gebhart/patrepeval huggingface dataset:
Dendritic cells modified to express CD40 ligand elicit therapeutic immunity against preexisting murine tumors (2000)

CD40 ligand (CD40L) is essential for the initiation of antigen-specific T-cell responses. This study is based on the hypothesis that dendritic cells (DCs) genetically modified ex vivo to express CD40L will enhance in vivo presentation of tumor antigen to the cellular immune system with consequent induction of antitumor immunity to suppress tumor growth. To examine this concept, subcutaneous murine tumors were injected with bone marrow-derived DCs that had been modified in vitro with an adenovirus (Ad) vector expressing murine CD40L (AdmCD40L). In B16 (H-2b, melanoma) and CT26 (H-2d, colon cancer) murine models, intratumoral injection of 2 × 106 AdmCD40L-modified DCs (CD40L-DCs) to established (day 8) subcutaneous tumors resulted in sustained tumor regression and survival advantage. This antitumor effect was sustained when the number of CD40L-DCs were reduced 10-fold to 2 × 105. Analysis of spleens from CD40L-DC–treated animals demonstrated that CD40L-DCs injected into the subcutaneous CT26 flank tumors migrated to the spleen, resulting in activation of immune-relevant processes. Consistent with this concept, intratumoral administration of CD40L-DCs elicited tumor-specific cytotoxic T-lymphocyte responses, and the transfer of spleen cells from CD40L-DC–treated mice efficiently protected naive mice against a subsequent tumor challenge. In a distant 2-tumor model of metastatic disease, an untreated B16 tumor in the right flank regressed in parallel with a left B16 tumor treated with direct injection of CD40L-DCs. These results support the concept that genetic modification of DCs with a recombinant CD40L adenovirus vector may be a useful strategy for directly activating DCs for cancer immunotherapy.
Increased heat shock protein 90 (hsp90) expression leads to increased apoptosis in the monoblastoid cell line U937 following induction with TNF-alpha and cycloheximide: a possible role in immunopathology (1996)

In this study, we examined the hypothesis that heat shock proteins (hsp) (such as hsp72 and hsp90) are implicated in the regulation of forms of cell injury that lead to programmed cell death. The monoblastoid cell line U937 has been used as a model system. For hsp90, which is not heat inducible in this cell line, we used stable U937 transfectants that either hyperexpress or hypoexpress the protein. For hsp72 (which is reproducibly induced in all three cell lines to relatively high levels of expression), we studied U937 cells before and after heat shock. We showed that apoptosis does occur in the monoblast/mononuclear phagocyte lineage, and that it could be induced in vitro by serum deprivation, UV light, or TNF-alpha in combination with cycloheximide (cx). However, an excess of hsp90 is associated with increased apoptosis when the cells are treated with a combination of TNF-alpha and cx but not when they are exposed to UV B radiation. This was complemented by the finding that reduced hsp90 levels correlate with protection against apoptosis in the TNF-alpha- and cx-treated cells. Furthermore, new synthesis of hsp72 does not protect against apoptosis. Thus, hsp90 levels may play a role in controlling the part played by mononuclear phagocytes in immunopathology.
Effect of dexmedetomidine on emergence agitation in male patients undergoing closed reduction of a nasal bone fracture (2015)

Objective: Emergence agitation (EA) is defined as a transient condition in which emergence from general anesthesia is accompanied by psychomotor agitation. Dexmedetomidine (Dex) is known to reduce EA in children. The objective of this study was to determine the effects of intraoperative Dex on EA undergoing closed reduction of a nasal bone fracture.
Methodology: Thirty-eight male patients, ages 18 to 60 years, were randomized to receive a single intraoperative dose of Dex 1.0 µg/kg (Group D) or the same volume as normal saline (Group N) over 5 minutes before endotracheal intubation. The Richmond agitation sedation scale (RASS) was utilized to assess the intensity of the EA. 
Results: EA was observed in 12 patients in group D compared with 18 patients in group N (P=0.042). Heart rate was significantly lower one minute after intubation (P=0.032), one minute before extubation (P=0.023), and upon arrival in the PACU (P=0.013). The mean blood pressure was lower one minute after extubation (P=0.004). Postoperative pain was significantly less in group D (P=0.050).
Conclusion: A single intraoperative dose of Dex was an effective method to reduce EA in adult patients undergoing closed reduction for a nasal bone fracture.
Abstract 2602: KRAS G12D and G12V specific alkylating agent (KR12) inhibits growth of colon cancer with those KRAS mutations in vitro as well as in vivo (2014)

Abstract Despite extensive efforts to develop chemotherapeutic drug(s) targeting mutated RAS, the successful drug discovery, especially targeting KRAS codon 12 mutation, has never been made. We have found that Pyrrole-Imidazole polyamide seco-CBI conjugate (KR12) selectively recognized mutated KRAS sequence (ACGCCT-A/T-CA) at codon 12 and significantly suppressed tumor growth specifically in human colon cancer cells with G12D or G12V mutation. KRAS expression suppressed preferentially at mutated allele and active KRAS were markedly reduced. G2/M arrest, senescence and subsequent apoptosis by activating the p53 pathway were observed in KR12-exposed LS180 cells with G12D heterozygous mutation. In LS180 and SW480 (G12V homozygous mutation) xenograft colon cancer models, KR12 treatment induced massive tumor growth suppression with low host toxicity. Collectively, our current results strongly suggest that KR12 is a specific alkylating agent against KRAS codon 12 mutations, and could become a powerful candidate compound for the unmet need of KRAS-mutant tumor treatment. Citation Format: Hiroki Nagase, Kiriko Hiraoka, Takahiro Inoue, Takayoshi Watanabe, Ken-Ichi Shinohara, Nobuko Koshikawa, Ozaki Toshinori. KRAS G12D and G12V specific alkylating agent (KR12) inhibits growth of colon cancer with those KRAS mutations in vitro as well as in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2602. doi:10.1158/1538-7445.AM2014-2602
Development of a PCR-Based Assay for Detection, Quantification, and Genotyping of Human Adenoviruses (2005)

The presented assay is a suitable tool for the detection and genotyping of human AdVs in clinical samples.
Methylnaltrexone Mechanisms of Action and Effects on Opioid Bowel Dysfunction and Other Opioid Adverse Effects (2007)

Methylnaltrexone has the potential to prevent or treat opioid-induced peripherally mediated ADEs on bowel dysfunction without interfering with central analgesia. The study of methylnaltrexone leads to a greater understanding of the mechanisms of action of opioid pharmacology.
REsource LOcation And Discovery (RELOAD) (2008)

This document outlines the motivation, requirements, and architectural
design for a extensible and lightweight distributed REsource LOcation
And Discovery (RELOAD) protocol. RELOAD is a Peer- to-Peer (P2P) based
approach for registration and resource discovery using distributed
hash tables maintained with binary messages. This design removes the
need for central servers from SIP, while offering full backward
compatibility with SIP, allowing reuse of existing clients, and
allowing P2P enabled peers to communicate with conventional SIP
entities. A basic introduction to the concepts of P2P is presented,
backward compatibility issues addressed, and security considerations
are discussed. RELOAD is one possible implementation of the protocols
being discussed for creation in the P2PSIP WG. In the context of the
work being proposed, this draft represents a concrete proposal for the
P2PSIP Peer Protocol. RELOAD uses binary messages, derived as much as
possible from the STUN protocol, as the underlying protocol. Note that
in order to be as similar to STUN as possible, some text has been re-
used verbatim from I-Ds and RFCs describing STUN. In this
architecture, no P2PSIP Client Protocol is needed, rather unmodified
SIP is used for access by non-peers. This protocol considers NAT
traversal and fragmentation, supports storage of information other
than registrations, allows for multiple DHT and hash algorithms, and
provides hooks for multiple security schemes. The protocol described
here derives from a fully implemented and commercially available
system with running code.
Renal nerve ablation after SYMPLICITY HTN-3: confused at the higher level? (2014)

In spite of all the medical progress, hypertension remains a highly prevalent chronic disease worldwide, contributing importantly to cardiovascular morbidity and mortality in Europe1 and around the globe. Indeed, it has been estimated that in the not too distant future up to 50% of the adult population will develop high blood pressure according to currently used definitions.2 Since Franklin D. Roosevelt died of a cerebral haemorrhage in 1945 due to uncontrolled high blood pressure with values up to 300/190 mmHg, the management of hypertension has made impressive progress. Indeed, while at that time only Kempner's rice diet was available, after the war diuretics, reserpine, guanethidine, and later beta-blockers, spironolactone, calcium antagonists, and angiotensin-converting enzyme (ACE) inhibitors became available. Today, with the advent of angiotensin receptor blockers, renin inhibitors, eplerenone, and beta-blockers, the pharmacological armamentarium to treat high blood pressure has become quite vast, and most patients can be controlled with 1–3 antihypertensive drugs to levels of ≤140/90 mmHg.3

Thanks to this success, it appeared that antihypertensive management had reached its goals and no further developments would be required. Nevertheless, it has been recognized that a small, but significant portion of patients remains uncontrolled in spite of the many drugs available today.4 The European Society of Cardiology together with the European Society of Hypertension, as well as their American counterparts have defined treatment-resistant hypertension as blood pressure values > 140/90 mmHg in spite of three antihypertensive drugs including a diuretic.2 It has been estimated that between 3% and 5% of the patients would fall into this category.5 As the event rates are staggeringly high in this patient population, additional treatment options are an unmet clinical need.6 It has been argued that many of the patients with so-called treatment-resistant hypertension are in fact just non-compliant …
Proofreading by the epsilon subunit of Escherichia coli DNA polymerase III increases the fidelity of calf thymus DNA polymerase alpha. (1989)

Addition of the 3'----5' proofreading exonuclease, epsilon subunit of Escherichia coli DNA polymerase III, to DNA polymerase alpha from calf thymus has been studied. Alone, calf thymus DNA polymerase alpha terminates in vitro DNA synthesis upon insertion of noncomplementary nucleotides. Upon addition of the epsilon subunit, DNA polymerase alpha elongates the newly synthesized DNA as a result of hydrolysis of the 3'-terminal mispair. The fidelity of DNA polymerase alpha in vitro is increased 7-fold by addition of the exonuclease. The functional interaction between DNA polymerase alpha and the epsilon subunit is independent of any detectable physical association. This suggests that a mechanism for proofreading could exist in mammalian cells involving sequential catalysis by DNA polymerase alpha excision of errors by a separate 3'----5' exonuclease, and further elongation onto correctly base-paired 3' termini by DNA polymerase alpha.
Low cost additive manufacturing of microneedle masters (2019)

The described 3D printing technique enables investigators to accurately fabricate microneedles within minutes at low cost. Rapid, iterative optimization of microneedle geometry through 3D printing will accelerate microneedle research through improved understanding of the relationship between microneedle structure and function.
VEGF is necessary for exercise‐induced adult hippocampal neurogenesis (2003)

Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic-pituitary-adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced neurogenesis but had no detectable effect on baseline neurogenesis in non-running animals. These data suggest that VEGF is an important element of a 'somatic regulator' of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.
Host adaptation and the emergence of infectious disease: the Salmonella paradigm (2000)

The recent emergence of food-borne pathogens, such as Salmonella enterica serotype Enteritidis (S. enteritidis) and Escherichia coli O157:H7, has generated increasing interest in how infectious diseases can invade, persist and spread within new host populations. To alter their host range pathogens require adaptations, which ensure their circulation in a new animal population. Adaptations for circulation in different populations of vertebrate hosts seem to have been acquired multiple times within the genus Salmonella because extant Salmonella serotypes differ greatly with regard to host range. In this article, mechanisms involved in host adaptation are deduced by considering the influence of the host immune response on circulation of Salmonella serotypes within populations of vertebrate animals. This approach contributes to the identification of genes involved in host adaptation and provides new insights into the emergence of food-borne pathogens.
Data clustering (1999)

Clustering is the unsupervised classification of patterns (observations, data items, or feature vectors) into groups (clusters). The clustering problem has been addressed in many contexts and by researchers in many disciplines; this reflects its broad appeal and usefulness as one of the steps in exploratory data analysis. However, clustering is a difficult problem combinatorially, and differences in assumptions and contexts in different communities has made the transfer of useful generic concepts and methodologies slow to occur. This paper presents an overview of pattern clustering methods from a statistical pattern recognition perspective, with a goal of providing useful advice and references to fundamental concepts accessible to the broad community of clustering practitioners. We present a taxonomy of clustering techniques, and identify cross-cutting themes and recent advances. We also describe some important applications of clustering algorithms such as image segmentation, object recognition, and information retrieval.
Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial? (1999)

Sterically stabilized liposome is characterized by a surface coating of polyethylene glycol (PEG) or other polymers that can reduce opsonization of the liposome by plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of liposomes with cells and hinder entry of liposomes into the tumor tissue. Using a stable liposomal system composed of distearoyl phosphatidylcholine/cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of liposomal doxorubicin with C-26 syngeneic tumor model in BALB/c mice. The plasma AUC of liposomal doxorubicin with 6 mol-% PEG-modified distearoyl phosphatidylethanolamine (PEG-DSPE) was approximately twice that of liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were tumor-bearing. Paradoxically, the group of mice treated with liposomal doxorubicin without PEG had higher tumor doxorubicin concentrations. The 72-h tumor AUC was 1.44 times that of liposomal doxorubicin with 6% PEG-DSPE. The tumor-accumulation efficiency (AUC(Tumor)/AUC(Plasma)) of liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the liposomal doxorubicin with 6% PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the two liposomal drug groups. In this stable liposome system, surface coating with PEG offered no benefit for liposomal doxorubicin in the C-26 tumor model. To enhance the therapeutic index of liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.
Normal Control of Growth Hormone Secretion (1993)

Growth hormone (GH) is secreted by the anterior pituitary gland in a pulsatile fashion under the regulation of two hypothalamic peptides: GH-releasing hormone (GHRH) stimulates GH synthesis and secretion while somatostatin inhibits GH release. Studies in rats, sheep and humans indicate that whereas GHRH is required for the initiation of GH pulses, the amplitude of GH pulses is modulated by somatostatin. In humans, these interactions result in a pattern of volleys of GH-secretory pulses with intervening periods of relative secretory quiescence. The amplitude and frequency of GH-secretory pulses are regulated by a complex array of external and internal stimuli including age, gender, menstrual cycle phase, pubertal status, nutrition, sleep, body composition and exercise. Changes in plasma concentrations of gonadal hormones, insulin and insulin-like growth factor-I likely mediate the effects of several of these factors. A greater understanding of the physiology of GH secretion will enable the development of future strategies to enhance GH secretion in GH-deficient states including the use of GH secretagogues and modification of nutrition and exercise habits.
On-Chip Coupling of Isoelectric Focusing and Free Solution Electrophoresis for Multidimensional Separations (2003)

We have developed an acrylic microfluidic device that sequentially couples liquid-phase isoelectric focusing (IEF) and free solution capillary electrophoresis (CE). Rapid separation (<1 min) and preconcentration (73x) of species were achieved in the initial IEF dimension. Using full-field fluorescence imaging, we observed nondispersive mobilization velocities on the order of 20 microm/s during characterization of the IEF step. This transport behavior allowed controlled electrokinetic mobilization of focused sample bands to a channel junction, where voltage switching was used to repeatedly inject effluent from the IEF dimension into an ampholyte-based CE separation. This second dimension was capable of analyzing all fluid volumes of interest from the IEF dimension, as IEF was 'parked' during each CE analysis and refocused prior to additional CE analyses. Investigation of each dimension of the integrated system showed time-dependent species displacement and band-broadening behavior consistent with IEF and CE, respectively. The peak capacity of the 2D system was approximately 1300. A comprehensive 2D analysis of a fluid volume spanning 15% of the total IEF channel length was completed in less than 5 min.
A novel small molecule CFTR inhibitor attenuates HCO3− secretion and duodenal ulcer formation in rats (2005)

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) plays a crucial role in mediating duodenal bicarbonate (HCO(3)(-)) secretion (DBS). Although impaired DBS is observed in CF mutant mice and in CF patients, which would predict increased ulcer susceptibility, duodenal injury is rarely observed in CF patients and is reduced in CF mutant mice. To explain this apparent paradox, we hypothesized that CFTR dysfunction increases cellular [HCO(3)(-)] and buffering power. To further test this hypothesis, we examined the effect of a novel, potent, and highly selective CFTR inhibitor, CFTR(inh)-172, on DBS and duodenal ulceration in rats. DBS was measured in situ using a standard loop perfusion model with a pH stat under isoflurane anesthesia. Duodenal ulcers were induced in rats by cysteamine with or without CFTR(inh)-172 pretreatment 1 h before cysteamine. Superfusion of CFTR(inh)-172 (0.1-10 microM) over the duodenal mucosa had no effect on basal DBS but at 10 microM inhibited acid-induced DBS, suggesting that its effect was limited to CFTR activation. Acid-induced DBS was abolished at 1 and 3 h and was reduced 24 h after treatment with CFTR(inh)-172, although basal DBS was increased at 24 h. CFTR(inh)-172 treatment had no effect on gastric acid or HCO(3)(-) secretion. Duodenal ulcers were observed 24 h after cysteamine treatment but were reduced in CFTR(inh)-172-pretreated rats. CFTR(inh)-172 acutely produces CFTR dysfunction in rodents for up to 24 h. CFTR inhibition reduces acid-induced DBS but also prevents duodenal ulcer formation, supporting our hypothesis that intracellular HCO(3)(-) may be an important protective mechanism for duodenal epithelial cells.
A class of low-density parity-check codes constructed based on Reed-Solomon codes with two information symbols (2003)

This letter presents an algebraic method for constructing regular low-density parity-check (LDPC) codes based on Reed-Solomon codes with two information symbols. The construction method results in a class of LDPC codes in Gallager's original form. Codes in this class are free of cycles of length 4 in their Tanner graphs and have good minimum distances. They perform well with iterative decoding.
Osteomyelitis and the role of biofilms in chronic infection (2008)

Understanding the mechanisms implicated in the initial attachment, development, and maturation of a biofilm phenotype are of tremendous importance for their effect on the medical, industrial, and public health arenas. This review explores the current understanding of the nature of biofilms and the impact that molecular interactions between the bacteria themselves, as well as between bacteria and the host, may have on biofilm development and phenotype using the nonmotile Gram-positive coccus, Staphylococcus aureus, as an example.