gebhart/patrepeval huggingface dataset:
Colonic carcinogenesis: The microbial feast or famine mechanism (1987)

A mechanism is presented which suggests that high-fat, high-protein, low-fiber diets can cause an unfavorable microbial environment in the human colon which predisposes some individuals towards large bowel diseases. The digesta leaving the ileum on high-fat, high-protein, low-fiber diets has a high proportion of mucins, malabsorbed carbohydrates and proteins, bile acids, and sloughed epithelial cells. The irregular (pulsatile) emptying of rapidly fermentable ileal digesta into the colon causes a massive surge in microbial activity. The sudden availability of rapidly fermentable substrate generates a large microbial population in the exponential growth phase that soon depletes its substrate. For microorganisms to perpetuate until the next high-fat, high-protein, low-fiber meal propels ileal digesta into the colon, they must induce enzymes to ferment dying or dead microbes (cannibalism) in addition to colonic epithelial mucosa and mucins. As the carbohydrate-to-nitrogen ratio of the colonic contents decreases, the fermentation becomes more proteolytic and subacute levels of fermentation products such as ammonia may be generated. Carcinogens are concentrated within a small colonic mass and the probability of precancerous lesions and polyps developing in the colonic mucosa is directly related to the severity, frequency, and duration of these microbial "feast or famine" situations in the colon.
Definition of the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex protein activation domain by functional exchange (1992)

The human retroviruses human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) are characterized by complex regulation of gene expression. Each virus encodes a posttranscriptional regulator, the 19-kDa HIV-1 Rev protein and the 27-kDa HTLV-I Rex protein, which is required for viral replication. Expression of these trans activators results in the cytoplasmic accumulation of unspliced or singly spliced viral mRNA which encode the gag, pol, and env gene products. The finding that the HTLV-I Rex protein is able to functionally substitute for the Rev protein of HIV-1 indicates that HIV-1 Rev and HTLV-I Rex may interact with the same component of a cellular pathway involved in either mRNA splicing or transport. In this study, we have generated functional Rev/Rex hybrid proteins by domain exchange. We have defined, using in vivo and in vitro analyses, the activation domains of Rev and Rex which are the putative targets of a common host cell factor(s) required for Rev and Rex function.
Cannabinoids as Therapeutics (2005)

Cannabis in India: ancient lore and modern medicine.- Cannabinoid chemistry: an overview.- Cannabidiol as a potential medicine.- Endocannabinoids and regulation of fertility.- Cannabinoids in neurodegeneration and neuroprotection.- Role of the endocannabinoid system in learning and memory.- Cannabinoids and anxiety.- Cannabinoid targets for pain therapeutics.- Potential use of cannabimimetics in the treatment of cancer.- Cannabinoids: effects on vomiting and nausea in animal models.- The skeleton: stone bones and stoned heads?.- Cannabinoids and drugs of abuse.- Cannabinoids in appetite and obesity.- The development of Sativex(R) - a natural cannabis-based medicine.
Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells (2014)

Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0(460) in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.
Hepatocyte Nuclear Factor 4α Coordinates a Transcription Factor Network Regulating Hepatic Fatty Acid Metabolism (2009)

Adaptation of liver to nutritional signals is regulated by several transcription factors that are modulated by intracellular metabolites. Here, we demonstrate a transcription factor network under the control of hepatocyte nuclear factor 4alpha (HNF4alpha) that coordinates the reciprocal expression of fatty acid transport and metabolizing enzymes during fasting and feeding conditions. Hes6 is identified as a novel HNF4alpha target, which in normally fed animals, together with HNF4alpha, maintains PPARgamma expression at low levels and represses several PPARalpha-regulated genes. During fasting, Hes6 expression is diminished, and peroxisome proliferator-activated receptor alpha (PPARalpha) replaces the HNF4alpha/Hes6 complex on regulatory regions of target genes to activate transcription. Gene expression and promoter occupancy analyses confirmed that HNF4alpha is a direct activator of the Pparalpha gene in vivo and that its expression is subject to feedback regulation by PPARalpha and Hes6 proteins. These results establish the fundamental role of dynamic regulatory interactions between HNF4alpha, Hes6, PPARalpha, and PPARgamma in the coordinated expression of genes involved in fatty acid transport and metabolism.
Candidate Gene for the Chromosome 1 Familial Alzheimer's Disease Locus (1995)

A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence for STM2 is homologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in STM2, resulting in the substitution of an isoleucine for an asparagine (N141l), was identified in affected people from Volga German AD kindreds. This N141l mutation occurs at an amino acid residue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic.
Amelogenin Protein Exhibits a Modular Design: Implications for Form and Function (2003)

The most abundant protein of forming enamel is amelogenin, a protein capable of self-assembly to form nanospheres. Naturally occurring mutations in the human amelogenin gene are responsible for at least some of the disease entities known collectively as amelogenesis imperfecta (AI), although it is clear that the AI phenotype may be caused by alteration to other genes responsible for the biogenesis of the enamel extracellular matrix. Mutations that create changes in the functional domains of the amelogenin protein do adversely affect enamel biomineralization. Protein engineering of amelogenin that phenocopies several of the known AI mutations exhibits defects in self-assembly. Amino acid alterations that occur within a domain of amelogenin appear to cause "mineral defects," that is to say hypocalcification of the enamel, whereas mutations that occur elsewhere in another domain of the amelogenin molecule result in "hypoplastic defects," a decrease in thickness of the enamel. However, not all patients with AI phenotypes segregate precisely into these arbitrary designations. Nonetheless, correlating the domain of the amelogenin protein that contains a specific mutation with the type of enamel structural alteration suggests a modular design for amelogenin that is corroborated by protein engineering using recombinant DNA techniques and transgenic animal studies.
Enzymatic Placement of 6-O-Sulfo Groups in Heparan Sulfate (2011)

Heparan sulfate is a highly sulfated polysaccharide that exhibits important physiological and pathological functions. The glucosamine residue of heparan sulfate can carry sulfo groups at the 2-N, 3-O, and 6-O positions, leading to diverse polysaccharide structures. 6-O-Sulfation at the glucosamine residue contributes to a wide range of biological functions. Here, we report a method for controlling the positioning of 6-O-sulfo groups in oligosaccharides. This was achieved by synthesizing oligosaccharide backbones from a disaccharide building block utilizing glycosyltransferases followed by modifications using heparan sulfate N-sulfotransferase and 6-O-sulfotransferases. This method offers a viable approach for preparing heparan sulfate oligosaccharides with precisely located 6-O-sulfo groups.
Comparison of the Kirchhoff and the Rayleigh–Sommerfeld Theories of Diffraction at an Aperture (1964)

With a view to elucidating the effect of a well-known mathematical inconsistency in Kirchhoff’s diffraction theory, a comparison is made of the predictions relating to the field diffracted at an aperture, based on Kirchhoff’s theory (UK) and on formulas due to Rayleigh and Sommerfeld (UR). It is shown that, when the incident wave is plane or spherical, the difference δ = UK−UR represents a boundary wave, i.e., a wave which may be thought of as originating at each point of the edge of the aperture. It is shown further that, when the linear dimensions of the aperture are large compared with the wavelength, the boundary values of δ in the plane of the aperture change very rapidly and almost periodically from point to point, with the mean period close to the wavelength of the incident radiation. This result is shown to imply that if the linear dimensions of the aperture are large compared with the wavelength, the two theories predict essentially the same behavior for the diffracted field in the far zone, at moderate angles of diffraction.
Assignment of 30 Microsatellite Loci to the Linkage Map of Arabidopsis (1994)

Thirty microsatellite loci were assigned to the Arabidopsis linkage map. Several microsatellite sequences in Arabidopsis DNA were found by searching the EMBL and GenBank databases, and a number of these were subsequently found to detect polymorphisms between different Arabidopsis strains by the polymerase chain reaction (PCR). After the presence of microsatellites in Arabidopsis and their utility for genetic mapping had been demonstrated, systematic screening for (CA)n and (GA)n sequences was carried out on marker-selected plasmid libraries and a small-insert genomic library. Positive clones were sequenced, PCR primers flanking the repeats were synthesized, and PCR was carried out on different strains to look for useful polymorphisms. Surprisingly, of 18 (CA)n repeats (n > 13), only one was polymorphic. In contrast, 25 of 30 (GA)n repeats, 2 of 3 (AT)n repeats, and 2 of 4 (A)n repeats were polymorphic. The majority of the (CA)n repeats were complex, with adjacent short di-, tri-, or tetranucleotide repeats, whereas most of the (GA)n, (TA)n, and (A)n repeats were simple. The (CA)n repeats were also refractory to PCR analysis, requiring extensive optimization of PCR conditions, whereas the other repeat classes were mostly amplified with a single set of standard conditions. When polymorphisms were detected, the microsatellites were mapped using a set of recombinant inbred lines originating from a cross between the strains Columbia and Landsberg erecta.
Electromechanical properties of wearable strain gauge transducers (2008)

Electro-conductive yarns can be used to create electrically active areas in textile structures to develop wearable strain gauges. The electromechanical properties of the strain gauge have been studied. Three lab experiments have been conducted: the first analyses the electrometrical properties of the yarns which were used to produce knitted sensors; the second investigates the properties of a single stitch to understand the effect of contact points between yarns on the electrical properties of knitted fabric. Finally, the electrical properties of the knitted fabrics which contain electrically active conductive areas, i.e. knitted sensors, were tested.
Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores (1989)

A new group of fluorescent indicators with visible excitation and emission wavelengths has been synthesized for measurements of cytosolic free Ca2+. The five compounds, "rhod-1," "rhod-2," "fluo-1," "fluo-2," and "fluo-3" (Figs. 2 and 3), combine the 8-coordinate tetracarboxylate chelating site of 1,2-bis(2-amino-phenoxyethane-N,N,N',N'-tetraacetic acid with a xanthene chromophore to give a rhodamine-like or fluorescein-like fluorophore. Binding of Ca2+ increases the fluorescence by up to 40-fold. The Ca2+ dissociation constants are in the range 0.37-2.3 microM, so that the new indicators should give better resolution of high [Ca2+] levels than previously obtainable with quin-2 or fura-2. The visible excitation wavelengths of the new compounds are more convenient for fluorescence microscopy and flow cytometry than the UV required by previous indicators. However, the new dyes' increase in fluorescence upon binding calcium is not accompanied by a wavelength shift, so they are unsuitable for measurements using ratios at two wavelengths. The most promising dye of this series is fluo-3, whose initial biological testing in fibroblasts is described in the following paper (Kao, J. P. Y., Harootunian, A. T., and Tsien, R. Y. (1989) J. Biol. Chem. 264, 8171-8178).
Colloidal quantum dots. From scaling laws to biological applications (2000)

Abstract Over a twenty-year period, condensed matter physicists and physical chemists have elucidated a series of scaling laws which successfully describe the size dependence of solid state properties [1,2]. Often the experiments were performed under somewhat exotic conditions, for instance on mass-selected clusters isolated in molecular beams or on quantum dots grown by molecular beam epitaxy and interrogated at low temperatures and in high magnetic fields. As a result, we now have an understanding of how thermodynamic, optical, electrical, and magnetic properties evolve from the atomic to the solid state limit. This area of research is presently undergoing a remarkable transformation. The scaling laws, previously the direct subject of research, now provide a tool for the design of advanced new materials. In the case of colloidal quantum dots, or semiconductor nanocrystals, these new insights are poised to have impact in disciplines remote from solid state physics [3].
A Dynamic Instrumentation Approach to Software Transactional Memory (2007)

With the advent of chip-multiprocessors, we are faced with the challenge of parallelizing performance-critical software. Transactional memory has been proposed as a promising programming model, with software implementations (STMs) being especially compelling for today&apos;s use. However, in addition to high overheads, existing STMs are limited to either managed languages or intrusive APIs. Furthermore, transactions in STMs cannot normally contain calls to unobservable code such as shared libraries or system calls. In this dissertation we present JudoSTM, a novel dynamic binary-rewriting approach to implementing STM that supports C and C++ code. By using value-based conflict detection, JudoSTM additionally supports the transactional execution of both (i) irreversible system calls and (ii) code that contains locks. We lower overhead through several novel optimizations that improve invisible-reader and validate/commit performance. We show that our approach performs comparably to RSTM—demonstrating that a dynamic binary-rewriting approach to implementing STM is an interesting alternative.
Anisotonic media and glutamate-induced ion transport and volume responses in primary astrocyte cultures. (1987)

1. The responses of primary monolayer astrocyte cultures prepared from neonatal rat brains to hyper- and hypotonic media and to the addition of L-glutamic acid were examined as part of a systematic approach to use these cultures to obtain information on the mechanisms of the volume changes seen in astroglial cells in situ. 2. Addition of 200 mM mannitol to the medium to make it hypertonic caused cell shrinkage as measured with [14C]3-O-methyl-D-glucose, and also activated K+ and Cl- uptake measured with 86Rb+ and 36Cl- respectively. The increased ion uptake was completely inhibited by 0.1 mM bumetanide, showing that the Na+ + K+ + 2 Cl- co-transport system was being activated by cell shrinkage. 3. Studies of 86Rb+ uptake as a function of external K+ and hypertonic media showed a complex pattern. Increased bumetanide-sensitive, hypertonic-stimulated uptake of 86Rb+ was seen up to 20 mM K+0, with maximum stimulation being first reached at around 2 to 5 mM K+. At concentrations greater than 20 mM K+0 there was a further increase in bumetanide-sensitive 86Rb+ uptake, but there was no stimulation of this uptake by hypertonicity. There were also increases in bumetanide-insensitive 86Rb+ fluxes at [K+]0 higher than 20 mM that may have been due to opening of voltage-dependent K+ channels; this increased 86Rb+ flux was decreased in hypertonic medium. 4. When primary astrocyte cultures were swollen in hypotonic medium there was a rapid increase in volume as measured with [14C] 3-O-methyl-D-glucose, which then decreased in the continued presence of hypotonic medium. Thus, these cells exhibit volume regulatory decrease or RVD, as described for other cells. The possible ionic bases of this phenomenon have not yet been fully examined but the initial RVD did not appear to stimulate a furosemide-sensitive cotransport system. 5. Glutamate has been implicated as a possible endogenous effector of volume change in astrocytes. In the presence of ouabain, L-glutamate led to swelling of cultured astrocytes and increased uptake of 22Na+ and 36Cl-. It is suggested that this is due to uptake of L-glutamate with cotransport of Na+ and Cl-. Increased uptake was also seen for 86Rb+ in the absence of ouabain, and this was not seen in the absence of Na+.(ABSTRACT TRUNCATED AT 400 WORDS)
Crystal Structure of Leukocyte Ig-like Receptor LILRB4 (ILT3/LIR-5/CD85k) (2011)

The myeloid inhibitory receptor LILRB4 (also called ILT3, LIR-5, CD85k), a member of the leukocyte immunoglobulin-like receptors (LILRs/LIRs), is an important mediator of immune tolerance. Up-regulated on tolerogenic dendritic cells, it has been shown to modulate immune responses via induction of T cell anergy and differentiation of CD8(+) T suppressor cells and may play a role in establishing immune tolerance in cancer. Consequently, characterizing the molecular mechanisms involved in LILRB4 function and in particular its structure and ligands is a key aim but has remained elusive to date. Here we describe the production, crystallization, and structure of the LILRB4 ectodomain to 1.7 Å using an expression strategy involving engineering of an additional disulfide bond in the D2 domain to enhance protein stability. LILRB4 comprises two immunoglobulin domains similar in structure to other LILRs; however, the D2 domain, which is most closely related to the D4 domains of other family members, contains 3(10) helices not previously observed. At the D1-D2 interface, reduced interdomain contacts resulted in an obtuse interdomain angle of ∼107°. Comparison with MHC class I binding Group 1 LILRs suggests LILRB4 is both conformationally and electrostatically unsuited to MHC ligation, consistent with LILRB4 status as a Group 2 LILR likely to bind novel non-MHC class I ligands. Finally, examination of the LILRB4 surface highlighted distinctive surface patches on the D1 domain and D1D2 hinge region, which may be involved in ligand binding. These findings will facilitate our attempts to precisely define the role of LILRB4 in the regulation of immune tolerance.
New discoveries on the biology and detection of human chorionic gonadotropin (2009)

Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic disease, diagnosing placental site trophoblastic tumor, managing testicular germ cell malignancies, and monitoring other human malignancies. There are very few molecules with such wide and varying functions as regular hCG and its variants, and very few tests with such a wide spectrum of clinical applications as total hCG.
Pharmaceutical Formulation Development of Peptides and Proteins (2012)

The rapid advances in recombinant DNA technology and the increasing availability of peptides and proteins with therapeutic potential are a challenge for pharmaceutical scientists who have to formulate these compounds as drug products. Pharmaceutical Formulation Development of Peptides and Proteins, Second Edition discusses the development of therap
Use of neem oil as a mosquito repellent in tribal villages of mandla district, madhya pradesh. (1995)

A field study was carried out to evaluate the mosquito repellent action of neem (Azadirachta indica) oil in tribal forested villages of District Mandla. Various concentrations of neem oil mixed in coconut oil (1-4%) were applied to the exposed body parts of human volunteers. Results revealed 81-91% protection during 12 h period of observation from the bites of anopheline mosquitoes. Neem oil is an indigenous product and a practical solution to curtail mosquito nuisance.
Effect of Immunization with a Common Recall Antigen on Viral Expression in Patients Infected with Human Immunodeficiency Virus Type 1 (1996)

Activation of the immune system by an ongoing antigen-specific immune response to an exogenous stimulus transiently increases the expression of HIV-1 and may enhance the susceptibility of uninfected subjects to HIV-1.