Use of gender distribution in routine surveillance data to detect potential transmission of gastrointestinal infections among men who have sex with men in England.

Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed for Shigella spp. (annual maximum 71% male); most pronounced for those aged 25-49 years and living in London, Brighton and Manchester. An adult male excess was observed every year for Entamoeba histolytica (range 59.8-76.1% male), Giardia (53.1-57.6%) and Campylobacter (52.1-53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak of Shigella among MSM. Stratified analyses by geography and age group were consistent with MSM transmission for Shigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation.

The impact of new national guidance for the public health management of enteric fever in England.

OBJECTIVES: New guidance was published in England in February 2012 to support the public health management of enteric fever and reduce the risks of secondary transmission. The new guidance was evaluated to assess: STUDY DESIGN: Quantitative and qualitative evaluation of the implementation of new public health guidance. METHODS: A qualitative review of all non-travel-related cases from February 2010 to January 2014 to compare the risk of secondary transmission before and after the guidance introduction; an audit of clearance sampling for each case and their contacts reported in London from February 2012-January 2015 to compare with a previous London audit; and an online user survey in November 2014. RESULTS: The proportions of non-travel cases reported before and after the introduction of the new guidance were similar, 6% in 2010-2012 compared to 7% in 2012-2014 (P = 0.33). There was a 32% reduction in the number of clearance samples required for cases and the estimated period of exclusion from work or school was reduced from 54 days to 16 days. Compliance in case clearance improved from 53% to 90% and contact screening compliance improved from 42% to 80%. The targeted screening of contacts led to a significantly higher positive yield (3.6% from 1.5%, P = 0.003). All symptomatic co-travellers presented to a healthcare professional, suggesting that screening could be restricted to those in risk groups for transmission. Feedback from users highlighted additional areas, such as management of large organised groups of co-travellers and those diagnosed abroad, which has informed the update of the national guidance. CONCLUSIONS: The new guidance has not led to an increase in secondary transmission of enteric fever in England and findings have been used to inform an update of the guidance. The new guidance also represents a reduced burden of investigation and thus a likely reduced cost to patients, healthcare professionals, laboratories and environmental health officers.

Thermal scanning probe lithography for the directed self-assembly of block copolymers.

Thermal scanning probe lithography (t-SPL) is applied to the fabrication of chemical guiding patterns for directed self-assembly (DSA) of block copolymers (BCP). The two key steps of the overall process are the accurate patterning of a poly(phthalaldehyde) resist layer of only 3.5 nm thickness, and the subsequent oxygen-plasma functionalization of an underlying neutral poly(styrene-random-methyl methacrylate) brush layer. We demonstrate that this method allows one to obtain aligned line/space patterns of poly(styrene-block-methyl methacrylate) BCP of 18.5 and 11.7 nm half-pitch. Defect-free alignment has been demonstrated over areas of tens of square micrometres. The main advantages of t-SPL are the absence of proximity effects, which enables the realization of patterns with 10 nm resolution, and its compatibility with standard DSA methods. In the brush activation step by oxygen-plasma exposure, we observe swelling of the brush. This effect is discussed in terms of the chemical reactions occurring in the exposed areas. Our results show that t-SPL can be a suitable method for research activities in the field of DSA, in particular for low-pitch, high-χ BCP to achieve sub-10 nm line/space patterns.

The North Wyke Farm Platform: effect of temperate grassland farming systems on soil moisture contents, runoff and associated water quality dynamics.

The North Wyke Farm Platform was established as a United Kingdom national capability for collaborative research, training and knowledge exchange in agro-environmental sciences. Its remit is to research agricultural productivity and ecosystem responses to different management practices for beef and sheep production in lowland grasslands. A system based on permanent pasture was implemented on three 21-ha farmlets to obtain baseline data on hydrology, nutrient cycling and productivity for 2 years. Since then two farmlets have been modified by either (i) planned reseeding with grasses that have been bred for enhanced sugar content or deep-rooting traits or (ii) sowing grass and legume mixtures to reduce nitrogen fertilizer inputs. The quantities of nutrients that enter, cycle within and leave the farmlets were evaluated with data recorded from sensor technologies coupled with more traditional field study methods. We demonstrate the potential of the farm platform approach with a case study in which we investigate the effects of the weather, field topography and farm management activity on surface runoff and associated pollutant or nutrient loss from soil. We have the opportunity to do a full nutrient cycling analysis, taking account of nutrient transformations in soil, and flows to water and losses to air. The NWFP monitoring system is unique in both scale and scope for a managed land-based capability that brings together several technologies that allow the effect of temperate grassland farming systems on soil moisture levels, runoff and associated water quality dynamics to be studied in detail. HIGHLIGHTS: Can meat production systems be developed that are productive yet minimize losses to the environment?The data are from an intensively instrumented capability, which is globally unique and topical.We use sensing technologies and surveys to show the effect of pasture renewal on nutrient losses.Platforms provide evidence of the effect of meteorology, topography and farm activity on nutrient loss.

An unusual case of bilateral pyoderma gangrenosum with Achilles tendon rupture.

Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory disease characterized by neutrophilic infiltration of the dermis and destruction of tissue. PG is a diagnostic challenge, which can lead to late diagnosis, delayed treatment and detrimental surgical interventions. We describe a presentation not previously reported, affecting deep muscle and tendon leading to tendon rupture. Furthermore, we show the multidisciplinary team approach to management of a patient with PG and the reconstructive surgical element. A 31-year-old woman presented with a rapid onset painful, tender, left calf and ankle, which was associated with a mild flare of ulcerative colitis. Investigations revealed a white cell count of 26 × 10(9) cells L(-1) , a C-reactive protein count of 226 mg L(-1) , no deep vein thrombosis on ultrasound, no bone or joint involvement on X-ray and no organisms on joint aspirate. Debridement was undertaken after the left ankle developed a foul-smelling discharging wound. Repeat debridement led to worsening of the condition (pathergy). Intraoperative tissue cultures and microscopy showed no evidence of fungi, bacteria or mycobacteria. Histology showed granulation, inflammatory infiltrate, abscess formation and focal necrotizing vasculitis. Dermatology opinion confirmed PG. Awareness of the diagnosis of PG, and early involvement of dermatology, in a rapidly progressing wound is essential to avoid delayed treatment and prevent worsening through pathergy.

Multi Tbit/in(2) storage densities with thermomechanical probes.

Exploiting the spatial resolution of scanning probes presents an attractive approach for novel data storage technologies in particular for large-scale data repositories because of their inherent potential for high storage density. We show that multi-Tbit/in(2) density can be achieved by means of thermomechanically embossing the information as indentation marks into a polymer film. The data density is determined by the nonlinear interaction between closely spaced indents and the fundamental scaling relations governing the shape and size of the indents. We find that cooperative effects in polymers give rise to a minimum indentation radius on the order of the correlation length of the cooperatively rearranged region even if formed by an infinitely sharp indenter. Thus, cooperativity coupled to alpha-transitions in polymers is evinced in a real space geometrical experiment. Furthermore, we predict that indentation marks cannot be made smaller than 5 nm in diameter, which limits the feature resolution for embossing technologies in general.

Are grammatical representations useful for learning from biological sequence data?--a case study.

This paper investigates whether Chomsky-like grammar representations are useful for learning cost-effective, comprehensible predictors of members of biological sequence families. The Inductive Logic Programming (ILP) Bayesian approach to learning from positive examples is used to generate a grammar for recognising a class of proteins known as human neuropeptide precursors (NPPs). Collectively, five of the co-authors of this paper, have extensive expertise on NPPs and general bioinformatics methods. Their motivation for generating a NPP grammar was that none of the existing bioinformatics methods could provide sufficient cost-savings during the search for new NPPs. Prior to this project experienced specialists at SmithKline Beecham had tried for many months to hand-code such a grammar but without success. Our best predictor makes the search for novel NPPs more than 100 times more efficient than randomly selecting proteins for synthesis and testing them for biological activity. As far as these authors are aware, this is both the first biological grammar learnt using ILP and the first real-world scientific application of the ILP Bayesian approach to learning from positive examples. A group of features is derived from this grammar. Other groups of features of NPPs are derived using other learning strategies. Amalgams of these groups are formed. A recognition model is generated for each amalgam using C4.5 and C4.5rules and its performance is measured using both predictive accuracy and a new cost function, Relative Advantage (RA). The highest RA was achieved by a model which includes grammar-derived features. This RA is significantly higher than the best RA achieved without the use of the grammar-derived features. Predictive accuracy is not a good measure of performance for this domain because it does not discriminate well between NPP recognition models: despite covering varying numbers of (the rare) positives, all the models are awarded a similar (high) score by predictive accuracy because they all exclude most of the abundant negatives.

Evaluation of colposuspension for treatment of incontinence in spayed female dogs.

OBJECTIVE: To determine the long-term effects of colposuspension in spayed female dogs with urinary incontinence and identify preoperative anatomic or urodynamic measurements associated with a successful outcome. DESIGN: Prospective study. ANIMALS: 23 client-owned spayed female dogs with urinary incontinence. PROCEDURE: Prior to surgery, a history was obtained, and a physical examination, CBC, serum biochemical analyses, urinalysis, bacterial culture of a urine sample, vaginourethrocystography, urethral pressure profilometry, and leak point pressure test were performed. Colposuspension was performed, and preoperative tests were repeated 2 months after surgery. Clients were interviewed 2 weeks, 1 month, and 1 year after surgery. RESULTS: 22 dogs were followed up for 1 year. Twelve had complete urinary control 2 months after surgery, and 3 had complete urinary control 1 year after surgery. Dogs with normal urinary control at 2 months had an increased leak point pressure (LPP), compared with preoperative measurements, and their LPP was the same as normal dogs. Eight dogs had complete urinary control, and 9 were considered greatly improved 1 year after surgery when medical treatment was added to the effect of colposuspension. Client satisfaction was high, with 19 of 22 (86%) owners being pleased with their decision to have surgery performed. The only predictors of complete urinary control 2 months after surgery were a more caudal position of the external urethral opening in relation to the pubis on preoperative radiographs and a longer overall urethral length. CONCLUSIONS AND CLINICAL RELEVANCE: Colposuspension alone will result in complete urinary control in few dogs with urinary incontinence but may improve urinary control sufficiently that owners will be pleased. Preoperative vaginourethrocystography may be helpful in predicting response to surgery, and the LPP test correlates with improved urinary control.

A rapid and strong laparoscopic-assisted gastropexy in dogs.

OBJECTIVE: To develop a technique for laparoscopic gastropexy in dogs and evaluate effects on stomach position and strength of the adhesion between the stomach and abdominal wall. ANIMALS: 8 healthy dogs. PROCEDURE: Dogs were anesthetized, and the abdomen was insufflated with carbon dioxide. A laparoscope was placed through a cannula inserted on the abdominal midline caudal to the umbilicus. Babcock forceps placed through a cannula inserted lateral to the right margin of the rectus abdominus muscle were used to exteriorize the pyloric antrum, a longitudinal incision was made through the serosa and muscular layer of the pyloric antrum, and the seromuscular layer of the pyloric antrum was sutured to the transversus abdominus muscle. After surgery, positive-contrast gastrography was used to evaluate stomach position and the onset of gastric emptying, and ultrasonography was used to assess stomach wall activity and mobility. Dogs were euthanatized 1 month after surgery, and tensile strength of the adhesion was tested. RESULTS: In all dogs, stomach position and the onset of gastric emptying were normal 25 days after surgery, and the pyloric antrum was firmly attached to the abdominal wall 30 days after surgery. Mean +/- SD ultimate load of the adhesion in tension was 106.5 +/- 45.6 N. CONCLUSIONS AND CLINICAL RELEVANCE: The laparoscopic gastropexy technique described in the present study could be performed quickly and easily by an experienced surgeon, resulted in a strong fibrous adhesion between the stomach and abdominal wall, and appeared to cause minimal stress to the dogs.

Results of cystometry and urethral pressure profilometry in dogs sedated with medetomidine or xylazine.

OBJECTIVE: To compare effects of medetomidine and xylazine hydrochloride on results of cystometry and micturition reflexes in healthy dogs and results of urethral pressure profilometry (UPP) in sedated and conscious dogs. ANIMALS: 20 dogs. PROCEDURES: Urodynamic testing was performed 6 times in each dog (3 times after administration of xylazine [1 mg/kg of body weight, IV] and 3 times after administration of medetomidine (30 microg/kg, IM). Before each episode of sedation, UPP was performed. Heart and respiratory rates and indirect blood pressures were recorded prior to and 5, 10, 20, and 30 minutes after injection of sedative. Cystometry measurements included threshold volume, threshold pressure, and tonus limb. The UPP measurements included maximal urethral closure pressure (MUCP), functional profile length, and, in male dogs, plateau pressure. RESULTS: Mean MUCP was decreased markedly in xylazine- and medetomidine-sedated dogs. Xylazine and medetomidine also decreased plateau pressure in male dogs. The MUCP measurements were consistent among days for conscious and xylazine-sedated dogs but were inconsistent for medetomidine-sedated female dogs. The proportion of valid cystometry measurements was greater for xylazine (39 of 60) than for medetomidine (27 of 60). Cystometry was considered invalid when bladder pressure reached 30 cm H2O without initiation of a micturition reflex. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and xylazine have similar effects on measurement of UPP and cystometry. Medetomidine was less consistent among days for UPP in female dogs and produced fewer valid cystometry tests, compared with xylazine. For urodynamic evaluations, medetomidine administered IM cannot be substituted for xylazine administered IV.

Response of dogs treated with ivermectin or milbemycin starting at various intervals after Dirofilaria immitis infection.

The response to heartworm infection before preventative programs were started was investigated in 56 dogs. Dogs were infected with third-stage larvae of Dirofilaria immitis and started on preventative programs (monthly treatment) with ivermectin/pyrantel pamoate (IVM/PP) or milbemycin oxime (MO) 3.5, 4.5, 5.5, or 6.5 months after infection. Each time period comprised a group of six dogs treated with IVM/PP and six treated with MO. Thoracic radiographs were obtained prior to infection, at the start of preventative treatment, and at regular intervals until dogs were necropsied 1 year after the preventative was started. All dogs developed radiographic signs of heartworm disease, and all had heartworm-related arterial changes at necropsy. From Day 210 to 330, interstitial lung disease was less severe in dogs started on MO 3.5 months after infection than in dogs given IVM/PP at the same time. Arterial surfaces were more severe at necropsy in the dogs started on MO at 4.5 months than in the dogs started on IVM/PP at the same time. There was increased caudal lobar arterial and interstitial disease in the dogs treated with IVM/PP compared with dogs treated with MO; this was attributed to the death of young worms within the caudal pulmonary arteries. Dogs started on either preventative at 5.5 and 6.5 months after infection had radiographic changes and necropsy evaluations that were similar to those of untreated controls. This study reinforces the recommendation of the American Heartworm Society that mature dogs be evaluated for infection prior to starting a monthly preventative and that any dog that tests positive by a heartworm antigen test receive treatment with an adulticide prior to starting a heartworm preventative program.

Immediate urodynamic and anatomic response to colposuspension in female Beagles.

OBJECTIVE: To characterize urodynamic function and anatomy before and after colposuspension in anesthetized female Beagles. ANIMALS: 12 adult female Beagles. PROCEDURE; During general anesthesia (thiopental sodium induction and halothane maintenance), urethral pressure profiles, leak point pressure measurements with a 50-ml bladder volume, positive contrast cystograms, and retrograde vaginourethrocystograms were performed. A caudal midline laparotomy was used to perform colposuspension. Urodynamic and radiographic studies were repeated after surgery. RESULTS: Leak point pressures were increased (120 to 168.9 cm H2O), and maximum urethral closure pressures decreased (43.7 to 19.3 cm H2O ) after colposuspension. The urethra and bladder were moved cranially; the external urethral orifice was positioned closer to the pelvic cavity, and the neck of the bladder was positioned more cranially into the abdomen. Length of the urethra, as measured by use of vaginourethrocystograms, was increased by 3%. As measured by use of urethral pressure profiles, total profile length was increased by 19.9%, and functional profile length was increased by 19.2%. CONCLUSIONS AND CLINICAL RELEVANCE: Increased leak-point pressure correlated with the expected clinical improvement attributable to colposuspension. Increased exposure of the urethra to abdominal and pelvic cavity pressures may be the mechanism by which incontinent dogs become continent after colposuspension. Results of the leak-point pressure test may correlate with clinical behavior before and after colposuspension for treatment of incontinence.

Serial laparoscopic biopsies of liver and spleen from Schistosoma-infected baboons (Papio spp.).

PURPOSE: To obtain large, serial biopsy samples from the liver and spleen by using laparoscopy. Large samples were needed for measurement of inflammatory mediators during various stages of schistosomiasis. METHODS: Each of the seven female baboons (Papio sp.) underwent as many as three laparoscopies, for a total of 19 laparoscopic procedures. This process permitted sampling of the liver, spleen, and mesenteric lymph nodes before and at 6 and 9 weeks after infection with Schistosoma mansoni. All surgery was performed through three trocar sites. Postoperative care included preemptive analgesia. After surgery, we monitored the animals' appetite and measured the core body temperature and activity by using implanted radiofrequency transmitters. RESULTS: We obtained samples of the liver and splenic biopsies during all 19 laparoscopic procedures. The mean weight of the liver biopsies was 3.7 g and that of the spleen samples was 5.3 g. We encountered small adhesions during 5 of the 12 reoperations. Eating and activity rapidly returned after surgery. CONCLUSIONS: Laparoscopy permitted collection of large, serial biopsies with apparently limited stress to the animals. Laparoscopy can be used for biopsies in studies to characterize disease response, confirm normal organ histology prior to drug toxicity studies, determine target-organ drug concentrations in pharmacokinetic studies, and measure drug residues. This refinement likely will reduce required animal numbers by decreasing the effect of surgery compared to that of the experimental conditions, enhance animal well-being, and permit repeated measurements in an animal that serves as its own control.

Development of a molecular probe to baboon interleukin-10 mRNA for in situ hybridization during experimental schistosomiasis.

A nucleic acid probe complementary to baboon interleukin 10 (IL-10) mRNA was developed for in situ hybridization. Highly conserved IL-10 protein sequences from several mammals were aligned to design oligonucleotide primers flanking a 270-bp sequence of the target cDNA. RNA was isolated from stimulated peripheral blood mononuclear cells (PBMC). IL-10 cDNA was reverse-transcribed from the total PBMC RNA and amplified with the polymerase chain reaction (PCR). Cloning and sequencing of the PCR product confirmed it to be of baboon IL-10 origin, with 97.8% identity to human and 100% identity to macaque mRNA sequences. The baboon IL-10 DNA probe hybridized in Southern blots to a 7.9-Kbp or 8.6-Kbp band after digestion of genomic baboon DNA with Bam H1 or Eco R1, respectively. Preliminary results with an antisense riboprobe derived from this sequence showed the presence of IL-10 mRNA in sections of granulomatous tissues.

Stress leak point pressures and urethral pressure profile tests in clinically normal female dogs.

OBJECTIVE: To develop a stress leak point pressure (LPP) test for dogs, determine LPP for continent female dogs, and determine urethral pressure profile (UPP) values for nonanesthetized, continent female dogs. ANIMALS: 22 continent female dogs weighing from 21 to 29 kg. PROCEDURE: A standard UPP test and a modification of the LPP test used in women were performed on all dogs. On 3 occasions, dogs underwent UPP testing while awake. They then were anesthetized with propofol, and LPP was measured at bladder volumes of 75, 100, and 150 ml. For LPP tests, abdominal pressure was applied by inflating a human blood pressure cuff placed around the dog's abdomen. LPP were recorded through a urethral catheter (bladder LPP) and a rectal balloon catheter (abdominal LPP). RESULTS: Mean +/- SD and median maximal urethral closure pressure was 110.1+/-20.2 and 109.0 cm water, respectively. Mean bladder LPP for the 75, 100, and 150 ml bladder volumes was 172.4 cm water. Significant differences among LPP for the 3 bladder volumes were not detected. CONCLUSIONS: Stress LPP can be recorded in female dogs.

Comparison of thoracic radiographs with images transmitted via advanced telecommunications equipment.

OBJECTIVE: To compare thoracic radiographs of clinically normal dogs and dogs with mild clinical heartworm disease with images transmitted by a desk-top, two-way audiovisual teleconferencing system. DESIGN: Prospective, matched-set study. STUDY POPULATION: 50 thoracic radiographs from clinically normal and heartworm-infected dogs and the digitally transmitted images of those radiographs. PROCEDURE: Thoracic radiographs from 25 clinically normal dogs and 25 dogs infected with 1 to 24 heartworms were evaluated by 3 clinicians. Using classic criteria for heartworm disease, evaluations of radiographs and images transmitted digitally over 2 high-speed data-transfer telephone lines (56 kilobits/s/line) were performed. Clinicians were asked to determine whether dogs had radiographic signs of heartworm disease. RESULTS: Clinicians' ability to detect heartworm disease did not differ between interpretations of radiographs and those of transmitted images. CLINICAL IMPLICATIONS: Radiographic images transmitted via a teleconference system can be used to provide reliable diagnostic information. Thoracic radiographs can be interpreted at a remote site permitting rapid consultation and immediate advice on clinical management.

Use of partial prostatectomy for treatment of prostatic abscesses and cysts in dogs.

OBJECTIVE: To determine whether dogs had prostatic disease, urinary incontinence, or urinary tract infection 1 year after partial prostatectomy to treat prostatic abscesses and cysts. DESIGN: Prospective study. ANIMALS: 20 male dogs with prostatic abscesses or cysts. Fifteen dogs had evidence of urinary tract infection. Only 8 dogs urinated normally; the remainder dribbled, had obstructions, or required medical treatment. PROCEDURE: Partial prostatectomy was performed on each dog. Sexually intact dogs (n = 12) also were castrated. RESULTS: None of the dogs had return of prostatic cystic enlargement or clinical signs of prostatic disease during the first year after surgery. Two dogs were euthanatized within 1 year after surgery, with 1 dog having prostatic enlargement and adenocarcinoma and 1 dog having unrelated lymphosarcoma. Fifteen dogs were continent. The remaining 5 dogs urinated normally but had intermittent and minor incontinence. Eleven dogs had no signs of infection 1 year after surgery, 5 had pyuria or positive urine bacteriologic culture results, 2 did not have urinalysis performed, and 2 were euthanatized. CLINICAL IMPLICATIONS: Dogs with severe prostatic abscesses or cysts and infections can be successfully treated by partial prostatectomy with an ultrasonic surgical aspirator and castration, resulting in long-term disease resolution. Although most dogs with severe prostatic disease do not urinate normally before surgery, nearly all dogs resume normal micturition after partial prostatectomy. Postoperative results of partial prostatectomy appear to be better than those of previous drainage techniques for treatment of prostatic cavitary disease.

Production of polyclonal antibodies to feline tumor necrosis factor.

Two 13-amino-acid peptides were synthesized based on the putative feline tumor necrosis factor (FeTNF) sequence. The synthesized peptides were conjugated to keyhole limpet hemocyanin, emulsified in complete Freund's adjuvant, and injected into rabbits. The gene for FeTNF was cloned into the FLAG (International Biotechnologies Inc. [IBI], Kodak, New Haven, Conn.) fusion protein expression vector. The expressed fusion protein was purified by using the M-1 anti-FLAG octapeptide monoclonal antibody (IBI, Kodak). The fusion protein was emulsified in complete Freund's adjuvant and injected into chickens. The immune sera generated to the synthetic peptides and the fusion protein recognized the recombinant FeTNF fusion protein on Western or dot blot assay. The preimmune and immune sera were incubated with naturally occurring FeTNF (supernatants from lipopolysaccharide-stimulated cultured feline peritoneal exudate or peripheral mononuclear cells). The antibody raised to the recombinant FeTNF fusion protein and N-terminal synthetic peptide neutralized bioactivity of native FeTNF and recombinant human TNF. Preimmune sera did not have any neutralizing activity. The polyclonal antibodies were not specific for FeTNF, since both porcine and human recombinant TNF were neutralized by the fusion protein antibodies. The synthetic peptide antibodies recognized recombinant feline and equine TNF on a Western blot.

Computational gene discovery and human disease.

Bioinformatics is now an essential tool in many aspects of human molecular genetics research. Methods for the prediction of gene structure are essential components in genomic sequencing projects and provide the key to deriving protein sequence and locating intron/exon junctions. Sequence comparison and database searching are the pre-eminent approaches for predicting the likely biochemical function of new genes, although sequence profiles derived from families of aligned sequences have advantages in the detection of remote sequence relationships. The use of sequence database analysis for large-scale comparative analysis of genome sequence data from model organisms is emerging as the most important recent development in the application of bioinformatics methods for characterizing candidate disease genes.