gebhart/patrepeval huggingface dataset:
Somatic mutations and germline sequence variants in patients with familial colorectal cancer (2010)

It is estimated that up to 35% of colorectal cancers (CRC) can be explained by hereditary factors. However, genes predisposing to highly penetrant CRC syndromes account for only a small fraction of all cases. Thus, most CRCs still remain molecularly unexplained. A recent systematic sequencing study on well-annotated human protein coding genes identified 280 somatically mutated candidate cancer genes (CAN genes) in breast and colorectal cancer. It is estimated that 8% of all reported cancer genes show both somatic and germline mutations. Therefore, the identified CAN genes serve as a distinct set of candidates for being involved in hereditary susceptibility. The aim of this study was to evaluate the role of colorectal CAN genes in familial CRC. Samples from 45 familial CRCs without known cancer predisposing mutations were screened for somatic and germline variants in 15 top-ranked CAN genes. Six of the genes were found to be somatically mutated in our tumor series. We identified 22 nonsynonymous somatic mutations of which the majority was of missense type. In germline, three novel nonsynonymous variants were identified in the following genes: CSMD3, EPHB6 and C10orf137, and none of the variants were present in 890 population-matched healthy controls. It is possible that the identified germline variants modulate predisposition to CRC. Functional validation and larger sample sets, however, will be required to clarify the role of the identified germline variants in CRC susceptibility.
Triterpene derivatives that block entry of human immunodeficiency virus type 1 into cells. (1994)

A series of triterpene compounds characterized by a stringent structure-activity relationship were identified as potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication. Currently studied botulinic derivatives have 50% inhibitory concentrations (IC50) against HIV-1 strain IIIB/LAI in the 10 nM range in several cellular infection assays but are inactive against HIV-2. These compounds did not significantly inhibit the in vitro activities of several purified HIV-1 enzymes. Rather, they appeared to block virus infection at a postbinding, envelope-dependent step involved in the fusion of the virus to the cell membrane.
Diverse Mechanisms for Regulating Ribosomal Protein Synthesis in Escherichia coli (1994)

This chapter describes the current knowledge of the organization and regulation of ribosomal genes, emphasizing recent work elucidating the molecular mechanisms regulating ribosomal protein synthesis and illustrating the diversity of these mechanisms. In E. coli, the small ribosomal subunit contains one rRNA molecule (16 S) and 21 proteins. The large subunit harbors two rRNA molecules (23 S and 5 S) and 34 proteins. All of the genes for these ribosomal components have been mapped on the E . coli chromosome. Furthermore, all but three of the r-protein genes have been sequenced. Because proteins are the most abundant cellular macromolecules, cell growth requires that a large fraction of the cell mass be devoted to the protein synthesis machinery— namely, the ribosomes and their ancillary factors. For example, in rapidly growing bacteria, ribosomes account for as much as 50% of cellular dry mass. Because ribosome formation commands such a large fraction of cellular resources, even minor adjustments in the rate of ribosome synthesis can have a major impact on the economy of the cell.
Inhibition of Stearoyl-Coenzyme A Desaturase 1 Dissociates Insulin Resistance and Obesity From Atherosclerosis (2008)

This study demonstrates that atherosclerosis can occur independently of obesity and insulin resistance and argues against SCD1 inhibition as a safe therapeutic target for the metabolic syndrome.
个人主义时代的社团——访A.埃齐奥尼 (1991)

社会学家阿米泰·埃齐奥尼(Amitai Etzioni)是美国正在形成中的思想家群体——“社团主义者”(communitarians)的一位带头人。社团主义者认为,必须以社会责任来制衡个人权利。埃齐奥尼是一本新季刊——《责任社团》的编辑,这本杂志为讨论权利与责任的关系问题提供了论坛。他在接受《未来学家》杂志记者T.维拉德和D.菲尔茨采访时,谈了社团主义者目前深入思考的问题。以下是这次采访的主要内容: 记者问(以下简称“问”):您和其他社团主义者说过,过分注重个人权利,正损害着社团需要。您能否举例说明,在哪些地方个
Iron deprivation increases erythropoietin production in vitro, in normal subjects and patients with malignancy (1996)

Although tissue hypoxia is the major stimulus for erythropoietin (EPO) production, serum EPO (sEPO) levels at any given Hb in iron-deficiency anaemia are relatively higher than in other anaemias. Iron chelators stimulate erythropoiesis in anaemia of chronic disease via unknown mechanisms. A recent study suggested that deferoxamine (DFO) regulates steady-state EPO RNA. Here we report that altered intracellular iron balance regulates EPO production both in vitro and in two unique clinical trials. In vitro, both iron chelation with DFO and blockade of Tf-mediated iron uptake with anti-Tf receptor antibody 42/6, stimulated EPO production in serum-deprived hepatoma cells. Conversely, iron repletion by haemin, inhibited EPO production in these cells. In clinical studies, sEPO levels rose in adult volunteers treated with DFO coupled to hydroxyethyl starch (HES-DFO) and in patients with advanced malignancy treated with anti-Tf receptor antibody 42/6, in a time- and dose-dependent manner. These studies indicate intracellular iron balance regulates EPO production in humans.
Preliminary structure determination of the capsular polysaccharide of Vibrio cholerae O139 Bengal Al1837 (1995)

Vibrio cholerae O139 Bengal has recently been identified as a cause of epidemic cholera in Asia. In contrast to V. cholerae O1, V. cholerae O139 Bengal has a polysaccharide capsule. As determined by high-performance anion-exchange chromatography and 1H nuclear magnetic resonance analysis, the capsular polysaccharide of V. cholerae O139 Bengal strain Al1837 has six residues in the repeating subunit; this includes one residue each of N-acetylglucosamine, N-acetylquinovosamine (QuiNAc), galacturonic acid (GalA), and galactose and two residues of 3,6-dideoxyxylohexose (Xylhex). The proposed structure is [formula: see text]
Facile and Efficient Synthesis of 6-(Hydroxymethyl)purines (2004)

[reaction: see text] A facile and efficient methodology of the synthesis of 6-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed based on Pd-catalyzed cross-coupling reactions of 6-halopurines with acyloxymethylzinc iodides followed by deprotection. Several title compounds are inhibitors of adenosine deaminase and exert cytostatic activity.
Simple COMA node implementations (1994)

Shared memory architectures often have caches to reduce the number of slow remote memory accesses. The largest possible caches exist in shared memory architectures called Cache-Only Memory Architectures (COMAs). In a COMA all the memory resources are used to implement large caches. Unfortunately, these large caches also have their price. Due to its lack of physically shared memory, COMA may suffer from a longer remote access latency than alternatives. Large COMA caches might also introduce an extra latency for local memory accesses, unless the node architecture is designed with care. The authors examine the implementation of COMAs, and consider how to move much of the complex functionality into software. They introduce the idea of a simple COMA architecture, a hybrid with hardware support only for the functionality frequently used. Such a system is expected to have good performance, and because of its simplicity it should be quick and cheap to develop and engineer.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: An open question (2015)

Non-alcoholic liver disease (NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders. The association between NAFLD and metabolic syndrome is well documented and widely recognized. Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma (HCC) risk factors. There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries. Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC. As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future. Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis (insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC. However, a comprehensive view of molecular mechanisms linking obesity, T2DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety. Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC. In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.
The Effect of a 1‐Stage Full‐Mouth Disinfection on Oral Malodor and Microbial Colonization of the Tongue in Periodontitis Patients. A Pilot Study (1998)

Oral malodor affects a large proportion of the population and may be the cause of a significant social and psychological handicap. This pilot study aimed to examine whether a 1-stage full-mouth disinfection in periodontitis patients (scaling and root planing of all pockets within 24 hours together with the application of chlorhexidine to all intra-oral niches followed by chlorhexidine mouth rinsing for 2 months) resulted in a significant improvement in malodor when compared to a fractionated periodontal therapy (consecutive root planings per quadrant, at a 1 to 2 week interval). The baseline and outcome data concerning oral malodor were linked to the presence of tongue coating and to its roughness (fissures). Twenty-four patients with severe periodontitis were randomly allocated to test and control groups. At baseline and after 1 and 2 months, the concentration of volatile sulfur compounds (VSC) in the mouth was measured and organoleptic ratings (expired air and total mouth air) were given. Plaque samples were collected from the dorsum of the tongue to calculate the number of colony forming units (CFU) per ml (anaerobic culturing) as well as the number of pigmented CFU/ml. Both the baseline organoleptic ratings and the VSC scores correlated well with the presence of tongue coating but not with the tongue roughness. Because a correlation between tongue coating and its microbial load could not be detected, it was hypothesized that the tongue coating per se, and not the bacteria, might be responsible for the malodor. The 1-stage full-mouth disinfection resulted in a faster and additional reduction in the organoleptic ratings of the oral malodor, even after 2 months. This might be explained by the improved periodontal outcome and/or the more significant reduction in the CFU/ml of pigmented species. In contrast to the organoleptic ratings, which were significantly reduced in both treatment groups (when compared to baseline), the VSC levels remained unchanged. This pilot study indicates that a 1-stage full-mouth disinfection has, in comparison to a standard periodontal therapy, additional beneficial effects in the treatment of oral malodor.
Enhanced histologic repair in a central wound in the anterior cruciate ligament with a collagen–platelet‐rich plasma scaffold (2007)

The anterior cruciate ligament (ACL) of the knee is an intra-articular ligament that fails to heal after primary repair. The medial collateral ligament (MCL) of the knee is an extra-articular ligament that heals uneventfully in the majority of cases. Why these two ligaments have such different responses to injury remains unclear. In this article, we address two hypotheses: first, that the histologic response to injury is different in intra-articular and extra-articular ligaments, and second, that the response of the intra-articular ligaments can be altered by placing a collagen-platelet-rich plasma (collagen-PRP) hydrogel in the wound site. Wounds were created in extra-articular ligaments (MCL and/or patellar ligament) and an intra-articular ligament (ACL) in canine knees, and the histologic response to injury evaluated at 3 days (n = 3), 7 days (n = 4), 3 weeks (n = 5), and 6 weeks (n = 5). In the 3-week (n = 5) and 6-week (n = 5) animals, bilateral central wounds were made in the ACLs and the wounds in one knee of each animal treated with a collagen-PRP hydrogel while the contralateral side was untreated. Extra-articular ligament wounds had greater filling of the wound site and increased presence in the wound site of fibrinogen, fibronectin, PDGF-A, TGF-beta1, FGF-2, and von Willebrand's factor when compared to intra-articular ligament wounds. Treatment of the intra-articular wound with a collagen-PRP hydrogel resulted in increased filling of the wound site with repair tissue that had similar profiles of growth factor and protein expression to the extra-articular ligament wounds. The use of a collagen-PRP scaffold can ameliorate histologic differences noted between healing extra-articular ligamentous wounds and nonhealing intra-articular ligamentous wounds. This study supports the hypothesis that premature scaffold failure may play a key role in the normally expected failure of the ACL to heal after injury.
Erwinia herbicola: A Bacterial Ice Nucleus Active in Increasing Frost Injury to Corn (2009)

Cell suspensions of an isolate of <i>Erwinia herbicola</i> from a corn leaf were active in ice nucleation at -2.3 C and below. Ice nucleation activity was affected by the medium on which the cells were grown. Nucleation at -2.3 and -2.5 C was detected in suspensions of cells that had been grown on nutrient agar supplemented with 2.5% glycerol or glucose, respectively, but was detected only at temperatures below -4 C in cells grown on nutrient agar alone. Corn seedlings sprayed with suspensions of this isolate of <i>E. herbicola</i> were severely damaged at -4 C, whereas control plants lacking leaf populations of <i>E. herbicola</i> or other bacteria active in ice nucleation were not injured. If plants were frozen 6 hr or less after they were sprayed with suspensions (10<sup>7</sup> cells/ml) of <i>E. herbicola</i>, frost damage was not significantly different from that to controls. The amount of damage increased greatly with increase in time of incubation between spraying and freezing, from 12 to about 36 hr. The amount of frost damage measured 48 hr after application of <i>E. herbicola</i> suspensions increased as applied bacterial cell densities were increased. <i>Erwinia herbicola</i> began rapid multiplication about 6 hr after the cells were sprayed onto leaves; populations of about 3 × 10<sup>3</sup> cells/g fresh weight of leaf at 6 hr after inoculation had increased to about 5 × 10<sup>6</sup> cells/g after 36 hr. Probit frost injury was directly proportional to the logarithm of <i>E. herbicola</i> population (<i>P</i> <0.001).
A new method for the synthesis of boronate macrocycles (2004)

The condensation of aryl boronic acids with 2,3-dihydroxypyridine gives boronates, which self-assemble to form tetrameric macrocycles as evidenced by X-ray crystallographic analyses.
The influence of crystallinity of the hydroxyapatite coating on the fixation of implants (1999)

We inserted two hydroxyapatite (HA)-coated implants with crystallinities of either 50% (HA-50%) or 75% (HA-75%) bilaterally into the medial femoral condyles of the knees of 16 dogs. The implants were allocated to two groups with implantation periods of 16 and 32 weeks. They were weight-bearing and subjected to controlled micromovement of 250 μm during each gait cycle. After 16 weeks, mechanical fixation of the HA-50% implants was increased threefold as compared with the HA-75% implants. After 32 weeks there was no difference between HA-50% and HA-75%. Fixation of HA-75% increased from 16 to 32 weeks whereas that of HA-50% was unchanged. HA-50% implants had 100% more bone ingrowth than HA-75% implants after 16 weeks. More HA coating was removed on HA-50% implants compared with HA-75% implants after both 16 and 32 weeks. No further loss of the HA coating was shown from 16 to 32 weeks. Our study suggests that the crystallinity of the HA coating is an important factor in its bioactivity and resorption during weight-bearing conditions. Our findings suggest two phases of coating resorption, an initial rapid loss, followed by a slow loss. Resorbed HA coating was partly replaced by bone ingrowth, suggesting that implant fixation will be durable.
Major histocompatibility complex class I‐specific receptors on human natural killer and T lymphocytes (1997)

Human NK cells express several specialized inhibitory receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more HLA class I alleles leads to NK-mediated target cell lysis. Receptors specific for groups of HLA-C (p58), HLA-B (p70) and HLA-A (p140) alleles belong to the Ig superfamily with two or three Ig-like domains in their extracellular portion, and a long cytoplasmic tail containing ITIM motifs and associated with a non-polar transmembrane portion. In contrast, the CD94/ NKG2-A receptor complex is composed of type II proteins with a C-type lectin domain which displays a more broad specificity for different class I alleles. Recently, activatory forms of the HLA-C-specific receptors have been identified in some donors. They are virtually identical to the inhibitory forms in their extracellular portions, but display a short cytoplasmic tail lacking ITIM motifs associated with a Lys-containing transmembrane portion (p50). A subset of activated T-lymphocytes, primarily CD8+ and oligoclonal or monoclonal in nature, express NK-type class I-specific receptors. These receptors exert an inhibitory activity on T-cell receptor-mediated functions and may provide an important mechanism of down-regulation of T-cell responses.
Use of Base-Modified Duplex-Stabilizing Deoxynucleoside 5′-Triphosphates To Enhance the Hybridization Properties of Primers and Probes in Detection Polymerase Chain Reaction (2008)

Several base-modified duplex-stabilizing deoxyribonucleoside 5'-triphosphates (dNTPs) have been evaluated as agents for enhancing the hybridization properties of primers and probes in real-time polymerase chain reaction (PCR). It was shown that pyrimidines substituted at the 5-position with bromine or iodine atoms and methyl or propynyl groups are incorporated into PCR amplicons by Taq DNA polymerase as efficiently as natural dNTPs. The dNTP of 2-aminoadenosine was incorporated somewhat less efficiently than dATP but still supported PCR. Incorporation of these modified nucleotides into the amplified DNA represents a simple and inexpensive way to stabilize duplexes of primers and probes and is particularly effective in improving the amplification and detection of A/T-rich sequences. This technology permits the use of higher PCR annealing temperatures or alternatively a reduction in the length of the oligonucleotide components. Examples of successful application in TaqMan and Scorpion real-time detection assays are provided. Limits of the approach are identified and discussed. For example, application of the 5-bromo and 5-iodo derivatives may be limited to relatively G/C-rich DNA targets and, in particular, to those lacking long runs of adenylate and/or thymidylate. Simultaneous use of base-modified analogues of dATP and dTTP should be avoided in PCR due to "overstabilization" of the amplicon.
Fluorescent Two-photon Absorption Benzothiadiazole Dyes Having Photoreleasing Quenchers (2009)

Abstract Fluorescent two-photon absorption benzothiadiazole dye 5 provides significant fluorescence quenching by introducing nitrobenzene quencher moieties. The florescence intensity is recovered by photoreleasing of the quencher moieties upon irradiation.
C-Mannosylation and O-Fucosylation of the Thrombospondin Type 1 Module (2001)

Thrombospondin-1 (TSP-1) is a multidomain protein that has been implicated in cell adhesion, motility, and growth. Some of these functions have been localized to the three thrombospondin type 1 repeats (TSRs), modules of approximately 60 amino acids in length with conserved Cys and Trp residues. The Trp residues occur in WXXW patterns, which are the recognition motifs for protein C-mannosylation. This modification involves the attachment of an alpha-mannosyl residue to the C-2 atom of the first tryptophan. Analysis of human platelet TSP-1 revealed that Trp-368, -420, -423, and -480 are C-mannosylated. Mannosylation also occurred in recombinant, baculovirally expressed TSR modules from Sf9 and "High Five" cells, contradictory to earlier reports that such cells do not carry out this reaction. In the course of these studies it was appreciated that the TSRs in TSP-1 undergo a second form of unusual glycosylation. By using a novel mass spectrometric approach, it was found that Ser-377, Thr-432, and Thr-489 in the motif CSX(S/T)CG carry the O-linked disaccharide Glc-Fuc-O-Ser/Thr. This is the first protein in which such a disaccharide has been identified, although protein O-fucosylation is well described in epidermal growth factor-like modules. Both C- and O-glycosylations take place on residues that have been implicated in the interaction of TSP-1 with glycosaminoglycans or other cellular receptors.
Hypothermia/Warming Protocols: Why Are They Not Widely Used in the OR? (2008)

Hypothermia, a common problem for patients having surgery, adversely affects multiple organ systems and physiologic functions. Research indicates that maintaining normothermia can reduce infection rates, operative blood loss, and length of hospital stay. Often, preventing hypothermia is not a high priority to surgical staff members because forced-air warming systems may cause field contamination and passive warming may increase the ambient OR temperature. In addition, inconsistent practices and lack of guidelines may affect team members' efforts. Surgical team awareness, education, and understanding of the effects of hypothermia are necessary components to enhance the ways clinicians provide quality, cost-effective patient care.
Expression of the human growth hormone variant gene in cultured fibroblasts and transgenic mice. (1988)

The nucleotide sequence of the human growth hormone variant gene, one of the five members of the growth hormone gene family, predicts that it encodes a growth hormone-like protein. As a first step in determining whether this gene is functional in humans, we have expressed a mouse metallothionein I/human growth hormone variant fusion gene in mouse L cells and in transgenic mice. The growth hormone variant protein expressed in transiently transfected L cells is distinct from growth hormone itself with respect to reactivity with anti-growth hormone monoclonal antibodies, behavior during column chromatography, and isoelectric point. Transgenic mice expressing the growth hormone variant protein are 1.4- to 1.9-fold larger than nontransgenic controls, suggesting that the protein has growth-promoting properties.