gebhart/patrepeval huggingface dataset:
Estrogen-Receptor Interaction (1973)

The interaction of estradiol with uterine cells involves the association of the hormone with an extranuclear receptor protein, followed by temperature dependent translocation of the resulting complex to the nucleus. During this process, the steroid binding unit of the protein undergoes an alteration, called "receptor transformation," that can be recognized by an increase in its sedimentation rate from 3.8S to 5.2S, and by its acquisition of the ability to bind to isolated uterine nuclei and to alleviate a tissue specific deficiency in the RNA synthesizing capacity of such nuclei. Receptor transformation can be effected in the absence of nuclei by warming uterine cytosol with estradiol. This preparation of transformed complex resembles that extracted from nuclei both in its sedimentation rate (5.3S) and in its ability to bind to uterine nuclei and augment RNA synthesis, properties that are not shown by the native complex. It is proposed that receptor transformation is an important step in estrogen action and that a principal role of the hormone is to induce conversion of the receptor protein to a biochemically functional form.
Performance and amino acid utilization of early lactation dairy cows fed regular or reduced-fat dried distillers grains with solubles (2010)

The objective of this study was to evaluate lactation response and AA utilization of early lactation cows fed 2 types of dried distillers grains with solubles (DG): regular (DDGS) or reduced-fat (RFDGS). Thirty-six Holstein cows 19.7+/-2.6 d in milk at the start of the experiment were used in a randomized complete block design for 14 wk including a 2-wk covariate period. Treatments consisted of the following diets: 1) control (CON) diet containing 0% DG; 2) diet containing 22% DDGS; and 3) diet containing 20% RFDGS. Distillers grains replaced soybean meal, expeller soybean meal, and soyhulls from the CON diet. Diets were formulated to be similar in crude protein, ether extract, neutral detergent fiber, and net energy for lactation concentrations. Dry matter intake (24.7 kg/d) and milk yield (39.3 kg/d) were similar for all diets. Milk fat and lactose percentages were unaffected by diets; however, protein percentage was greater for cows fed the DG diets compared with the CON diet. Consequently, milk protein yield was also greater for the DG diets compared with CON. Milk urea nitrogen decreased for cows fed DG diets and averaged 11.8, 10.9, and 10.1 mg/dL, respectively, for CON, DDGS, and RFDGS. Feed efficiency tended to be greater and N efficiency was greater for cows fed DG compared with CON. Body weight (711 kg), body weight change (+0.49 kg/d), and body condition score (3.36) were similar for all diets, but cows fed CON tended to gain more body condition (+0.14) than cows fed DG diets. Amino acid utilization was evaluated at the peak of milk production corresponding to wk 9 of lactation. Arterial Lys concentration was lower with DG diets (70.4, 58.6, and 55.8 microM/L). Cows fed DG had greater arterial Met concentration (21.3 microM) compared with CON (14.9 microM). Arterio-venous difference of Lys was similar across diets, whereas that of Met was greater for the DG diets compared with the CON diet (10.3 vs. 13.0 microM/L). Extraction efficiency of Lys by the mammary gland was greater for DG diets than for CON (76.1 vs. 65.4%). Mammary uptake of Lys (2.56 g/kg of milk) was similar for all diets, and the uptake of Met tended to increase in cows fed DG diets. Plasma glucose, triglyceride, and total cholesterol were unaffected by treatment; however, cows fed DG diets had lower beta-hydroxybutyrate and tended to have lower nonesterified fatty acid concentrations than cows fed the CON diet. Despite the apparent deficiency of Lys, milk protein percentage was increased in cows fed DG diets.
A rice homeotic gene, OSH1, causes unusual phenotypes in transgenic tobacco (1993)

A rice gene, OSH1, which shares homology with animal homeobox genes, has been isolated. We have introduced the OSH1 cDNA into tobacco in order to examine its function. Expression of the OSH1 cDNA in tobacco induced morphological abnormalities in the leaves, petals and stems of the transformants suggesting that OSH1 functions as a morphological regulator. OSH1 cDNA expression was analyzed under the control of three different promoters. This work revealed that not only the level of OSH1 expression but also the site and timing of the expression affect the morphology of the plant.
Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. (1990)

The basic carboxy terminus of p53 plays an important role in directing the protein into the nuclear compartment. The C terminus of the p53 molecule contains a cluster of several nuclear localization signals (NLSs) that mediate the migration of the protein into the cell nucleus. NLSI, the most active domain, is highly conserved in genetically diverged species and shares perfect homology with consensus NLS sequences found in other nuclear proteins. The other two NLSs, II and III, appear to be less effective and less conserved. Although nuclear localization is dictated primarily by the NLSs inherent in the primary amino acid sequence, the actual nuclear homing can be modified by interactions with other proteins expressed in the cell. Comparison between wild-type p53 and naturally occurring mutant p53 showed that both protein categories could migrate into the nucleus of rat primary embryonic fibroblasts by essentially similar mechanisms. Nuclear localization of both proteins was totally dependent on the existence of functional NLS domains. In COS cells, however, we found that NLS-deprived wild-type p53 molecules could migrate into the nucleus by complexing with another nuclear protein, simian virus 40 large-T antigen. Wild-type and mutant p53 proteins differentially complexed with viral or cellular proteins, which may significantly affect the ultimate compartmentalization of p53 in the cell; this finding suggests that the actual subcellular compartmentalization of proteins may differ in various cell type milieux and may largely be affected by the ability of these proteins to complex with other proteins expressed in the cell. Experiments designed to test the physiological significance of p53 subcellular localization indicated that nuclear localization of mutant p53 is essential for this protein to enhance the process of malignant transformation of partially transformed cells, suggesting that p53 functions within the cell nucleus.
A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells, and on one of two types of helper T cells. (1981)

Abstract A monoclonal antibody termed anti-Tac antibody, which reacts with human activated T cells, was functionally characterized in this study. T cells reactive with anti-Tac antibody [Tac (+)] were tested for their helper cell and suppressor cell activity in PWM-induced Ig production and for cytotoxic killer cell activity induced by a mixed leukocyte culture. Con A-stimulated T cells were depleted of Tac (+) cells by treatment with anti-Tac antibody and complement, and Con A-stimulated T cells were also separated into Tac (+) and Tac (−) cell populations by a Staphylococcal Protein A (SPA)-coated bovine red blood cell (BRBC) rosette technique. Con A-induced suppressor cell activity for PWM-induced Ig production was contained in the Tac (+) cell population but not in the Tac (−) cell population. T cells precultured with PWM and fractionated into Tac (+) and Tac (−) cell populations by a SPA-coated BRBC rosette method were also studied for helper and suppressor cell activity in a PWM-induced Ig production system. PWM-activated Tac (+) cells showed both radioresistant helper cell activity and radiosensitive suppressor cell activity. On the other hand, Tac (−) cells showed only helper cell activity. This helper activity was reduced after 2000 R irradiation. Tac (+) T cells separated from peripheral blood mononuclear cells after in vitro allosensitization showed specific cytotoxic killer cell activity against allogeneic cells, whereas Tac (−) cells did not have this function. These studies demonstrate that anti-Tac monoclonal antibody can define activated and functionally mature human T cells and also can be used to differentiate 2 different types of helper T cells, Tac (+) radioresistant and Tac (−) T cells that were more radiosensitive.
Cell Shape Determination: A Pivotal Role for Rho (1996)

During the formation of a daughter yeast cell, a small Ras-like GTPase acts as a morphogenetic coordinator and, as reported in two papers in this week's issue of Science [Drgonová ( p. 277 ) and Qadota et al. ( p. 279 )], regulates beta(1arrow pointing right3)glucan synthase, the enzyme that makes the glycans of the cell walls. In his Perspective, Bussey discusses this function of Rho and the parallels to its functions in mammalian cells.
Tomography of Reaction-Diffusion Microemulsions Reveals Three-Dimensional Turing Patterns (2011)

Spatially periodic, temporally stationary patterns that emerge from instability of a homogeneous steady state were proposed by Alan Turing in 1952 as a mechanism for morphogenesis in living systems and have attracted increasing attention in biology, chemistry, and physics. Patterns found to date have been confined to one or two spatial dimensions. We used tomography to study the Belousov-Zhabotinsky reaction in a microemulsion in which the polar reactants are confined to aqueous nanodroplets much smaller than the scale of the stationary patterns. We demonstrate the existence of Turing patterns that can exist only in three dimensions, including curved surfaces, hexagonally packed cylinders, spots, and labyrinthine and lamellar patterns.
Morpholino, siRNA, and S-DNA Compared: Impact of Structure and Mechanism of Action on Off-Target Effects and Sequence Specificity (2007)

Generally a gene knockdown agent should achieve high sequence specificity and should lack off-target effects (non-antisense effects due to interactions with structures other than gene transcripts). Three major gene knockdown types are compared with respect to off-target effects and sequence specificities: 1) phosphorothioate-linked DNA (S-DNA); 2) short interfering RNA (siRNA); and, 3) Morpholino. S-DNAs cause multiple off-target effects, largely because their backbone sulfurs bind to many different proteins. S-DNAs also achieve poor sequence specificity because S-DNA/RNA duplexes as short as 7 base-pairs are cleaved by RNase H. siRNAs cause several off-target effects, but improved designs may soon avoid such effects. siRNAs also provide only limited sequence specificity because their short guide sequences largely determine which gene transcripts will be blocked or cleaved, and those guide sequences appear to recognize insufficient sequence information to uniquely target a selected gene transcript. This specificity limitation is inherent in their mechanism of action and so probably cannot be greatly improved. Morpholinos are virtually free of off-target effects--probably because they cannot interact electrostatically with proteins. Morpholinos also achieve exquisite sequence specificity--in large part because they must bind at least about 14 to 15 contiguous bases to block a gene transcript, and this constitutes sufficient sequence information to uniquely target a selected gene transcript. Because of their freedom from off-target effects, exquisite sequence specificity, complete stability in biological systems, and highly predictable targeting, Morpholinos dominate the most demanding of all gene knockdown applications, studies in developing embryos.
Allosteric Modulators of the Human Calcium-Sensing Receptor:Structures, Sites of Action, and Therapeutic Potentials (2008)

The human extracellular Ca(2+)-sensing receptor (CaR) plays a key role in the regulation of serum calcium and parathyroid hormone. This large dimeric receptor consists of domains with topologically distinctive orthosteric and allosteric sites. Positive allosteric modulators of the CaR, which increase CaR activation and thereby decrease secretion of parathyroid hormone, are potential for the treatment of primary and secondary hyperparathyroidism. Conversely, negative allosteric modulators of the CaR, which decrease the receptor activation and thereby stimulate endogenous parathyroid hormone secretion, are potential for the treatment of osteoporosis and autosomal dominant hypocalcemia. Significant progress has been made in recent years in screening for allosteric modulators selectively targeting the CaR and identification of receptor residues important for allosteric modulation.
The selective and superoxide-independent disruption of intestinal epithelial tight junctions during leukocyte transmigration. (1988)

Polymorphonuclear leukocyte (PMN) transmigration across cultured intestinal epithelial monolayers has been shown to be associated with a decrease in transepithelial resistance to the passive flow of ions. Using flux techniques, we show that this effect reflects selective, PMN induced alterations in paracellular, as opposed to transcellular, ion permeability. Enhancement of paracellular permeability due to PMN transmigration is not simply due to expansion of the paracellular space resulting from cell death as cytotoxicity does not occur during this process. Thus, permeability alterations accompanying PMN transmigration can be specifically attributed to altered permeability of the rate limiting barrier of the paracellular pathway, the intercellular tight junction. We have also explored the mechanism by which PMN induce transient tight junction dissolution during transmigration. Use of inhibitors of toxic oxygen metabolites or use of PMN from patients with chronic granulomatous disease show that oxygen metabolites are neither required for transmigration or for the permeability abnormality accompanying transmigration. Similarly, use of protease inhibitors suggest that release of proteases by PMN during transmigration is not the basis by which PMN are able to cross tight junctions. Structural studies show that transient intimate PMN-epithelial cell plasma membrane associations and cytoskeletal specializations preceed junctional impalement by PMN. We speculate that such putative adhesion sites serve as the foothold from which PMN may generate the mechanical force necessary to cross tight junctions during transmigration.
Experimental study of phosphopeptide in promoting tooth remineralization. (2000)

Phosphopeptide was effective in the prevention and treatment of tooth decay. Clinically, it could be safely applied.
Photovoltaic properties of ZnCdS/CdTe heterojunctions prepared by spray pyrolysis (1978)

A series of photovoltaic heterojunctions of the type n-Zn0.1Cd0.9S/p-CdTe have been prepared by spray pyrolysis of ZnCdS films on single-crystal CdTe with variation of the CdTe substrate temperature and of the postdeposition heat-treatment temperature in hydrogen. Open-circuit voltages as high as 0.82 V are observed compared to maximum values of 0.74 V observed for n-CdS/p-CdTe junctions also prepared by spray pyrolysis. Cell efficiencies are in the 6–8% range without correction for reflection losses.
Recent Advances and Patents on Circulatory Support Devices for Pediatric Patients (2009)

Recent progress in medical management has significantly improved the range of treatments for children with severe heart failure; however, some patients still suffer from refractory heart failure, necessitating heart transplantation. Transplantation is the definitive therapy for end-stage heart failure in children and adults; however, many patients die before transplantation because of the shortage of donor organs. Mechanical circulatory support devices have offered new treatment options for these patients. For many years, extracorporeal membrane oxygenation (ECMO) has served as the main circulatory assist device for children. However, long-term support with ECMO is not recommended because of the accompanying severe complications, such as cerebral infarction, brain hemorrhage, and renal and multiorgan failure. The development of ventricular assist devices specifically for children is lagging behind efforts aimed at treating adults. Furthermore, a total artificial heart is not thought suitable for children because of their growth rate. The National Heart, Lung, and Blood Institute has supported efforts to develop pediatric-specific devices at five institutions in the United States since 2004. There are only a few patents for circulatory support devices designed for pediatric patients, and there is still much room to improve currently available pediatric circulatory devices.
Room-Temperature Detection of a Single Molecule’s Absorption by Photothermal Contrast (2010)

So far, single-molecule imaging has predominantly relied on fluorescence detection. We imaged single nonfluorescent azo dye molecules in room-temperature glycerol by the refractive effect of the heat that they release in their environment upon intense illumination. This photothermal technique provides contrast for the absorbing objects only, irrespective of scattering by defects or roughness, with a signal-to-noise ratio of ~10 for a single molecule in an integration time of 300 milliseconds. In the absence of oxygen, virtually no bleaching event was observed, even after more than 10 minutes of illumination. In a solution saturated with oxygen, the average bleaching time was of the order of 1 minute. No blinking was observed in the absorption signal. On the basis of bleaching steps, we obtained an average absorption cross section of 4 angstroms(2) for a single chromophore.
Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy (2009)

Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals transmitted by cellular damage (including antineoplastic drugs) or cytokine deprivation can initiate apoptosis via the intrinsic apoptotic pathway. It is controversial whether some BH3-domain proteins (Bim or tBid) directly activate multidomain pro-apoptotic proteins (e.g., Bax and Bak) or act via inhibition of those anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that stabilize pro-apoptotic proteins. Overexpression of anti-apoptotic Bcl-2 family members has been associated with chemotherapy resistance in various human cancers, and preclinical studies have shown that agents targeting anti-apoptotic Bcl-2 family members have preclinical activity as single agents and in combination with other antineoplastic agents. Clinical trials of several investigational drugs targeting the Bcl-2 family (oblimersen sodium, AT-101, ABT-263, GX15-070) are ongoing. Here, we review the role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl-2 family of proteins.
Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis (2004)

Constitutive activation of signal transducer and activator of transcription 3 (Stat3) has been found in a wide spectrum of human malignancies. Here, we have assessed the effect of Stat3 deficiency on skin tumor development using the 2-stage chemical carcinogenesis model. The epidermis of Stat3-deficient mice showed a significantly reduced proliferative response following treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) because of a defect in G1-to-S-phase cell cycle progression. Treatment with the tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) resulted in a significant increase in the number of keratinocyte stem cells undergoing apoptosis in the bulge region of hair follicles of Stat3-deficient mice compared with nontransgenic littermates. Notably, Stat3-deficient mice were completely resistant to skin tumor development when DMBA was used as the initiator and TPA as the promoter. Abrogation of Stat3 function using a decoy oligonucleotide inhibited the growth of initiated keratinocytes possessing an activated Ha-ras gene, both in vitro and in vivo. In addition, injection of Stat3 decoy into skin tumors inhibited their growth. To our knowledge, these data provide the first evidence that Stat3 is required for de novo epithelial carcinogenesis, through maintaining the survival of DNA-damaged stem cells and through mediating and maintaining the proliferation necessary for clonal expansion of initiated cells during tumor promotion. Collectively, these data suggest that, in addition to its emerging role as a target for cancer therapy, Stat3 may also be a target for cancer prevention strategies. Nonstandard abbreviations used:
Why a pomegranate? (2000)

<h3>Objective</h3> To examine health professionals9 experiences of and attitudes towards the provision of chemotherapy to patients with end stage cancer. <h3>Design</h3> Purposive, qualitative design based on in-depth interviews. <h3>Setting</h3> Oncology departments at university hospitals and general hospitals in the Netherlands. <h3>Participants</h3> 14 physicians and 13 nurses who cared for patients with metastatic cancer. <h3>Results</h3> Physicians and nurses reported trying to inform patients fully about their poor prognosis and treatment options. They would carefully consider the (side) effects of chemotherapy and sometimes doubted whether further treatment would contribute to patients9 quality of life. Both groups considered the patients9 wellbeing to be important, and physicians seemed inclined to try to preserve this by offering further chemotherapy, often followed by the patient. Nurses were more often inclined to express their doubts about further treatment, preferring to allow patients to make the best use of the time that is left. When confronted with a treatment dilemma and a patient9s wish for treatment, physicians preferred to make compromises, such as by “trying out one dose.” Discussing death or dying with patients while at the same time administering chemotherapy was considered contradictory as this could diminish the patients9 hope. <h3>Conclusions</h3> The trend to greater use of chemotherapy at the end of life could be explained by patients9 and physicians9 mutually reinforcing attitudes of “not giving up” and by physicians9 broad interpretation of patients9 quality of life, in which taking away patients9 hope by withholding treatment is considered harmful. To rebalance the ratio of quantity of life to quality of life, input from other health professionals, notably nurses, may be necessary.
A mathematical model of the hsp70 regulation in the cell (1998)

A mathematical model of the regulation process of the heat shock protein hsp70 in the cell is presented. The model describes the damaging effect of elevated temperature on proteins; the interaction of free hsp70 with injured proteins and its chaperone role in nascent protein translation; the relation between the amount of free hsp70 and the formation of the activated trimer form of the heat shock factor protein (HSF); the binding of activated HSF with the heat shock elements on the DNA; the transcription of mRNA of hsp70 and the synthesis of hsp70. The reaction of the model to a temporal rise in temperature shows an initial decline and a subsequent sharp rise to an ultimately increased level of free hsp70 in the cell. The response of the model to both a single and two consecutive heat shocks appears to closely resemble experimental data on hsp70 synthesis. This general agreement demonstrates the structure of the model to be sound and suitable as a basis for further modelling the complex tolerance mechanism of the cell.