Miracle-dz/UniFAR-FTUs huggingface dataset:
Forty-one near full-length HIV-1 sequences from Kenya reveal an epidemic of subtype A and A-containing recombinants

ObjectiveTo further define the genetic diversity of HIV-1 in Kenya using approaches that clearly distinguish subtypes from inter-subtype recombinants. DesignNear full genome sequencing and analysis were used, including sensitive new tools for detection and mapping of recombinants. MethodsPurified peripheral blood mononuclear cell DNA from 41 HIV-1 positive blood donations collected from six hospitals across southern Kenya was used to amplify near full-length genomes by nested PCR. These were sequenced on an ABI 3100 automated sequencer and analyzed phylogenetically. ResultsAmong 41 near full-length genomes, 25 were non-recombinant (61%) and 16 were recombinant (39%). Of the 25 pure subtypes, 23 were subtype A, one was subtype C and one was subtype D. Most recombinants consisted of subtype A and either subtype C or subtype D; a few contained A2, a recently identified sub-subtype. Two A2/D recombinants had identical breakpoints and may represent a circulating recombinant form. A third A2/D recombinant had the same structure as a previously described Korean isolate, and these may constitute a second A2-containing circulating recombinant form. ConclusionsIn Kenya, 93% of HIV-1 genomes were subtype A or A-containing recombinant strains. Almost 40% of all strains were recombinant. Vaccine candidates tested in Kenya should be based on subtype A strains, but the methods used for evaluation of breakthrough infections during future vaccine trials should be capable of identifying non-A subtypes, the A2 sub-subtype, and recombinants.
Area-Dependent Photodetection Frequency Response Characterization of Silicon Avalanche Photodetectors Fabricated With Standard CMOS Technology

We investigate the area-dependent characteristics of photodetection frequency responses of 850-nm silicon avalanche photodetectors (APDs) fabricated with standard complementary metal-oxide-semiconductor (CMOS) technology. CMOS-compatible APDs (CMOS-APDs) based on a p+/n-well junction with four different device areas are used for the investigation, and we identify factors that influence photodetection frequency responses with the goal of achieving optimal photodetection bandwidth performance. Their current-voltage characteristics, electrical reflection coefficients, and photodetection frequency responses are measured, and the characteristics of the CMOS-APD photodetection frequency responses are analyzed using equivalent circuit models. From this, it is clarified how the four different factors of photogenerated-carrier transit time, device RC time constant, inductive-peaking effect, and parasitics contribute to the photodetection frequency responses and how their contribution changes with device areas. Among the four types of CMOS-APDs investigated in this study, the 10 × 10 μm2 CMOS-APD has the largest 3-dB photodetection bandwidth of 7.6 GHz.
Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype.

OBJECTIVE In children with RET proto-oncogene mutation, curative treatment of medullary thyroid carcinoma (MTC) is possible by prophylactic thyroidectomy. Recommendations on the timing and extent of thyroidectomy are based upon a model that utilises genotype-phenotype correlations to stratify mutations into three risk groups. DESIGN We evaluated the long-term outcome (mean follow-up 6.4 years, 15 patients more than 10 years, 26 patients more than 5 years) of operated gene carriers stratified into two risk groups (levels 1 and 2) based on the biological aggressiveness of MTC. RESULTS In 46 RET gene carriers, prophylactic thyroidectomy was carried out between the ages of 4 and 21 years. Level 1 mutations were harboured by 11 patients (codons 790, 791, 804 and 891). Histology was completely normal in two patients; in seven patients C-cell hyperplasia (CCH) and in two patients T1 tumours were diagnosed. All patients with level 1 mutations were cured. Level 2 mutations were harboured by 35 patients (codons 618, 620, 630 and 634). Histology of these patients showed CCH in 11 patients, T1 tumours in 21, T2 tumour in 1, T3 tumour in 1 and Tx in 1 patient. Histology showed no lymph node involvement. Five patients with level 2 mutations failed to be cured; in two patients, persistence of MTC was diagnosed directly after thyroidectomy and in three during follow-up. In two patients carrying a 634 mutation, other endocrinopathies (hyperparathyroidism and bilateral pheochromocytoma) manifested during follow-up. CONCLUSIONS If prophylactic thyroidectomy is done at early ages, cure rate is high. Timing and extent of prophylactic thyroidectomy can be modified by individual RET mutation.
Interferential therapy effect on mechanical pain threshold and isometric torque after delayed onset muscle soreness induction in human hamstrings

Abstract This study was undertaken to examine the acute effect of interferential current on mechanical pain threshold and isometric peak torque after delayed onset muscle soreness induction in human hamstrings. Forty-one physically active healthy male volunteers aged 18−33 years were randomly assigned to one of two experimental groups: interferential current group (n = 21) or placebo group (n = 20). Both groups performed a bout of 100 isokinetic eccentric maximal voluntary contractions (10 sets of 10 repetitions) at an angular velocity of 1.05 rad · s−1 (60° · s−1) to induce muscle soreness. On the next day, volunteers received either an interferential current or a placebo application. Treatment was applied for 30 minutes (4 kHz frequency; 125 μs pulse duration; 80−150 Hz bursts). Mechanical pain threshold and isometric peak torque were measured at four different time intervals: prior to induction of muscle soreness, immediately following muscle soreness induction, on the next day after muscle soreness induction, and immediately after the interferential current and placebo application. Both groups showed a reduction in isometric torque (P < 0.001) and pain threshold (P < 0.001) after the eccentric exercise. After treatment, only the interferential current group showed a significant increase in pain threshold (P = 0.002) with no changes in isometric torque. The results indicate that interferential current was effective in increasing hamstrings mechanical pain threshold after eccentric exercise, with no effect on isometric peak torque after treatment.
THE GENETICS AND COST OF CHEMICAL DEFENSE IN THE TWO‐SPOT LADYBIRD (ADALIA BIPUNCTATA L.)

Ladybirds (Coccinellidae) defend themselves against attack by vertebrate predators by exuding a fluid from the femero‐tibial joints. This fluid carries a noxious or toxic alkaloid. The amount of fluid produced during a single attack can be very high (up to 20% of fresh body weight), and the weight of the self‐synthesized alkaloid can amount to several percent of the weight of the fluid. A study was carried out on these two defense characters and two other fitness characters (body weight and growth rate) to demonstrate a cost to defense in the form of genetic trade‐offs between characters. The two sexes were analyzed separately, and a jackknife procedure was used to attach errors to the estimates of Va and cova. All four characters were associated with high levels of Va, but the cova values were mixed, some being negative and others positive. Principal‐component analysis indicated the operation of factors constraining the cova values in males, and further possible reasons for the appearance of so many positive values are explored. A matrix analysis showed that the genetic variance/covariance matrices of the two sexes were significantly different from each other. Breeding values derived from sons plotted on breeding values from daughters had correlation coefficients significantly less than +1. This finding indicated that a substantial amount of sex‐dependent gene expression was occurring.
Effects of Lovastatin and Pravastatin on the Survival of Hamsters With Inherited Cardiomyopathy

Cardiomyopathic hamsters develop heart disease early in life, which leads to congestive heart failure and death as these hamsters age. Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to reduce ubiquinone concentrations and to deteriorate myocardial function in humans and in experimental animals. HMG-CoA reductase inhibitors differ regarding their ability to penetrate extrahepatic tissues. As a consequence, lovastatin inhibits cholesterol biosynthesis at least 100-Fold more effectively than pravastatin in extrahepatic cells. We examined the effect of lovastatin and pravastatin (approximately 10 mg per kilogram of body weight and per day mixed in the diet) compared with controls on the lifespan of cardiomyopathic hamsters (BIO 8262 strain) in the heart-failure period. In male hamsters, neither lovastatin nor pravastatin significantly affected survival. In female hamsters, lovastatin reduced median survival time from 89 days (control animals) to 30 days (P < .05); pravastatin (median survival, 115 days) had no statistically significant effect. We conclude that lovastatin, but not pravastatin, at a daily dose of 10 mg per kilogram of body weight significantly increases the mortality of cardiomyopathic hamsters. This effect may be the result of inhibition of myocardial ubiquinone supply.
Voluntary Ethanol Intake Predicts κ-Opioid Receptor Supersensitivity and Regionally Distinct Dopaminergic Adaptations in Macaques

The dopaminergic projections from the ventral midbrain to the striatum have long been implicated in mediating motivated behaviors and addiction. Previously it was demonstrated that κ-opioid receptor (KOR) signaling in the striatum plays a critical role in the increased reinforcing efficacy of ethanol following ethanol vapor exposure in rodent models. Although rodents have been used extensively to determine the neurochemical consequences of chronic ethanol exposure, establishing high levels of voluntary drinking in these models has proven difficult. Conversely, nonhuman primates exhibit similar intake and pattern to humans in regard to drinking. Here we examine the effects of chronic voluntary ethanol self-administration on dopamine neurotransmission and the ability of KORs to regulate dopamine release in the dorsolateral caudate (DLC) and nucleus accumbens (NAc) core. Using voltammetry in brain slices from cynomolgus macaques after 6 months of ad libitum ethanol drinking, we found increased KOR sensitivity in both the DLC and NAc. The magnitude of ethanol intake predicted increases in KOR sensitivity in the NAc core, but not the DLC. Additionally, ethanol drinking increased dopamine release and uptake in the NAc, but decreased both of these measures in the DLC. These data suggest that chronic daily drinking may result in regionally distinct disruptions of striatal outputs. In concert with previous reports showing increased KOR regulation of drinking behaviors induced by ethanol exposure, the strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism.
Word order, referential expression, and case cues to the acquisition of transitive sentences in Italian*

ABSTRACT In Study 1 we analyzed Italian child-directed-speech (CDS) and selected the three most frequent active transitive sentence frames used with overt subjects. In Study 2 we experimentally investigated how Italian-speaking children aged 2;6, 3;6, and 4;6 comprehended these orders with novel verbs when the cues of animacy, gender, and subject–verb agreement were neutralized. For each trial, children chose between two videos (e.g., horse acting on cat versus cat acting on horse), both involving the same action. The children aged 2;6 comprehended S + object-pronoun + V (soprov) significantly better than S + V + object-noun (svonoun). We explain this in terms of cue collaboration between a low cost cue (case) and the firstargument = agent cue which we found to be reliable 76% of the time. The most difficult word order for all age groups was the object-pronoun + V + S (oprovs). We ascribe this difficulty to cue conflict between the two most frequent transitive frames found in CDS, namely V + object-noun and object-pronoun + V.
The dynamic audio–motor system in pianists

This paper reports a preliminary study based on the theoretical assumption that continuous closed‐loop audio–motor control could be disadvantageous for pianists. It is argued that the functional relationship between the intracerebral electrical activations in the auditory and premotor cortex should be rhythmically decreased and increased. To test this hypothesis, intracerebral electrical activations for the auditory and premotor cortex were estimated using scalp EEG and standardized low‐resolution electrical tomography (sLORETA). The extracted times series were subjected to a Granger causality analysis, revealing a causal relationship from the auditory cortex to the premotor cortex that was considerably stronger during piano playing and weaker during rest. Importantly, this relationship varied rhythmically during the course of piano playing, with lags (obtained with cross‐correlations) between 666 ms and 820 milliseconds. This study thus delivers evidence that the functional coupling between the auditory and premotor cortex varies during piano playing.
Colonic H+-K+-ATPase is induced and mediates increased HCO3- reabsorption in inner medullary collecting duct in potassium depletion.

BACKGROUND Potassium depletion increases HCO3- reabsorption in outer medullary collecting duct (OMCD) by activation of colonic (c) H-K-ATPase (HKA). The purpose of the current experiments was to examine the role of the isoforms of HKA in HCO3- reabsorption by terminal inner medullary collecting duct (IMCD) cells in potassium depletion. METHODS Sprague-Dawley rats were fed a potassium-free diet and studied after 8 to 10 days. mRNA expression of HKA isoforms in terminal portion of inner medulla was examined and correlated with HCO3- reabsorption in the terminal IMCD. RESULTS Gastric (g) HKA mRNA decreased whereas colonic (c) HKA mRNA expression was heavily induced in terminal portion of inner medulla in potassium depleted rats. Net HCO3- flux (JtCO2) in terminal IMCD increased in potassium depletion (4.56 to 7.06 pmol/min/mm tubule length, P < 0.001). In normal rats, 1 mM ouabain in perfusate had no effect on JtCO2, whereas 10 microM Schering 28080 (SCH) decreased JtCO2 to 2.4 (P < 0.002). In KD rats, 1 mM ouabain decreased JtCO2 to 4.9 (P < 0.005) and 10 microM SCH decreased JtCO2 to 3.3 (P < 0.001). However, the inhibitory effects of SCH and ouabain on JtCO2 in potassium depleted animals were not additive. CONCLUSIONS The data indicate that gHKA is suppressed whereas cHKA is induced in potassium depletion and mediates increased HCO3- reabsorption in terminal IMCD. The results further indicate that cHKA in vivo is sensitive to both SCH and ouabain.
Successful transplantation of porcine liver grafts following 48-hour normothermic preservation

Current cold storage organ preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation of liver allografts. Long-term organ preservation using normothermic perfusion might not only allow organ viability assessment before transplantation, but also provide the means for further organ modifications under physiologic conditions. Previous research has shown that porcine livers can be transplanted successfully after normothermic preservation of 20 hours. In the present study we investigate whether similar methodology is capable of further extending the safe limit to 48 hours. In this study, livers from White Landrace pigs were preserved by normothermic, oxygenated sanguineous perfusion. After a 48-hour period of preservation, livers were transplanted into recipient pigs and followed for 5 days. Outcome parameters measured included markers of synthetic and metabolic liver function as well as hepatocellular injury and blood gas analysis during perfusion and follow-up. Histological assessment of morphological liver integrity was performed. All livers showed sustained bile production and metabolic activity throughout the preservation period. Low levels of hepatocellular damage were found. Following transplantation all liver grafts revealed excellent graft function and death-censored graft survival was 100%. Porcine livers were transplanted successfully following 48 hours normothermic machine preservation.
Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969–2002

Liver cirrhosis may be complicated by the development of esophageal varices. The treatment of esophageal varices has changed radically during the last 30 years. Our aim was to study whether the prognosis for patients with esophageal varices had improved in Sweden between 1969 and 2002. We linked register data from the Hospital Discharge Register and from the Causes of Death Register at The National Board of Health in Sweden between 1969 and 2002 to identify and follow‐up all patients with esophageal varices according to International Classification of Diseases—8, —9, and —10. There were 12,281 patients hospitalized with esophageal varices, and for all patients there was an increase in the 5‐year survival in the years between 1969 and 1979 as opposed to the years between 1990 and 2002. Better survival occurred for women compared with men, for younger patients compared with older, and for patients hospitalized in the latest decade compared with the earlier decades. We found a significant decrease in the mortality caused by esophageal varices during the years studied but no decrease attributable to other causes. In conclusion, mortality for patients hospitalized with esophageal varices in Sweden decreased between 1969 and 2002. The decrease is seen for both 1‐ and 5‐year mortality, and this suggests that the use of new treatment strategies both for acute variceal hemorrhage and secondary prophylaxis has had an impact on prognosis. (HEPATOLOGY 2006;43:500–505.).
Efficacy and tolerability of budesonide aqueous nasal spray in chronic rhinosinusitis patients.

This study evaluated the efficacy and tolerability of budesonide in an aqueous nasal spray (BANS) in patients with chronic rhinosinusitis. In this double-blind, placebo-controlled, multicentre, parallel-group study, patients (n = 167) with persistent rhinosinusitis symptoms despite 2-weeks' antibiotic treatment were randomised to receive BANS 128 micrograms b.i. d. or placebo for 20 weeks. Morning combined symptom scores (CSS) in patients receiving BANS decreased by a mean of -1.85 (95% CI -2.27, -1.43), versus -1.02 (-1.43, -0.61) in the placebo group (p = 0.005); corresponding values for evening CSS were -1.78 (-2.22, -1.35) and -1.02 (-1.45, -0.60), respectively (p = 0.012). BANS produced significant reductions in nasal congestion and discharge scores, and improved patients' sense of smell (morning only), versus placebo. Peak nasal inspiratory flow (PNIF) increased significantly during BANS treatment. In allergic patients, BANS significantly (p < 0.001) reduced both morning -1.40 (-2.18, -0.62) and evening -1.37 (-2.15, -0.58) CSS from baseline versus placebo, but changes in non-allergic patients (morning: -0.04 [-0.95, 0.87]; evening: 0.14 [-0.81, 1.09]) were not significant. PNIF was significantly (p < 0.01) increased in both allergic and non-allergic patients from baseline versus placebo. BANS is an effective and well-tolerated treatment for chronic rhinosinusitis.
Role of the spacer between the −35 and −10 regions in σs promoter selectivity in Escherichia coli

In vitro, the σs subunit of RNA polymerase (RNAP), RpoS, recognizes nearly identical −35 and −10 promoter consensus sequences as the vegetative σ70. In vivo, promoter selectivity of RNAP holoenzyme containing either σs (Eσs) or σ70 (Eσ70) seems to be achieved by the differential ability of the two holoenzymes to tolerate deviations from the promoter consensus sequence. In this study, we suggest that many natural σs‐dependent promoters possess a −35 element, a feature that has been considered as not conserved among σs‐dependent promoters. These −35 hexamers are mostly non‐optimally spaced from the −10 region, but nevertheless functional. A ± 2 bp deviation from the optimal spacer length of 17 bp or the complete absence of a −35 consensus sequence decreases overall promoter activity, but at the same time favours Eσs in its competition with Eσ70 for promoter recognition. On the other hand, the reduction of promoter activity due to shifting of the −35 element can be counterbalanced by an activity‐stimulating feature such as A/T‐richness of the spacer region without compromising Eσs selectivity. Based on mutational analysis of σs, we suggest a role of regions 2.5 and 4 of σs in sensing sub‐optimally located −35 elements.
Neurons in the monkey superior colliculus predict the visual result of impending saccadic eye movements.

1. Previous experiments have shown that visual neurons in the lateral intraparietal area (LIP) respond predictively to stimuli outside their classical receptive fields when an impending saccade will bring those stimuli into their receptive fields. Because LIP projects strongly to the intermediate layers of the superior colliculus, we sought to demonstrate similar predictive responses in the monkey colliculus. 2. We studied the behavior of 90 visually responsive neurons in the superficial and intermediate layers of the superior colliculus of two rhesus monkeys (Macaca mulatta) when visual stimuli or the locations of remembered stimuli were brought into their receptive fields by a saccade. 3. Thirty percent (18/60) of intermediate layer visuomovement cells responded predictively before a saccade outside the movement field of the neuron when that saccade would bring the location of a stimulus into the receptive field. Each of these neurons did not respond to the stimulus unless an eye movement brought it into its receptive field, nor did it discharge in association with the eye movement unless it brought a stimulus into its receptive field. 4. These neurons were located in the deeper parts of the intermediate layers and had relatively larger receptive fields and movement fields than the cells at the top of the intermediate layers. 5. The predictive responses of most of these neurons (16/18, 89%) did not require that the stimulus be relevant to the monkey's rewarded behavior. However, for some neurons the predictive response was enhanced when the stimulus was the target of a subsequent saccade into the neuron's movement field. 6. Most neurons with predictive responses responded with a similar magnitude and latency to a continuous stimulus that remained on after the saccade, and to the same stimulus when it was only flashed for 50 ms coincident with the onset of the saccade target and thus never appeared within the cell's classical receptive field. 7. The visual response of neurons in the intermediate layers of the colliculus is suppressed during the saccade itself. Neurons that showed predictive responses began to discharge before the saccade, were suppressed during the saccade, and usually resumed discharging after the saccade. 8. Three neurons in the intermediate layers responded tonically from stimulus appearance to saccade without a presaccadic burst. These neurons responded predictively to a stimulus that was going to be the target for a second saccade, but not to an irrelevant flashed stimulus. 9. No superficial layer neuron (0/27) responded predictively when a stimulus would not be brought into their receptive fields by a saccade. (ABSTRACT TRUNCATED AT 400 WORDS)