Search for low-mass weakly interacting massive particles with SuperCDMS.

We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass <30 GeV/c(2), with the signal region blinded. Eleven events were observed after unblinding. We set an upper limit on the spin-independent WIMP-nucleon cross section of 1.2×10(-42) cm(2) at 8 GeV/c(2). This result is in tension with WIMP interpretations of recent experiments and probes new parameter space for WIMP-nucleon scattering for WIMP masses <6 GeV/c(2).

Search for axions with the CDMS experiment.

We report on the first axion search results from the Cryogenic Dark Matter Search (CDMS) experiment at the Soudan Underground Laboratory. An energy threshold of 2 keV for electron-recoil events allows a search for possible solar axion conversion into photons or local galactic axion conversion into electrons in the germanium crystal detectors. The solar axion search sets an upper limit on the Primakov coupling g(agammagamma) of 2.4x10(-9) GeV-1 at the 95% confidence level for an axion mass less than 0.1 keV/c2. This limit benefits from the first precise measurement of the absolute crystal plane orientations in this type of experiment. The galactic axion search analysis sets a world-leading experimental upper limit on the axioelectric coupling g(aee) of 1.4x10(-12) at the 90% confidence level for an axion mass of 2.5 keV/c2.

Search for weakly interacting massive particles with the first five-tower data from the cryogenic dark matter search at the soudan underground laboratory.

We report results from the Cryogenic Dark Matter Search at the Soudan Underground Laboratory (CDMS II) featuring the full complement of 30 detectors. A blind analysis of data taken between October 2006 and July 2007 sets an upper limit on the weakly interacting massive particle (WIMP) nucleon spin-independent cross section of 6.6x10;{-44} cm;{2} (4.6x10;{-44} cm;{2} when combined with previous CDMS II data) at the 90% confidence level for a WIMP mass of 60 GeV/c;{2}. This achieves the best sensitivity for dark matter WIMPs with masses above 44 GeV/c;{2}, and significantly restricts the parameter space for some favored supersymmetric models.

First results from the Cryogenic Dark Matter Search in the Soudan Underground Laboratory.

We report the first results from a search for weakly interacting massive particles (WIMPs) in the Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory. Four Ge and two Si detectors were operated for 52.6 live days, providing 19.4 kg d of Ge net exposure after cuts for recoil energies between 10 and 100 keV. A blind analysis was performed using only calibration data to define the energy threshold and selection criteria for nuclear-recoil candidates. Using the standard dark-matter halo and nuclear-physics WIMP model, these data set the world's lowest exclusion limits on the coherent WIMP-nucleon scalar cross section for all WIMP masses above 15 GeV/c2, ruling out a significant range of neutralino supersymmetric models. The minimum of this limit curve at the 90% C.L. is 4 x 10(-43) cm2 at a WIMP mass of 60 GeV/c2.

Ambulatory 24-h colonic manometry in healthy humans.

Our aim was to investigate motor activity of the healthy, relatively unprepared colon in the ambulatory state. Twenty-five age- and gender-matched adults had a six-sensor solid-state probe inserted into the proximal transverse colon without sedation. Subjects ambulated freely and ate standard meals. In 528 h of recording, we found a lower (P < 0.05) area under the curve during the night. Waking induced a threefold increase in motility, whereas meals induced a twofold increase. Women showed less activity (P < 0.05) in the transverse/descending colon than men. The transverse/descending colon showed more (P < 0.05) activity than the rectosigmoid colon. Seven patterns were recognized; predominantly, they were simultaneous, propagated, or periodic bursts of 3-cycles/min (cpm) waves. A specialized propagating pressure wave with a high amplitude (>105 mmHg) and a prolonged duration (>14 s) occurred in all subjects (mean 10/day), mostly after waking, after meals, or with defecation. A 3-cpm motor activity was seen in the rectosigmoid region predominantly at night. The colon exhibits a wide spectrum of pressure activity around the clock, with gender and regional differences and circadian rhythm. This comprehensive study provides qualitative and quantitative normative data for colonic manometry.

Altered periodic rectal motor activity: a mechanism for slow transit constipation.

The pathophysiology of slow transit constipation is poorly understood. Both decreased and increased distal colonic motility have been reported. In healthy humans, a 3 cycles per minute (cpm), periodic rectal motor activity (PRMA) has been described. Our aim was to investigate the characteristics of PRMA and to assess its role in the pathogenesis of constipation. A six-sensor solid-state probe was placed with the tip sensor in the mid-transverse colon, without sedation, and prolonged colonic motility was recorded in nine patients with slow transit constipation (1M, 8F) and in 11 healthy subjects (3M, 8F). Subjects were free to ambulate. We examined the frequency, nocturnal vs. diurnal variation, and characteristics of PRMA, and its relationship to proximal colonic motility. All subjects showed PRMA. The rhythm was similar (2.5-4 cpm) in both groups. However, constipated patients exhibited a greater (P < 0.001) number of PRMA cycles than controls. The duration of each cycle and amplitude of pressure waves during PRMA were also greater (P < 0.05) at night in patients compared with controls. In patients, 40% of PRMA cycles were associated with a proximal colonic motor event compared with 81% in controls (P < 0.02). The area under the curve of all colonic pressure waves and incidence of specialized propagating pressure waves was lower (P < 0.05) in patients during daytime. When compared with controls, constipated patients exhibited reduced daytime colonic pressure waves and a higher frequency of PRMA. Most of the PRMA was unrelated to proximal colonic activity in constipated patients in contrast with findings in control patients. In addition to decreased colonic motility, this excessive and unco-ordinated phasic rectal activity may further impede stool transport and contribute to the pathogenesis of slow transit constipation.

Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy.

Failure of local tumor control still poses a problem for radiotherapy and translates into reduced survival. Combining radiation with chemotherapy or other newer modalities has shown promising results. Immunological approaches to tumor therapy have found renewed interest due to improved insight into mechanisms involved in the immune response to tumors. In this paper, we studied tumor growth delay after various combination regimens of locally injected adenovirus constitutively expressing IL12 and B7.1 (AdIL12/B7.1) and fractionated radiotherapy in two nonimmunogenic murine tumor models, 4T1 and B16.F10. Effects of radiation and virus infection on surface antigen expression in these tumor lines were assessed. Mechanisms of action of AdIL12/B7.1 were studied by conducting additional experiments with and without depletion of NK-cells and/or T-cells, and by cytotoxic T-lymphocyte assays, and immunohistochemical evaluation of tumor blood vessels. Both B7.1 and IL12 were effectively expressed in both irradiated and unirradiated 4T1 and B16.F10 tumor cells but did not add significantly to radiation-induced cell killing in vitro. However, local tumor infection by AdIL12/B7.1 after irradiation significantly increases the effectiveness of radiotherapy when applied after completion of radiotherapy. The mechanism appears to be complicated, involving a host of factors that included the ability of IL12 to activate T-cells and NK-cells and to inhibit angiogenesis and the ability of radiation to induce apoptosis or necrosis among tumor cells. These data support the combination of radiotherapy with adenovirus-mediated immunotherapy and suggest that the concept of adding genetic immunotherapy after radiotherapy in a combined regimen merits further study.

Effects of fat and carbohydrate meals on colonic motor response.

BACKGROUND: Ingestion of a meal stimulates colonic motility. It is unclear whether the nutrient composition of a meal affects colonic motor response. AIMS: To investigate and compare the effects of a predominantly fat or carbohydrate meal on colonic motility. METHODS: In 18 healthy subjects, ambulatory colonic manometry was performed by placing a six sensor, solid state probe from the mid-transverse colon to the rectum. In a randomised, crossover design, 10 and 27 hours after probe placement, subjects received 4.18 MJ meals containing 60% calories from fat or carbohydrate sources. Preprandial and postprandial pressure activity and motor patterns were evaluated. RESULTS: Both meals induced phasic activity with a greater area under the curve (p<0.03) in the first postprandial hour, compared with the control period. Fat induced motor activity persisted longer (p<0.05) than that of the carbohydrate meal, but the onset of motor response was slower (p<0.001). Although both meals induced more (p<0.001) propagating pressure waves, only the fat meal induced more (p<0.05) simultaneous and retrograde waves. After both meals, 50% of subjects exhibited high amplitude (more than 103 mm Hg), prolonged duration (more than 13 seconds) propagating waves. Both meals induced greater activity (p<0.05) in the transverse/descending colon than in the rectosigmoid colon. CONCLUSIONS: Carbohydrate meals induce colonic motor response, but the effects are short lived when compared with fat meals. The prolonged, segmental, and retrograde phasic activity induced by the fat meal may delay colon transit. Thus meal composition influences colonic motor response.

MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition.

Antigen-specific T cell recognition is dependent on the functional density of the TCR-ligand, which consists of specific MHC molecules and a specifically bound peptide. We have examined the influence of the affinity and concentration of exogenous peptide and the density of specific MHC molecules on the proliferation of a CD4+, DQA1*0501/DQB1*0201 (DQ2.1)-restricted, HSV-2-specific T cell clone. Using antigen peptide analogs with different mutations of known DQ2-anchor residues, T cell response was reduced in an peptide-affinity and - concentration specific manner. The decrease using weaker binding peptides was gradual as stimulation with a peptide with intermediate affinity yielded intermediate T cell proliferation and the poorest binding peptide induced an even weaker T cell response. MHC class II density on the APC was modified using DQ2 homo- and heterozygous B-LCLs as APCs, however this variation of MHC concentration had no effect on T cell proliferation. We interpret this as a reflection of a low threshold for activation of the T cell clone, in which peptide-MHC avidity is the over-riding determinant of the strength of ligand signal.

Effects of acute graded exercise on human colonic motility.

Whether physical exercise stimulates colonic motility is unclear. Our aim was to determine the immediate effects of graded exercise on colonic motility. Colonic motility was recorded at six sites in 11 untrained subjects, by colonoscopically placing a solid-state probe. Subjects were free to ambulate. The next day, subjects exercised on a bicycle at 25, 50, and 75% of peak oxygen uptake for 15 min, with each followed by a 15-min rest. Motor patterns, motility indexes, and regional variations before, during exercise, during rest, and during postexercise periods were compared. During exercise, there was an intensity-dependent decrease (P < 0.001) in the number and area under the curve of pressure waves. The incidence of propagated or simultaneous pressure waves and cyclical events also decreased (P < 0.05). After exercise, the pressure activity reverted to baseline, but the number and amplitude of propagated waves increased (P < 0.01), whereas the simultaneous waves and cyclical events remained lower. Acute graded exercise decreases colonic phasic activity. This may offer less resistance to colonic flow, whereas the postexercise increase in propagated activity may enhance colonic propulsion.

Manometric tests of anorectal function in healthy adults.

OBJECTIVE: Although tests of anorectal function are useful in the assessment of defecation disorders, there is inadequate and inconsistent information regarding normative data. Also, there are discrepancies in manometric techniques and data interpretation. Our aim was to perform a comprehensive evaluation of anorectal function in healthy adults. METHODS: We used a 6-mm diameter probe containing six radially arrayed microtransducers, and a 4-cm-long latex balloon for performing anorectal manometry in 45 healthy subjects who were controlled for gender and age. Sequentially, subjects were asked to squeeze, bear down, or blow up a party balloon. Subsequently, rectal sensation, rectal compliance, and rectoanal reflexes were assessed simultaneously by performing intermittent phasic balloon distentions. Additionally, balloon defecation, pudendal nerve latency, and saline continence tests were performed. RESULTS: In men, the anal sphincter was longer (p < 0.05) and squeeze sphincter pressure and squeeze duration were higher (p < 0.01), but resting sphincter pressure was similar to that in women. When bearing down, although not significant, the defecation index was higher in men. Distinct thresholds for rectal sensation were identified but there was no gender difference. Likewise, rectal compliance and balloon expulsion time were similar. However, during saline infusion, the onset of first leak and total volume retained were higher (p < 0.001) and pudendal nerve latency was shorter (p < 0.05) in men. Overall, parity or age did not influence anorectal function. CONCLUSIONS: This study represents the most comprehensive age- and gender-controlled assessment of anorectal function using solid state technology. Gender influences some parameters of anorectal function. Our results could serve as a valuable resource of normative data.

The PowerChecker: a visual basic program for ensuring data integrity.

Data entry and encoding errors can jeopardize the integrity of data sets generated in a variety of research settings. Despite researchers' pursuits of more accurate entry methods, data entry errors persist. Although techniques exist for identifying such errors, the PowerChecker program described here provides a more efficient method of data set validation. Rather than enter data twice and then manually search for the correct values when there are discrepancies between the two sets, with PowerChecker the user can correct entry errors as the data are entered the second time. In addition, the time-stamped record of changes to the original data set aids in meeting quality assurance requirements of the Good Clinical Practice standards.

Slipped capital femoral epiphysis associated with radiation therapy.

We reviewed 32 children with 41 radiation-therapy associated slipped capital femoral epiphyses (RTASCFE). Ten were from the authors' institutions and 22 from the literature. Gender distribution was equal. The age at diagnosis of the malignancy was 4.3 +/- 3.1 years; the amount of radiation was 4,240 +/- 1,445 rads. Children with RTASCFE presented younger (10.4 +/- 3.2 years) than a routine SCFE. The average symptom duration was 5 +/- 6 months. Children with RTASCFE are usually thin (median weight, 10th percentile) in contrast to children with typical SCFE, who are usually obese (<95th percentile). The majority (82%) of the slips were mild, compared to routine SCFEs (approximately 50%); 28% were bilateral. There was a positive linear relationship between the age at presentation of the SCFE and the age at diagnosis of the malignancy; there was a negative linear relationship between the age at presentation of the SCFE and the amount of radiation therapy.

Orthopedic aspects of child abuse.

Child abuse remains a relatively frequent cause of orthopedic injuries in infants and children, and, although the classic signs of abuse are still useful for identifying victims, more careful observation and more sophisticated diagnostic tests, such as collagen synthesis, may be required to identify less severely injured victims. Recently observed changes in injury patterns and age incidences should be considered in the evaluation of a child suspected of being a child abuse victim.

Chondrolysis after slipped capital femoral epiphysis.

Chondrolysis, or acute cartilage necrosis, is a controversial and perplexing complication of slipped capital femoral epiphysis (SCFE) in adolescents. It usually leads to deformity, pain, limping, and limitation of motion in the affected extremity. Although several theories have been proposed, no agreement has been reached as to the etiology or the pathogenesis of chondrolysis. Furthermore, no treatment program has been completely successful, and the general prognosis and natural history of this condition are not clear. An overview of the latest knowledge of the matter is presented.

Functional effects of a natural polymorphism in the transcriptional regulatory sequence of HLA-DQB1.

DNA sequence polymorphism in the genes encoding HLA class II proteins accounts for allelic diversity in antigen recognition and presentation and, thus, in the role of these cell surface glycoproteins as determinants of the scope of the T-cell repertoire. In addition, sequence polymorphism in the promoter-proximal transcriptional regulatory regions of these genes has been described, particularly for the HLA-DQB1 locus, where these differences may contribute to variation in locus- and allele-specific expression. In this study, we measured the effect of such regulatory sequence polymorphism on the expression of endogenous alleles of DQB1 in heterozygous cells. Quantitative reverse transcriptase-mediated PCR analysis showed that expression of the DQB1*0301 allele responded more rapidly to gamma interferon induction than that of DQB1*0302. We have analyzed functional effects of a prominent allelic polymorphism that consists of a TG dinucleotide present between the W and X1 consensus elements in the DQB1*0302 allele but missing in the DQB1*0301 allele. The dominant effect of this polymorphism was to introduce a variation in the spacing between the W and X1 elements of these two alleles. A secondary compensatory effect was specific for the TG dinucleotide itself, which was essential for the binding of a nuclear protein complex to the *0302 regulatory region immediately 5' of the X1 element. Derivatives of the DQB1 5' regulatory region were used to drive expression of the chloramphenicol acetyltransferase gene in transient transfections of human B-lymphoblastoid and gamma interferon-treated melanoma cell lines, demonstrating that the additional spacing between the W and X1 elements caused by the presence of the TG dinucleotide in the *0302 allele resulted in reduced expression compared with that driven by the *0301 fragment; this difference overshadowed an up-regulating effect on expression which corresponded to the binding of the TG-dependent nuclear protein complex. The presence of this polymorphism in multiple HLA-DQB1 alleles and in several species suggests selection for two alternative transcriptional regulatory mechanisms influencing expression of alleles of the same HLA locus.

Influence of processing supplemental alfalfa on intake and digestion of dormant bluestem-range forage by steers.

Four ruminally and duodenally fistulated, 2-yr-old Angus x Hereford steers (average initial BW = 370 kg) were used to evaluate the effect of method of processing supplemental alfalfa on intake and digestion of dormant bluestem-range forage (2.8% CP, 78% NDF). Treatments (4 x 4 Latin square) were 1) control, no supplement; 2) ground and pelleted alfalfa hay (PELLET; 21% CP, 37% NDF); 3) ground and pelleted dehydrated alfalfa (DEHY; 21% CP, 44% NDF); and 4) longstem alfalfa hay (HAY; 20% CP, 37% NDF). All supplements were from a single cutting of alfalfa and fed at .5% BW (as-fed basis). Supplementing steers with alfalfa increased (P < or = .07) bluestem forage OM intake (FOMI); total OM intake (TOMI); true ruminal OM digestibility; total tract OM digestibility (TTOMD); total N, microbial N, and nonammonia-nonmicrobial N (NANM) flows to the duodenum; ruminal OM and fluid fill; fluid dilution rates; dietary DE concentration; and ruminal total VFA and NH3 N concentrations. Because of the enhanced FOMI and TOMI associated with alfalfa supplementation and the concomitant improvement in TTOMD, digestible OM intake (DOMI) also increased (P < .01) when supplemental alfalfa was fed. Method of processing alfalfa had little impact on forage utilization, except FOMI (P = .11), TOMI (P = .10), and ruminal OM fill (P = .09) tended to be greater when supplemental alfalfa pellets were dehydrated. Similarly, processing method tended to alter the molar proportions of some minor VFA. In conclusion, alfalfa supplementation exerted a dramatic impact on utilization of low-quality forage.(ABSTRACT TRUNCATED AT 250 WORDS)