Miracle-dz/UniFAR-FTUs huggingface dataset:
Clonal relationships in recurrent B-cell lymphomas

Immunoglobulin (Ig) gene rearrangements remain largely unmodified during the clonal expansion of neoplastic cells. We investigated the clonal relationships between lymphoma components at diagnosis and at relapse by analyzing Ig gene rearrangements. A BIOMED-2 multiplex polymerase chain reaction (PCR) assay was performed in 27 patients using formalin-fixed paraffin embedded tissues, with subsequent cloning and sequencing of the amplified Ig genes in 17 patients. All 27 cases of primary and corresponding relapsed tumors showed monoclonal rearrangements of the Ig genes by BIOMED-2 PCR. Whereas IgVH or IgVK fragment lengths were identical in 8/27 pairs (30%), fragment lengths differed in 19/27 pairs (70%). In 17 cases analyzed by sequencing, an identical VDJ gene rearrangement was confirmed in 4/4 pairs (100%) with the same fragment lengths and in 10/13 pairs (77%) with different fragment lengths. Four of 17 primary lymphomas had multiple VDJ rearrangements, and three of them showed an unrelated relapse. Unrelated relapse was observed in 1/8 mantle cell lymphomas, 1/5 diffuse large B-cell lymphomas, and a large B cell lymphoma developed in a patient with a small lymphocytic lymphoma. Unrelated relapses developed after a longer disease-free interval and tended to show poorer outcome compared with related relapse. In summary, relapse of a lymphoma from an unrelated clone is uncommon, but can occur in B-cell lymphomas. Clonal relationships should be determined by sequencing of the Ig genes, and not just by comparing the PCR product size.
RGS4 is a negative regulator of insulin release from pancreatic β-cells in vitro and in vivo

Therapeutic strategies that augment insulin release from pancreatic β-cells are considered beneficial in the treatment of type 2 diabetes. We previously demonstrated that activation of β-cell M3 muscarinic receptors (M3Rs) greatly promotes glucose-stimulated insulin secretion (GSIS), suggesting that strategies aimed at enhancing signaling through β-cell M3Rs may become therapeutically useful. M3R activation leads to the stimulation of G proteins of the Gq family, which are under the inhibitory control of proteins known as regulators of G protein signaling (RGS proteins). At present, it remains unknown whether RGS proteins play a role in regulating insulin release. To address this issue, we initially demonstrated that MIN6 insulinoma cells express functional M3Rs and that RGS4 was by far the most abundant RGS protein expressed by these cells. Strikingly, siRNA-mediated knockdown of RGS4 expression in MIN6 cells greatly enhanced M3R-mediated augmentation of GSIS and calcium release. We obtained similar findings using pancreatic islets prepared from RGS4-deficient mice. Interestingly, RGS4 deficiency had little effect on insulin release caused by activation of other β-cell GPCRs. Finally, treatment of mutant mice selectively lacking RGS4 in pancreatic β-cells with a muscarinic agonist (bethanechol) led to significantly increased plasma insulin and reduced blood glucose levels, as compared to control littermates. Studies with β-cell-specific M3R knockout mice showed that these responses were mediated by β-cell M3Rs. These findings indicate that RGS4 is a potent negative regulator of M3R function in pancreatic β-cells, suggesting that RGS4 may represent a potential target to promote insulin release for therapeutic purposes.
Comparative responsiveness of Parkinson's disease scales to change over time

The objective of the study is to examine the comparative responsiveness of outcome measures to assess progression over time in Parkinson's disease (PD). One hundred twenty‐eight patients participating in a clinic‐based naturalistic study of PD were assessed with the Hoehn and Yahr, UPDRS, MMSE, PDQ‐39, PDQL, EQ‐5D, and BDI scales at baseline and at 1 year. In addition, 82 patients in a community‐based study of patients with PD who had completed self‐rated Schwab and England, PDQ‐39, EQ‐5D, and BDI scales at baseline, were sent the same questionnaires at 1 and 4 years. Responsiveness was assessed using t‐tests, standardised effect size, and standardised response mean. In both samples, the Hr‐QoL measures were less responsive to change over time than the impairment and disability scales (Hoehn and Yahr, UPDRS, Schwab and England scales). In addition, in the clinic‐based sample, Hoehn and Yahr and UPDRS ADL scale (“on”) were more responsive to progression over time than UPDRS motor part and ADL part (“off”). Hr‐QoL measures are less responsive to change over time than measures of impairment and disability. Although this suggests that these measures are less accurate in detecting subtle changes, it may also indicate that the multifactorial subjective assessment of Hr‐QoL adapts to changes over time. Global assessment of overall impairment and disability (which incorporates motor and nonmotor features of PD), however, appeared relatively responsive to change over time in patients in a naturalistic setting. © 2009 Movement Disorder Society
Anatomy of thoracic splanchnic nerves for surgical resection

Thoracic splanchnic nerves conduct pain sensation from the abdominal organs around the celiac ganglion. Splanchnicectomy is the procedure used mainly for the control of intractable visceral pain. Forty‐six human posterior thoracic walls were dissected. The formation pattern, course, and incidence of communication of the thoracic splanchnic nerves were investigated. The greater splanchnic nerves (GSNs) were formed by nerve branches from the T4–T11 thoracic sympathetic ganglia and the most common type was formed by T5–T9 (21.7%). The uppermost branches originated from T4–T9 while the lowermost branches emanated from the T7–T11. Two to seven ganglia contributed to the GSNs. In 54.3% of the specimens, at least one ganglion in the GSN‐tributary ganglionic array did not branch to the GSN. The lesser splanchnic nerves (LSNs) were formed by the nerve branches of the T8–T12 thoracic sympathetic ganglia and the most common type was formed by T10 and T11 (32.6%). One to five ganglia were involved in the LSNs. The least splanchnic nerves (lSNs) were composed of branches from the T10–L1 thoracic sympathetic ganglia and the most common type was composed of nerve branches from T11 and T12 or from T12 only (each 30.4%). One to three ganglia were involved in the lSNs. In 54.3% of the specimens, interconnection between the GSNs and the LSNs existed, bringing the possible bypass around the transection of the GSNs. The splanchnic nerves that appear in textbooks occurred in a minority of our specimens. We provided expanded anatomical data for splanchnicectomy in this report. Clin. Anat. 21:171–177, 2008. © 2008 Wiley‐Liss, Inc.
E2F1 inhibits c-Myc-driven apoptosis via PIK3CA/Akt/mTOR and COX-2 in a mouse model of human liver cancer.

BACKGROUND & AIMS Resistance to apoptosis is essential for cancer growth. We previously reported that hepatic coexpression of c-Myc and E2F1, 2 key regulators of proliferation and apoptosis, enhanced hepatocellular carcinoma (HCC) development in transgenic mice. Here, we investigated the molecular mechanisms underlying oncogenic cooperation between c-Myc and E2F1 in relationship to human liver cancer. METHODS Activation of pro- and antiapoptotic cascades was assessed by immunoblotting in experimental HCC models and in human HCC. Effect of antisense oligodeoxy nucleotides against c-Myc and E2F1 was studied in human HCC cell lines. Suppression of catalytic subunit p110alpha of phosphatidylinositol 3-kinase (PIK3CA)/Akt, mammalian target of rapamycin (mTOR), and cyclooxygenase (COX)-2 pathways was achieved by pharmacologic inhibitors and small interfering RNA in human and mouse HCC cell lines. RESULTS Coexpression with E2F1 did not increase proliferation triggered by c-Myc overexpression but conferred a strong resistance to c-Myc-initiated apoptosis via concomitant induction of PIK3CA/Akt/mTOR and c-Myb/COX-2 survival pathways. COX-2 was not induced in c-Myc and rarely in E2F1 tumors. In human HCC, PIK3CA/Akt/mTOR and c-Myb/COX-2 pathways were similarly activated, with levels of PIK3CA/Akt, mTOR, and c-Myb being inversely associated with patients' survival length. Silencing c-Myc and E2F1 reduced PIK3CA/Akt and mTOR and completely abolished c-Myb and COX-2 expression in human HCC cell lines. Finally, simultaneous inhibition of PIK3CA/Akt/mTOR and COX-2 activity in in vitro models caused massive apoptosis of neoplastic hepatocytes. CONCLUSIONS E2F1 may function as a critical antiapoptotic factor both in human and in rodent liver cancer through its ability to counteract c-Myc-driven apoptosis via activation of PIK3CA/Akt/mTOR and c-Myb/COX-2 pathways.
suPAR: The Molecular Crystal Ball

soluble urokinase Plasminogen Activator Receptor (suPAR) levels reflect inflammation and elevated suPAR levels are found in several infectious diseases and cancer. suPAR exists in three forms; suPARI-III, suPARII-III and suPARI which show different properties due to structural differences. Studies suggest that full-length suPAR is a regulator of uPAR/uPA by acting as uPA-scavenger, whereas the cleaved suPARII-III act as a chemotactic agent promoting the immune response via the SRSRY sequence in the linker-region. This review focus on the various suPAR fragments and their involvement in inflammation and pathogenic processes. We focus on the molecular mechanisms of the suPAR fragments and the link to the inflammatory process, as this could lead to medical applications in infectious and pathological conditions.
Recent advances in the diagnosis, impact on production and prediction of Fasciola hepatica in cattle

SUMMARY Fasciola hepatica is a pathogenic trematode parasite of ruminants with a global distribution. Here, we briefly review the current epidemiology of bovine fasciolosis in Europe and discuss the progress made over the last decade in the diagnosis, impact on production and prediction of F. hepatica in cattle. Advances in diagnosis have led to significantly improved coprological and serological methods to detect presence of infection. Diagnostic test results have been correlated with intensity of infection and associated production losses, unravelling the impact on carcass weight and milk yield in modern cattle production systems. The economic impact of fasciolosis may, however, go beyond the direct impacts on production as evidence shows that F. hepatica can modulate the immune response to some co-infections. Control of bovine fasciolosis remains hampered by the limitations of the currently available flukicidal drugs: few drugs are available to treat dairy cows, many have low efficacies against juvenile stages of F. hepatica and there is evidence for the development of drug resistance. This makes research into the prediction of risk periods, and thus the optimum application of available drugs more pertinent. In this field, the recent research focus has been on understanding spatial risk and delivering region-specific spatial distribution maps. Further advances in epidemiological and economic research on bovine fasciolosis are expected to deliver farm-specific economic assessments of disease impact, to leverage non-chemotherapeutic management options and to enhance a more targeted use of anthelmintics.
Euclidean distance for combinations of some Hamming codes and binary CPFSK modulation

The integration of channel coding and modulation in a communication system to increase the Euclidean distance between modulated signals is analyzed. Systems using binary continuous-phase frequency-shift keying modulation and some block codes, such as Hamming codes and shortened Hamming codes, are considered. It is shown that the minimum Euclidean distance depends on the configuration of the parity-check matrix H of the code. For the examined codes the optimum configurations of H , which give the maximum values of the minimum Euclidean distance, are determined.
Piezoresistance in p-type silicon revisited

We calculate the shear piezocoefficient π44 in p-type Si with a 6×6 k⋅p Hamiltonian model using the Boltzmann transport equation in the relaxation-time approximation. Furthermore, we fabricate and characterize p-type silicon piezoresistors embedded in a (001) silicon substrate. We find that the relaxation-time model needs to include all scattering mechanisms in order to obtain correct temperature and acceptor density dependencies. The k⋅p results are compared to results obtained using a recent tight-binding (TB) model. The magnitude of the π44 piezocoefficient obtained from the TB model is a factor of 4 lower than experimental values; however, the temperature and acceptor density dependencies of the normalized values agree with experiments. The 6×6 Hamiltonian model shows good agreement between the absolute value of π44 and the temperature and acceptor density dependencies when compared to experiments. Finally, we present a fitting function of temperature and acceptor density to the 6×6 model that can be .
The Acquisiton of Word-final Clusters in French

L’estructura de les sil·labes del frances ha estat tema de debat durant molt de temps, sobretot pel que fa a l’estatus de les consonants finals de paraula. Alguns investigadors han suggerit que les consonants finals de mot se sil·labifiquen com a codes, mentre que d’altres han proposat que cons-titueixen atacs de sil·labes sense nucli. Aquest debat planteja certes preguntes sobre la natura de les representacions sil·labiques del frances infantil en desenvolupament, tema que ha rebut poca atencio. El present estudi examina produccions de grups consonantics finals de mot formats per obstruent i liquida (OL), que han estat el·licitats a nens de 2 anys, i les compara amb l’adquisicio de grups OL a principi de mot. Tambe tracta l’adquisicio de consonants individuals a final de mot. Tot i que els grups consonantics finals de mot s’adquireixen mes tard que els grups inicials de mot i que les consonants individuals a final de mot, els tipus d’errors son els mateixos, es a dir, les obstruents s’adquireixen mes de pressa i es preserven. En alguns casos trobem epentesi de vocal final, cosa que suggereix la possibilitat que algunes criatures que adquireixen el frances sil·labifiquin les consonants finals de mot com a atacs. L’article acaba amb una discussio de les implicacions interlinguistiques d’aquests resultats i identifica diverses arees per a la recerca futura.
H-store: a high-performance, distributed main memory transaction processing system

Our previous work has shown that architectural and application shifts have resulted in modern OLTP databases increasingly falling short of optimal performance [10]. In particular, the availability of multiple-cores, the abundance of main memory, the lack of user stalls, and the dominant use of stored procedures are factors that portend a clean-slate redesign of RDBMSs. This previous work showed that such a redesign has the potential to outperform legacy OLTP databases by a significant factor. These results, however, were obtained using a bare-bones prototype that was developed just to demonstrate the potential of such a system. We have since set out to design a more complete execution platform, and to implement some of the ideas presented in the original paper. Our demonstration presented here provides insight on the development of a distributed main memory OLTP database and allows for the further study of the challenges inherent in this operating environment.
Using Shuttle Radar Topography Mission Elevation Data to Map Mangrove Forest Height in the Caribbean

In this paper we describe a methodology to map mangrove forests in 3D in the Caribbean region. We used shuttle radar topography mission (SRTM) elevation, lidar and field data to estimate mangrove mean tree height at the landscape scale. This paper emphasizes two regions which are undergoing ecosystem restoration activities: The Everglades National Park, USA and Cienaga Grande de Santa Marta, Colombia. In these regions we used, respectively, airborne and spaceborne (ICEsat (ice, cloud,and land elevation satellite )) lidar data to calibrate SRTM data and estimate mean tree height. Our results show the method is accurate if mangrove forest canopy vertical structure is well characterized.
PreBötzinger Complex Neurokinin-1 Receptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

The analgesic properties of the opium poppy Papever somniferum were first mentioned by Hippocrates around 400 BC, and opioid analgesics remain the mainstay of pain management today. These drugs can cause the serious side-effect of respiratory depression that can be lethal with overdose, however the critical brain sites and neurochemical identity of the neurons mediating this depression are unknown. By locally manipulating neurotransmission in the adult rat, we identify the critical site of the medulla, the preBötzinger complex, that mediates opioid-induced respiratory depression in vivo. Here we show that opioids at the preBötzinger complex cause respiratory depression or fatal apnea, with anesthesia and deep-sleep being particularly vulnerable states for opioid-induced respiratory depression. Importantly, we establish that the preBötzinger complex is fully responsible for respiratory rate suppression following systemic administration of opioid analgesics. The site in the medulla most sensitive to opioids corresponds to a region expressing neurokinin-1 receptors, and we show in rhythmically active brainstem section in vitro that neurokinin-1 receptor-expressing preBötzinger complex neurons are selectively inhibited by opioids. In summary, neurokinin-1 receptor-expressing preBötzinger complex neurons constitute the critical site mediating opioid-induced respiratory rate depression, and the key therapeutic target for its prevention or reversal.
Recycled fiber treated with NaOH/urea aqueous solution: effects on physical properties of paper sheets and on hornification

Abstract Hydrogen bonding among fiber microfibrils is the primary cause of fiber hornification, wherein NaOH/urea aqueous solution precooled to −13 °C can disassemble inter- and intramolecular hydrogen bonds. Whether hornified fibers treated with this process can significantly improve fiber swelling ability and physical properties of the resulting paper sheets remains a problem. In this investigation, the 6th cycle fiber was pretreated with this procedure, and the water retention value of the fiber before and after treatment and the physical properties of the resulting paper sheets were studied. The results indicate that the lignin decline, complete swelling of flat fiber, filling of cellulose film between the interfiber network, and decreasing crystalline region all contribute to the increase in water retention value. The water retention value of repaired fiber is equivalent to that of virgin pulp, and hornification reverses by 89 %. In addition, the cellulose film filling among the fiber network constructs a similar reinforced concrete structure, which causes the tear, burst, and tensile index of the resulting paper sheets to increase by 145 %, 98 %, and 43 %, respectively.
Simultaneous stabilization with near optimal LQR performance

In this paper, we consider the use of linear time-varying controllers for simultaneous stabilization and performance. We prove that for every finite set of plants, we can design a linear time-varying controller which provides not only closed-loop stability but also near-optimal LQR (linear quadratic regulator) type performance.
Ductile Fracture Modeling of DH36 Grade Steels

A Hosford-Coulomb type ductile fracture surface was developed for DH36 grade steels. The fracture experiments reported in the literature, which consist of tests with notched tensile specimens, tensile specimens with a central hole, shear specimen and disc specimens for punch specimens, were utilized in a detailed finite element analysis of each experiment to evaluate the evolution of local stress and strain fields and identify plasticity and fracture response of DH36. The developed plasticity model consists of a von Mises yield surface, an associated flow rule and a combined Swift-Voce type isotropic hardening rule. The loading paths to fracture initiation were determined in terms of stress triaxiality and normalized Lode angle parameter histories. Finally, the Hosford-Coulomb fracture surface was calibrated using the finite element analysis results and adapting a linear damage accumulation law.
The effects of gabapentin on acute and chronic pain after inguinal herniorrhaphy

Background and objective To find out whether preoperative gabapentin use had a favourable effect on long-term postoperative pain in patients undergoing inguinal herniorrhaphy. Methods Sixty male patients – aged 20–40 years – who were scheduled for unilateral inguinal herniorrhaphy under spinal anaesthesia were included in this prospective, randomized, double-blind study. The patients were randomly allocated to two groups: the gabapentin group (n = 30) received single-dose 1.2 g oral gabapentin 1 h before surgery, and the placebo group received a placebo capsule instead. Spinal anaesthesia was performed with heavy bupivacaine, and all operations were performed by the same surgeon with the same technique. Postoperative analgesia was evaluated during sitting and lying with a visual analogue scale. Assessment of postoperative pain at 1, 3 and 6 months was carried out with an 11-point numerical rating scale; 0 indicating ‘no pain’ and 10 indicating ‘worst pain imaginable’. Patients who had numerical rating scale scores of more than 0 were further evaluated with regard to the impact of pain on their daily activities. Results When compared with the placebo group, the gabapentin group displayed significantly lower visual analogue scale scores (lying and sitting) and total tramadol consumption at 8, 12, 16, 20 and 24 h after surgery (P < 0.05) and higher postoperative patient satisfaction scores (P < 0.05). Numerical rating scale scores at 1, 3 and 6 months after surgery were lower in the gabapentin group than in the placebo group (P < 0.05). The number of patients whose daily activities were adversely affected by pain was smaller in the gabapentin group at the first month; however, the two groups were found to be similar at 3 and 6 months. Conclusion We conclude that preoperative single-dose gabapentin decreases the intensity of acute postoperative pain, tramadol consumption and the incidence and intensity of pain in the first 6 months after inguinal herniorrhaphy.
Implicit and Explicit Components of Prejudice

Research on implicit and explicit prejudice has treated implicit prejudice as a unitary construct characterized by automatic access to negative concepts. The present article makes the case that tasks purported to measure implicit prejudice actually assess 2 different processes. Some assess the extent to which prejudice is activated automatically on the perception of a member of the target group. Other implicit tasks assess the extent to which prejudice is automatically applied in judgment. In the reported study, participants completed 4 implicit and 2 explicit measures of prejudice against women. Factor analysis yielded a 3-factor solution. The solution provides support for the distinction between explicit prejudice and 2 types of implicit prejudice corresponding to automatic activation and automatic application of prejudice. Prejudice appears to be a multifaceted construct, different aspects of which are measured by different tasks.