gebhart/patrepeval huggingface dataset:
Rescue of non-sense mutated p53 tumor suppressor gene by aminoglycosides (2010)

Mutation-based treatments are a new development in genetic medicine, in which the nature of the mutation dictates the therapeutic strategy. Interest has recently focused on diseases caused by premature termination codons (PTCs). Drugs inducing the readthrough of these PTCs restore the production of a full-length protein. In this study, we explored the possibility of using aminoglycoside antibiotics to induce the production of a full-length functional p53 protein from a gene carrying a PTC. We identified a human cancer cell line containing a PTC, for which high levels of readthrough were obtained in the presence of aminoglycosides. Using these cells, we demonstrated that aminoglycoside treatment stabilized the mutant mRNA, which would otherwise have been degraded by non-sense-mediated decay, resulting in the production of a functional full-length p53 protein. Finally, we showed that aminoglycoside treatment decreased the viability of cancer cells specifically in the presence of nonsense-mutated p53 gene. These results open possibilities of developing promising treatments of cancers linked with non-sense mutations in tumor suppressor genes. They show that molecules designed to induce stop-codon readthrough can be used to inhibit tumor growth and offer a rational basis for developing new personalized strategies that could diversify the existing arsenal of cancer therapies.
Harnessing the Actuation Potential of Solid‐State Intercalation Compounds (2006)

Abstract High‐strain, high‐force mechanical actuation technologies are desirable for numerous applications ranging from microelectromechanical systems (MEMS) to large‐scale “smart structures” that are able to change shape to optimize performance. Here we show that electrochemical intercalation of inorganic compounds of high elastic modulus offers a low‐voltage mechanism (less than 5 V) with intrinsic energy density approaching that of hydraulics and more than a hundred times greater than that of existing field‐operated mechanisms, such as piezostriction and magnetostriction. Exploitation of the reversible crystallographic strains (several percent) of intercalation compounds while under high stress is key to realization of the available energy. Using a micromachined actuator design, we test the strain capability of oriented graphite due to electrochemical lithiation under stresses up to 200 MPa. We further demonstrate that simultaneous electrochemical expansion of the LiCoO 2 /graphite cathode/anode couple can be exploited for actuation under stresses up to ∼ 20 MPa in laminated macroscopic composite actuators of similar design to current lithium‐ion batteries. While the transport‐limited actuation mechanism of these devices results in intrinsically slower actuation compared to most ferroic materials, we demonstrate up to 6.7 mHz (150 s) cyclic actuation in a laminated actuator designed for a high charge/discharge rate. The potential for a new class of high‐strain, high‐force, moderate‐frequency actuators suitable for a broad range of applications is suggested.
Protein Crystals as Novel Catalytic Materials (2001)

In this era of molecular biology, protein crystallization is often considered to be a necessary first step in obtaining structural information through X-ray diffraction analysis. In a different light, protein crystals can also be thought of as materials, whose chemical and physical properties make them broadly attractive and useful across a larger spectrum of disciplines. The full potential of these protein crystalline materials has been severely restricted in practice, however, both by their inherent fragility, and by strongly held skepticism concerning their routine and predictable growth, formulation, and practical application. Fortunately, these problems have turned out to be solvable. A systematic exploration of the biophysics and biochemistry of protein crystallization has shown that one can dependably create new protein crystalline materials more or less at will. In turn, these crystals can be readily strengthened, both chemically and mechanically, to make them suitable for practical commercialization. Today, these novel materials are used as industrial catalysts on a commercial scale, in bioremediation and "green chemistry" applications, and in enantioselective chromatography of pharmaceuticals and fine chemicals. In the near future, their utility will expand, to include the purification of protein drugs, formulation of direct protein therapeutics, and development of adjuvant-less vaccines.
A CMOS-Compatible Spectrum Analyzer for Cognitive Radio Exploiting Crosscorrelation to Improve Linearity and Noise Performance (2011)

A spectrum analyzer requires a high linearity to handle strong signals, and at the same time a low NF to enable detection of much weaker signals. This is not only important for lab equipment, but also for the spectrum sensing part of cognitive radio, where low cost and integration is at a premium. Often there is a trade-off between linearity and noise: improving one degrades the other. Crosscorrelation can break this trade-off by reducing noise at the expense of measurement time. An existing RF frontend in CMOS-technology with <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">${{\rm IIP3}}\!=\!{+}11$</tex></formula> dBm and <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">${\rm NF}\!=\!5.5$</tex></formula> dB is duplicated and attenuators are put in front to increase linearity to <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex Notation="TeX">${\rm IIP3}={+}24$</tex></formula> dBm. The attenuation degrades NF, but by using crosscorrelation of the outputs of the two frontends, the effective NF is reduced to around 5 dB. In total, this results in a spurious-free dynamic range of 88 dB in 1 MHz resolution bandwidth.
Nitrification at Low Oxygen Concentration in Biofilm Reactor (2001)

A nitrification process under low dissolved oxygen (DO) concentration is proposed in a completely stirred biofilm reactor. The reactor was fed with a synthetic wastewater containing 250 mg NH4–N/L. A stable nitrite accumulation in the effluent was obtained during >110 days' operation; NO2–N:(NO2–N + NO3–N) in the effluent reached >90% under 0.5 mg DO/L. Ammonium was completely converted and NH4–N in the outlet was as low as 5 mg/L. A transient increase of the DO concentration in the reactor induced a complete conversion of ammonia and nitrite to nitrate after only 2 days. A return to a low DO concentration again induced nitrite accumulation. These results show that the nitrite oxidizers were always present in the reactor but were outcompeted at low DO concentration, due to their lower affinity for oxygen, compared with ammonia oxidizers. Nitrite accumulation could also be favored by free nitrous acid accumulation inside the biofilm.
The antibacterial activity of a siderophore (1994)

The in vitro activity of deferoxamine (DFO) both per se and in combination with the reductant ascorbic acid (AA) was determined against 10 E. coli strains, 5 P. mirabilis strains, and 10 coagulase‐negative staphylococci. In terms of interaction, the influence of DFO on the activities of cephalothin and gentamicin was furthermore investigated against the same panel of strains employing a macrobroth dilution technique and killing‐curve kinetics. The MICs of cephalothin and gentamicin were lowered for one half of the strains. Moreover, DFO prolonged the generation times of logarithmic growth phase considerably, especially when the reductant AA was present. The interactions between DFO or DFO + A A and subinhibitory concentrations of antibiotics were established by the application of growth constants, and resulted in synergy for 15 out of 25 strains with cephalothin and 9 out of 25 strains with gentamicin.
Research of Fault Location in Low-Voltage Distribution Networks (2013)

The low-voltage distribution networks have some structural features, such as short supply line, more lines branch and influence of transition resistance of the short-circuit current. These characteristics seriously affect the development of fault location technology. The paper, based on the basis of the structural features about the low-voltage distribution networks, create the distribution networks of description matrix by knowledge of mathematical topology and use the distribution network fault location algorithm based on web-based structure matrix. By the algorithm, the area of fault judgment and the actual distribution network fault location are fully consistent. The new theory provides a new way of thinking for fault location in low-voltage distribution networks.
Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography (1997)

In this study, we have used time-lapse video cinematography to study fertilization in 50 human oocytes that had undergone intracytoplasmic sperm injection (ICSI). Time-lapse recording commenced shortly after ICSI and proceeded for 17-20 h. Oocytes were cultured in an environmental chamber which was maintained under standard culture conditions. Overall, 38 oocytes (76%) were fertilized normally, and the fertilization rate and embryo quality were not significantly different from 487 sibling oocytes cultured in a conventional incubator. Normal fertilization followed a defined course of events, although the timing of these events varied markedly between oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular waves of granulation within the ooplasm which had a periodicity of 20-53 min. The sperm head decondensed during this granulation phase. The second polar body was then extruded, and this was followed by the central formation of the male pronucleus. The female pronucleus formed in the cytoplasm adjacent to the second polar body at the same time as, or slightly after, the male pronucleus, and was subsequently drawn towards the male pronucleus until the two abutted. Both pronuclei then increased in size, the nucleoli moved around within the pronuclei and some nucleoli coalesced. During pronuclear growth, the organelles contracted from the cortex towards the centre of the oocyte, leaving a clear cortical zone. The oocyte decreased in diameter from 112 to 106 microm (P < 0.0001) during the course of the observation period. The female pronucleus was significantly smaller in diameter than the male pronucleus (24.1 and 22.4 microm respectively, P = 0.008) and contained fewer nucleoli (4.2 and 7.0 respectively, P < 0.0001). After time-lapse recording, oocytes were cultured for 48 h prior to embryo transfer or cryopreservation. Embryo quality was related to fertilization events and periodicity of the cytoplasmic wave, and it was found that good quality embryos arose from oocytes that had more uniform timing from injection to pronuclear abuttal and tended to have a longer cytoplasmic wave. In conclusion, we have shown that time-lapse video cinematography is an excellent tool for studying fertilization and early embryo development, and have demonstrated that human fertilization comprises numerous complex dynamic events.
“No Time” Assignments: A Spiritual Perspective in Teacher Education (2007)

In this observational and reflective essay, I would like to discuss my experience with a type of assignment offered for educators in a holistic and integrative masters program who are interested in professional growth. I call this a “No Time” assignment and have found this type of assignment to be powerful in facilitating teacher growth, reasonably easy to formulate, and requiring little time outside of the educator’s normal activities. In this essay I will (1) briefly summarize a framework for the essence of a “No Time” assignment based on a perspective of spirituality in education, (2) describe the basic components of a “No Time” assignment, and (3) further clarify “No Time” assignments through examples from my work integrating the assignments into course work for the MA in Education, Holistic and Integrative Education program.
THYROID ADENYLATE CYCLASE STIMULATING IMMUNOGLOBULINS IN THYROID DISEASES* (1979)

The occurrence of serum immunoglobulins with capacity to stimulate thyroid adenylate cyclase (TSAb) was studied in seventy-two healthy volunteers and 120 unselected patients with various thyroid diseases. A high frequency of TSAb (82.5%, P less than 0.00006) was found in Graves' disease, while TSAb was present only in 13--20% of serum from patients with nontoxic nodular goitre, nontoxic diffuse goitre, toxic adenoma, toxic nodular goitre and myxoedema. These patients had low level of TSAb compared to patients with Graves' disease. In patients with Graves' disease there was no correlation between the level of TSAb and hormonal status except serum triiodothyronine (rs = 0.29, P less than 0.05), and no relation with eye involvement or presence of microsomal thyroid antibodies was found. The results indicate that the human thyroid adenylate cyclase assay system with 1 hour incubation periods is a sensitive method for detection of immunoglobulins with TSH-like capacity to stimulate the thyroid gland.
Increased envelope spike density and stability are not required for the neutralization resistance of primary human immunodeficiency viruses (1996)

Previous observations that the gp120 envelope glycoprotein contents of some primary, clade B human immunodeficiency virus type 1 (HIV-1) isolates were higher than those of laboratory-passaged HIV-1 isolates suggested the hypothesis that increased envelope glycoprotein spike density or stability contributes to the relative neutralization resistance of the primary viruses. To test this, the structural, replicative, and neutralization properties of a panel of recombinant viruses with HIV-1 envelope glycoproteins from divergent clades were examined in an env complementation assay. In this system, although the spike density and stability of envelope glycoproteins from primary HIV-1 isolates were not greater than those from a laboratory-adapted isolate, relative resistance to neutralizing antibodies and soluble CD4 was observed for the viruses with primary envelope glycoproteins. Thus, neither high envelope glycoprotein spike density nor stability is necessary for the relative neutralization resistance of primary HIV-1 viruses.
1.3 μm to 1.55 μm Tunable Electroluminescence from PbSe Quantum Dots Embedded within an Organic Device (2003)

Large area (mm 2 in size) infrared electroluminescent devices are demonstrated using colloidally grown PbSe quantum dots (QDs) in organic host materials. By changing the QD size the electroluminescence is tuned from λ = 1.33–1.56 μm. The fabrication of this light‐emitting device (see Figure) combines the thin film processing techniques available to organic materials with the tunable optical properties of PbSe QDs.
New Unified PON-RAN Access Architecture for 4G LTE Networks (2014)

This work presents a new converged access architecture for LTE mobile backhaul networks. In the proposed architecture, evolved NodeBs (eNBs) are interconnected with local ring-based wavelength-division-multiplexed (WDM) passive optical networks (PONs), which aggregate and efficiently transport traffic to the evolved packet core (EPC). The proposed WDM-PON ring design supports a dynamic setup of virtual circuits for inter-base-station communication, over a dedicated &#x3BB;LAN channel. It also supports load balancing, by dynamically reallocating and sharing the capacity of the downstream wavelengths. The reservation mechanism is arbitrated by the optical line terminal, which monitors the traffic imbalances of downstream channels and orchestrates the setup of subwavelength &#x201C;transient flows.&#x201D;
Progress and Challenges in VLSI Placement Research (2015)

Given the significance of placement in integrated circuit (IC) physical design, extensive research studies performed over the last 50 years addressed numerous aspects of global and detailed placement. The objectives and the constraints dominant in placement have been revised many times over, and continue to evolve. Additionally, the increasing scale of placement instances affects the algorithms of choice for high-performance tools. We survey the history of placement research, the progress leading up to the state of the art, and outstanding challenges.
Canine Lipoproteins and Atherosclerosis (1974)

Canine plasma lipoproteins were fractionated into four distinct classes by ultracentrifugation combined with Geon-Pevikon block electrophoresis and characterized with respect to physical and chemical properties. The distribution of plasma lipids and lipoproteins was quite unlike that in man, the dog having approximately five to six times as much high density as lower density lipoproteins. Despite the marked difference in distribution, human lipoprotein equivalents were present. Very low density lipoproteins (VLDL) isolated at density less than 1.006 g/ml were triglyceride-rich particles ranging in size from 260 to 900 Å in diameter. The density range from 1.006 to 1.063 g/ml contained two classes of lipoproteins: one closely resembled aolow density lipoprotein (LDL) with β mobility and a particle size of approximately 200 Å and the other (called HDL 1 ) was closely related to the high density lipoproteins with respect to immunochemical reactivity, electrophoretic mobility, and apoprotein content. The HDL 1 particles ranged in size from 100 to 350 Å in diameter and appeared to be unlike any of the commonly described human lipoproteins. High density lipoproteins called HDL 2 isolated in the density range from 1.087 to 1.21 g/ml were protein-rich particles ranging in size from 55 to 85 Å. The apolipoprotein patterns of VLDL, LDL, and HDL 2 on polyacrylamide gel electrophoresis were similar to those of the corresponding lipoproteins of man.
COMPARISON OF THE ACTIONS OF U‐46619, A PROSTAGLANDIN H2‐ANALOGUE, WITH THOSE OF PROSTAGLANDIN H2 AND THROMBOXANE A2 ON SOME ISOLATED SMOOTH MUSCLE PREPARATIONS (1981)

1 The actions of the prostaglandin H2 (PGH2) analogue, U-46619, have been compared with those of PGH2 on thromboxane A2 (TxA2) on a range of isolated smooth muscle preparations in a superfusion cascade system. 2 U-46619 was a potent agonist on guinea-pig lung strip, dog saphenous vein and rat and rabbit aortae. In contrast, U-46619 was weak or inactive on guinea-pig ileum and fundic strip, cat trachea and dog and cat iris sphincter muscles, preparations on which either PGE2 or PGF2 alpha was the most potent agonist studied. 3 PGH2 was active on all of the preparations and displayed little selectivity. On some of the preparations, the actions of PGH2 may have been mediated indirectly by conversion to other prostanoids. 4 In contrast, TxA2 displayed the same pattern of selectivity as U-46619, being a potent agonist on the lung strip and vascular preparations but weak or inactive on the others. 5 It is suggested that U-46619 is a selective TxA2-mimetic and that it should therefore be a valuable tool in the study of the actions of TxA2.
An Annexin 1 N-Terminal Peptide Activates Leukocytes by Triggering Different Members of the Formyl Peptide Receptor Family (2004)

The human N-formyl peptide receptor (FPR) is a key modulator of chemotaxis directing granulocytes toward sites of bacterial infections. FPR is the founding member of a subfamily of G protein-coupled receptors thought to function in inflammatory processes. The other two members, FPR-like (FPRL)1 and FPRL2, have a greatly reduced affinity for bacterial peptides or do not bind them at all, with FPRL2 being considered an orphan receptor so far. In this study we show that a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. The annexin 1 peptide initiates chemotactic responses in human monocytes that express all three FPR family members and also desensitizes the cells toward subsequent stimulation with bacterial peptide agonists. Experiments using HEK 293 cells stably expressing a single FPR family member reveal that all three receptors can be activated and desensitized by the N-terminal annexin 1 peptide. These observations identify the annexin 1 peptide as the first endogenous ligand of FPRL2 and indicate that annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family.
Achieving a better balance (2009)

The latest policy developments in mental health take a broader approach than their precursors, with a focus on social equality and inclusion, says Melba Wilson
Frequent somatic deletion of the 13q12.3 locus encompassing BRCA2 in chronic lymphocytic leukemia (1996)

Abstract Chronic lymphocytic leukemia (CLL) has consistent 13q chromosomal abnormalities detected by conventional cytogenetics. Using interphase cytogenetics we show deletion of a 1-megabase 13q12.3 locus, encompassing the BRCA2 gene, in 80% of 35 CLL cases studied. Homozygous deletion of BRCA2, located within the minimal deletion consensus, was detected in a significant population of cells in 60% of the cases. Deletion of the previously described 13q14 locus (analyzed with RB1 and D13S25 probes) was seen in 63% of the cases. Homozygous deletion of RB1 was seen in one case. Seven of the cases (32%) with D13S25 deletion had a population of cells with homozygous deletion. Deletions at the 13q12 and 13q14 loci result from distinct events because they were not contiguous. These data provide evidence for the existence of a new tumor suppressor locus in B-cell CLL located at 13q12.3. BRCA2, located within the minimal deletion consensus, is a candidate for the gene whose somatic inactivation could play a role in the initiation and or progression of B-cell CLL.
Physical map of the human immunoglobulin K locus and its implications for the mechanisms of VK–JKrearrangement (1987)

Genomic regions containing numerous cloned VK genes (abbreviations in ref. 2) were investigated by pulsed-field gel electrophoresis. 31 and 32 genes were linked within 1.0 and 1.3 Mb NotI fragments, respectively; the latter fragment includes also the JKCK gene segment. A 0.25 Mb NotI fragment comprises further 10 VK genes. Since the transcriptional polarities of the VK genes within the genomic regions are known the linking of the regions allows us now to answer unequivocally some longstanding questions concerning the mechanism of VK-JK rearrangement. The VK genes of the 1.3 Mb NotI fragment except for the two JK proximal ones (accompanying paper) are arranged in the same transcriptional polarity as JKCK and therefore must rearrange by a deletion mechanism. The VK genes of the 1.0 Mb NotI fragment which has not yet been linked to VKJK have identical polarity within the fragment. They should be arranged in opposite polarity to JKCK since reciprocal recombination products derived from them are known to exist; such recombination products must have been formed by inversion of oppositely oriented gene segments.
Immunometabolism governs dendritic cell and macrophage function (2015)

Recent studies on intracellular metabolism in dendritic cells (DCs) and macrophages provide new insights on the functioning of these critical controllers of innate and adaptive immunity. Both cell types undergo profound metabolic reprogramming in response to environmental cues, such as hypoxia or nutrient alterations, but importantly also in response to danger signals and cytokines. Metabolites such as succinate and citrate have a direct impact on the functioning of macrophages. Immunogenicity and tolerogenicity of DCs is also determined by anabolic and catabolic processes, respectively. These findings provide new prospects for therapeutic manipulation in inflammatory diseases and cancer.