gebhart/patrepeval huggingface dataset:
Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins (2008)

Sulfur atoms have been known to participate in hydrogen bonds (H-bonds) and these sulfur-containing H-bonds (SCHBs) are suggested to play important roles in certain biological processes. This study aims to comprehensively characterize all the SCHBs in 500 high-resolution protein structures (< or =1.8 A). We categorized SCHBs into six types according to donor/acceptor behaviors and used explicit hydrogen approach to distinguish SCHBs from those of nonhydrogen bonding interactions. It is revealed that sulfur atom is a very poor H-bond acceptor, but a moderately good H-bond donor. In alpha-helix, considerable SCHBs were found between the sulphydryl group of cysteine residue i and the carbonyl oxygen of residue i-4, and these SCHBs exert effects in stabilizing helices. Although for other SCHBs, they possess no specific secondary structural preference, their geometric characteristics in proteins and in free small compounds are significantly distinct, indicating the protein SCHBs are geometrically distorted. Interestingly, sulfur atom in the disulfide bond tends to form bifurcated H-bond whereas in cysteine-cysteine pairs prefer to form dual H-bond. These special H-bonds remarkably boost the interaction between H-bond donor and acceptor. By oxidation/reduction manner, the mutual transformation between the dual H-bonds and disulfide bonds for cysteine-cysteine pairs can accurately adjust the structural stability and biological function of proteins in different environments. Furthermore, few loose H-bonds were observed to form between the sulphydryl groups and aromatic rings, and in these cases the donor H is almost over against the rim rather than the center of the aromatic ring.
Similarity of Folate Receptor Expression in UMSCC 38 Cells to Squamous Cell Carcinoma Differentiation Markers (1995)

The fact that folate receptor expression in these malignant cells can be manipulated using retinoids and steroids suggests that these hormones could modulate the efficiency of folate and antifolate uptake via the folate receptor and may enhance the usefulness of the receptor as a target for immunotherapy.
Gene Expression Profiling of Nasal Polyps Associated With Chronic Sinusitis and Aspirin‐Sensitive Asthma (2008)

Nasal polyps appear to have characteristic transcriptional signatures compared to normal sinonasal mucosa. The five genes identified in this study likely play roles in the pathogenesis of polyps associated with CRS and ASA, and are therefore attractive targets for novel medical therapies for these common debilitating diseases.
The energetics and structure of nickel clusters: Size dependence (1991)

The energetics of nickel clusters over a broad size range are explored within the context of the many-body potentials obtained via the embedded atom method. Unconstrained local minimum energy configurations are found for single crystal clusters consisting of various truncations of the cube or octahedron, with and without (110) faces, as well as some monotwinnings of these. We also examine multitwinned structures such as icosahedra and various truncations of the decahedron, such as those of Ino and Marks. These clusters range in size from 142 to over 5000 atoms. As in most such previous studies, such as those on Lennard-Jones systems, we find that icosahedral clusters are favored for the smallest cluster sizes and that Marks’ decahedra are favored for intermediate sizes (all our atomic systems larger than about 2300 atoms). Of course very large clusters will be single crystal face-centered-cubic (fcc) polyhedra: the onset of optimally stable single-crystal nickel clusters is estimated to occur at 17 000 atoms. We find, via comparisons to results obtained via atomistic calculations, that simple macroscopic expressions using accurate surface, strain, and twinning energies can usefully predict energy differences between different structures even for clusters of much smaller size than expected. These expressions can be used to assess the relative energetic merits of various structural motifs and their dependence on cluster size.
Erythropoietin treatment during complement inhibition with eculizumab in a patient with paroxysmal nocturnal hemoglobinuria (2007)

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis leading to anemia and other clinical manifestations. Transfusions are often required to support hemoglobin at tolerable levels. A PNH patient with aplastic anemia was treated with the complement inhibitor eculizumab, followed by concurrent treatment with recombinant human erythropoietin (rHuEpo). Eculizumab alone reduced hemolysis, increased PNH red blood cell (RBC) mass, and decreased transfusions. Addition of rHuEpo during eculizumab therapy, enhanced erythropoiesis, further increased PNH RBC mass and hemoglobin levels, and rendered the patient transfusion independent for more than two years. These data show that driving erythropoiesis during eculizumab treatment provided further benefit to a patient with PNH and underlying bone marrow failure.
Studies on encephalitogenic fragments of myelin protein. IV. Synthesis of glycine analogs of tryptophan-containing fragment. (1974)

Synthesis of five glycine analogs of H-Arg-Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Arg-OH, in which amino acid residues at positions 3, 6 and 7 are replaced by glycine, is reported. Correlation of structure and activity of the encephalitogenic decapeptide fragment is discussed on the basis of the activity in guinea pigs and circular dichroism spectra of the synthetic glycine analogs.
Meniscal replacement using a cryopreserved allograft. An experimental study in the dog. (1990)

The medial menisci of 14 adult dogs were replaced using a cryopreserved meniscal allograft. The morphology and metabolic activity of the transplanted allografts were then evaluated using routine histology, a vascular-injection (Spalteholz) technique, and autoroentgenography (Na2(35)SO4 incorporation) at various intervals, from two weeks to six months postoperatively. After transplantation, the allografts retained their normal gross appearance and healed to the capsular tissues of the host by fibrovascular scar tissue. Histologically, the grafts demonstrated a decrease in the number of metabolically active cells after transplantation but had a normal cellular distribution and Na2(35)SO4 uptake by three months. The allografts appeared to function normally after transplantation. Although some degenerative changes were noted in the tibial articular cartilage not covered by the meniscus, the cartilage beneath the allograft appeared normal.
Targeted Gene Knock In and Sequence Modulation Mediated by a Psoralen-linked Triplex-forming Oligonucleotide* (2008)

Information from exogenous donor DNA can be introduced into the genome via homology-directed repair (HDR) pathways. These pathways are stimulated by double strand breaks and by DNA damage such as interstrand cross-links. We have employed triple helix-forming oligonucleotides linked to psoralen (pso-TFO) to introduce a DNA interstrand cross-link at a specific site in the genome of living mammalian cells. Co-introduction of duplex DNA with target region homology resulted in precise knock in of the donor at frequencies 2-3 orders of magnitude greater than with donor alone. Knock-in was eliminated in cells deficient in ERCC1-XPF, which is involved in recombinational pathways as well as cross-link repair. Separately, single strand oligonucleotide donors (SSO) were co-introduced with the pso-TFO. These were 10-fold more active than the duplex knock-in donor. SSO efficacy was further elevated in cells deficient in ERCC1-XPF, in contrast to the duplex donor. Resected single strand ends have been implicated as critical intermediates in sequence modulation by SSO, as well as duplex donor knock in. We asked whether there would be a competition between the donor species for these ends if both were present with the pso-TFO. The frequency of duplex donor knock in was unaffected by a 100-fold molar excess of the SSO. The same result was obtained when the homing endonuclease I-SceI was used to initiate HDR at the target site. We conclude that the entry of double strand breaks into distinct HDR pathways is controlled by factors other than the nucleic acid partners in those pathways.
Protective effect of trehalose-loaded liposomes against UVB-induced photodamage in human keratinocytes (2014)

Trehalose, a naturally occurring non-reducing disaccharide, is known to act as a major protein stabilizer that can reduce ultraviolet B (UVB)-induced corneal damage when topically applied to the eye. However, due to the low skin permeability of trehalose, which makes the development of topical formulations difficult, its use as a skin photoprotective agent has been limited. Previous findings demonstrated that liposomes may significantly improve the intracellular delivery of trehalose. Therefore, the present study aimed to assess the protective effects of trehalose-loaded liposomes against UVB-induced photodamage using the immortalized human keratinocyte cell line, HaCaT. The effects were also compared to those of the common skin photoprotective compounds, including L-carnosine, L-(+)-ergothioneine, L-ascorbic acid and DL-α-tocopherol. The levels of cyclobutane pyrimidine dimers, 8-hydroxy-2'-deoxyguanosine and protein carbonylation in HaCaT cells were used as biological markers of UVB-induced damage. Compared to other compounds, trehalose-loaded liposomes showed the highest efficacy in reducing the levels of the three markers following UVB irradiation of HaCaT cells (all P<0.001 when compared to each of the four other photoprotective compounds). Therefore, these findings indicate that there may be a clinical application for trehalose-loaded liposomes, and further studies should be performed to assess the potential usefulness in skin photoprotection and the prevention of non-melanoma skin cancer.
Pharmacotherapy of Narcolepsy: Focus on Sodium Oxybate (2010)

Narcolepsy is a complex disease with multiple symptoms that include excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Pharmacologic management of patients with narcolepsy is based on treating these symptoms. Sodium oxybate, a neurotransmitter product of γ-amino butyric acid (GABA), is a Schedule III controlled substance in the US, approved for the treatment of excessive daytime sleepiness (EDS), and cataplexy in patients with narcolepsy. The purpose of this review is to summarize the current knowledge about treatment of narcolepsy with sodium oxybate and to familiarize readers with the safety and efficacy of sodium oxybate, thus enabling clinicians to optimize their management of narcolepsy. A review of the pharmacokinetics, pharmacodynamics, efficacy in different symptoms of narcolepsy, adverse effects, tolerability, and dosing of sodium oxybate is presented. Sodium oxybate administered as an oral solution has a rapid onset of effect, a short duration of action, and nearly complete metabolism with negligible unchanged γ-hydroxybutyrate (GHB) appearing in the urine. There is mounting evidence suggesting that GHB may function as an endogenous neuromodulator/neurotransmitter. The mechanism by which sodium oxybate has a therapeutic effect in narcolepsy is unclear. The efficacy of oral sodium oxybate on the treatment of narcolepsy was evaluated in two randomized, double-blind, placebo- controlled, multicenter, US and International trials. Treatment of patients with narcolepsy-cataplexy with sodium oxybate leads to reduction in the frequency of cataplexy attacks in a dose-related manner, improved EDS, increased level of alertness and ability to concentrate. The major problem with sodium oxybate remains in its potential for non-medical use to elicit altered states of consciousness; however, abuse and misuse of sodium oxybate has been rare over the 7 years since its introduction in the market. Other issues revolve around twice nightly dosing, and salty taste. The most commonly reported adverse events associated with the use of sodium oxybate and occurring with at least 5% greater frequency than seen in placebo-treated patients were dizziness, headache, nausea, pain, night terrors, enuresis, confusion, infection, vomiting, and urinary incontinence. In conclusion, sodium oxybate significantly improves all symptoms in patients with narcolepsy and is well tolerated.
Effect of Gelonin Immunoconjugate with Monoclonal Antibody MSN‐1 to Endometrial Adenocarcinoma on Antigen‐producing Tumor Cells in vivo (1998)

Missile therapy, which destroys cancer cells specifically, has been advocated as an effective modality for the treatment of carcinoma. We have developed an immunoconjugate consisting of the monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, combined with a plant hemitoxin named gelonin via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate and 2-iminothiolane, and examined its selective cytotoxicity in athymic mice. The reductions in resected weights of target tumor cells, at the local site of MSN-1-gelonin immunoconjugate treatment, were 96% with local administration and 75% with caudal vein administration, as compared with the untreated group. There was no weight loss in treated mice. Our results suggest that this MSN-1-gelonin immunoconjugate has potential clinical applications in the treatment of endometrial adenocarcinomas.
Immunofluorometric assay for sensitive and specific measurement of human prostatic glandular kallikrein (hK2) in serum (1996)

Prostate-specific antigen (PSA) and human prostatic glandular kallikrein (hK2) have 79% identity with the primary structure. When we used recombinant hK2 protein, only 7 of 23 monoclonal anti-PSA IgGs (monoclonal antibodies, MAbs) cross-reacted with hK2, which enabled us to design a novel immunofluorometric MAb-MAb assay for the specific detection of hK2. In the first incubation, an excess of MAb 2H11, which does not cross-react with hK2, is added to prevent both free and complexed PSA from reacting in subsequent immunoreactions. In the second incubation, biotinylated MAb H50, which cross-reacts with hK2 by an epitope overlapping with MAb 2H11, served to bind only hK2 to the microtitration wells coated with streptavidin. In the third step, Eu-labeled MAb H117, which cross-reacts with hK2, detected the immobilized hK2. The hK2 assay was calibrated with recombinant hK2. The detection limit of the assay was 0.1 microgram/L, and the cross-reactivity with recombinant PSA was < or = 0.7%. The concentration of hK2 was measured in serum samples from 334 males with total PSA concentrations ranging from 1 to 3400 microgram/L. Most of the samples (57%) had hK2 concentrations below the detection limit. The proportions of hK2 relative to total PSA were 0-2% in 79%, 2-5% in 14%, 5-10% in 4%, and >10% in 3% of the samples. Gel filtration of 10 serum samples with increased hK2 concentrations showed a single peak of hK2 immunoreactivity with an apparent molecular size of approximately 30 kDa, corresponding to that of recombinant hK2 and free PSA.
Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity (2015)

Selected cytotoxic chemicals can provoke the immune system to recognize and destroy malignant tumors. Most of the studies on immunogenic cell death are focused on the signals that operate on a series of receptors expressed by dendritic cells to induce tumor antigen-specific T-cell responses. Here, we explored the effects of oxaliplatin, an immunogenic cell death inducer, on the induction of stress ligands and promotion of natural killer (NK) cell-mediated cytotoxicity in human ovarian cancer cells. The results indicated that treatment of tumor cells with oxaliplatin induced the production of type I interferons and chemokines and enhanced the expression of major histocompatibility complex class I-related chains (MIC) A/B, UL16-binding protein (ULBP)-3, CD155 and TNF-related apoptosis-inducing ligand (TRAIL)-R1/R2. Furthermore, oxaliplatin but not cisplatin treatment enhanced susceptibility of ovarian cancer cells to NK cell-mediated cytolysis. In addition, activated NK cells completely abrogated the growth of cancer cells that were pretreated with oxaliplatin. However, cancer cells pretreated with the same concentration of oxaliplatin alone were capable of potentiating regrowth over a period of time. These results suggest an advantage in combining oxaliplatin and NK cell-based therapy in the treatment of ovarian cancer. Further investigation on such potential combination therapy is warranted.
Design of an Intervertebral Disc Prosthesis (1991)

This article presents criteria for the design of a lumbar intervertebral disc prosthesis that take into consideration issues of endurance, materials behavior, geometry, kinetics, motion constraints, fixation to bone, and safety. The criteria and design philosophies discussed are generally applicable in the synthesis of any new implant system. Specifications of the design of a disc prosthesis are presented along with an evaluation of the design based on some of the preliminary test data.
Quality of Service Routing in Integrated Services Networks (1998)

Abstract : Future integrated services networks will support multiple classes of service to meet the diverse quality of service (QoS) requirements of applications. To meet these end to end QoS requirements, strict resource constraints may have to be imposed on the paths being used. QoS routing refers to a set of protocols and algorithms that can select paths that satisfy such constraints while achieving high network throughput. QoS routing is challenging because (1) different service classes employ different resource sharing models, (2) service classes dynamically share link resources, and (3) selecting paths that meet multiple QoS constraints is a complex algorithmic problem. This dissertation shows QoS routing in integrated services networks is both desirable and feasible. To support this claim, this dissertation develops an integrated QoS routing framework that has two components. The first component consists of routing algorithms for individual service classes that support either bandwidth guarantees, delay guarantees, or high throughput. By exploiting the relationship between QoS constraints, we develop polynomial routing algorithms for traffic classes that require stringent end to end performance guarantees. By coupling routing with finer time scale resource management mechanisms such as congestion control and scheduling, we develop routing algorithms that achieve high throughput for best effort traffic and low blocking rate for guaranteed traffic. By striking an appropriate balance between per flow resource consumption and the distribution of network load, these algorithms improve resource utilization efficiency and network throughput under dynamic load conditions. In a network that supports multiple classes of service, best effort flows can experience congestion or even starvation if guaranteed flows are not routed appropriately.
Characterization of sugar chain structures of human α‐fetoprotein by lectin affinity electrophoresis (1998)

Alpha-Fetoprotein (AFP) glycoforms, defined as AFP with different chemical structures of carbohydrate, were analyzed by affinity electrophoresis with several lectins of known specificities against complex-type oligosaccharides. Serum AFP samples from cord blood on full-term delivery and from patients with hepatocellular carcinoma and extrahepatic malignancies including gastrointestinal tumors and yolk sac tumors were used. Two-dimensional lectin affinity electrophoresis and also lectin affinity chromatography coupled with lectin affinity electrophoresis were employed. More than ten AFP glycoforms were identified or characterized using the above-mentioned AFP samples. Known specificities of the lectins against complex-type oligosaccharides were refined or their additional specificities were found in this study. Lectin appeared to have specificity against carbohydrates by recognizing not only specific residues but also the whole carbohydrate molecule containing the residues, resulting in differential affinities for the lectin.
Picomolar Amyloid-β Positively Modulates Synaptic Plasticity and Memory in Hippocampus (2008)

Amyloid-beta (Abeta) peptides are produced in high amounts during Alzheimer's disease, causing synaptic and memory dysfunction. However, they are also released in lower amounts in normal brains throughout life during synaptic activity. Here we show that low picomolar concentrations of a preparation containing both Abeta(42) monomers and oligomers cause a marked increase of hippocampal long-term potentiation, whereas high nanomolar concentrations lead to the well established reduction of potentiation. Picomolar levels of Abeta(42) also produce a pronounced enhancement of both reference and contextual fear memory. The mechanism of action of picomolar Abeta(42) on both synaptic plasticity and memory involves alpha7-containing nicotinic acetylcholine receptors. These findings strongly support a model for Abeta effects in which low concentrations play a novel positive, modulatory role on neurotransmission and memory, whereas high concentrations play the well known detrimental effect culminating in dementia.
Broadband Visible Light Induced NO Formation (2009)

Nitric oxide formation is a potential mechanism for photobiomodulation because it is synthesized in cells by nitric oxide synthase (NOS), which contains both flavin and heme, and thus absorbs visible light. The purpose of this work was to study broadband visible light induced NO formation in various cells. Cardiac, endothelial, sperm cells and RAW 264.7 macrophages were illuminated with broadband visible light, 40–130 mW/cm2, 2.4–39 J/cm2, and nitric oxide production was quantified by using the Griess reagent. The results showed that visible light illumination increased NO concentration both in sperm and endothelial cells, but not in cardiac cells. Activation of RAW 264.7 macrophages was very small. It thus appears that NO is involved in photobiomodulation, though different light parameters and illumination protocols are needed to induce NO in various cells.
Quantum Dot Solar Cells. Semiconductor Nanocrystals as Light Harvesters (2008)

The emergence of semiconductor nanocrystals as the building blocks of nanotechnology has opened up new ways to utilize them in next generation solar cells. This paper focuses on the recent developments in the utilization of semiconductor quantum dots for light energy conversion. Three major ways to utilize semiconductor dots in solar cell include (i) metal−semiconductor or Schottky junction photovoltaic cell (ii) polymer−semiconductor hybrid solar cell, and (iii) quantum dot sensitized solar cell. Modulation of band energies through size control offers new ways to control photoresponse and photoconversion efficiency of the solar cell. Various strategies to maximize photoinduced charge separation and electron transfer processes for improving the overall efficiency of light energy conversion are discussed. Capture and transport of charge carriers within the semiconductor nanocrystal network to achieve efficient charge separation at the electrode surface remains a major challenge. Directing the future research efforts toward utilization of tailored nanostructures will be an important challenge for the development of next generation solar cells.
Suppression of CHK1 by ETS Family Members Promotes DNA Damage Response Bypass and Tumorigenesis (2015)

Genetic translocation and aberrant expression of ETS family members is a common event in different types of human tumors. Here, we show that through the transcriptional repression of CHK1, ETS factors may favor DNA damage accumulation and consequent genetic instability in proliferating cells. Importantly, our findings provide a rationale for testing DNA replication inhibitor agents in ETS-positive TP53-proficient tumors.