gebhart/patrepeval huggingface dataset:
Speed adaptation in a powered transtibial prosthesis controlled with a neuromuscular model (2011)

Control schemes for powered ankle-foot prostheses would benefit greatly from a means to make them inherently adaptive to different walking speeds. Towards this goal, one may attempt to emulate the intact human ankle, as it is capable of seamless adaptation. Human locomotion is governed by the interplay among legged dynamics, morphology and neural control including spinal reflexes. It has been suggested that reflexes contribute to the changes in ankle joint dynamics that correspond to walking at different speeds. Here, we use a data-driven muscle-tendon model that produces estimates of the activation, force, length and velocity of the major muscles spanning the ankle to derive local feedback loops that may be critical in the control of those muscles during walking. This purely reflexive approach ignores sources of non-reflexive neural drive and does not necessarily reflect the biological control scheme, yet can still closely reproduce the muscle dynamics estimated from biological data. The resulting neuromuscular model was applied to control a powered ankle-foot prosthesis and tested by an amputee walking at three speeds. The controller produced speed-adaptive behaviour; net ankle work increased with walking speed, highlighting the benefits of applying neuromuscular principles in the control of adaptive prosthetic limbs.
BMP-2 Controls Alkaline Phosphatase Expression and Osteoblast Mineralization by a Wnt Autocrine Loop (2003)

Our data strongly suggest that the capacity of BMP-2 and Shh to induce ALP relies on Wnt expression and the Wnt/LRP5 signaling cascade. Moreover the effects of BMP-2 on extracellular matrix mineralization by osteoblasts are mediated, at least in part, by the induction of a Wnt autocrine/paracrine loop. These results may help to explain the phenotype of OPPG patients and HBM.
Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions (2017)

Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, we set out to find a soluble mediator for this phenomenon. We found that extracellular vesicles (EVs) shed from astrocytes in response to intracerebral injection of interleukin-1β (IL-1β) rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral acute cytokine response. Bioinformatic analysis of the protein and microRNA cargo of EVs identified peroxisome proliferator-activated receptor α (PPARα) as a primary molecular target of astrocyte-shed EVs. We confirmed in mice that astrocytic EVs promoted the transmigration of leukocytes into the brain by inhibiting PPARα, resulting in the increase of nuclear factor κB (NF-κB) activity that triggered the production of cytokines in liver. These findings expand our understanding of the mechanisms regulating communication between the brain and peripheral immune system and identify astrocytic EVs as a molecular regulator of the immunological response to inflammatory brain damage.
Einleitung (1973)

Unternehmungen stehen zur Bewältigung ihrer Aufgaben drei Erfüllungsalternativen zur Verfügung1):
Polarity of transcriptional enhancement revealed by an insulator element (2000)

Transcriptional enhancers for genes transcribed by RNA polymerase II may be localized upstream or downstream of the stimulated promoter in their normal chromosomal context. They stimulate transcription in an orientation-independent manner when assayed on circular plasmids. We describe a transient transformation system to evaluate the orientation preference of transcriptional enhancers in Drosophila. To accomplish this, the gypsy insulator element was used to block bidirectional action of an enhancer on circular plasmids. In this system, as in the chromosome, blocking of enhancer activity requires wild-type levels of the su(Hw) protein. We evaluated the orientation preference for the relatively large (4.4 kb) Adh larval enhancer from Drosophila melanogaster, used in conjunction with a luciferase reporter gene under the control of a minimal Adh promoter. An orientation preference was revealed by insertion of a single copy of the insulator between the enhancer and the promoter. This orientation effect was greatly amplified when the promoter was weakened by removing binding sites for critical transcription factors, consistent with a mechanism of insulator action in which the insulator intercepts signals from the enhancer by competing with the promoter. The orientation preference, as much as 100-fold, is a property of the enhancer itself because it is displayed by gene constructions introduced into the chromosome regardless of the presence of the insulator in a distal location. These findings are most easily reconciled with a facilitated tracking mechanism for enhancer function in a native chromosomal environment.
The murine interleukin 2 receptor. Irreversible cross-linking of radiolabeled interleukin 2 to high affinity interleukin 2 receptors reveals a noncovalently associated subunit. (1987)

The murine interleukin 2 (IL-2) receptor is a 55- to 60-kDa glycoprotein (p58) that binds IL-2 at a high and low affinity. In this investigation, we have identified sublines of EL4 that vary in their capacity to express high affinity IL-2 receptors after transfection of the IL-2 receptor cDNA. These and other cell populations were used to determine whether unique membrane molecules were specifically associated with the high affinity IL-2 receptor. Irreversible chemical cross-linking of [125I]IL-2 to only high affinity IL-2 receptors resulted in detection of IL-2 cross-linked to p58 as a 70- to 75-kDa band and other complexes of 90 to 95 kDa, 115 kDa, 150 kDa, 170 to 190 kDa, and 245 kDa. Antibodies specific for p58 resulted in precipitation of each of these complexes. However, disruption of noncovalent interactions prior to immunoprecipitation resulted in an inability to detect the material at 90 to 95 kDa. Therefore, we conclude that this complex most likely represented IL-2 cross-linked to a 75- to 80-kDa subunit that was noncovalently associated with p58. The other complexes greater than 150 kDa may represent these subunits cross-linked to each other. The detection of all the cross-linked complexes larger than 75 kDa appeared to be directly related to formation of high affinity IL-2 receptors because IL-2 was cross-linked only to p58 for three cell lines that exclusively expressed low affinity IL-2 receptors. Thus, high affinity murine IL-2 receptors are comprised of at least one alpha (p58)- and beta (p75)-subunit. Our data also raise the possibility of a more complex subunit structure.
Developing and mature oligodendrocytes respond differently to the immune cytokine interferon-gamma (1998)

Increasing evidence suggests that the immune cytokine interferon-gamma (IFN-gamma) plays a deleterious role in immune-mediated demyelinating disorders. To further understand the effects of IFN-gamma on oligodendrocytes, we have compared and quantitated the response of developing and mature oligodendrocytes in vitro to IFN-gamma and have observed several differences. Morphological changes and cell death occurred in developing cultures after 2 days in IFN-gamma, and in mature oligodendrocytes after 4-7 days. Developing oligodendrocytes underwent significantly increased apoptotic cell death in the presence of IFN-gamma, but mature oligodendrocytes exposed to IFN-gamma died of necrosis. Prior to morphological changes or cell death in mature oligodendrocytes exposed to IFN-gamma, steady-state levels of myelin-specific mRNAs and proteins were reduced. Thus, these results indicate that the sensitivity of oligodendrocytes to IFN-gamma is related to the developmental state of the cell. Such information is crucial for understanding the response of oligodendrocytes in immune-mediated demyelinating disorders and during remyelination in these diseases.
Cerebral hemodynamics in preterm infants during positional intervention measured with diffuse correlation spectroscopy and transcranial Doppler ultrasound (2009)

Four very low birth weight, very premature infants were monitored during a 12 degrees postural elevation using diffuse correlation spectroscopy (DCS) to measure microvascular cerebral blood flow (CBF) and transcranial Doppler ultrasound (TCD) to measure macrovascular blood flow velocity in the middle cerebral artery. DCS data correlated significantly with peak systolic, end diastolic, and mean velocities measured by TCD (p(A) =0.036, 0.036, 0.047). Moreover, population averaged TCD and DCS data yielded no significant hemodynamic response to this postural change (p>0.05). We thus demonstrate feasibility of DCS in this population, we show correlation between absolute measures of blood flow from DCS and blood flow velocity from TCD, and we do not detect significant changes in CBF associated with a small postural change (12 degrees ) in these patients.
The Fusion of Broken Ends of Chromosomes Following Nuclear Fusion (1942)

This article, written during McClintock's very active period of research on the breakage-fusion-bridge (BFB) cycle, addressed
 some specific questions regarding the necessary conditions under which BFB occurred.
Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients (2016)

Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus are a common and predictable problem in transplant recipients. While cellular immune therapies have been successfully used to tackle infectious complications in transplant recipients, manufacturing immunotherapies to address the multitude of possible pathogens can be technically challenging and labor-intensive. Here we describe a novel adenoviral antigen presentation platform (Ad-MvP) as a tool for rapid generation of multivirus-specific T-cells in a single step. Ad-MvP encodes 32 CD8+ T-cell epitopes from cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus as a contiguous polyepitope. We demonstrate that Ad-MvP vector can be successfully used for rapid in vitro expansion of multivirus-specific T-cells from transplant recipients and in vivo priming of antiviral T-cell immunity. Most importantly, using an in vivo murine model of Epstein-Barr virus-induced lymphoma, we also show that adoptive immunotherapy with Ad-MvP expanded autologous and allogeneic multivirus-specific T-cells is highly effective in controlling Epstein-Barr virus tumor outgrowth and improving overall survival. We propose that Ad-MvP has wide ranging therapeutic applications in greatly facilitating in vivo priming of antiviral T-cells, the generation of third-party T-cell banks as "off-the-shelf" therapeutics as well as autologous T-cell therapies for transplant patients.
Resistance of lymphocytic choriomeningitis virus to alpha/beta interferon and to gamma interferon (1994)

The susceptibility to alpha/beta interferon (IFN-alpha/beta) or to gamma interferon (IFN-gamma) of various lymphocytic choriomeningitis virus (LCMV) strains was evaluated in C57BL/6 mice and in various cell lines. Anti-IFN-gamma treatment in vivo revealed that the LCMV strains Armstrong, Aggressive, and WE were most susceptible to IFN-gamma whereas Traub, Cl 13-Armstrong, and Docile were resistant. The same pattern of susceptibility to recombinant IFN-gamma was observed in vitro. In vivo treatment with anti-IFN-alpha/beta showed a sizeable increase in replication of Aggressive, Armstrong, and WE; effects were less pronounced for Docile, Cl 13-Armstrong, or Traub. Correspondingly, WE, Armstrong, and Aggressive were all relatively sensitive to purified IFN-alpha/beta in vitro, and Cl 13-Armstrong, Docile, and Traub were more resistant. Overall, there was a good correlation between the capacity of LCMV strains to establish a persistent infection in adult immunocompetent mice and their relative resistance to IFN-gamma and IFN-alpha/beta.
Nipple Aspirate Cytology for the Study of Breast Cancer Precursors<xref ref-type="fn" rid="FN2">2</xref> (1983)

The association of abnormal nonmalignant cells in nipple aspirate fluid (NAF) and atypical proliferative disease (APD) of breast ducts was examined in the presence and absence of breast cancer in 134 patients. A high frequency of NAF samples with cellular abnormalities (atypical hyperplasia) was found when APD occurred with either breast cancer (70%) or benign breast biopsy specimens (54%). APD was present in 27 malignant cases (80%) and in 39 benign cases (39%). Inasmuch as APD may represent an intermediate step in the malignant transformation of duct epithelium, the cytologic examination of NAF offers a new approach with which to study the spectrum of breast cancer precursors and to assist in identifying women at risk for breast cancer.
Calculating the dielectric anisotropy of nematic liquid crystals: a reinvestigation of the Maier–Meier theory (2009)

This paper investigates the average dielectric permittivity () in the Maier–Meier theory for calculating the dielectric anisotropy (Δe) of nematic liquid crystals. For the reason that of nematics has the same expression as the dielectric permittivity of the isotropic state, the Onsager equation for isotropic dielectric was used to calculate it. The computed shows reasonable agreement with the results of the numerical methods used in the literature. Molecular parameters, such as the polarizability and its anisotropy, the dipole moment and its angle with the molecular long axis, were taken from semi-empirical quantum chemistry (MOCPAC/AM1) modeling. The calculated values of Δe according to the Maier–Meier equation are in good agreement with the experimental results for the investigated compounds having different core structures and polar substituents.
Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart (2008)

Toll-like receptors (TLRs) represent the first line of host defense against microbial infection and play a pivotal role in both innate and adaptive immunity. TLRs recognize invading pathogens through molecular pattern recognition, transduce signals via distinct intracellular pathways involving a unique set of adaptor proteins and kinases, and ultimately lead to the activation of transcription factors and inflammatory responses. Among 10 TLRs identified in humans, at least two exist in the heart, i.e., TLR2 and TLR4. In addition to the critical role of these in mediating cardiac dysfunction in septic conditions, emerging evidence suggests that the TLRs can also recognize endogenous ligands and may play an important role in modulating cardiomyocyte survival and in ischemic myocardial injury. In animal models of ischemia-reperfusion injury or in hypoxic cardiomyocytes in vitro, the administration of a sublethal dose of lipopolysaccharide, which signals through TLR4, reduces subsequent myocardial infarction, improves cardiac functions, and attenuates cardiomyocyte apoptosis. By contrast, a systemic deficiency of TLR2, TLR4, or myeloid differentiation primary-response gene 88, an adaptor critical for all TLR signaling, except TLR3, leads to an attenuated myocardial inflammation, a smaller infarction size, a better preserved ventricular function, and a reduced ventricular remodeling after ischemic injury. These loss-of-function studies suggest that both TLRs contribute to myocardial inflammation and ischemic injury in the heart although the exact contribution of cardiac (vs. circulatory cell) TLRs remains to be defined. These recent studies demonstrate an emerging role for TLRs as a critical modulator in both cell survival and tissue injury in the heart.
Progestins and antiprogestins in mammary tumour growth and metastasis (1994)

Growth of the normal mammary gland involves proliferation, differentiation, programmed cell death and remodelling of the basement membrane throughout the cyclic ovarian stimulation of the menstrual cycle and the pregnancy/lactation cycle. The regulation of these processes involves a balance between the actions of oestrogen and progesterone. Although it is generally accepted that oestrogens are the major adverse hormonal factor in onset and progression of human breast cancer, recent studies suggest that progesterone and its synthetic progestins may be more important than oestrogen as an ovarian stimulus in driving proliferation of normal human and rodent mammary epithelium. One might expect that some aspects of these complex progestin-regulated events might be retained in breast cancer. This review focuses on evidence that progesterone has proliferative actions in breast cancers; on the role of progestins in regulation of metastasis-related adhesion molecules on breast cancer cells and on the preliminary data showing that progesterone antagonists may be powerful new tools for the management of metastastic breast cancer. This evidence suggests that progesterone is a stimulus for onset and progression of breast tumours and that antiprogestins can interrupt these processes.
Microfabricated Porous Membrane Structure for Sample Concentration and Electrophoretic Analysis (1999)

A microfabricated injection valve incorporating a porous membrane structure is reported that enables electrokinetic concentration of DNA samples using homogeneous buffer conditions followed by injection into a channel for electrophoretic analysis. The porous membrane was incorporated in the microchannel manifold by having two channels separated from each other by 3-12 microns and connected by a thin porous silicate layer. This design allows the passage of current to establish an electrical connection between the separated channels but prevents large molecules, e.g., DNA, from traversing the membrane. Concentrated DNA can be injected into the separation channel and electrophoretically analyzed. Experiments exhibit a nonlinear increase in concentration with time, and DNA fragments can be concentrated up to 2 orders of magnitude as shown by comparison of peak intensities for analysis performed with and without concentration.
Continous haemodynamic monitoring during withdrawal of diuretics in patients with congestive heart failure (2002)

Haemodynamic changes due to increased volume load can be detected with an implantable haemodynamic monitor. Such data provide useful information for tailoring an optimal diuretic dose in patients with congestive heart failure.
CZT detector for dual-energy x-ray absorptiometry (DEXA) (2000)

A cadmium-zinc-telluride (CZT) detector has been developed for a bone densitometer that uses dual-energy x-ray absorptiometry (DEXA) to determine bone mineral density in vivo. A linear array of 16 discrete CZT detectors is used with a narrow fan-shaped x-ray beam to scan the patient. Each detector is 3 mm thick and 7 mm by 3 mm in area and has simple planar contacts. The x-ray beam has two broad energy lobes with effective energies of approximately 38 keV and approximately 65 keV. The energy sensitivity of the CZT detectors allows discrimination between low and high energy x-rays. Using DEXA, the relative difference in these two count rates permits a quantitative measurement of the real densities of bone mineral and soft tissue. The detectors demonstrate good performance characteristics and stable operation in a clinical environment. This paper discusses the suitability of CZT for use in DEXA applications and describes its successful implementation and performance in this bone densitometer.
Short Takeoff Performance using Circulation Control (2008)

Historically, powered lift takeoff analysis has been prohibitively expensive for use in preliminary design. For powered lift, the coupling of aircraft systems invalidates traditional simplistic methods often used in early aircraft sizing. This research creates a tool that will automate the process of takeoff and balanced field length calculations for a circulation control wing aircraft. The process will use high fidelity techniques, such as computational fluid dynamics in order to capture the coupled effects present in circulation control along with Gaussian processes to create a metamodel of that same data to be implemented in a modular takeoff/BFL model. The model was used to examine the performance of a STOL transport and it showed an optimal flap deflection of 64˚ and diminishing returns on mass flow rates exceeding 12 kg/s. Additional analysis of the STOL transport showed that delaying either the mass flow or the flap deflection until later in the ground roll reduced the balanced field length by up to 8%. In the process of creating the takeoff code, additional consideration was put into the determination of the rotation velocity. It was found that a relationship between lift to weight better defined the rotation velocity with the circulation control model and was found to be within about 10% of traditional techniques.
Fetal growth and infantile colic (2000)

Low birth weight may be associated with infantile colic, and further research will be aimed to focus on fetal growth and infantile colic.
One-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering (2013)

The development of facile and versatile strategies for thin-film and particle engineering is of immense scientific interest. However, few methods can conformally coat substrates of different composition, size, shape, and structure. We report the one-step coating of various interfaces using coordination complexes of natural polyphenols and Fe(III) ions. Film formation is initiated by the adsorption of the polyphenol and directed by pH-dependent, multivalent coordination bonding. Aqueous deposition is performed on a range of planar as well as inorganic, organic, and biological particle templates, demonstrating an extremely rapid technique for producing structurally diverse, thin films and capsules that can disassemble. The ease, low cost, and scalability of the assembly process, combined with pH responsiveness and negligible cytotoxicity, makes these films potential candidates for biomedical and environmental applications.
Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial (2012)

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (–18 min (P = 0.02)) and WASO (–54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.
Synthesis and structure activity relationships of potent new angiotensin converting enzyme inhibitors containing saturated bicyclic amino acids (1987)

The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfhydryl and non-sulfhydryl ACE inhibitors to give compounds equipotent to captopril and enalapril both in vitro and in vivo. Structure-activity relationships are discussed. Compound 11a (CI-907, indolapril) has advanced to clinical evaluation.