gebhart/patrepeval huggingface dataset:
Positive and negative regulation of granulopoiesis by endogenous RARα (2001)

Acute promyelocytic leukemia (APL) is always associated with chromosomal translocations that disrupt the retinoic acid receptor alpha (RARalpha) gene. Whether these translocations relate to a role for endogenous RARalpha in normal granulopoiesis remains uncertain because most studies addressing this question have used non-physiological overexpression systems. Granulocyte differentiation in cells derived from RARalpha-deficient (RARalpha(-/-)) mice was studied and evaluated in the context of agonist-bound and ligand-free RARalpha. Our results demonstrate that RARalpha is dispensable for granulopoiesis, as RARalpha(-/-) mice have a normal granulocyte population despite an impaired ability to respond to retinoids. However, although it is not absolutely required, RARalpha can bidirectionally modulate granulopoiesis. RARalpha stimulates differentiation in response to exogenous retinoic acid. Furthermore, endogenous retinoids control granulopoiesis in vivo, as either vitamin A-deficient mice or animals treated with an RAR antagonist accumulate more immature granulocytes in their bone marrow. Conversely, RARalpha acts to limit differentiation in the absence of ligand because granulocyte precursors from RARalpha(-/-) mice differentiate earlier in culture. Thus, the block in granulopoiesis exerted by RARalpha fusion proteins expressed in APL cells may correspond to an amplification of a normal function of unliganded RARalpha.
Marked differences in neurochemistry and aggregates despite similar behavioural and neuropathological features of Huntington disease in the full-length BACHD and YAC128 mice (2012)

The development of animal models of Huntington disease (HD) has enabled studies that help define the molecular aberrations underlying the disease. The BACHD and YAC128 transgenic mouse models of HD harbor a full-length mutant huntingtin (mHTT) and recapitulate many of the behavioural and neuropathological features of the human condition. Here, we demonstrate that while BACHD and YAC128 animals exhibit similar deficits in motor learning and coordination, depressive-like symptoms, striatal volume loss and forebrain weight loss, they show obvious differences in key features characteristic of HD. While YAC128 mice exhibit significant and widespread accumulation of mHTT striatal aggregates, these mHTT aggregates are absent in BACHD mice. Furthermore, the levels of several striatally enriched mRNA for genes, such as DARPP-32, enkephalin, dopamine receptors D1 and D2 and cannabinoid receptor 1, are significantly decreased in YAC128 but not BACHD mice. These findings may reflect sequence differences in the human mHTT transgenes harboured by the BACHD and YAC128 mice, including both single nucleotide polymorphisms as well as differences in the nature of CAA interruptions of the CAG tract. Our findings highlight a similar profile of HD-like behavioural and neuropathological deficits and illuminate differences that inform the use of distinct endpoints in trials of therapeutic agents in the YAC128 and BACHD mice.
Moderate endurance exercise is not a risk for rhabdomyolysis or renal failure in sickle cell trait carriers (2012)

This study tested the hypothesis that trained sickle cell trait (SCT) carriers are not subjected to greater risk of rhabdomyolysis or renal failure in response to moderate submaximal exercise than subjects with normal hemoglobin (CONT). Blood markers in 11 trained SCT carriers and 12 control counterparts were measured before and after 40 min of exercise at 55% of peak power output (Ppeak) conducted in thermoneutral environment. Body weights decreased with exercise in the same proportion in the two groups (from 65.1 ± 7.0 kg to 64.1 ± 7.0 kg and from 70.2 ± 6.6 to 68.6 ± 6.6 kg at the end of exercise in SCT and CONT, respectively). Heart rate and rectal temperature increased in the two groups in response to exercise, but the groups remained closely matched. Serum urea, CRP, CK and LDH were similar in the two groups and remained unchanged in response to exercise. Creatinine, Na(+), K(+), Cl(-) and myoglobin concentrations increased above baseline in response to exercise, with changes of the same magnitude in the two groups. In summary, the results of the present study suggest that moderate submaximal exercise is not unsafe from a biochemical point of view for sportsmen carrying SCT.
Association Between Myeloperoxidase Levels and Risk of Coronary Artery Disease (2001)

Elevated levels of leukocyte- and blood-MPO are associated with the presence of CAD. These findings support a potential role for MPO as an inflammatory marker in CAD and may have implications for atherosclerosis diagnosis and risk assessment.
Inhibition of established pancreatic cancers following specific active immunotherapy with interleukin-2 gene-transduced tumor cells. (1997)

Pancreatic cancer has a poor prognosis even when complete resection can be accomplished. Recent studies have demonstrated that the immune system is capable of mounting effective tumor-specific immune responses even against "nonimmunogenic" tumors. The studies reported herein were conducted to determine if induction of tumor-specific immune responses of inhibiting in vivo pancreatic tumor growth could be achieved through active immunization with pancreatic tumor cells genetically engineered to secrete interleukin-2 (IL-2). A relevant poorly immunogenic subcutaneous model of murine ductal pancreatic cancer was first developed using an implantable tumor cell line Panc02 in C57BL/6 mice. Panc02 cells were then genetically engineered to secrete human IL-2 (Panc02/IL2). The ability of irradiated Panc02/IL2 cells to stimulate an immune response capable of rejecting a subsequent tumor challenge was first demonstrated. Ninety percent of animals vaccinated with irradiated parental Panc02 and subsequently challenged with parental Panc02 cells developed tumors by 48 days (mean tumor volume of 234 mm3) compared to only 40% (P < .05, chi square) of animals vaccinated with irradiated Panc02/IL2 and challenged with parental Panc02 (14 mm3, P < .004, tau test). The therapeutic benefit of active immunization in tumor-bearing animals was then examined. Mice with 3-day-old established subcutaneous tumors were administered a series of 4 weekly vaccinations with irradiated Panc02 or Panc02/IL2 cells. A significant reduction in tumor growth was present in those animals vaccinated with Panc02/IL2 (P < .005, tau test) versus Panc02 or saline. Animals whose established tumors regressed following vaccinations with IL-2-secreting Panc02 cells were found to have long-lasting immunity as demonstrated by rejection of a tumor challenge presented over 140 days following inoculation of the primary tumor. We conclude that an immune response capable of inhibiting established pancreatic tumors can be generated by vaccination with IL-2-secreting tumor cells. Furthermore, long-term immunological memory was established in mice that rejected the original established tumor. These studies provide preclinical evidence to support the use of cytokine gene-transduced tumor cell vaccinations in patients with pancreatic cancer.
Noble Metals on the Nanoscale: Optical and Photothermal Properties and Some Applications in Imaging, Sensing, Biology, and Medicine (2008)

Noble metal nanostructures attract much interest because of their unique properties, including large optical field enhancements resulting in the strong scattering and absorption of light. The enhancement in the optical and photothermal properties of noble metal nanoparticles arises from resonant oscillation of their free electrons in the presence of light, also known as localized surface plasmon resonance (LSPR). The plasmon resonance can either radiate light (Mie scattering), a process that finds great utility in optical and imaging fields, or be rapidly converted to heat (absorption); the latter mechanism of dissipation has opened up applications in several new areas. The ability to integrate metal nanoparticles into biological systems has had greatest impact in biology and biomedicine. In this Account, we discuss the plasmonic properties of gold and silver nanostructures and present examples of how they are being utilized for biodiagnostics, biophysical studies, and medical therapy. For instance, taking advantage of the strong LSPR scattering of gold nanoparticles conjugated with specific targeting molecules allows the molecule-specific imaging and diagnosis of diseases such as cancer. We emphasize in particular how the unique tunability of the plasmon resonance properties of metal nanoparticles through variation of their size, shape, composition, and medium allows chemists to design nanostructures geared for specific bio-applications. We discuss some interesting nanostructure geometries, including nanorods, nanoshells, and nanoparticle pairs, that exhibit dramatically enhanced and tunable plasmon resonances, making them highly suitable for bio-applications. Tuning the nanostructure shape (e.g., nanoprisms, nanorods, or nanoshells) is another means of enhancing the sensitivity of the LSPR to the nanoparticle environment and, thereby, designing effective biosensing agents. Metal nanoparticle pairs or assemblies display distance-dependent plasmon resonances as a result of field coupling. A universal scaling model, relating the plasmon resonance frequency to the interparticle distance in terms of the particle size, becomes potentially useful for measuring nanoscale distances (and their changes) in biological systems. The strong plasmon absorption and photothermal conversion of gold nanoparticles has been exploited in cancer therapy through the selective localized photothermal heating of cancer cells. For nanorods or nanoshells, the LSPR can be tuned to the near-infrared region, making it possible to perform in vivo imaging and therapy. The examples of the applications of noble metal nanostructures provided herein can be readily generalized to other areas of biology and medicine because plasmonic nanomaterials exhibit great range, versatility, and systematic tunability of their optical attributes.
Dengue Fever, Hawaii, 2001–2002 (2005)

Autochthonous dengue infections were last reported in Hawaii in 1944. In September 2001, the Hawaii Department of Health was notified of an unusual febrile illness in a resident with no travel history; dengue fever was confirmed. During the investigation, 1,644 persons with locally acquired denguelike illness were evaluated, and 122 (7%) laboratory-positive dengue infections were identified; dengue virus serotype 1 was isolated from 15 patients. No cases of dengue hemorrhagic fever or shock syndrome were reported. In 3 instances autochthonous infections were linked to a person who reported denguelike illness after travel to French Polynesia. Phylogenetic analyses showed the Hawaiian isolates were closely associated with contemporaneous isolates from Tahiti. Aedes albopictus was present in all communities surveyed on Oahu, Maui, Molokai, and Kauai; no Ae. aegypti were found. This outbreak underscores the importance of maintaining surveillance and control of potential disease vectors even in the absence of an imminent disease threat.
PHYSICAL ASPECTS OF REVERSIBLE INACTIVATION OF ENDOTOXIN* (1966)

Peer Reviewed
Characterization of genes for a second Mo-dependent nitrogenase in the cyanobacterium Anabaena variabilis (1997)

Anabaena variabilis ATCC 29413 is a filamentous heterocystous cyanobacterium that fixes nitrogen under a variety of environmental conditions. Under aerobic growth conditions, nitrogen fixation depends upon differentiation of heterocysts and expression of either a Mo-dependent nitrogenase or a V-dependent nitrogenase in those specialized cells. Under anaerobic conditions, a second Mo-dependent nitrogenase gene cluster, nifII, was expressed in vegetative cells long before heterocysts formed. A strain carrying a mutant gene in the nifII cluster did not fix nitrogen under anaerobic conditions until after heterocysts differentiated. The nifII cluster was similar in organization to the nifI cluster that is expressed in heterocysts and that includes nifBSUHDKENXW as well as three open reading frames that are conserved in both cyanobacterial nif clusters.
ROCK‐I and ROCK‐II, two isoforms of Rho‐associated coiled‐coil forming protein serine/threonine kinase in mice (1996)

We recently identified a novel human protein kinase, p160 ROCK, as a putative downstream target of the small GTPase Rho. Using the human ROCK cDNA as a probe, we isolated cDNA of two distinct, highly related sequences from mouse libraries. One encoded a mouse counterpart of human ROCK (ROCK-I), and the other encoded a novel ROCK-related kinase (ROCK-II). Like ROCK/ROCK-I, ROCK-II also bound to GTP-Rho selectively. ROCK-I mRNA was ubiquitously expressed except in the brain and muscle, whereas ROCK-II mRNA was expressed abundantly in the brain, muscle, heart, lung and placenta. These results suggest that at least two ROCK isoforms are present in a single species and play distinct roles in Rho-mediated signalling pathways.
Purification and characterization of a protein tyrosine phosphatase containing SH2 domains. (1993)

A protein tyrosine phosphatase (PTP) containing two SH2 domains (PTP1C) was purified to near homogeneity from an adenovirus expression system by a two-step chromatographic procedure with a yield of 67%. The purified enzyme behaves as a monomer of 68 kDa on gel filtration and is totally specific for phosphotyrosyl residues. Its optimal pH is around neutrality for protein substrates such as reduced, carboxyamidomethylated, maleylated (RCM)-lysozyme and myelin basic protein but below 5 for low molecular weight compounds such as para-nitrophenyl phosphate (p-NPP) and phosphotyrosine. Furthermore, with the protein substrates, it displays an activity less than 1% of that obtained with other known PTPs but comparable activities toward p-NPP and phosphotyrosine. Its responsiveness toward the usual PTP activators (e.g. spermine) or inhibitors (e.g. vanadate, molybdate, heparin, or Zn2+) varied considerably with the nature of the substrates involved. Limited digestion with trypsin caused the cleavage of a C-terminal segment of the enzyme, giving rise to a 63-kDa fragment; this cleavage resulted in an approximately 20- and 10-fold activation of the enzyme toward RCM-lysozyme and myelin basic protein, respectively.
Reactions of fatty acids with amines. Part 2. Sequential thermal reactions of stearic (octadecanoic) acid with some 1,2- and 1,3-aminoalcohols and bis-amines (1978)

Thermal reactions of stearic (octadecanoic) acid with 2-aminoethanol and 3-aminopropanol in a heavy hydrocarbon oil as solvent involved (i) salt formation, (ii) stearoylation of the amino-nitrogen, and (iii) a stearoyl transfer between two molecules of the stearamidoalcohol to give the amido-ester. Each successive step took place at a higher temperature. The reaction of the stearamidoalcohols with thionyl chloride involved N ⇌ O stearoyl rearrangements, and did not yield stable cyclised products. Thermal reactions of stearic acid with some propane-1,3-diamine and with bis-(2-hydroxyethyl)amine gave diamides and amidoesters.
Biomimetic hydroxyapatite-containing composite nanofibrous substrates for bone tissue engineering (2010)

The fracture of bones and large bone defects owing to various traumas or natural ageing is a typical type of tissue malfunction. Surgical treatment frequently requires implantation of a temporary or permanent prosthesis, which is still a challenge for orthopaedic surgeons, especially in the case of large bone defects. Mimicking nanotopography of natural extracellular matrix (ECM) is advantageous for the successful regeneration of damaged tissues or organs. Electrospun nanofibre-based synthetic and natural polymer scaffolds are being explored as a scaffold similar to natural ECM for tissue engineering applications. Nanostructured materials are smaller in size falling, in the 1-100 nm range, and have specific properties and functions related to the size of the natural materials (e.g. hydroxyapatite (HA)). The development of nanofibres with nano-HA has enhanced the scope of fabricating scaffolds to mimic the architecture of natural bone tissue. Nanofibrous substrates supporting adhesion, proliferation, differentiation of cells and HA induce the cells to secrete ECM for mineralization to form bone in bone tissue engineering. Our laboratory (NUSNNI, NUS) has been fabricating a variety of synthetic and natural polymer-based nanofibrous substrates and synthesizing HA for blending and spraying on nanofibres for generating artificial ECM for bone tissue regeneration. The present review is intended to direct the reader's attention to the important subjects of synthetic and natural polymers with HA for bone tissue engineering.
Stimulating Effect of Beta(3)Indoleacetic Acid on Synthesis of Solid Matter by Bean Plants (1938)

1. The stem tips of bean plants were removed and lanolin containing different concentrations of indoleacetic acid applied to the cut surface. When concentrations stronger than approximately 0.00185 per cent were used, the development of axillary buds was retarded, the stem ends produced tumors and roots, and those parts of the plants near the point of treatment increased more in fresh and dry weight than did similar parts of untreated plants. 2. When concentrations of indoleacetic acid lower than approximately 0.00185 per cent were used, its inhibitive effect on development of axillary buds was less, the plants produced much smaller tumors, and no roots were developed. 3. By removing the axillary buds from both treated and untreated plants it was possible to study the effects of indoleacetic acid other than its inhibitive action on bud development. Dilute concentrations caused plants with the axillary buds removed to gain 23-85 per cent more solid matter as compared with untreated plants during a period of six days. The final dry weights of plants treated with these concentrations were between 6 and 11 per cent greater than the final weights of untreated plants at the end of a six day period, although the average weight of all of the plants was the same at the time of treatment. 4. Plants with axillary buds removed were stimulated to synthesize a much greater amount of solid matter when grown in light of a relatively high intensity than when treated with the same concentration of indoleacetic acid and grown during a period of relatively low light intensity. 5. The area of leaf surface of treated plants with axillary buds removed was not appreciably greater than that of untreated plants at the end of a six day period of treatment.
Thermal Energy Storage and Phase Change Materials: An Overview (2006)

The storage of thermal energy in the form of sensible and latent heat has become an important aspect of energy management with the emphasis on efficient use and conservation of the waste heat and solar energy in industry and buildings. Latent heat storage is one of the most efficient ways of storing thermal energy. Solar energy is a renewable energy source that can generate electricity, provide hot water, heat and cool a house, and provide lighting for buildings. Paraffin waxes are cheap and have moderate thermal energy storage density but low thermal conductivity and, hence, require a large surface area. Hydrated salts have a larger energy storage density and a higher thermal conductivity. In response to increasing electrical energy costs and the desire for better lad management, thermal storage technology has recently been developed. The storage of thermal energy in the form of sensible and latent heat has become an important aspect of energy management with the emphasis on the efficient use and conservation of the waste heat and solar energy in the industry and buildings. Thermal storage has been characterized as a kind of thermal battery.
Development of advanced endoscopes for Natural Orifice Transluminal Endoscopic Surgery (NOTES) (2006)

Natural orifice transluminal endoscopic surgery (NOTES) is a hybrid procedure which uses flexible endoscopic technology to perform laparoscopic surgical procedures within the abdominal cavity. Initial reports of animal studies describe the use of standard endoluminal endoscopes to accomplish intra-abdominal surgeries. Current flexible scopes suffer from several deficiencies which make them unlikely to be able to be used for large scale human NOTES experiences. This review analyzes the deficiencies of current endoscopes, discusses the requirements of the ideal NOTES endoscope and reviews some of the possible "endoscopes of the future" that are being developed for the next generation of surgery. Discussion focuses on the "R" scope (Olympus, Tokyo, Japan) and the Transport and Cobra scopes (USGI Medical, San Capistrano, CA).
Candidate cytomegalovirus strain for human vaccination (1975)

A strain of human cytomegalovirus called Towne was isolated in WI-38 human fibrolast cell cultures from the urine of an infected infant. It was then passaged 125 times in WI-38, including three clonings, and a pool was prepared in the same cell substrate for use as a potential live attenuated vaccine. The Towne virus has a broad antigenicity and cross-reacts with the AD-169 strain. Several markers of the Towne virus were found which differentiated it from fresh isolates. One of these was resistance of the former to trypsin. The Towne virus was tested for freedom from oncogenicity or other harmful effects in preparation for tests in humans.
The HMG-I Oncogene Causes Highly Penetrant, Aggressive Lymphoid Malignancy in Transgenic Mice and Is Overexpressed in Human Leukemia (2004)

HMG-I/Y is overexpressed in human cancer, although a direct role for this gene in transformation has not been established. We generated transgenic mice with HMG-I targeted to lymphoid cells. All seven informative founder HMG-I mice developed aggressive lymphoma by a mean age of 4.8 months. Tumors express T-cell markers and are transplantable. We also demonstrate that HMG-I mRNA and protein are increased in human acute lymphocytic leukemia samples. Our results show that HMG-I functions as an oncogene and suggest that it contributes to the pathogenesis of leukemia and other cancers with increased HMG-I expression.
A β 3 Integrin Mutation Abolishes Ligand Binding and Alters Divalent Cation-Dependent Conformation (1990)

The ligand-binding function of integrin adhesion receptors depends on divalent cations. A mutant alpha IIb beta 3 integrin (platelet gpIIb/IIIa) that lacks ligand recognition shows immunologic evidence of a perturbed interaction with divalent cations. This was found to be caused by a G----T mutation that resulted in an Asp119----Tyr119 substitution in the beta 3 subunit. This residue is proximal to bound ligand and is in a conserved region among integrins that are enriched in oxygenated residues. The spacing of these residues aligns with the calcium-binding residues in EF hand proteins, suggesting interaction with receptor-bound divalent cation as a mechanism of ligand binding common to all integrins.