IBD. Intestinal epithelial cells have a steep oxygen gradient where the tips of the villi are hypoxic and the oxygenation increases at the base of the villi. IBD results in heightened hypoxia throughout the mucosa. Hypoxia signals through a well-conserved family of transcription factors, where hypoxia-inducible factor (HIF)-1α and HIF-2α are essential in maintaining intestinal homeostasis. In inflamed mucosa, HIF-1α increases barrier protective genes, elicits protective innate immune responses, and activates an antimicrobial response through the increase in β-defensins. HIF-2α is essential in maintaining an epithelial-elicited inflammatory response and the regenerative and proliferative capacity of the intestine following an acute injury. HIF-1α activation in colitis leads to a protective response, whereas chronic activation of HIF-2α increases the pro-inflammatory response, intestinal injury, and cancer. In this mini-review, we detail the role of HIF-1α and HIF-2α in intestinal inflammation and injury and therapeutic implications of targeting HIF signaling in IBD.
Characterization of genetically modified human retinal pigment epithelial cells developed for in vitro and transplantation studies. (2002)

RPE lines h1RPE-7 and h1RPE-116 retain many of the morphologic and biochemical characteristics of RPE cells in vivo and may serve as a source of cells for in vitro analysis of RPE cell function, as well as for orthotopic transplantation studies.
Dose-dependent effects of small-molecule antagonists on the genomic landscape of androgen receptor binding (2012)

Our study provides a global and dynamic view of AR's regulatory program upon antagonism, which may serve as a molecular basis for deciphering and developing AR therapeutics.