gebhart/patrepeval huggingface dataset:
Running stability is enhanced by a proximo-distal gradient in joint neuromechanical control (2007)

We currently know little about how animals achieve dynamic stability when running over uneven and unpredictable terrain, often characteristic of their natural environment. Here we investigate how limb and joint mechanics of an avian biped, the helmeted guinea fowl Numida meleagris, respond to an unexpected drop in terrain during running. In particular, we address how joint mechanics are coordinated to achieve whole limb dynamics. Based on muscle-tendon architecture and previous studies of steady and incline locomotion, we hypothesize a proximo-distal gradient in joint neuromechanical control. In this motor control strategy, (1) proximal muscles at the hip and knee joints are controlled primarily in a feedforward manner and exhibit load-insensitive mechanical performance, and (2) distal muscles at the ankle and tarsometatarso-phalangeal (TMP) joints are highly load-sensitive, due to intrinsic mechanical effects and rapid, higher gain proprioceptive feedback. Limb kinematics and kinetics during the unexpected perturbation reveal that limb retraction, controlled largely by the hip, remains similar to level running throughout the perturbed step, despite altered limb loading. Individual joints produce or absorb energy during both level and perturbed running steps, such that the net limb work depends on the balance of energy among the joints. The hip maintains the same mechanical role regardless of limb loading, whereas the ankle and TMP switch between spring-like or damping function depending on limb posture at ground contact. Initial knee angle sets limb posture and alters the balance of work among the joints, although the knee contributes little work itself. This distribution of joint function results in posture-dependent changes in work performance of the limb, which allow guinea fowl to rapidly produce or absorb energy in response to the perturbation. The results support the hypothesis that a proximo-distal gradient exists in limb neuromuscular performance and motor control. This control strategy allows limb cycling to remain constant, whereas limb posture, loading and energy performance are interdependent. We propose that this control strategy provides simple, rapid mechanisms for managing energy and controlling velocity when running over rough terrain.
Specific interaction between Lex and Lex Determinants (1989)

The Lex determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc-beta 1----R) has been implicated as having a role in mediating compaction of the mouse embryo at the morula stage (Fenderson, B., Zehavi, U., and Hakomori, S. (1984) J. Exp. Med. 160, 1591-1596). Here, we present evidence suggesting a role for Lex in F9 embryonal carcinoma cell adhesion and a mechanism for Lex recognition based on carbohydrate-carbohydrate interaction. Homotypic aggregation of F9 cells was inhibited by lacto-N-fucopentaose III, and F9 cells showed a preferential interaction with Lex liposomes. The following observations suggest that the structure capable of recognizing Lex per se on F9 cells is Lex: (i) Cell surface-labeled components solubilized in octylglucoside, affinity-bound on an Lex-octyl-Sepharose column, contained glycoproteins reactive with anti-Lex antibody. (ii) Liposomes containing Lex showed significant interaction with Lex glycolipid, but not other glycolipids, coated on a plastic surface. (iii) Liposomes containing Lex glycolipid were found to self-aggregate, whereas liposomes containing paragloboside (nLc4) or sialylparagloboside (IV3NeuAcnLc4) did not. (iv) The diffusibility of 3H-labeled lacto-N-fucopentaitol III (but not I or II), incubated with Lex liposome, from the lower to the upper Boyden chamber through a semipermeable membrane was inhibited. In all these experiments (i-iv), the interaction of Lex to Lex (or Lex to lacto-N-fucopentaose III) was clearly observed only in the presence of Ca2+ and Mg2+ and was enhanced by the presence of Mn2+. These interactions were inhibited by EDTA. The results suggest the novel hypothesis that carbohydrate-carbohydrate interactions may play an important role in controlling cell recognition during F9 cell aggregation and during embryonic development.
Late enlargement of radiofrequency lesions in infant lambs. Implications for ablation procedures in small children. (1994)

RF lesion formation in immature sheep myocardium is similar to that in adult myocardium acutely but is associated with late lesion enlargement and fibrous tissue invasion of normal myocardium. These findings may have implications for clinical RF ablation procedures in infants.
Vagal Stimulation Reduces the Severity of Maximal Electroshock Seizures in Intact Rats: Use of a Cuff Electrode for Stimulating and Recording (1991)

J. Zabara showed that repetitive vagal stimulation (VS) prevents or ameliorates convulsive seizures in dogs. We have studied the effects of VS on maximal electroshock seizures (MES) in intact rats: (1) A 5 wire cuff electrode was developed for stimulating and recording from the vagus. Compound action potentials (AP) were recorded and strength-duration curves obtained for A and C fibers. There is a monotonic relationship with a negative slope between heart rate (HR) and AP amplitude. C fibers remain excitable for 25 days after cuff implant. (2) The anticonvulsant efficacy of VS is directly related to the fraction of vagal C fibers stimulated and the frequency of stimulation. (3) The anticonvulsant efficacy of VS has been established using two rat models of human epilepsy. VS abolishes the extensor component of the tonic phase of a MES and shortens or prevents tonic seizures induced by pentylenetetrazol (PTZ). (4) VS appears to act via release of large quantities of the inhibitory mediators GABA and glycine throughout large volumes of the brain. (5) It is rational to test VS in man as a treatment for intractable seizures.
Clinical practice review on telehealth for managing a population with chronic urinary tract infections during the COVID-19 pandemic (2022)

Abstract: Population health management (PHM) is an essential health infrastructure that relies on collaborative data and interprofessional co-production to manage patients with long term conditions. PHM for patients with chronic urinary tract infections (UTIs) and lower urinary tract symptoms is the anchor for a holistic approach to bladder health. The COVID-19 pandemic has hastened the use of digital health technology including telehealth to manage patients diagnosed with chronic illnesses. The aim of this clinical practice review was to identify the key successes of telehealth when caring for a population diagnosed with a chronic UTI during the COVID-19 pandemic. We searched PubMed and CINHAL Plus for publications dated between December 2019 and April 2022. We gathered key data on PHM and UTIs from several countries around the world, including the countries that had a healthcare system driven by PHM for long term chronic illnesses. PHM is recognized as an integrative, holistic and data driven approach to managing patients with a chronic UTI. Although there are many advantages of an integrated evidence-based approach for managing patients with chronic UTI, there are also the challenges of interprofessional theories that become a barrier to providing a consistent collaborative care. The available literature on telehealth, PHM and chronic UTIs has evidenced the successful outcomes during the COVID-19 pandemic. It is certain that PHM for patients with chronic UTIs is a sustainable and cost-efficient program that will streamline care provision now and in the future.
Combination therapy targeting ectopic ATP synthase and 26S proteasome induces ER stress in breast cancer cells (2014)

F1Fo ATP synthase is present in all organisms and is predominantly located on the inner membrane of mitochondria in eukaryotic cells. The present study demonstrated that ATP synthase and electron transport chain complexes were ectopically expressed on the surface of breast cancer cells and could serve as a potent anticancer target. We investigated the anticancer effects of the ATP synthase inhibitor citreoviridin on breast cancer cells through proteomic approaches and revealed that differentially expressed proteins in cell cycle regulation and in the unfolded protein response were functionally enriched. We showed that citreoviridin triggered PERK-mediated eIF2α phosphorylation, which in turn attenuated general protein synthesis and led to cell cycle arrest in the G0/G1 phase. We further showed that the combination of citreoviridin and the 26S proteasome inhibitor bortezomib could improve the anticancer activity by enhancing ER stress, by ameliorating citreoviridin-caused cyclin D3 compensation, and by contributing to CDK1 deactivation and PCNA downregulation. More interestingly, the combined treatment triggered lethality through unusual non-apoptotic caspase- and autophagy-independent cell death with a cytoplasmic vacuolization phenotype. The results imply that by boosting ER stress, the combination of ATP synthase inhibitor citreoviridin and 26S proteasome inhibitor bortezomib could potentially be an effective therapeutic strategy against breast cancer.
Intramolecular Hydroamination of Aminoalkynes with Silver−Phenanthroline Catalysts (2008)

Intramolecular hydroamination of several aminoalkynes catalyzed by silver-phenanthroline complexes is reported. This catalyst system complements previous protocols by employing air- and moisture-stable complexes without compromising activity or reaction control. Some of the hydroamination products are subject to a useful aerobic oxidation. Silver-phenanthroline complexes have successfully demonstrated efficacy in the desymmetrization of a prochiral diyne.
AXL Inhibition Sensitizes Mesenchymal Cancer Cells to Antimitotic Drugs (2014)

Molecularly targeted drug therapies have revolutionized cancer treatment; however, resistance remains a major limitation to their overall efficacy. Epithelial-to-mesenchymal transition (EMT) has been linked to acquired resistance to tyrosine kinase inhibitors (TKI), independent of mutational resistance mechanisms. AXL is a receptor tyrosine kinase associated with EMT that has been implicated in drug resistance and has emerged as a candidate therapeutic target. Across 643 human cancer cell lines that were analyzed, elevated AXL was strongly associated with a mesenchymal phenotype, particularly in triple-negative breast cancer and non-small cell lung cancer. In an unbiased screen of small-molecule inhibitors of cancer-relevant processes, we discovered that AXL inhibition was specifically synergistic with antimitotic agents in killing cancer cells that had undergone EMT and demonstrated associated TKI resistance. However, we did not find that AXL inhibition alone could overcome acquired resistance to EGFR TKIs in the EMT setting, as previously reported. These findings reveal a novel cotreatment strategy for tumors displaying mesenchymal features that otherwise render them treatment refractory.
Rapid Induction of Androgen Receptor Splice Variants by Androgen Deprivation in Prostate Cancer (2014)

AR-V7 at these low levels is not adequate to restore AR activity, but its rapid induction after androgen deprivation allows tumors to retain basal AR activity that may be needed for survival until more potent mechanisms emerge to activate AR. Agents targeting AR splice variants may be most effective when used very early in conjunction with therapies targeting the AR ligand-binding domain.
Rail and turnout detection using gradient information and template matching (2013)

This paper presents a railway track and turnout detection algorithm which is not based on an empirical threshold. The railway track extraction is based on an edge detection using the width of the rolling pads. This edge detection scheme is then used as an input to the RANSAC algorithm to determine the model of the rails. The turnout detection scheme is based on the Histogram of Oriented Gradient (HOG) and Template Matching (TM). The results show (i) reliable performance for our railway track extraction scheme and (ii) a correction rate of 97.31 percent for the turnout detection scheme using a Support Vector Machine (SVM) classifier.
Reasons for Revision Hip Surgery (2004)

The purpose of this study was to determine the indications for contemporary revision hip surgery in a consecutive series of patients. We retrospectively reviewed the clinical records and radiographs of 439 revision hip surgeries done between 1996 and 2003. Fifty-five percent of the surgeries were for aseptic loosening, 14% were for instability, 13% were for osteolysis around a well-fixed implant, 7% were for infection, 5% were for periprosthetic fracture, 3% were for conversion of a hemiarthroplasty, 1% was for psoas impingement, 1% was for loose recalled implants, and 1% was for implant fracture. As expected, aseptic loosening was the most common reason for revision surgery. Instability was a common reason for early revision whereas revision for osteolysis around a well-fixed implant was a more common reason for late revision.
A new family of sugar-inducible expression vectors for Escherichia coli (1991)

A set of 11 expression vectors was constructed, each of them harbouring a cloning cassette under the control of the araB promoter. Some of these vectors enable expression of foreign proteins in the cytoplasm, while others include a synthetic sequence coding for a very efficient secretion signal sequence. Other features are an f1 origin of replication (in plus or minus orientation) and a promoter(up) mutation that enhances the already very high level of expression from these vectors. With such a versatile vector family, cloning, sequencing and site-directed mutagenesis can be performed on the same vector, and the level of expression can be defined according to the specific constraints of a given protein.
A Low Curing Temperature Silver Ink for Use in Ink‐Jet Printing and Subsequent Production of Conductive Tracks (2005)

Abstract Summary: A drop‐on‐demand ink‐jet printer has been used to print a silver‐organic solution onto glass substrates. Conductive silver tracks were obtained by heat treatment of the ink‐jet printed deposits at temperatures ranging from 125 °C–200 °C in air. Resistivity values were found to have dropped to two to three times the theoretical resisitivity of bulk silver after temperatures of 150 °C and above were used. Resistivity values of a silver‐based ink. magnified image Resistivity values of a silver‐based ink.
Constituents of Human Milk (1996)

Breastmilk contains all the nutrients required by the newborn baby. It also contains non-nutritional components that may promote infant health, growth, and development, such as antimicrobial factors, digestive enzymes, hormones, trophic factors, and growth modulators. In some situations, breastmilk may also contain harmful components, such as pollutants, drugs, allergens, and viruses. Human milk has a unique composition, which differs from that of other mammals in its ingredients and their concentrations. Breastmilk composition is not constant and varies with stage of lactation, breastfeeding pattern, season, and parity. It also differs among individuals and among communities, for reasons that are not well understood. Maternal nutrition is an obvious candidate, but the situation is complex. Supplementation studies and cross-cultural comparisons have demonstrated that the total concentrations of fat, protein, and lactose are relatively insensitive to current dietary intake and nutritional status, whereas the fatty acid profile and the concentrations of several micronutrients, particularly water-soluble vitamins, are responsive to maternal diet. For many infants, nutrient intake from breastmilk becomes insufficient after four to six months, and other foods should be added to the diet. Nevertheless, breastmilk can continue to be a valuable nutrient source and to provide non-nutritional factors even for older children. Consequently, breastfeeding for one to two years as part of a mixed diet has many advantages, particularly for children living in impoverished circumstances.
Atomic Layer Deposition on Biological Macromolecules:  Metal Oxide Coating of Tobacco Mosaic Virus and Ferritin (2006)

Decoration of nanoparticles, in particular biomolecules, gathered high attention in recent years.(1-7) Of special interest is the potential use of biomolecules as templates for the fabrication of semiconducting or metallic nanostructures.(1-7,26) In this work we show the application of atomic layer deposition, a gas-phase thin film deposition process, to biological macromolecules, which are frequently used as templates in nanoscale science, and the possibility to fabricate metal oxide nanotubes and thin films with embedded biomolecules.(1-13).
Soluble IL-6 Receptor Governs IL-6 Activity in Experimental Arthritis: Blockade of Arthritis Severity by Soluble Glycoprotein 130 (2003)

Studies in IL-6-deficient (IL-6(-/-)) mice highlight that IL-6 contributes to arthritis progression. However, the molecular mechanism controlling its activity in vivo remains unclear. Using an experimental arthritis model in IL-6(-/-) mice, we have established a critical role for the soluble IL-6R in joint inflammation. Although intra-articular administration of IL-6 itself was insufficient to reconstitute arthritis within these mice, a soluble IL-6R-IL-6 fusion protein (HYPER-IL-6) restored disease activity. Histopathological assessment of joint sections demonstrated that HYPER-IL-6 increased arthritis severity and controlled intrasynovial mononuclear leukocyte recruitment through the CC-chemokine CCL2. Activation of synovial fibroblasts by soluble IL-6R and IL-6 emphasized that these cells may represent the source of CCL2 in vivo. Specific blockade of soluble IL-6R signaling in wild-type mice using soluble gp130 ameliorated disease. Consequently, soluble IL-6R-mediated signaling represents a promising therapeutic target for the treatment of rheumatoid arthritis.
Synthetic Studies of Amphotericin B. II. A Facile Synthesis of the C-1–C-12 Segments of the Amphotericin B Aglycon (1987)

Abstract 3-Deoxy-1,2-O-isopropylidene-α-d-glycero-d-erythro-pentofuranose (11) was stereoselectively converted into the Witting salt 8 corresponding to the C-1–C-6 portion of amphotericin B aglycon (1) in 57% overall yield in 8 steps. The aldehydic segment 9 or 10 corresponding to the C-7–C-12 portion of 1 was also derived in 6 steps from 11 in 53 or 38% overall yield, respectively. Wittig condensation of 8 with 9 or 10 followed by four-step conversion afforded the C-1–C-12 segment, (3S,5R,8R,9R,11S)-1-O-t-butyldimethylsilyl-12-iodo-3,5:8,9-di-O-isopropylidene-11-O-[(2-methoxyethoxy)methyl]-1,3,5,8,9,11-dodecanehexol(4)or(2S,4R,5R,8R,10S)-1,2-anhydro-12-O-t-butyldimethylsilyl-4,5:8,10-di-O-isopropylidene-1,2,4,5,8,10,12-dodecaneheptol (5) in 26 or 15% overall yield from 11, respectively.
Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc−/−mice improves engraftment of human hematopoietic cells in humanized mice (2011)

Transplantation of human hematopoietic stem cells into severely immunocompromised newborn mice allows the development of a human hematopoietic and immune system in vivo. NOD/scid/γ(c)(-/-) (NSG) and BALB/c Rag2(-/-)γ(c)(-/-) mice are the most commonly used mouse strains for this purpose and a number of studies have demonstrated the high value of these model systems in areas spanning from basic to translational research. However, limited cross-reactivity of many murine cytokines on human cells and residual host immune function against the xenogeneic grafts results in defective development and maintenance of human cells in vivo. Whereas NSG mice have higher levels of absolute human engraftment than similar mice on a BALB/c background, they have a shorter lifespan and NOD ES cells are unsuitable for the complex genetic engineering that is required to improve human hematopoiesis and immune responses by transgenesis or knockin of human genes. We have generated mice that faithfully express a transgene of human signal regulatory protein alpha (SIRPa), a receptor that negatively regulates phagocytosis, in Rag2(-/-)γ(c)(-/-) mice on a mixed 129/BALB/c background, which can easily be genetically engineered. These mice allow significantly increased engraftment and maintenance of human hematopoietic cells reaching levels comparable to NSG mice. Furthermore, we found improved functionality of the human immune system in these mice. In summary, hSIRPa-transgenic Rag2(-/-)γ(c)(-/-) mice represent a unique mouse strain supporting high levels of human cell engraftment, which can easily be genetically manipulated.
Cost of tumor necrosis factor blockers per patient with rheumatoid arthritis in a multistate Medicaid population (2014)

Etanercept had lower costs per treated patient than adalimumab or infliximab in both new and continuing Medicaid enrollees with RA.
Invariant chain alters the malignant phenotype of MHC class II+ tumor cells (1992)

T lymphocytes usually recognize endogenously encoded Ag in the context of MHC class I molecules, whereas exogenous Ag is usually presented by MHC class II molecules. In vitro studies in model systems suggest that presentation of endogenous Ag by class II molecules is inhibited by the association of class II with its invariant chain (Ii). In the present study we test this hypothesis in an in vivo system in which endogenously encoded tumor peptides are presented by tumor cell MHC class II molecules. In this system, transfection of syngeneic MHC class II genes (Aak and Abk) into a highly malignant, Ii negative, mouse tumor (SaI sarcoma) produces an immunogenic tumor (SaI/Ak) that is rejected by the autologous host. The class II+ transfectants also effectively immunize autologous A/J mice against a subsequent challenge of wild-type class II- tumor cells. We have hypothesized that the SaI/Ak transfectants induce protective immunity because they function as APC for endogenously synthesized tumor peptides, and thereby stimulate tumor-specific Th cells, by-passing the need for professional APC. To test the role of Ii as an inhibitor of presentation of endogenous peptides, SaI/Ak tumor cells were supertransfected with Ii gene (SaI/Ak/Ii cells), and the tumorigenicity of the resulting cells determined. Nine SaI/Ak/Ii clones were tested, and their malignancy compared with that of SaI/Ak and SaI cells. Seven of the nine class II+/Ii+ tumor cells are more malignant than class II+/Ii- tumor cells in autologous A/J mice. Expression of Ii therefore restores the malignant phenotype, presumably by preventing presentation of endogenously synthesized tumor peptides. Ii therefore regulates Ag presentation and can be a critical parameter for in vivo tumor immunity.
Brownian dynamics with hydrodynamic interactions (1978)

A method for simulating the Brownian dynamics of N particles with the inclusion of hydrodynamic interactions is described. The particles may also be subject to the usual interparticle or external forces (e.g., electrostatic) which have been included in previous methods for simulating Brownian dynamics of particles in the absence of hydrodynamic interactions. The present method is derived from the Langevin equations for the N particle assembly, and the results are shown to be consistent with the corresponding Fokker–Planck results. Sample calculations on small systems illustrate the importance of including hydrodynamic interactions in Brownian dynamics simulations. The method should be useful for simulation studies of diffusion limited reactions, polymer dynamics, protein folding, particle coagulation, and other phenomena in solution.