gebhart/patrepeval huggingface dataset:
Stabilization of Barstar by Chemical Modification of the Buried Cysteines (1996)

The internal packing of residues in the small monomeric protein barstar was severely perturbed by chemical modification of the two buried cysteine residues with the thiol reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) after prior unfolding of the protein using guanidine hydrochloride (GdnHCl). The modification produces mixed disulfides between 5-thio(2-nitrobenzoic acid) and the two Cys residues. To understand the effects of the modification of the individual cysteine residues, Cys40 and Cys82, the modification was also carried out on the two single Cys --> Ala mutant forms of barstar, C40A and C82A, whose structures, activities, and stabilities were first shown to be similar to those of wt barstar. Equilibrium GdnHCl-induced denaturation studies on wt barstar show that the modification causes the midpoint of the denaturation curve to increase by 0.6 M and the stability to increase by 1.3 kcal mol-1. Both C40A and C82A also denature at higher concentrations of GdnHCl after modification. Modification of Cys40 has approximately the same stabilizing contribution as does modification of Cys82. The structures of the modified and unmodified proteins have been compared using circular dichroism (CD) spectroscopy, UV difference absorption spectroscopy, and fluorescence spectroscopy. It is shown that the 5-thio(2-nitrobenzoic acid) groups introduced by reaction with DTNB are buried in hydrophobic environments in the modified C40A and C82A mutant proteins, as well as in modified wt barstar. The far-UV CD spectra of the modified and unmodified proteins are similar, but the mean residue ellipticity at 220 nm of wt barstar is reduced by 30% upon modification. Such a decrease is not seen for either C40A or C82A. The barnase-inhibiting activities of the three modified proteins are shown to be similar to those of the corresponding unmodified proteins. Thus, the severe perturbations of the internal packing, which result in a significant increase in stability, do not appear to affect the overall fold of barstar.
Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated (2001)

Na channel NaN (Na(v)1.9) produces a persistent TTX-resistant (TTX-R) current in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia. Na(v)1.9-specific antibodies react in immunoblot assays with a 210 kDa protein from the membrane fractions of adult DRG and trigeminal ganglia. The size of the immunoreactive protein is in close agreement with the predicted Na(v)1.9 theoretical molecular weight of 201 kDa, suggesting limited glycosylation of this channel in adult tissues. Neonatal rat DRG membrane fractions, however, contain an additional higher molecular weight immunoreactive protein. Reverse transcription-PCR analysis did not show additional longer transcripts that could encode the larger protein. Enzymatic deglycosylation of the membrane preparations converted both immunoreactive proteins into a single faster migrating band, consistent with two states of glycosylation of Na(v)1.9. The developmental change in the glycosylation state of Na(v)1.9 is paralleled by a developmental change in the gating of the persistent TTX-R Na(+) current attributable to Na(v)1.9 in native DRG neurons. Whole-cell patch-clamp analysis demonstrates that the midpoint of steady-state inactivation is shifted 7 mV in a hyperpolarized direction in neonatal (postnatal days 0-3) compared with adult DRG neurons, although there is no significant difference in activation. Pretreatment of neonatal DRG neurons with neuraminidase causes an 8 mV depolarizing shift in the midpoint of steady-state inactivation of Na(v)1.9, making it indistinguishable from that of adult DRG neurons. Our data show that extensive glycosylation of rat Na(v)1.9 is developmentally regulated and changes a critical property of this channel in native neurons.
The operational profile in software reliability engineering: an overview (2003)

Provides an overview of a step-by-step approach for developing the operational profile used in software reliability engineering. The operational profile can help guide managerial and engineering decisions throughout the product life cycle, including requirements specification, design, implementation and testing. It is particularly valuable in guiding test planning and testing. The development and use of this profile typically involves product and market managers and systems engineers. It is used by software developers and managers, system test planners and testers, and quality assurance and reliability engineers. The presented material has been drawn from experience in developing operational profiles for a variety of applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ambulatory small intestinal motility in 'diarrhoea' predominant irritable bowel syndrome. (1994)

Dysmotility of the duodenum and proximal jejunum has been reported in patients with irritable bowel syndrome. This study extended these findings by recording fasting ambulatory motility from electronic strain gauge sensors sited in the jejunum and ileum of eight diarrhoea predominant irritable bowel syndrome patients and 12 healthy controls. During the day, periodicity of migrating motor complexes mean (SEM) did not differ between patients (92 (10) min) and controls (85 (7) min). At night, periodicity was shorter in both patients and controls, and the daytime dominance of phase II was replaced by phase I. In both groups, aboral progression of phase III fronts was associated with a slowing of propagation velocity and maximum contractile rate, but an increase in mean amplitude of contraction. Discrete clustered contractions were seen in seven patients and 10 controls occupying 14 and 16% of daytime phase II activity, respectively. Pain episodes were not associated with any specific motility patterns. Despite the lack of motility differences between the two groups, orocaecal transit time in the irritable bowel syndrome patients was shorter at 57 (9) min than in the controls, 82 (6) min (p < 0.05). This ambulant study has failed to show any abnormalities of fasting small intestinal motility that might distinguish diarrhoea predominant irritable bowel syndrome patients from healthy controls.
논문 : 영업실적 정보를 이용한 내부자 거래 (2010)

본 연구는 내부자 거래의 행태에 초점을 맞춘 연구로서 내부자 거래의 투자성과를 중심으로 분석한 기존의 연구결과를 보완하는 성격을 지니고 있다. 기업의 내부자는 사전에 인지한 실적정보를 이용한 거래를 통해 초과수익을 취할 가능성이 있다. 그러므로 해외 각국에서는 실적발표 자체를 중요한 미공개 정보로 간주하여 실적발표 이전 일정기간 동안의 내부자 거래를 엄격히 금지하고 있다. 하지만 한국에서는 내부자에 대해 직전 거래로부터 6개월 이내의 반대매매를 금지하는 규정이 실적발표와 연관된 내부자 거래의 사실상의 유일한 규제수단이다. 그러므로 실적발표 이전에 내부정보를 이용한 내부자 거래의 개연성이 존재한다. 본 연구는 실적충격에 대한 내부자들의 사전 인지능력과 그를 이용한 내부자 거래 가능성을 검증하였다. 내부자 거래의 공시행태를 분석한 결과, 내부자들은 매수거래에 비해 매도거래의 사실을 늦게 공시하는 경향을 보이고 있다. 또한 내부자들의 거래행태를 분석한 결과, 전반적으로 임직원들이 실적정보를 사전에 이용하여 내부자 거래를 수행하고 있을 가능성이 존재함을 시사한다. 본 연구결과는 한국에서 실적발표 전의 내부자 거래를 좀 더 실효성 있게 규제할 필요성을 제기하고 있다.
The amino acid sequences of chains a, b, and c that form the trimer subunit of the extracellular hemoglobin from Lumbricus terrestris. (1988)

The extracellular hemoglobin of Lumbricus terrestris comprises four major heme-containing chains, a, b, c, and d in equal proportions. We have determined the amino acid sequences of chains a, b, and c which form a disulfide-linked trimer. Chains a, b, and c have 151, 145, and 153 residues and calculated molecular weights of 17,525, 16,254, and 17,289, respectively. The sequence of chain b, reported previously (Garlick, R. L., and Riggs, A. F. (1982) J. Biol. Chem. 287, 9005-9015) has been completely redetermined and found to contain 12 fewer residues than originally reported. Chains a and c both contain unusual, highly polar NH2-terminal extensions of 7 residues before the A helix. These segments must be close together because they are joined by a disulfide bond. We suggest that this structure, with seven negatively charged groups, may be part of a functionally important Ca2+-binding site in the trimer. Comparison of the sequences of chains a, b, and c with those of chain d (Shishikura, F., Snow, J. W., Gotoh, T., Vinogradov, S. N., and Walz, D. A. (1987) J. Biol. Chem. 262, 3123-3131) and the four chains of the hemoglobin of Tylorrhynchus heterochaetus (Suzuki, T., and Gotoh, T. (1986) J. Biol. Chem. 261, 9257-9267) shows that the number and positions of the cysteinyl residues are all conserved. This suggests that the extracellular hemoglobins from both the Oligochaeta and Polychaeta have the same number and configuration of disulfide bonds within the molecule. Phylogenetic analysis suggests that gene duplication first generated an intracellular hemoglobin branch and an extracellular hemoglobin branch. DNA coding for a signal peptide would have been acquired by the extracellular globin gene after this event. At least two further gene duplications are required to account for the present four polypeptide chains.
Autotaxin Is Overexpressed in Glioblastoma Multiforme and Contributes to Cell Motility of Glioblastoma by Converting Lysophosphatidylcholine TO Lysophosphatidic Acid (2006)

Autotaxin (ATX) is a multifunctional phosphodiesterase originally isolated from melanoma cells as a potent cell motility-stimulating factor. ATX is identical to lysophospholipase D, which produces a bioactive phospholipid, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC). Although enhanced expression of ATX in various tumor tissues has been repeatedly demonstrated, and thus, ATX is implicated in progression of tumor, the precise role of ATX expressed by tumor cells was unclear. In this study, we found that ATX is highly expressed in glioblastoma multiforme (GBM), the most malignant glioma due to its high infiltration into the normal brain parenchyma, but not in tissues from other brain tumors. In addition, LPA1, an LPA receptor responsible for LPA-driven cell motility, is predominantly expressed in GBM. One of the glioblastomas that showed the highest ATX expression (SNB-78), as well as ATX-stable transfectants, showed LPA1-dependent cell migration in response to LPA in both Boyden chamber and wound healing assays. Interestingly these ATX-expressing cells also showed chemotactic response to LPC. In addition, knockdown of the ATX level using small interfering RNA technique in SNB-78 cells suppressed their migratory response to LPC. These results suggest that the autocrine production of LPA by cancer cell-derived ATX and exogenously supplied LPC contribute to the invasiveness of cancer cells and that LPA1, ATX, and LPC-producing enzymes are potential targets for cancer therapy, including GBM.
Abstract MP32: Effectiveness Of Investigational RNAi Therapeutics Targeting Liver Angiotensinogen In Experimental Chronic Kidney Disease (2020)

Background: RNAi therapeutics targeting angiotensinogen (AGT) lower blood pressure in animal models of essential hypertension, but whether this treatment is beneficial in hypertensive chronic kidney disease (CKD) is yet unknown. Our aim was to assess the effectiveness of a small interfering RNA (siRNA) targeting hepatic AGT in a rat model of hypertensive CKD. Methods: Sprague Dawley rats (n=7-12 per group) were subjected to 5/6th nephrectomy, allowed to recover for four weeks, and subsequently subjected to one of five treatments: (1) vehicle, (2) AGT siRNA (10-30 mg/kg, s.c. every 2 weeks), (3) AGT siRNA + losartan (30 mg/kg/d), (4) losartan (30 mg/kg/d), or (5) losartan + captopril (30 and 6 mg/kg/d). Mean arterial pressure (MAP) was measured by radiotelemetry for 4 weeks, glomerular filtration rate (GFR) was measured by transcutaneous FITC-sinistrin clearance. Results: AGT siRNA and AGT siRNA + losartan reduced plasma AGT by 96.5 ± 1.4% and 97.0 ± 2.3%, respectively. Over the course of 4 weeks, proteinuria increased with vehicle and this increase was abrogated by all treatments (Δ proteinuria at 4 weeks versus baseline: +0.17 [0.12, 0.23], +0.02 [-0.04, 0.05], -0.01 [-0.07, 0.06], -0.05 [-0.12, 0.00], -0.01 [-0.06, 0.11] for vehicle, AGT siRNA, AGT siRNA + losartan, losartan, losartan + captopril, P &lt; 0.05 for all groups compared with vehicle). Similarly, heart weight was equally reduced by all treatments except vehicle. No intervention affected GFR. Over the course of 4 weeks, MAP increased (from a baseline of 154 ± 18 mmHg) during vehicle treatment and this rise was prevented by AGT siRNA (+13 ± 15 mmHg vs. -2 ± 14 mmHg, P &gt; 0.05 for difference between groups). Combination treatment with AGT siRNA + losartan, losartan + captopril, and losartan alone caused a similar and marked reduction in MAP (-17 ± 14 mmHg, -21 ± 17 mmHg, and -33 ± 20 mmHg, P &lt; 0.05 versus vehicle for all; differences between groups not significant). Conclusion: In experimental CKD, AGT siRNA monotherapy appears to reduce proteinuria and heart weight in a blood pressure-independent fashion, to a similar degree as losartan or combination treatment. Thus, an siRNA targeting hepatic AGT may be a potential therapeutic approach for providing renal and cardioprotection in CKD.
Comparing risk management information: An invitation to disaster? (2000)

Abstract While many healthcare entities want to compare their risk management data with other entities, most such projects fail. This is usually due to weaknesses in terminology and differences in work practices. In addition, virtually all data in healthcare risk management are subjective and may readily be manipulated. To benchmark their data, facilities should be careful to understand what their data represents, and how the data compare with the data generated by other facilities. This usually requires an in‐depth review of work practices and procedures, coverages, and culture. Risk management data can be shared, but it must be done carefully.
Visceral Protein Levels in Trauma Patients Are Greater with Peptide Diet Than with Intact Protein Diet (1990)

Early enteral nutrition may preserve gut function and prevent bacterial translocation after trauma. Standard enteral nutrition uses products which contain intact protein and require digestion for absorption. Peptide-based enteral nutritional products are better absorbed and stimulate the release of gut trophic hormones. This study was performed to determine whether a peptide-based (PEP) product (Reabilan HN) was better tolerated and/or produced better hepatic protein responses in patients after trauma when compared to an intact-protein (PRO) formula (Osmolite HN). Eighteen trauma patients were prospectively randomized to PEP (n = 9) or PRO (n = 9) enteral diets administered via nasoduodenal tubes (within 1-2 days of injury). Visceral protein synthesis was assessed by measuring baseline and 1 week pre-albumin and transferrin levels. Diarrhea was defined as greater than 300 gm/day of stool. Groups were similar in age, Injury Severity Score (ISS), caloric intake, and protein intake. Protein levels increased significantly faster in PEP patients despite similar urea nitrogen excretion. Diarrhea developed in four (44%) PRO patients and none of the PEP patients. Three of the PRO patients were switched to PEP after one week and diarrhea subsided in all three patients. Peptide-based enteral diets are associated with better hepatic protein responses and less diarrhea compared to intact-protein diets.
Perivascular cells for regenerative medicine (2012)

Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We and others recently described that MSC originate from two types of perivascular cells, namely pericytes and adventitial cells and contain the in situ counterpart of MSC in developing and adult human organs, which can be prospectively purified using well defined cell surface markers. Pericytes encircle endothelial cells of capillaries and microvessels and express the adhesion molecule CD146 and the PDGFRβ, but lack endothelial and haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is a pericyte marker exclusively associated with the arterial system. Besides its expression in smooth muscle cells, smooth muscle actin (αSMA) is also detected in subsets of pericytes. Adventitial cells surround the largest vessels and, opposite to pericytes, are not closely associated to endothelial cells. Adventitial cells express CD34 and lack αSMA and all endothelial and haematopoietic cell markers, as for pericytes. Altogether, pericytes and adventitial perivascular cells express in situ and in culture markers of MSC and display capacities to differentiate towards osteogenic, adipogenic and chondrogenic cell lineages. Importantly, adventitial cells can differentiate into pericyte-like cells under inductive conditions in vitro. Altogether, using purified perivascular cells instead of MSC may bring higher benefits to regenerative medicine, including the possibility, for the first time, to use these cells uncultured.
Secure public internet access handler (SPINACH) (1997)

Abstract: This paper describes a system that controls access to computer networks through publicly accessible LANs, enabling network administrators to authorize users either on a permanent or occasional basis. The system has been designed with minimal assumptions about the software and hardware required of users, and requires very little specialized equipment within the network infrastructure. We enumerate the requirements for such a system, describe the design and implementation of the system, and note tradeoffs between security and efficiency.
Emerging Roles of Ubiquitin in Transcription Regulation (2002)

Ubiquitin is a small protein that was initially found to function as a tag that can be covalently attached to proteins to mark them for destruction by a multisubunit, adenosine 5'-triphosphate-dependent protease called the proteasome. Ubiquitin is now emerging as a key regulator of eukaryotic messenger RNA synthesis, a process that depends on the RNA synthetic enzyme RNA polymerase II and the transcription factors that control its activity. Ubiquitin controls messenger RNA synthesis not only by mechanisms involving ubiquitin-dependent destruction of transcription factors by the proteasome, but also by an intriguing collection of previously unknown and unanticipated mechanisms that appear to be independent of the proteasome.
Comparative evaluation of multiple lymphoid and recombinant human interleukin-2 preparations. (1986)

Six lymphoid human interleukin-2s (nIL-2s) [four from peripheral blood mononuclear cells (PBMC) and two from JURKAT cells] and six recombinant IL-2s (rIL-2s) were obtained for comparative evaluation. The main issues addressed were possible differences among the preparations in potency in T cell growth assays and other functional assays, and the possible presence of other cytokine activities or contaminants. Each preparation was assigned a standardized IL-2 activity in reference units (RU) by comparing its T cell growth promoting activity against the Biological Response Modifiers Program IL-2 (JURKAT) reference reagent. Relative to the IL-2 unitage indicated by the suppliers, the RU varied from 110-fold less to 38.5-fold more for the various preparations. Two nIL-2s and two rIL-2s contained significant levels of endotoxin. One nIL-2 contained low levels of both alpha and gamma interferon (IFN), and one nIL-2 had a high level of gamma IFN. All other IL-2s were negative for IFN activity. All IL-2 preparations significantly augmented human natural killer (NK) activity, although the amount of RU required varied from 0.1 to 50 RU. Four nIL-2s and three rIL-2s induced human PBMC to produce gamma IFN, whereas two nIL-2s and one rIL2 did not. All nIL-2s had substantial amounts of B cell growth factor activity, whereas none of the rIL-2s consistently displayed this activity. All IL-2s stimulated the tritiated thymidine [3H]TdR incorporation of human PBMC in the absence of other stimuli, in addition to augmenting the response to mitogen or alloantigens. Some nILs and IL-2s had effects on human monocytes such as inhibiting migration, inducing cytotoxic or growth inhibitory activity against tumor cells, and causing changes in cell surface markers. The IL-2s were also tested for activity in vitro and in vivo in mice. Although there was a 12-fold variation in activity among the preparations, all but one of the IL-2s showed augmentation of the mixed lymphocyte reaction activity and all IL-2s tested stimulated macrophage cytotoxicity in vitro. All IL-2s tested enhanced the mixed lymphocyte-allogeneic tumor cell reaction resulting in greater production of cytotoxic T cells. However, significant quantitative differences in potency were evident among the various IL-2 preparations, especially the nIL-2s. Only very high doses of IL-2 (intraperitoneal injection of 100,000 RU/animal) induced in vivo augmentation of splenic or peritoneal NK cells, although all IL-2s tested increased NK activity against tumor target cells in vitro with substantially lower doses (10-100 RU/ml).(ABSTRACT TRUNCATED AT 400 WORDS)
Recent progress in surface-enhanced Raman spectroscopy for biological and biomedical applications: from cells to clinics (2017)

The application of surface-enhanced Raman spectroscopy (SERS) in biological and biomedical detection schemes is feasible due to its excellent molecular specificity and high sensitivity as well as the capability of SERS to be performed in complex biological compositions. SERS-based investigation of cells, which are the basic structure and functional unit of organisms, represents the starting point of this review. It is demonstrated that SERS provides a deep understanding of living cells as well as their microenvironment which is needed to assess the development of diseases. The clinical relevance of SERS is proved by its application for the detection of cancer cells and tumour margins under in vivo conditions and examples for theranostic approaches are discussed. This review article provides a comprehensive overview of the recent progress within the last 3 years.
Influence of Bulk Fluid Velocity on the Efficiency of Electrohydrodynamic Pumping (2005)

Abstract The efficiency of conversion of electrical power into fluidic power in an electrohydrodynamic (EHD) pump depends on the bulk fluid velocity. An analytical formulation is developed for calculation of the efficiency of an EHD pump, with and without the presence of a superimposed flow due to an externally imposed pressure gradient. This formulation is implemented into a numerical model, which is used to investigate the effect of bulk fluid velocity on the efficiency of the EHD action. In particular, the net flow due to the combined action of EHD and a positive or negative external pressure gradient is computed. Both ion-drag pumps and induction EHD pumps are considered. Pumps based on the ion-drag principle that are studied include a one-dimensional pump, a two-dimensional pump driven by a stationary potential gradient, and another driven by a traveling potential wave. Two-dimensional repulsion-type and attraction-type induction pumping caused by a gradual variation in the electrical conductivity of the fluid is also investigated. The efficiency of EHD pumps exhibited a strong dependence on bulk fluid velocity: for the two-dimensional steady ion-drag pump, for example, the efficiency increased from less than 2% to 22% under the influence of an external pressure gradient. The corresponding increase in efficiency for a two-dimensional repulsion-type EHD pump was from 0.26% to 24.5%.